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Marco VINCETI

Professore Ordinario
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze Sede ex Sanità Pubblica

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Pubblicazioni

2024 - A survey on hydration and use of plastic water bottles among Italian health sector workers [Articolo su rivista]
Lugli, Camilla; Palandri, Lucia; Pedretti, Simona; Bacchi, Romana; Altariva, Daniela; Guerzoni, Giulia; Sala, Alessia; Vaccari, Claudia; Filippini, Tommaso; Righi, Elena; Vinceti, Marco; Romani, Gabriele
abstract

Background: Modena's Local Health Authority (AUSL) is a public service with more than 5,000 employees. In its facilities, drinking water is available as tap water. However, disposable plastic bottles are also widely used, thus increasing plastic waste. Study design and methods: In the present study, we aimed to investigate employees' drinking habits through an ad hoc 10-item online questionnaire, which was administered in spring 2023. Results: Of the 584 participants (10.8% response rate), 75% of workers reported drinking less than 1.5 liters of water per day. In addition, 74% of workers brought water from home, while 62% used disposable plastic containers bought in the workplace or outside. When asked if they would appreciate a water refilling station in the workplace, whether that would induce them to consume less plastic and to drink more water, 91%, 82%, and 72% of workers said "yes", respectively. By installing water coolers, the estimated mean number of plastic bottles spared every day at the AUSL would be about 6,000. Conclusions: Our data shed light on most employees' perceived need for alternative sources of drinking water, not only in order to drink more for health benefits, but also to reduce plastic usage in favor of reusable, more environmentally friendly materials.

2024 - Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and exposure to selenium species: A cross-sectional study [Articolo su rivista]
Urbano, Teresa; Filippini, Tommaso; Malavolti, Marcella; Fustinoni, Silvia; Michalke, Bernhard; Wise, Lauren A.; Vinceti, Marco
abstract

Selenium is a trace element found in many chemical forms. Selenium and its species have nutritional and toxicologic properties, some of which may play a role in the etiology of neurological disease. We hypothesized that adherence to the Mediterranean-Dietary Approach to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet could influence intake and endogenous concentrations of selenium and selenium species, thus contributing to the beneficial effects of this dietary pattern. We carried out a cross-sectional study of 137 non-smoking blood donors (75 females and 62 males) from the Reggio Emilia province, Northern Italy. We assessed MIND diet adherence using a semiquantitative food frequency questionnaire. We assessed selenium exposure through dietary intake and measurement of urinary and serum concentrations, including speciation of selenium compound in serum. We fitted non-linear spline-based regression models to investigate the association between MIND diet adherence and selenium exposure concentrations. Adherence to the MIND diet was positively associated with dietary selenium intake and urinary selenium excretion, whereas it was inversely associated with serum concentrations of overall selenium and organic selenium, including serum selenoprotein P-bound selenium, the most abundant circulating chemical form of the metalloid. MIND diet adherence also showed an inverted U-shaped relation with inorganic selenium and particularly with its hexavalent form, selenate. Our results suggest that greater adherence to the MIND diet is non-linearly associated with lower circulating concentrations of selenium and of 2 potentially neurotoxic species of this element, selenoprotein P and selenate. This may explain why adherence to the MIND dietary pattern may reduce cognitive decline.

2024 - Adverse human health effects of climate change: an update [Articolo su rivista]
Filippini, Tommaso; Paduano, Stefania; Veneri, Federica; Barbolini, Giulia; Fiore, Gianluca; Vinceti, Marco
abstract

Background: The world is currently facing a process of climate change, which may adversely impact human health in many different ways. The safety of food, water and urban environments is endangered by the consequences of climate change. Sea level and temperature rise, along with more frequent and longer heat waves, represent only a few of the effects of climate change. The increased risk of extreme climate events (e.g., cyclones, droughts and floods) is another serious public health issue. These adverse effects are enhanced in areas and countries not having the capacity to effectively deal with climate change. Study design: We primarily aimed at summarizing the impacts of climate change on public health. A further aim was to identify the most concerning consequences of this phenomenon and the vulnerability factors that amplify the negative effects of climate change. Methods: PubMed and other literature databases were used as literature sources for this narrative review based on the search terms 'climate change' and 'diseases categories' up to January 2024, in order to assess the most recent and relevant scientific evidence about the relation between climate change and public health, identify knowledge gaps and priorities for future research. We also screened the websites of major agencies devoted to human health protection and environmental health. Results and conclusions: Climate change appears to induce a broad spectrum of generally adverse effects on public health. It may increase the risk of infectious diseases, psychiatric disorders, cancer and other diseases. Currently, we are not effectively counteracting this phenomenon, since pollutant and greenhouse gas emissions have been increasing alongside temperatures. A host of measures are required in order to prevent and fight climate change and related health effects. These include the adoption of a holistic approach and the collaboration of different kinds of expertise in order to design more effective strategies. Special attention should be paid to those who live in disadvantaged countries, and those who are more vulnerable to the adverse health consequences of climate change.

2024 - Age-specific prevalence of the different clinical presentations of AD and FTD in young-onset dementia [Articolo su rivista]
Zamboni, G.; Maramotti, R.; Salemme, S.; Tondelli, M.; Adani, G.; Vinceti, G.; Carbone, C.; Filippini, T.; Vinceti, M.; Pagnoni, G.; Chiari, A.
abstract

Background Studies have shown that the prevalence of all-variants Alzheimer's disease (AD) and frontotemporal dementia (FTD) both increase with age, even before the age of 65. However, it is not known whether their different clinical presentations all increase in prevalence with age in the same way.Methods We studied the prevalence of the different clinical presentations of young-onset AD and FTD by 5-year age groups in a population-based study identifying all dementia patients with a diagnosis of AD and FTD and symptoms onset before age 65 in the Modena province, Italy. By using regression models of cumulative occurrences, we also estimated age-specific prevalence and compared the growth curves of the clinical presentations.Results The prevalence of all-variants AD increased with age, from 18/1,000,000 in the 40-44 age group to 1411/1,000,000 in the 60-64 age group. The prevalence of all-variants FTD also increased with age, from 18/1,000,000 to 866/1,000,000. An estimation of age-specific prevalence functions of each clinical presentation showed that atypical non-amnestic AD and aphasic FTD grew the most in early ages, followed by the behavioural variant of FTD (bvFTD). Then, around the age of 60, amnestic AD took over and its age-specific prevalence continued to increase disproportionally compared to all the other clinical variants of AD and FTD, which, instead, started to decrease in prevalence.Conclusions Amnestic AD is the clinical presentation that increases the most with advancing age, followed by bvFTD, suggesting that there is a differential vulnerability to the effect of ageing within the same neurodegenerative disease.

2024 - Alcohol Intake and Risk of Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Nonexperimental Cohort Studies [Articolo su rivista]
Cecchini, M.; Filippini, T.; Whelton, P. K.; Iamandii, I.; Di Federico, S.; Boriani, G.; Vinceti, M.
abstract

BACKGROUND: Alcohol consumption has been associated with higher blood pressure and an increased risk of hypertension. However, the possible exposure thresholds and effect-modifiers are uncertain. METHODS: We assessed the dose-response relationship between usual alcohol intake and hypertension incidence in nonexperimental cohort studies. After performing a systematic literature search through February 20, 2024, we retrieved 23 eligible studies. We computed risk ratios and 95% CI of hypertension incidence using a nonlinear meta-analytic model based on restricted cubic splines, to assess the dose-response association with alcohol consumption. RESULTS: We observed a positive and almost linear association between alcohol intake and hypertension risk with risk ratios of 0.89 (0.84-0.94), 1.11 (1.07-1.15), 1.22 (1.14-1.30), and 1.33 (1.18-1.49) for 0, 24, 36 and 48 g/d, respectively, using 12 g alcohol/d as the reference value. In sex-specific analyses, the association was almost linear in men over the entire range of exposure but only observed above 12 g/d in women, although with a steeper association at high levels of consumption compared with men. The increased risk of hypertension above 12 to 24 g alcohol/d was similar in Western and Asian populations and considerably greater in White than in Black populations, mainly due to the positive association in women at moderate-to-high intake. CONCLUSIONS: Overall, our results lend support to a causal association between alcohol consumption and risk of hypertension, especially above an alcohol intake of 12 g/d, and are consistent with recommendations to avoid or limit alcohol intake. Sex and ethnicity appear to be major effect-modifiers of such association.

2024 - Atrial Fibrillation and Other Cardiovascular Factors and the Risk of Dementia: An Italian Case–Control Study [Articolo su rivista]
Mazzoli, R.; Chiari, A.; Vitolo, M.; Garuti, C.; Adani, G.; Vinceti, G.; Zamboni, G.; Tondelli, M.; Galli, C.; Costa, M.; Salemme, S.; Boriani, G.; Vinceti, M.; Filippini, T.
abstract

: Dementia is a major neurologic syndrome characterized by severe cognitive decline, and it has a detrimental impact on overall physical health, leading to conditions such as frailty, changes in gait, and fall risk. Depending on whether symptoms occur before or after the age of 65, it can be classified as early-onset (EOD) or late-onset (LOD) dementia. The present study is aimed at investigating the role of cardiovascular factors on EOD and LOD risk in an Italian population. Using a case-control study design, EOD and LOD cases were recruited at the Modena Cognitive Neurology Centers in 2016-2019. Controls were recruited among caregivers of all the dementia cases. Information about their demographics, lifestyles, and medical history were collected through a tailored questionnaire. We used the odds ratio (OR) and 95% confidence interval (CI) to estimate the EOD and LOD risk associated with the investigated factors after adjusting for potential confounders. Of the final 146 participants, 58 were diagnosed with EOD, 34 with LOD, and 54 were controls. According to their medical history, atrial fibrillation was associated with increased disease risk (ORs 1.90; 95% CI 0.32-11.28, and 3.64; 95% CI 0.32-41.39 for EOD and LOD, respectively). Dyslipidemia and diabetes showed a positive association with EOD, while the association was negative for LOD. We could not evaluate the association between myocardial infarction and EOD, while increased risk was observed for LOD. No clear association emerged for carotid artery stenosis or valvular heart disease. In this study, despite the limited number of exposed subjects and the high imprecision of the estimates, we found positive associations between cardiovascular disease, particularly dyslipidemia, diabetes, and atrial fibrillation, and EOD.

2024 - Cadmium exposure and cardiovascular disease risk: A systematic review and dose-response meta-analysis [Articolo su rivista]
Verzelloni, Pietro; Urbano, Teresa; Wise, Lauren A.; Vinceti, Marco; Filippini, Tommaso
abstract

: Exposure to toxic metals is a global public health threat. Among other adverse effects, exposure to the heavy metal cadmium has been associated with greater risk of cardiovascular disease (CVD). Nonetheless, the shape of the association between cadmium exposure and CVD risk is not clear. This systematic review summarizes data on the association between cadmium exposure and risk of CVD using a dose-response approach. We carried out a literature search in PubMed, Web of Science, and Embase from inception to December 30, 2023. Inclusion criteria were: studies on adult populations, assessment of cadmium exposure, risk of overall CVD and main CVD subgroups as endpoints, and observational study design (cohort, cross-sectional, or case-control). We retrieved 26 eligible studies published during 2005-2023, measuring cadmium exposure mainly in urine and whole blood. In a dose-response meta-analysis using the one-stage method within a random-effects model, we observed a positive association between cadmium exposure and risk of overall CVD. When using whole blood cadmium as a biomarker, the association with overall CVD risk was linear, yielding a risk ratio (RR) of 2.58 (95 % confidence interval-CI 1.78-3.74) at 1 μg/L. When using urinary cadmium as a biomarker, the association was linear until 0.5 μg/g creatinine (RR = 2.79, 95 % CI 1.26-6.16), after which risk plateaued. We found similar patterns of association of cadmium exposure with overall CVD mortality and risks of heart failure, coronary heart disease, and overall stroke, whereas for ischemic stroke there was a positive association with mortality only. Overall, our results suggest that cadmium exposure, whether measured in urine or whole blood, is associated with increased CVD risk, further highlighting the importance of reducing environmental pollution from this heavy metal.

2024 - Cadmium exposure and risk of hypertension: A systematic review and dose-response meta-analysis [Articolo su rivista]
Verzelloni, P.; Giuliano, V.; Wise, L. A.; Urbano, T.; Baraldi, C.; Vinceti, M.; Filippini, T.
abstract

Background: Exposure to environmental toxic metals represents a significant global public health concern. Many studies have reported that cadmium (Cd) exposure increases the risk of hypertension. Since the shape of such relation has not been well characterized, we assessed it by performing a systematic review and dose-response meta-analysis of human studies. Methods: We searched the literature through September 5, 2024 to identify papers related to Cd, hypertension, and blood pressure. Inclusion criteria were: observational design, adult population, assessment of exposure using Cd biomarkers, and availability of exposure category-specific risk estimates for hypertension. We performed a dose-response meta-analysis of the results from included studies. Results: Of the 18 studies published between 2006 and 2024, most had a cross-sectional design. Cd was measured in whole blood and/or urine in almost all studies, whereas only two studies measured Cd in serum. The dose-response meta-analysis indicated an almost linear relation between urinary Cd concentrations and hypertension risk with RR = 1.18, 95% CI 1.02–1.37 at 2.0 μg/g creatinine compared with no exposure. In contrast, the association between blood Cd concentrations and hypertension risk was non-linear: there was a steep monotonic increase in risk for Cd concentrations below 2 μg/L, reaching a RR of 1.48 (95% CI 1.17–1.86) at 2.0 μg/L, after which a plateau seemed reached. We found similar trends when restricting to studies of Asian population, while when considering North American studies, hypertension risk increased above 1.0 μg/g creatinine. Conclusions: In this dose-response meta-analysis, risk of hypertension showed a non-linear positive association with blood Cd concentrations and a linear positive association with urinary Cd concentrations. Inconsistency in the shape of associations could relate to the different timing of exposure assessed by the biomarkers or the alteration Cd excretion at increasing exposure levels. Mitigation of Cd exposure is confirmed as a public health priority for chronic disease prevention.

2024 - Changes in Cerebrospinal Fluid Concentrations of Selenium Species Induced by Tofersen Administration in Subjects with Amyotrophic Lateral Sclerosis Carrying SOD1 Gene Mutations [Articolo su rivista]
Vinceti, Marco; Urbano, Teresa; Filippini, Tommaso; Bedin, Roberta; Simonini, Cecilia; Sorarù, Gianni; Trojsi, Francesca; Michalke, Bernhard; Mandrioli, Jessica
abstract

: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the brain and spinal cord motor neurons. On 25 April 2023, the drug tofersen, an antisense oligonucleotide, received the US Food and Drug Administration approval for treating ALS in adults carrying mutations of the SOD1 gene. We aimed at assessing whether cerebrospinal fluid concentrations of selenium, an element of both toxicological and nutritional interest possibly involved in disease etiology and progression, are modified by tofersen administration. We determined concentrations of selenium species by anion exchange chromatography hyphenated to inductively coupled plasma-dynamic reaction cell-mass spectrometry and overall selenium by using inductively coupled plasma sector-field mass spectrometry, at baseline and 6 months after active tofersen treatment in ten Italian ALS patients carrying the SOD1 gene mutation. Concentrations of total selenium and many selenium species substantially increased after the intervention, particularly of inorganic (tetravalent and hexavalent) selenium and of the organic species selenomethionine and a compound co-eluting with the selenocystine standard. Overall, these findings suggest that tofersen treatment markedly alters selenium status and probably the redox status within the central nervous system, possibly due to a direct effect on neurons and/or the blood-brain barrier. Further studies are required to investigate the biological and clinical relevance of these findings and how they might relate to the pharmacological effects of the drug and to disease progression.

2024 - Climate change-related factors and west nile virus spread in italy: a systematic review [Abstract in Atti di Convegno]
Granata, Michele; Tommasi, Luigi; Verzelloni, Pietro; Lorenzon, Antonio; Paduano, Stefania; Malavolti, Marcella; Bargellini, Annalisa; Filippini, Tommaso; Righi, Elena; Vinceti, Marco
abstract

West Nile Virus (WNV) is a vector-transmitted pathogen affecting both humans and animals, whose presence has recently risen in Europe and particularly in Italy, concurrently with climate changes that favoured the diffusion of mosquitoes. Our review aims to assess such relation with environmental and meteorological factors focusing on the WNV spread in the Italian territory. Following PRISMA guidelines, we performed a literature search in online databases up to May 31, 2023 on four different databases: PubMed, Web of Science, Embase, Scopus. We used keywords and MeSH terms related to WNV and its vectors (C. pipiens and modestus). Following the PECOS criteria, we included observational studies examining vector dynamics and the WNV infection epidemiology in the Italian population and the possible association with environmental factors. The protocol registration on PROSPERO is in process. Out of the 341 articles retrieved, 222 remained after duplicates exclusion and 44 papers were selected after screening of title and abstract by two blinded reviewers. After full-text screening, 31 studies (published between 2011 and 2023) were included. Climatic factors such as temperature, daylight hours and humidity seem to be strongly associated with the spread of WNV and its vectors, while rainfall showed less influence. Among environmental factors, soil characteristics and population dynamics (of both vector and host) were found to be the most predictive. By contrast, distance from specific areas (e.g. urban or protected areas) seems to have no influence. These findings suggest that some climatic and environmental factors linked with climate change strongly affect the presence of WNV and its vectors. This issue can be considered a warning bell about the potential future increase in cases related to climate change, but offers helpful resources for predicting its spread and implement tailored public health interventions.

2024 - Correction: Comment on “Relation of fruit juice with adiposity and diabetes depends on how fruit juice is defined: a re-analysis of the EFSA draft scientific opinion on the tolerable upper intake level for dietary sugars” by Chen et al. 2023 (European Journal of Clinical Nutrition, (2023), 77, 12, (1176-1177), 10.1038/s41430-023-01337-0) [Articolo su rivista]
Valtuena Martinez, S.; Turck, D.; Craciun, I.; Vinceti, M.
abstract

Correction to: European Journal of Clinical Nutrition , published online 15 September 2023 The following disclaimer was added in the article backmatter: “The authors Silvia VALTUEÑA MARTINEZ and Ionut CRACIUN are employed with the European Food Safety Authority (EFSA) in NIF Unit that provides scientific and administrative support to the EFSA NDA Panel in the area of nutrition. However, the present article is published under the sole responsibility of the authors and may not be considered as an EFSA scientific output. The positions and opinions presented in this article are those of the authors alone and do not necessarily represent any official position of EFSA. To know about the views or scientific outputs of EFSA, please consult its website under.” The original article has been corrected.

2024 - Dairy Intake and Risk of Cognitive Decline and Dementia: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies [Articolo su rivista]
Villoz, F.; Filippini, T.; Ortega, N.; Kopp-Heim, D.; Voortman, T.; Blum, M. R.; Del Giovane, C.; Vinceti, M.; Rodondi, N.; Chocano-Bedoya, P. O.
abstract

Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis has been conducted yet. Therefore, we performed a systematic review with a dose-response meta-analysis about the association between dairy intake and cognitive decline or incidence of dementia. We investigated prospective studies with a follow-up ≥6 mo on cognitive decline or dementia incidence in adults without known chronic conditions through a systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar from inception to 11 July 2023. We evaluated the dose-response association using a random-effects model. We identified 15 eligible cohort studies with >300,000 participants and a median follow-up of 11.4 y. We observed a negative nonlinear association between cognitive decline/dementia incidence and dairy intake as assessed through the quantity of consumption, with the nadir at ∼150 g/d (risk ratio: 0.88; 95% confidence interval: 0.78, 0.99). Conversely, we found an almost linear negative association when we considered the frequency of consumption (risk ratio for linear trend: 0.84; 95% confidence interval: 0.77, 0.92 for 1 time/d increase of dairy products). Stratified analysis by dairy products showed different shapes of the association with linear inverse relationship for milk intake, whereas possibly nonlinear for cheese. The inverse association was limited to Asian populations characterized by generally lower intake of dairy products, compared with the null association reported by European studies. In conclusion, our study suggests a nonlinear inverse association between dairy intake and cognitive decline or dementia, also depending on dairy types and population characteristics, although the heterogeneity was still high in overall and several subgroup analyses. Additional studies should be performed on this topic, including a wider range of intake and types of dairy products, to confirm a potential preventing role of dairy intake on cognitive decline and identify ideal intake doses. This review was registered at PROSPERO as CRD42020192395.

2024 - Dietary patterns, inflammatory biomarkers and cognition in older adults: An analysis of three population-based cohorts [Articolo su rivista]
Ortega, N.; Schutte, L.; de Crom, T. O. E.; Voortman, T.; Okereke, O. I.; Vinceti, M.; von Gunten, A.; Marques-Vidal, P.; Rodondi, N.; Chiolero, A.; Chocano-Bedoya, P. O.
abstract

Background: Targeting effective strategies to prevent cognitive decline is key in the aging population. Some diets have been linked to a slower cognitive decline, potentially through reducing inflammation. We aimed at determining the effect of inflammatory dietary patterns (IDPs) on cognitive function in three population-based cohorts. Methods: In this longitudinal study, we analyzed data from the Canadian Longitudinal Study of Aging, CoLaus|PsyCoLaus and Rotterdam Study. Our analytical sample included participants over 55 years old with baseline data on cognition, dietary intake, and inflammatory markers. IDPs were derived for each cohort using reduced rank regression to reflect maximal variation in three inflammatory markers. We calculated scores of consumption of the IDPs, higher scores indicating more IDP consumption. We used inverse probability of treatment and censoring weights in the marginal structural models to estimate associations of higher versus lower quarters of consumption of an IDP on general cognition (Mini-Mental State Evaluation) and four cognitive domains (memory, verbal fluency, verbal learning and processing speed and executive function) during at least 3 years of follow-up. Results: We included 10,366 participants (mean age 68) followed-up for a mean of 5 years. Diet explained between 1 and 2% of the variation of the inflammatory markers. There were no differences in general cognition when comparing the highest to the lowest quarter of consumption of IDPs among the three cohorts. Mean differences for the four cognitive domains were of small magnitude across cohorts and not clinically relevant. Conclusion: Diet explained low variation in inflammatory markers. Consuming IDPs was not associated with mean differences in general or domain-specific cognitive function.

2024 - Early fluoride intake and Molar Incisor Hypomineralisation (MIH) defects: A systematic review and dose-response meta-analysis [Articolo su rivista]
Veneri, F.; Filippini, T.; Cecchini, M.; Vinceti, M.; Consolo, U.; Generali, L.
abstract

Background: Excessive intake of fluoride has been implicated in the complex multifactorial etiology of hypomineralisation (MIH) defects. Objective: To study the possible effect of early exposure to fluoride on the risk of molar incisor hypomineralisation, also through a dose-response approach. Methods: Observational and clinical studies investigating the relation between fluoride exposure from any source or evaluating exposure biomarkers and MIH defects. PubMed MEDLINE, Embase and Web of Science databases were con-sulted up to December 1, 2023, using terms related to “fluoride”, “enamel defects” and “demarcated opacities”. We performed a meta-analysis comparing the highest versus lowest fluoride exposure using a random-effects model, and we quantitively assessed this relation using piece-wise linear meta-regression. Results: Thirteen studies were included in the meta-analysis, 12 of which were eligible for the dose-response analysis, all regarding exposure from fluoride in drinking water. Three of them specifically addressed MIH, while the remaining concerned “demarcated opacities”, yet with features attributable to MIH. Comparing the highest versus lowest water fluoride exposure categories, virtually no evidence of a fluoride effect was identified, with an overall odds ratio of 0.93 [95% confidence interval 0.60; 1.45]. The dose-response meta-regression showed a decreasing risk for MIH defects exposure up to 1 mg/L, whereas an increase in risk emerged at higher exposure levels. Conclusions: This meta-analysis suggests that early systemic exposure to fluoride may affect the occurrence of MIH defects differently depending on fluoride concentration. However, these results need to be evaluated with caution due to potential methodological limitations of the studies included. (www.actabiomedica.it).

2024 - Exposure to residential greenness, perceived stress, and depressive symptoms in a North American preconception cohort [Articolo su rivista]
Reimer, C. J.; Willis, M. D.; Wesselink, A. K.; Hystad, P.; Campbell, E. J.; Hatch, E. E.; Kirwa, K.; Gradus, J. L.; Vinceti, M.; Wise, L. A.; Jimenez, M. P.
abstract

Background: Studies suggest that greater exposure to natural vegetation (i.e., greenness) is associated with better mental health. However, there is limited research on greenness and mental health in the preconception period, a critical window of exposure in the life course. We investigated the associations of residential greenness with perceived stress and depressive symptoms using cross-sectional data from a cohort of pregnancy planners. Methods: From 2013 to 2019, we enrolled female-identified participants aged 21–45 years who were trying to conceive without the use of fertility treatment into a North American preconception cohort study (Pregnancy Study Online [PRESTO]). On the baseline questionnaire, participants completed the 10-item Perceived Stress Scale (PSS) and the Major Depression Inventory (MDI). Using geocoded addresses, we estimated residential greenness exposure via satellite imagery (Normalized Difference Vegetation Index [NDVI]) in a 100m buffer. We estimated mean differences and 95% confidence intervals for the association of greenness with perceived stress and depression scores using linear regression models, adjusting for individual and neighborhood sociodemographic characteristics. We also evaluated the extent to which associations were modified by urbanicity and neighborhood socioeconomic status (SES). Results: Among 9718 participants, mean age was 29.9 years, 81.5% identified as non-Hispanic White, 25% had household incomes <$50,000, and mean neighborhood income was $61,932. In adjusted models, higher greenness was associated with lower stress and depression scores (mean difference per interquartile range in greenness: −0.20, 95% CI: −0.39, −0.01; and −0.19, 95% CI: −0.48, 0.10, respectively). The association was stronger among residents of lower SES neighborhoods in urban areas (PSS: −0.57, 95% CI: −1.00, −0.15; MDI: −0.72, 95% CI: −1.40, −0.04). Conclusions: Higher greenness exposure was associated with lower stress and depressive symptoms among pregnancy planners, particularly in lower-SES neighborhoods.

2024 - Extension of use of isomalto‐oligosaccharide as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Poulsen, Morten; Prieto Maradona, Miguel; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Albert, Océane; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of isomalto-oligosaccharide (IMO) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of glucose oligomers with degrees of polymerisation of 3-9, along with various amounts of mono- and disaccharides. The NF comes in both syrup and powder form. The applicant intends to extend the current uses of the NF as an ingredient in several foods, and use the NF in food supplements aimed at the general population older than 10 years of age. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. Along with literature data, the applicant carried out a tolerability study in adult volunteers with the NF at doses up to 120 g/day. The Panel concludes that this study provides reassurance that the NF is tolerable at doses of 120 g/day. Conservative intake estimates resulting from the use of the NF as an ingredient according to the currently authorised uses and new proposed uses result in a highest intake estimate in adolescents of 112 g/day at the 95th percentile, and reach 142 g/day in adolescents when the use as a food supplement is included. The Panel notes this amount is higher than the dose of 120 g/day for which tolerability has been demonstrated. However, considering the source, compositional characterisation, production process and nature of the NF, as well as the available nutritional and toxicological data on the NF, the Panel considers that the NF does not present safety concerns under the proposed conditions of use.

2024 - Greenness and diabetes: a systematic review and meta-analysis of observational studies [Abstract in Atti di Convegno]
De Pasquale, L; Iamandii, I; Mullalli, A; Righi, E; Vinceti, M; Filippini, T
abstract

Since diabetes represents a serious Public Health problem and access to green spaces seems to influence some of its risk behaviors, we performed a systematic review to evaluate the association between greenness exposure and diabetes mellitus type 2 (TDM2), prediabetes and gestational diabetes. Following the PRISMA guidelines, we conducted an online literature search in PubMed, Embase and Web of Science databases by using terms related to «green space», «diabetes mellitus», «gestational diabetes» and «prediabetes». The identified studies were imported into the Rayyan web app where we performed a triple-blind screening of title, abstract and full-text, including only original studies with observational design that assessed the relation between exposure to greenness and diabetes incidence/mortality reporting effect measures (relative risk, hazard ration and odds ratio) with 95% confidence intervals (CI). Lastly, we performed a metaanalysis using both a restricted maximum likehood random effects model, comparing the highest versus lowest greenness categories or continuous increase of greenness, and a onestage dose-response using a 3-knots restricted cubic spline model with fixed percentiles (10th, 50th and 90th). We identified 212 potentially eligible articles, 34 of which were eventually included in the quantitative analyses. In the preliminary forest-plot analyses almost all studies reported a decreased TDM2 risk, regardless of the heterogeneity in the satellite-based methodologies to assess greenness. Furthermore, the dose-response curve showed a progressive reduction of the RR of TDM2 incidence, especially for exposure above 0.5 NDVI (risk ratio=0.93; 95% CI: 0.15, 5.67). We observed a growing interest concerning the topic in recent years, and, considering the increasing disease burden, the identification of a protective role of greenness could help implement community preventive measures.

2024 - It is (not) rocket science: Public health communication experience as expressed by participants at an international workshop [Articolo su rivista]
Lugli, C.; Ferrari, E.; Filippini, T.; Corsini, A. G.; Odone, A.; Vinceti, M.; Righi, E.; Palandri, L.
abstract

2024 - Joselito® and lowering of LDL-cholesterol concentration, blood pressure, and reduction of coronary heart disease risk: Evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De , ; Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. L.; Fiolet, T.; Siani, A.
abstract

Following an application from C & aacute;rnicas Joselito S.A. pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Spain, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to 'Joselito ham increases antioxidant substances in the body, reduces blood pressure and plasma triglycerides, decreases oxidative stress and prevents effect in diseases related to the cardiovascular and intestinal systems'. The scope of the application was proposed to fall under a health claim referring to disease risk reduction. The food constituent that is the subject of the health claim is Joselito, an Iberian ham characterised by a high content of oleic acid. The Panel considers that the food is sufficiently characterised. The Panel considers that lowering of LDL-cholesterol concentration and blood pressure is a beneficial effect by decreasing the risk of coronary heart disease. Upon a request from EFSA, the applicant identified one human intervention study as being pertinent to the claim. However, due to methodological limitations, the Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panel notes that no human intervention studies from which conclusions could be drawn for the scientific substantiation of the claim were provided by the applicant. The Panel concludes that a cause and effect relationship has not been established between the intake of Joselito (R) ham and the reduction of LDL-cholesterol concentration or blood pressure.

2024 - Maternal Exposure to Heavy Metals from Industrial Sources during Pregnancy and Childhood Cancer Risk in California [Articolo su rivista]
Chen, Y.; Van Deventer, D.; Nianogo, R.; Vinceti, M.; Kang, W.; Cockburn, M.; Federman, N.; Heck, J. E.
abstract

Objective: The study investigated maternal exposure to heavy metals from industrial sources during pregnancy as potential risk factors for childhood cancer. Methods: Cases ages 0-19 were identified from California Cancer Registry. Controls (20:1 ratio) were randomly selected from California Birth Registry, frequency-matched by birth year (1998-2016). We estimated maternal exposure to lead, nickel, and cobalt in ambient air from the Toxics Release Inventory. We examined "ever/never" and "high/low" exposures categorized by median exposure. Models were adjusted for maternal age, race/ethnicity, method of payment for prenatal care, neighborhood socioeconomic status, and urban/rural residence. Results: Among highly exposed persons, lead was associated with an increased teratoma risk (adjusted odds ratio [aOR]: 1.52; 95% confidence interval [CI]: 0.97, 2.37), whereas nickel was associated with an increased rhabdomyosarcoma risk (aOR: 1.45; 95% CI: 1.03, 2.04). Cobaltwas associated with an increased glioma risk (aOR: 2.25; 95% CI: 1.39, 3.65) among ever-exposed persons. Inverse associations were found between Wilms tumor and nickel among the ever exposed and highly exposed (ever: aOR: 0.75; 95% CI: 0.59, 0.96; high: aOR: 0.64; 95% CI: 0.45, 0.93). Conclusions: Findings suggest that air pollution from heavy metals released by industrial sources may elevate childhood cancer risk.

2024 - Maternal residential exposure to solvents from industrial sources during pregnancy and childhood cancer risk in California [Articolo su rivista]
Chen, Y.; Van Deventer, D.; Nianogo, R.; Vinceti, M.; Kang, W.; Cockburn, M.; Federman, N.; Heck, J. E.
abstract

Background: Maternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer. Methods: The present study included 15,744 cancer cases (aged 0–19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998–2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned “ever/never” and “high/low exposed/unexposed” exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy. Results: 1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the “ever exposed” group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74). Conclusions: Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

2024 - Ozone Treatment for the Management of Caries in Primary Dentition: A Systematic Review of Clinical Studies [Articolo su rivista]
Veneri, F.; Filippini, T.; Consolo, U.; Vinceti, M.; Generali, L.
abstract

Dental caries in children is a frequent and debilitating condition, whose management is often challenging. The aim of this systematic review was to investigate the effectiveness of ozone applications for the treatment of caries in primary dentition. According to PRISMA guidelines, a systematic literature search was performed up to 6 January 2024. Clinical studies using ozone to treat caries of deciduous teeth were considered for inclusion. Out of the 215 records retrieved, seven studies were eventually included in the review, all of which used gaseous ozone. Four studies were judged at high risk of bias, two at low risk, and one of some concerns. The great heterogeneity of designs, outcomes, and protocols made it impossible to conduct a meta-analysis. Despite some limitations, the evidence yielded by the included studies suggests that ozone application, regardless of the protocol applied, is comparable to other interventions in terms of clinical outcomes and anti-bacterial activity, with no reported adverse effects and good patient acceptance. Therefore, ozone application may be a non-invasive approach to treat caries in primary dentition, especially in very young and poorly cooperative patients. Further standardized and rigorous studies are, however, needed to identify the best clinical protocols for this specific field.

2024 - Ozone therapy in dentistry: An overview of the biological mechanisms involved (Review) [Articolo su rivista]
Veneri, Federica; Filippini, Tommaso; Consolo, Ugo; Vinceti, Marco; Generali, Luigi
abstract

At low medically‑relevant concentrations, ozone serves as an oxidant with a wide spectrum of antimicrobial activity and the ability to promote healing and reduce inflammation. Despite providing therapeutic benefits in a range of diseases, certain adverse effects and contraindications of ozone treatment must be considered. These are primarily related to toxicity from inhalation and systemic types of administration and can be avoided by following relevant guidelines and recommendations. Ozone therapy has been implemented in a number of fields of dentistry and the most commonly used formulations for the oral cavity are gaseous ozone, ozonized water and ozonized oil. The biological mechanisms underlying the molecular effects of ozone have been increasingly reported, but currently remain largely unknown. The aim of the present review was to provide an overview of the mechanisms involved in ozone interaction with dental tissues. The present review focused on relevant evidence regarding the effect of ozone on dental tissues, including periodontal structures, dental cells, enamel and dentine, considering in vitro studies in addition to animal and human studies. A variety of biological mechanisms acting through multiple biochemical target pathways were reported to be responsible for the therapeutic effects of ozone. The main beneficial effects of ozone occurred in the following domains: antimicrobial activity, remineralization and microstructural changes of hard dental tissues, immunomodulation and biostimulation of dental and periodontal cells. Additional research could provide further insights into the use of ozone, increase its use for broader clinical applications and assist in the selection of targeted protocols.

2024 - Proposing new procedures for the management and prevention of foodborne diseases: An Italian experience [Articolo su rivista]
Di Federico, S.; Maione, D.; Cilloni, S.; Raschi, E.; Montanari, N.; Di Ruocco, S.; Rizzi, S.; Lionetti, F. P.; Bisaccia, E.; Poeta, A.; De Vita, D.; Bedeschi, E.; Vinceti, M.; Filippini, T.
abstract

Background and aim: Foodborne diseases are a public health issue with more than 4,000 outbreaks in 2021 in European Union countries and United Kingdom and their management is important for prevention and controls of outbreaks. Recently, new technological tools and strategies, including whole genome sequencing (WGS), have become available to allow the highest level of discrimination in the investigation of foodborne outbreak. In this study, we presented the updated procedure for assessment of foodborne disease in a community of a Northern-Italy region, Emilia-Romagna. Methods: In the Reggio Emilia National Health Service Local Unit (AUSL-RE), foodborne disease monitoring and control are managed by the following health services: public health and hygiene (SIP); hygiene of foodstuffs and nutrition (SIAN) and veterinary public health (SSPV) composing the developed MTA group (‘Gruppo Malattie Trasmesse da Alimenti’). Among the new tools being implemented, there is a shared computerized folder and new related managements procedures available to MTA members only, allocating information regarding any material useful to the MTA group. Results: The main new features of the new procedure are: information sharing in all phases of the management of the infectious episode, integration of the three services through the creation of the MTA group and updated criteria for procedure activation, and finally a dedicated training programme. Conclusions: Timely investigation, management and control of MTA outbreaks is essential for both health and economic reasons. The new features and procedures implemented in this Italian community may allow to identify rapidly the causes of a case or outbreak and better counteract their spread. (www.actabiomedica.it).

2024 - Residential exposure to magnetic fields from transformer stations and risk of childhood leukemia [Articolo su rivista]
Malavolti, M.; Malagoli, C.; Wise, L. A.; Poli, M.; Notari, B.; Taddei, I.; Fabbi, S.; Teggi, S.; Balboni, E.; Pancaldi, A.; Palazzi, G.; Vinceti, M.; Filippini, T.
abstract

Background: Several studies have documented an increased risk of leukemia among children exposed to magnetic fields from high-voltage power lines, with some evidence of dose-response relation. However, findings in some studies have been inconsistent, and data on the effects of different sources of exposure are lacking. In this study, we evaluated the relation of childhood leukemia risk to exposure to magnetic fields from transformer stations. Methods: We conducted a population-based case-control study in a pediatric population of two Northern Italian provinces of Modena and Reggio Emilia. We included 182 registry-identified childhood leukemia cases diagnosed during 1998-2019 and 726 population controls matched on sex, year of birth, and province of residence. We assessed exposure by calculating distance from childhood residence to the nearest transformer station within a geographical information system, computing disease odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for potential confounders. We evaluated exposure using two buffers (15 m and 25 m radius) and assessed two case groups: leukemia (all subtypes) and acute lymphoblastic leukemia (ALL). Results: Residing within 15 m of a transformer station (vs. ≥15 m) was not appreciably associated with risk of leukemia (all subtypes) or ALL. We found similar results using a less stringent exposure buffer (25 m). Among children aged ≥5 years, the adjusted ORs were 1.3 (95% CI 0.1-12.8) for leukemia and 1.3 (95% CI 0.1-12.4) for ALL using the 15 m buffer, while they were 1.7 (95% CI 0.4-7.0) for leukemia and 0.6 (95% CI 0.1-4.8) for ALL using the 25 m buffer. Conclusions: While we found no overall association between residential proximity to transformer stations and childhood leukemia, there was some evidence for elevated risk of childhood leukemia among children aged ≥5 years. Precision was limited by the low numbers of exposed children.

2024 - Safety of Acheta domesticus powder as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De , ; Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gómez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Neuhäuser-Berthold, M.; Siskos, A.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Azzollini, D.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on Acheta (A.) domesticus powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The main components of the NF are protein, fat and dietary fibre (chitin). The Panel notes that the concentration of contaminants in the NF depends on the occurrence levels of these substances in the insect feed. The Panel further notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The NF has a high protein content, although the true protein content is overestimated when using the nitrogen-to-protein conversion factor of 6.25 due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as food ingredient in a number of food products. The target population proposed by the applicant is the general population. Considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The panel notes that no safety concerns arise from the toxicological information of A. domesticus. The panel considers that the consumption of the NF might trigger primary sensitisation to A. domesticus proteins and may cause allergic reactions in subjects allergic to crustaceans, mites and molluscs. Additionally, allergens from the feed may end up in the NF. The panel concludes that the NF is safe under the proposed uses and use levels.

2024 - Safety of HelixComplex snail mucus (HSM) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Peláez, Carmen; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Magani, Maura; Muñoz, Alejandra; Rossi, Annamaria; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on HelixComplex Snail Mucus (HSM) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of snail mucus collected from Helix aspersa maxima and is proposed to be used by adults as a food supplement. The data provided by the applicant about the composition and stability of the NF together with the report of the subchronic toxicity study were overall considered unsatisfactory. The Panel noted inconsistencies in the reporting of the certificates of analysis and of the data on the subchronic toxicity provided by the applicant. Owing to these deficiencies, the Panel cannot establish a safe intake level of the NF. The Panel concludes that the safety of the NF has not been established.

2024 - Safety of ashitaba sap as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Prieto Maradona, Miguel; Neuhäuser‐berthold, Monika; Poulsen, Morten; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Glymenaki, Maria; Kouloura, Eirini; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on ashitaba sap as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Ashitaba sap is collected from harvested stems of Angelica keiskei plants. The principal constituents of the sap with regard to the safety assessment are chalcones (1%-2.25%) and furanocoumarins (< 0.01%). The applicant proposed to use the NF in food supplements at a maximum dose of 780 mg per day. The target population is adults excluding pregnant and lactating women. Taking into consideration the composition of the NF and the proposed uses, the composition of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study performed with the product as intended to be placed on the market (30% ashitaba sap powder and 70% cyclodextrins), the Panel establishes a safe dose of 0.5 mg/kg body weight (bw) per day for the product as it is intended to be placed on the market. For the target population, i.e. adults, this safe dose corresponds to 35 mg per day of the product as it is intended to be placed on the market and 137 mg per day of the NF, which is lower than the use level proposed by the applicant. The Panel concludes that the NF is safe for the target population at intake levels up to 137 mg per day.

2024 - Safety of glucosyl hesperidin as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Kouloura, E.; Matijevic, L.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on glucosyl hesperidin (GH) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF, which is produced from hesperidin and dextrin by enzymatic reactions, is a powder consisting mainly of monoglucosyl hesperidin (MGH) and unreacted hesperidin (flavonoid), which account in total for up to 92.8% (on dry basis) of the product. The applicant proposed to use the NF in specific drinks and food supplements leading to a maximum intake of up to 364 mg per day for adults. The target population is the general population, except for food supplements for which the proposed target population is children from 1 year onwards and adults. Taking into consideration the composition of the NF and the proposed uses, the consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study conducted with the NF, the Panel considers the NOAEL at the mid-dose group, i.e. ~ 1000 mg/kg body weight (bw) per day. By applying an uncertainty factor of 200, the resulting intake providing sufficient margin of exposure for humans would be 5 mg/kg bw per day. The available human intervention studies did not report clinically relevant changes in haematological or clinical chemistry parameters following the administration of GH/MGH at supplemental doses of up to 3 g/day for 12 weeks. Overall, the Panel considers that the margin of exposure (~ 200) between the intake of the NF at the proposed uses and use levels and the NOAEL from the 90-day study is sufficient. The Panel concludes that the NF, glucosyl hesperidin, is safe for the target population at the proposed uses and use levels.

2024 - Safety of isomaltulose syrup (dried) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Poulsen, Morten; Prieto Maradona, Miguel; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Ferreira da Costa, Lucien; Albert, Océane; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on isomaltulose syrup (dried) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of a mixture of mono- and disaccharides in powder form, mainly composed of isomaltulose (>= 75%) and trehalulose (< 13%). The applicant intends to use the NF as a replacement for sucrose already on the market. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. No absorption, distribution, metabolism and excretion (ADME) or toxicological data were provided for the NF. Instead, the safety of the NF was assessed based on literature data available on isomaltulose and mixtures of isomaltulose and trehalulose. In addition, considering the nature, compositional characterisation and production process of the NF, the Panel considered that such data were sufficient to conclude that the NF is as safe as sucrose.

2024 - Safety of magnesium l‐threonate as a novel food pursuant to regulation (EU) 2015/2283 and bioavailability of magnesium from this source in the context of Directive 2002/46/EC [Articolo su rivista]
Null, Null; Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De , ; Henauw, Stefaan; Hirsch‐ernst, Karen Ildico; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J.; Naska, Androniki; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aguilera‐gómez, Margarita; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; Siskos, Alexandros; van Loveren, Henk; Gelbmann, Wolfgang; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of magnesium l-threonate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of magnesium from this source in the context of Directive 2002/46/EC. The NF, produced by chemical synthesis, is intended to be used as new source for magnesium in food supplements at a maximum intake level of 3000 mg per day by adults, except for pregnant and lactating women. This dose corresponds to similar to 2730 mg l-threonate and 250 mg magnesium, which also corresponds to the UL for supplemental magnesium from readily dissociable magnesium salts. Based on results obtained from a dissociation study, two rat studies and one human trial, the Panel considers that magnesium is bioavailable from the NF. The NF may contain up to 1% oxalic acid. The Panel considers that an additional exposure to oxalic acid, that is up to 30 mg daily from the NF, is not to be of safety concern. The Panel concludes that the NF is not nutritionally disadvantageous. In 2008, the EFSA ANS Panel concluded that a human intake of l-threonate of 2700 mg per day is safe. This intake is similar to the maximum intake of l-threonate from the NF under the maximum proposed uses, and the NDA Panel concurs with the ANS Panel that this intake is safe. The Panel considers that there are no concerns regarding the genotoxicity of the NF. The Panel concludes that the NF, Mg l-threonate, is safe under the proposed conditions of use. The Panel concludes that the NF is a source from which magnesium is bioavailable.

2024 - Safety of vitamin D2 mushroom powder as a Novel food pursuant to Regulation (EU) 2015/2283 (NF 2020/2226) [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Gerazova-Efremova, K.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on vitamin D2 mushroom powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced from Agaricus bisporus mushroom powder that has been exposed to ultraviolet (UV) irradiation to induce the conversion of provitamin D2 (ergosterol) to vitamin D2 (ergocalciferol). The NF contains concentrations of vitamin D in the form of vitamin D2 in the range of 245–460 μg/g. The information provided on the production process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF as an ingredient in a variety of foods and beverages in amounts that result in either 1.2 or 2.4 μg vitamin D2 per 100 g or 100 mL of the food as consumed. The applicant also intends to add the NF in food supplements at a maximum of 15 μg vitamin D2/day for individuals above 1 year of age, as well as in foods for special medical purposes (FSMPs). The estimates for combined intake of vitamin D from the NF, the background diet and fortified foods, were below the ULs for vitamin D as established previously by the NDA Panel for children, adolescents and adults, i.e. 50 and 100 μg/day. The estimated combined vitamin D intake in infants (6–12 months) is also below the UL for vitamin D of 35 μg/day. The Panel considers that taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous for the proposed target population. The Panel concludes that the NF is safe under the proposed conditions of use.

2024 - Scientific Committee guidance on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments [Articolo su rivista]
More, S.; Bampidis, V.; Benford, D.; Bragard, C.; Hernandez-Jerez, A.; Bennekou, S. H.; Koutsoumanis, K.; Lambre, C.; Machera, K.; Mennes, W.; Mullins, E.; Nielsen, S. S.; Schlatter, J.; Schrenk, D.; Turck, D.; Younes, M.; Fletcher, T.; Greiner, M.; Ntzani, E.; Pearce, N.; Vinceti, M.; Vrijheid, M.; Georgiadis, M.; Gervelmeyer, A.; Halldorsson, T. I.
abstract

EFSA requested its Scientific Committee to prepare a guidance document on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments. The guidance document provides an introduction to epidemiological studies and illustrates the typical biases, which may be present in different epidemiological study designs. It then describes key epidemiological concepts relevant for evidence appraisal. This includes brief explanations for measures of association, exposure assessment, statistical inference, systematic error and effect modification. The guidance then describes the concept of external validity and the principles of appraising epidemiological studies. The customisation of the study appraisal process is explained including tailoring of tools for assessing the risk of bias (RoB). Several examples of appraising experimental and observational studies using a RoB tool are annexed to the document to illustrate the application of the approach. The latter part of this guidance focuses on different steps of evidence integration, first within and then across different streams of evidence. With respect to risk characterisation, the guidance considers how evidence from human epidemiological studies can be used in dose–response modelling with several different options being presented. Finally, the guidance addresses the application of uncertainty factors in risk characterisation when using evidence from human epidemiological studies.

2024 - Scientific Opinion on additional scientific data related to the safety of preparations of Rheum palmatum L., Rheum officinale Baill. and their hybrids, Rhamnus purshiana DC., Rhamnus frangula L. and Cassia senna L., submitted pursuant to Article 8(4) of Regulation (EC) No 1925/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Rossi, A.; Titz, A.; Fiolet, T.; Maciuk, A.
abstract

The Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the safety of plant preparations from the root or rhizome of Rheum palmatum L., Rheum officinale Baill. and their hybrids, from the bark of Rhamnus frangula L. and Rhamnus purshiana DC. and from the leaf or fruit of Cassia senna L., which have been placed under Union scrutiny in Part C of Annex III in accordance with Article 8(4) of Regulation (EC) No 1925/2006. The NDA Panel reviewed the additional scientific data submitted during the period of scrutiny and the public consultation by interested parties. The pertinent scientific data were in vitro and in vivo genotoxicity studies on the plant preparations under consideration. All the results of the genotoxicity studies on plant preparations were negative. However, the plant preparations that were tested in the submitted studies were not sufficiently characterised with respect to the content of total and individual hydroxyanthracene derivatives (HADs) and components other than HADs. The studies confirmed the presence of ■■■■■, known to be genotoxic in vivo, and ■■■■■, shown to be genotoxic in vitro. In line with the EFSA Scientific Committee statement on genotoxicity assessment of chemical mixtures, considering the presence of an in vivo genotoxic compound, the plant preparations used in these studies have to be considered of concern for genotoxicity. Thus, the safety of preparations containing HADs from the root or rhizome of Rheum palmatum L., Rheum officinale Baill. and their hybrids, from the leaf or fruit of Cassia senna L. and from the bark of Rhamnus frangula L. and Rhamnus purshiana DC. cannot be established based on the submitted studies.

2024 - Scientific opinion on the tolerable upper intake level for iron [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aggett, P.; Fairweather-Tait, S.; de SesmaisonsLecarre, A.; Fabiani, L.; Karavasiloglou, N.; Saad, R. M.; Sofroniou, A.; Titz, A.; Naska, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for iron. Systematic reviews were conducted to identify evidence regarding high iron intakes and risk of chronic diseases, adverse gastrointestinal effects and adverse effects of iron supplementation in infancy, young childhood and pregnancy. It is established that systemic iron overload leads to organ toxicity, but no UL could be established. The only indicator for which a dose–response could be established was black stools, which reflect the presence of large amounts of unabsorbed iron in the gut. This is a conservative endpoint among the chain of events that may lead to systemic iron overload but is not adverse per se. Based on interventions in which black stools did not occur at supplemental iron intakes of 20–25 mg/day (added to a background intake of 15 mg/day), a safe level of intake for iron of 40 mg/day for adults (including pregnant and lactating women) was established. Using allometric scaling (body weight0.75), this value was scaled down to children and adolescents and safe levels of intakes between 10 mg/day (1–3 years) and 35 mg/day (15–17 years) were derived. For infants 7–11 months of age who have a higher iron requirement than young children, allometric scaling was applied to the supplemental iron intakes (i.e. 25 mg/day) and resulted in a safe level of supplemental iron intake of 5 mg/day. This value was extended to 4–6 month-old infants and refers to iron intakes from fortified foods and food supplements, not from infant and follow-on formulae. The application of the safe level of intake is more limited than a UL because the intake level at which the risk of adverse effects starts to increase is not defined.

2024 - Scientific opinion on the tolerable upper intake level for preformed vitamin A and β-carotene [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Lietz, G.; Passeri, G.; Craciun, I.; Fabiani, L.; Horvath, Z.; Valtuena Martinez, S.; Naska, A.
abstract

Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and β-carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether β-carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 μg RE/day for adults. This UL applies to men and women, including women of child-bearing age, pregnant and lactating women and post-menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 μg RE/day (infants 4–11 months) and 2600 μg RE/day (adolescents 15–17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental β-carotene. The available data were not sufficient and suitable to characterise a dose–response relationship and identify a reference point; therefore, no UL could be established. There is no indication that β-carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing β-carotene. The use of supplemental β-carotene by the general population should be limited to the purpose of meeting vitamin A requirements.

2024 - Scientific opinion on the tolerable upper intake level for vitamin E [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Traber, M. G.; Vrolijk, M.; Bercovici, C. M.; de Sesmaisons Lecarre, A.; Fabiani, L.; Karavasiloglou, N.; Mendes, V.; Valtuena Martinez, S.; Naska, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for vitamin E. As α-tocopherol is recognised as the only essential form of vitamin E, the Panel restricted its evaluation to α-tocopherol. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of vitamin E, namely risk of impaired coagulation and bleeding, cardiovascular disease and prostate cancer. The effect on blood clotting and associated increased risk of bleeding is considered as the critical effect to establish an UL for vitamin E. No new evidence has been published that could improve the characterisation of a dose–response. The ULs for vitamin E from all dietary sources, which were previously established by the Scientific Committee on Food, are retained for all population groups, i.e. 300 mg/day for adults, including pregnant and lactating women, 100 mg/day for children aged 1–3 years, 120 mg/day for 4–6 years, 160 mg/day for 7–10 years, 220 mg/day for 11–14 years and 260 mg/day for 15–17 years. A UL of 50 mg/day is established for infants aged 4–6 months and a UL of 60 mg/day for infants aged 7–11 months. ULs apply to all stereoisomeric forms of α-tocopherol. ULs do not apply to individuals receiving anticoagulant or antiplatelet medications (e.g. aspirin), to patients on secondary prevention for CVD or to patients with vitamin K malabsorption syndromes. It is unlikely that the ULs for vitamin E are exceeded in European populations, except for regular users of food supplements containing high doses of vitamin E.

2024 - Selenium: A global contaminant of significant concern to environment and human health [Capitolo/Saggio]
Vinceti, Marco; Filippini, Tommaso; Biswas, Ashis; Michalke, Bernhard; Dhillon, Karaj S.; Naidu, Ravi
abstract

Selenium (Se) is one of the most interesting and controversial elements found in the environment. It has long attracted interest due to its strong toxicity and potential carcinogenicity, while more recently it garnered interest as an essential nutrient, as a cofactor of selenoproteins, and due to the claim of a beneficial effect against cancer and other chronic diseases, which was recently found to be unwarranted. Selenium is ubiquitous in the environment, being present particularly in rocks, soils, combustion sources, such as smoking and industrial emissions, and water bodies, and therefore living organisms can be overly exposed to it. Selenium is found in several valence states and organic and inorganic compounds, and exposure is generally done by determining overall Se, its species and the selenoproteins in environmental and biological samples. Examples are serum and plasma, urine, hair and nails, and cerebrospinal fluid Se and Se species concentrations. The environmental effects and health outcomes attributable to both Se deficiency and excess, in animals and humans, have been the subject of a large number of studies, and attracted strong interest in environmental sciences and environmental health, also fueling considerable debate. While little evidence of adverse effects of Se deficiency has been detected so far, except for a cardiomyopathy described in some parts of China, a number of serious effects have been reported or suggested by human and animal studies, particularly those carried out in seleniferous areas and by those with experimental design, such as randomized controlled trials. Legislation and recommendations to control Se exposure and avoid the risk of overexposure widely differ throughout the world, and most of them need to be updated taking into account the most recent epidemiological and toxicological evidence. This is particularly due to the toxic effects on human health of even unexpectedly small doses of Se and some selenoproteins, such as type 2 diabetes, dermatological alterations, liver toxicity, endocrine alterations, and neurological disease. Due to the potential contamination of the environment, particularly soil, food, and water with excessive amounts of Se, effective remediation approaches and technologies are being devised and need to be implemented.

2024 - The key role of public health in renovating Italian biomedical doctoral programs [Articolo su rivista]
Palandri, Lucia; Urbano, Teresa; Pezzuoli, Carla; Miselli, Francesca; Caraffi, Riccardo; Filippini, Tommaso; Bargellini, Annalisa; Righi, Elena; Mazzi, Davide; Vigezzi, Giacomo Pietro; Odone, Anna; Marmiroli, Sandra; Boriani, Giuseppe; Vinceti, Marco
abstract

Background: A key renovation of doctoral programs is currently ongoing in Italy. Public health and its competencies may play a pivotal role in high-level training to scientific research, including interdisciplinary and methodological abilities. Methods: As a case study, we used the ongoing renovation of the Clinical and Experimental Medicine doctoral program at the University of Modena and Reggio Emilia. We focused on how the program is designed to meet national requirements as well as students' needs, thus improving educational standards for scientific research in the biomedical field, and on the specific contribution of public health and epidemiology in such an effort. Results: The renovation process of doctoral programs in Italy, with specific reference to the biomedical field, focuses on epidemiologic-statistical methodology, ethics, language and communication skills, and open science from an interdisciplinary and international perspective. In the specific context of the doctoral program assessed in the study and from a broader perspective, public health appears to play a key role, taking advantage of most recent methodological advancements, and contributing to the renovation of the learning process and its systematic quality monitoring. Conclusions: From a comparative assessment of this case study and Italian legislation, the key role of public health has emerged in the renovation process of doctoral programs in the biomedical field.

2024 - Trends in Hospital Admissions for Patients with Amyotrophic Lateral Sclerosis: Insights from a Retrospective Cohort Study in a Province in Northern Italy [Articolo su rivista]
Gianferrari, G.; Zucchi, E.; Martinelli, I.; Simonini, C.; Fini, N.; Ferro, S.; Mercati, A.; Ferri, L.; Filippini, T.; Vinceti, M.; Mandrioli, J.
abstract

: ALS is characterized by a highly heterogeneous course, ranging from slow and uncomplicated to rapid progression with severe extra-motor manifestations. This study investigated ALS-related hospitalizations and their connection to clinical aspects, comorbidities, and prognosis. We performed a retrospective cohort study including patients residing in Modena, Italy, newly diagnosed between 2007 and 2017 and followed up until 31 December 2022. Data were obtained from the Emilia Romagna ALS registry, regional hospitals, and medical records. Among the 249 patients, there were 492 hospital admissions, excluding those for diagnostic purposes; 63% of the patients had at least one hospitalization post-diagnosis, with an average stay of 19.90 ± 23.68 days. Younger patients were more likely to be hospitalized multiple times and experienced longer stays (44.23 ± 51.71 days if <65 years; 26.46 ± 36.02 days if older, p < 0.001). Patients who were hospitalized at least once more frequently underwent gastrostomy (64.97%) or non-invasive (66.24%) and invasive (46.50%) ventilation compared to those never hospitalized (21.74%, 31.52%, 13.04%, respectively, p < 0.001 for all). Emergency procedures led to longer hospitalizations (62.84 ± 48.91 days for non-invasive ventilation in emergencies vs. 39.88 ± 46.46 days electively, p = 0.012). Tracheostomy-free survival was not affected by hospitalizations. In conclusion, younger ALS patients undergo frequent and prolonged hospitalizations, especially after emergency interventions, although these do not correlate with reduced survival.

2024 - ‘Citicoline’ and support of the memory function: Evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Fiolet, T.; Siani, A.
abstract

Following an application from Egde Pharma Sp. z o.o, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Poland, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to citicoline and memory. The Panel considers that the food, citicoline (cytidine 5-diphosphocholine, CDP-Choline) inner salt, is sufficiently characterised. Improvement, maintenance or reduced loss of memory is a beneficial physiological effect for middle-aged or elderly adults encountering age-associated subjective memory impairment. The applicant identified three pertinent human intervention studies in healthy individuals that investigated the effect of citicoline on memory. In weighing the evidence, the Panel took into account that only one randomised controlled trial in healthy participants showed a beneficial effect of citicoline on episodic memory when consumed at doses of 500 mg/day for 12 weeks, whereas this effect has not been observed in another study using citicoline at doses of 1 g/day for 3 months or supported by data obtained in patients with dementia using doses of 1 g/day for 12 weeks and 12 months. No convincing evidence of a plausible mechanism by which citicoline or any of its components (in addition to their endogenous synthesis) could exert an effect on memory in humans has been provided. The Panel concludes that a cause-and-effect relationship has not been established between the consumption of citicoline (CDP-Choline) inner salt and improvement, maintenance or reduced loss of memory in middle-aged or elderly adults encountering age-associated subjective memory impairment.

2023 - A potential role for zinc to enhance treatment for COVID-19? [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Fairweather-Tait, Susan
abstract

2023 - Alcohol Intake and Blood Pressure Levels: A Dose-Response Meta-Analysis of Nonexperimental Cohort Studies [Articolo su rivista]
Di Federico, Silvia; Filippini, Tommaso; Whelton, Paul K; Cecchini, Marta; Iamandii, Inga; Boriani, Giuseppe; Vinceti, Marco
abstract

Background: Alcohol consumption may increase blood pressure but the details of the relationship are incomplete, particularly for the association at low levels of alcohol consumption, and no meta-analyses are available for nonexperimental cohort studies. Methods: We performed a systematic search of longitudinal studies in healthy adults that reported on the association between alcohol intake and blood pressure. Our end points were the mean differences over time of systolic (SBP) and diastolic blood pressure (DBP), plotted according to baseline alcohol intake, by using a dose-response 1-stage meta-analytic methodology. Results: Seven studies, with 19 548 participants and a median follow-up of 5.3 years (range, 4-12 years), were included in the analysis. We observed a substantially linear positive association between baseline alcohol intake and changes over time in SBP and DBP, with no suggestion of an exposure-effect threshold. Overall, average SBP was 1.25 and 4.90 mm Hg higher for 12 or 48 grams of daily alcohol consumption, compared with no consumption. The corresponding differences for DBP were 1.14 and 3.10 mm Hg. Subgroup analyses by sex showed an almost linear association between baseline alcohol intake and SBP changes in both men and women, and for DBP in men while in women we identified an inverted U-shaped association. Alcohol consumption was positively associated with blood pressure changes in both Asians and North Americans, apart from DBP in the latter group. Conclusions: Our results suggest the association between alcohol consumption and SBP is direct and linear with no evidence of a threshold for the association, while for DBP the association is modified by sex and geographic location.

2023 - Alcohol intake and risk of hypertension: a systematic review and dose-response meta-analysis of cohort studies [Abstract in Rivista]
Cecchini, M.; Di Federico, S.; Iamandii, I.; Filippini, T.; Vinceti, M.
abstract

2023 - Appethyl® and reduction of body weight: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Fiolet, T.; Siani, A.
abstract

Following an application from Greenleaf Medical AB, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Sweden, the EFSA Panel on Nutrition, Novel Foods and Food allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Appethyl® and reduction of body weight. Appethyl® is an aqueous extract from spinach leaves standardised by the manufacturing process and its lipase/colipase inhibition capacity in vitro. The Panel considers that the food is sufficiently characterised. A reduction in body weight is a beneficial physiological effect for overweight/obese individuals. The applicant identified a total of three human intervention studies that investigated the effects of Appethyl® on body weight as being pertinent to the claim. In weighing the evidence, the Panel took into account that Appethyl® (5 g/day for 12 weeks) had no effect on body weight as compared to placebo under minimal dietary counselling and moderate physical activity, and that no beneficial physiological effects are to be expected for the target population of overweight/obese individuals from the weight loss that could be attributed to the intervention with Appethyl® under predefined energy restriction and moderate physical activity. The Panel also considered that the effect of Appethyl® (5 g/day for 24 weeks) on body weight maintenance after initial weight loss shown in one study has not been replicated in different settings, which questions the external validity of the results, and that no evidence was provided for a plausible mechanism by which daily consumption of Appethyl® could exert a sustained effect on body weight in humans. The Panel concludes that a cause-and-effect relationship has not been established between the consumption of Appethyl® and a reduction of body weight under the conditions of use proposed by the applicant.

2023 - Artificial light at night and night-shift work: Emerging threats for human health [Articolo su rivista]
Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

2023 - Association between metals and metalloids with cognitive status in Mild Cognitive Impairment subjects [Abstract in Rivista]
Urbano, T; Filippini, T; Carbone, C; Chiari, A; Marti, A; Zamboni, G; Michalke, B; Vinceti, M
abstract

2023 - Availability of open data related to COVID-19 epidemic in Italy [Articolo su rivista]
Di Federico, S; Filippini, T; Marchesi, C; Vinceti, M
abstract

Since the beginning of the COVID-19 outbreak in Italy, health authorities have released epidemiologic data about this disease. These data were the most important sources of information which were periodically updated and analyzed by researchers to predict the spread of the epidemic. However, comprehensive and timely data on the evolution of COVID-19 have not always been made available to researchers and physicians.

2023 - Cadmium and risk of cardiovascular disease and stroke: a systematic review and dose-response meta-analysis [Abstract in Rivista]
Verzelloni, Pietro; Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

2023 - Cadmium exposure and hypertension: a systematic review and a dose-response meta-analysis [Abstract in Rivista]
Giuliano, V.; Vinceti, M.; Filippini, T.
abstract

Background and Objective: Cadmium (Cd) is a silvery white, malleable metal present in trace amounts in the Earths crust, air and water. Its name derives from that of the city of Cadmo, near Thebes, where it was extracted in antiquity. This heavy metal reacts easily with zinc and to a lesser extent with lead forming various compounds. The main routes of exposure for humans are diet and inhalation. Breathing low levels of Cd for many years (e.g. smokers) or consuming food and water contaminated at levels normally present in the environment (chronic exposure) can cause its accumulation in the body and lead to various pathological conditions, including hypertension. Our aim is to quantify the increase in blood pressure following chronic Cd exposure. Methods: The protocol of the review has been submitted in PROSPERO. The literature search has been carried out on 3 different databases: PubMed, Web of Science and Embase. We used as mesh-terms: “hypertension”, “cadmium” and “blood pressure”. We defined the following inclusion criteria according to PICOS statement: P = healthy adult population, I = exposure to cadmium, C = subjects not exposed to cadmium, O = variation of arterial blood pressure in relation to the cadmium dose to which one is exposed, S = observational studies (cohort, cross-sectional or case-control). We also plan to perform a dose-response meta-analysis whenever possible. Results: We found 678 articles, of which 95 duplicates. After removing these duplicates, we are scanning the abstract and full-text of the remaining 583 papers. Conclusions: The study is currently ongoing and its results will be presented at the Congress.

2023 - Cardiac Surgery in Jehovah's Witnesses Patients and Association With Peri-Operative Outcomes: A Systematic Review and Meta-Analysis [Articolo su rivista]
Vitolo, M.; Mei, D. A.; Cimato, P.; Bonini, N.; Imberti, J. F.; Cataldo, P.; Menozzi, M.; Filippini, T.; Vinceti, M.; Boriani, G.
abstract

Background: Strategies for blood conservation, coupled with a careful preoperative assessment, may be applied to Jehovah's Witnesses (JW) patients who are candidates for cardiac surgery interventions. There is a need to assess clinical outcomes and safety of bloodless surgery in JW patients undergoing cardiac surgery. Methods: We performed a systematic review and meta-analysis of studies comparing JW patients with controls undergoing cardiac surgery. The primary endpoint was short-term mortality (in-hospital or 30-day mortality). Peri-procedural myocardial infarction, re-exploration for bleeding, pre-and postoperative Hb levels and cardiopulmonary bypass (CPB) time were also analyzed. Results: A total of 10 studies including 2,302 patients were included. The pooled analysis showed no substantial differences in terms of short-term mortality among the two groups (OR 1.13, 95% CI 0.74-1.73, I2=0%). There were no differences in peri-operative outcomes among JW patients and controls (OR 0.97, 95% CI 0.39-2.41, I2=18% for myocardial infarction; OR 0.80, 95% CI 0.51-1.25, I2=0% for re-exploration for bleeding). JW patients had a higher level of preoperative Hb (Standardized Mean Difference [SMD] 0.32, 95% CI 0.06-0.57) and a trend toward a higher level of postoperative Hb (SMD 0.44, 95% CI -0.01-0.90). A slightly lower CPB time emerged in JWs compared with controls (SMD -0.11, 95% CI -0.30-0.07). Conclusions: JW patients undergoing cardiac surgery, with avoidance of blood transfusions, did not have substantially different peri-operative outcomes compared with controls, with specific reference to mortality, myocardial infarction, and re-exploration for bleeding. Our results support the safety and feasibility of bloodless cardiac surgery, applying patient blood management strategies.

2023 - Choline and contribution to normal liver function of the foetus and exclusively breastfed infants: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Fiolet, T.; Siani, A.
abstract

Following an application from Procter & Gamble BV pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to choline and contribution to normal liver function of the foetus and exclusively breastfed infant. The scope of the application was proposed to fall under a health claim referring to children's development and health. The Panel considers that choline is sufficiently characterised. The claimed effect proposed by the applicant is contribution ‘to normal foetal and infant development, especially liver’. The proposed target population is ‘unborn fetuses and breastfed infants’. Choline is involved in the structure of cell membranes, cell signalling, metabolism and transport of lipids and cholesterol and neurotransmitter synthesis. Although choline can be synthesised de novo by the human body, depletion-repletion studies in humans show that low choline intake leads to liver dysfunction and muscle damage, which are reverted by the administration of dietary choline. For these functions, de novo synthesis of choline by the human body is insufficient and choline must be obtained from dietary sources. No human studies have addressed the effect of low maternal dietary choline intake on liver function in the fetus or exclusively breastfed infants. However, the Panel considers that the biological role of choline in normal liver function and dietary choline being essential for the function applies to all ages, including fetus and infants. The Panel concludes that a cause and effect relationship has been established between the intake of choline by pregnant and lactating women and contribution to normal liver function of the fetus and exclusively breastfed infants.

2023 - Comment on “Relation of fruit juice with adiposity and diabetes depends on how fruit juice is defined: a re-analysis of the EFSA draft scientific opinion on the tolerable upper intake level for dietary sugars” by Chen et al. 2023 [Articolo su rivista]
Valtuena Martinez, S.; Turck, D.; Craciun, I.; Vinceti, M.
abstract

2023 - Does fluoride exposure affect thyroid function? A systematic review and dose-response meta-analysis [Articolo su rivista]
Iamandii, Inga; De Pasquale, Lisa; Giannone, Maria Edvige; Veneri, Federica; Generali, Luigi; Consolo, Ugo; Birnbaum, Linda S; Castenmiller, Jacqueline; Halldorsson, Thorhallur I; Filippini, Tommaso; Vinceti, Marco
abstract

Introduction: Fluoride exposure may have various adverse health effects, including affecting thyroid function and disease risk, but the pattern of such relation is still uncertain. Methods: We systematically searched human studies assessing the relation between fluoride exposure and thyroid function and disease. We compared the highest versus the lowest fluoride category across these studies, and we performed a one-stage dose-response meta-analysis for aggregated data to explore the shape of the association. Results: Most retrieved studies (27 of which with a cross-sectional design) were conducted in Asia and in children, assessing fluoride exposure through its concentrations in drinking water, urine, serum, or dietary intake. Twenty-four studies reported data on thyroid function by measuring thyroid-related hormones in blood (mainly thyroid-stimulating-hormone - TSH), 9 reported data on thyroid disease, and 4 on thyroid volume. By comparing the highest versus the lowest fluoride categories, overall mean TSH difference was 1.05 μIU/mL. Dose-response curve showed no change in TSH concentrations in the lowest water fluoride exposure range, while the hormone levels started to linearly increase around 2.5 mg/L, also dependending on the risk of bias of the included studies. The association between biomarkers of fluoride exposure and TSH was also positive, with little evidence of a threshold. Evidence for an association between fluoride exposure and blood concentrations of thyroid hormones was less evident, though there was an indication of inverse association with triiodothyronine. For thyroid disease, the few available studies suggested a positive association with goiter and with hypothyroidism in both children and adults. Conclusions: Overall, exposure to high-fluoride drinking water appears to non-linearly affect thyroid function and increase TSH release in children, starting above a threshold of exposure, and to increase the risk of some thyroid diseases.

2023 - Effect of tauroursodeoxycholic acid on survival and safety in amyotrophic lateral sclerosis: a retrospective population-based cohort study [Articolo su rivista]
Zucchi, E.; Musazzi, U. M.; Fedele, G.; Martinelli, I.; Gianferrari, G.; Simonini, C.; Fini, N.; Ghezzi, A.; Caputo, M.; Sette, E.; Vacchiano, V.; Zinno, L.; Anceschi, P.; Canali, E.; Vinceti, M.; Ferro, S.; Mandrioli, J.; Ferri, L.; Gessani, A.; Liguori, R.; Cortelli, P.; Michelucci, R.; Salvi, F.; Bartolomei, I.; Borghi, A. M.; Zini, A.; Rinaldi, R.; Tugnoli, V.; Pugliatti, M.; Codeluppi, L.; Valzania, F.; Stragliati, F.; Nuredini, A.; Romano, S.; D'Orsi, A.; Parrino, L.; Medici, D.; Pilurzi, G.; Terlizzi, E.; Guidetti, D.; De Pasqua, S.; Santangelo, M.; De Massis, P.; Gizzi, M.; Casmiro, M.; Querzani, P.; Morresi, S.; Vitiello, M.; Longoni, M.; Patuelli, A.; Malagu, S.; Bianchi, F.; Dossi, M. C.; Ganino, C.
abstract

Background: Oral tauroursodeoxycholic acid (TUDCA) is a commercial drug currently tested in patients with amyotrophic lateral sclerosis (ALS) both singly and combined with sodium phenylbutyrate. This retrospective study aimed to investigate, in a real-world setting, whether TUDCA had an impact on the overall survival of patients with ALS who were treated with this drug compared to those patients who received standard care only. Methods: This propensity score–matched study was conducted in the Emilia Romagna Region (Italy), which has had an ALS regional registry since 2009. Out of 627 patients with ALS diagnosed from January 1st, 2015 to June 30th, 2021 and recorded in the registry with available information on death/tracheostomy, 86 patients took TUDCA and were matched in a 1:2 ratio with patients who received only usual care according to age at onset, sex, phenotype, diagnostic latency, ALS Functional Rating Scale-Revised (ALSFRS-R) at first visit, disease progression rate at first visit, and BMI at diagnosis. The primary outcome was survival difference (time from onset of symptoms to tracheostomy/death) between TUDCA exposed and unexposed patients. Findings: A total of 86 patients treated with TUDCA were matched to 172 patients who did not receive treatment. TUDCA-exposed patients were stratified based on dosage (less than or equal to 1000 mg/day or greater) and duration (less than or equal to 12 months or longer) of treatment. The median overall survival was 49.6 months (95% CI 41.7–93.5) among those treated with TUDCA and 36.2 months (95% CI 32.7–41.6) in the control group, with a reduced risk of death observed in patients exposed to a higher dosage (defined as ≥ 1000 mg/day) of TUDCA (HR 0.56; 95% CI 0.38–0.83; p = 0.0042) compared to both the control group and those with lower TUDCA dosages (defined as < 1000 mg/day). TUDCA was generally well-tolerated, except for a minority of patients (n = 7, 8.1%) who discontinued treatment due to side effects, primarily gastrointestinal and mild in severity; only 2 adverse events required hospital access but resolved without sequelae. Interpretation: In this population-based exploratory study, patients with ALS who were treated with TUDCA may have prolonged survival compared to patients receiving standard care only. Additional prospective randomized studies are needed to confirm the efficacy and safety of this drug. Funding: Emilia-Romagna Region.

2023 - Effects of selenium supplementation on blood lipids: a systematic review and a dose-response meta-analysis [Abstract in Rivista]
Fiore, G.; Vinceti, M.; Filippini, T.
abstract

Background and Objective: Selenium is a trace element with both nutritional and toxicological properties, depending on the dose and the chemical species. Several studies have shown an association between selenium exposure and cardiovascular risk, focusing on lipid profile and blood pressure. In particular, there is an indication that selenium overexposure may raise the risk of dyslipidemia, but uncertainties still apply to such evidence. The aim of our study is to assess the relation between selenium exposure and the effects on lipid profile in experimental human studies. Material and Methods: The protocol registration in PROSPERO has been submitted for publication. We conducted a preliminary literature search in the following databases: PubMed, Web of Science, Embase and Cochrane Library with no language restrictions. We used MeSH terms and keywords related to “selenium”, “lipid profile”, “LDL”, “VLDL”, “HDL”, “cholesterol”, and “randomized clinical trials”. We defined the following inclusion criteria according the PICOS statement: adult population, exposure to selenium through supplementation as specific difference between intervention and control groups and evaluation of internal exposure using blood biomarker (e.g. serum/plasma levels), assessment of lipid profile as outcome, randomized clinical controlled trials as study design. Results: In the preliminary search, we found 865 records. After duplicate removal, 622 articles were screened by title and abstract. At this stage, we discarded 565 articles, and we reviewed the full-texts of the remaining 56 records to confirm eligibility. Five articles were additionally found through citation chasing techniques and added to the review. We excluded 29 articles due to missing data about outcome of interest. In total, 27 studies met the inclusion criteria and were could be included. Conclusions: The study is currently ongoing and results will be presented during the Congress.

2023 - Exposure to alcohol and risk of dementia: a systematic review and dose-response meta-analysis [Abstract in Rivista]
Rossetti, A.; Mazzoleni, E.; Filippini, T.; Vinceti, M.
abstract

Background: The relation between alcohol intake and cognitive function risk has been established, especially for high levels of exposure. Conversely, the effects at low-moderate levels is still debated and the aim of this study is to characterize the dose-response relation between different degree of alcohol intake and cognitive decline and dementia. Methods: We carried out a comprehensive literature search in PubMed and Embase online databases for cohort and case-control studies investigating the association between alcohol intake on cognitive function. For study identification and selection, we will use the Rayyan online open-source program. Whenever possible, we will conduct a dose-response meta-analysis using the new one stage cubic spline mixed-effects model in order to evaluate the nonlinear relation of such association. According to inclusion criteria, we selected studies on human population with no major comorbidities (e.g. CVD, diabetes, immunological deficits and cancer) and without a diagnosis of dementia and MCI at baseline. Further exclusion criteria were binge drinking and alcoholism, in addition to articles in which no exposure dose was reported. Results: Out of total 3676 articles, we excluded 951 duplicates and after title and abstract screening, we further excluded 2496 records to be subjected to a more accurate analysis. After full-text evaluation, of the 266 resulting articles, we identified 20 eligible studies, with alcohol intake ranging from 0 to 50.4 g alcohol/day and 0 to 4.8 drinks/day. Conclusions: The study is currently ongoing; data extraction and prediction of the database for the dose-response meta- analysis will be presented at the Congress.

2023 - Factors predicting disease progression in C9ORF72 ALS patients [Articolo su rivista]
Mandrioli, Jessica; Zucchi, Elisabetta; Martinelli, Ilaria; Van der Most, Laura; Gianferrari, Giulia; Moglia, Cristina; Manera, Umberto; Solero, Luca; Vasta, Rosario; Canosa, Antonio; Grassano, Maurizio; Brunetti, Maura; Mazzini, Letizia; De Marchi, Fabiola; Simonini, Cecilia; Fini, Nicola; Tupler, Rossella; Vinceti, Marco; Chiò, Adriano; Calvo, Andrea
abstract

Objective To unveil clinical features, comorbidities, disease progression and prognostic factors in a population-based cohort of ALS patients carrying C9ORF72 expansion (C9 + ALS). Methods This is a retrospective observational study on ALS patients residing in Emilia Romagna and Piedmont-Valle D'Aosta regions whose data are available through population based registers. We analysed patients who underwent genetic testing, focusing on C9 + ALS subgroup. Results Among 2204 genotyped patients of the two registers, 150 were C9 + ALS. In comparison with patients without mutation, a higher proportion of family history (12.85 vs 68%, p < 0.001) and frontotemporal dementia (3.93% vs 10.67%, p < 0.001) was detected in C9 + ALS. C9 + ALS presented a faster disease progression as measured by monthly decline in ALS Functional Rating Scale-Revised (1.86 +/- 3.30 vs 1.45 +/- 2.35, p < 0.01) and in forced vital capacity (5.90 +/- 5.24 vs 2.97 +/- 3.47, p < 0.01), a shorter diagnostic delay (8.93 +/- 6.74 vs 12.68 +/- 12.86 months, p < 0.01) and earlier onset (58.91 +/- 9.02 vs 65.04 +/- 11.55 years, p < 0.01). Consistently, they reached death or tracheostomy earlier than other patients (31 vs 37 months, HR = 1.52, 95% C.I. 1.27-1.82, p < 0.001). With respect to other genotyped patients, C9 + ALS patients did not present a significantly higher prevalence of concomitant diseases. Independent prognostic factors of survival of C9 + ALS included sex, age, progression rate, presence of frontotemporal dementia and thyroid disorders, with the latter being associated with prolonged ALS survival (43 vs 29 months, HR = 0.42, 95% C.I. 0.24-0.74, p = 0.003). Conclusion Even in the context of a more aggressive disease, C9 + ALS had a longer survival in presence of thyroid disorders. This finding may suggest protective pathogenic pathways in C9 + ALS to be explored, looking for therapeutic strategies to slow disease course.

2023 - Fluoride Exposure and ADHD: A Systematic Review of Epidemiological Studies [Articolo su rivista]
Fiore, Gianluca; Veneri, Federica; Di Lorenzo, Rosaria; Generali, Luigi; Vinceti, Marco; Filippini, Tommaso
abstract

Background and objectives: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder characterized by two dimensions: inattentiveness and hyperactivity/impulsivity. ADHD may be the result of complex interactions between genetic, biological and environmental factors possibly including fluoride exposure. Materials and methods: A literature search was performed on 31 March 2023 in the following databases: PubMed, Embase and Web of Science. We defined the following inclusion criteria according to the PECOS statement: a healthy child and adolescent population (P), fluoride exposure of any type (E), comparison with low or null exposure (C), ADHD spectrum disorder (O), and ecological, cross-sectional, case-control and cohort studies (S). Results: We found eight eligible records corresponding to seven different studies investigating the effect of fluoride exposure on children and adolescents. One study had a cohort design and one a case-control one, while five were cross-sectional. Only three studies applied validated questionnaires for the purpose of ADHD diagnosis. As regards exposure assessment, levels of fluoride in urine and tap water were, respectively used in three and two studies, while two used both. Three studies reported a positive association with ADHD risk, all assessing exposure through fluoride levels. By using urinary fluoride, conversely, a positive correlation with inattention, internalizing symptoms, cognitive and psychosomatic problems was found in three studies, but no relation was found in the other one. Conclusions: The present review suggests that early exposure to fluoride may have neurotoxic effects on neurodevelopment affecting behavioral, cognitive and psychosomatic symptoms related to ADHD diagnosis. However, due to the heterogeneity of the studies included, current evidence does not allow to conclusively confirm that fluoride exposure is specifically linked to ADHD development.

2023 - Fluoride Exposure and Skeletal Fluorosis: a Systematic Review and Dose-response Meta-analysis [Articolo su rivista]
Veneri, F.; Iamandii, I.; Vinceti, M.; Birnbaum, L. S.; Generali, L.; Consolo, U.; Filippini, T.
abstract

Purpose of Review: We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for dose-response modeling. Recent Findings: Skeletal fluorosis, a major health issue that is endemic in some regions, affects millions of people worldwide. However, data regarding the dose-response relation between fluoride exposure and SF are limited and outdated. Summary: We included twenty-three studies in the meta-analysis. When comparing the highest versus the lowest fluoride category, the summary risk ratio (RR) for SF prevalence was 2.05 (95% CI 1.60; 2.64), with a value of 2.73 (95% CI 1.92; 3.90) for drinking water and 1.40 (95% CI 0.90; 2.17) for urinary fluoride. The RR by the risk of bias (RoB) was 2.37 (95% CI 1.56; 3.58) and 1.78 (95% CI 1.34; 2.36) for moderate and high RoB studies, respectively. The dose-response curve based on a one-stage cubic spline regression model showed an almost linear positive relation between exposure and SF occurrence starting from relatively low concentrations up to 5 mg/L and 2.5 mg/L, respectively, for water and urinary fluoride, with no substantial increase above this threshold. The RR for developing moderate-severe forms increases at 5.00 mg/L and 2.5 mg/L of water and urinary fluoride, respectively. Better-quality studies are needed to confirm these results, but greater attention should be given to water fluoride levels to prevent SF, in addition to the other potential adverse effects of fluoride exposure.

2023 - Fluoride exposure and cognitive neurodevelopment: Systematic review and dose-response meta-analysis [Articolo su rivista]
Veneri, Federica; Vinceti, Marco; Generali, Luigi; Giannone, Maria Edvige; Mazzoleni, Elena; Birnbaum, Linda S; Consolo, Ugo; Filippini, Tommaso
abstract

: Many uncertainties still surround the possible harmful effect of fluoride exposure on cognitive neurodevelopment in children. The aim of this systematic review and meta-analysis was to characterize this relation through a dose-response approach, by comparing the intelligence quotient (IQ) scores in the highest versus the lowest fluoride exposure category with a random-effects model, within a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Out of 1996 potentially relevant literature records, 33 studies were eligible for this review, 30 of which were also suitable for meta-analysis. The summary mean difference of IQ score, comparing highest versus lowest fluoride categories and considering all types of exposure, was -4.68 (95% confidence interval-CI -6.45; -2.92), with a value of -5.60 (95% CI -7.76; -3.44) for drinking water fluoride and -3.84 (95% CI -7.93; 0.24) for urinary fluoride. Dose-response analysis showed a substantially linear IQ decrease for increasing water fluoride above 1 mg/L, with -3.05 (95% CI -4.06; -2.04) IQ points per 1 mg/L up to 2 mg/L, becoming steeper above such level. A weaker and substantially linear decrease of -2.15 (95% CI -4.48; 0.18) IQ points with increasing urinary fluoride emerged above 0.28 mg/L (approximately reflecting a water fluoride content of 0.7 mg/L). The inverse association between fluoride exposure and IQ was particularly strong in the studies at high risk of bias, while no adverse effect emerged in the only study judged at low risk of bias. Overall, most studies suggested an adverse effect of fluoride exposure on children's IQ, starting at low levels of exposure. However, a major role of residual confounding could not be ruled out, thus indicating the need of additional prospective studies at low risk of bias to conclusively assess the relation between fluoride exposure and cognitive neurodevelopment.

2023 - GRADE guidance 38: updated guidance for rating up certainty of evidence due to a dose-response gradient [Articolo su rivista]
Murad, M Hassan; Verbeek, Jos; Schwingshackl, Lukas; Filippini, Tommaso; Vinceti, Marco; Akl, Elie A; Morgan, Rebecca L; Mustafa, Reem A; Zeraatkar, Dena; Senerth, Emily; Street, Renee; Lin, Lifeng; Falck-Ytter, Yngve; Guyatt, Gordon; Schünemann, Holger J
abstract

Introduction: This updated guidance from the Grading of Recommendations Assessment, Development, and Evaluation addresses rating up certainty of evidence due to a dose-response gradient (DRG) observed in synthesis of intervention and exposure studies. Study design and setting: This guidance was developed using iterative discussions and consensus in multiple meetings and was presented to attendees of the Grading of Recommendations Assessment, Development, and Evaluation Working Group meeting for feedback in November 2022 and for final approval in May 2023. Results: The guidance consists of two steps. The first is to determine whether the DRG is credible. We describe five items for assessing credibility: a) is DRG identified using a proper analytical approach; b) is confounding the cause of the DRG; c) is there serious concern about ecological bias; d) is the DRG consistent across studies; and e) is there indirect evidence supporting the DRG. The first two of these items are the most critical. If the DRG was judged to be credible, then the second step is to apply the DRG domain and consider rating up, but only by one level due to the concern about residual confounding. Conclusion: Systematic review authors should only rate up certainty in evidence when a DRG is deemed credible.

2023 - Healthy dietary patterns and cognitive status in Mild Cognitive Impairment subjects [Abstract in Rivista]
Urbano, T; Filippini, T; Carbone, C; Malavolti, M; Marti, A; Agnoli, C; Sieri, S; Chiari, A; Zamboni, G; Vinceti, M
abstract

2023 - Human serum albumin-bound selenium (Se-HSA) in serum and its correlation with other selenium species [Articolo su rivista]
Filippini, Tommaso; Urbano, Teresa; Grill, Peter; Malagoli, Carlotta; Ferrari, Angela; Marchesi, Cristina; Natalini, Nicoletta; Michalke, Bernhard; Vinceti, Marco
abstract

Introduction: Selenium (Se) is a trace element with different toxicological and nutritional properties according to its chemical forms. Among the wide range of selenium species, human serum albumin-bound selenium (Se-HSA) has still uncertain composition in terms of organic or inorganic selenium species. This study aimed at investigating the relation between Se-HSA levels with total selenium and the specific organic and inorganic selenium species. Methods: We determined levels of total selenium and selenium species in serum of participants enrolled in two populations of the Emilia-Romagna region, in Northern Italy. Anion exchange chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry was used as quantification method. Correlations between Se-HSA and the other selenium compounds were analyzed using linear regression and restricted cubic spline regression models, adjusted for potential confounders. Results: The first cohort comprised 50 participants (men/women: 26/24) with median (interquartile range, IQR) age 50 (55-62) years, while the second was composed of 104 participants (M/W: 50/54), median (IQR) age 48 (44-53) years. Median (IQR) levels of total selenium were 118.5 (109-136) µg/L and 116.5 (106-128) µg/L, respectively, while Se-HSA was 25.5 µg/L (16.2-51.5) and 1.1 (0.03-3.1) µg/L, respectively. In both populations, Se-HSA was positively associated with inorganic selenium species. Conversely, Se-HSA was inversely associated with organic selenium, especially with selenoprotein P-bound-Se (Se-SELENOP) and less strongly with selenomethionine-bound-Se (Se-Met), while the relation was null or even positive with other organic species. Evaluation of non-linear trends showed a substantially positive association with inorganic selenium, particularly selenite, until a concentration of 30 µg/L, above which a plateau was reached. The association with Se-SELENOP was inverse and strong until 100 µg/L, while it was almost null at higher levels. Conclusions: Our findings seem to indicate that Se-HSA incorporates more selenium when circulating levels of inorganic compounds are higher, thus supporting its mainly inorganic nature, particularly at high circulating levels of selenite.

2023 - Influence of dietary patterns on urinary excretion of cadmium in an Italian population: A cross-sectional study [Articolo su rivista]
Urbano, Teresa; Verzelloni, Pietro; Malavolti, Marcella; Sucato, Sabrina; Polledri, Elisa; Agnoli, Claudia; Sieri, Sabina; Natalini, Nicoletta; Marchesi, Cristina; Fustinoni, Silvia; Vinceti, Marco; Filippini, Tommaso
abstract

Introduction: Cadmium is a toxic heavy metal with detrimental effects on human health. Apart from smoking and occupational factors, diet is the main source of cadmium. However, the relation between adherence to so-called "healthy" dietary patterns and cadmium exposure has not been investigated in detail. In this study, we aimed at assessing such association in a Northern Italian population. Methods: Using a cross-sectional study design, we investigated a population of non-smokers aged 30-60 years in the period 2017-2019. Each subject completed a validated food frequency questionnaire (FFQ) in order to estimate adherence to four dietary patterns, namely the Dietary Approach to Stopping Hypertension-DASH diet, Greek Mediterranean Index-GMI, the Italian Mediterranean Index-IMI, and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. We collected a fasting morning urinary sample to measure urinary levels of cadmium and cotinine. The association between increasing adherence to dietary patterns and cadmium exposure was evaluated using a cubic spline regression non-linear model and adjusting for relevant confounders (age, sex, body mass index, urinary cotinine levels, intake of fiber, and alcohol). Results: We recruited 137 participants (males/females: 62/75) with median (interquartile range-IQR) age of 47 (IQR: 43-53) years. Median scores for the investigated dietary patterns were 24 (IQR: 21-28), 4 (IQR: 3-6), 4 (IQR: 3-5), and 7.5 (IQR: 6.5-8.5) for DASH, GMI, IMI and MIND diets, respectively. The median urinary cadmium level was 0.21 μg/L (IQR: 0.11-0.34 μg/L). Spline regression analysis showed an inverse linear association between increasing adherence to the DASH and MIND diets and urinary cadmium levels, reaching a plateau at high adherence scores, approximately > 25 and > 9 for DASH and MIND diets, respectively. An increase of cadmium exposure with increasing MIND score also emerged. Conversely, the association was almost null for IMI, and slightly positive for GMI. Conclusions: The present findings suggest that increasing adherence to the DASH and MIND diets are associated with decreased cadmium levels only at moderate level. Overall, these results indicate that public health strategies, including the decrease of cadmium contamination in healthy foods should be implemented.

2023 - Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study [Articolo su rivista]
Gianferrari, Giulia; Martinelli, Ilaria; Simonini, Cecilia; Zucchi, Elisabetta; Fini, Nicola; Caputo, Maria; Ghezzi, Andrea; Gessani, Annalisa; Canali, Elena; Casmiro, Mario; De Massis, Patrizia; Curro' Dossi, Marco; De Pasqua, Silvia; Liguori, Rocco; Longoni, Marco; Medici, Doriana; Morresi, Simonetta; Patuelli, Alberto; Pugliatti, Maura; Santangelo, Mario; Sette, Elisabetta; Stragliati, Filippo; Terlizzi, Emilio; Vacchiano, Veria; Zinno, Lucia; Ferro, Salvatore; Amedei, Amedeo; Filippini, Tommaso; Vinceti, Marco; Errals Group, Null; Mandrioli, Jessica
abstract

: Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m2), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patient's prognosis, it should be more extensively applied to this fragile group of patients.

2023 - Interplay of Metallome and Metabolome in Amyotrophic Lateral Sclerosis: A Study on Cerebrospinal Fluid of Patients Carrying Disease-Related Gene Mutations [Articolo su rivista]
Solovyev, N.; Lucio, M.; Mandrioli, J.; Forcisi, S.; Kanawati, B.; Uhl, J.; Vinceti, M.; Schmitt-Kopplin, P.; Michalke, B.
abstract

2023 - It's (not) rocket science! a quick guide to a successful scientific communication in public health [Abstract in Rivista]
Palandri, Lucia; Filippini, Tommaso; Ferrari, Eleonora; Lugli, Camilla; Odone, Anna; Grignolio, Andrea; Righi, Elena; Vinceti, Marco
abstract

A Brief Outline Of The Overall Workshop: Our workshop is intended to act as an overview of effective Public Health communication. We will examine various contexts, beneficiaries, and actors in Preventive Medicine and Public Health communication, stressing the importance of effective knowledge transfer in this field. * First sub-session “HOW TO: COMMUNICATE DATA TO HEALTH PROFESSIONALS” (20 min): * How to: Data Visualization - Lucia Palandri, MD, DrPH, PhDc * How to: Digital Communication - Prof. Tommaso Filippini, MD, DrPH, PhD - [HALF-TIME - 10 min]: DO’S AND DON’TS: INFOGRAPHICS FOR HEALTH PROFESSIONALS VS GENERAL PUBLIC - Eleonora Ferrari, MD; Camilla Lugli, MD * Second sub-session “COMMUNICATE HEALTH TO PEOPLE: SUCCESSFUL EXAMPLES” (20 min): * Leo and Giulia - Prof. Anna Odone, MD, MSc, MPH, PhD * Vaccine Pills on TV - Prof. Andrea Grignolio, MA, PhD * Q&A session (10 min) Moderator: Prof. Elena Righi, PhD Specific Aims/Objectives And Component Parts As Public Health professionals and residents, COVID-19 pandemic had a significant impact on our work, shedding light on a major issue: communication. As a matter of fact, in the last few years, scientific communication has undoubtedly been a challenge in two ways. On one hand, communication has been difficult even among professionals due to the significant volume of data constantly gathered and analyzed during the pandemic. On the other hand, we faced some difficulty with the necessity to constantly interface with the population in an infodemic setting. Both challenges should be considered as important priorities in public health: the lessons learnt from the pandemic (and beyond) should routinely and inextricably guide us in carrying out our roles as PH specialists. Hence, our necessity to delve into this topic and share what we have learnt with coworkers. To this end, we chose to organize our workshop into two sections. A first skill-building sub-session will be dedicated to the communication of scientific information and data among health professionals and “insiders”. In the second sub-session we would like to present a couple of examples of successful general public scientific communication campaigns. We will merge the two sub-session with a practical guide about do’s and don’ts in scientific posters and general public infographic creation. The Key Questions That The Workshop Will Address - How to present scientific findings and relevant data to scientists and health professionals? How to make data more comprehensible? - How to deliver a clear message and maintain public trust in science through successful campaigns?”

2023 - Mercuric chloride (HgCl2) [Capitolo/Saggio]
Urbano, Teresa; Malavolti, Marcella; Vinceti, Marco; Filippini, Tommaso
abstract

2023 - Nutritional safety and suitability of a specific protein hydrolysate derived from a whey protein concentrate and used in an infant formula and follow-on formula manufactured from hydrolysed protein by FrieslandCampina Nederland B.V [Articolo su rivista]
Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Castle, L.; Fewtrell, M.; Przyrembel, H.; Dumas, C.; Titz, A.; Turck, D.
abstract

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from a whey protein concentrate and used in an infant and follow-on formula manufactured by FrieslandCampina Nederland B.V., which submitted a dossier to the European Commission to request an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in the manufacture of infant and/or follow-on formula. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 2.4 g/100 kcal and consumed as the sole source of nutrition by infants for 3 months led to a growth equivalent to a formula manufactured from intact cow's milk protein with a protein content of 2.1 g/100 kcal. Data on gastrointestinal tolerance of the formula did not raise any concerns. No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. Given that it is consumed with complementary foods and the protein source is nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 2.4 g/100 kcal protein and complies with the compositional criteria of Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

2023 - Outdoor artificial light at night and risk of early-onset dementia: A case-control study in the Modena population, Northern Italy [Articolo su rivista]
Mazzoleni, E.; Vinceti, M.; Costanzini, S.; Garuti, C.; Adani, G.; Vinceti, G.; Zamboni, G.; Tondelli, M.; Galli, C.; Salemme, S.; Teggi, S.; Chiari, A.; Filippini, T.
abstract

Background Dementia is a neurological syndrome characterized by severe cognitive impairment with functional impact on everyday life. It can be classified as young onset dementia (EOD) in case of symptom onset before 65, and late onset dementia (LOD). The purpose of this study is to assess the risk of dementia due to light pollution, and specifically outdoor artificial light at night (LAN). Methods Using a case-control design, we enrolled dementia patients newly-diagnosed in the province of Modena in the period 2017–2019 and a referent population from their caregivers. We geo-referenced the address of residence on the date of recruitment, provided it was stable for the previous five years. We assessed LAN exposure through 2015 nighttime luminance satellite images from the Visible Infrared Imaging Radiometer Suite (VIIRS). Using a logistic regression model adjusted for age, sex, and education, we calculated the risk of dementia associated with increasing LAN exposure, namely using <10 nW/cm2/sr as reference and considering ≥10-<40 nW/cm2/sr intermediate and ≥40 nW/cm2/sr high exposure, respectively We also implemented non-linear assessment using a spline regression model. Results We recruited 58 EOD cases, 34 LOD cases and 54 controls. Average LAN exposure levels overlapped for EOD cases and controls, while LOD cases showed higher levels. Compared with the lowest exposure, the risk of EOD associated with LAN was higher in the intermediate exposure (OR = 1.36, 95% CI 0.54–3.39), but not in the high exposure category (OR = 1.04, 95% CI 0.32–3.34). In contrast, the risk of LOD was positively associated with LAN exposure, with ORs of 2.58 (95% CI 0.26–25.97) and 3.50 (95% CI 0.32–38.87) in the intermediate and high exposure categories, respectively. The spline regression analysis showed substantial lack of association between LAN and EOD, while almost linear although highly imprecise association emerged for LOD. Conclusions Although the precision of the estimates was affected by the limited sample size and the study design did not allow us to exclude the presence of residual confounding, these results suggest a possible role of LAN in the etiology of dementia, particularly of its late-onset form.

2023 - Particulate matter exposure and dementia risk: a prospective cohort study in Northern Italy [Abstract in Atti di Convegno]
Urbano, T.; Malagoli, C.; Vinceti, M.; Filippini, T.
abstract

2023 - Particulate matter exposure from motorized traffic and risk of conversion from mild cognitive impairment to dementia: An Italian prospective cohort study [Articolo su rivista]
Urbano, Teresa; Chiari, Annalisa; Malagoli, Carlotta; Cherubini, Andrea; Bedin, Roberta; Costanzini, Sofia; Teggi, Sergio; Maffeis, Giuseppe; Vinceti, Marco; Filippini, Tommaso
abstract

Background: Based on epidemiologic and laboratory studies, exposure to air pollutants has been linked to many adverse health effects including a higher risk of dementia. In this study, we aimed to evaluate the effect of long-term exposure to outdoor air pollution on risk of conversion to dementia in a cohort of subjects with mild cognitive impairment (MCI). Methods: We recruited 53 Italian subjects newly-diagnosed with MCI. Within a geographical information system, we assessed recent outdoor air pollutant exposure, by modeling air levels of particulate matter with equivalent aerodynamic diameter ≤10 μm (PM10) from motorized traffic at participants' residence. We investigated the relation of PM10 concentrations to subsequent conversion from MCI to any type of dementia. Using a Cox-proportional hazards model combined with a restricted cubic spline model, we computed the hazard ratio (HR) of dementia with its 95% confidence interval (CI) according to increasing PM10 exposure, adjusting for sex, age, and educational attainment. Results: During a median follow up of 47.3 months, 34 participants developed dementia, in 26 cases diagnosed as Alzheimer's dementia. In non-linear restricted spline regression analysis, mean and maximum annual PM10 levels positively correlated with cerebrospinal fluid total and phosphorylated tau proteins concentrations, while they were inversely associated with β-amyloid. Concerning the risk of dementia, we found a positive association starting from above 10 μg/m3 for mean PM10 levels and above 35 μg/m3 for maximum PM10 levels. Specific estimates for Alzheimer's dementia were substantially similar. Adding other potential confounders to the multivariable model or removing early cases of dementia onset during the follow-up had little effect on the estimates. Conclusions: Our findings suggest that exposure to outdoor air pollutants, PM10 in particular, may non-linearly increase conversion from MCI to dementia above a certain ambient air concentration.

2023 - Predictors for progression in amyotrophic lateral sclerosis associated to SOD1 mutation: insight from two population-based registries [Articolo su rivista]
Martinelli, Ilaria; Ghezzi, Andrea; Zucchi, Elisabetta; Gianferrari, Giulia; Ferri, Laura; Moglia, Cristina; Manera, Umberto; Solero, Luca; Vasta, Rosario; Canosa, Antonio; Grassano, Maurizio; Brunetti, Maura; Mazzini, Letizia; De Marchi, Fabiola; Simonini, Cecilia; Fini, Nicola; Vinceti, Marco; Pinti, Marcello; Chiò, Adriano; Calvo, Andrea; Mandrioli, Jessica
abstract

BackgroundUncovering distinct features and trajectories of amyotrophic lateral sclerosis (ALS) associated with SOD1 mutations (SOD1-ALS) can provide valuable insights for patient' counseling and stratification for trials, and interventions timing. Our study aims to pinpoint distinct clinical characteristics of SOD1-ALS by delving into genotype-phenotype correlations and factors that potentially impact disease progression.MethodsThis is a retrospective observational study of a SOD1-ALS cohort from two Italian registers situated in the regions of Emilia-Romagna, Piedmont and Valle d'Aosta.ResultsOut of 2204 genotyped ALS patients, 2.5% carried SOD1 mutations, with a M:F ratio of 0.83. SOD1-ALS patients were younger, and more frequently reported a family history of ALS and/or FTD. SOD1-ALS had a longer survival compared to patients without ALS-associated gene mutations. However, here was considerable variability in survival across distinct SOD1 mutations, with an average survival of less than a year for the L39V, G42S, G73S, D91N mutations. Among SOD1-ALS, multivariate analysis showed that, alongside established clinical prognostic factors such as advanced age at onset and high progression rate at diagnosis, mutations located in exon 2 or within highly conserved gene positions predicted worse survival. Conversely, among comorbidities, cancer history was independently associated with longer survival.InterpretationWithin the context of an overall slower disease, SOD1-ALS exhibits some degree of heterogeneity linked to the considerable genetic diversity arising from the multitude of potential mutations sites and specific clinical prognostic factors, including cancer history. Revealing the factors that modulate the phenotypic heterogeneity of SOD1-ALS could prove advantageous in improving the efficacy of upcoming therapeutic approaches.

2023 - Re-evaluation of behenic acid from mustard seeds to be used in the manufacturing of certain emulsifiers pursuant to Article 21(2) of Regulation (EU) No 1169/2011 – for permanent exemption from labelling [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Marchelli, R.; Van Loveren, H.; Valtuena Martinez, S.; de Henauw, S.
abstract

Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to review a scientific assessment related to a notification from DuPont Nutrition Biosciences Aps on behenic acid from mustard seeds to be used in the manufacturing of certain emulsifiers pursuant to Article 21(2) of Regulation (EU) No 1169/2011 – for permanent exemption from labelling. The EC requested EFSA to consider comments raised by the German authorities in relation to: (a) the maximum amount of mustard protein that could be consumed from the emulsifiers manufactured from behenic acid (E470a, E471 and E477) on a single occasion and (b) the minimal observed eliciting dose (MOED) triggering allergic reactions in mustard-allergic individuals. The maximum amount of mustard protein content in behenic acid was re-assessed in view of new analytical data provided by the applicant. Intake estimates by the EFSA ANS Panel for E471 (adults) were used as a proxy for the combined intake (E470a, E471 and E477). Food challenge data and systematic reviews thereof deriving population minimal observed eliciting dose distributions for mustard protein were used to calculate the MOED and estimate the risk. The margin of exposure between the MOED (0.26 mg mustard protein) and the maximum amount of mustard protein that could be consumed from the emulsifiers on a single occasion (0.00895475 mg) is 29. It is predicted that between 0.1% and 1% of the mustard allergic population would react with mild objective symptoms to that dose. Overall, the assessment is conservative, particularly in relation to the exposure. Based on the information and data available, the NDA Panel concludes that it is extremely unlikely (≤ 1% probability) that oral consumption of emulsifiers to be manufactured using behenic acid from mustard seeds (i.e. E470a, E471 and E477) will trigger an allergic reaction in mustard-allergic individuals under the proposed conditions of use.

2023 - Residential exposure to magnetic fields from high-voltage power lines and risk of childhood leukemia [Articolo su rivista]
Malagoli, C.; Malavolti, M.; Wise, L. A.; Balboni, E.; Fabbi, S.; Teggi, S.; Palazzi, G.; Cellini, M.; Poli, M.; Zanichelli, P.; Notari, B.; Cherubini, A.; Vinceti, M.; Filippini, T.
abstract

Background: Several studies have suggested an excess risk of leukemia among children living close to high-voltage power lines and exposed to magnetic fields. However, not all studies have yielded consistent results, and many studies may have been susceptible to confounding and exposure misclassification. Methods: We conducted a case-control study to investigate the risk of leukemia associated with magnetic field exposure from high-voltage power lines. Eligible participants were children aged 0–15 years residing in the Northern Italian provinces of Modena and Reggio Emilia. We included all 182 registry-identified childhood leukemia cases diagnosed in 1998–2019, and 726 age-, sex- and province-matched population controls. We assessed exposure by calculating distance from house to nearest power line and magnetic field intensity modelling at the subjects’ residence. We used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders (distance from nearest petrol station and fuel supply within the 1000 m-buffer, traffic-related particulate and benzene concentrations, presence of indoor transformers, percentage of urban area and arable crops). Results: In multivariable analyses, the OR comparing children living <100 m from high-voltage power-lines with children living ≥400 m from power-lines was 2.0 (95% CI 0.8–5.0). Results did not differ substantially by age at disease diagnosis, disease subtype, or when exposure was based on modeled magnetic field intensity, though estimates were imprecise. Spline regression analysis showed an excess risk for both overall leukemia and acute lymphoblastic leukemia among children with residential distances <100 m from power lines, with a monotonic inverse association below this cutpoint. Conclusions: In this Italian population, close proximity to high-voltage power lines was associated with an excess risk of childhood leukemia.

2023 - Residential exposure to magnetic fields from high-voltage power lines and risk of childhood leukemia in an Italian population [Abstract in Rivista]
Malavolti, M.; Malagoli, C.; Filippini, T.; Poli, M.; Cellini, M.; Palazzi, G.; Vinceti, M.
abstract

Background: An excess risk of leukemia in children living close to high-voltage power-lines and therefore exposed to extremely low frequency magnetic fields has been suggested, though not all studies yielded consistent results, and a possible role of confounding and exposure misclassification could not be entirely ruled out. Methods: We investigated the risk of childhood leukemia associated with magnetic fields exposure from 132+ kV power lines within a population-based case-control study in two Northern Italy provinces, Modena and Reggio Emilia. We included all the 182 registry-based childhood leukemia cases diagnosed from 1998 to 2019, and 726 age, sex and province of residence-matched controls. We assessed exposure by calculating distance from house to nearest power line in a geographical information system database and by modeling magnetic fields at the subjects’ residence. We run analyses in the overall population, restricted to acute lymphoblastic leukemia (ALL) cases, and stratified by age (<5 and ≥5 years). Results: Compared to those living ≥ 400 m from high-voltage power-lines, children living <50 m and 50-<100 m from power lines showed a disease odds ratio (OR) of 3.0 (95% CI 0.7–13.3) and 1.6 (95% CI 0.5–5.1), respectively. The excess risk close to the power lines was higher for the ALL subtype (OR 3.0, 95% CI 0.7–13.3) and among children diagnosed after 5 years (4.1, 95% CI 0.8–20.6). Results did not substantially differ when exposure was based on modeled magnetic fields, though risk ratio estimates became more statistically unstable. Conclusions: We found a statistically imprecise excess risk for childhood leukemia associated with close proximity to high-voltage power lines, which appeared to be stronger for the youngest children.

2023 - Residential proximity to petrol stations and risk of childhood leukemia [Articolo su rivista]
Malavolti, Marcella; Malagoli, Carlotta; Filippini, Tommaso; Wise, Lauren A; Bellelli, Alessio; Palazzi, Giovanni; Cellini, Monica; Costanzini, Sofia; Teggi, Sergio; Vinceti, Marco
abstract

Petrol stations emit benzene and other contaminants that have been associated with an increased risk of childhood leukemia. We carried out a population-based case-control study in two provinces in Northern Italy. We enrolled 182 cases of childhood leukemia diagnosed during 1998-2019 and 726 age- and sex-matched population controls. We geocoded the addresses of child residences and 790 petrol stations located in the study area. We estimated leukemia risk according to distance from petrol stations within a 1000 m buffer and amount of supplied fuel within a buffer of 250 m from the child's residence. We used conditional logistic regression models to approximate risk ratios (RRs) and 95% confidence intervals (CIs) for associations of interest, adjusted for potential confounders. We also modeled non-linear associations using restricted cubic splines. In secondary analyses, we restricted to acute lymphoblastic leukemia (ALL) cases and stratifed by age (<5 and >= 5 years). Compared with children who lived >= 1000 m from a petrol station, the RR was 2.2 (95% CI 0.5-9.4) for children living<50 m from nearest petrol station. Associations were stronger for the ALL subtype (RR=2.9, 95% CI 0.6-13.4) and among older children (age >= 5 years: RR=4.4, 95% CI 0.6-34.1; age<5 years: RR=1.6, 95% CI 0.1-19.4). Risk of leukemia was also greater (RR=1.6, 95% CI 0.7-3.3) among the most exposed participants when assigning exposure categories based on petrol stations located within 250 m of the child's residence and total amount of gasoline delivered by the stations. Overall, residence within close proximity to a petrol station, especially one with more intense refueling activity, was associated with an increased risk of childhood leukemia, though associations were imprecise.

2023 - Role of vegetarian and plant-based diet in the prevention of mild cognitive impairment and dementia [Abstract in Rivista]
Barbolini, G.; Vinceti, M.; Filippini, T.
abstract

Background and Objective: The increasing number of people with Mild Cognitive Impairment (MCI) and dementia represents a relevant public health problem. For this reason, there is interest in the assessment of factors affecting disease risk, in order to implement effective prevention strategies and promote a healthy lifestyle. In particular, diet as a determinant of cognitive impairment and dementia represents an important field of research, and many studies focused on the effects of plant-based, vegetarian or vegan diets on cognitive functions and dementia risk. The aim of this systematic review is to assess whether a plant-based or a ‘strict’ vegetarian diet is protective or detrimental towards cognitive functions. Methods: The protocol of this systematic review and meta-analysis has been submitted to PROSPERO. The literature search has been conducted on 4 different databases: PubMed, Web of Science, Embase and Cochrane library. We used MeSH terms and keywords related to “plant-based diet”, “vegetarian diet”, “Mild Cognitive Impairment”, “dementia” and “memory impairment”. We found 2 additional articles through citation chasing techniques. We defined the following inclusion criteria according to the PICOS statement: adult population, adherence to plant-based, vegetarian or vegan diets, assessment of cognitive functions through dementia risk or cognitive decline at increasing adherence to different dietary patterns, and both observational studies (cohort, cross-sectional or case-control) and randomized clinical controlled trials. We will also perform a dose-response meta-analysis whenever possible. Results: In the preliminary literature search, we found a total of 1537 articles (including 2 studies added through citations), 255 of which were duplicates. After duplicate removal, the abstract and the full-text of 1282 articles were screened, leading to the exclusion of 1263 of them. Nineteen studies met our inclusion criteria and could be included in the systematic review. Conclusions: The study is currently ongoing and its results will be presented at the Congress.

2023 - Safety of 2′-fucosyllactose (2’-FL) produced by a derivative strain (Escherichia coli SGR5) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Pelaez, C.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2′-fucosyllactose (2’-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 2’-FL, but it also contains d-lactose, l-fucose, fucosylgalactose, difucosyllactose, d-glucose and d-galactose, and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli SGR5) of E. coli W (ATCC 9637). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant applies for the same use and use levels as already authorised for 2’-FL and included in the Union list of NFs, with the general population as target population. The Panel noted that the available intake estimate is not recent (2015) and based on a different database (2008–2010 UK data) than that used by EFSA. For this reason, the Panel decided to perform a new intake estimate according to the current EFSA approach. The Panel notes that the highest P95 daily intake of the NF from the use as food ingredient is higher than the estimated natural highest mean daily intake in breastfed infants and marginally higher in young children. The applicant also proposes to extend the use of 2’-FL in food supplements (FS) for infants at the use level of 1.2 g/day. The resulting estimated intake in infants from the proposed use in FS is within the natural intake of 2’-FL in breastfed infants. FS are not intended to be used if other foods with added 2’-FL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of 3-fucosyllactose (3-FL) produced by a derivative strain of Escherichia coli K-12 DH1 as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3-fucosyllactose (3-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3-FL, but it also contains d-lactose, l-fucose, 3-fucosyllactulose and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli K-12 DH1 MDO MAP1834) of E. coli K-12 DH1 (DSM 4235). The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements (FS). The target population is the general population. The anticipated daily intake of 3-FL from both proposed and combined (authorised and proposed) uses at their respective maximum use levels in all population categories does not exceed the highest intake level of 3-FL from human milk in infants on a body weight basis. The intake of 3-FL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 3-FL is also considered of no safety concern. FS are not intended to be used if other foods with added 3-FL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of 3′-sialyllactose (3′-SL) sodium salt produced by a derivative strain (Escherichia coli NEO3) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Pelaez, C.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3′-sialyllactose (3′-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3′-SL (sodium salt), but it also contains sialic acid, d-glucose, d-lactose, 3′-sialyllactulose and 6′-sialyllactose sodium salts and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli NEO3) of E. coli W (ATCC 9637). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements (FS). The target population is the general population. The applicant applies for the same uses and use levels as already assessed for 3′-SL sodium salt produced by a genetically modified strain of E. coli K-12 DH1, with the exception for the use in FS, which is proposed to be higher (from 0.5 to 1.0 g/day) in individuals from 3 years of age. Since the NF as a food ingredient would be consumed at the same extent as the already assessed 3′-SL sodium salt, no new estimates of the intakes have been carried out. The Panel notes that the maximum daily intake of 3′-SL from the proposed use of the NF in FS for individuals from 3 years of age (1.0 g/day) is lower than the estimated highest mean daily intake of 3′-SL in breastfed infants. FS are not intended to be used if other sources of 3′-SL are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of 6′-sialyllactose (6′-SL) sodium salt produced by a derivative strain (Escherichia coli NEO6) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 6′-sialyllactose (6′-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 6′-SL (sodium salt), but it also contains sialic acid, d-glucose, d-lactose, 6′-sialyllactulose sodium salt, 3′-sialyllactose (3′-SL) sodium salt and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli NEO6) of E. coli W (ATCC 9637). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements (FS). The target population is the general population. The applicant applies for the same uses and use levels already assessed for 6′-SL sodium salt produced by fermentation by a genetically modified strain of E. coli K-12 DH1. Therefore, since the NF would be consumed at the same extent as the already assessed 6′-SL sodium salt, no new estimates of the intake have been carried out. Similarly, FS are not intended to be used if other foods with added 6′-SL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of UV-treated powder of whole yellow mealworm (Tenebrio molitor larva) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Siskos, A.; Schlatter, J. R.; van Loveren, H.; Zakidou, P.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on UV-treated powder of whole yellow mealworm (Tenebrio molitor larva) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The term yellow mealworm refers to the larval form of the insect species T. molitor. The NF is the UV-treated powder of the whole, thermally dried yellow mealworm. The NF consists mainly of crude protein, fat, digestible carbohydrates and fibre (chitin). The Panel notes that the levels of contaminants in the NF highly depend on the occurrence levels of these substances in the insect feed. The Panel notes furthermore that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf life. The NF has a high protein content, although the true protein content in the NF is overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen. The applicant proposed to use the NF as an ingredient in various food products, such as bakery products, pasta, compotes of fruit/vegetables and cheese. The target population is the general population. The Panel notes that considering the composition of the NF, the proposed conditions of use and that the NF will not be the sole source of dietary protein, the consumption of the NF is not nutritionally disadvantageous. Despite the UV treatment, the Panel notes that the NF is not a significant dietary contributor of vitamin D3. The submitted toxicity studies from the literature did not raise safety concerns. The Panel considers that the consumption of the NF may induce primary sensitisation and allergic reactions to yellow mealworm proteins and may cause allergic reactions in subjects with allergies to crustaceans and dust mites. Additionally, allergens from the feed may end up in the NF. With the exception of possible allergenicity, the Panel concludes that the NF is safe under the proposed uses and use levels.

2023 - Safety of a change in specifications of the novel food oleoresin from Haematococcus pluvialis containing astaxanthin pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of a change of specifications of the novel food (NF) oleoresin from Haematococcus pluvialis containing astaxanthin (ATX) pursuant to Regulation (EU) 2015/2283. The NF is already authorised as ingredient for the use in food supplements as defined in Directive 2002/46EC in accordance to Regulation (EU) 2017/2470. The NF concerns an oleoresin which contains ~ 10% ATX, obtained by supercritical CO2 extraction of the homogenised and dried biomass of cultivated H. pluvialis. This NF has been assessed by the Panel in 2014. With the present dossier, the applicant proposed to lower the minimum specification limits for protein and ATX monoesters for the NF, and to increase the maximum specification limit for the relative amount of ATX diesters in total ATX. An increase of the maximum specification limit for the 9-cis isomer is also applied for. Although the data are limited regarding bioavailability and distribution in humans of these three naturally occurring ATX isomers, the available in vitro and in vivo data suggest that the 13-cis rather than the 9-cis ATX is selectively absorbed, i.e. has a higher bioavailability and/or possibly emerges from isomerisation of all-trans ATX. The Panel notes that the toxicity of the individual ATX isomers has not been studied individually. However, the ADI of 0.2 mg/kg, which was established for synthetic ATX and ATX from H. pluvialis, applies also for ATX in the oleoresin from H. pluvialis with the proposed changes of specifications. The Panel concludes that the NF, oleoresin from H. pluvialis containing ATX, is safe with the proposed specification limits.

2023 - Safety of an ethanolic extract of the dried biomass of the microalga Phaeodactylum tricornutum as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Siskos, A.; Schlatter, J. R.; van Loveren, H.; Munoz Gonzalez, A.; Rossi, A.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on an ethanolic extract of the dried biomass of the microalga Phaeodactylum tricornutum as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an ethanolic extract of the dried biomass of the microalga P. tricornutum diluted in a medium-chain triglyceride oil carrier, with standardised fucoxanthin and tocopherol content. The main component of the NF is fat (78% on average), followed by crude protein (10% on average). The Panel is of the view that a consistent and safe production process has not been demonstrated. Additionally, the Panel considers that the information provided on the composition of the NF is not complete and may raise safety concerns. The applicant proposed to use the NF as a food supplement at the use level of 437 mg/day, with the target population being adults, excluding pregnant and breastfeeding women. There is no history of use of the NF or of its source, i.e. P. tricornutum. The Panel notes that the source of the NF, P. tricornutum, was not granted the qualified presumption of safety (QPS) status by the EFSA Panel on Biological Hazards (BIOHAZ), due to the lack of a safe history of use in the food chain and on its potential for production of bioactive compounds with toxic effects. There were no concerns regarding genotoxicity of the NF. In the 90-day study provided, a number of adverse effects were observed, some of them seen already at the lowest dose tested (750 mg/kg body weight (bw) day), which was identified by the Panel as the lowest-observed-adverse-effect-level (LOAEL). The potential phototoxicity of pheophorbide A and pyropheophorbide A in the NF was not addressed in this study. Although noting the uncertainties identified by the Panel regarding the analytical determination of these substances in the NF and the limitations in the publicly available toxicity data, a low margin of exposure (MoE) was calculated for these substances at the proposed use levels. The Panel concludes that the safety of the NF under the proposed uses and use levels has not been established.

2023 - Safety of an extension of use of Yarrowia lipolytica yeast biomass as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of Yarrowia (Y.) lipolytica yeast biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The extension of use pertains to the use of the NF as a food ingredient in a number of food categories, in foods for special medical purposes and in foods for total diet replacement for weight control. In 2018, Y. lipolytica was attributed the qualified presumption of safety (QPS) status for production purposes, including food and feed products based on biomass. The Panel considers that the data provided sufficient information with respect to the stability of the NF, also when used as a food ingredient. The concentrations of the analysed processing contaminants do not raise safety concerns. The Panel also considers that consumption of the NF is not nutritionally disadvantageous under the proposed conditions of use. The Panel concludes that the NF, Y. lipolytica yeast biomass, is safe under the proposed conditions of use.

2023 - Safety of apple fruit cell culture biomass as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an apple fruit cell culture biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and intended as an ingredient for food supplements in adults. The cells have been sourced from the callus grown on a piece of apple placed on a solid medium under sterile conditions. The de-differentiated apple cells are then cultivated in liquid medium. The medium contains sucrose, vitamins, minerals, trace elements and the two synthetic plant hormone analogues, benzylaminopurine (< 0.1 mg/kg) and 2,4-dichlorophenoxyacetic acid (< 0.25 mg/kg). These plant hormones are regulated under the EU pesticide legislation and their residue levels in the NF are in compliance with the EU maximum residue levels. The main components of the NF are carbohydrates (including sugars and non-digestible carbohydrates), ash, proteins and smaller amounts of fatty acids and organic acids. Except for the amount of total fat and the organic acids (succinic and l-malic acid), the quantities of the compositional parameters of the NF and apple have little in common. The Panel considers that a provided subchronic toxicity study was not needed to establish the safety of this NF, when taking into account the source of the NF, i.e. apples, the production process, the low intended use level and the composition of the NF, despite the noted differences to apple. The Panel considers that the NF contains proteins, which were not detected in apple and which may be allergenic. The Panel concludes that the NF, an apple fruit cell culture biomass, is safe under the proposed conditions of use.

2023 - Safety of lacto-N-fucopentaose I/2’-fucosyllactose (LNFP-I/2’-FL) mixture as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Pelaez, C.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on lacto-N-fucopentaose I (LNFP-I)/2′-fucosyllactose (2’-FL) mixture as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharides (HiMO) LNFP-I and 2’-FL, but it also contains d-lactose, lacto-N-tetraose, difucosyllactose, 3-fucosyllactose, LNFP-I fructose isomer, 2′-fucosyl-d-lactulose, l-fucose and 2′-fucosyl-d-lactitol, and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli K-12 DH1 MDO MP2173b) of E. coli K-12 DH1 (DSM 4235). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant formula (IF) and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements (FS). The target population is the general population. The anticipated daily intake of LNFP-I from use in IF is similar to the estimated natural mean highest daily intake in breastfed infants. Overall, the anticipated daily intake of LNFP-I from the NF as a food ingredient at the maximum proposed use levels is unlikely to exceed the intake level of breastfed infants on a body weight basis. The intake in breastfed infants on a body weight basis is expected to be safe also for other population groups. The anticipated 2’-FL intake is generally rather low. The use of the NF in FS is not intended if other foods with added NF components or human milk (for infants and young children) are consumed on the same day. The Panel concludes that the NF, a mixture of LNFP-I and 2’-FL, is safe under the proposed conditions of use.

2023 - Safety of monosodium salt of l-5-methyltetrahydrofolic acid as a novel food pursuant to Regulation (EU) 2015/2283 and the bioavailability of folate from this source in the context of Directive 2002/46/EC, Regulation (EU) No 609/2013 and Regulation (EC) No 1925/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Matijevic, L.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on monosodium salt of l-5-methyltetrahydrofolic acid (5-MTHF) as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of folate from this source in the context of Directive 2002/46/EC, Regulation (EU) No 609/2013 and Regulation (EC) No 1925/2006. The NF is produced by chemical synthesis and consists of at least 95% (w/w) of 5-MTHF and 4%–5% (w/w) of sodium. It is proposed to be used as a partial or complete substitute to folic acid and other sources of added folate in a number of food categories. The production process, composition, specifications and stability of the NF do not raise safety concerns. When used as an ingredient in different food matrices, proper processing/storage conditions need to be considered to preserve the stability of the NF. Regarding bioavailability, the Panel considers that the NF readily dissociates into Na and l-methylfolate ions, which subsequently are absorbed and enter the circulation. Thus, the bioavailability of 5-MTHF from the NF is comparable to that of other currently authorised salts of 5-MTHF. The Panel considers that the consumption of the NF is not nutritionally disadvantageous as long as the combined intake of the NF and the other supplemental forms of folate under their authorised conditions of use is below the ULs established for the different age groups of the general population. The Panel concludes that the NF is safe under the proposed conditions of use. The Panel also concludes that the NF is a source from which folate is bioavailable.

2023 - Safety of oil from Schizochytrium limacinum (strain TKD-1) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. (TKD-1) oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain TKD-1, used by the applicant (ATK Biotech Co. Ltd.), belongs to the species Schizochytrium limacinum. The NF is a mixture of triglycerides in which docosahexaenoic acid (DHA) represents 53%–61% of fatty acids. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use levels proposed by the applicant were derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20–50 mg/100 kcal. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of marine biotoxins and viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of oil from Schizochytrium sp. (strain CABIO-A-2) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; Dehenauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. (strain CABIO-A-2) oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. S. sp. is a single-cell microalga. The NF is a mixture of triglycerides in which docosahexaenoic acid (DHA) represents 38%–44% of fatty acids. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use levels proposed by the applicant were derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20–50 mg/100 kcal. The evidence provided demonstrated that the strain S. sp. CABIO-A-2 is phylogenetically closely related to the strain S. sp. ATCC 20888. The assessment of some already authorised S. sp. oils in the Union list were also based on similarities with the strain ATCC 20888. The applicant provided a 90-day repeated dose toxicity study in rats with the NF. No adverse effects were observed up to the highest dose tested, i.e. 10.2 g/kg body weight (bw) per day. Taking into account the toxicity studies performed with the NF and with DHA-oils derived from strains belonging to the genus Schizochytrium, its phylogenetical profile, the production process, the composition of the NF and the absence of marine biotoxins and viable cells in the NF, the Panel considers that there are no concerns with regard to the toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

2023 - Safety of paramylon as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on paramylon as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Paramylon is a linear, unbranched beta-1,3-ᴅ-glucan polymer that is isolated from the single-cell microalga Euglena gracilis. The NF consists of at least 95% beta-glucan and minor amounts of protein, fat, ash and moisture. The applicant proposed to use the NF in food supplements, as a food ingredient added to a number of food categories and in foods for total diet replacement for weight control. In 2019, E. gracilis was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’, which includes food products based on microbial biomass of the microalga. Based on the information provided, E. gracilis is not expected to survive the manufacturing process. The submitted toxicity studies did not raise safety concerns. No adverse effects were observed in the subchronic toxicity studies, up to the highest dose tested, i.e. 5,000 mg NF/kg body weight per day. In view of the QPS status of the source of the NF, supported by the manufacturing process, compositional data and lack of toxicity observed in the toxicity studies, the Panel has no safety concerns and concludes that the NF, i.e. paramylon, is safe under the proposed uses and use levels.

2023 - Safety of partially hydrolysed protein from spent barley (Hordeum vulgare) and rice (Oryza sativa) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Aguilera-Gomez, M.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Siskos, A.; Schlatter, J. R.; van Loveren, H.; Zakidou, P.; Mendes, V.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on partially hydrolysed protein from spent barley (Hordeum vulgare) and rice (Oryza sativa) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced by enzymatically treating the pasteurised spent barley and rice residues of the mash step of beer production. Several mechanical treatment steps of the partial hydrolysate are employed to obtain the final product. The NF consists mainly of partially-hydrolysed proteins from spent barley and rice and it is in powdered form. The Panel notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf life of 15 months. The NF is proposed to be used as an ingredient in various foods such as dairy products, bakery products, pasta, fruit and vegetable spreads, snacks, and single meal replacements for weight reduction. The target population is the general population. Considering protein quality aspects, the Panel concludes that the NF is not a suitable protein source for the nutrition of infants. The Panel notes that, considering the composition of the NF, the proposed conditions of use and that the NF will not be the sole source of dietary protein, the consumption of the NF is not nutritionally disadvantageous. Taking into account the production process, the extensive compositional characterisation of the NF and the history of use of the source the Panel considers that no toxicological studies are required on the NF. Moreover, the Panel considers that the NF has the potential capacity to sensitise individuals and to induce allergic reactions in individuals allergic to barley and rice. With the exception of possible allergenicity, the Panel concludes that the NF is safe under the proposed uses and use levels.

2023 - Safety of the extension of use of 2′-fucosyllactose (2′-FL) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Pelaez, C.; Poulsen, M.; Schlatter, J. R.; Siskos, A.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of the extension of use of 2′-fucosyllactose (2′-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is already authorised as ingredient in several food categories, including infant formula (IF) and follow-on formula (FOF). The applicant proposed to increase the maximum use levels of the NF in IF and FOF. EFSA estimated the anticipated daily intake of the NF from the proposed extension of use, including the already authorised conditions of use in other food categories. Additionally, a new intake estimate limited to the already authorised conditions of use of the NF was carried out following EFSA's current approach. The estimated daily intake of the NF from high consumption of IF alone at the proposed maximum use level in infants < 16 weeks of age is similar to the estimated natural highest mean daily intake of 2′-FL from human milk in breastfed infants. The estimated highest P95 daily intakes of the NF from the proposed extension of use in IF and FOF (including the authorised uses in other food categories) and from the already authorised conditions of use, are comparable and both higher than the estimated natural highest mean daily intake of 2′-FL from human milk in infants and to a lesser extent in young children. The Panel considers that the proposed extension of use of the NF in IF and FOF only marginally affects the highest P95 daily intake estimate from the authorised conditions of use, and therefore does not affect the safety of the NF. The Panel concludes that the NF, 2′-FL, is safe under the proposed conditions of use.

2023 - Safety of the extension of use of partially defatted chia seed (Salvia hispanica L.) powder with a high fibre content as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Gerazova-Efremova, K.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of the extension of use of partially defatted chia seed (Salvia hispanica L.) powder with a high fibre content as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is already authorised and included in the Union list of NFs and is produced according to the same production process. This application is limited to an assessment of the extension of use of the NF as a food ingredient in several food categories with a high moisture content that are subject to thermal processing. The target population for the extension of use is the general population. The information provided on the formation of process contaminants (acrylamide, furan and methylfurans) in a selected food category with added NF (bread) subjected to heat treatment is sufficient for this assessment and does not raise safety concerns. Noting that no safety concerns were identified from the information available on the production process, composition, specifications and proposed uses of the NF, the Panel considers that intake estimates for the NF are not needed for this assessment. The Panel concludes that the NF, partially defatted chia seeds powder with a high fibre content, is safe under the proposed conditions of use.

2023 - Safety of water lentil protein concentrate from a mixture of Lemna gibba and Lemna minor as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Kouloura, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on water lentil protein concentrate from a mixture of Lemna gibba and Lemna minor as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Water lentil protein concentrate is produced from two water lentil species (L. gibba and L. minor) by separation of the protein fraction of the plant material from fibres, followed by pasteurisation and spray drying. The NF consists mainly of protein, fibre, fat and ash. The applicant proposed to use the NF as a food ingredient in a variety of food categories and as a food supplement. The target population is the general population when used as a food ingredient and exclusively adults when used as a food supplement. The Panel considers that taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. The Panel considers that the risk of the NF triggering allergic reactions is low. The Panel concludes that the NF, water lentil protein concentrate from a mixture of L. gibba and L. minor, is safe under the proposed conditions of use.

2023 - Safety of whole seeds of oilseed rape (Brassica napus L emend. Metzg.) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Fernandez Dumont, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on whole seeds of oilseed rape as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of seeds of oilseed rape, in particular double low white flowering varieties of Brassica napus (oilseed rape Brassica napus L. emend. Metzg). The NF's oilseed rape is produced following drying, cleaning and storage procedures traditionally used for oilseed rape in oil production. The NF is proposed to be used as an ingredient in ‘Bread and rolls with special ingredients added’ and ‘Gluten free bread’. The target population is the general population. The highest daily intake of the NF was estimated for young children as 92.6 mg/kg body weight (bw) per day. The Panel notes that intakes of the NF can result in considerably increased levels of glucosinolates consumption as compared to intakes of glucosinolates from background diets. The Panel asked the applicant for additional studies to support the safety of the NF, but these were not provided. The Panel concludes that the safety of whole seeds of oilseed rape under the proposed conditions of use has not been established.

2023 - Safety of yellow/orange tomato extract as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aguilera-Gomez, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Gerazova-Efremova, K.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on yellow/orange tomato extract used as a novel food (NF) pursuant to Regulation (EU) 2283/2015. The NF which is the subject of the application is a carotenoid-rich extract from the yellow/orange tomato containing predominantly phytoene and phytofluene, as well as a lesser amount of beta-carotene, zeta-carotene and lycopene. The NF is produced from the tomato pulp using supercritical CO2 extraction. The applicant proposes the use of the NF in cereal bars, functional drinks and as a food supplement in individuals above 15 years of age. For the use of the NF in cereal bars and functional drinks, the Panel considers, the target population is the general population. According to EFSA's latest exposure assessment for lycopene as a food additive (EFSA ANS Panel, 2017), the highest P95 intakes for children (< 10 and 10–17 years) and adults when combined to the use of lycopene as a food colour from natural occurrence would exceed the established acceptable daily intake (ADI) for lycopene (0.5 mg/kg body weight (bw) day). The estimated intakes of the NF would lead to an exceedance of the ADI when considering natural occurrence and exposure to lycopene when used as a food additive. Due to the absence of safety data regarding phytoene and phytofluene intake from the NF, and the contribution of the NF to the estimated high daily intakes of lycopene, the Panel considers that it cannot be established whether or not the consumption of the NF is nutritionally disadvantageous. The Panel concludes that the safety of the NF has not been established under the proposed conditions of use.

2023 - Scientific opinion on the tolerable upper intake level for folate [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Crous-Bou, M.; Molloy, A.; Ciccolallo, L.; De, Sesmaisons ; Lecarré, A.; Fabiani, L.; Horvath, Z.; Karavasiloglou, N.; Naska, A.
abstract

2023 - Scientific opinion on the tolerable upper intake level for manganese [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bornhorst, J.; Cubadda, F.; Dopter, A.; Fitzgerald, R.; de SesmaisonsLecarre, A.; das NevesFerreira, P.; Fabiani, L.; Horvath, Z.; Matijevic, L.; Naska, A.
abstract

Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for manganese. Systematic reviews of the literature of human and animal data were conducted to assess evidence regarding excess manganese intake (including authorised manganese salts) and the priority adverse health effect, i.e. manganese-induced neurotoxicity. Available human and animal studies support neurotoxicity as a critical effect, however, data are not sufficient and suitable to characterise a dose–response relationship and identify a reference point for manganese-induced neurotoxicity. In the absence of adequate data to establish an UL, estimated background dietary intakes (i.e. manganese intakes from natural dietary sources only) observed among high consumers (95th percentile) were used to provide an indication of the highest level of intake where there is reasonable confidence on the absence of adverse effects. A safe level of intake of 8 mg/day was established for adults ≥ 18 years (including pregnant and lactating women) and ranged between 2 and 7 mg/day for other population groups. The application of the safe level of intake is more limited than an UL because the intake level at which the risk of adverse effects starts to increase is not defined.

2023 - Scientific opinion on the tolerable upper intake level for selenium [Articolo su rivista]
Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; de Henauw, Stefaan; Hirsch-Ernst, Karen-Ildico; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Peláez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Aggett, Peter; Crous Bou, Marta; Cubadda, Francesco; Ciccolallo, Laura; de Sesmaisons Lecarré, Agnès; Fabiani, Lucia; Titz, Ariane; Naska, Androniki
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for selenium. Systematic reviews of the literature were conducted to identify evidence regarding excess selenium intake and clinical effects and potential biomarkers of effect, risk of chronic diseases and impaired neuropsychological development in humans. Alopecia, as an early observable feature and a well-established adverse effect of excess selenium exposure, is selected as the critical endpoint on which to base a UL for selenium. A lowest-observed-adverse-effect-level (LOAEL) of 330 mu g/day is identified from a large randomised controlled trial in humans (the Selenium and Vitamin E Cancer Prevention Trial (SELECT)), to which an uncertainty factor of 1.3 is applied. A UL of 255 mu g/day is established for adult men and women (including pregnant and lactating women). ULs for children are derived from the UL for adults using allometric scaling (body weight(0.75)). Based on available intake data, adult consumers are unlikely to exceed the UL, except for regular users of food supplements containing high daily doses of selenium or regular consumers of Brazil nuts. No risk has been reported with the current levels of selenium intake in European countries from food (excluding food supplements) in toddlers and children, and selenium intake arising from the natural content of foods does not raise reasons for concern. Selenium-containing supplements in toddlers and children should be used with caution, based on individual needs.

2023 - Scientific opinion on the tolerable upper intake level for vitamin B6 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Fairweather-Tait, S.; Vrolijk, M.; Fabiani, L.; Titz, A.; Naska, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for vitamin B6. Systematic reviews of the literature were conducted by a contractor. The relationship between excess vitamin B6 intakes and the development of peripheral neuropathy is well established and is the critical effect on which the UL is based. A lowest-observed-effect-level (LOAEL) could not be established based on human data. A reference point (RP) of 50 mg/day is identified by the Panel from a case–control study, supported by data from case reports and vigilance data. An uncertainty factor (UF) of 4 is applied to the RP to account for the inverse relationship between dose and time to onset of symptoms and the limited data available. The latter covers uncertainties as to the level of intake that would represent a LOAEL. This leads to a UL of 12.5 mg/day. From a subchronic study in Beagle dogs, a LOAEL of 50 mg/kg body weight (bw) per day can be identified. Using an UF of 300, and a default bw of 70 kg, a UL of 11.7 mg/day can be calculated. From the midpoint of the range of these two ULs and rounding down, a UL of 12 mg/day is established by the Panel for vitamin B6 for adults (including pregnant and lactating women). ULs for infants and children are derived from the UL for adults using allometric scaling: 2.2–2.5 mg/day (4–11 months), 3.2–4.5 mg/day (1–6 years), 6.1–10.7 mg/day (7–17 years). Based on available intake data, EU populations are unlikely to exceed ULs, except for regular users of food supplements containing high doses of vitamin B6.

2023 - Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Lanham-New, S.; Passeri, G.; Craciun, I.; Fabiani, L.; De Sousa, R. F.; Martino, L.; Martinez, S. V.; Naska, A.
abstract

Following two requests from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for vitamin D and to propose a conversion factor (CF) for calcidiol monohydrate into vitamin D3 for labelling purposes. Vitamin D refers to ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), and calcidiol monohydrate. Systematic reviews of the literature were conducted to assess the relative bioavailability of calcidiol monohydrate versus vitamin D3 on serum 25(OH)D concentrations, and for priority adverse health effects of excess vitamin D intake, namely persistent hypercalcaemia/hypercalciuria and endpoints related to musculoskeletal health (i.e. falls, bone fractures, bone mass/density and indices thereof). Based on the available evidence, the Panel proposes a CF for calcidiol monohydrates of 2.5 for labelling purposes. Persistent hypercalciuria, which may be an earlier sign of excess vitamin D than persistent hypercalcaemia, is selected as the critical endpoint on which to base the UL for vitamin D. A lowest-observed-adverse-effect-level (LOAEL) of 250 μg/day is identified from two randomised controlled trials in humans, to which an uncertainty factor of 2.5 is applied to account for the absence of a no-observed-adverse-effect-level (NOAEL). A UL of 100 μg vitamin D equivalents (VDE)/day is established for adults (including pregnant and lactating women) and for adolescents aged 11–17 years, as there is no reason to believe that adolescents in the phase of rapid bone formation and growth have a lower tolerance for vitamin D compared to adults. For children aged 1–10 years, a UL of 50 μg VDE/day is established by considering their smaller body size. Based on available intake data, European populations are unlikely to exceed the UL, except for regular users of food supplements containing high doses of vitamin D.

2023 - Selenium and immune function: a systematic review and meta-analysis of experimental human studies [Articolo su rivista]
Filippini, Tommaso; Fairweather-Tait, Susan; Vinceti, Marco
abstract

Background Selenium is an essential trace element with both beneficial and detrimental effects on health depending on dose and chemical form. Currently, there is debate about recommendations for selenium supplementation as a public health measure to improve immune function and reduce infectious disease susceptibility. Objectives We performed a systematic review and meta-analysis of experimental studies assessing the effect of selenium supplementation on immunity-related outcomes in healthy people. Methods We undertook a search of published and unpublished studies in literature databases PubMed/MEDLINE, Embase and Clinicaltrials.gov up to October 17, 2022, and performed a meta-analysis comparing the effects on immunity-related outcomes between supplemented versus control arms. Whenever possible we assessed the nonlinear relation using a dose-response approach. Results Nine trials were included, five in North America, and four in Europe, with duration between 8-48 weeks and supplementation of both inorganic and organic selenium forms. Selenium supplementation did not substantially affect immunoglobulin or white blood cell levels, and the dose-response meta-analysis indicated that an increase in plasma selenium concentrations above 100 μg/L did not further increase IgA levels nor T-cells. An inverted U-shaped relation emerged for Natural killer (NK) cell count, with lower number of these cells both below and above 120 μg/L. The only beneficial effect of selenium supplementation was increased activity for NKlysis, but the available data did not permit dose-response analysis. Cytokine levels were substantially unaffected by selenium supplementation. Conclusions Although some of the data suggested beneficial effects of selenium supplementation on immune function, the overall picture appears to be inconsistent and heterogenous due to differences in trial duration and interventions, plus evidence of null and even detrimental effects. Overall, the evidence that we extracted from the literature in this systematic review does not support the need to supplement selenium beyond the recommended dietary intake to obtain beneficial effects on immune function. Keywords seleniumimmune functioninfectious diseaseexperimental studiessystematic reviewdose-response meta-analysis

2023 - Selenium exposure and oxidative stress and genotoxicity risk in a healthy Italian population: a cross sectional study [Abstract in Rivista]
Urbano, Teresa; Filippini, Tommaso; Malavolti, Marcella; Michalke, Bernhard; Fustinoni, Silvia; Vinceti, Marco
abstract

2023 - Selenium exposure and urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine: Major effects of chemical species and sex [Articolo su rivista]
Urbano, Teresa; Filippini, Tommaso; Wise, Lauren A; Sucato, Sabrina; Polledri, Elisa; Malavolti, Marcella; Fustinoni, Silvia; Michalke, Bernhard; Vinceti, Marco
abstract

: Selenium is an element present in trace amounts and different chemical forms. It may exert both beneficial and adverse effects on cellular redox status and on the generation of reactive oxygen species. 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine, and a sensitive biomarker of oxidative stress and genotoxicity. The present study assessed the extent to which selenium status was associated with urinary 8-oxodG concentrations in a Northern Italian population. We recruited healthy, non-smoking blood donors living in the Reggio Emilia province during 2017-2019. We measured urinary 8-oxodG concentrations and used restricted cubic spline regression analyses to investigate the association between selenium status (estimated using food frequency questionnaires, urinary concentrations, and serum concentrations of selenium and selenium species) and 8-oxodG/g creatinine. Among 137 participants aged 30-60 years, median urinary selenium and 8-oxodG concentrations were 22.02 μg/L and 3.21 μg/g creatinine, respectively. Serum samples and selenium speciation analyses were available for 104 participants. Median total serum selenium levels and dietary intake were 116.5 μg/L and 78.7 μg/day, respectively. In spline regression analysis, there was little association between dietary, serum, or urinary selenium with 8-oxodG concentrations. In sex-specific analyses, urinary selenium showed a positive association with the endpoint among males. For single selenium species, we observed positive associations with urinary 8-oxodG for serum organic selenium species, and negative associations for inorganic selenium forms. In the most adjusted analysis, urinary 8-oxodG concentrations showed a strong positive association with selenomethione-bound selenium (Se-Met) and a negative association with inorganic tetravalent selenium, selenite. In sex-specific analyses, these associations were considerably stronger in males than in females. Overall, study findings indicate that selenium species exhibited very different patterns of associations with the biomarker of oxidative stress, and that these associations also depended on sex. Background exposure to Se-Met appears to be strongly and positively associated with oxidative stress.

2023 - Selenoprotein P concentrations and risk of progression from mild cognitive impairment to dementia [Articolo su rivista]
Vinceti, Marco; Urbano, Teresa; Chiari, Annalisa; Filippini, Tommaso; Wise, Lauren A; Tondelli, Manuela; Michalke, Bernhard; Shimizu, Misaki; Saito, Yoshiro
abstract

: There is a growing literature investigating the effects of selenium on the central nervous system and cognitive function. However, little is known about the role of selenoprotein P, the main selenium transporter, which can also have adverse biological effects. We conducted a prospective cohort study of individuals aged 42-81 years who received a clinical diagnosis of mild cognitive impairment. Using sandwich ELISA methods, we measured full-length selenoprotein P concentrations in serum and cerebrospinal fluid to assess the relation with dementia incidence during a median follow-up of 47.3 months. We used Cox proportional hazards regression and restricted cubic splines to model such relation. Of the 54 participants, 35 developed dementia during follow-up (including 26 cases of Alzheimer's dementia). Selenoprotein P concentrations in serum and cerebrospinal fluid were highly correlated, and in spline regression analyses they each showed a positive non-linear association with dementia risk, particularly after excluding dementia cases diagnosed within 24 months of follow-up. We also observed differences in association according to the dementia subtypes considered. Risk ratios of dementia peaked at 2-6 at the highest levels of selenoprotein P, when compared to its median level, also depending on matrix, analytical methodology and dementia subtype. Findings of this study, the first to assess selenoprotein P levels in the central nervous system in vivo and the first to use a prospective study design to evaluate associations with dementia, suggest that higher circulating concentrations of selenoprotein P, both in serum and cerebrospinal fluid, predict progression of MCI to dementia. However, further confirmation of these findings is required, given the limited statistical precision of the associations and the potential for residual confounding.

2023 - Serum selenium concentrations and adherence to the MIND diet in a Northern Italian population: a cross sectional study [Abstract in Rivista]
Filippini, Tommaso; Urbano, Teresa; Malavolti, Marcella; Grioni, Sara; Agnoli, Claudia; Sieri, Sabina; Michalke, Bernhard; Vinceti, Marco
abstract

2023 - Social disparities and unhealthy lifestyles increase risk of dementia, particularly at a young age [Articolo su rivista]
Filippini, Tommaso; Vinceti, Marco
abstract

2023 - Sulfur content in foods consumed in an Italian population and impact of diet quality on sulfur intake [Articolo su rivista]
Passafiume, A.; Rossetti, A.; Vescovi, L.; Malavolti, M.; Baraldi, C.; Rovesti, S.; Vinceti, M.; Filippini, T.
abstract

Sulfur is an essential nutrient but data about its intake are scarce. We aimed to measure sulfur content in food samples and assess its habitual intake in relation to adherence to healthy dietary patterns in 719 Italian adults. Using a food frequency questionnaire, we estimated overall sulfur intake, and its relation with adherence to healthy dietary patterns. The highest sulfur content was found in preserved/canned fish (3.0 g/kg), seafood (2.8 g/kg), white meat (2.8 g/kg) and dairy products, particularly aged cheeses (2.1 g/kg) and lowest in fresh fruit (87 mg/kg), oils and fats (157 mg/kg), and beverages (141 mg/kg), with the exception of onion and garlic (1.3 g/kg). The mean sulfur intake in the study population was 1.1 g/day, slightly higher in men than women. The foods contributing most to sulfur intake were meat (29%) and cereals (19%), with also substantial contribution (>10%) from beverages and dairy products. Adherence to dietary patterns had little influence on sulfur intake, except for adherence to MIND diet positively and linearly associated with sulfur intake. Our study provides an updated overview of sulfur content in foods composing the Italian diet, as well as of sulfur intake in an Italian community of Northern Italy.

2023 - Tea and coffee consumption and risk of dementia: a systematic review and dose-response meta-analysis [Abstract in Rivista]
Mazzoleni, E.; Rossetti, A.; Filippini, T.; Vinceti, M.
abstract

Background and Objective: Dementia is a chronic progressive disease characterized by multifactorial aetiology. Among the factors of greatest interest for prevention is lifestyle, including dietary habits. In particular, tea and coffee are still a matter of debate, being associated both with protective and detrimental effects. The aim of our study is to assess the relation between tea and coffee intake and risk of developing dementia through a dose-response meta-analysis based on cohort studies. Methods: We performed a literature search in PubMed and EMBASE databases up to 28 November 2022. Inclusion criteria were: population without chronic diseases or previous dementia diagnosis, cohort study design, assessment of tea or coffee intake by increasing categories of exposure, assessment of incident dementia risk. Exclusion criteria were: type of study (non-cohort), type of publication (letters, commentaries and systematic reviews), missing information about exposure level for tea and coffee in each category. For statistical analysis, we used cubic splines through a non-linear random-effects regression model (drmeta routine in Stata/SE 17.0). Results: We identified 9 articles published between 2009-2021, 1 assessing tea consumption, 6 coffee and 2 both. As the amount of tea consumed increases, risk of dementia decreases progressively. Conversely, we found a U-shaped association between coffee intake and dementia risk: as the number of cups of coffee consumed increases, the risk of dementia decreases progressively up to two cups of coffee (approx. 300 mL) per day, whereas as the daily amount increases, there is a reversal up to five cups (approx. 750 mL) per day. Conclusions: Moderate coffee intake appears to have a protective effect, while intake in higher amounts seems to increase the risk of dementia. Concerning tea, the relation is almost linear in a protective way.

2023 - The dark side of light at night: assessing breast cancer risk with a dose-response meta-analysis [Abstract in Rivista]
Urbano, T; Vinceti, M; Wise, L A; Filippini, T
abstract

2023 - The influence of meteorological factors on COVID-19 spread in Italy during the first and second wave [Articolo su rivista]
Balboni, Erica; Filippini, Tommaso; Rothman, Kenneth J; Costanzini, Sofia; Bellino, Stefania; Pezzotti, Patrizio; Brusaferro, Silvio; Ferrari, Fabrizio; Orsini, Nicola; Teggi, Sergio; Vinceti, Marco
abstract

: The relation between meteorological factors and COVID-19 spread remains uncertain, particularly with regard to the role of temperature, relative humidity and solar ultraviolet (UV) radiation. To assess this relation, we investigated disease spread within Italy during 2020. The pandemic had a large and early impact in Italy, and during 2020 the effects of vaccination and viral variants had not yet complicated the dynamics. We used non-linear, spline-based Poisson regression of modeled temperature, UV and relative humidity, adjusting for mobility patterns and additional confounders, to estimate daily rates of COVID-19 new cases, hospital and intensive care unit admissions, and deaths during the two waves of the pandemic in Italy during 2020. We found little association between relative humidity and COVID-19 endpoints in both waves, whereas UV radiation above 40 kJ/m2 showed a weak inverse association with hospital and ICU admissions in the first wave, and a stronger relation with all COVID-19 endpoints in the second wave. Temperature above 283 K (10 °C/50 °F) showed a strong non-linear negative relation with COVID-19 endpoints, with inconsistent relations below this cutpoint in the two waves. Given the biological plausibility of a relation between temperature and COVID-19, these data add support to the proposition that temperature above 283 K, and possibly high levels of solar UV radiation, reduced COVID-19 spread.

2023 - The shape of water - preliminary data from a cluster of patients infected by Mycobacterium saskatchewanense in Haemodialysis setting in Emilia-Romagna, Northern Italy [Abstract in Rivista]
Ferrari, Eleonora; Vecchi, Elena; Mattei, Giovanna; Belloli, Gian; Diegoli, Giuseppe; Monte, Paola; Santoro, Antonio; Palma, Alessandra; Amadori, Nicola; Falcone, Patrizia; Patuelli, Melania; Palandri, Lucia; Vinceti, Marco; Righi, Elena
abstract

Background and Objective: Nontuberculous mycobacteria (NTM) are common environmental contaminants and, as opportunistic pathogens, they can colonize/infect immunocompromised patients. Our work Aims to report the main features of a cluster of haemodialysis patients infected by Mycobacterium saskatchewanense, and to describe the infection prevention and control (IPC) strategies implemented accordingly. Methods: We conducted a descriptive analysis of data coming from the infectious diseases data stream of the Emilia-Romagna Region. Spectrometric and DNA-sequencing analyses in ultrafiltered liquid were done in the regional reference laboratory, while blood cultures were performed in the local hospital laboratory. Results: Between 04/01/2022 and 18/07/2022, a cluster of 6 patients (3 males and 3 females, median age 63.5 years) with positive blood culture for Mycobacterium saskatchewanense was reported in two HUB hospitals of the Region Emilia-Romagna, Northern Italy. All patients underwent online haemodiafiltration before the symptom’s onset; water samples from the dialysis machines’ ultrafilters also tested positive. The key clinical features reported were varied, including weight loss, asthenia, gastrointestinal symptoms, cough, night sweats, recurrent fever of unknown origin. In addition, common Findings were cytopenia, increased blood levels of systemic inflammation markers, splenomegaly, osteo-medullary granulomas, and pulmonary pathologic imaging. Conclusions: The application of the best IPC strategies (clinical and environmental surveillance, switch to traditional haemodialysis and heat disinfection...) is currently supervised by a regional interdisciplinary team, and preliminary data indicate positive outcomes. As a precaution, considering the extreme fragility of haemodialysis patients, a constant epidemiological monitoring based on clinical and diagnostic criteria is still in place, and regular environmental sampling is being performed.

2023 - Unique cerebrospinal fluid peptides: potential amyotrophic lateral sclerosis biomarkers and etiological factors [Articolo su rivista]
Wormser, Uri; Sintov, Amnon; Vinceti, Marco; Mandrioli, Jessica; Brodsky, Berta; Proscura, Elena; Finkelstein, Yoram
abstract

2022 - A Systematic Review and Dose-response Meta-analysis on Fluoride Exposure and Neurodevelopmental Toxicity in Children [Abstract in Atti di Convegno]
Veneri, Federica; Giannone, Maria Edvige; Mazzoleni, Elena; Filippini, Tommaso; Consolo, Ugo; Generali, Luigi; Vinceti, Marco
abstract

Background The possible harmful effect of fluoride exposure on neurodevelopment in children is widely discussed, however, the magnitude of this relation is still controversial. The aim of this systematic review and meta-analysis was to characterize this relation through a dose-response approach. Methods/Approach We performed an online literature search in PubMed, Web of Science and Embase up to September 10, 2022. From each eligible study we extracted the effect size as a mean difference (MD) of intelligence quotient (IQ) scores and its 95% confidence intervals (CI). We performed a meta-analysis comparing the highest versus lowest fluoride exposure using a random-effects model, stratifying for type of exposure (fluoride in drinking water or urinary fluoride). Finally, we quantitively assessed such relation by performing a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Results Out of 1955 potentially relevant records retrieved through a systematic literature search, we identified 34 eligible studies for review; 32 were also included for meta-analysis. The analysis comparing the highest-versus-lowest exposure showed decreased IQ scores for both water and urinary fluoride with MD of -6.62 (95% CI -8.61, -4.63) and -3.58 (95% CI -7.28, 0.12), respectively. The dose-response analysis showed a decrease in IQ score from 1 mg/L, considerably steeper above 2.5 mg/L for water fluoride. The dose-response curve for urinary fluoride showed a weaker but constant decrease in IQ scores with increasing fluoride levels. Conclusions Overall, a substantial consistency in the effect direction emerged, with adverse effects of different magnitude on children’s intelligence, arising from rather low fluoride exposure previously considered safe from a public health perspective. However, potential methodological limitations, such as heterogeneity in outcome measures and lack of consideration of possible confounders in some of the studies, may have affected these findings.

2022 - A deep learning approach for Spatio-Temporal forecasting of new cases and new hospital admissions of COVID-19 spread in Reggio Emilia, Northern Italy [Articolo su rivista]
Sciannameo, Veronica; Goffi, Alessia; Maffeis, Giuseppe; Gianfreda, Roberta; Jahier Pagliari, Daniele; Filippini, Tommaso; Mancuso, Pamela; Giorgi Rossi, Paolo; Dal Zovo, Leonardo Alberto; Corbari, Angela; Vinceti, Marco; Berchialla, Paola
abstract

Since February 2020, the COVID-19 epidemic has rapidly spread throughout Italy. Some studies showed an association of environmental factors, such as PM10, PM2.5, NO2, temperature, relative humidity, wind speed, solar radiation and mobility with the spread of the epidemic. In this work, we aimed to predict via Deep Learning the real-time transmission of SARS-CoV-2 in the province of Reggio Emilia, Northern Italy, in a grid with a small resolution (12 km × 12 km), including satellite information.

2022 - Artificial light at night and risk of mental disorders: A systematic review [Articolo su rivista]
Tancredi, Stefano; Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

Background: Emerging evidence suggests a possible association between artificial light at night (LAN) exposure and physiological and behavioral changes, with implications on mood and mental health. Due to the increased amount of individuals' LAN exposure, concerns have been raised regarding harmful impact of LAN on mental health at the population level. Aim: To perform a systematic review of observational studies to investigate if light-at-night, assessed both indoor and outdoor, may be associated with an increased risk of mental diseases in humans. Methods: We reviewed the epidemiological evidence on the association between LAN exposure, assessed either via satellite photometry or via measurements of bedroom brightness, and mental disorders. We systematically searched the MEDLINE, Embase and Web of Science databases up to April 1, 2022. Studies were included if they assessed the link between indoor or outdoor artificial light at night and one or more mental disorders in human populations. Results: Nine eligible studies were included in this review: six studies had a cross-sectional design, two had a longitudinal design with a median follow-up of 24 months, and one was a case-cohort study. Overall, we found moderate evidence of a positive association between LAN exposure and depressive symptoms and to a lesser extent other mental disorders, though the number of studies was limited and potential residual confounding such as socioeconomic factors, noise, or pollution may have influenced the results. Conclusions: Although more robust evidence is needed, the epidemiological evidence produced so far seems to support an association between LAN and depressive disorders. Keywords: Depression; Environmental risk factors; Light-at-night; Mental disorders; Systematic review.

2022 - Association between dietary patterns and urinary cadmium levels in an Italian population [Abstract in Atti di Convegno]
Filippini, T.; Urbano, T.; Malavolti, M.; Fustinoni, S.; Vinceti, M.
abstract

2022 - Association between selenium species and hippocampal volume in subjects with mild cognitive impairment [Abstract in Atti di Convegno]
Vinceti, Marco; Balboni, Erica; Filippini, Tommaso; Wise, Lauren A.; Nocetti, Luca; Eichmüller, Marcel; Tondelli, Manuela; Vinceti, Giulia; Zamboni, Giovanna; Chiari, Annalisa; Michalke, Bernhard
abstract

Background Selenium is a trace element with nutritional and toxicological properties. Its influence on human health is thought to depend on exposure dose and chemical form. The effects of selenium exposure on medical conditions that involve the central nervous system have been insufficiently studied. In a cohort of individuals with mild cognitive impairment, we have previously documented a positive relation between cerebrospinal fluid (CSF) levels of inorganic hexavalent selenium (selenate) and risk of dementia. Methods/Approach We assessed the relation between CSF levels of selenium species and volume of the hippocampus among the 33 cohort members aged 43-82 years who had undergone magnetic resonance imaging at baseline (2008-2014) using both linear and spline regression analyses. We also performed a surface-based analysis using SPHARM-PDM to evaluate differences in shape of the hippocampus in addition to its volume in relation to CSF levels of selenium species. Results We found an inverse association between selenate and total hippocampal volume (β regression coefficient in multivariable linear regression analysis -3.05, 95% confidence interval -5.74 to -0.37), which was similar for the right and left hippocampus and emerged mainly at the highest exposure levels. We found little association between the other selenium forms and hippocampal volume. In the surface-based analysis, the left hippocampus showed considerably more pronounced shape differences in the ventro-medial region of the head. Conclusions This is the first study to analyze selenium species in relation to hippocampal volume and structure, suggesting that a selenium form with high toxicological potential may adversely affect a key structure involved in dementia onset and progression as the hippocampus, possibly the left one in particular. However, we cannot entirely rule out the influence of reverse causation or unmeasured confounding on these results.

2022 - Association between serum selenium species and 8-oxo-7,8-dihydro-2’deoxyguanosine levels: an Italian cross-sectional study [Abstract in Atti di Convegno]
Urbano, T.; Filippini, T.; Michalke, B.; Fustinoni, S.; Vinceti, M.
abstract

Introduction: Selenium (Se) is a metalloid present in trace amounts in the organism, with toxicological and nutritional properties depending on the dose and the species considered. Both organic and inorganic selenium species are involved in oxidoreduction reaction regulation and pathways. 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxodG) is a derivative of deoxyguanosine, used as biomarker of oxidative stress in urine. In this study, we aimed to assess total serum selenium levels along with its species in a population in Northern Italy and to evaluate the associations between selenium exposure with 8-oxodG levels. Material and methods: The present study consisted in a cross-sectional survey carried out in blood donors aged 30-60 years enrolled in the Transfusion Medicine Center ‘Casa del Dono’ of the AUSL-IRCCS of Reggio Emilia, Northern Italy, in the period April 2017-April 2019. Of 148 eligible subjects, 137 were eventually enrolled. They were all non-smokers, and not affected by any disease or clinical condition. Each participant gave urinary and blood samples in order to quantify selenium levels in these matrices; urinary samples were used to quantify cotinine and 8-oxodG levels, while speciation analysis was performed in serum samples. We performed spline regression analyses to assess the possible nonlinear associations of the different biomarkers of selenium exposure with 8-oxodG levels using a multivariable model adjusted for potential confounders. Results: Our population had a mean age of 47.4 years. Mean (standard deviation) level of serum selenium was 117.4±19.1 mcg/L, respectively. Association of serum selenium level with 8-oxodG levels adjusted for urinary creatinine was almost null. For what concerns selenium species, selenoprotein P-bound-Se showed a slightly inverted U-shaped association with 8-oxodG levels with a positive association until 90 mcg/L and negative above that amount. Selenomethionine-bound-Se, glutathione peroxidase-bound-Se, and selenocysteine-bound-Se were positively associate with 8-oxodG, though for the latter two the association was very imprecise. A negative association emerged for thioredoxin reductase-bound-Se. Total inorganic selenium along with the two inorganic species, i.e., selenite and selenate, were negatively and linearly associated with 8-oxodG levels. For Se-bound to human serum albumin-bound-Se the association was almost null. Conclusion: Our results suggest that even though total selenium exposure seems not associated with 8-oxodG, selected selenium species may largely differ in their association with this oxidative stress biomarker, thus strengthening the importance of selenium speciation analysis for the evaluation of selenium health effects.

2022 - Associations of human serum albumin-bound selenium (Se-HSA) with other selenium species in two cohorts of Northern Italy [Abstract in Atti di Convegno]
Urbano, T.; Michalke, B.; Filippini, T.; Vinceti, M.
abstract

2022 - Associations of urinary and dietary cadmium with urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine and blood biochemical parameters [Articolo su rivista]
Urbano, Teresa; Filippini, Tommaso; Wise, Lauren A.; Lasagni, Daniela; De Luca, Tiziana; Sucato, Sabrina; Polledri, Elisa; Malavolti, Marcella; Rigon, Chiara; Santachiara, Annalisa; Pertinhez, Thelma A.; Baricchi, Roberto; Fustinoni, Silvia; Vinceti, Marco
abstract

Cadmium is a heavy metal with established adverse effects on human health, namely on bone, liver and kidney function and the cardiovascular system. We assessed cadmium exposure and its correlation with biomarkers of toxicity. We recruited 137 non-smoking blood donors without a history of chronic disease or cancer who resided in the Northern Italy province of Reggio Emilia (mean age 47 years, range 30–60 years) in the 2017–2019 period. We used a semi-quantitative food frequency questionnaire to estimate dietary cadmium intake and urine samples to assess concentrations of urinary cadmium and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). Median urinary cadmium and 8-oxodG concentrations were 0.21 μg/L (interquartile range (IQR): 0.11–0.34 μg/L) and 3.21 μg/g creatinine (IQR: 2.21–4.80 μg/g creatinine), respectively, while median dietary cadmium intake was 6.16 μg/day (IQR: 5.22–7.93 μg/day). We used multivariable linear and spline regression models to estimate mean differences exposure concentrations. Dietary and urinary cadmium were positively correlated, and both were positively and linearly correlated with 8-oxodG. We found a positive association of urinary cadmium with blood alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL)-cholesterol and thyroid-stimulating hormone (TSH) concentrations. We also observed a positive association with triglycerides, in both linear (beta regression coefficient = 77.03, 95% confidence interval 32.27–121.78) and non-linear spline regression analyses. Despite the positive correlation between dietary and urinary cadmium estimates, dietary cadmium intake showed inconsistent results with the study endpoints and generally weaker associations, suggesting a decreased capacity to reflect actual cadmium exposure. Overall, these findings suggest that even low levels of cadmium exposure may adversely alter hematological and biochemical variables and induce oxidative stress.

2022 - Associazione tra livelli di cadmio e 8‑oxo‑7,8‑diidro‑2’‑deossiguanosina in una popolazione italiana [Articolo su rivista]
Urbano, Teresa; Filippini, Tommaso; Malavolti, Marcella; Fustinoni, Silvia; Vinceti, Marco
abstract

2022 - Associazione tra livelli di cadmio e parametri ematologici e biochimici in una popolazione del Nord Italia [Abstract in Atti di Convegno]
Urbano, Teresa; Filippini, Tommaso; Lasagni, Daniela; De Luca, Tiziana; Sucato, Sabrina; Polledri, Elisa; Malavolti, Marcella; Santachiara, Annalisa; Pertinhez Thelma, A.; Baricchi, Roberto; Fustinoni, Silvia; Vinceti, Marco
abstract

2022 - Atrial Fibrillation and the Risk of Early‐Onset Dementia: A Systematic Review and Meta‐Analysis [Articolo su rivista]
Giannone, Maria Edvige; Filippini, Tommaso; Whelton, Paul K.; Chiari, Annalisa; Vitolo, Marco; Boriani, Giuseppe; Vinceti, Marco
abstract

BACKGROUNDRecent studies have identified an increased risk of dementia in patients with atrial fibrillation (AF). However, both AF and dementia usually manifest late in life. Few studies have investigated this association in adults with early‐onset dementia. The aim of this study was to investigate the relationship between AF and early‐onset dementia. METHODS AND RESULTSWe searched the PubMed/MEDLINE, Embase, and Scopus databases through April 15, 2022, for studies reporting on the association between AF and dementia in adults aged <70 years, without language restrictions. Two reviewers independently performed the study selection, assessed the risk of bias, and extracted the study data. We performed a meta‐analysis of early‐onset dementia risk according to occurrence of AF using a random‐effects model. We retrieved and screened 1006 potentially eligible studies. We examined the full text of 33 studies and selected the 6 studies that met our inclusion criteria. The pooled analysis of their results showed an increased risk of developing dementia in individuals with AF, with a summary relative risk of 1.50 (95% CI, 1.00–2.26) in patients aged <70 years, and 1.06 (95% CI, 0.55–2.06) in those aged <65 years. CONCLUSIONSIn this systematic review and meta‐analysis, AF was a risk factor for dementia in adults aged <70 years, with an indication of a slight and statistically imprecise excess risk already at ages <65 years. Further research is needed to assess which characteristics of the arrhythmia and which mechanisms play a role in this relationship.

2022 - Blood and cerebrospinal fluid selenoprotein P levels and risk of progression from mild cognitive impairment to dementia [Abstract in Atti di Convegno]
Vinceti, M.; Urbano, T.; Chiari, A.; Filippini, T.; Wise, L.; Tondelli, M.; Michalke, B.; Shimizu, M.; Saito, Y.
abstract

2022 - Conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt into dietary folate equivalents [Articolo su rivista]
Turck, Dominique; Bohn, Torsten; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Peláez, Carmen; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Abrahantes, José Cortiñas; Dumas, Céline; Ercolano, Valeria; Titz, Ariane; Pentieva, Kristina
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt (collectively called 5-MTHF hereafter) into dietary folate equivalents (DFE). Following a systematic review, the conclusions of the opinion are based on one intervention study in adults for intakes < 400 μg/day and three intervention studies in adults for intakes ≥ 400 μg/day. At intakes below 400 μg/day, folic acid (FA) is assumed to be linearly related to responses of biomarkers of intake and status and is an appropriate comparator for deriving a DFE conversion factor for 5-MTHF. It is proposed to use the same factor as for folic acid for conversion of 5-MTHF into DFE for intakes < 400 μg/day. As such intake levels are unlikely to be exceeded through fortified food consumption, the conversion factor of 1.7 relative to natural food folate (NF) could be applied to 5-MTHF added to foods and to food supplements providing < 400 μg/day. At 400 μg/day, 5-MTHF was found to be more bioavailable than folic acid and a conversion factor of 2 is proposed for this intake level and for higher intakes. The derived DFE equations are DFE = NF + 1.7 × FA + 1.7 × 5-MTHF for fortified foods and food supplements providing intakes < 400 μg/day; and DFE = NF + 1.7 × FA + 2.0 × 5-MTHF for food supplements providing intakes ≥ 400 μg/day. Although this assessment applies to calcium-L-methylfolate and 5-MTHF glucosamine salt, it is considered that the influence of the cation on bioavailability is likely to be within the margin of error of the proposed DFE equations. Therefore, the proposed equations can also be applied to 5-MTHF associated with other cations.

2022 - Dietary Acrylamide Exposure and Risk of Site-Specific Cancer: A Systematic Review and Dose-Response Meta-Analysis of Epidemiological Studies [Articolo su rivista]
Filippini, Tommaso; Halldorsson, Thorhallur I; Capitão, Carolina; Martins, Raquel; Giannakou, Konstantinos; Hogervorst, Janneke; Vinceti, Marco; Åkesson, Agneta; Leander, Karin; Katsonouri, Andromachi; Santos, Osvaldo; Virgolino, Ana; Laguzzi, Federica
abstract

: Diet is a main source of acrylamide exposure to humans. Existing observational data on the relationship between dietary exposure to acrylamide and risk of cancer are inconsistent. We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the association between dietary acrylamide exposure and several site-specific cancer. A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases until March 7, 2022. Studies were eligible if they were carried out in non-occupationally exposed adults, assessed dietary acrylamide exposure (μg/day) and reported risk estimates of cancer incidence (all but gynecological cancers). Using a random-effects model, we performed a meta-analysis of site-specific cancer risk comparing the highest vs. lowest category of dietary acrylamide exposure. We also carried out a one-stage dose-response meta-analysis assessing the shape of the association. Out of 1,994 papers screened, 31 were eligible (total of 16 studies), which included 1,151,189 participants in total, out of whom 48,175 developed cancer during the median follow-up period of 14.9 years (range 7.3-33.9). The mean estimated dose of dietary acrylamide across studies was 23 μg/day. Pooled analysis showed no association between the highest vs. lowest dietary acrylamide exposure and each site-specific cancer investigated, with no evidence of thresholds in the dose-response meta-analysis. There were also no associations between dietary acrylamide exposure and the risk of cancers when stratifying by smoking status, except for increased risk of lung cancer in smokers. In conclusion, high dietary acrylamide exposure was not associated with an increased risk of site-specific non-gynecological cancer.

2022 - Dietary Patterns and Blood Biochemical and Metabolic Parameters in an Italian Population: A Cross-Sectional Study [Articolo su rivista]
Cecchini, Marta; Urbano, Teresa; Lasagni, Daniela; De Luca, Tiziana; Malavolti, Marcella; Baraldi, Claudia; Grioni, Sara; Agnoli, Claudia; Sieri, Sabina; Santachiara, Annalisa; Pertinhez, Thelma A.; Fustinoni, Silvia; Baricchi, Roberto; Vinceti, Marco; Filippini, Tommaso
abstract

Diet has long been identified as a major determinant of cardiovascular and other chronic diseases. In this study, we assess the relation between adherence to different dietary patterns and biochemical and metabolic parameters as well as the 10-year risk of major cardiovascular diseases (CVDs) in a community of blood donors in Northern Italy. We assess their adherence to four dietary patterns, namely, the Dietary Approach to Stop Hypertension (DASH) diet, the Mediterranean diet through the Greek and Italian Mediterranean Indices (GMI and IMI) and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, using a validated semi-quantitative food frequency questionnaire (FFQ). We then assess their association with blood parameters and the 10-year risk of major CVD using a spline regression model. We found an inverse association between the DASH and MIND diets and total and LDL cholesterol, and triglyceride and HDL cholesterol values for the Mediterranean diets (IMI and GMI). Additionally, according to our sex-stratified analyses, men who have greater adherence to dietary patterns have a decreased risk of major CVD for all patterns. The results suggest that greater adherence to dietary patterns positively influences blood biochemical and metabolic parameters, thus reducing the risk of developing cardiovascular disease and delaying the use of drug treatments

2022 - Dietary intake of potentially toxic elements and children's chemical exposure [Articolo su rivista]
Urbano, T.; Zagnoli, F.; Malavolti, M.; Halldorsson, T. I.; Vinceti, M.; Filippini, T.
abstract

Environmental pollution is a major global public health problem, which has been extensively associated with several adverse health outcomes in both developed and undeveloped countries. In this review, we aimed at summarizing the most recent epidemiological evidence on the association between environmental pollutants intake and possible adverse health effects in children. What emerged is that several contaminants negatively affect children's health. In particular, exposure to heavy metals, plastic-derived chemicals, pesticides, and per- and polyfluoroalkyl substances have been associated with developmental disorders, cancers, allergies, and obesity in children.

2022 - Environmental and lifestyle risk factors for early-onset dementia: a systematic review [Articolo su rivista]
Bosi, Matteo; Malavolti, Marcella; Garuti, Caterina; Tondelli, Manuela; Marchesi, Cristina; Vinceti, Marco; Filippini, Tommaso
abstract

The term early-onset dementia (EOD) encompasses several forms of neurodegenerative diseases characterized by symptom onset before 65 years and leading to severe impact on subjects already in working activities, as well as on their family and caregivers. Despite the increasing incidence, the etiology is still unknown, with possible association of environmental factors, although the evidence is still scarce. In this review, we aimed to assess how several environmental and lifestyle factors may be associated with the onset of this disease.

2022 - Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy [Articolo su rivista]
Gianferrari, G.; Martinelli, I.; Zucchi, E.; Simonini, C.; Fini, N.; Vinceti, M.; Ferro, S.; Gessani, A.; Canali, E.; Valzania, F.; Sette, E.; Pugliatti, M.; Tugnoli, V.; Zinno, L.; Stano, S.; Santangelo, M.; De Pasqua, S.; Terlizzi, E.; Guidetti, D.; Medici, D.; Salvi, F.; Liguori, R.; Vacchiano, V.; Casmiro, M.; Querzani, P.; Dossi, M. C.; Patuelli, A.; Morresi, S.; Longoni, M.; De Massis, P.; Rinaldi, R.; Borghi, A.; Amedei, A.; Mandrioli, J.
abstract

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype–phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age-and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70–75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype–genotype correlations in the ALS population of ERR.

2022 - Exposure to overhead high-voltage power lines and childhood leukemia risk: an Italian population-based case-control study [Abstract in Atti di Convegno]
Malagoli, Carlotta; Malavolti, Marcella; Fabbi, Sara; Zanichelli, Paolo; Notari, Barbara; Poli, Maurizio; Palazzi, Giovanni; Cellini, Monica; Filippini, Tommaso; Teggi, Sergio; Vinceti, Marco
abstract

Background Previous epidemiologic findings suggest a positive association between magnetic field exposure induced by high voltage power lines and childhood leukemia (CL). Contrasting results are still reported, possibly biased by exposure misclassification, relying on different assessment methods across studies, and by unmeasured confounders. Methods/Approach We further studied this relation in the Modena and Reggio Emilia provinces (Northern Italy), and through a modelling exposure assessment we identified the corridors along high voltage power lines with magnetic field intensity in the 0.1-0.4 µT ranges. Then we identified 182 cases of newly-diagnosed CL within these provinces from 1998 to 2019. We sampled four age-, sex-, province of residence- and calendar year- matched controls for each case. We computed the odds ratio (OR) and its 95% confidence interval (CI) of CL in a conditional logistic regression analysis according to distance between home address at the time of diagnosis of the case and the nearest high voltage power line and also to residential magnetic field modeled intensity. Results OR of CL was 0.9 (95% CI 0.5-1.6), 0.9 (95% CI 0.4-2.0), 1.5 (95% CI 0.5-4.7) and 4.0 (95% CI 1.0-16.0) for children living respectively 200-400 m, 100-200 m, 50-100 m, and less than 50 m from the nearest high voltage power line compared to those residing further than 400 m. OR of CL associated with residence in the area with exposure >0.1 µT was 8.0 (95% CI 0.7-88.2). Conclusions Though the number of exposed children in this study was too low to allow firm conclusions, yielding in such cases high but very imprecise estimates, our results seem more suggestive of an excess risk of leukemia among children living close to electric power lines or exposed to higher magnetic fields intensity.

2022 - GRADE Guidance article 35: Update on rating imprecision for assessing contextualized certainty of evidence and making decisions [Articolo su rivista]
Schünemann, Holger J; Neumann, Ignacio; Hultcrantz, Monica; Brignardello-Petersen, Romina; Zeng, Linan; Murad, M Hassan; Izcovich, Ariel; Morgano, Gian Paolo; Baldeh, Tejan; Santesso, Nancy; Cuello, Carlos Garcia; Mbuagbaw, Lawrence; Guyatt, Gordon; Wiercioch, Wojtek; Piggott, Thomas; De Beer, Hans; Vinceti, Marco; Mathioudakis, Alexander G; Mayer, Martin G; Mustafa, Reem; Filippini, Tommaso; Iorio, Alfonso; Nieuwlaat, Robby; Marcucci, Maura; Coello, Pablo Alonso; Bonovas, Stefanos; Piovani, Daniele; Tomlinson, George; Akl, Elie A
abstract

GRADE guidance to rate the certainty domain of imprecision is presently not fully operationalized for rating down by two levels and when different or uncertainty in baseline risks are considered. In addition, there are scenarios in which lowering the certainty of evidence by three levels for imprecision is more appropriate than lowering it by two levels. In this article, we conceptualize and operationalize rating down for imprecision by one, two and three levels for imprecision using the contextualized GRADE approaches.

2022 - Guidance for establishing and applying tolerable upper intake levels for vitamins and essential minerals: Draft for internal testing [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aggett, P.; Crous Bou, M.; Cubadda, F.; de Sesmaisons Lecarre, A.; Martino, L.; Naska, A.
abstract

Vitamins and essential minerals are micronutrients that are essential for the normal functioning of the human body. However, they may lead to adverse health effects if consumed in excess. The concept of a tolerable upper intake level (UL) is a science-based reference value, which was introduced to support policy-makers and other relevant actors in managing the risks of excess nutrient intake. EFSA’s principles for establishing ULs for vitamins and minerals were originally developed by the Scientific Committee on Food in 2000. Since then, experience has been gained and the scientific field developed. This guidance from the EFSA Panel on Nutrition, Novel Foods and Food Allergens provides an updated framework to support EFSA’s UL assessments. It covers aspects related to the planning of the risk assessment (problem formulation and definition of methods) and its implementation (evidence retrieval, appraisal, synthesis, integration, uncertainty analysis). As in the previous framework, the general principles developed for the risk assessment of chemicals in food are applied (hazard identification, hazard characterisation, intake assessment, risk characterisation). Peculiar to nutrients are their biochemical and physiological roles and the specific and selective mechanisms that maintain the systemic homoeostasis and body burden of the nutrient. These must be considered when conducting a risk assessment of nutrients. This document constitutes a draft guidance that will be applied in EFSA’s assessments during a 1-year pilot phase and be revised and complemented as necessary. Before finalisation of the guidance, a public consultation will be launched.

2022 - Healing Time of Skin Ulcers in Homecare Residents in the Province of Reggio Emilia, Northern Italy [Articolo su rivista]
Iamandii, Inga; Kouassi, Abram Beatrice; Simonazzi, Davide; Marchesi, Cristina; Vinceti, Marco; Filippini, Tommaso
abstract

The growing phenomenon of skin ulcers represents an important health problem; therefore, we conducted a pilot study to evaluate the ulcer healing time among adult subjects followed by the Home Nursing Service of the AUSL-IRCCS of Reggio Emilia, Northern Italy, and diagnosed with at least one skin ulcer during the period of January-August 2020. We recruited 138 subjects (45.5% men) with a mean age of 86.1 years. The subjects presented with 232 ulcers, of which 76.7% were pressure ulcers (60.1% were stage II), 18.1% were vascular ulcers, and 4.7% were diabetic foot ulcers. Ulcer management required only one weekly access for the majority of subjects, with a recovery frequency of 53.6% at the end of the observation period. The median ulcer healing time was 3.6 months and was shorter in women (2.6 months) than men (5.1 months), with an increasing trend according to the number of ulcers and the severity of pressure ulcers for vascular and diabetic foot ulcers. In conclusion, this is the first study carried out in an Italian population describing the distribution and characteristics of homecare residents with skin ulcers and highlighting the factors influencing the healing time and as consequence the duration of nursing care.

2022 - Is Greenness Associated with Dementia? A Systematic Review and Dose–Response Meta-analysis [Articolo su rivista]
Zagnoli, Federico; Filippini, Tommaso; Jimenez, Marcia P.; Wise, Lauren A.; Hatch, Elizabeth E.; Vinceti, Marco
abstract

Purpose of review: We assessed the relation between environmental greenness and risk of dementia and cognitive impairment, based on a systematic review and meta-analysis up to March 30, 2022, characterizing whenever possible the shape of the association using dose-response meta-analysis. Recent findings: Twelve studies were included in this review, either using normalized difference vegetation index (NDVI) or land use/cover (LU/LC) methodology to assess greenness. Comparing the highest versus lowest exposure categories of greenness assessed using the NDVI (6 studies) or LU/LC (6 studies), we found no association with dementia. Dose-response meta-analysis of the association between greenness measured by LU/LC and dementia, based on only 3 studies, indicated a U-shaped association, but estimates were imprecise. Our systematic review and meta-analysis provided some evidence of a slight inverse association between greenness and dementia at intermediate exposure levels, but not at high levels. Potential methodological limitations, such as exposure misclassification and unmeasured confounding, may have affected the results.

2022 - Light at night exposure and risk of depression and other mental disorders: a systematic review [Abstract in Atti di Convegno]
Tancredi, Stefano; Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

Background In modern society, individuals are increasingly exposed to artificial light at night (LAN) i.e., different sources of light altering the natural day-night cycle. Emerging evidence suggests a possible association between LAN exposure and physiological and behavioral changes, with implications on mood and mental health at the population level. We performed a systematic review of observational studies to investigate if LAN exposure, may be associated with an increased risk of mental diseases in humans. Methods/Approach We reviewed the epidemiological evidence about the association between LAN exposure as assessed either via satellite photometry (outdoor LAN) or via measurements of bedroom brightness (indoor LAN), and risk of mental disorders. We systematically searched the PubMed, Embase and Web of Science databases up to September 1, 2022. Studies were included if they assessed the link between exposure to indoor or outdoor LAN and one or more mental disorders. Results Ten eligible studies were included in this review: six studies had a cross-sectional design, two had a longitudinal design with a median follow-up of 24 months, and one was a case-cohort study. Studies were published between 2002 and 2022. Eight studies were conducted in adult populations, one in adolescents, and one in children. Mental disorders investigated include anxiety and mood disorders, depression, bipolar disorder, autism and mild cognitive impairment. Overall, we found moderate evidence of a positive association between LAN exposure and depressive symptoms and to a lesser extent other mental disorders, though the number of studies was limited and potential residual confounding such as socioeconomic factors, noise, or air pollution may have influenced the results. Conclusions Although more robust evidence is needed, the epidemiological evidence produced so far seems to support an association between LAN and risk of depressive disorders.

2022 - Light at night exposure and risk of depression and other mental disorders: a systematic review [Abstract in Rivista]
Tancredi, Stefano; Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

BACKGROUND AND AIM: In modern society, individuals are increasingly exposed to artificial light at night (LAN) i.e., different sources of light altering the natural day-night cycle. Emerging evidence suggests a possible association between LAN exposure and physiological and behavioral changes, with implications on mood and mental health at the population level. We performed a systematic review of observational studies to investigate if LAN exposure, may be associated with an increased risk of mental diseases in humans. METHODS: We reviewed the epidemiological evidence about the association between LAN exposure as assessed either via satellite photometry (outdoor LAN) or via measurements of bedroom brightness (indoor LAN), and risk of mental disorders. We systematically searched the PubMed, Embase and Web of Science databases up to April 1, 2022. Studies were included if they assessed the link between exposure to indoor or outdoor LAN and one or more mental disorders. RESULTS: Nine eligible studies were included in this review: six studies had a cross-sectional design, two had a longitudinal design with a median follow-up of 24 months, and one was a case-cohort study. Studies were published between 2002 and 2022. Seven studies were conducted in adult populations, one in adolescents, and one in children. Mental disorders investigated include anxiety and mood disorders, depression, bipolar disorder and autism. Overall, we found moderate evidence of a positive association between LAN exposure and depressive symptoms and to a lesser extent other mental disorders, though the number of studies was limited and potential residual confounding such as socioeconomic factors, noise, or air pollution may have influenced the results. CONCLUSIONS: Although more robust evidence is needed, the epidemiological evidence produced so far seems to support an association between LAN and risk of depressive disorders. KEYWORDS: mental disorders; light at night; depression; systematic review, environmental risk factors

2022 - Maternal acrylamide exposure during pregnancy and fetal growth: A systematic review and dose-response meta-analysis of epidemiological studies [Articolo su rivista]
Hogervorst, Janneke; Virgolino, Ana; Halldorsson, Thorhallur I; Vinceti, Marco; Åkesson, Agneta; Leander, Karin; Nawrot, Tim; Filippini, Tommaso; Laguzzi, Federica
abstract

Background: Acrylamide is a food contaminant linked to developmental toxicity in animals and possibly in humans. Objectives: We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the relationship between maternal acrylamide exposure during pregnancy and the risk of being small for gestational age (SGA) and birth weight, birth head circumference and birth length. Methods: We performed the literature search in PubMed, Scopus, and Web of Science, until June 6th, 2022. Studies carried out in mother-newborn pairs, assessing maternal acrylamide exposure during pregnancy, either via dietary assessments or biomarkers i.e., hemoglobin adducts of acrylamide (AA-Hb) and glycidamide (GA-Hb), and evaluating birth outcomes were included. We employed a random-effects model to assess the pooled effect estimates and their 95% confidence intervals (CI) for the association between acrylamide exposure and birth outcomes. Risk of Bias for Nutrition Observational Studies tool was used for bias assessment. Results: Out of 169 records identified, five original studies were eligible, including 53,870 mother-newborn pairs in total. Means were 21.9 μg/day for estimated dietary acrylamide exposure (3 studies), and 18.4 and 14.9 pmol/g for AA-Hb and GA-Hb, respectively (2 studies). Higher risk of SGA and lower birth weight and head circumference were observed in the highest quartile of AA-Hb [odds ratio (OR): 1.20 (95% CI: 1.08; 1.33); mean difference (MD): -131 g (95% CI: -204; -58) and -0.31 cm (95% CI: -0.58; -0.04), respectively], and GA-Hb [OR: 1.36 (95% CI: 1.13; 1.64), MD: -161 g (95% CI: -271; -52); and MD: -0.38 cm (95% CI: -0.66; -0.10), respectively], whereas a lower birth length was observed only in the highest quartile of GA-Hb (MD: -0.85 cm (95% CI: -1.38; -0.33). Results from the dose-response meta-analysis between increasing maternal acrylamide exposure during pregnancy and birth weight showed no clear evidence of a deviation from linearity. Conclusions: Overall, our findings strengthen the evidence of an adverse effect of maternal acrylamide exposure during pregnancy on fetal growth. These results encourage to increase preventive actions towards lowering acrylamide exposure in the population.

2022 - Mitigating Indoor Risk of Airborne Infections: the MIRAI project [Abstract in Atti di Convegno]
Filippini, Tommaso; Vinceti, Marco; Ghermandi, Grazia; Bigi, Alessandro
abstract

2022 - Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by HIPP-Werk Georg Hipp OHG (dossier submitted by meyer.science GmbH) [Articolo su rivista]
Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Katrine Knutsen, H.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Castle, L.; Fewtrell, M.; Przyrembel, H.; Dumas, C.; Titz, A.; Turck, D.
abstract

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from whey protein concentrate and used in infant and follow-on formula by HIPP-Werk Georg Hipp OHG. The dossier that was submitted to the European Commission aimed at requesting an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in infant and/or follow-on formula. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 1.9 g/100 kcal and consumed as the sole source of nutrition by infants for 3 months led to growth equivalent to a formula manufactured from intact cow’s milk protein with the same protein content. No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. However, given that it is consumed with complementary foods and the protein source is considered nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 1.9 g/100 kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

2022 - Prediagnostic Levels of Copper and Zinc and Breast Cancer Risk in the ORDET Cohort [Articolo su rivista]
Pala, V.; Agnoli, C.; Cavalleri, A.; Rinaldi, S.; Orlandi, R.; Segrado, F.; Venturelli, E.; Vinceti, M.; Krogh, V.; Sieri, S.
abstract

Background: Case–control studies show that copper (Cu) is high and zinc (Zn) low in blood and urine of women with breast cancer compared with controls. Methods: To assess whether prediagnostic Cu and Zn are associated with breast cancer risk, OR of breast cancer according to Cu, Zn, and Cu/Zn ratio in plasma and urine was estimated in a nested case–control study within the ORDET cohort, using conditional logistic regression adjusted for multiple variables: First 496 breast cancer cases and matched controls, diagnosed ≥2 years after recruitment (to eliminate reverse causation) were analyzed. Then all eligible cases/controls were analyzed with stratification into years from recruitment to diagnosis. Results: For women diagnosed ≥2 years, compared with lowest tertiles, breast cancer risk was higher in the highest tertile of plasma Cu/Zn ratio (OR, 1.75; 95% CI, 1.21–2.54) and the highest tertile of both plasma and urine Cu/Zn ratio (OR, 2.37; 95% CI, 1.32–4.25). Risk did not vary with ER/PR/HER2 status. For women diagnosed <2 years, high Cu/Zn ratio was strongly associated with breast cancer risk. Conclusions: Our prospective findings suggest that increased Cu/Zn ratio in plasma and urine may be both an early marker of, and a risk factor for, breast cancer development. Further studies are justified to confirm or otherwise our results and to investigate mechanisms. Impact: Our finding that prediagnostic Cu/Zn ratio is a strong risk factor for breast cancer development deserves further investigation and, if confirmed, might open the way to interventions to reduce breast cancer risk in women with disrupted Cu/Zn homeostasis.

2022 - Relation between adherence to dietary patterns and serum selenium species levels in a healthy Italian cohort [Abstract in Atti di Convegno]
Urbano, T.; Filippini, T.; Malavolti, M.; Michalke, B.; Vinceti, M.
abstract

2022 - Relation between adherence to dietary patterns and urinary selenium levels in an Italian cohort [Abstract in Atti di Convegno]
Malavolti, M.; Urbano, T.; Filippini, T.; Fustinoni, S.; Vinceti, M.
abstract

2022 - Residence in proximity of petrol stations and childhood leukemia risk [Abstract in Atti di Convegno]
Malavolti, Marcella; Malagoli, Carlotta; Costanzini, Sofia; Palazzi, Giovanni; Cellini, Monica; Filippini, Tommaso; Teggi, Sergio; Vinceti, Marco
abstract

Background Air pollutant concentrations close to petrol stations tend to increase, especially for benzene and other carcinogenic contaminants, depending on meteorological factors, features of nearby buildings and station activity. For this reason, it is suggested that petrol stations increase the risk of cancer, in particular, childhood leukemia. Methods/Approach We carried-out a population-based case-control study in two Northern Italy provinces, Modena and Reggio Emilia. We included 182 cases of childhood leukemia diagnosed in the period 1998-2019, and 726 age and sex-matched controls. We geocoded child residence and the 790 petrol stations located in the study area, of which we retrieved the annual refueling activity. Exposure was assessed based on both residential distance from the nearest petrol station and on the activity of all plants located up to 1000 m from the home. Risk ratio of leukemia was estimated by computing disease odds ratio (OR) through conditional logistic regression models adjusted for potential confounders. Results We found an increased risk for childhood leukemia associated to residence in close proximity to petrol stations. Compared to those who live ≥ 1000m, OR was 2.30 (95% CI 0.53-9.97) for children living <50 m from nearest petrol station in bivariate analysis and 2.16 (95% CI 0.49-9.42) in multivariable analysis. The excess risk was higher when considering acute lymphoblastic leukemia (ALL) subtype (OR=2.83, 95% CI 0.61-13.21), and in children diagnosed after 5 years of age (OR=4.68, 95% CI 0.61-35.95) compared with < 5 years (OR=1.63, 95% CI 0.14-18.84). Conclusions Our study found an increased childhood leukemia risk for residence in close proximity (<50 meters) to a petrol station. Such excess risk was higher for the ALL subtype and for children diagnosed after 5 years.

2022 - Safety of 2′-fucosyllactose (2’-FL) produced by a derivative strain (APC199) of Corynebacterium glutamicum ATCC 13032 as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

: Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2'-fucosyllactose (2'-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 2'-FL, but it also contains d-lactose, l-fucose, 3-fucosyllactose, difucosyllactose, d-glucose and d-galactose. The NF is produced by fermentation with a genetically modified strain (APC199) of Corynebacterium glutamicum ATCC 13032. 2'-FL, when chemically synthesised or produced by fermentation with derivative strains of Escherichia coli K-12 DH1 or E. coli BL21 (DE3), is already authorised and included in the EU list of NFs. This application refers to a change in the production process and specifications, while target population, conditions of use and consequently, the anticipated intake remain unchanged. The information provided on the identity, production process, composition and specifications of the NF does not raise safety concerns. The intake of other carbohydrate-type compounds structurally related to 2'-FL is also considered of no safety concern. In line with other milk oligosaccharides that are natural components of human milk, the safety assessment of this NF is mainly based on the comparison between the intake of breastfed infants and the estimated intake as NF. Given that the NF would be consumed at the same extent as the already authorised 2'-FL, the Panel considers that the consumption of the NF at the proposed uses and use levels does not raise safety concerns. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of 3-fucosyllactose (3-FL) produced by a derivative strain of Escherichia coli BL21 (DE3) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3-fucosyllactose (3-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3-FL, but it also contains d-lactose, l-fucose, d-glucose and d-galactose, and a small fraction of other related saccharides. The NF is produced by fermentation with a genetically modified strain of Escherichia coli BL21 (DE3). The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for infants and young children, food for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of 3-FL from both proposed and combined (authorised and proposed) uses at their respective maximum use levels in all population categories does not exceed the highest intake level of 3-FL from human milk in infants on a body weight basis. The intake of 3-FL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 3-FL is also considered of no safety concern. Food supplements are not intended to be used if other foods with added 3-FL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of 3’-sialyllactose (3’-SL) sodium salt produced by derivative strains of Escherichia coli BL21 (DE3) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3’-sialyllactose (3’-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3’-SL, but it also contains d-lactose, 3’-sialyllactulose, sialic acid, N-acetyl-d-glucosamine and a small fraction of other related oligosaccharides. The NF is produced by fermentation with two genetically modified strains of Escherichia coli BL21 (DE3), the production strain and the optional degradation strain. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for infants and young children, food for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of 3’-SL from both proposed and combined (authorised and proposed) uses at their respective maximum use levels in all population categories does not exceed the highest intake level of 3’-SL from human milk in infants on a body weight basis. The intake of 3’-SL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 3’-SL is also considered of no safety concern. Food supplements are not intended to be used if other foods with added 3’-SL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of 6′-sialyllactose (6’-SL) sodium salt produced by derivative strains of Escherichia coli BL21 (DE3) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 6′-sialyllactose (6’-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 6’-SL, but it also contains d-lactose, 6′-sialyllactulose, sialic acid, N-acetyl-d-glucosamine and a small fraction of other related oligosaccharides. The NF is produced by fermentation with two genetically modified strains of Escherichia coli BL21 (DE3), the production strain and the optional degradation strain. The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements. The target population is the general population. In some scenarios at the maximum use levels, the estimated intakes per kg body weight were higher than the high average natural intake of 6’-SL from human milk. However, given the intrinsic nature of human milk oligosaccharides (HMOs), the wide range of intakes from human milk, and considering that infants are naturally exposed to similar amounts of these substances, the Panel considers that the consumption of the NF at the proposed conditions of use does not raise safety concerns. The intake of 6’-SL in breastfed infants on a body weight basis is also expected to be safe for other population groups. The intake of other carbohydrate-type compounds structurally related to 6’-SL is also considered of no safety concern. Food supplements are not intended to be used if other foods with added 6’-SL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of Beta-lactoglobulin as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Fernandez Dumont, A.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on beta-lactoglobulin (BLG) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF (≥ 90% w/w dry matter protein) consists of BLG as primary component (≥ 90% of total protein), which is equivalent to BLG present in bovine milk and whey protein isolate (WPI). The NF is produced from bovine whey by crystallisation under acidic or neutral conditions. The NF is proposed to be used as a food ingredient in isotonic and sport drinks, whey powder and milk-based drinks and similar products, and in food for special medical purposes as defined in Regulation (EU) No 609/2013. The target population is the general population. The highest daily intake of the NF was estimated for children of 3 to < 10 years of age as 667 mg/kg body weight (bw) per day. The NF presents proximate composition and content of essential amino acids similar to those in WPI. The Panel notes that the highest mean and highest 95th percentile daily protein intakes from the NF are below the protein population reference intakes for all population groups. Although a tolerable upper intake level has not been derived for protein, the protein intake from the NF may nevertheless further contribute to an already high dietary protein intake in Europe. The exposure to the reported minerals does not raise concerns. The Panel considers that the consumption of the NF is not nutritionally disadvantageous. No genotoxic concerns were identified from the standard in vitro test battery. No adverse effects were observed in the subchronic toxicity study, up to the highest dose tested, i.e. 1,000 mg NF/kg bw per day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of Lemna minor and Lemna gibba whole plant material as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Kouloura, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on Lemna minor and Lemna gibba whole plant material as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Lemna minor and Lemna gibba are aquatic plants commonly named water lentils. The NF is produced by cultivation of Lemna minor and Lemna gibba plants, washing with water and heat treatment. The main constituents of the NF are water, protein and fibre. The Panel notes that the concentration of trace elements and contaminants in the NF is highly dependent on the conditions of cultivation of the plant and the fertiliser composition. The NF is intended to be used as a vegetable, similar to other leafy vegetables. The target population is the general population. The Panel considers that, with the exception of concerns related to the manganese intake, taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The Panel considers that the risk that the consumption of the NF may trigger allergic reactions in humans is low. The Panel concludes that the NF, in consideration of its proposed uses and the concentration of manganese as compared to the normally present concentration of manganese in other leafy vegetables, may be of safety concern, therefore, the safety of the NF cannot currently be established.

2022 - Safety of an aqueous ethanolic extract of Labisia pumila as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; Albert, O.; Matijevic, L.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on aqueous extract of Labisia pumila as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a standardised hydroalcoholic extract from a dried whole plant (including roots) of L. pumila, mixed with maltodextrin (as a drying aid), and proposed by the applicant to be used as a food supplement in amounts up to 750 mg/day. The target population is the general adult population, except pregnant and lactating women. The major constituents of this NF are carbohydrates (up to 85.5%), with a smaller amount of proteins (up to 6.5%), gallic acid (up to 3.7%) and fats (up to 1.6%). The Panel considers that taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. The provided genotoxicity studies do not raise concerns about the genotoxicity of the NF. Based on the available toxicological data, the Panel considers an intake of up to 5 mg/kg body weight per day as safe. For the target population, this level corresponds to 350 mg/day, which is lower than the use level proposed by the applicant. The Panel concludes that the NF is safe for the target population up to 350 mg/day.

2022 - Safety of an extension of use of Yarrowia lipolytica yeast biomass as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use for Yarrowia lipolytica yeast biomass as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The extension of use pertains to the use of the NF as a food ingredient in single meal replacement products for weight reduction for adults at a maximum amount of 6 g NF per day, which is the same amount of NF as already authorised in food supplements for this population group. According to the applicant, food supplements with Yarrowia lipolytica biomass (as already authorised) should not be consumed concomitantly with the meal replacement products in order not to exceed the 6 g NF per day. The Panel considers that the consumption of the NF is not nutritionally disadvantageous under the proposed conditions of use. The Panel concludes that the NF, Yarrowia lipolytica yeast biomass, is safe under the proposed conditions of use.

2022 - Safety of bovine milk osteopontin as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on bovine milk osteopontin (bmOPN) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF concerns OPN derived from bovine whey. The NF is intended to be used at a maximum use level of 151 mg/L, in infant formula (IF), follow-on formula (FoF) and ready-to-eat dairy-based meals for children up to 35 months of age. As compared to the concentrations naturally present in cow’s milk and concentrations found in IF on the market reported in the literature, the proposed use level of the NF represents an about 10-fold higher concentration of bmOPN. The intended use levels of the NF would provide bmOPN at a concentration within the range of human milk (hm) OPN. In a 6-month study, 14, 72 and 140 mg bmOPN/L in reconstituted (as consumed) IF were given to 279 infants in order to study possible effects on frequency and severity of adverse events, and growth, formula intake and stool consistency. Despite that a number of inconsistencies and limitations were noted in the study report, the Panel considers that the results obtained from this study do not raise safety concerns. Considering the source of the NF, that neither the toxicological studies nor the provided infant study do raise safety concerns, and the low bmOPN plasma levels in infants resulting from the consumption of the NF, the Panel considers that the margin of exposure (i.e. 36) between the NOAEL of the subchronic toxicity study (1,200 mg/kg bw per day) and the highest P95 estimate for infants (33.4 mg/kg bw per day) is sufficient. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of cellobiose as a novel food pursuant to regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Albert, O.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on cellobiose as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of two glucose monomers linked by a β-(1–4) glucosidic bond. The applicant intends to add the NF to a variety of foods, and to food supplements aimed at the general population 3 years and older. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. The applicant provided a subchronic toxicological study which did not raise safety concerns. The applicant provided a human dose-escalation study from which the Panel concludes that the consumption of 20 g per day of cellobiose (equivalent to 290 mg/kg body weight (bw) per day in a 70-kg adult) does not raise concern regarding gastrointestinal tolerability. The maximum anticipated daily intake of cellobiose from the proposed uses is below 290 mg/kg bw per day in the target population. Considering the nature, source, compositional characterisation, and production process of the NF, as well as the toxicological data provided, the Panel considers that the NF does not raise safety concerns under the proposed conditions of use.

2022 - Safety of dried coffee husk (cascara) from Coffea arabica L. as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubbada, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J.; van Loveren, H.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on dried coffee husk (cascara) from Coffea arabica L. as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF comprises the skin (exocarp), pulp (mesocarp), mucilage (pectin), parchment (endocarp) and a portion of the silver skin of the coffee fruit, and consists mainly of digestible carbohydrates, dietary fibre and water. The Panel considers that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The NF as such will not be consumed, instead, beverages produced with the infusion of the NF in water will be available to consumers. Considering an 100% extraction of caffeine from the NF to the beverage, the specification limit set for caffeine and the proposed use levels, the maximum concentration of caffeine in infusions produced using the NF could be up to 600 mg/L of drink, a concentration comparable to those in coffee beverages. The Panel notes that consumption of beverages produced using the NF will add significantly to the total dietary intake of caffeine of the general population. The consumption of beverages containing caffeine is not recommended for children, pregnant or breast-feeding women if the caffeine content exceeds 150 mg/L. Taking into account the nature of the NF, the history of use of the NF as food and the proposed uses and use levels, the Panel considers that no toxicological studies are required on the NF. The risk of allergic reactions to the NF is considered low. The Panel concludes that the NF, dried husk of the fruit of Coffea arabica L., is safe under the proposed conditions of use.

2022 - Safety of freeze-dried mycelia of Antrodia camphorata as a novel food pursuant to regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on freeze-dried mycelia of Antrodia camphorata as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced by solid-state cultivation from tissue cultures derived from the fungus Antrodia camphorata. The applicant intends to market the NF in food supplements at a maximum dose of 990 mg per day. The target population is the general population. The NF mainly consists of carbohydrates, proteins and fats, and it contains numerous constituents, such as β-glucans, antroquinonol and triterpenoids. Taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day repeated dose toxicity study and a prenatal developmental toxicity study performed with the NF, the Panel derives a safe level of 16.5 mg/kg body weight per day. The Panel concludes that the NF, freeze-dried mycelia of Antrodia camphorata, is safe at the proposed use level for individuals aged 14 years and above.

2022 - Safety of frozen and freeze-dried formulations of the lesser mealworm (Alphitobius diaperinus larva) as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on frozen and dried formulations from whole lesser mealworm (Alphitobius diaperinus larva) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The term lesser mealworm refers to the larval form of the insect species Alphitobius diaperinus. The NF comprises the frozen and freeze-dried formulations of the lesser mealworm as whole or in the form of a paste or powder. Apart from water in the frozen formulations (whole, paste), the main components of the NF are crude protein and fat, besides smaller amounts of digestible carbohydrates and fibre (chitin). The Panel notes that the levels of contaminants in the NF depend on the concentration of such substances in the insect feed. The Panel notes furthermore that the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF formulations added as an ingredient to various food products such as cereal bars, pasta, meat imitates and bakery products. The target population is the general population. Additionally, the applicant proposed to use the NF as a food supplement in adults. The Panel notes that, considering that the NF will not be the sole source of dietary protein, and the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The submitted subchronic 90-day toxicity study with the NF as testing material did not raise safety concerns. The Panel considers that the consumption of the NF may induce primary sensitisation and allergic reactions to lesser mealworm proteins and may cause allergic reactions in subjects with allergy to crustaceans and dust mites. Additionally, allergens from the feed may end up in the NF. Allergenicity aside, the Panel concludes that the NF is safe under the proposed uses and use levels.

2022 - Safety of hydrothermally treated kernels from edible Jatropha curcas L. (Chuta) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on hydrothermally treated kernels from edible Jatropha curcas (Chuta) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Although Jatropha curcas is generally considered a toxic plant due to the presence of phorbol esters (PEs), edible varieties exist in Central America. The applicant has developed a breeding programme for an edible cultivar and proposes the kernels from this cultivar as an NF as whole kernels or fragments thereof to be used as a snack or as a food ingredient. Procedures are in place to avoid commingling with non-edible kernels, with the last steps being the analytical control of PEs concentrations in all produced batches. The Panel considers that the production process of the NF is sufficiently described and that the information provided on the composition of the NF is sufficient for its characterisation. Components of the NF were tested for genotoxicity applying the standard in vitro test battery and no genotoxic concerns have been identified. In a conservative scenario for exposure to PEs from the NF, it was assumed that all kernels contain PEs at the level of detection of the analytical method. When comparing the estimated maximum exposure to PEs with a reference point from a subchronic study in pigs, a margin of exposure ≥ 900 is obtained, which is considered sufficiently large. The presence of anti-nutritional factors does not pose safety concerns as they are within the ranges found in vegetables. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of iron milk proteinate as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of iron from this source in the context of Directive 2002/46/EC [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on iron milk proteinate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of iron from this source in the context of Directive 2002/46/EC. The NF is a complex of iron, casein and phosphate, which is produced from iron salts (i.e. ferric chloride or ferric sulfate), sodium caseinate and potassium orthophosphate. The NF is proposed by the applicant to be used as a source of iron, of which the NF contains 2–4%. The applicant intends to market the NF as an ingredient in a number of food categories; in food supplements, in total diet replacement for weight control and in foods for special medical purposes. The Panel considers that, taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. The studies provided for ADME and bioavailability indicate that iron from the NF is bioavailable. Overall, the evidence indicates that upon ingestion the NF undergoes digestion into small peptides to yield iron-bound caseinophosphopeptides that are normal constituents of the human diet, and that the iron from the NF does not bypass the homeostatic control of iron as a nutrient. The Panel concludes that the NF, iron milk proteinate, is safe under the proposed conditions of use. The Panel also concludes that the NF is a source from which iron is bioavailable.

2022 - Safety of lacto-N-tetraose (LNT) produced by derivative strains of Escherichia coli BL21 (DE3) as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on lacto-N-tetraose (LNT) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a powdered mixture mainly composed of the human-identical milk oligosaccharide (HiMO) LNT, but it also contains d-lactose, lacto-N-triose II and para-lacto-N-hexaose, and a small fraction of other related saccharides. The NF is produced by fermentation with two genetically modified strains of Escherichia coli BL21 (DE3), the production strain and the optional degradation strain. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant and follow-on formula, food for infants and young children, food for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of LNT from the NF at the maximum proposed use levels does not exceed the intake level of naturally occurring LNT in breastfed infants on a body weight basis. The intake of LNT in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to LNT is also considered of no safety concern. Food supplements are not intended to be used if other foods with added LNT or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2022 - Safety of oil from Schizochytrium sp. (strain ATCC 20889) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF which is the subject of the application is an oil rich in docosahexaenoic acid (DHA) that is produced by the microalgae Schizochytrium sp. (strain ATCC-20889). The applicant proposed to add the NF in infant formulae (IF) and follow-on formulae (FOF) at use levels in accordance with Regulation (EU) No 609/2013. The evidence provided by the applicant does not demonstrate to which species the strain Schizochytrium sp. ATCC 20889 belongs. As the source organism of the NF is not characterised at species level, no assessment for inclusion in the Qualified Presumption of Safety (QPS) list can be performed by EFSA. Marine biotoxins (including cyanotoxins) in the NF were below their limits of quantification. However, since it is unknown to which species the strain Schizochytrium sp. ATCC 20889 belongs, the concern that this strain has the potential to produce other toxins remains. No toxicological studies with the NF were provided by the applicant. Toxicological studies are available with DHA-rich algal oils produced from other strains of Schizochytrium sp. However, the Panel considers that those toxicological studies cannot be used to establish the safety of the oil produced by the strain which is under assessment in this application (Schizochytrium sp. ATCC 20889). Therefore, based on the information provided by the applicant, the Panel concludes that the safety of the NF has not been established.

2022 - Safety of partially defatted house cricket (Acheta domesticus) powder as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Azzollini, D.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on defatted house cricket (Acheta domesticus) powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is proposed as dry powder. The main components of the NF are protein, fat and fibre (chitin). The Panel notes that the concentration of contaminants in the NF depends on the occurrence levels of these substances in the insect feed. The Panel further notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf life. The NF has a high protein content, although the true protein levels are overestimated when using the nitrogen-to-protein conversion factor of 6.25 due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as food ingredient in a number of food products. The target population proposed by the applicant is the general population. The Panel notes that, considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The Panel notes that no genotoxicity and no subchronic toxicity studies with the NF were provided by the applicant. Considering that no safety concerns arise from the history of use of the source of the NF (A. domesticus), and the limited difference between the whole insect and the partially defatted NF, the Panel identified no other safety concerns than allergenicity. The Panel considers that the consumption of the NF might trigger primary sensitisation to A. domesticus proteins and may cause allergic reactions in subjects allergic to crustaceans, mites and molluscs. Additionally, allergens from the feed may end up in the NF. That aside, the Panel concludes that the NF is safe under the proposed uses and use levels.

2022 - Safety of pea and rice protein fermented by Shiitake (Lentinula edodes) mycelia as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on pea and rice protein fermented by Shiitake mushroom (Lentinula edodes) mycelia as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a mixture of fermented pea and rice protein concentrates (65% and 35%, respectively). The NF is proposed to be used as a food ingredient in specific food categories. The target population is the general population. The major constituent of this NF is protein (≥ 75% dry weight), which is well digestible and provides sufficient amounts of essential amino acids. Although a tolerable upper intake level (UL) has not been derived for protein, the protein intake from the NF may nevertheless further contribute to an already high dietary protein intake in Europe. The Panel notes that the cumulative exposure to the nutrients and contaminants analysed does not raise concern. The reported values for the levels of antinutritional factors in the NF are comparable to those in other foodstuffs. The Panel considers that taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. No toxicological studies with the NF were provided by the applicant; however, the Panel considers that no toxicological studies are required for this NF. The NF has the potential capacity to sensitise individuals or to induce allergic reactions in individuals allergic to pea, rice and Shiitake mushroom. However, this risk is expected not to be higher than that resulting from the normal consumption of pea, rice or the fruiting body of the Shiitake mushroom. The Panel considers that the NF is safe at the proposed conditions of use.

2022 - Safety of selenium exposure and limitations of selenoprotein maximization: Molecular and epidemiologic perspectives [Articolo su rivista]
Vinceti, M.; Filippini, T.; Jablonska, E.; Saito, Y.; Wise, L. A.
abstract

Recent evidence from laboratory and epidemiologic studies has shed a different light on selenium health effects and its recommended range of environmental exposure, compared with earlier research. Specifically, epidemiologic studies in Western populations have shown adverse effects of selenium exposure at low levels, sometimes below or slightly above selenium intakes needed to maximize selenoprotein expression and activity. In addition, three recent lines of evidence in molecular and biochemical studies suggest some potential drawbacks associated with selenoprotein maximization: 1) the possibility that selenoprotein upregulation is a compensatory response to oxidative challenge, induced by selenium itself or other oxidants; 2) the capacity of selenoproteins to trigger tumor growth in some circumstances; and 3) the deleterious metabolic effects of selenoproteins and particularly of selenoprotein P. The last observation provides a toxicological basis to explain why in humans selenium intake levels as low as 60 μg/day, still in the range of selenium exposure upregulating selenoprotein expression, might start to increase risk of type 2 diabetes. Overall, these new pieces of evidence from the literature call into question the purported benefit of selenoprotein maximization, and indicate the need to reassess selenium dietary reference values and upper intake level. This reassessment should clarify which range of selenoprotein upregulation follows restoration of adequate selenium availability and which range is driven by a compensatory response to selenium toxicity and oxidative stress.

2022 - Safety of the extension of use of 2’-fucosyllactose (2’-FL) and lacto-N-neotetraose (LNnT) as novel foods in food supplements for infants pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of the extensions of use of the authorised novel foods (NFs) 2’-fucosyllactose (2’-FL) and lacto-N-neotetraose (LNnT) in food supplements (FS) for infants pursuant to Regulation (EU) 2015/2283. The NFs are produced by fermentation with genetically modified strains of Escherichia coli K-12 and already included in the EU list of NFs. The applicant stated that no changes in the production process or the identity of the NFs occurred. The applicant proposes an extension of use of the NF containing 2’-FL in FS intended for infants (< 1 year), at a maximum use level of 1.2 g/day. The applicant also proposes an extension of use of LNnT in FS intended for infants, at a maximum use level of 0.6 g/day. The intake of 2’-FL per kg body weight from the proposed maximum use levels in FS for infants is lower than the lowest estimated mean intake of naturally occurring 2’-FL from human milk. Similarly, the intake of LNnT per kg body weight is lower than the highest estimated mean intake of naturally occurring 2’-FL from human milk. Furthermore, the Panel notes that the proposed uses of 2’-FL in FS for infants are lower than the estimated intake from the already authorised uses of the NF for the same population group. The Panel also notes that the proposed uses of LNnT in FS for infants are similar to the estimated intake from the already authorised uses of the NF for the same population group. The Panel concludes that the use of the NFs containing 2’-FL or LNnT in FS for infants is safe under the proposed conditions of use.

2022 - Safety of the extension of use of 2’-fucosyllactose/difucosyllactose (2’-FL/DFL) mixture and lacto-N-tetraose (LNT) as novel foods in food supplements for infants pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; Loveren, H. V.; Colombo, P.; Noriega Fernandez, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of the extensions of use of the authorised novel foods (NFs) 2’-fucosyllactose/difucosyllactose (2’-FL/DFL) mixture and lacto-N-tetraose (LNT) in food supplements (FS) for infants pursuant to Regulation (EU) 2015/2283. The NFs are produced by fermentation with genetically modified strains of Escherichia coli K-12 DH1 and already included in the EU list of NF. The applicant stated that no changes in the production process or the identity of the NFs occurred. The applicant proposes an extension of use of the NF containing 2’-FL/DFL mixture in FS intended for infants (< 1 year), at a maximum use level of 1.6 g/day for infants ≤ 6 months and up to 1.2 g/day for infants > 6 months. The applicant also proposes an extension of use of LNT in FS intended for infants (< 1 year), at a maximum use level of 0.8 g/day for infants ≤ 6 months and up to 0.6 g/day for infants > 6 months. The intake per kg body weight of 2’-FL/DFL and LNT from the proposed maximum use levels of the respective NFs in FS for infants does not exceed the lowest estimated mean intake of naturally occurring 2’-FL/DFL and it is similar to the highest estimated mean intake of LNT by breastfed infants. In addition, the Panel notes that the proposed uses of the NFs in FS for infants result in lower maximum daily intakes than those from the already authorised uses of the NFs for the same population group. The Panel concludes that the uses of the NFs containing either 2’-FL/DFL or LNT in FS for infants are safe under the proposed conditions of use.

2022 - Safety of the extension of use of galacto-oligosaccharides (GOS) as a novel food in food for special medical purposes pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of galacto-oligosaccharides (GOS) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF (β-GOS) is produced from milk lactose using a β-galactosidase derived from Bifidobacterium bifidum and it is proposed to be used in food for special medical purposes (FSMP). The target population is the general population from 4 years of age onwards. GOS produced according to the same production process are already authorised and included in the EU Union list of novel foods. The applicant stated that the maximum daily intake from the use in FSMP is 8.25 g GOS. GOS are already authorised for use in food supplements up to a daily dose of 16.2 g. FSMP containing GOS are not intended to be used if food supplements containing GOS are consumed on the same day. The information provided on the proposed use levels and anticipated intake does not raise safety concerns. The Panel concludes that the proposed extension of use of GOS in FSMP is safe under the proposed conditions of use.

2022 - Safety of vitamin D2 mushroom powder as a Novel food pursuant to Regulation (EU) 2015/2283 (NF 2019/1471) [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Gerazova-Efremova, K.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on vitamin D2 mushroom powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced from Agaricus bisporus mushroom that has been exposed to ultraviolet (UV) irradiation to induce the conversion of provitamin D2 (ergosterol) to vitamin D2 (ergocalciferol). The NF contains levels of vitamin D in the form of vitamin D2 in the range of 125–375 µg/g. The information provided on the production process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF as an ingredient in a variety of foods and beverages in amounts that result in either 1.125 or 2.25 µg vitamin D2 per 100 g or 100 mL of the food as consumed. The applicant also intends to add the NF in food supplements, for infants from 7 to 11 months at a maximum of 10 µg vitamin D2/day and of 15 µg vitamin D2/day for individuals aged 1 year or older, as well as in foods for special medical purposes (FSMPs) and total and meal diet replacement for weight control. For the adult population, the maximum intended use level in FSMPs is 15 µg vitamin D2/day and 5 µg vitamin D2/meal in total and meal diet replacement for weight control. The Panel concludes that the NF is safe under the proposed conditions of use. The Panel notes uncertainty regarding the calculated combined exposures to vitamin D for the general population, given the fact that the range of foods fortified with vitamin D has increased over the years, as well as the marketing of high-dose vitamin D supplements.

2022 - Safety of zinc l-carnosine as a Novel food pursuant to Regulation (EU) 2015/2283 and the bioavailability of zinc from this source in the context of Directive 2002/46/EC on food supplements [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on zinc l-carnosine as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and as a source of zinc for use in food supplements. The NF is produced by chemical synthesis and is proposed to be used in food supplements as a source of zinc. The target population proposed by the applicant is individuals above the age of 12, excluding pregnant and lactating women. The NF which is the subject of the application is a chelate-complex, formed between Zn2+ and l-carnosine and is present as a mixture of a monomer and a dimer. The material is a powder with particulate nature and is insoluble in water at neutral pH. No relevant data using an existing zinc source as comparator have been made available by the applicant and the actual bioavailability of the zinc provided by the NF at the proposed use levels remains uncharacterised. Owing to the lack of a correct characterisation of the fraction of small particles, including nanoparticles of the NF, the Panel is not in the position to evaluate specification limits for the size of the constituent particles in the NF. Owing to the lack of information on the size distribution and the physico-chemical properties of the particles constituting the NF, the Panel is not in the position to confirm whether the ADME studies and the toxicological studies provided by the applicant are appropriate to assess the safety of the NF. The Panel concludes that the NF is absorbed and provides zinc, but as it is in an insufficiently characterised particulate form, its safety has not been established and the bioavailability has not been determined.

2022 - Safety of β-hydroxybutyrate salts as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Albert, O.; Goumperis, T.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on β-hydroxybutyrate (BHB) salts as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of sodium, magnesium and calcium BHB salts, and is proposed to be used by adults as a food ingredient in a number of food categories and as food supplement. The data provided by the applicant about the identity, the production process and the compositional data of the NF over the course of the risk assessment period were overall considered unsatisfactory. The Panel noted inconsistencies in the reporting of the test item used in the subchronic toxicity study and human studies provided by the applicant. Owing to these deficiencies, the Panel cannot establish a safe intake level of the NF. The Panel concludes that the safety of the NF has not been established.

2022 - Scientific advice related to nutrient profiling for the development of harmonised mandatory front-of-pack nutrition labelling and the setting of nutrient profiles for restricting nutrition and health claims on foods [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver scientific advice related to nutrient profiling for the development of harmonised mandatory front-of-pack nutrition labelling and the setting of nutrient profiles for restricting nutrition and health claims on foods. This Opinion is based on systematic reviews and meta-analyses of human studies on nutritionally adequate diets, data from the Global Burden of Disease framework, clinical practice guidelines, previous EFSA opinions and the priorities set by EU Member States in the context of their Food-Based Dietary Guidelines and associated nutrient/food intake recommendations. Relevant publications were retrieved through comprehensive searches in PubMed. The nutrients included in the assessment are those likely to be consumed in excess or in inadequate amounts in a majority of European countries. Food groups with important roles in European diets have been considered. The Panel concludes that dietary intakes of saturated fatty acids (SFA), sodium and added/free sugars are above, and intakes of dietary fibre and potassium below, current dietary recommendations in a majority of European populations. As excess intakes of SFAs, sodium and added/free sugars and inadequate intakes of dietary fibre and potassium are associated with adverse health effects, they could be included in nutrient profiling models. Energy could be included because a reduction in energy intake is of public health importance for European populations. In food group/category-based nutrient profiling models, total fat could replace energy in most food groups owing to its high-energy density, while the energy density of food groups with low or no fat content may be well accounted for by the inclusion of (added/free) sugars. Some nutrients may be included in nutrient profiling models for reasons other than their public health importance, e.g. as a proxy for other nutrients of public health importance, or to allow for a better discrimination of foods within the same food category.

2022 - Selenium Species in Cerebrospinal Fluid and Hippocampal Volume among Individuals with Mild Cognitive Impairment [Articolo su rivista]
Vinceti, Marco; Balboni, Erica; Filippini, Tommaso; Wise, Lauren A; Nocetti, Luca; Eichmüller, Marcel; Zamboni, Giovanna; Chiari, Annalisa; Michalke, Bernhard
abstract

2022 - Selenium and its association with oxidative stress and genotoxicity risk in a healthy Italian population: a cross sectional study [Abstract in Atti di Convegno]
Urbano, Teresa; Filippini, Tommaso; Malavolti, Marcella; Fustinoni, Silvia; Michalke, Bernhard; Vinceti, Marco
abstract

Background Selenium is present in trace amounts and different chemical forms in living organisms, which may beneficially and adversely affect cellular redox status. 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine and a sensitive biomarker of oxidative stress and genotoxicity in biological systems. In this study, we aimed to determine if selenium exposure in a population in Northern Italy may be associated with 8-oxodG levels in urine and if sex and other factors may influence such association. Methods/Approach We recruited 137 substantially healthy and non-smoking blood donors from the Reggio Emilia province at the Transfusion Medicine Unit of the Reggio Emilia Hospital. Their median age was 48.2 years, and the recruitment occurred 2017-19. We assessed selenium in urine and serum, and urinary 8-oxodG levels. We also speciated selenium in serum. We used cubic spline regression analyses to investigate the association between selenium matrices and urinary content of 8-oxodG/g creatinine. Results Median urinary selenium and 8-oxodG levels were 22.02 µg/L and 3.21 µg/g creatinine, respectively. Median total serum concentrations were 116.50 µg/L in the 104 individuals for which a serum sample was available. We found that urinary selenium positively correlated with 8-oxodG levels in men, while in women an inverted U-shaped association emerged. Total organic selenium and selenoprotein P levels were positively associated with 8-oxodG until 100 µg/L and then the association became slightly inverse in both sexes. In males, glutathione peroxidase-bound selenium, selenomethionine and human serum albumin-bound selenium were positively correlated with 8-oxodG, while negative associations emerged for inorganic selenium species. In females, positive associations, though slightly positive, emerged for organic species. Conclusions Our study highlights the different role played by selenium compounds, suggesting that organic selenium - but not its inorganic species - may exert genotoxic effects, and that sex considerably influences the risk of oxidative stress and genotoxicity associated with selenium exposure.

2022 - Selenium status and immunity [Articolo su rivista]
Fairweather-Tait, S. J.; Filippini, T.; Vinceti, M.
abstract

Selenium is found at the active centre of twenty-five selenoproteins which have a variety of roles, including the well-characterised function of antioxidant defense, but it also is claimed to be involved in the immune system. However, due to limited and conflicting data for different parameters of immune function, intakes of selenium that have an influence on immune function are uncertain. This review covers the relationship between selenium and immune function in man, focusing on the highest level of evidence, namely that generated by randomized controlled trials (RCTs), in which the effect of selective administration of selenium, in foods or a supplement, on immune function was assessed. A total of nine RCTs were identified from a systematic search of the literature, and some of these trials reported effects on T and NK cells, which were dependent on the dose and form of selenium administered, but little effect of selenium on humoral immunity. There is clearly a need to undertake dose-response analysis of cellular immunity data in order to derive quantitative relationships between selenium intake and measures of immune function. Overall, limited effects on immunity emerged from experimental studies in humans, though additional investigation on the potential influence of selenium status on cellular immunity appears to be warranted.

2022 - Selenocompounds and neurological disease [Abstract in Atti di Convegno]
Vinceti, M.; Ferrante, M; Filippini, T.; Urbano, T.
abstract

2022 - Selenoprotein P Concentrations in the Cerebrospinal Fluid and Serum of Individuals Affected by Amyotrophic Lateral Sclerosis, Mild Cognitive Impairment and Alzheimer’s Dementia [Articolo su rivista]
Urbano, Teresa; Vinceti, Marco; Mandrioli, Jessica; Chiari, Annalisa; Filippini, Tommaso; Bedin, Roberta; Tondelli, Manuela; Simonini, Cecilia; Zamboni, Giovanna; Shimizu, Misaki; Saito, Yoshiro
abstract

Selenoprotein P, a selenium-transporter protein, has been hypothesized to play a role in the etiology of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's dementia (AD). However, data in humans are scarce and largely confined to autoptic samples. In this case-control study, we determined selenoprotein P concentrations in both the cerebrospinal fluid (CSF) and the serum of 50 individuals diagnosed with ALS, 30 with AD, 54 with mild cognitive impairment (MCI) and of 30 controls, using sandwich enzyme-linked immunosorbent assay (ELISA) methods. We found a positive and generally linear association between CSF and serum selenoprotein P concentrations in all groups. CSF selenoprotein P and biomarkers of neurodegeneration were positively associated in AD, while for MCI, we found an inverted-U-shaped relation. CSF selenoprotein P concentrations were higher in AD and MCI than in ALS and controls, while in serum, the highest concentrations were found in MCI and ALS. Logistic and cubic spline regression analyses showed an inverse association between CSF selenoprotein P levels and ALS risk, and a positive association for AD risk, while an inverted-U-shaped relation with MCI risk emerged. Conversely, serum selenoprotein P concentrations were positively associated with risk of all conditions but only in their lower range. Overall, these findings indicate some abnormalities of selenoprotein P concentrations in both the central nervous system and blood associated with ALS and neurocognitive disorders, though in different directions. These alterations may reflect either phenomena of etiologic relevance or disease-induced alterations of nutritional and metabolic status.

2022 - Seroprevalence Survey of Anti-SARS-CoV-2 Antibodies in a Population of Emilia-Romagna Region, Northern Italy [Articolo su rivista]
Paduano, Stefania; Galante, Pasquale; Berselli, Nausicaa; Ugolotti, Luca; Modenese, Alberto; Poggi, Alessandro; Malavolti, Marcella; Turchi, Sara; Marchesi, Isabella; Vivoli, Roberto; Perlini, Paola; Bellucci, Rossana; Gobba, Fabriziomaria; Vinceti, Marco; Filippini, Tommaso; Bargellini, Annalisa
abstract

taly was the first Western European country to be severely hit by the COVID-19 pandemic. Variations in seroprevalence rates were reported according to geographical and temporal differences of previous surveys, as well as depending on demographic and occupational factors. In this cross-sectional study, we evaluated the prevalence of anti-SARS-CoV-2 antibodies in a population of the Emilia-Romagna region in Northern Italy after the first wave in the period from 26 September 2020–26 March 2021. We included 5128 subjects who voluntarily underwent serological tests to determine anti-SARS-CoV-2 antibody positivity, including both self-referred individuals (24.2%) and workers adhering to company screening programs (76.8%). Overall, seroprevalence was 11.3%, higher in self-referred (13.8%) than employed-referred (10.5%) individuals. A slightly higher seroprevalence emerged in women compared to men (12.3% and 10.7%), as well as in the extreme age categories (18.6% for 60–69 years, 18.0% for ≥70 years, and 17.1% for <20 years compared to 7.6% for 20–39 years). Healthcare professionals showed the highest prevalence of seropositivity (22.9%), followed by workers in direct contact with customers, such as the communication, finance, and tourism sectors (15.7%). Overall subgroups seroprevalence increased compared to the first wave data but the trends agreed between the first and subsequent waves, except for an increase in the younger age group and in the sector in direct contact with customers. Among the occupational categories, our study confirms that healthcare workers and workers in the sports sector were at high risk of exposure to SARS-CoV-2.

2022 - Sodium Intake and Risk of Hypertension: A Systematic Review and Dose-Response Meta-analysis of Observational Cohort Studies [Articolo su rivista]
Filippini, Tommaso; Malavolti, Marcella; Whelton, Paul K; Vinceti, Marco
abstract

Purpose of the review: To assess the relationship between sodium intake and hypertension risk in cohort studies, based on a systematic review up to January 21, 2022, that also employed a dose-response meta-analysis. Recent findings: Dose-response analysis of available cohort studies (n = 11), using a dietary intake or urinary sodium excretion of 2 g/day as the reference category, showed an excess risk starting at 3 g/day. However, we found a linear relationship across the entire range of sodium exposure in an analysis restricted to studies that used 24 h urinary sodium excretion information and had a low risk of bias. This review confirms prior findings based on experimental studies and identified an almost linear relationship between sodium intake/excretion and hypertension risk in cohort studies, reinforcing the validity of recommendations to prevent cardiovascular disease through the reduction of sodium intake in both normotensive and hypertensive adults.

2022 - Sodium intake and cardiovascular diseases: a systematic review and dose–response meta‑analysis [Abstract in Atti di Convegno]
Malavolti, M; Filippini, T; Urbano, T; Vinceti, M.
abstract

2022 - Statement on safety of cannabidiol as a novel food: data gaps and uncertainties [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; Trezza, V.; van Loveren, H.; Albert, O.; Dumas, C.; Germini, A.; Gelbmann, W.; Kass, G.; Kouloura, E.; Noriega Fernandez, E.; Rossi, A.; Knutsen, H. K.
abstract

The European Commission has determined that cannabidiol (CBD) can be considered as a novel food (NF), and currently, 19 applications are under assessment at EFSA. While assessing these, it has become clear that there are knowledge gaps that need to be addressed before a conclusion on the safety of CBD can be reached. Consequently, EFSA has issued this statement, summarising the state of knowledge on the safety of CBD consumption and highlighting areas where more data are needed. Literature searches for both animal and human studies have been conducted to identify safety concerns. Many human studies have been carried out with Epidyolex®, a CBD drug authorised to treat refractory epilepsies. In the context of medical conditions, adverse effects are tolerated if the benefit outweighs the adverse effect. This is, however, not acceptable when considering CBD as a NF. Furthermore, most of the human data referred to in the CBD applications investigated the efficacy of Epidyolex (or CBD) at therapeutic doses. No NOAEL could be identified from these studies. Given the complexity and importance of CBD receptors and pathways, interactions need to be taken into account when considering CBD as a NF. The effects on drug metabolism need to be clarified. Toxicokinetics in different matrices, the half-life and accumulation need to be examined. The effect of CBD on liver, gastrointestinal tract, endocrine system, nervous system and on psychological function needs to be clarified. Studies in animals show significant reproductive toxicity, and the extent to which this occurs in humans generally and in women of child-bearing age specifically needs to be assessed. Considering the significant uncertainties and data gaps, the Panel concludes that the safety of CBD as a NF cannot currently be established.

2022 - Substantial impact of mobility restrictions on reducing COVID-19 incidence in Italy in 2020 [Articolo su rivista]
Vinceti, Marco; Balboni, Erica; Rothman, Kenneth J; Teggi, Sergio; Bellino, Stefania; Pezzotti, Patrizio; Ferrari, Fabrizio; Orsini, Nicola; Filippini, Tommaso
abstract

Italy was the first country after China to be severely affected by the COVID-19 pandemic, in early 2020. The country responded swiftly to the outbreak with a nationwide two-step lockdown, the first one light, and the second one tight. By analysing 2020 national mobile phone movements, we assessed how lockdown compliance influenced its efficacy.

2022 - The questionnaire design process in the European Human Biomonitoring Initiative (HBM4EU) [Articolo su rivista]
Gonzalez-Alzaga, B.; Hernandez, A. F.; Kim Pack, L.; Iavicoli, I.; Tolonen, H.; Santonen, T.; Vinceti, M.; Filippini, T.; Moshammer, H.; Probst- Hensch, N.; Kolossa-Gehring, M.; Lacasana, M.
abstract

Background: Designing questionnaires is a key point of epidemiological studies assessing human exposure to chemicals. The lack of validated questionnaires can lead to the use of previously developed and sub-optimally adapted questionnaires, which may result in information biases that affect the study's validity. On this ground, a multidisciplinary group of researchers developed a series of tools to support data collection within the HBM4EU initiative. The objective of this paper is to share the process of developing HBM4EU questionnaires, as well as to provide researchers with harmonized procedures that could help them to design future questionnaires to assess environmental exposures. Methods: In the frame of the work package on survey design and fieldwork of the HBM4EU, researchers carried out procedures necessary for the development of quality questionnaires and related data collection tools. These procedures consisted of a systematic search to identify questionnaires used in previous human biomonitoring (HBM) studies, as well as the development of a checklist and evaluation sheet to assess the questionnaires identified. The results of these evaluations were taken into consideration for the development of the final questionnaires. Results: The main points covered by each of the sections included in HBM4EU questionnaires are described and discussed in detail. Additional tools developed for data collection in the HBM4EU (e.g. non-responder questionnaire, satisfaction questionnaire, matrix-specific questionnaire) are also addressed. Special attention is paid to the limitations faced and hurdles overcome during the process of questionnaire development. Conclusions: Designing questionnaires for use in HBM studies requires substantial effort by a multidisciplinary team to guarantee that the quality of the information collected meets the study's objectives. The process of questionnaire development described herein will contribute to improve the harmonization of HBM studies within the social and environmental context of the EU countries.

2022 - Tolerable upper intake level for dietary sugars [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Adan, R.; Emmett, P.; Galli, C.; Kersting, M.; Moynihan, P.; Tappy, L.; Ciccolallo, L.; de Sesmaisons-Lecarre, A.; Fabiani, L.; Horvath, Z.; Martino, L.; Munoz Guajardo, I.; Valtuena Martinez, S.; Vinceti, M.
abstract

Following a request from five European Nordic countries, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was tasked to provide scientific advice on a tolerable upper intake level (UL) or a safe level of intake for dietary (total/added/free) sugars based on available data on chronic metabolic diseases, pregnancy-related endpoints and dental caries. Specific sugar types (fructose) and sources of sugars were also addressed. The intake of dietary sugars is a well-established hazard in relation to dental caries in humans. Based on a systematic review of the literature, prospective cohort studies do not support a positive relationship between the intake of dietary sugars, in isocaloric exchange with other macronutrients, and any of the chronic metabolic diseases or pregnancy-related endpoints assessed. Based on randomised control trials on surrogate disease endpoints, there is evidence for a positive and causal relationship between the intake of added/free sugars and risk of some chronic metabolic diseases: The level of certainty is moderate for obesity and dyslipidaemia (> 50–75% probability), low for non-alcoholic fatty liver disease and type 2 diabetes (> 15–50% probability) and very low for hypertension (0–15% probability). Health effects of added vs. free sugars could not be compared. A level of sugars intake at which the risk of dental caries/chronic metabolic diseases is not increased could not be identified over the range of observed intakes, and thus, a UL or a safe level of intake could not be set. Based on available data and related uncertainties, the intake of added and free sugars should be as low as possible in the context of a nutritionally adequate diet. Decreasing the intake of added and free sugars would decrease the intake of total sugars to a similar extent. This opinion can assist EU Member States in setting national goals/recommendations.

2022 - Zinc and selenium supplementation in COVID-19 prevention and treatment: a systematic review of the experimental studies [Articolo su rivista]
Balboni, E.; Zagnoli, F.; Filippini, T.; Fairweather-Tait, S. J.; Vinceti, M.
abstract

Background and aim: The COVID-19 pandemic has severely affected the world's population in the last two years. Along with non-pharmacological public health interventions, major efforts have also been made to identify effective drugs or active substances for COVID-19 prevention and treatment. These include, among many others, the trace elements zinc and selenium, based on laboratory studies and some observational human studies. However, both of these study designs are not adequate to identify and approve treatments in human medicine, and experimental studies in the form of randomized controlled trials are needed to demonstrate the effectiveness and the safety of any interventions. Methods: We undertook a systematic review in which we searched for published and unpublished clinical trials using zinc or selenium supplementation to treat or prevent COVID-19 in the Pubmed, Scopus and ClinicalTrials databases up to 10 January 2022. Results: Amongst the published studies, we did not find any trial with selenium, whereas we retrieved four eligible randomized clinical trials using zinc supplementation, only one of which was double-blind. One of these trials looked at the effect of the intervention on the rate of new SARS-CoV-2 infections, and three at the COVID-19 clinical outcome in already infected individuals. The study populations of the four trials were very heterogeneous, ranging from uninfected individuals to those hospitalized for COVID-19. Only two studies investigated zinc alone in the intervention arm with no differences in the endpoints. The other two studies examined zinc in association with one or more drugs and supplements in the intervention arm, therefore making it impossible to disentangle any specific effects of the element. In addition, we identified 22 unpublished ongoing clinical trials, 19 on zinc, one on selenium and two on both elements. Conclusion: No trials investigated the effect of selenium supplementation on COVID-19, while the very few studies on the effects of zinc supplementation did not confirm efficacy. Therefore, preventive or therapeutic interventions against COVID-19 based on zinc or selenium supplementation are currently unjustified, although when the results of the on-going studies are published, this may change our conclusion.

2021 - A systematic review and dose-response meta-analysis of exposure to environmental selenium and the risk of type 2 diabetes in nonexperimental studies [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Wise, Lauren A; Rothman, Kenneth J
abstract

Accumulating evidence from both experimental and nonexperimental human studies in the last 15 years indicates that exposure to high levels of the trace element selenium increases the risk of type 2 diabetes. However, the relation of dose to effect is not well understood because randomized controlled trials used only one dose (200 mug/day) of selenium supplementation. While no new trial on this topic has been published since 2018, several nonexperimental studies have appeared. We therefore updated a previous meta-analysis to include recently published observational studies, and incorporated the recently developed one-stage random-effects model to display the dose-response relation between selenium and diabetes. We retrieved 34 potentially eligible nonexperimental studies on selenium and diabetes risk up to April 15, 2021. The bulk of the evidence indicates a direct relation between blood, dietary and urinary levels of selenium and risk of diabetes, but not with nail selenium, which is considered a less reliable biomarker. The association was nonlinear, with risk increasing above 80 mug/day of dietary selenium. Whole blood/plasma/serum selenium concentrations of 160 mug/L corresponded to a risk ratio of 1.96 (95% CI 1.27-3.03) compared with a concentration of 90 mug/L (approximately 60 mug of daily selenium intake). The cohort studies, which are less susceptible to reverse causation bias, indicated increased risk for both blood and urine selenium levels and dietary selenium intake, whereas no such pattern emerged from studies relying on nail selenium content. Overall, the nonexperimental studies agree with findings from randomized controlled trials, indicating that moderate to high levels of selenium exposure are associated with increased risk for type 2 diabetes.

2021 - Affron® and increase in positive mood: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Bresson, Jean-Louis; Siani, Alfonso
abstract

Following an application from Pharmactive Biotech Products, S.L. submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Spain, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to affron (R) and contributes to maintain a healthy mood. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is affron (R), an aqueous saffron extract with a content of the sum of crocins and safranal typically between 3.5% and 3.9%. The Panel notes that affron (R) is sufficiently characterised. The claimed effect proposed by the applicant is 'contributes to maintain a healthy mood'. The Panel notes that increase in positive mood is a beneficial physiological effect for individuals with low mood or anxiety. One human intervention study showed that consumption of affron (R) at a dose of 28 mg/day for 4 weeks improves mood in a population of adults with low mood. However, the results have not been replicated in other studies. The information supplied by the applicant did not provide evidence for a plausible mechanism by which affron (R) could exert the claimed effect. The Panel concludes that the evidence is insufficient to establish a cause and effect relationship between the consumption of affron (R) and increase in positive mood. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2021 - An assessment of case-fatality and infection-fatality rates of first and second COVID-19 waves in italy [Articolo su rivista]
Filippini, T.; Zagnoli, F.; Bosi, M.; Giannone, M. E.; Marchesi, C.; Vinceti, M.
abstract

Background and aim: The exact COVID-19 severity is still not well defined and it is hotly debated due to a few methodological issues such as the uncertainties about the spread of the SARS-CoV-2 infection. Methods: We investigated COVID-19 case-fatality rate and infection-fatality rate in 2020 in Italy, a country severely affected by the pandemic, basing our assessment on publicly available data, and calculating such measures during the first and second waves. Results: We found that province-specific crude case-fatality rate in the first wave (February-July 2020) had a median value of 12.0%. Data about infection-fatality rate was more difficult to compute, due to large underestimation of SARS-CoV-2 infection during the first wave when asymptomatic individuals were very rarely tested. However, when using reference population-based seroprev-alence data for anti-SARS-CoV-2 antibodies collected in May-July 2020, we computed an infection-fatality rate of 2.2%. During the second wave (Sep-Dec 2020), when SARS-CoV-2 testing was greatly increased and extended to many asymptomatic individuals, we could only compute a ‘hybrid’ case/infection-fatality rate with a value of 2.2%, similar to the infection-fatality rate of the first wave. Conclusions: Overall, this study al-lowed to assess the COVID-19 case-and infection-fatality rates in Italy before of variant spread and vaccine availability, confirming their high values compared with other airborne infections like influenza. Our findings for Italy were similar to those characterizing other Western European countries.

2021 - Anti-SARS-CoV-2 antibodies frequency in non-Health Care Workers in a highly industrialized province of northern Italy [Relazione in Atti di Convegno]
Modenese, Alberto; Mazzoli, Tommaso; Berselli, Nausicaa; Ferrari, Davide; Bargellini, Annalisa; Borella, Paola; Filippini, Tommaso; Marchesi, Isabella; Paduano, Stefania; Vinceti, Marco; Gobba, Fabriziomaria
abstract

2021 - Artificial light at night and breast cancer risk: A systematic review and dose-response meta-analysis [Abstract in Rivista]
Urbano, Teresa; Vinceti, Marco; Wise, Lauren Anne; Filippini, Tommaso
abstract

BACKGROUND AND AIM: Artificial lightning has been suggested to be one of the environmental risk factor of breast cancer onset and progression, based on epidemiologic evidence and biological plausibility. Possible mechanisms include DNA damage, impairment of melatonin and estrogens secretion, inflammation, and metabolic function. METHODS: We performed a systematic review of the epidemiological studies examining the association between light-at-night (LAN) exposure and breast cancer risk and we modeled the shape of the relation using a dose-response meta-analysis. After performing an online literature search up to March 21, 2021, we retrieved 16 eligible publications, including eight cohort and eight case-control studies. RESULTS:In analyses comparing highest versus lowest LAN exposure, there was a positive association between LAN exposure and disease risk (risk ratio (RR)=1.10, 95% confidence interval (CI): 1.06-1.14), with relatively consistent associations observed in case-control studies (RR=1.14, 95% CI: 0.98-1.34) and cohort studies (RR=1.10, 95% CI: 1.06-1.14). In stratified analyses, RRs were similar for outdoor and indoor LAN exposure, while a stronger RR was observed among premenopausal women, women in the BMI category 20-25 kg/m2, and for estrogen-receptor positive breast cancer. The dose-response meta-analysis, implemented in studies investigating outdoor LAN only (for comparable exposure assessment), indicated a linear association with increasing risk up to 40 nW/cm2/sr after which a plateau was reached, especially among premenopausal women. CONCLUSIONS:Overall, this first review assessing the dose-response relation between LAN and breast cancer generally supports a positive association. KEYWORDS: Light pollution, Cancer and cancer precursors, Environmental epidemiology, Non-chemical stressors

2021 - Association between cadmium and genotoxicity and oxidative stress risk biomarkers in a population of Northern Italy [Abstract in Rivista]
Urbano, Teresa; Filippini, Tommaso; Lasagni, Daniela; De Luca, Tiziana; Sucato, Sabrina; Polledri, Elisa; Malavolti, Marcella; Baraldi, Claudia; Santachiara, Annalisa; Pertinhez, Thelma A.; Baricchi, Roberto; Fustinoni, Silvia; Vinceti, Marco
abstract

Cadmium is a toxic heavy metal exerting several adverse effects in humans, especially for kidney, bone, liver, and cardiovascular system. In particular, genotoxic effects may occur through several epigenetic mechanisms, but a direct genotoxicity has been suggested. 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine, largely used as biomarker of oxidative stress in urine. In this study, we aimed to assess cadmium levels in a population in Northern Italy, in order to evaluate the correlation between cadmium exposure with different haematological and biochemical parameters, as well as the relationship with 8-oxodG levels. METHODS: We recruited healthy and non-smoking subjects living in the Reggio Emilia province in the period 2017-2019 at the Transfusion Medicine Unit of Santa Maria Nuova Hospital, AUSL-IRCCS of Reggio Emilia, Northern Italy. Urinary cadmium and 8-oxodG, and fasting blood haematological and biochemical parameters were assessed. RESULTS:We eventually recruited 140 participants (mean age 47.4 years). Mean urinary cadmium and 8-oxodG levels were 0.25 µg/L (range: 0.01–1.33 µg/L) and 3.68 µg/g creatinine respectively. All haematological and biochemical parameters were in the normal range. We found a positive association of cadmium concentrations with alanine aminotransferase, total cholesterol, triglyceride, and TSH levels, while a negative one was observed with glycaemia, HDL levels. In addition, we found a strong positive correlation between urinary cadmium and 8-oxodG. CONCLUSIONS:Our study suggests that cadmium exposure is associated with detrimental effects on some haematological and biochemical parameters even at very low levels, generally considered safe for the general population. The positive association between urinary cadmium levels and oxidative stress, as assessed through 8-oxodG levels, highlights the potential role of this heavy metal in causing direct genotoxic effects. We acknowledge the collaboration of Transfusion Medicine Unit-Reggio Emilia Hospital personnel, AVIS-Section of Reggio Emilia staff and volunteers, and all blood donors who participated to this study

2021 - Association between outdoor traffic air pollutants and spread of SARS-CoV-2 pandemic in Modena, Northern Italy [Abstract in Rivista]
Filippini, Tommaso; Bigi, Alessandro; Teggi, Sergio; Bargellini, Annalisa; Vinceti, Marco
abstract

BACKGROUND AND AIM: Italy was the first European country severely affected by the SARS-CoV-2 pandemic, especially during the first wave in the North of the country. In particular, Modena is a city of Emilia-Romagna which is a region entirely included in the Po valley, one of European areas characterized by the heaviest air pollution levels due also to its orography. Previous studies yielded at a regional level suggested that higher air pollutant levels may increase both SARS-CoV-2 infection and mortality. METHODS: In this study, we further investigated the association between air pollutant exposure and spread of the SARS-CoV-2 using data collected from Modena municipality in the period February 2020-April 2021. We used traffic pollutant levels collected from an urban air quality monitoring station in the period January 2020-January 2021, including particulate matter (PM10), nitrogen oxides (NO2 and NOx), benzene, and black carbon (BC). We used a random-effects linear regression model within panel data analysis over the study period and we computed beta correlation coefficients (beta) with 95% confidence interval-CI between mean daily pollutant concentrations and SARS-CoV-2 daily positive cases diagnosed in Modena. RESULTS:We found a positive correlation between all traffic pollutants and SARS-CoV-2 cases, namely for PM10 beta was 1.23 (95%CI 1.00-1.46), lower for NOx (beta=0.66, 95%CI 0.56-0.75), and higher for NO2 (beta=1.95, 95%CI 1.59-2.31), benzene (beta=41.41, 95%CI 36.23-46.59), and BC (beta=5.95, 95%CI 1.19-10.72). CONCLUSIONS:Notwithstanding the limitations of use of aggregated data and potential the residual confounding, these findings seem to support the hypothesis that high levels of air pollution may favor the spread of SARS-CoV-2 infection, or alternatively that they reflect a higher mobility and number of social contacts that favor the spread of the infection. KEYWORDS: Air pollution, Traffic-related, Infectious diseases, Environmental epidemiology, Exposure assessment

2021 - Association of urinary and dietary selenium and of serum selenium species with serum alanine aminotransferase in a healthy italian population [Articolo su rivista]
Urbano, T.; Filippini, T.; Lasagni, D.; De Luca, T.; Grill, P.; Sucato, S.; Polledri, E.; Noumbi, G. D.; Malavolti, M.; Santachiara, A.; Pertinhez, T. A.; Baricchi, R.; Fustinoni, S.; Michalke, B.; Vinceti, M.
abstract

The trace element selenium is of considerable interest due to its toxic and nutritional properties, which markedly differ according to the dose and the chemical form. It has been shown that excess selenium intake increases the risk of type 2 diabetes and, possibly, other metabolic diseases like hyperlipidemia and non-alcoholic fatty liver disease (NAFLD). For the latter, however, epidemiologic evidence is still limited. We carried out a cross-sectional study recruiting 137 healthy blood donors living in Northern Italy and assessed their exposure to selenium through different methods and measuring serum selenium species. We performed linear and spline regression analyses to assess the relation of selenium and its forms with serum alanine aminotransferase (ALT) levels, a marker of NAFLD. Urinary selenium levels were positively and somewhat linearly correlated with ALT (beta regression coefficient (β) 0.11). Conversely, the association of dietary selenium intake with ALT was positive up to 100 µg/day and null above that amount (β 0.03). Total serum selenium was inversely associated with ALT up to 120 µg/L, and slightly positive above that amount. Concerning the different serum selenium species, ALT positively correlated with two organic forms, selenocysteine (β 0.27) and glutathione peroxidase-bound selenium (β 0.09), showed a U-shaped relation with the inorganic tetravalent form, selenite, and an inverse association with human serum albumin-bound selenium (β −0.56). Our results suggest that overall exposure to selenium, and more specifically to some of its chemical forms, is positively associated with ALT, even at levels so far generally considered to be safe. Our findings add to the evidence suggesting that low-dose selenium overexposure is associated with NAFLD.

2021 - Associations between mortality from COVID-19 in two Italian regions and outdoor air pollution as assessed through tropospheric nitrogen dioxide [Articolo su rivista]
Filippini, T.; Rothman, K. J.; Cocchio, S.; Narne, E.; Mantoan, D.; Saia, M.; Goffi, A.; Ferrari, F.; Maffeis, G.; Orsini, N.; Baldo, V.; Vinceti, M.
abstract

After the appearance of COVID-19 in China last December 2019, Italy was the first European country to be severely affected by the outbreak. The first diagnosis in Italy was on February 20, 2020, followed by the establishment of a light and a tight lockdown on February 23 and on March 8, 2020, respectively. The virus spread rapidly, particularly in the North of the country in the ‘Padan Plain’ area, known as one of the most polluted regions in Europe. Air pollution has been recently hypothesized to enhance the clinical severity of SARS-CoV-2 infection, acting through adverse effects on immunity, induction of respiratory and other chronic disease, upregulation of viral receptor ACE-2, and possible pathogen transportation as a virus carrier. We investigated the association between air pollution and subsequent COVID-19 mortality rates within two Italian regions (Veneto and Emilia-Romagna). We estimated ground-level nitrogen dioxide through its tropospheric levels using data available from the Sentinel-5P satellites of the European Space Agency Copernicus Earth Observation Programme before the lockdown. We then examined COVID-19 mortality rates in relation to the nitrogen dioxide levels at three 14-day lag points after the lockdown, namely March 8, 22 and April 5, 2020. Using a multivariable negative binomial regression model, we found an association between nitrogen dioxide and COVID-19 mortality. Although ecological data provide only weak evidence, these findings indicate an association between air pollution levels and COVID-19 severity.

2021 - Associations between urinary and dietary selenium and blood metabolic parameters in a healthy northern italy population [Articolo su rivista]
Urbano, T.; Filippini, T.; Lasagni, D.; De Luca, T.; Sucato, S.; Polledri, E.; Bruzziches, F.; Malavolti, M.; Baraldi, C.; Santachiara, A.; Pertinhez, T. A.; Baricchi, R.; Fustinoni, S.; Vinceti, M.
abstract

Selenium is both an essential nutrient and a highly toxic element, depending on its dose and chemical forms. We aimed to quantify urinary selenium excretion and dietary selenium intake in 137 healthy non-smoking blood donors living in the northern Italian province of Reggio Emilia. We assessed selenium status by determining urinary selenium levels (mean 26.77 µg/L), and by estimating dietary selenium intake (mean 84.09 µg/day) using a validated semi-quantitative food frequency questionnaire. Fasting blood levels of glucose, lipids and thyroid-stimulating hormone were measured using automatized laboratory procedures. Dietary and urinary selenium were correlated (beta coefficient (β) = 0.19). Despite this, the association of the two indicators with health endpoints tended to diverge. Using linear regression analysis adjusted for age, sex, body mass index, cotinine levels and alcohol intake, we observed a positive association between urinary selenium and blood triglyceride (β = 0.14), LDL-cholesterol (β = 0.07) and glucose levels (β = 0.08), and an inverse one with HDL-cholesterol (β = −0.12). Concerning dietary selenium, a slightly positive association could be found with glycemic levels only (β = 0.02), while a negative one emerged for other endpoints. The two selenium indicators showed conflicting and statistically highly imprecise associations with circulating TSH levels. Our findings suggest that higher selenium exposure is adversely associated with blood glucose levels and lipid profile. This is the case even at selenium exposures not exceeding tolerable upper intake levels according to current guidelines.

2021 - Atrial fibrillation and other risk factors for early-onset dementia: an Italian case-control study [Abstract in Rivista]
Filippini, T; Adani, G; Garuti, C; Malavolti, M; Vinceti, G; Zamboni, G; Tondelli, M; Galli, C; Costa, M; Chiari, A; Vinceti, M
abstract

2021 - Back to basics in COVID-19: Antigens and antibodies—Completing the puzzle [Articolo su rivista]
Neagu, M.; Calina, D.; Docea, A. O.; Constantin, C.; Filippini, T.; Vinceti, M.; Drakoulis, N.; Poulas, K.; Nikolouzakis, T. K.; Spandidos, D. A.; Tsatsakis, A.
abstract

The outbreak of the coronavirus disease 2019 (COVID-19) has gathered 1 year of scientific/clinical information. This informational asset should be thoroughly and wisely used in the coming year colliding in a global task force to control this infection. Epidemiology of this infection shows that the available estimates of SARS-CoV-2 infection prevalence largely depended on the availability of molecular testing and the extent of tested population. Within molecular diagnosis, the viability and infectiousness of the virus in the tested samples should be further investigated. Moreover, SARS-CoV-2 has a genetic normal evolution that is a dynamic process. The immune system participates to the counterattack of the viral infection by pathogen elimination, cellular homoeostasis, tissue repair and generation of memory cells that would be reactivated upon a second encounter with the same virus. In all these stages, we still have knowledge to be gathered regarding antibody persistence, protective effects and immunological memory. Moreover, information regarding the intense pro-inflammatory action in severe cases still lacks and this is important in stratifying patients for difficult to treat cases. Without being exhaustive, the review will cover these important issues to be acknowledged to further advance in the battle against the current pandemia.

2021 - Beta-glucans from oats and/or barley in a ready-to-eat cereal manufactured via pressure cooking and reduction of blood-glucose rise after consumption: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Bresson, Jean-Louis; Siani, Alfonso
abstract

Following an application from Nestle S.A. submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to beta-glucans from oats and/or barley in a ready-to-eat cereal manufactured via pressure cooking and reduction of blood glucose rise after consumption. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed is `beta- glucans from oats and/or barley incorporated into ready-to-eat breakfast cereals manufactured via pressure cooking'. The applicant proposed that at least 1.3 g of beta-glucans/ 25 g of available carbohydrates in ready-to-eat breakfast cereals manufactured via pressure cooking should be consumed. Beta-glucans from oats, barley or any combination thereof incorporated into readyto-eat cereals manufactured by pressure cooking, are sufficiently characterised. The claimed effect proposed is `reduction of the blood glucose rise after the meal'. The reduction of post-prandial glycaemic responses (as long as post-prandial insulinaemic responses are not disproportionally increased) may be a beneficial physiological effect. One human intervention study showed an effect of beta-glucans from oats and/or barley, incorporated into breakfast cereals manufactured via pressure cooking at a level of at least 1.2 g/25 g available carbohydrates, on decreasing post-prandial glycaemic responses without disproportionally increasing insulinaemic responses. Dose-response relationships were not tested, and no evidence has been provided that beta-glucans incorporated into cereals processed using pressure cooking would exert a higher effect on post-prandial glucose responses than beta-glucans added to other carbohydrate containing foods. Whereas the effect of beta- glucans in reducing post-prandial blood glucose responses is well established, the evidence provided is insufficient to establish such an effect at doses of 1.3 g beta- glucans per 25 g of available carbohydrate incorporated into ready-to-eat breakfast cereals manufactured via pressure cooking (i.e. either batch cooking or extrusion). (c) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2021 - Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies [Articolo su rivista]
Filippini, Tommaso; Malavolti, Marcella; Whelton, Paul K; Naska, Androniki; Orsini, Nicola; Vinceti, Marco
abstract

2021 - Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis [Articolo su rivista]
Filippini, Tommaso; Wise, Lauren A; Vinceti, Marco
abstract

Background: Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association. Objective: To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association. Data source: After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes. Study eligibility criteria: We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only. Study appraisal and synthesis methods: Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model. Results: In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96-1.59), 1.21 (1.00-1.45), and 1.47 (1.01-2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15-1.73) and blood (RR = 1.38, 95% CI: 1.16-1.63). In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90-1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12-1.76) at 2 µg/g creatinine. Limitations and conclusions: This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.

2021 - Cadmium exposure and risk of prediabetes and diabetes: A systematic review and dose-response meta-analysis [Abstract in Rivista]
Filippini, Tommaso; Wise, Lauren Anne; Vinceti, Marco
abstract

BACKGROUND AND AIM: Elevated cadmium exposure has been associated with altered glucose metabolism, albeit the shape of such relation is still debated. We aimed at investigating the shape of the relation between cadmium exposure and type 2 diabetes and prediabetes. METHODS: We performed a systematic review with meta-analysis on the relation between biomarkers of cadmium exposure and disease risk. After performing an online literature search through March 15, 2021, we identified 34 eligible studies with cohort, cross-sectional and case-control design. RESULTS:In the meta-analysis comparing highest-versus-lowest cadmium exposure, there was an increased type 2 diabetes risk, with summary risk ratios (RRs) of 1.30 (95% confidence interval (CI): 1.00-1.69), 1.22 (95% CI 1.00-1.50), and 1.47 (95% CI 1.01-2.13) for blood, urine, and toenail cadmium concentrations, respectively. Similarly, we found a higher prediabetes risk in subjects with higher both urine and blood cadmium concentrations with RRs of 1.41 (95% CI 1.15-1.73) and 1.38 (95% CI 1.16-1.63), respectively. In the dose-response meta-analysis, compared with no exposure, prediabetes risk increased up to approximately 2 µg Cd/g creatinine, above which it reached a plateau with RR of 1.40 (95% CI 1.12-1.76) at 2 µg Cd/g creatinine. We also detected a substantial linear positive association between diabetes risk and urinary cadmium, with RR of 1.30 (95% CI 0.92-1.84) at 2.0 µg Cd/g creatinine. Diabetes risk also appeared to increase with higher blood cadmium concentrations but only above 1 µg/L, with RR of 3.25 (95% CI 1.13-9.37) at 2 µg/L. Despite limited data, there was little indication of differences in association by study design (cohort vs. case-control or cross-sectional), method of cadmium assessment, or sex (male vs. female). CONCLUSIONS:Overall, there was consistent evidence for a positive association between cadmium exposure and both prediabetes and diabetes risk. KEYWORDS: Heavy metals, Cardiovascular diseases, Endocrine disrupting chemicals, Environmental epidemiology, Toxicology

2021 - Characteristics and risk factors of isolated and quarantined children and adolescents during the first wave of SARS-CoV-2 pandemic: A cross-sectional study in Modena, Northern Italy [Articolo su rivista]
Paduano, S.; Facchini, M. C.; Greco, A.; Borsari, L.; Mingrone, V. M.; Tancredi, S.; Fioretti, E.; Creola, G.; Iacuzio, L.; Casaletti, G.; Vinceti, M.; Bargellini, A.; Filippini, T.
abstract

Background and aim: In early 2020, SARS-CoV-2 was declared a pandemic by the WHO and Italy was one of the first and most severely affected country in Europe. Despite the global interest about COVID-19 pandemic, several aspects of this infection are still unclear, especially in pediatric population. This study aims to investigate the characteristics of the isolated or quarantined children and adolescents followed by the Public Health Department of the Italian province of Modena during the first wave of COVID-19. Methods: The study population included all non-adult subjects aged 0-18 years who underwent isolation or quarantine during the first wave of SARS-CoV-2 pandemic from February 24 to June 18, 2020 in Modena province, Northern Italy. Results: In Modena province, 1230 children and adolescents were isolated in case of SARS-CoV-2 infection (6.3%), or quarantined due to close contact with confirmed cases (88.7%) or travelling from a high-risk area (5.0%). Among 349 individuals who underwent swab testing, 294 (84.2%) reported close contact with an infected cohabiting relative and 158 (45.3%) were symptomatic. Among all tested subjects, 78 (22.4%) resulted positive, with a higher proportion of symptomatic subjects compared with the SARS-CoV-2-negative (78.2% vs. 35.8%). Fever was mostly present in SARS-CoV-2-positive children (48.7% vs. 12.6%). Both anosmia (58.3% vs. 41.7%) and dysgeusia (54.5% vs. 45.5%) had only slightly higher frequency in SARS-CoV-2-positive. Conclusions: These findings allow to expand the knowledge regarding characteristics of non-adult subjects isolated or quarantined during the first wave of SARS-CoV-2 pandemic. (www.actabiomedica.it).

2021 - Dietary acrylamide and risk of specific subtypes of cancer: a dose response meta-analysis of epidemiological studies [Abstract in Rivista]
Filippini, Tommaso; Halldorsson, Thorhallur I.; Capitão, Carolina; Martins, Raquel; Vinceti, Marco; Santos, Osvaldo; Virgolino, Ana; Laguzzi, Federica
abstract

BACKGROUND AND AIM: Acrylamide is a probable carcinogen in humans. The main source of exposure to acrylamide in the general population is through diet. We performed a systematic literature review and dose-response meta-analysis of epidemiological studies evaluating the associations between dietary intake and specific subtypes of cancers. METHODS: A systematic literature search following PRISMA guidelines was conducted using Pubmed, Scopus and Web of Science until October 2020. Eligible studies included adults,assessment of dietary acrylamide (μg/day), risk estimates for increasing exposure to acrylamide, and cancer incidence. Quality of papers was assessed using the NIH’s Quality Assessment Tools for Observational Cohort and Case-Control Studies. We employed random-effects models comparing the highest versus the lowest intake of acrylamide and using the one-stage approach for dose-response meta-analysis. RESULTS:Out of 835 studies screened 28 studies were eligible for this meta-analysis. A total of 1 109 365 (mean age 60 years, range 45-70 years) participants were included, of which 61957 developed cancer. The mean follow-up period was 15.1 years (range 7.3-33.9). Mean estimated dose of acrylamide intake across studies was 22.6 µg/day. Pooled HR showed that high intake of acrylamide (35 µg/day) vs low intake (10 µg/day) was associated with increased risk of hematological malignances (summary HR: 1.4 95%CI:1.03-1.23). Dose-response meta-analysis showed evidence of linear association. No clear associations were noted between high intake of acrylamide (vs low) and esophageal, stomach, pancreatic, lung, renal, bladder-urothelial, and prostate cancers. Similar results were observed in the smoking stratification analysis CONCLUSIONS:From this dose-response meta-analysis of epidemiological studies investigating the association between dietary intake of acrylamide and specific subtypes of cancer, high intake of acrylamide was noted to be associated with increased risk of hematological malignancies. Further studies based on human biomonitoring data are needed to clarify the relationship of dietary acrylamide and cancers in humans. KEYWORDS: acrylamide, dietary exposure, neoplasms, epidemiological studies, Systematic Review

2021 - Dietary selenium intake and risk of hospitalization for type 2 diabetes in the Moli-sani study cohort [Articolo su rivista]
Vinceti, M.; Bonaccio, M.; Filippini, T.; Costanzo, S.; Wise, L. A.; Di Castelnuovo, A.; Ruggiero, E.; Persichillo, M.; Cerletti, C.; Donati, M. B.; de Gaetano, G.; Iacoviello, L.
abstract

Background and aims: Experimental and non-experimental human studies have consistently shown a positive association between exposure to the trace element selenium, which occurs primarily through diet, and risk of type 2 diabetes mellitus. Plausible biological mechanisms include adverse effects of selenium and selenium-containing proteins on glucose metabolism. However, the levels of exposure above which risk increases are uncertain. Methods and results: We examined the association between selenium intake and first hospitalization for type 2 diabetes during a median follow-up period of 8.2 years among 21,335 diabetes-free participants in the Moli-sani cohort, Italy. Selenium intake was ascertained at baseline using a food frequency questionnaire, showing a median value of 59 μg/day. During follow-up, we identified 135 incident cases of hospitalization for diabetes, based on population-based hospital discharge data. We used a Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization for diabetes, adjusting for potential confounders. HRs (95% CIs) were 1.01 (0.60–1.70), 1.13 (0.66–1.96) and 1.75 (0.99–3.10) comparing the second, third, and fourth sex-specific quartiles with the first quartile, respectively. Risk was 64% greater in the fourth quartile as compared with the previous three. Spline regression analysis also indicated a steeper increase in risk occurring among men compared with women. Conclusions: In a large population of Italian adults free of type 2 diabetes at cohort entry, high dietary selenium intake was associated with increased risk of hospitalization for diabetes.

2021 - Disentangling the association of hydroxychloroquine treatment with mortality in covid-19 hospitalized patients through hierarchical clustering [Articolo su rivista]
Di Castelnuovo, A.; Gialluisi, A.; Antinori, A.; Berselli, N.; Blandi, L.; Bonaccio, M.; Bruno, R.; Cauda, R.; Costanzo, S.; Guaraldi, G.; Menicanti, L.; Mennuni, M.; My, I.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Stefanini, G.; Vergori, A.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Moghazi, S. A.; Arboretti, R.; Aucella, F.; Barbieri, G.; Barchitta, M.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Cannata, F.; Carrozzi, L.; Cascio, A.; Castiglione, G.; Cicullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Colombo, C.; Crisetti, A.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; de Gaetano Donati, K.; Di Gennaro, F.; Di Tano, G.; D'Offizi, G.; Fusco, F. M.; Gaudiosi, C.; Gentile, I.; Gianfagna, F.; Giuliano, G.; Graziani, E.; Guarnieri, G.; Langella, V.; Larizza, G.; Leone, A.; Maccagni, G.; Magni, F.; Maitan, S.; Mancarella, S.; Manuele, R.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marongiu, S.; Marotta, C.; Marra, L.; Mastroianni, F.; Mengozzi, A.; Meschiari, M.; Milic, J.; Minutolo, F.; Mussinelli, R.; Mussini, C.; Musso, M.; Odone, A.; Olivieri, M.; Palimodde, A.; Pasi, E.; Pesavento, R.; Petri, F.; Pivato, C. A.; Poletti, V.; Ravaglia, C.; Righetti, G.; Rognoni, A.; Rossato, M.; Rossi, I.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Moriello, N. S.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinicci, M.; Tamburrini, E.; Torti, C.; Trecarichi, E. M.; Vettor, R.; Vianello, A.; Vinceti, M.; Virdis, A.; de Caterina, R.; Iacoviello, L.
abstract

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR [CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

2021 - Dismissing the use of P-values and statistical significance testing in scientific research: new methodological perspectives in toxicology and risk assessment [Capitolo/Saggio]
Berselli, Nausicaa; Filippini, Tommaso; Adani, Giorgia; Vinceti, Marco
abstract

2021 - Efficacy of an infant formula manufactured from a specific protein hydrolysate derived from whey protein isolate and concentrate produced by Société des Produits Nestlé S.A. in reducing the risk of developing atopic dermatitis [Articolo su rivista]
Castenmiller, Jacqueline; Hirsch-Ernst, Karen-Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Turck, Dominique; Vinceti, Marco; Marchelli, Rosangela; van Loveren, Henk; Dumas, Céline; Titz, Ariane; de Henauw, Stefaan
abstract

The European Commission asked EFSA to evaluate the efficacy of an infant formula, containing a specific protein hydrolysate derived from whey protein isolate and concentrate and manufactured by Société des Produits Nestlé S.A., in reducing the risk of developing atopic dermatitis in infants with a family history of allergy. This was following the submission of a dossier by Société des Produits Nestlé S.A. to the European Commission, in the context of Regulation (EU) 2016/127. The protein hydrolysate from which the infant formula is produced is included in Annex I and II of Commission delegated Regulation (EU) 2016/127 as suitable protein source for the manufacture of infant and follow-on formulae. This opinion does not cover the assessment of the nutritional safety and suitability of the infant formula or the safety of the food enzymes used in the manufacture of the protein hydrolysate. The Panel considers that, in relation to the effect that is claimed, the infant formula under evaluation is not sufficiently characterised with respect to the molecular weight distribution of peptides. From the human intervention studies submitted, no conclusions could be drawn on the efficacy of the infant formula in reducing the risk of developing atopic dermatitis. The Panel concludes that a cause-and-effect relationship has not been established between the consumption of the infant formula under evaluation and the reduction in the risk of developing atopic dermatitis in infants with a family history of allergy.

2021 - Epidemiology of early onset dementia and its clinical presentations in the province of Modena, Italy [Articolo su rivista]
Chiari, A.; Vinceti, G.; Adani, G.; Tondelli, M.; Galli, C.; Fiondella, L.; Costa, M.; Molinari, M. A.; Filippini, T.; Zamboni, G.; Vinceti, M.
abstract

Introduction: Patients with early onset dementia (EOD), defined as dementia with symptom onset at age <65, frequently present with atypical syndromes. However, the epidemiology of different EOD presentations, including variants of Alzheimer's disease (AD) and frontotemporal dementia (FTD), has never been investigated all together in a population-based study. Epidemiologic data of all-cause EOD are also scarce. Methods: We investigated EOD epidemiology by identifying patients with EOD seen in the extended network of dementia services of the Modena province, Northern Italy (≈700,000 inhabitants) from 2006 to 2019. Results: In the population age 30 to 64, incidence was 13.2 per 100,000/year, based on 160 new cases from January 2016 to June 2019, and prevalence 74.3 per 100,000 on June 30, 2019. The most frequent phenotypes were the amnestic variant of AD and behavioral variant of FTD. Discussion: EOD affects a significant number of people. Amnestic AD is the most frequent clinical presentation in this understudied segment of the dementia population.

2021 - Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Albert, O.; de Sesmaisons Lecarre, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of the novel food (NF) nicotinamide riboside chloride (NRC) pursuant to Regulation (EU) 2015/2283. The assessment addresses the use of NRC in ‘meal replacement products’ and ‘nutritional drink mixes’ at levels up to 300 mg/day for the general population, and in food for special medical purposes (FSMP) and total diet replacement for weight control (TDRWC) (as per Regulation (EU) No 609/2013) at levels up to 500 mg/day in adults. Benchmark dose modelling was carried out on data from the 90-day oral toxicity studies in rats relevant to the safety assessment. Considering the lack of tolerable upper intake level (UL) for nicotinamide in infants and the narrow margin of exposure between the estimated intake in infants and the lower confidence bound of the benchmark doses (BMDL05) estimated by the models, the Panel concludes that the safety of the NF has not been established for use in ‘meal replacement products’ and ‘nutritional drink mixes’ under the proposed conditions of use. For FSMP and TDRWC, the proposed maximum use level corresponds to an intake of 210 mg nicotinamide per day, which is below the current UL for nicotinamide of 900 mg/day for adults. The Panel considers that the NF is as safe as pure nicotinamide for use in FSMP and TDRWC. The Panel, however, notes experimental data which indicate several pathways by which intakes of nicotinamide (or its precursors), at levels that are substantially higher than the physiological requirement, might cause adverse effects. The Panel considers that further investigations are required and that a re-evaluation of the UL for nicotinamide may be warranted.

2021 - Frequency of anti-sars-cov-2 antibodies in various occupational sectors in an industrialized area of northern italy from may to october 2020 [Articolo su rivista]
Modenese, A.; Mazzoli, T.; Berselli, N.; Ferrari, D.; Bargellini, A.; Borella, P.; Filippini, T.; Marchesi, I.; Paduano, S.; Vinceti, M.; Gobba, F.
abstract

The results of a voluntary screening campaign for the presence of anti-SARS-CoV-2 serum antibodies are presented, performed on workers in the highly industrialized province of Modena in northern Italy in the period 18 May–5 October 2020. The employment activities of the subjects that tested positive for anti-SARS-CoV-2 IgM and/or IgG antibodies were determined and classified using the International Standard Industrial Classification of All Economic Activities (ISIC). The distribution across different sectors was compared to the proportion of workers employed in the same sectors in the province of Modena as a whole. Workers with anti-SARS-CoV-2 serum antibodies were mainly employed in manufacturing (60%), trade (12%), transportation (9%), scientific and technical activities (5%), and arts, entertainment and recreation activities (4.5%). Within the manufacturing sector, a cluster of workers with positive serological tests was observed in the meat processing sector, confirming recent data showing a possible increased risk of SARS-CoV-2 infection in these workers.

2021 - Frutalose®, a mixture of fructans obtained from enzymatic hydrolysis of chicory inulin, and normal defecation: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Vinceti, Marco
abstract

Following an application from Sensus B.V. (Royal Cosun), submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Frutalose® and maintenance of normal defecation. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The Panel considers that Frutalose®, a mixture of fructans obtained from enzymatic hydrolysis of chicory inulin, is sufficiently characterised. The claimed effect proposed by the applicant is ‘contributes to regular bowel function by increasing stool frequency’. The proposed target population is ‘the general healthy adult population’. Maintenance of normal defecation is a beneficial physiological effect provided that it does not result in diarrhoea. One human intervention study showed an effect of Frutalose® on the maintenance of normal defecation by increasing stool frequency and improving stool consistency (softer stools) when consumed daily at a dose of 15 g for 8 weeks. The results have not been replicated in other studies. There is a plausible mechanism by which Frutalose® could exert the claimed effect. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of Frutalose® and maintenance of normal defecation under the proposed conditions of use.

2021 - Green kiwifruit (lat. Actinidia deliciosa var. Hayward) and maintenance of normal defecation: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Bresson, Jean-Louis; Siani, Alfonso
abstract

Following an application from Zespri International Limited, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to green kiwifruit (lat. Actinidia deliciosa var. Hayward) and maintenance of normal defecation. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is green kiwifruit. The Panel considers that green kiwifruit (Actinidia deliciosa var. Hayward) is sufficiently characterised. The claimed effect proposed by the applicant is 'maintenance of normal defecation'. Maintenance of normal defecation is a beneficial physiological effect provided that it does not result in diarrhoea. All human intervention studies submitted had different limitations and could not be used on their own for the scientific substantiation of the claim. However, the results of six pertinent human intervention studies are consistent with respect to an effect of consuming daily between two and four green kiwifruits var. Hayward on an increase in stool frequency. Two out of four studies in which a validated instrument was used to assess stool consistency showed an effect also on stool consistency. There is evidence for a plausible mechanism by which kiwifruit could exert an effect on normal defecation. The consumption of kiwifruit in the studies did not result in diarrhoea. A cause and effect relationship has been established between the consumption of green kiwifruit (Actinidia deliciosa var. Hayward) and maintenance of normal defecation. The following wordings reflect the scientific evidence: 'consumption of kiwifruit contributes to the maintenance of normal defecation'. In order to obtain the claimed effect, two large green kiwifruits (i.e. around 200 g of kiwi flesh) should be consumed.

2021 - Greenness, cognitive impairment and dementia: a systematic review and meta-analysis [Abstract in Rivista]
Zagnoli, Federico; Giannone, Maria Edvige; Filippini, Tommaso; Vinceti, Marco
abstract

BACKGROUND AND AIM: Many recent studies identified the benefits of green space exposure for the improvment of human health, especially mental health. The involved patways could be increased physical activity, improved sleep quality, reduced stress and also increased social interaction. The relation between greenness and cognitive decline, however, is still uncertain. METHODS: We searched epidemiological studies related to green space exposure and cognitive impairment and dementia in two electronic databases (PubMed and EMBASE) using terms related to residential greenness, including Normalized Difference Vegetation Index-NDVI, land cover, land use, green index, greenness, green space, urban park, urban green and recreational park, along with cognitive impairment, decline and dementia. A meta-analysis comparing the highest versus the lowest greenness exposure and risk of cognitive decline was performed using a random-effects model. RESULTS:Out of 64 studies retrieved from the online search 11 studies were eligible for the review. The majority of included reports used satellied-derived NDVI, while the remaining studies used land cover maps to determine the greenness-related exposure areas. Cognitive impairment or dementia risk are calculated using different exposure types (greenness within a buffer, the areal radius, or greenness of census block) at subject residential address. Overall, summary risk ratio-RR showed no effect of greenness on cognitive decline (RR 0.99, 95% confidence interval-CI 0.91-1.07), whereas a slight indication of a beneficial effect of NDVI emerged (RR 0.96, 95%CI 0.90-1.03). Two studies that reported correlation coefficents only did not suggest an association between cognitive impairment and dementia measurement. CONCLUSIONS:Overall, our study yielded limited evidence of a protective effect of greenness on cognitive decline. The rapid evolution of greenness definition over time and the limitations in exposure assessment, however, suggest the need to further investigate this issue in order to draw more reliable conclusions. KEYWORDS: Green space, Neurodegenerative outcomes, Environmental epidemiology

2021 - Guidance on the preparation and submission of an application for authorisation of a novel food in the context of Regulation (EU) 2015/22831 (Revision 1)2 [Articolo su rivista]
Nutrition, ; Allergies, A.; Turck, D.; Bresson, J. -L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Vinceti, M.; Willatts, P.; Engel, K. -H.; Marchelli, R.; Poting, A.; Poulsen, M.; Salminen, S.; Schlatter, J.; Arcella, D.; Gelbmann, W.; de Sesmaisons-Lecarre, A.; Verhagen, H.; van Loveren, H.
abstract

(Table presented.). Following the adoption of Regulation (EU) 2015/2283 on novel foods, the European Commission requested EFSA develop scientific and technical guidance for the preparation and submission of applications for authorisation of novel foods. This guidance presents a common format for the organisation of the information to be presented by the applicant when preparing a well-structured application to demonstrate the safety of the novel food. It outlines the data needed for the safety assessments of novel foods. Requirements relate to the description of the novel food, production process, compositional data, specification, proposed uses and use levels, and anticipated intake of the novel food. Further sections on the history of use of the novel food and/or its source, absorption, distribution, metabolism, excretion, nutritional information, toxicological information and allergenicity should be considered by the applicant by default. If not covered in the application, this should be justified. The applicant should integrate the data presented in the different sections to provide their overall considerations on how the information supports the safety of the novel food under the proposed conditions of use. Where potential health hazards have been identified, they should be discussed in relation to the anticipated intakes of the novel food and the proposed target populations. On the basis of the information provided, EFSA will assess the safety of the novel food under the proposed conditions of use. This guidance was originally adopted in 2016.It has beenrevised to informapplicants of the new provisions introduced by Regulation (EC) No 178/2002, as amended by Regulation (EU) 2019/1381 on the transparency and sustainability of the EU risk assessment in the food chain.This revised guidance applies to all dossiers submitted as of 27 March 2021. The 2016 version of this guidance remains applicable to applications submitted before 27 March 2021.

2021 - Guidance on the preparation and submission of the notification and application for authorisation of traditional foods from third countries in the context of Regulation (EU) 2015/2283 (Revision 1)1 [Articolo su rivista]
Turck, D.; Bresson, J. -L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Siani, A.; Sjodin, A.; Stern, M.; Tome, D.; Vinceti, M.; Willatts, P.; Engel, K. -H.; Marchelli, R.; Poting, A.; Poulsen, M.; Schlatter, J.; Gelbmann, W.; de Sesmaisons-Lecarre, A.; Verhagen, H.; van Loveren, H.
abstract

(Table presented.). Following the adoption of Regulation (EU) 2015/2283 on Novel Foods, the European Commission requested EFSA to develop a scientific and technical guidance for the preparation and submission of notifications for traditional foods from third countries. This guidance presents a common format for the organisation of the information to be presented by applicant for the preparation of a well-structured dossier. The safety of a traditional food should be substantiated by reliable data on its composition, its experience of continued use and its proposed conditions of use. Its normal consumption should not be nutritionally disadvantageous. This guidance is also intended to support applicants in providing the type and quality of information EU Member States and EFSA need for the assessments of traditional foods from third countries. The applicant should integrate the information on the composition and the experience of continued use and provide a concise overall consideration on how this substantiates the history of safe use of the traditional food and how this relates to the proposed conditions of use for the EU. Where potential health hazards have been identified on the basis of the composition and/or data from the experience of continued use, they should be discussed. On the basis of the information provided, EFSA will assess the safety related to the consumption of the traditional food under the proposed conditions of use. This guidance was originally adopted by the NDA Panel in 2016. It has been revised in 2020 to inform applicants of the new provisions introduced by Regulation (EC) No 178/2002, as amended by Regulation (EU) 2019/1381 on the transparency and sustainability of the EU risk assessment in the food chain.It is applicable to allnotifications and applications submitted as of 27 March 2021. The 2016 version remains applicable to notifications and applications submitted before 27 March 2021.

2021 - Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study [Articolo su rivista]
Di Castelnuovo, A.; Costanzo, S.; Antinori, A.; Berselli, N.; Blandi, L.; Bonaccio, M.; Cauda, R.; Guaraldi, G.; Menicanti, L.; Mennuni, M.; Parruti, G.; Patti, G.; Santilli, F.; Signorelli, C.; Vergori, A.; Abete, P.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Al Moghazi, S.; Arboretti, R.; Astuto, M.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Carrozzi, L.; Cascio, A.; Ciccullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Colombo, C.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; De Gaetano Donati, K.; Di Gennaro, F.; Di Tano, G.; D'Offizi, G.; Fantoni, M.; Fusco, F. M.; Gentile, I.; Gianfagna, F.; Grandone, E.; Graziani, E.; Grisafi, L.; Guarnieri, G.; Larizza, G.; Leone, A.; Maccagni, G.; Madaro, F.; Maitan, S.; Mancarella, S.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marongiu, S.; Marotta, C.; Marra, L.; Mastroianni, F.; Mazzitelli, M.; Mengozzi, A.; Menichetti, F.; Meschiari, M.; Milic, J.; Minutolo, F.; Molena, B.; Montineri, A.; Mussini, C.; Musso, M.; Niola, D.; Odone, A.; Olivieri, M.; Palimodde, A.; Parisi, R.; Pasi, E.; Pesavento, R.; Petri, F.; Pinchera, B.; Poletti, V.; Ravaglia, C.; Rognoni, A.; Rossato, M.; Rossi, M.; Sangiovanni, V.; Sanrocco, C.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Taddei, E.; Torti, C.; Vettor, R.; Vianello, A.; Vinceti, M.; Virano, A.; Vocciante, L.; De Caterina, R.; Iacoviello, L.
abstract

Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusion In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

2021 - Impact of the environment on the health: From theory to practice [Articolo su rivista]
Carducci, A. L.; Agodi, A.; Ancona, C.; Angelini, P.; Bagordo, F.; Barbone, F.; Birbaum, L.; Carreri, V.; Casuccio, A.; Conti, A.; Conversano, M.; De Donno, A.; De Giglio, O.; Desiante, F.; Di Pietro, A.; Dogliotti, E.; Donato, F.; Fara, G. M.; Fiore, M.; Forastiere, F.; Giammanco, G.; Izzotti, A.; Montagna, M. T.; Oliveri Conti, G.; Petronio, M. G.; Sciacca, S.; Signorelli, C.; Testai, E.; Verani, M.; Vinceti, M.; Vitale, F.; Ferrante, M.; Adani, G.; Berghella, L.; Calia, C.; Calzolari, R.; Canale, A.; Castiglione, D.; Copat, C.; Cristaldi, A.; Cuffari, G.; Coronel Vargas, G.; De Vita, E.; De Nard, F.; Federigi, I.; Filippini, T.; Grasso, A.; Leonardi, N.; Letzgus, M.; Lo Bianco, G.; Mazzucco, W.; Nicolosi, I.; Orlandi, P.; Paladino, G.; Pizzo, S.; Pousis, C.; Raffo, M.; Rivolta, S.; Scarpitta, F.; Trani, G.; Triggiano, F.; Tumbarello, A.; Vecchio, V.; Zuccarello, P.; Vassallo, M.
abstract

The Erice 56 Charter titled “Impact of the environment on the health: from theory to practice” was unanimously approved at the end of the 56th course of the “International School of Epidemiology and Preventive Medicine G. D'Alessandro” held from 3rd to November 7, 2019 in Erice – Sicily (Italy) and promoted by the Study Group of “Environment and Health” of the Italian Society of Hygiene, Preventive Medicine and Public Health. The course, that included lectures, open discussions and guided working groups, was aimed to provide a general training on epidemiological and toxicological aspects of the environmental health impact, to be used by public health professionals for risk assessment, without forgetting the risk communications. At the end of the course 12 key points were agreed among teachers and students: they underlined the need of specific training and research, in the perspective of “One Health” and “Global Health”, also facing emerging scientific and methodological issues and focusing on communication towards stakeholders. This Discussion highlight the need to improve knowledge of Health and Environment topic in all sectors of health and environmental prevention and management.

2021 - Is artificial light-at-night associated with increased breast cancer risk? A systematic review and dose-response meta-analysis [Abstract in Rivista]
Urbano, Teresa; Vinceti, Marco; Filippini, Tommaso
abstract

2021 - Is dairy intake associated with less cognitive decline? A systematic review and meta-analysis of longitudinal studies [Abstract in Rivista]
Villoz, Fanny; Filippini, Tommaso; Blum, Manuel; DEL GIOVANE, Cinzia; Vinceti, Marco; Rodondi, Nicolas; Chocano-Bedoya, Patricia
abstract

Introduction: With aging population, prevention of cognitive de- cline is a major concern in primary care. Nutrition is a modifiable factor that could have a clinical impact in this prevention. In par- ticular, the effects of the dairy intake on cognition are still contro- versial. We conducted a systematic review and meta-analysis on association between the dairy intake and cognitive decline or inci- dence of dementia with dose-response analysis. Methods: We included longitudinal studies with community-dwell- ing adults ≥ 18 years unselected on the basis of chronic conditions. Our primary outcomes were the decline of cognitive function as de- fined in studies and incidence of dementia at end of follow-up. We identified relevant literature through a systematic search of Em- base, Medline Ovid, Cochrane, Web of Science and Google Scholar from inception to end of July 2020. Two investigators conducted abstract and full-text screenings, data extractions, and risk-of-bias assessments using the Academy of Nutrition and Dietetics Quality Criteria Checklist (QCC). We performed a meta-analysis using a random-effects model. Results: We included 11 prospective studies with 46,896 partici- pants. We rated all studies at low risk of bias. Mean follow-up time was 11.7 years. Seven studies assessed cognitive decline through decrease in scores of various neuropsychological tests including MMSE (Mini-Mental State Examination). Three studies assessed dementia incidence using either MMSE threshold or DSM-IIIR/ DSM-IV criteria. Comparing highest vs. lowest dairy intake, we found no association between dairy and cognitive decline. (Sum- mary risk ratio-sRR=0.97; 95%CI 0.82, 1.16; 7 studies) although with large statistical heterogeneity (I2=76.75%). The dose-response anal- yses using g/day with 4 studies showed U-shaped curve, with low- est risk at approximately 120-130 g/day. We found an inverse asso- ciation between the dairy intake and dementia incidence (sRR=0.61; 95%CI 0.44, 0.86; I2 =43.65%; 3 studies)

2021 - Isomaltulose and normal energy-yielding metabolism: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from BENEO GmbH submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to isomaltulose and normal energy-yielding metabolism. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is isomaltulose. The Panel considers that isomaltulose is sufficiently characterised. The claimed effect proposed by the applicant is ‘normal energy-yielding metabolism’. The Panel considers that contribution to normal energy-yielding metabolism is a beneficial physiological effect. A number of human studies applying indirect calorimetry measurements or stable isotope methodologies have shown the postprandial metabolic utilisation of isomaltulose as energy source. However, all energy-containing macronutrients (i.e. carbohydrates, proteins, and lipids) supply the body with energy and this property is not specific to isomaltulose. The Panel concludes that a cause and effect relationship has been established between the intake of isomaltulose and contribution to energy-yielding metabolism. The following wording reflects the scientific evidence: ‘isomaltulose contributes to normal energy-yielding metabolism’. Since the contribution to energy-yielding metabolism is not specific to isomaltulose but applies to all energy containing macronutrients (i.e. carbohydrates, proteins, and lipids) that supply the body with metabolisable energy and any amount would contribute to the claimed effect, the Panel cannot set conditions of use for this claim. The applicant proposes that isomaltulose should replace other sugars in foods and/or beverages. The target population is the general population.

2021 - La pandemia Covid-19 a Modena nel 2020: quadro epidemiologico ed efficacia degli interventi di sanità pubblica. [Monografia/Trattato scientifico]
Vinceti, Marco; Filippini, Tommaso
abstract

2021 - Light at night and risk of breast cancer: a systematic review and dose–response meta-analysis [Articolo su rivista]
Urbano, Teresa; Vinceti, Marco; Wise, Lauren A.; Filippini, Tommaso
abstract

Breast cancer is the most common malignancy in women and the second leading cause of cancer death overall. Besides genetic, reproductive, and hormonal factors involved in disease onset and progression, greater attention has focused recently on the etiologic role of environmental factors, including exposure to artificial lighting such as light-at-night (LAN). We investigated the extent to which LAN, including outdoor and indoor exposure, affects breast cancer risk. We performed a systematic review of epidemiological evidence on the association between LAN exposure and breast cancer risk, using a dose-response meta-analysis to examine the shape of the relation. We retrieved 17 eligible studies through September 13, 2021, including ten cohort and seven case-control studies. In the analysis comparing highest versus lowest LAN exposure, we found a positive association between exposure and disease risk (risk ratio [RR] 1.11, 95% confidence interval-CI 1.07-1.15), with comparable associations in case-control studies (RR 1.14, 95% CI 0.98-1.34) and cohort studies (RR 1.10, 95% CI 1.06-1.15). In stratified analyses, risk was similar for outdoor and indoor LAN exposure, while slightly stronger risks were observed for premenopausal women (premenopausal: RR 1.16, 95% CI 1.04-1.28; postmenopausal: 1.07, 95% CI 1.02-1.13) and for women with estrogen receptor (ER) positive breast cancer (ER + : RR 1.09, 95% CI 1.02-1.17; ER-: RR 1.07, 95% CI 0.92-1.23). The dose-response meta-analysis, performed only in studies investigating outdoor LAN using comparable exposure assessment, showed a linear relation up to 40 nW/cm2/sr after which the curve flattened, especially among premenopausal women. This first assessment of the dose-response relation between LAN and breast cancer supports a positive association in selected subgroups, particularly in premenopausal women.

2021 - Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study [Articolo su rivista]
Di Castelnuovo, Augusto; Costanzo, Simona; Antinori, Andrea; Berselli, Nausicaa; Blandi, Lorenzo; Bonaccio, Marialaura; Bruno, Raffaele; Cauda, Roberto; Gialluisi, Alessandro; Guaraldi, Giovanni; Menicanti, Lorenzo; Mennuni, Marco; My, Ilaria; Parruti, Agostino; Patti, Giuseppe; Perlini, Stefano; Santilli, Francesca; Signorelli, Carlo; Stefanini, Giulio G; Vergori, Alessandra; Ageno, Walter; Aiello, Luca; Agostoni, Piergiuseppe; Al Moghazi, Samir; Arboretti, Rosa; Aucella, Filippo; Barbieri, Greta; Barchitta, Martina; Bartoloni, Alessandro; Bologna, Carolina; Bonfanti, Paolo; Caiano, Lucia; Carrozzi, Laura; Cascio, Antonio; Castiglione, Giacomo; Chiarito, Mauro; Ciccullo, Arturo; Cingolani, Antonella; Cipollone, Francesco; Colomba, Claudia; Colombo, Crizia; Crosta, Francesco; Dalena, Giovanni; Dal Pra, Chiara; Danzi, Gian Battista; D'Ardes, Damiano; de Gaetano Donati, Katleen; Di Gennaro, Francesco; Di Tano, Giuseppe; D'Offizi, Gianpiero; Filippini, Tommaso; Maria Fusco, Francesco; Gaudiosi, Carlo; Gentile, Ivan; Gini, Giancarlo; Grandone, Elvira; Guarnieri, Gabriella; Lamanna, Gennaro L F; Larizza, Giovanni; Leone, Armando; Lio, Veronica; Losito, Angela Raffaella; Maccagni, Gloria; Maitan, Stefano; Mancarella, Sandro; Manuele, Rosa; Mapelli, Massimo; Maragna, Riccardo; Marra, Lorenzo; Maresca, Giulio; Marotta, Claudia; Mastroianni, Franco; Mazzitelli, Maria; Mengozzi, Alessandro; Menichetti, Francesco; Milic, Jovana; Minutolo, Filippo; Molena, Beatrice; Mussinelli, R; Mussini, Cristina; Musso, Maria; Odone, Anna; Olivieri, Marco; Pasi, Emanuela; Perroni, Annalisa; Petri, Francesco; Pinchera, Biagio; Pivato, Carlo A; Poletti, Venerino; Ravaglia, Claudia; Rossato, Marco; Rossi, Marianna; Sabena, Anna; Salinaro, Francesco; Sangiovanni, Vincenzo; Sanrocco, Carlo; Scorzolini, Laura; Sgariglia, Raffaella; Simeone, Paola Giustina; Spinicci, Michele; Trecarichi, Enrico Maria; Veronesi, Giovanni; Vettor, Roberto; Vianello, Andrea; Vinceti, Marco; Visconti, Elena; Vocciante, Laura; De Caterina, Raffaele; Iacoviello, Licia
abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

2021 - MegaNatural®-BP grape seed extract and maintenance of normal blood pressure: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Vinceti, Marco
abstract

Following an application from Praline i Čokolada j.d.o.o. submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Croatia, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to MegaNatural®-BP grape seed extract and maintenance of normal blood pressure. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. MegaNatural®-BP, a grape seed extract standardised for total phenolics, gallic acid and the catechin and epicatechin content, is sufficiently characterised. The proposed claimed effect, maintenance of normal blood pressure (BP), is a beneficial physiological effect. Among the two human intervention studies provided from which conclusions could be drawn, one showed an effect of MegaNatural®-BP (300 mg/day) on BP in adults with normal and high normal BP when consumed daily for 6 weeks, whereas the second study did not show an effect of MegaNatural®-BP at the same daily dose consumed for 8 weeks in adults with normal and high normal blood pressure or stage 1 hypertension. The evidence provided did not establish a plausible mechanism by which the food could exert the claimed effect in vivo in humans. The evidence provided is insufficient to establish a cause and effect relationship between the consumption of MegaNatural®-BP and maintenance of normal blood pressure.

2021 - Modeling Early Phases of COVID-19 Pandemic in Northern Italy and Its Implication for Outbreak Diffusion [Articolo su rivista]
Gandolfi, Daniela; Pagnoni, Giuseppe; Filippini, Tommaso; Goffi, Alessia; Vinceti, Marco; D'Angelo, Egidio; Mapelli, Jonathan
abstract

The COVID-19 pandemic has sparked an intense debate about the hidden factors underlying the dynamics of the outbreak. Several computational models have been proposed to inform effective social and healthcare strategies. Crucially, the predictive validity of these models often depends upon incorporating behavioral and social responses to infection. Among these tools, the analytic framework known as “dynamic causal modeling” (DCM) has been applied to the COVID-19 pandemic, shedding new light on the factors underlying the dynamics of the outbreak. We have applied DCM to data from northern Italian regions, the first areas in Europe to contend with the outbreak, and analyzed the predictive validity of the model and also its suitability in highlighting the hidden factors governing the pandemic diffusion. By taking into account data from the beginning of the pandemic, the model could faithfully predict the dynamics of outbreak diffusion varying from region to region. The DCM appears to be a reliable tool to investigate the mechanisms governing the spread of the SARS-CoV-2 to identify the containment and control strategies that could efficiently be used to counteract further waves of infection.

2021 - Organic foods and contribution to the protection of body cells and molecules (lipids and DNA) from oxidative damage: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Cyprus, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to organic foods and contribution to the protection of body cells and molecules (lipids and DNA) from oxidative damage. The scope of the application was proposed to fall under a health claim referring to children's development and health. The food proposed by the applicant as the subject of the health claim is ‘organic foods’. The applicant claimed that organic foods are characterised by their lower level of pesticides residues compared with foods not labelled as organic. The Panel notes, however, that in the application and the human studies submitted the nutritional composition and the pesticide concentration in ‘organic food’ are not reported. The Panel considers that organic foods which are the subject of the health claim, and the foods that they are intended to replace are not sufficiently characterised. Therefore, the Panel concludes that a cause and effect relationship cannot be established between the consumption of organic foods and contribution to the protection of body cells and molecules (lipids and DNA) from oxidative damage.

2021 - Pro-environmental behaviors: Determinants and obstacles among italian university students [Articolo su rivista]
Carducci, A.; Fiore, M.; Azara, A.; Bonaccorsi, G.; Bortoletto, M.; Caggiano, G.; Calamusa, A.; De Donno, A.; De Giglio, O.; Dettori, M.; Di Giovanni, P.; Di Pietro, A.; Facciola, A.; Federigi, I.; Grappasonni, I.; Izzotti, A.; Libralato, G.; Lorini, C.; Montagna, M. T.; Nicolosi, L. K.; Paladino, G.; Palomba, G.; Petrelli, F.; Schiliro, T.; Scuri, S.; Serio, F.; Tesauro, M.; Verani, M.; Vinceti, M.; Violi, F.; Ferrante, M.
abstract

The awareness of citizens concerning the health risks caused by environmental pollution is growing, but studies on determinants of pro-environmental behaviors have rarely examined health-related aspects. In this study, we investigated these determinants using data from a large survey among Italian university students (15 Universities: 4778 filled questionnaires). Besides the health-related aspects, represented by environmental health risk perception and functional health literacy, we considered social and demographic characteristics (gender, area of residence, sources of information, trust in institutional and non-institutional subjects, and students’ capacity of positive actions, indicated as internal locus of control). The attitudes towards pro-environmental behaviors were positive for more than 70% of students and positively related with health risk perception, internal locus of control, and health literacy. The correspondence between the positive attitudes towards pro-environmental behaviors and the real adoption of such behaviors was approximately 20% for most behaviors, except for the separate collection of waste (60%). Such a discrepancy can be attributable to external obstacles (i.e., lack of time, costs, lack of support). The health-related aspects were linked to the pro-environmental attitudes, but to a lesser extent to pro-environmental behaviors, owing to the complexity of their determinants. However, they should be taken in account in planning education interventions.

2021 - Residential exposure to electromagnetic fields and risk of amyotrophic lateral sclerosis: a dose-response meta-analysis [Articolo su rivista]
Filippini, Tommaso; Hatch, Elizabeth E; Vinceti, Marco
abstract

Amyotrophic lateral sclerosis (ALS) is neurodegenerative disease characterized by a fatal prognosis and still unknown etiology. Some environmental risk factors have been suggested, including exposure to magnetic fields. Studies have suggested positive associations in occupationally-exposed populations, but the link with residential exposure is still debated as is the shape of such relation. Due to recent availability of advanced biostatistical tools for dose-response meta-analysis, we carried out a systematic review in order to assess the dose-response association between ALS and residential exposure to magnetic fields. We performed an online literature searching through April 30, 2021. Studies were included if they assessed residential exposure to electromagnetic fields, based either on distance from overhead power lines or on magnetic field modelling techniques, and if they reported risk estimates for ALS. We identified six eligible studies, four using distance-based and one modelling-based exposure assessment, and one both methods. Both distance-based and particularly modelling-based exposure estimates appeared to be associated with a decreased ALS risk in the highest exposure category, although estimates were very imprecise (summary RRs 0.87, 95% CI 0.63-1.20, and 0.27, 95% CI 0.05-1.36). Dose-response meta-analysis also showed little association between distance from power lines and ALS, with no evidence of any threshold. Overall, we found scant evidence of a positive association between residential magnetic fields exposure and ALS, although the available data were too limited to conduct a dose-response analysis for the modelled magnetic field estimates or to perform stratified analyses.

2021 - Response by Filippini et al to Letter Regarding Article, "Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies" [Articolo su rivista]
Filippini, Tommaso; Malavolti, Marcella; Whelton, Paul K; Naska, Androniki; Orsini, Nicola; Vinceti, Marco
abstract

2021 - Risk of Amyotrophic Lateral Sclerosis and Exposure to Particulate Matter from Vehicular Traffic: A Case-Control Study [Articolo su rivista]
Filippini, Tommaso; Mandrioli, Jessica; Malagoli, Carlotta; Costanzini, Sofia; Cherubini, Andrea; Maffeis, Giuseppe; Vinceti, Marco
abstract

(1) Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with still unknown etiology. Some occupational and environmental risk factors have been suggested, including long-term air pollutant exposure. We carried out a pilot case-control study in order to evaluate ALS risk due to particulate matter with a diameter of ≤10 µm (PM10) as a proxy of vehicular traffic exposure. (2) Methods: We recruited ALS patients and controls referred to the Modena Neurology ALS Care Center between 1994 and 2015. Using a geographical information system, we modeled PM10 concentrations due to traffic emissions at the geocoded residence address at the date of case diagnosis. We computed the odds ratio (OR) and 95% confidence interval (CI) of ALS according to increasing PM10 exposure, using an unconditional logistic regression model adjusted for age and sex. (3) Results: For the 132 study participants (52 cases and 80 controls), the average of annual median and maximum PM10 concentrations were 5.2 and 38.6 µg/m3, respectively. Using fixed cutpoints at 5, 10, and 20 of the annual median PM10 levels, and compared with exposure <5 µg/m3, we found no excess ALS risk at 5-10 µg/m3 (OR 0.87, 95% CI 0.39-1.96), 10-20 µg/m3 (0.94, 95% CI 0.24-3.70), and ≥20 µg/m3 (0.87, 95% CI 0.05-15.01). Based on maximum PM10 concentrations, we found a statistically unstable excess ALS risk for subjects exposed at 10-20 µg/m3 (OR 4.27, 95% CI 0.69-26.51) compared with those exposed <10 µg/m3. However, risk decreased at 20-50 µg/m3 (OR 1.49, 95% CI 0.39-5.75) and ≥50 µg/m3 (1.16, 95% CI 0.28-4.82). ALS risk in increasing tertiles of exposure showed a similar null association, while comparison between the highest and the three lowest quartiles lumped together showed little evidence for an excess risk at PM10 concentrations (OR 1.13, 95% CI 0.50-2.55). After restricting the analysis to subjects with stable residence, we found substantially similar results. (4) Conclusions: In this pilot study, we found limited evidence of an increased ALS risk due to long-term exposure at high PM10 concentration, though the high statistical imprecision of the risk estimates, due to the small sample size, particularly in some exposure categories, limited our capacity to detect small increases in risk, and further larger studies are needed to assess this relation.

2021 - SARS-CoV-2 infection incidence during the first and second COVID-19 waves in Italy [Articolo su rivista]
Vinceti, M.; Filippini, T.; Rothman, K. J.; Di Federico, S.; Orsini, N.
abstract

We assessed the relation between COVID-19 waves in Italy, which was severely affected during the pandemic. We evaluated the hypothesis that a larger impact from the first wave (February-May 2020) predicts a smaller peak during the second wave (September-October 2020), in the absence of local changes in public health interventions and area-specific differences in time trends of environmental parameters. Based on publicly available data on province-specific SARS-CoV-2 infections and both crude and multivariable cubic spline regression models, we found that for provinces with the lowest incidence rates in the first wave, the incidence in the second wave increased roughly in proportion with the incidence in the first wave until an incidence of about 500-600 cases/100,000 in the first wave. Above that value, provinces with higher incidences in the first wave experienced lower incidences in the second wave. It appears that a comparatively high cumulative incidence of infection, even if far below theoretical thresholds required for herd immunity, may provide noticeable protection during the second wave. We speculate that, if real, the mechanism for this pattern could be depletion of most susceptible individuals and of superspreaders in the first wave. A population learning effect regarding cautious behavior could have also contributed. Since no area-specific variation of the national policy against the SARS-CoV-2 outbreak was allowed until early November 2020, neither individual behaviors nor established or purported environmental risk factors of COVID-19, such as air pollution and meteorological factors, are likely to have confounded the inverse trends we observed in infection incidence over time.

2021 - Safety of 3-FL (3-Fucosyllactose) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Colombo, Paolo; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3-fucosyllactose (3-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3-FL but also contains D-lactose and its monomers, L-fucose and a small fraction of other related saccharides. The NF is produced by fermentation with a genetically modified strain of Escherichia coli K-12. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements. The target population is the general population, except for food supplements for which the target population is individuals above 1 year of age. The anticipated daily intake of 3-FL from the NF at the maximum proposed use levels is unlikely to exceed the intake level of breastfed infants on a body weight basis. The intake of 3-FL in breastfed infants on a body weight basis is expected to be safe also for other population groups. In infants below 1 year of age, a possible exceedance of a natural intake was observed, but the degree of this exceedance is not considered of safety concern in view of the wide range of 3-FL concentrations in human milk. Food supplements are not intended to be used if other foods with the added NF (as well as human milk for young children) are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2021 - Safety of Cetylated Fatty Acids as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on an application for cetylated fatty acids as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF concerns primarily a mixture of cetylated myristic acid and cetylated oleic acid synthesised from cetyl alcohol, myristic acid and oleic acid, and to a lesser degree, other cetylated fatty acids and other compounds from olive oil. The NF is intended for use in food supplements for the general adult population. The highest dose tested in a subchronic toxicity study in rats, i.e. 4,500 mg/kg per day, was considered to be the no-observed-adverse effect level. By applying the default uncertainty factor of 200 as suggested by the EFSA Scientific Committee (2012), and considering a default body weight of 70 kg for the adult target population, this would result in an intake of 1.6 g per day, which is lower than the maximum intake proposed by the applicant (i.e. 2.1 g per day). The Panel concludes that the NF, cetylated fatty acids, is safe at an intake of 1.6 g per day for the intended target population, i.e. adults.

2021 - Safety of Eurycoma longifolia (Tongkat Ali) root extract as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhaeuser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Matijevic, L.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on Eurycoma longifolia (Tongkat Ali) root extract as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is standardised water extract prepared from the dried ground root chips of Tongkat Ali (Eurycoma longifolia Jack) and proposed by the applicant to be used as food supplement in amounts up to 200 mg/day. The target population is the adult population, except pregnant and lactating women. The characteristic components of the NF are glycosaponins (40–65%) and eurycomanone (0.8–1.5%). It can also contain canthin-6-one alkaloids and isoscopoletin (coumarin). The NF has been present in various international markets since 2009. The Panel notes positive results from the submitted in vitro chromosome aberration test, which indicates clastogenic properties of the NF. In the requested follow-up in vivo mammalian alkaline comet assay, the NF induced positive results at the highest dose tested (2,000 mg/kg body weight (bw)) at the tissues of the first site of contact (stomach and duodenum). Histopathological evaluation of the tested tissues indicated that the positive results of the comet assay were rather due to genotoxicity than cytotoxicity. Taken together, the Panel concludes that the NF has the potential to induce DNA damage, which is of concern, particularly locally for tissues that represent first sites of contact. The Panel concludes that the safety of NF has not been established under any condition of use.

2021 - Safety of Vitamin D2 mushroom powder (Agaricus bisporus) as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Roldan-Torres, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on vitamin D2 mushroom powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an ingredient produced from Agaricus bisporus mushroom powder that has been exposed to ultraviolet (UV) irradiation to induce the conversion of provitamin D2 (ergosterol) to vitamin D2 (ergocalciferol). The NF contains concentrations of vitamin D provided by vitamin D2 in the ranges of 580–595 μg/g. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods and beverages, including food for special medical purposes and food supplements. The target population is the general population except for food supplements and Foods for Special Medical Purposes (FSMPs), for which the target population is individuals above 1 year of age. The Panel concludes that the NF, used as an ingredient, is safe for the general population at the proposed condition of use in foods and beverages and that the NF used as a food supplement, is safe for individuals above 1 year.

2021 - Safety of Wolffia globosa powder as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Kouloura, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on Wolffia globosa powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Wolffia globosa is an aquatic plant, one out of the 38 species of the water lentil family which is composed by five genera (i.e. Spirodela, Landoltia, Lemna, Wolffiella and Wolffia). The NF is produced by cultivation of Wolffia globosa plants under controlled conditions, washing with hot water and drying. The main constituents of the NF are protein, fibre and fat. The Panel notes that the concentration of trace elements and contaminants in the NF is highly dependent on the conditions of cultivation of the plant and the fertiliser composition. The NF is intended to be used as food ingredient in a variety of food categories and as food supplement. The target population is the general population except for food supplements which are intended to be consumed exclusively by adults. The Panel considers that with the exception of concerns related to the manganese intake, taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The subchronic toxicity study provided with the NF revealed a number of significant findings and the Panel considers the middle dose (6.5 g/kg body weight (bw) per day) as the no observed adverse effect level (NOAEL). Based on the protein concentration, the Panel considers that the consumption of the NF may trigger allergic reactions. The Panel concluded that an increase in manganese intake from the NF used as food ingredient or food supplements is of safety concern and the safety of the NF cannot be established.

2021 - Safety of a change in the conditions of use of galacto-oligosaccharides as a novel food ingredient in food supplements pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the change in the conditions of use of galacto-oligosaccharides (GOS) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of GOS, consisting of different galactosyl residues (two to nine) linked to a terminal glucose by a β-glycosidic bond but also contains lactose and its monomers (galactose and glucose). The NF is a syrup containing ≥ 55% GOS (w/w dry matter) and is produced enzymatically by two β-galactosidases. GOS produced by β-galactosidases according to the same production process is already authorised and included in the EU Union list of novel foods. This application is limited to an assessment of the proposed increase of the use level as food supplement. The proposed change in the conditions of use increases the maximum level in food supplements from 0.333 kg GOS/kg food supplement (33.3%) to 0.450 kg GOS/kg food supplement (45.0%). Since it is recommended that individuals consume no more than 3 servings of 12 g/day, the maximum recommended daily intake would be no more than 16.2 g GOS. No new food uses or other increases to the already approved use levels are being proposed. The information provided on the proposed use levels and anticipated intake do not raise safety concerns. The Panel concludes that the proposed increase in the maximum level of galacto-oligosaccharides as a NF in food supplements is safe under the proposed changes in conditions of use.

2021 - Safety of calcidiol monohydrate produced by chemical synthesis as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Peláez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhauser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Dumas, Céline; Roldán-Torres, Ruth; Steinkellner, Hans; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of calcidiol monohydrate as a novel food (NF) pursuant to Regulation (EU) 2015/2283, including its bioavailability as a metabolite of vitamin D3 when added for nutritional purposes to food supplements. The NF is produced chemically. It is proposed in food supplements up to 10 lg/day for individuals > 11 years of age, including pregnant and lactating women and up to 5 lg/day in 3- to 10-year-old children. The production process, composition, specifications and stability of the NF do not raise safety concerns. Animal and human data indicate efficient absorption. The NF contains a fraction of nanoparticles, which are fat soluble and unlikely to reach systemic distribution. There are no concerns regarding genotoxicity. Human adult studies do not raise safety concerns. Combined intake estimates of calcidiol from the NF and calcidiol and vitamin D from the diet were below the tolerable upper intake level (UL) for vitamin D for subjects above 11 years of age. The achieved mean serum 25(OH)D concentration in adults supplemented with 10 lg NF per day remained below 200 nmol/L. The Panel concludes that the NF is safe under the proposed conditions of use and use levels for individuals > 11 years old, including pregnant and lactating women. The applicant did not provide data on the bioavailability and safety of the NF in children. The combined intake estimation in children (3-10 years) is close to the UL for vitamin D. Therefore, the Panel could not conclude on the safety of consumption of the NF in children (3-10 years) at the proposed daily intake. The NF is a bioavailable source of the biologically active metabolite of vitamin D, i.e. 1,25-dihydroxyvitamin D. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2021 - Safety of calcium fructoborate as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Peláez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhauser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Rossi, Annamaria; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on calcium fructoborate as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF, produced by chemical synthesis, contains a maximum of 2.9% of boron and on average 4.7% calcium and 84.2% fructose. It is intended to be marketed as food supplements targeting the general adult population, excluding pregnant and lactating women, at a maximum level of 220 mg/day (maximum boron intake of 6.4 mg per day). The combined intake of boron from the background diet and the NF is in the range of 9.6-9.9 mg/day (corresponding to up to 0.14 mg/kg body weight (bw) per day given a default bw of 70 kg). This is in the range of the acceptable daily intake (ADI) of 0.16 mg/kg bw per day. Under conditions mimicking the gastrointestinal (GI) environment, the NF is fully hydrolysed and the Panel considered boron toxicity relevant for the safety assessment. The Panel considers that there is no concern with respect to genotoxicity of the NF. The effect induced by the NF in a 13-week rat study is consistent with toxicological findings induced by treatment with boron compounds in animal studies. Epididymides-to-brain weight ratio was identified as the most relevant endpoint and the reference point derived was the lowest model averaged BMDL10 value of 529 mg/kg bw per day. This corresponds to 14.8 mg/kg bw per day of boron, which is higher than the critical no observed adverse effect level (NOAEL) (9.6 mg boron/kg bw per day) used for establishing the ADI of 0.16 mg/kg bw per day for boron. The Panel therefore applied the present ADI for boron in the assessment of the NF. The Panel concludes that the NF, calcium fructoborate, is safe under the proposed uses and use levels.

2021 - Safety of dried fruits of Synsepalum dulcificum as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Matijević, Leonard; Knutsen, Helle Katrine
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on dried fruits of Synsepalum dulcificum as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is pitted and dried (by lyophilisation) fruits of S. dulcificum. The NF contains the glycoprotein miraculin (≤ 2.5%) which causes sour and acidic foods to taste sweet. The fruits have a documented history of consumption in Africa and products thereof can be found in different markets worldwide. Information on the production process and the composition of the NF is sufficient and does not raise safety concerns. The applicant proposes to use the NF as or in food supplements for the adult population, excluding pregnant and lactating women, at a maximum daily amount of 0.9 g. Taking into account these conditions of use, the Panel considers that the consumption of the NF is not nutritionally disadvantageous. The provided genotoxicity studies do not raise concerns for genotoxicity of the NF. The Panel concludes that the only dose tested in a 90-day oral toxicity study of 2,000 mg/kg body weight (bw) per day was not associated with adverse effects. By applying an uncertainty factor of 200, the Panel concludes that the NF is safe at an intake level of 10 mg/kg bw per day, corresponding to a maximum daily intake of 0.7 g of the NF for the target population, rather than 0.9 g/day as proposed by the applicant.

2021 - Safety of dried yellow mealworm (Tenebrio molitor larva) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on dried yellow mealworm (Tenebrio molitor larva) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The term yellow mealworm refers to the larval form of the insect species Tenebrio molitor. The NF is the thermally dried yellow mealworm, either as whole dried insect or in the form of powder. The main components of the NF are protein, fat and fibre (chitin). The Panel notes that the levels of contaminants in the NF depend on the occurrence levels of these substances in the insect feed. The Panel notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf life. The NF has a high protein content, although the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as whole, dried insect in the form of snacks, and as a food ingredient in a number of food products. The target population proposed by the applicant is the general population. The Panel notes that considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The submitted toxicity studies from the literature did not raise safety concerns. The Panel considers that the consumption of the NF may induce primary sensitisation and allergic reactions to yellow mealworm proteins and may cause allergic reactions in subjects with allergy to crustaceans and dust mites. Additionally, allergens from the feed may end up in the NF. The Panel concludes that the NF is safe under the proposed uses and use levels.

2021 - Safety of extended uses of UV-treated baker's yeast as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Maradona, Miguel Prieto; Schlatter, Josef Rudolf; van Loveren, Henk; Gelbmann, Wolfgang; Knutsen, Helle Katrine
abstract

In 2014, the EFSA NDA Panel concluded that UV-treated baker's yeast containing up to 3.5 Mio IU of vitamin D/100 g, is safe under the proposed conditions of use for yeast-leavened breads, rolls and fine bakery wares, and food supplements. Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on an application for an extension of the use of UV-treated baker's yeast as a novel food (NF) pursuant to Regulation (EU) 2015/2283. In this extension of use, the applicant proposed a broad range of food categories to which the NF can be added. On the basis of the proposed uses and maximum use levels, the Panel estimated the potential exposure to vitamin D from the NF and the potential combined exposure to vitamin D including also exposure from the background diet and food supplements. The Panel notes that the upper level (UL) for one age group, i.e. children aged 4-10 years, is exceeded by 4%, when summing up the highest P95 estimate for the background diet (including food supplements) and the highest P95 estimate for vitamin D from the NF under the proposed uses and maximum use levels. The Panel notes, however, the highly conservative approach for estimating the potential intake of vitamin D from the NF, given that the applicant has proposed 34 FoodEx2 level 2 food categories. Thus, the Panel considers that the UL for children aged between 4 and 10 years is highly unlikely to be exceeded. The Panel concludes that the NF is safe under the proposed conditions of use.

2021 - Safety of frozen and dried formulations from migratory locust (Locusta migratoria) as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Azzollini, D.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Food and Food Allergens (NDA) was asked to deliver an opinion on the safety of frozen and dried formulations from migratory locust (Locusta migratoria) as a novel food pursuant to Regulation (EU) 2015/2283. The term migratory locust refers to the adult of the insect species Locusta migratoria. The NF is proposed in three formulations i) frozen without legs and wings; ii) dried without legs and wings; iii) ground with legs and wings. The main components of the NF are protein, fat and fibre (chitin) in the dried form of the NF, and water, protein, fat and fibre (chitin) in the frozen form of the NF. The Panel notes that the concentration of contaminants in the NF depends on the occurrence levels of these substances in the insect feed. The Panel notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The NF has a high protein content, although the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as frozen, dried and ground in the form of snack, and as a food ingredient in a number of food products. The target population proposed by the applicant is the general population. The Panel notes that considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The submitted history of use and toxicity studies from literature did not raise safety concerns. The Panel considers that the consumption of the NF might trigger primary sensitisation to L. migratoria proteins and may cause allergic reactions in subjects with allergy to crustaceans, mites and molluscs. Additionally, allergens from the feed may end up in the NF. The Panel concludes that the NF is safe under the proposed uses and use levels.

2021 - Safety of frozen and dried formulations from whole house crickets (Acheta domesticus) as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Goumperis, T.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Food and Food Allergens (NDA) was asked to deliver an opinion on the safety of frozen and dried formulations from house crickets (Acheta domesticus) as a novel food pursuant to Regulation (EU) 2015/2283. The NF is proposed in three formulations: (i) frozen, (ii) dried, (iii) ground. The main components of the NF are protein, fat and fibre (chitin) in the dried form of the NF, and water, protein, fat and fibre (chitin) in the frozen form of the NF. The Panel notes that the concentrations of contaminants in the NF depend on the occurrence levels of these substances in the insect feed. The Panel further notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The NF has a high-protein content, although the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF in the form of a snack, and as a food ingredient in a number of food products. The target population proposed by the applicant is the general population. The Panel notes that, considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The Panel notes that no genotoxicity and no subchronic toxicity studies with the NF were provided by the applicant. Considering that no safety concerns arise from the history of use of A. domesticus or from the compositional data of the NF, the Panel identified no other safety concerns than allergenicity. The Panel considers that the consumption of the NF might trigger primary sensitisation to A. domesticus proteins and may cause allergic reactions in subjects allergic to crustaceans, mites and molluscs. Additionally, allergens from the feed may end up in the NF. The Panel concludes that the NF is safe under the proposed uses and use levels.

2021 - Safety of frozen and dried formulations from whole yellow mealworm (Tenebrio molitor larva) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ververis, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on frozen and dried formulations from whole yellow mealworm (Tenebrio molitor larva) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The term yellow mealworm refers to the larval form of the insect species Tenebrio molitor. The NF comprises the frozen and freeze-dried formulations of the yellow mealworm, whole or in the form of powder. The frozen formulation consists mainly of water, crude protein and fat whereas the freeze-dried formulations of crude protein, fat, digestible carbohydrates and fibre (chitin). The Panel notes that the levels of contaminants in the NF depend on the occurrence levels of these substances in the insect feed. The Panel notes furthermore that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The dried formulations of the NF have a high protein content, although the true protein levels in the NF are overestimated when using the nitrogen-to-protein conversion factor of 6.25, due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as whole frozen or whole dried insect, or in the form of powder, added as an ingredient to various food products such as cereal bars, pasta, meat imitates and bakery products. The target population is the general population. The Panel notes that, considering that the NF will not be the sole source of dietary protein, and the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The submitted toxicity studies from the literature did not raise safety concerns. The Panel considers that the consumption of the NF may induce primary sensitisation and allergic reactions to yellow mealworm proteins and may cause allergic reactions in subjects with allergy to crustaceans and dust mites. Additionally, allergens from the feed may end up in the NF. The Panel concludes that the NF is safe under the proposed uses and use levels.

2021 - Safety of iron hydroxide adipate tartrate as a novel food pursuant to Regulation (EU) 2015/2283 and as a source of iron in the context of Directive 2002/46/EC [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Ildico Hirsch-Ernst, K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Rudolf Schlatter, J.; van Loveren, H.; Germini, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on iron hydroxide adipate tartrate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and as a source of iron in the context of Directive 2002/46/EC. The NF is intended to be used in food supplements up to a maximum dose of 100 mg per day, corresponding to a maximum daily intake of iron of 36 mg. The target population proposed by the applicant is the general population above 3 years of age. The NF which is the subject of the application is an engineered nanomaterial having primary particles, of almost spherical morphology, with a diameter typically smaller than 5 nm. The studies provided for absorption, distribution, metabolism and excretion (ADME) and bioavailability indicate that iron, once taken up into the epithelial cells of the gut, is subject to the same mechanisms of regulation and absorption as that of other forms of iron. Further studies provided in the context of the toxicological assessment indicate that the NF does not lead to iron bioaccumulation in tissues and organs at the doses tested. The Panel notes that the NF contains nickel at concentrations that may increase the risk of flare-up reactions in nickel-sensitised young individuals up to 10 years of age. In the 90-day toxicity study, findings related to haematology, clinical biochemistry and organ weights were observed and the Panel defined a no observed adverse effect level (NOAEL) of 231 mg/kg body weight (bw) per day, that is, the mid-dose used in the study. The Panel considers that the NF is a source from which iron is bioavailable and it is safe under the proposed conditions of use.

2021 - Safety of mung bean protein as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Maradona, M. P.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Fernandez, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on mung bean protein as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF, which is the subject of the application, is mung bean protein extracted from seeds of the plant Vigna radiata. The NF is proposed to be used as a food ingredient added to ‘protein products, excluding products covered in category 1.8’. The target population is the general population. The maximum estimated intake of the NF is 758 and 260 mg/kg body weight (bw) per day in children and adults, respectively. The major constituents of this NF are protein (~85%), fat (3–4%) and moisture (3–5.5%). The NF is rich in protein which is well digestible and provides sufficient amounts of most essential amino acids but only limited amounts of sulfur-containing amino acids. The Panel notes that the cumulative exposure to the minerals analysed does not raise concern. The reported values for the levels of antinutritional factors in the NF are comparable to those in other foodstuffs. The Panel considers that taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. No toxicological studies with the NFs were provided by the applicant; however, the Panel considers that no toxicological studies are required on this NF. This NF has the potential capacity to sensitise individuals and to induce allergic reactions in individuals allergic to soybean, peanuts, lupin and to birch pollen. The Panel considers that the NF, i.e. mung bean protein, is safe at the proposed conditions of use.

2021 - Safety of oil from Schizochytrium limacinum (strain FCC-3204) for use in food supplements as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain FCC-3204, used by the applicant (Fermentalg), belongs to the species Schizochytrium limacinum. The NF, an oil rich in docosahexaenoic acid (DHA), is obtained from microalgae after enzymatic lysis. The applicant proposed to increase the use level of the NF as a food supplement, from 250 mg DHA/day (currently authorised for the general population, excluding pregnant and lactating women) to 3 g DHA/day for adults, excluding pregnant and lactating women. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel considers that the data provided by the applicant are not sufficient to conclude on the safety of the NF at the proposed uses (3 g DHA/day as a food supplement) in adults. However, in 2012, the Panel concluded that supplemental intakes of DHA alone up to about 1 g/day do not raise safety concerns for the general population. The Panel concludes that the NF is safe for the use in food supplements at the maximum intake level of 1 g DHA/day for the target population (adults, excluding pregnant and lactating women).

2021 - Safety of oil from Schizochytrium limacinum (strain FCC-3204) for use in infant and follow-on formula as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain FCC- 3204, used by the applicant (Fermentalg), belongs to the species Schizochytrium limacinum. The NF, an oil rich in docosahexaenoic acid (DHA), is obtained from microalgae after enzymatic lysis. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use level defined by the applicant was derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20–50 mg/100 kcal. The intake of DHA resulting from the use of the NF in IF and FOF is not expected to pose safety concerns. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided by the applicant demonstrated the absence of viable cells in the NF. No toxicological studies were performed with the NF. However, based on the available toxicological data on oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process, the composition of the NF and the absence of viable cells in the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

2021 - Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on pasteurised Akkermansia muciniphila as a novel food (NF) pursuant to Regulation (EU) 2015/2283. A. muciniphila is a well-characterised non-toxin producing, avirulent microorganism that has been reported as part of normal gut microbiota. The NF, pasteurised A. muciniphila, is proposed by the applicant to be used as a food supplement at max. 5 × 1010 cells/day by adults excluding pregnant and lactating women, and in foods for special medical purposes. The Panel considers that the production process of the NF is sufficiently described and that the information provided on the composition of the NF is sufficient for its characterisation. Taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. Based on literature data, and by applying an uncertainty factor of 200 to the no observed adverse effect level (NOAEL) of a 90-day repeated dose oral toxicity study in rats, the Panel concludes that the consumption of 3.4 × 1010 cells/day is safe for the target population under the provision that the number of viable cells in the NF is < 10 colony forming units (CFU)/g (i.e. limit of detection).

2021 - Safety of tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Kouloura, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Tetrahydrocurcuminoids are derivatives of curcuminoids, produced chemically by hydrogenation of curcuminoids extracted from the rhizomes of C. longa L. The NF consists of more than 95% of tetrahydrocurcuminoids. The applicant proposed to use the NF in food supplements at a maximum dose of 300 mg/day for adults excluding pregnant and lactating women. Taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study and a reproduction/developmental toxicity screening test performed with the NF, the Panel derives a safe level of 2 mg/kg body weight per day. For the target population this level corresponds to 140 mg/day, which is lower than the use level as proposed by the applicant. The Panel concludes that the NF, tetrahydrocurcuminoids from turmeric (C. longa L.), is safe for the target population at 140 mg/day.

2021 - Safety of the extension of use of galacto-oligosaccharides as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Prieto Maradona, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of galacto-oligosaccharides (GOS) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a syrup containing ≥ 57% w/w GOS (w/w dry matter), consisting of different galactosyl residues linked to a terminal glucose by a β-glycosidic bond and also containing lactose and the constituent monomers of lactose (galactose and glucose). The NF is already authorised and included in the Union list of NFs and is produced according to the same production process. This application is limited to an assessment of the extension of use as a food ingredient in dairy confectionary, cheese and processed cheese, butter and spreads. There is a 10–30% increase in total GOS intake from the requested extension of use compared to the currently authorised uses at the highest 95th percentile. It is noted that the total intake at the highest mean (8.7–22.0 g/day) is below the adequate intake (AI) of 25 g/day for dietary fibre set to ensure a normal laxation in adults, while the highest 95th percentile (27.2–41.6 g/day) is higher than the AI. When the maximum use as a food supplement is added to the highest 95th percentile combined intake from all proposed and authorised food categories a total intake up to 58 g GOS/day is estimated. This highest intake level would exceed the AI for dietary fibre; however, no tolerable upper intake level for dietary fibre has been set and only transient gastrointestinal symptoms may be related to high intake of fibre. The Panel concludes that the NF, that is composed of ≥ 57% GOS dry matter, lactose and related saccharides, is safe under the proposed extension of use.

2021 - Safety of water extract of Cistanche tubulosa stems as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on water extract of Cistanche tubulosa stems as a novel food (NF) for its use in food supplements (FS) and foods for special medical purposes (FSMP). The target population is the general adult population excluding pregnant and lactating women. The applicant proposes a maximum daily intake of 2 g for FS and a maximum use level of 10% in FSMP. The characteristic components of the extract are phenylethanoid glycosides (at least 70% of the NF), in particular, echinacoside (25–45% of the NF). The NF has been authorised as a prescription drug in China in 2005 for the treatment of vascular dementia. The Panel notes that an integrated analysis of three studies covering 1,076 patients with vascular dementia treated with the proposed NF at a daily dose of 1,800 mg, reported that 12 adverse events (AEs) were classified to be ‘definitely’, ‘probably’ or ‘possibly related’ to the exposure to the NF. Two of these AE were classified as severe (cerebral haemorrhage and epilepsy). The Panel considers that the reported AEs raise safety concerns. The Panel also notes the limitations of the provided toxicological studies, in particular the non-compliance with the EFSA approach on the genotoxicity testing strategy and the non-compliance with good laboratory practice (GLP) and the respective OECD Guidance documents of the repeated dose toxicity studies. In view of the AEs in the human studies, the Panel considers that additional toxicological studies, following testing guidelines would not be able to overcome the concerns raised from the human studies. The Panel concludes that the safety of the NF has not been established.

2021 - Safety of water lentil powder from Lemnaceae as a Novel Food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Bohn, T.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Prieto Maradona, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Kouloura, E.; Steinkellner, H.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of water lentil powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Water lentils refer to aquatic plants belonging to the Araceae family and represented by five genera (Lemna, Wolffia, Wolffiella, Landoltia and Spirodela). The NF is thermally washed and dried water lentils, which are produced as a polyculture crop consisting of species from the Lemna genus (70–100%) and the Wolffia genus (0–30%). The main constituents of the NF are protein, fibre and fat. The Panel notes that the concentration of trace elements and contaminants in the NF is highly dependent on the conditions of cultivation of the plant and the fertiliser composition. The NF is expected to be stable and to comply with the specifications during the suggested shelf life. The NF is intended for human consumption as a food ingredient in herbs, spices and seasonings, sauces, soups and broths, protein products, dietary food for weight control and as a food supplement. The target population is the general population, except for food supplements which are exclusively intended for consumption by adults. The Panel considers that based on the composition of the NF and the proposed intended uses, the NF is not nutritionally disadvantageous, except for the concerns regarding intake of manganese from the NF. No adverse effect was observed in the submitted 90-day subchronic study, at the highest dose, 1,000 mg/kg body weight (bw) per day of NF. The Panel considers that, based on the protein concentration, the consumption of the NF may trigger allergic reactions. The Panel concluded that an increase in manganese intake from the NF used as food ingredient or food supplements is of safety concern and the safety of the NF cannot be established.

2021 - Scientific and technical guidance for the preparation and presentation of a dossier for evaluation of an infant and/or follow-on formula manufactured from protein hydrolysates (Revision 1) 1 [Articolo su rivista]
Turck, D.; Bresson, J. -L.; Burlingame, B.; Dean, T.; Fairweather-Tait, S.; Heinonen, M.; Hirsch-Ernst, K. I.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Neuhauser-Berthold, M.; Nowicka, G.; Pentieva, K.; Sanz, Y.; Sjodin, A.; Stern, M.; Tome, D.; Loveren, H. V.; Vinceti, M.; Willatts, P.; Fewtrell, M.; Przyrembel, H.; Titz, A.; Martinez, S. V.
abstract

(Table presented.). Following a request from the European Commission, EFSA was asked to provide scientific and technical guidance for the preparation and presentation of a dossierfor evaluation of an infant and/or follow-on formula manufactured from protein hydrolysates. This guidance document addresses the information and data to be submitted to EFSA on infant and follow-on formulae manufactured from protein hydrolysates with respect to the nutritional safety and suitability of the specific formula and/or the formula's efficacy in reducing the risk of developing allergy to milk proteins. The guidance will be further reviewed and updated with the experience gained from the evaluation of specificdossiers, and in the light of applicable Unionguidelines and legislation. The guidance was adopted by the Panel on Dietetic Products, Nutrition and Allergies on 5 April 2017.Upon request from the European Commission in 2020, it has been revised to inform food business operators of the new provisions in the pre-submission phase and in the procedure set out in the General Food Law, as amended by the Transparency Regulation. This revised guidance applies to all dossiers submitted as of 27 March 2021 and shall be consulted for the preparation of dossiers intended to be submitted from that date onwards. For dossiers submitted prior to 27 March 2021, the previous guidance, published in May 2017 remains applicable.

2021 - Scientific opinion on the relationship between intake of alpha-lipoic acid (thioctic acid) and the risk of insulin autoimmune syndrome [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; de Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Mangelsdorf, Inge; McArdle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cappellani, Daniele; Ijzerman, Richard; Van Loveren, Henk; Titz, Ariane; Maciuk, Alexandre
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the relationship between alpha-lipoic acid (ALA) and the risk of insulin autoimmune syndrome (IAS). The Panel was also asked to advise on the dose below which ALA added to foods is not expected to cause IAS. A review of all possible adverse effects associated with consumption of ALA was not requested. This mandate refers to the procedure under Article 8(2) of Regulation (EC) No 1925/2006 on addition of vitamins, minerals and certain other substances to foods. No pre-established rule exists for the evaluation of the safety of foods when classical toxicity tests cannot be used, e.g. for autoimmune diseases. Published scientific evidence was retrieved through comprehensive literature searches, particularly 49 case reports in which IAS developed following ALA consumption. In all cases, IAS resolved after a few weeks to months when ALA was discontinued. No publication linking the intake of ALA naturally occurring in foods to IAS was identified. The Panel concludes that the consumption of ALA added to foods, including food supplements, is likely to increase the risk of developing IAS in individuals with certain genetic polymorphisms, who cannot be readily identified without genetic testing. The plausible mechanism of such an effect has not yet been fully elucidated. The incidence of IAS in Europe is low and likely lower than in Japan where it has been estimated to be 0.017 per 100,000 inhabitants in 2017-2018. Considering the limited data available, the risk associated with the development of IAS following ALA consumption cannot be quantified precisely. An ALA dose below which IAS is not expected to occur is likely to vary between individuals and cannot be determined from the available data. (c) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2021 - Seroprevalence of anti-SARS-CoV-2 antibodies after the first COVID-19 wave: a cross-sectional study in the province of Modena, city of a Northern Italy region [Abstract in Rivista]
Berselli, N; Filippini, T; Paduano, S; Malavolti, M; Modenese, A; Gobba, F; Borella, P; Marchesi, I; Vivoli, R; Perlini, P; Bellucci, R; Bargellini, A; Vinceti, M
abstract

2021 - Seroprevalence of anti-SARS-CoV-2 antibodies in the Northern Italy population before the COVID-19 second wave [Articolo su rivista]
Berselli, Nausicaa; Filippini, Tommaso; Paduano, Stefania; Malavolti, Marcella; Modenese, Alberto; Gobba, Fabriziomaria; Borella, Paola; Marchesi, Isabella; Vivoli, Roberto; Perlini, Paola; Bellucci, Rossana; Bargellini, Annalisa; Vinceti, Marco
abstract

The COVID-19 pandemic is due to SARS-CoV-2 coronavirus infections. It swept across the world in the spring of 2020, and so far it has caused a huge number of hospitalizations and deaths. In the present study, the authors investigated serum anti-SARS-CoV-2 antibody prevalence in the period of June 1-September 25, 2020, in 7561 subjects in Modena, Northern Italy.

2021 - Sodium and potassium content of foods consumed in an italian population and the impact of adherence to a mediterranean diet on their intake [Articolo su rivista]
Malavolti, M.; Naska, A.; Fairweather-Tait, S. J.; Malagoli, C.; Vescovi, L.; Marchesi, C.; Vinceti, M.; Filippini, T.
abstract

High sodium and low potassium intakes are associated with increased levels of blood pressure and risk of cardiovascular diseases. Assessment of habitual dietary habits are helpful to evaluate their intake and adherence to healthy dietary recommendations. In this study, we determined sodium and potassium food-specific content and intake in a Northern Italy community, focusing on the role and contribution of adherence to Mediterranean diet patterns. We collected a total of 908 food samples and measured sodium and potassium content using inductively coupled plasma mass spectrometry. Using a validated semi-quantitative food frequency questionnaire, we assessed habitual dietary intake of 719 adult individuals of the Emilia-Romagna region. We then estimated sodium and potassium daily intake for each food based on their relative contribution to the overall diet, and their link to Mediterranean diet patterns. The estimated mean sodium intake was 2.15 g/day, while potassium mean intake was 3.37 g/day. The foods contributing most to sodium intake were cereals (33.2%), meat products (24.5%, especially processed meat), and dairy products (13.6%), and for potassium they were meat (17.1%, especially red and white meat), fresh fruits (15.7%), and vegetables (15.1%). Adherence to a Mediterranean diet had little influence on sodium intake, whereas potassium intake was greatly increased in subjects with higher scores, resulting in a lower sodium/potassium ratio. Although we may have underestimated dietary sodium intake by not including discretionary salt use and there may be some degree of exposure misclassification as a result of changes in food sodium content and dietary habits over time, our study provides an overview of the contribution of a wide range of foods to the sodium and potassium intake in a Northern Italy community and of the impact of a Mediterranean diet on intake. The mean sodium intake was above the dietary recommendations for adults of 1.5–2 g/day, whilst potassium intake was only slightly lower than the recommended 3.5 g/day. Our findings suggest that higher adherence to Mediterranean diet patterns has limited effect on restricting sodium intake, but may facilitate a higher potassium intake, thereby aiding the achievement of healthy dietary recommendations.

2021 - Statement on additional scientific evidence in relation to the essential composition of total diet replacement for weight control [Articolo su rivista]
Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Titz, A.; Turck, D.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to revise the Opinion on the essential composition of total diet replacements for weight control (TDRs) regarding the minimum content of linoleic acid (LA) and alpha-linolenic acid (ALA) and the maximum content of magnesium (Mg). Through a comprehensive literature search, human studies were retrieved reporting on LA and ALA concentrations in adipose tissue (AT), on weight loss and gallstone formation following TDR consumption and on diarrhoea after supplemental Mg intake. The distribution of the amount of LA and ALA release from AT during weight loss when consuming TDRs was estimated using statistical simulations. Using the fifth percentile, the coverage of the adequate intake (AI) for both FA was estimated. For the risk of developing diarrhoea when consuming TDRs with an Mg content of 350 mg/day, four cross-over studies using 360–368 mg Mg/day were reviewed. The Panel concludes that (1) there is no need to add LA to TDRs, as the amount released from AT during weight loss when consuming TDRs is sufficient to cover the AI for LA; (2) a minimum of 0.8 g/day ALA is needed in TDRs in order to meet the AI for ALA; (3) the minimum fat content of TDRs of 20 g/day as derived in the Panel's previous opinion is proposed to be maintained until the availability of further evidence, given the considerable uncertainty as to the amount of fat required for reducing the risk of gallstone formation; and (4) the likelihood that Mg-induced diarrhoea occurs at a severity that may be considered of concern for overweight and obese individuals consuming TDRs is low when the total maximum Mg content in TDRs is 350 mg/day.

2021 - Studio di fattori di rischio/protettivi associati alla risposta anticorpale anti-SARS-CoV-2 in un campione di lavoratori della provincia di Modena e province limitrofe [Abstract in Rivista]
Paduano, S; Modenese, A; Filippini, T; Berselli, N; Marchesi, I; Vinceti, M; Borella, P; Gobba, F; Bargellini, A
abstract

2021 - Systematic Review and Meta-analysis on Association Between Air Pollutants and Hippocampal Volume from Magnetic Resonance Imaging in Adults [Abstract in Rivista]
Balboni, Erica; Filippini, Tommaso; Vinceti, Marco
abstract

BACKGROUND AND AIM: The neurotoxicity of air pollutants has been actively investigated in recent years, and there is increasing epidemiological evidence suggesting that air pollution can adversely affect the central nervous system. In neurodegenerative disease, one important diagnostic biomarker is volume reduction in a key brain structure, the hippocampus, as assessed with neuroimaging techniques. Few epidemiological articles investigated the association of hippocampal volume with air pollution, with inconsistent results. In this paper, we aimed to estimate such association through a systematic review and meta-analysis. METHODS: Scopus and PubMed literature databases were searched through 31 March 2021. Eligibility criteria were: 1) assessment of air pollutant levels; 2) assessment of hippocampal volume through structural magnetic resonance imaging; 3) reporting of correlation coefficients along with standard error. We performed a meta-analysis using a random-effects model. RESULTS:We retrieved four studies using linear regression models to evaluate the possible effect of air pollutants on hippocampal volume of adult populations. The investigated air pollutants were nitrogen dioxide (NO2) and particulate matter, with diameter ≤2.5µm (PM2.5) and ≤10μm (PM10). All studies used a similar methodology based on standard spatial coordinates of images, and considered intracranial volume as a covariate. We found that hippocampal volume was inversely associated with PM2.5 concentration (β regression coefficient -7.90, 95% confidence interval (CI) -14.60 to -1.20) and more slightly with PM10 concentrations (β -1.70, 95%CI -3.96 to 0.57), whereas no association with NO2 concentrations emerged (β -0.29, 95%CI -1.13 to 0.55). CONCLUSIONS:Our results suggest that PM2.5 and less clearly PM10 have an adverse effect on hippocampal volume, a phenomenon associated with cognitive decline and increased risk of neurodegenerative disease. These epidemiologic findings appear to be biologically plausible especially for PM2.5, also taking into account some studies carried out in animals. KEYWORDS: Neurotoxicity, Neuroimaging, Magnetic Resonance Imaging, Hippocampus, Meta-analysis, Nitrogen dioxide

2021 - The association between air pollutants and hippocampal volume from magnetic resonance imaging: A systematic review and meta-analysis [Articolo su rivista]
Balboni, Erica; Filippini, Tommaso; Crous-Bou, Marta; Guxens, Monica; Erickson, Lance D; Vinceti, Marco
abstract

Growing epidemiological evidence suggests that air pollution may increase the risk of cognitive decline and neurodegenerative disease. A hallmark of neurodegeneration and an important diagnostic biomarker is volume reduction of a key brain structure, the hippocampus. We aimed to investigate the possibility that outdoor air nitrogen dioxide (NO2) and particulate matter with diameter ≤2.5  μm (PM2.5) and ≤10 μm (PM10) adversely affect hippocampal volume, through a meta-analysis. We considered studies that assessed the relation between outdoor air pollution and hippocampal volume by structural magnetic resonance imaging in adults and children, searching in Pubmed and Scopus databases from inception through July 13, 2021. For inclusion, studies had to report the correlation coefficient along with its standard error or 95% confidence interval (CI) between air pollutant exposure and hippocampal volume, to use standard space for neuroimages, and to consider at least age, sex and intracranial volume as covariates or effect modifiers. We meta-analyzed the data with a random-effects model, considering separately adult and child populations. We retrieved four eligible studies in adults and two in children. In adults, the pooled summary β regression coefficients of the association of PM2.5, PM10 and NO2 with hippocampal volume showed respectively a stronger association (summary β -7.59, 95%CI -14.08 to -1.11), a weaker association (summary β -2.02, 95%CI -4.50 to 0.47), and no association (summary β -0.44, 95%CI -1.27 to 0.40). The two studies available for children, both carried out in preadolescents, did not show an association between PM2.5 and hippocampal volume. The inverse association between PM2.5 and hippocampal volume in adults appeared to be stronger at higher mean PM2.5 levels. Our results suggest that outdoor PM2.5 and less strongly PM10 could adversely affect hippocampal volume in adults, a phenomenon that may explain why air pollution has been related to memory loss, cognitive decline, and dementia.

2021 - The association between first and second wave COVID-19 mortality in Italy [Articolo su rivista]
Vinceti, M.; Filippini, T.; Rothman, K. J.; Di Federico, S.; Orsini, N.
abstract

Background: The relation between the magnitude of successive waves of the COVID-19 outbreak within the same communities could be useful in predicting the scope of new outbreaks. Methods: We investigated the extent to which COVID-19 mortality in Italy during the second wave was related to first wave mortality within the same provinces. We compared data on province-specific COVID-19 2020 mortality in two time periods, corresponding to the first wave (February 24–June 30, 2020) and to the second wave (September 1–December 31, 2020), using cubic spline regression. Results: For provinces with the lowest crude mortality rate in the first wave (February–June), i.e. < 22 cases/100,000/month, mortality in the second wave (September–December) was positively associated with mortality during the first wave. In provinces with mortality greater than 22/100,000/month during the first wave, higher mortality in the first wave was associated with a lower second wave mortality. Results were similar when the analysis was censored at October 2020, before the implementation of region-specific measures against the outbreak. Neither vaccination nor variant spread had any role during the study period. Conclusions: These findings indicate that provinces with the most severe initial COVID-19 outbreaks, as assessed through mortality data, faced milder second waves.

2020 - A new threat from an old enemy: Re-emergence of coronavirus (Review) [Articolo su rivista]
Docea, A. O.; Tsatsakis, A.; Albulescu, D.; Cristea, O.; Zlatian, O.; Vinceti, M.; Moschos, S. A.; Tsoukalas, D.; Goumenou, M.; Drakoulis, N.; Dumanov1, J. M.; Tutelyan, V. A.; Onischenko, G. G.; Aschner, M.; Spandidos, D. A.; Calina, D.
abstract

The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades.

2020 - Anxiofit-1 and reduction of subthreshold and mild anxiety: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from Anxiofit Ltd., submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Hungary, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Anxiofit-1 and reduction of subthreshold and mild anxiety. The food, Anxiofit-1, Echinacea angustifolia root extract, standardised for the content of echinacoside (at least 3%) and the profile of alkamides, which is the subject of the health claim, is sufficiently characterised. The Panel considers that reduction of subthreshold and mild anxiety is a beneficial physiological effect. Subthreshold and mild anxiety are risk factors for anxiety and depressive disorders. One human intervention study showed an effect of Anxiofit-1 (80 mg/day given for 7 days) on the state anxiety and not on the trait subscale in subjects with subthreshold or mild anxiety. These results are supported by two human intervention studies conducted with Anxiofit-1 at 40 mg/day for 7 days and 6 weeks, respectively, which, on their own, cannot be used for the substantiation of the claim either because of methodological limitations or because the results cannot be extrapolated to the target population for the claim. All the human intervention studies submitted have been conducted in a similar setting, the results of the study with Anxiofit-1 given at 80 mg/day have not been confirmed by other research groups. The information submitted by the applicant does not provide evidence for a plausible mechanism by which Anxiofit-1 could exert the claimed effect. The Panel concludes that the scientific evidence is insufficient to establish a cause and effect relationship between the consumption of Anxiofit-1 and reduction of subthreshold and mild anxiety.

2020 - Bifidobacterium animalis subsp. lactis Bi-07 contributes to increasing lactose digestion: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; s Bresson, J. -L.; Siani, A.
abstract

Following an application from DuPont Nutrition Biosciences ApS submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Bifidobacterium animalis subsp. lactis Bi-07 (Bi-07) and contribution to increasing lactose digestion. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Bi-07. The Panel considers that Bi-07 is sufficiently characterised. The claimed effect proposed by the applicant is ‘improvement of lactose digestion’. The Panel considers that increasing lactose digestion is a beneficial physiological effect for individuals with lactose maldigestion provided that the symptoms of lactose maldigestion are improved. Two human intervention studies which investigated a single dose effect of Bi-07 on lactose digestion using the hydrogen breath test, as well as on gastrointestinal symptoms were submitted. These studies show that consumption of Bi-07 (1012 CFU) increases lactose digestion in individuals with lactose maldigestion and that Bi-07 exhibits lactase activity in vitro. However, these studies provide no evidence that increasing lactose digestion through the consumption of Bi-07 (1012 CFU) improves gastrointestinal symptoms of lactose maldigestion, which is considered a beneficial physiological effect. The Panel concludes that a cause and effect relationship has not been established between the consumption of Bifidobacterium animalis subsp. lactis Bi-07 and a beneficial physiological effect (i.e. the improvement of symptoms of lactose maldigestion) in individuals with lactose maldigestion.

2020 - COVID-19, an opportunity to reevaluate the correlation between long-term effects of anthropogenic pollutants on viral epidemic/pandemic events and prevalence [Articolo su rivista]
Tsatsakis, A.; Petrakis, D.; Nikolouzakis, T. K.; Docea, A. O.; Calina, D.; Vinceti, M.; Goumenou, M.; Kostoff, R. N.; Mamoulakis, C.; Aschner, M.; Hernandez, A. F.
abstract

Occupational, residential, dietary and environmental exposures to mixtures of synthetic anthropogenic chemicals after World War II have a strong relationship with the increase of chronic diseases, health cost and environmental pollution. The link between environment and immunity is particularly intriguing as it is known that chemicals and drugs can cause immunotoxicity (e.g., allergies and autoimmune diseases). In this review, we emphasize the relationship between long-term exposure to xenobiotic mixtures and immune deficiency inherent to chronic diseases and epidemics/pandemics. We also address the immunotoxicologic risk of vulnerable groups, taking into account biochemical and biophysical properties of SARS-CoV-2 and its immunopathological implications. We particularly underline the common mechanisms by which xenobiotics and SARS-CoV-2 act at the cellular and molecular level. We discuss how long-term exposure to thousand chemicals in mixtures, mostly fossil fuel derivatives, exposure toparticle matters, metals, ultraviolet (UV)–B radiation, ionizing radiation and lifestyle contribute to immunodeficiency observed in the contemporary pandemic, such as COVID-19, and thus threaten global public health, human prosperity and achievements, and global economy. Finally, we propose metrics which are needed to address the diverse health effects of anthropogenic COVID-19 crisis at present and those required to prevent similar future pandemics.

2020 - Cadmium exposure and risk of breast cancer: A dose-response meta-analysis of cohort studies [Articolo su rivista]
Filippini, T.; Torres, D.; Lopes, C.; Carvalho, C.; Moreira, P.; Naska, A.; Kasdagli, M. -I.; Malavolti, M.; Orsini, N.; Vinceti, M.
abstract

Background: Cadmium is a toxic heavy metal that has been implicated in breast cancer etiology, albeit with inconsistent results. Objective: To investigate the shape of the relation between cadmium exposure and breast cancer incidence and mortality in cohort studies. Data sources: Following a literature search through April 14, 2020, we carried out a systematic review and dose-response meta-analysis to investigate the shape of the relation between cadmium exposure (assessed either through diet or urine excretion) and disease incidence and mortality. Study eligibility criteria: For inclusion, a study had to report incidence or mortality for breast cancer according to baseline cadmium exposure category; be a prospective cohort, case-cohort or nested case-control study with a minimum one-year follow-up, and reporting effect estimates for all exposure categories. Study appraisal and synthesis methods: Studies were evaluated using the ROBINS-E risk of bias tool. The effects in humans were assessed quantitatively using one-stage dose-response meta-analysis in a random effects meta-analytical model. Results: We identified 10 studies eligible for inclusion in the dose-response meta-analysis, six based on cadmium dietary intake, and four on urinary excretion levels. We found a marginal and imprecise positive relation between dietary cadmium intake and breast cancer, and no association when urinary cadmium excretion was used for exposure assessment. Compared to no exposure, at 20 µg/day of cadmium intake the summary risk ratio was 1.12 (95% confidence interval 0.80–1.56), while at 2 µg/g creatinine of cadmium excretion the summary risk ratio was 0.89 (95% confidence interval 0.38–2.14). Analysis restricted to post-menopausal women showed no association between either dietary or urinary cadmium and subsequent breast cancer incidence and mortality. Limitations and conclusions: Overall, we found scant evidence of a positive association between cadmium and breast cancer. Available data were too limited to carry out stratified analyses according to age, smoking and hormone receptor status. Therefore, possible associations between cadmium exposure and breast cancer in selected subgroups cannot be entirely ruled out.

2020 - Calcium l-methylfolate as a source of folate added for nutritional purposes to infant and follow-on formula, baby food and processed cereal-based food [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Bernasconi, G.; Germini, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the extension of use of calcium l-methylfolate to be used as a source of folate added for nutritional purposes to infant and follow-on formula, baby food and processed cereal-based food pursuant to Regulation (EU) 609/2013. In 2004, EFSA assessed the use of calcium l-methylfolate as a source of folate in foods for particular nutritional uses, food supplements and foods intended for the general population. The new alternative synthetic step proposed to produce the nutrient source, using platinum as a catalyst, did not raise any safety concern and the production process was found to consistently yield a product in line with the proposed specifications. Based on the studies assessed in the previous evaluation, it was concluded that calcium l-methylfolate is non-genotoxic and that subchronic and embryotoxicity/teratogenicity studies in rats did not reveal any adverse effects up to the highest doses tested. The Panel considered that no additional toxicological studies are required on the nutrient source. The intervention study in healthy infants provided by the applicant did not indicate differences in growth and tolerance parameters in infants who consumed either an infant formula supplemented with calcium l-methylfolate or with folic acid, and did not raise concerns regarding safety or tolerability of the infant formula with the proposed nutrient source. The study also provided further supporting evidence for the bioavailability of calcium l-methylfolate. The Panel considers that calcium l-methylfolate is a source from which folate is bioavailable and concludes that calcium l-methylfolate is safe under the proposed uses and use levels for infants and young children.

2020 - Clinical and Lifestyle Factors and Risk of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study [Articolo su rivista]
Filippini, Tommaso; Fiore, Maria; Tesauro, Marina; Malagoli, Carlotta; Consonni, Michela; Violi, Federica; Arcolin, Elisa; Iacuzio, Laura; Oliveri Conti, Gea; Cristaldi, Antonio; Zuccarello, Pietro; Zucchi, Elisabetta; Mazzini, Letizia; Pisano, Fabrizio; Gagliardi, Ileana; Patti, Francesco; Mandrioli, Jessica; Ferrante, Margherita; Vinceti, Marco
abstract

Background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease of the motor neurons. The etiology of ALS remains largely unknown, particularly with reference to the potential environmental determinants. Methods: We performed a population-based case-control study in four provinces from both Northern and Southern Italy in order to assess non-genetic ALS risk factors by collecting through tailored questionnaires information about clinical and lifestyle factors. We estimated ALS risk by calculating odds ratio (OR) with its 95% confidence interval (CI) using unconditional logistic regression models adjusted for sex, age and educational attainment. Results: We recruited 230 participants (95 cases and 135 controls). We found a possible positive association of ALS risk with trauma, particularly head trauma (OR = 2.61, 95% CI 1.19-5.72), electric shock (OR = 2.09, 95% CI 0.62-7.06), and some sports, although at a competitive level only. In addition, our results suggest an increased risk for subjects reporting use of private wells for drinking water (OR = 1.38, 95% CI 0.73-2.27) and for use of herbicides during gardening (OR = 1.95, 95% CI 0.88-2.27). Conversely, there was a suggestion of an inverse association with overall fish consumption (OR = 0.27, 95% CI 0.12-0.60), but with no dose-response relation. Consumption of some dietary supplements, namely those containing amino acids and, in the Southern Italy population, vitamins and minerals such as selenium, seemed associated with a statistically imprecise increased risk. Conclusions: Our results suggest a potential etiologic role a number of clinical and lifestyle factors with ALS risk. However, caution is needed due to some study limitations. These include the small sample size and the low number of exposed subjects, which affect statistical precision of risk estimates, the potential for exposure misclassification, and the uncertainties about mechanisms underpinning the possible association between these factors and disease risk.

2020 - Coffee C21 and protection of DNA from strand breaks: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Ildico Hirsch-Ernst, K.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from Tchibo GmbH submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Coffee C21 and protection of DNA from strand breaks. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is Coffee C21. The Panel considers that Coffee C21, a coffee standardised by its concentration of caffeoylquinic acids (CQA), trigonelline and N-methylpyridinium (NMP), is sufficiently characterised in relation to the claimed effect. The Panel considers that the claimed effect, protection of DNA from strand breaks, is a beneficial physiological effect. Out of the two human intervention studies from which conclusion could be drawn, one study provides some evidence that daily consumption of Coffee C21 (750 mL/day) for 4 weeks decreases DNA strand breaks in habitual coffee drinkers after coffee withdrawal over the previous four weeks. However, the results of this study were not replicated in another study conducted under similar conditions in the same study centre. No studies performed in a different setting, from which conclusions could be drawn, were available. No evidence has been provided for a mechanism by which coffee (including Coffee C21) would reduce DNA damage in human cells by reducing DNA strand breaks. The Panel concludes that a cause and effect relationship has not been established between the consumption of Coffee C21 and protection of DNA from strand breaks.

2020 - Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study [Articolo su rivista]
Di Castelnuovo, A.; Bonaccio, M.; Costanzo, S.; Gialluisi, A.; Antinori, A.; Berselli, Nausicaa; Blandi, L.; Bruno, R.; Cauda, R.; Guaraldi, Giovanni; My, I.; Menicanti, L.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Stefanini, G. G.; Vergori, A.; Abdeddaim, A.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Al Moghazi, S.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bologna, C.; Bonfanti, P.; Brancati, S.; Cacciatore, F.; Caiano, L.; Cannata, F.; Carrozzi, L.; Cascio, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Crisetti, A.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; de Gaetano Donati, K.; Di Gennaro, F.; Di Palma, G.; Di Tano, G.; Fantoni, M.; Filippini, Tommaso; Fioretto, P.; Fusco, F. M.; Gentile, I.; Grisafi, L.; Guarnieri, G.; Landi, F.; Larizza, G.; Leone, A.; Maccagni, G.; Maccarella, S.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marotta, C.; Marra, L.; Mastroianni, F.; Mengozzi, A.; Menichetti, F.; Milic, Jovana; Murri, R.; Montineri, A.; Mussinelli, R.; Mussini, Cristina.; Musso, M.; Odone, A.; Olivieri, M.; Pasi, E.; Petri, F.; Pinchera, B.; Pivato, C. A.; Pizzi, R.; Poletti, V.; Raffaelli, F.; Ravaglia, C.; Righetti, G.; Rognoni, A.; Rossato, M.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Scarafino, A.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinoni, E.; Torti, C.; Trecarichi, E. M.; Vezzani, F.; Veronesi, G.; Vettor, R.; Vianello, A.; Vinceti, Marco; De Caterina, R.; Iacoviello, L.
abstract

Background and aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5–3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.

2020 - Comparison of Methodologies to Estimate Dietary Cadmium Intake in an Italian Population [Articolo su rivista]
Filippini, Tommaso; Upson, Kristen; Adani, Giorgia; Malagoli, Carlotta; Baraldi, Claudia; Michalke, Bernhard; Vinceti, Marco
abstract

Cadmium is a metal that is toxic to humans, and the major source of cadmium exposure in the non-smoking general population is diet. To identify major food sources and lower exposure from diet, an accurate estimate of dietary cadmium intake is needed. Hence, the objectives of this study are to develop a method to assess dietary cadmium intake using a biomarker measurement and to improve the estimation of dietary cadmium intake when using a food frequency questionnaire (FFQ). In a random sample of an Italian population, we collected dietary habits by FFQ and measured cadmium in foods and beverages. These data were used to compute the estimated weekly dietary intake (WDI) of cadmium (µg) by kilogram (kg) of body weight (bw) (WDIFFQ). We also measured fasting serum cadmium levels by inductively-coupled plasma mass spectrometry. We used these data to develop a model for the estimation of the biomarker-derived dietary cadmium intake (WDIbio). In the 51 subjects recruited, the median level of serum cadmium was 0.041 µg/L (interquartile range (IQR): 0.030-0.054). The median WDIFFQ and WDIbio were 1.34 µg/kg bw/week (IQR: 0.86-1.70) and 0.72 µg/kg bw/week (IQR: 0.55-1.11), respectively. The correlation between the two estimates was low-to-moderate (r = 0.291). In exploratory analyses, the correlation was slightly higher in women and participants ages <50 years, and markedly higher in participants with body mass index <25 kg/m2 and smokers. Our approach allows for the dietary contribution to be isolated from the overall cadmium exposure measured with a biomarker; the estimated dietary cadmium intake was roughly similar to that estimated using the FFQ, especially in select subgroups. Future refinements to the biomarker-derived dietary cadmium intake approach should take into consideration additional sources of cadmium exposure, as well as factors affecting its absorption and metabolism.

2020 - Deregulated PTEN/PI3K/AKT/mTOR signaling in prostate cancer: Still a potential druggable target? [Articolo su rivista]
Braglia, L.; Zavatti, M.; Vinceti, M.; Martelli, A. M.; Marmiroli, S.
abstract

Although the prognosis of patients with localized prostate cancer is good after surgery, with a favorable response to androgen deprivation therapy, about one third of them invariably relapse, and progress to castration-resistant prostate cancer. Overall, prostate cancer therapies remain scarcely effective, thus it is mandatory to devise alternative treatments enhancing the efficacy of surgical castration and hormone administration. Dysregulation of the phosphoinositide 3-kinase pathway has attracted growing attention in prostate cancer due to the highly frequent association of epigenetic and post-translational modifications as well as to genetic alterations of both phosphoinositide 3-kinase and PTEN to onset and/or progression of this malignancy, and to resistance to canonical androgen-deprivation therapy. Here we provide a summary of the biological functions of the major players of this cascade and their deregulation in prostate cancer, summarizing the results of preclinical and clinical studies with PI3K signaling inhibitors and the reasons of failure independent from genomic changes.

2020 - Dietary Estimated Intake of Trace Elements: Risk Assessment in an Italian Population [Articolo su rivista]
Filippini, T.; Tancredi, S.; Malagoli, C.; Malavolti, M.; Bargellini, A.; Vescovi, L.; Nicolini, F.; Vinceti, M.
abstract

Dietary intake to trace elements may represent the most relevant source of exposure for the general, non-occupationally population, but some of them have been rarely evaluated. We measured content of fifteen trace elements (antimony, barium, beryllium, boron, cobalt, lithium, molybdenum, nickel, silver, strontium, tellurium, thallium, titanium, uranium, and vanadium) in 908 food and beverage samples through inductively coupled plasma mass spectrometry. We estimated their dietary intake using a validated semi-quantitative food frequency questionnaire collected from a population of the Emilia-Romagna Region in Northern Italy. We compared our estimates with tolerable upper intake levels reported by international agencies and we assessed the non-carcinogenic risk through calculation of total hazard quotient for each trace element according to the US-EPA approach. Overall, estimates of their dietary intake were substantially similar to those reported from other countries, and they fell below the tolerable upper intake levels provided by international agencies. The total hazard quotient for each trace element was below 1. Our findings provide updated estimates of food levels and dietary intake of trace elements far frequently evaluated in a sample of Italian adult consumers. They also suggest that any non-carcinogenic risk associated with intake of investigated trace elements may be ruled out in our population.

2020 - Dietary Habits and Risk of Early-Onset Dementia in an Italian Case-Control Study [Articolo su rivista]
Filippini, Tommaso; Adani, Giorgia; Malavolti, Marcella; Garuti, Caterina; Cilloni, Silvia; Vinceti, Giulia; Zamboni, Giovanna; Tondelli, Manuela; Galli, Chiara; Costa, Manuela; Chiari, Annalisa; Vinceti, Marco
abstract

Risk of early-onset dementia (EOD) might be modified by environmental factors and lifestyles, including diet. The aim of this study is to evaluate the association between dietary habits and EOD risk. We recruited 54 newly-diagnosed EOD patients in Modena (Northern Italy) and 54 caregivers as controls. We investigated dietary habits through a food frequency questionnaire, assessing both food intake and adherence to dietary patterns, namely the Greek-Mediterranean, the Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. We modeled the relation between dietary factors and risk using the restricted cubic spline regression analysis. Cereal intake showed a U-shaped relation with EOD, with risk increasing above 350 g/day. A high intake (>400 g/day) of dairy products was also associated with excess risk. Although overall fish and seafood consumption showed no association with EOD risk, we found a U-shaped relation with preserved/tinned fish, and an inverse relation with other fish. Similarly, vegetables (especially leafy) showed a strong inverse association above 100 g/day, as did citrus and dry fruits. Overall, sweet consumption was not associated with EOD risk, while dry cake and ice-cream showed a positive relation and chocolate products an inverse one. For beverages, we found no relation with EOD risk apart from a U-shaped relation for coffee consumption. Concerning dietary patterns, EOD risk linearly decreased with the increasing adherence to the MIND pattern. On the other hand, an inverse association for the Greek-Mediterranean and DASH diets emerged only at very high adherence levels. To the best of our knowledge, this is the first study that explores the association between dietary factors and EOD risk, and suggests that adherence to the MIND dietary pattern may decrease such risk.

2020 - Dietary acrylamide intake and risk of cancer: a systematic review [Abstract in Atti di Convegno]
Capitão, Carolina; Martins, Raquel; Halldorsson, Thorhallur I.; Filippini, Tommaso; Vinceti, Marco; Santos, Osvaldo; Virgolino, Ana; Laguzzi, Federica
abstract

2020 - Dietary intake of acrylamide and risk of breast, endometrial and ovarian cancers: A systematic review and dose-response meta-analysis [Articolo su rivista]
Adani, Giorgia; Filippini, Tommaso; Wise, Lauren A; Halldorsson, Thorhallur I; Blaha, Ludek; Vinceti, Marco
abstract

Acrylamide is a probable human carcinogen. Aside from occupational exposures and smoking, diet is the main source of exposure in humans. We performed a systematic review of the association between estimated dietary intake of acrylamide and risk of female breast, endometrial, and ovarian cancers in non-experimental studies published through February 25, 2020, and conducted a dose-response meta-analysis. We identified 18 papers covering 10 different study populations: 16 cohort and 2 case-control studies. Acrylamide intake was associated with a slightly increased risk of ovarian cancer, particularly among never-smokers. For endometrial cancer, risk was highest at intermediate levels of exposure, whereas the association was more linear and positive among never-smokers. For breast cancer, we found evidence of a null or inverse relation between exposure and risk, particularly among never-smokers and post-menopausal women. In a subgroup analysis limited to premenopausal women, breast cancer risk increased linearly with acrylamide intake starting at 20 µg/day of intake. High acrylamide intake was associated with increased risks of ovarian and endometrial cancers in a relatively linear manner, especially among never-smokers. Conversely, little association was observed between acrylamide intake and breast cancer risk, with the exception of premenopausal women.

2020 - Draft for internal testing Scientific Committee guidance on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments [Articolo su rivista]
More, S.; Bambidis, V.; Benford, D.; Bragard, C.; Hernandez-Jerez, A.; Bennekou, S. H.; Koutsoumanis, K.; Machera, K.; Naegeli, H.; Nielsen, S. S.; Schlatter, J. R.; Schrenk, D.; Silano, V.; Turck, D.; Younes, M.; Fletcher, T.; Greiner, M.; Ntzani, E.; Pearce, N.; Vinceti, M.; Ciccolallo, L.; Georgiadis, M.; Gervelmeyer, A.; Halldorsson, T. I.
abstract

EFSA requested its Scientific Committee to prepare a guidance document on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments. The guidance document provides an introduction to epidemiological studies and illustrates the typical biases of the different epidemiological study designs. It describes key epidemiological concepts relevant for evidence appraisal. Regarding study reliability, measures of association, exposure assessment, statistical inferences, systematic error and effect modification are explained. Regarding study relevance, the guidance describes the concept of external validity. The principles of appraising epidemiological studies are illustrated, and an overview of Risk of Bias (RoB) tools is given. A decision tree is developed to assist in the selection of the appropriate Risk of Bias tool, depending on study question, population and design. The customisation of the study appraisal process is explained, detailing the use of RoB tools and assessing the risk of bias in the body of evidence. Several examples of appraising experimental and observational studies using a Risk of Bias tool are annexed to the document to illustrate the application of the approach. This document constitutes a draft that will be applied in EFSA's assessments during a 1-year pilot phase and be revised and complemented as necessary. Before finalisation of the document, a public consultation will be launched.

2020 - Environmental Risk Factors for Early-Onset Alzheimer's Dementia and Frontotemporal Dementia: A Case-Control Study in Northern Italy [Articolo su rivista]
Adani, G.; Filippini, T.; Garuti, C.; Malavolti, M.; Vinceti, G.; Zamboni, G.; Tondelli, M.; Galli, C.; Costa, M.; Vinceti, M.; Chiari, A.
abstract

Background: Early-onset dementia (EOD) is defined as dementia with symptom onset before 65 years. The role of environmental risk factors in the etiology of EOD is still undefined. We aimed at assessing the role of environmental risk factors in EOD etiology, taking into account its different clinical types. Methods: Using a case-control study, we recruited all EOD cases referred to Modena hospitals from 2016 to 2019, while the referent population was drawn from cases' caregivers. We investigated residential history, occupational and environmental exposures to chemicals and lifestyle behaviors through a self-administered questionnaire. We computed the odds ratios of EOD risk (overall and restricting to the Alzheimer's dementia (AD) or frontotemporal dementia (FTD) diagnoses) and the corresponding 95% confidence intervals using an unconditional logistic regression model. Results: Fifty-eight EOD patients (19 FTD and 32 AD) and 54 controls agreed to participate. Most of the investigated exposures, such as occupational exposure to aluminum, pesticides, dyes, paints or thinners, were associated with an increased odds ratio (OR) for FTD but not for AD. Long-term use of selenium-containing dietary supplements was associated with increased OR for EOD and, particularly, for FTD. For both EOD forms, smoking and playing football showed an increased odds ratio, while cycling was associated with increased risk only in FTD. Overall sports practice appeared to be a protective factor for both types. Conclusions: Our results suggest a role of environmental and behavioral risk factors such as some chemical exposures and professional sports in EOD etiology, in particular with reference to FTD. Overall sports practice may be associated with a reduced EOD risk.

2020 - Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study [Articolo su rivista]
Filippini, Tommaso; Tesauro, Marina; Fiore, Maria; Malagoli, Carlotta; Consonni, Michela; Violi, Federica; Iacuzio, Laura; Arcolin, Elisa; Oliveri Conti, Gea; Cristaldi, Antonio; Zuccarello, Pietro; Zucchi, Elisabetta; Mazzini, Letizia; Pisano, Fabrizio; Gagliardi, Ileana; Patti, Francesco; Mandrioli, Jessica; Ferrante, Margherita; Vinceti, Marco
abstract

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with still unknown etiology. We aimed at investigating the association between environmental and occupational factors with ALS risk. Methods: We performed a population-based case-control study in four Italian provinces (Catania, Modena, Novara, and Reggio Emilia) by administration of tailored questionnaires to ALS cases (n = 95) and randomly selected population referents (n = 135). We estimated ALS risk by calculating the odds ratio (OR) with its 95% confidence interval (CI) using an unconditional logistic regression model. Results: We found a positive association with disease risk for history of occupation in the agricultural sector (OR = 2.09, 95% CI 0.79-7.54), especially for longer than 10 years (OR = 2.72, 95% 1.02-7.20). Overall occupational exposure to solvents also suggested a positive association, especially for thinners (OR = 2.27, 95% CI 1.14-4.54) and paint removers (OR = 2.01, 95% CI 0.90-4.48). Both occupational and environmental exposure to electromagnetic fields show a slightly increased risk with OR = 1.69 (95% CI 0.70-4.09) and 2.41 (95% CI 1.13-5.12), respectively. Occupational but not environmental exposure to pesticides (OR = 1.22, 95% CI 0.63-2.37), particularly fungicides, and exposure to metals (OR = 4.20, 95% CI 1.88-9.38), particularly lead, mercury, and selenium, showed an imprecise but positive association. Finally, there was an indication of increased risk for living in proximity to water bodies. Conclusions: Despite the caution that needs to be used due to some study limitations, such as the low number of exposed subjects and the possibility of recall bias, these results suggest the potential role of some environmental and occupational factors in ALS etiology.

2020 - Environmental and occupational risk factors for early onset dementia in an Italian community [Abstract in Rivista]
Adani, G.; Filippini, T.; Garuti, C.; Malavolti, M.; Vinceti, G.; Zamboni, G.; Tondelli, M.; Galli, C.; Costa, M.; Vinceti, M.; Chiari, A.
abstract

Background: Early onset dementia (EOD) is defined as dementia with symptoms onset before 65 years. Little is known about the etiological role of environmental and occupational risk factors. We aimed at assessing the role of these factors in disease etiology.Methods: Using a case-control design, we recruited all EOD cases resident in Modena province from October, 2016 to October, 2019, as well as a referent population drawn from patients’ care-givers. We investigated residential history of study participants, and their occupational and environmental exposures to pesticides, solvents and metals through a self-administered questionnaire. We computed the odds ratios (ORs) of disease risk, and the corresponding 95% confidence intervals (CIs), according to exposure to the investigated risk factors, using an unconditional logistic regression model adjusted for sex, age, and education. Results: Fifty-eight EOD cases and fifty-four controls agreed to participate. Among occupational factors, disease risk was associated with exposure to aluminum (OR 2.6, 95% CI 0.4-15.7), pesticides (OR 2.3, 95% CI 0.7-7.8) particularly from agricultural occupational exposure (OR 3.1, 95% CI 0.7-13.3) and dyes, paints or thinners (OR 1.7, 95% CI 0.6-5.0). Among lifestyles factors, smoking (OR 1.3, 95% CI 0.6-2.9) and playing football (OR 2.2, 95% CI 0.5-9.3) or cycling (OR 2.3, 95% CI 0.4-13.4) were associated with higher EOD risk, although overall sports practice appeared to be protective factor (OR 0.4, 95% CI 0.2-0.9). Risk was also positively associated with history of head trauma (OR 1.2, 95% CI 0.3-4.1) and particularly upper arm trauma (OR 2.2, 95% CI 0.7-7.5), but not overall trauma. No association emerged for exposure to electromagnetic fields. Conclusions:Despite the study limitations, our results appear to support a role of environmental risk factors in EOD etiology, particularly of some chemical exposures and professional sports, while overall sports practice may have a beneficial effect.

2020 - Exposure to a high selenium environment in Punjab, India: Biomarkers and health conditions [Articolo su rivista]
Chawla, R.; Filippini, T.; Loomba, R.; Cilloni, S.; Dhillon, K. S.; Vinceti, M.
abstract

Seleniferous areas have been identified and described in many parts of the world. Despite the interest in selenium as a trace element of considerable toxicologic and nutritional relevance, however, only a few studies have been carried out on human health effects of such high selenium environments. We collected blood, hair and nail samples from 680 adult volunteers (267 men and 413 women) living in seven villages located in the seleniferous area of Punjab, India. We measured selenium levels in these specimens. We also administered a questionnaire to collect information about diet and other lifestyle characteristics, to identify the sources of selenium exposure and to correlate it with a number of health conditions. Serum and hair selenium contents were highly correlated, while the association of these biomarkers with nail selenium content was weaker. Serum selenium showed limited association with consumption of locally produced foods, while pulses and vegetables, along with cereals and pulses, were associated to higher hair and nail selenium contents, respectively. Association of a number of adverse health endpoints with serum and hair selenium was stronger than for nail selenium contents. Such endpoints included higher prevalence of nausea and vomiting, bad breath, worm infestation, breathlessness exert and bad breath, chest pain, hair and nail abnormalities and loss, garlic odor, edema, spontaneous abortion, and overall selenosis. In contrast, we gathered no evidence of dermatitis or loss of appetite in residents most exposed to selenium. Overall, and despite some statistical imprecision in effect estimates, these results confirm the occurrence of adverse health effects in subjects exposed to high levels of environmental selenium. Nail selenium contents may be less adequate to reflect and monitor such overexposure, compared with blood and hair levels.

2020 - Exposure to a high selenium environment in Punjab, India: Effects on blood chemistry [Articolo su rivista]
Loomba, R.; Filippini, T.; Chawla, R.; Chaudhary, R.; Cilloni, S.; Datt, C.; Singh, S.; Dhillon, K. S.; Vinceti, M.
abstract

Many studies have shown that overexposure to environmental selenium may exert a wide pattern of adverse effects on human health, but much uncertainty still surrounds some of them as well as the exact amounts of exposure involved. In particular, very few studies have addressed the possible changes in blood chemistry following high selenium exposure. In a Northeastern part of Punjab, India, very high soil selenium content has been documented, with a value exceeding 2 mg/kg (up to 5) as compared with the <0.5 mg/kg selenium content characterizing the surrounding referent areas. In seven villages located in that seleniferous areas, we carried out a survey by recruiting volunteers and sampling blood, hair and nail specimens. We administered a questionnaire to the participants and analyzed the specimens for the selenium, along with a series of biochemical and haematological parameters in blood. We included 680 adult volunteers (267 men and 413 women), who showed median selenium levels of 171.30 µg/L in serum, 1.25 µg/g in hair, and 5.7 µg/g in nails. Overall, increasing selenium exposure tended to correlate with higher levels of total cholesterol, albumin, free triiodothyronine, deionidase activity, and with red cell and platelet counts. After stratifying the subjects according to category of selenium exposure, we observed a dose-response relation between serum selenium and risk of high total cholesterol, and between hair selenium and risk of high total and low-density lipoprotein cholesterol, high pancreatic lipase, altered thyroid-stimulating hormone and free triiodothyronine levels. Nail selenium exposure category positively correlated with risk of high alanine-aminotransferase, altered albumin levels, high pancreatic lipase and low levels of thyroid-stimulating hormone. Chronic selenium overexposure appears to adversely affect lipid profiles and pancreatic, liver, and thyroid function, with selenium biomarkers having different abilities to predict such effects.

2020 - Exposure to particulate matter and risk of amyotrophic lateral sclerosis: A case-control study in Northern Italy [Abstract in Rivista]
Filippini, T.; Mandrioli, J.; Malagoli, C.; Cherubini, A.; Maffeis, G.; Vinceti, M.
abstract

Background: Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease with still unknown etiology. Role of occupational and environmental risk factors has been investigated, including outdoor air pollutants, which have been recently associated to an excess disease risk. We carried out a case-control study in order to assess if environmental exposure to particulate matter ≤10 µm (PM10) may increase ALS risk. Methods: We recruited patients referred to the Modena Neurology Unit between 1994-2015 and controls from the Modena province population. Using a validated geographical information system-based dispersion model, we geocoded subjects’ addresses of residence at the time of diagnosis and we estimated outdoor air PM10 concentrations for each subjects. We computed odds ratio (OR) and 95% confidence interval (CI) of ALS according to increasing PM10 exposure, using an unconditional logistic regression model age- and sex-adjusted. Results: For the 132 study participants (52 cases/80 controls), mean of annual average and maximum PM10 concentrations were 5.2 and 38.6µg/m3, respectively. Using fixed cutpoints at 5, 10 and 20 of average annual PM10 concentrations, compared with subjects <5µg/m3, we did not find evidence for an excess ALS risk associated with PM10 exposure, since OR was 0.87 (95% CI 0.39-1.96), 0.94 (0.24-3.70), and 0.87 (0.05-15.01) at 5-10, 10-20 and ≥20µg/m3, respectively. Using maximum annual PM10 concentrations, we found an excess ALS risk for subjects exposed at 10-20µg/m3 (OR=4.27, 0.69-26.51) compared with exposure below 10µg/m3, although the risk tended to decrease at higher PM10 concentrations, with OR of 1.49 (0.39-5.75) at 20-50, and 1.16 (0.98-4.82) at ≥50µg/m3. Conclusions:Our findings do not suggest that PM10exposure is associated with ALS risk. However, some evidence of an increased risk associated with maximum annual exposure concentrations, although statistically imprecise, suggests the need of further investigations, also considering the high concentrations of particulate matter characterizing Northern Italy.

2020 - Exposure to particulate matter and risk of conversion from mild cognitive impairment to dementia: a cohort study in a Northern Italy population [Abstract in Rivista]
Vinceti, M.; Filippini, T.; Malagoli, C.; Cherubini, A.; Maffeis, G.; Chiari, A.
abstract

Background/Aim Exposure to air pollutants such as inhalable particulate matter has been linked to increased risk of chronic disease including neurodegenerative diseases, such as Alzheimer’s dementia. In this study, we aimed to evaluate the effect of long-term exposure to outdoor air pollution, and specifically to particulate matter ≤10 μm (PM10), on the risk of dementia in a cohort of subjects with mild cognitive impairment. MethodsWe recruited 53 subjects newly-diagnosed with mild cognitive impairment of non-vascular origin and residing in the Modena and Reggio Emilia provinces of Northern Italy. Using a Geographical Information System and a validated air pollution dispersion model, we assessed exposure to outdoor PM10 from motorized traffic at subjects’ residence. We investigated the relation of these concentrations to subsequent onset of dementia, using a Cox proportional hazards model. We computed hazard ratio (HR) and 95% confidence interval (CI) according to fixed categories of PM10 exposure, adjusting for sex, age, and educational attainment level. ResultsDuring a median follow-up of 42 months, 19 participants developed Alzheimer’s dementia, 3 frontotemporal dementia and 2 Lewy body dementia. Baseline PM10 exposure levels were 9.6 µg/m3 on average. Using PM10 levels below 5 µg/m3 as reference, we found a dose-response increase in any dementia risk with HR of 1.04 (95% CI 0.41-2.66) at 5-10 µg/m3, 1.32 (95% CI 0.36-4.92) at 10-20 µg/m3, and 1.38 (95% CI 0.14-13.13) above 20 µg/m3, respectively. Conclusions Our results suggest that exposure to particulate matter emitted by motorized vehicles increases the risk of conversion from mild cognitive impairment to dementia, though the low number of study participants suggests caution in the interpretation of these findings.

2020 - Green tea (Camellia sinensis) for the prevention of cancer [Articolo su rivista]
Filippini, T.; Malavolti, M.; Borrelli, F.; Izzo, A. A.; Fairweather-Tait, S. J.; Horneber, M.; Vinceti, M.
abstract

Background: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects. Objectives: To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes. Search methods: We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies. Selection criteria: We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both. Data collection and analysis: Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type. Main results: In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a d

2020 - Identification of cement in atmospheric particulate matter using the hybrid method of laser diffraction analysis and Raman spectroscopy [Articolo su rivista]
Kholodov, A.; Zakharenko, A.; Drozd, V.; Chernyshev, V.; Kirichenko, K.; Seryodkin, I.; Karabtsov, A.; Olesik, S.; Khvost, E.; Vakhnyuk, I.; Chaika, V.; Stratidakis, A.; Vinceti, M.; Sarigiannis, D.; Hayes, A. W.; Tsatsakis, A.; Golokhvast, K.
abstract

Environmental science; Atmospheric science; Ecology; Environmental chemistry; Environmental pollution; Atmospheric particulate matter, Laser diffraction analysis, PM10, Raman spectroscopy

2020 - Insights into the association of potassium intake with blood pressure: results of a dose-response meta-analysis of randomized controlled trials [Abstract in Atti di Convegno]
Filippini, T; Torres, D; Lopes, C; Carvalho, C; Moreira, P; Naska, A; Kasdagli, M-I; Malavolti, M; Orsini, N; Vinceti, M
abstract

Introduction: Observational studies provide evidence for an association between potassium intake and BP levels. However, uncertainties still exist about the size and the shape of this relation. Conversely, experimental studies have not been used to estimate dose-response curves, since standard methods can only be applied in trials including at least three exposure groups. Materials and Methods: We carried out a systematic review of the evidence concerning the effect of potassium supplementation on blood pressure in epidemiologic experimental studies. Following a PubMed search up to June 20, 2019, we included randomized controlled trials (RCTs) encompassing potassium supplementation as the only intervention for at least four weeks. We used a restricted cubic spline model and the ‘one-stage’ approach to perform a dose-response meta-analysis, a newly-developed statistical procedure which allows inclusion of studies with as few as two categories of exposure (Stat Methods Med Res. 2019;28:1579-1596). Finally, we repeated the analyses stratifying for hypertensive status and use of anti-hypertensive medication. Results: Overall, we included 33 studies carried out in adult population, with potassium supplementation ranging from 30 to 140 mmol/day. RCTs’ duration ranged from 4 up to 26 weeks. Most of the studies have a cross-over design (N=24), include hypertensive individuals (N=27) and subjects not under anti-hypertensive medication (N=27). Overall, an increase of 40, 80 and 120 mmol/day of potassium resulted in reductions of SBP by -5.64 (95% CI - 8.78, -2.50), -4.62 (-6.41, -2.84) and -2.54 mmHg (95% CI -5.14, +0.06), respectively. Higher potassium intakes also resulted in reduced DBP levels by -3.57 (95% CI -5.55, -1.59), -3.07 (95% CI -5.07, -1.08), and -1.92 mmHg (95% CI -5.65, 1.81). The effect of increasing potassium intake on BP was larger among hypertensives than normotensives, and among pharmacologically untreated hypertensives compared to their treated counterparts. Subgroup analyses according to study design (parallel vs. crossover) yielded similar results. Discussion: With the application of advanced dose-response modeling on RCT results, we found a U-shaped relation between potassium intake and blood pressure. A low to moderate increase in potassium intake resulted in a progressive reduction in blood pressure, which was reversed at higher levels of potassium supplementation. The effect was stronger among untreated hypertensives. Supported by grant GP-EFSA-AFSCO-2017-01 GA09 of the European Food Safety Authority - EFSA. The text reflects only the authors' view; and EFSA is not responsible for any use that may be made of the information it contains. Conflict of Interest: There is no conflict of interest

2020 - Lead exposure in an Italian population: Food content, dietary intake and risk assessment [Articolo su rivista]
Malavolti, M.; Fairweather-Tait, S. J.; Malagoli, C.; Vescovi, L.; Vinceti, M.; Filippini, T.
abstract

Background and aim: Lead is a highly toxic heavy metal released into the environment after natural and anthropogenic activities. Excluding populations in occupations where there is possible lead contamination, food is the major source of human exposure. In this study, we determined lead contamination in food and beverages consumed in a Northern Italy community and performed a health risk assessment. Methods: We collected a total of 908 food samples and measured lead levels using inductively coupled plasma mass spectrometry. Using a validated food frequency questionnaire, we assessed the dietary habits and estimated daily lead dietary intakes in a sample of 719 adult individuals. We performed risk assessment using a benchmark dose and margin of exposure approach, based on exposure levels for both adverse effect of systolic blood pressure and chronic kidney disease. Results: Foods with the highest lead levels include non-chocolate confectionery (48.7 µg/kg), leafy (39.0 µg/kg) and other vegetables (42.2 µg/kg), and crustaceans and molluscs (39.0 µg/kg). The estimated mean lead intake was 0.155 µg/kg bw-day in all subjects, with little lower intakes in men (0.151 µg/kg bw-day) compared to women (0.157 µg/kg bw-day). Top food contributors were vegetables, cereals, and beverages, particularly wine. In relation to risk assessment, the estimated dietary intake was lower than levels associated with cardiovascular risk and nephrotoxicity. Conclusions: Our study provides an updated assessment of lead food contamination and dietary exposure in a Northern Italian community. The margin of exposure risk assessment approach suggests that risk of detrimental effects due to dietary lead intake is low in the investigated population. Nonetheless, these exposure levels for adverse effects are not reference health standards, and no safety threshold value can be established for lead. As a consequence, other and more subtle adverse effects may still occur in vulnerable and occupationally exposed individuals, particularly in relation to the nervous system.

2020 - Living near waterbodies as a proxy of cyanobacteria exposure and risk of amyotrophic lateral sclerosis: a population based case-control study [Articolo su rivista]
Fiore, Maria; Parisio, Roberto; Filippini, Tommaso; Mantione, Valerio; Platania, Armando; Odone, Anna; Signorelli, Carlo; Pietrini, Vladimiro; Mandrioli, Jessica; Teggi, Sergio; Costanzini, Sofia; Cristaldi, Antonio; Zuccarello, Pietro; Oliveri Conti, Gea; Nicoletti, Alessandra; Zappia, Mario; Vinceti, Marco; Ferrante, Margherita
abstract

Background: Epidemiological studies highlighted the possibility that exposure to cyanotoxins leads to the development of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Methods: We devised a population-based case-control study in two Italian populations. We used residential proximity of the residence to water bodies as a measure of possible exposure to cyanotoxins. Results: Based on 703 newly-diagnosed ALS cases and 2737 controls, we calculated an ALS odds ratio (OR) of 1.41 (95% CI: 0.72–2.74) for current residence in the vicinity of water bodies, and a slightly lower estimate for historical residence (OR: 1.31; 95% CI: 0.57–2.99). Subjects <65 years and people living in the Northern Italy province of Modena had higher ORs, especially when historical residence was considered. Conclusions: Overall, despite some risk of bias due to exposure misclassification and unmeasured confounding, our results appear to support the hypothesis that cyanotoxin exposure may increase ALS risk.

2020 - Lockdown timing and efficacy in controlling COVID-19 using mobile phone tracking [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Rothman, Kenneth J.; Ferrari, Fabrizio; Goffi, Alessia; Maffeis, Giuseppe; Orsini, Nicola
abstract

Background Italy's severe COVID-19 outbreak was addressed by a lockdown that gradually increased in space, time and intensity. The effectiveness of the lockdown has not been precisely assessed with respect to the intensity of mobility restriction and the time until the outbreak receded. Methods We used processed mobile phone tracking data to measure mobility restriction, and related those data to the number of new SARS-CoV-2 positive cases detected on a daily base in the three most affected Italian regions, Lombardy, Veneto and Emilia-Romagna, from February 1 through April 6, 2020, when two subsequent lockdowns with increasing intensity were implemented by the Italian government. Findings During the study period, mobility restriction was inversely related to the daily number of newly diagnosed SARS-CoV-2 positive cases only after the second, more effective lockdown, with a peak in the curve of diagnosed cases of infection occurring 14 to 18 days from lockdown in the three regions and 9 to 25 days in the included provinces. An effective reduction in transmission must have occurred nearly immediately after the tighter lockdown, given the lag time of around 10 days from asymptomatic infection to diagnosis. The period from lockdown to peak was shorter in the areas with the highest prevalence of the infection. This effect was seen within slightly more than one week in the most severely affected areas. Interpretation It appears that the less rigid lockdown led to an insufficient decrease in mobility to reverse an outbreak such as COVID-19. With a tighter lockdown, mobility decreased enough to bring down transmission promptly below the level needed to sustain the epidemic. Funding No funding sources have been used for this work.

2020 - Metal(loid)s role in the pathogenesis of amyotrophic lateral sclerosis: Environmental, epidemiological, and genetic data [Articolo su rivista]
Tesauro, M.; Bruschi, M.; Filippini, T.; D'Alfonso, S.; Mazzini, L.; Corrado, L.; Consonni, M.; Vinceti, M.; Fusi, P.; Urani, C.
abstract

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance. In the remaining sporadic cases, a multifactorial origin is supposed in which several predisposing genes interact with environmental factors. The etiological role of environmental factors, such as pesticides, exposure to electromagnetic fields, and metals has been frequently investigated, with controversial findings. Studies in the past two decades have highlighted possible roles of metals, and ionic homeostasis dysregulation has been proposed as the main trigger to motor-neuron degeneration. This study aims at evaluating the possible role of environmental factors in etiopathogenesis of ALS, with a particular attention on metal contamination, focusing on the industrial Briga area in the province of Novara (Piedmont region, North Italy), characterized by: i) a higher incidence of sporadic ALS (sALS) in comparison with the entire province, and ii) the reported environmental pollution. Environmental data from surface, ground and discharge waters, and from soils were collected and specifically analyzed for metal content. Considering the significance of genetic mechanisms in ALS, a characterization for the main ALS genes has been performed to evaluate the genetic contribution for the sALS patients living in the area of study. The main findings of this study are the demonstration that in the Briga area the most common metal contaminants are Cu, Zn, Cr, Ni (widely used in tip-plating processes), that are above law limits in surface waters, discharge waters, and soil. In addition, other metals and metalloids, such as Cd, Pb, Mn, and As show a severe contamination in the same area. Results of genetic analyses show that sALS patients in the Briga area do not carry recurrent mutations or an excess of mutations in the four main ALS causative genes (SOD1, TARDBP, FUS, C9ORF72) and for ATXN2 CAG repeat locus. This study supports the hypothesis that the higher incidence of sALS in Briga area may be related to environmental metal(loid)s contamination, along with other environmental factors. Further studies, implementing analysis of genetic polymorphisms, as well as investigation with long term follow-up, may yield to key aspects into the etiology of ALS. The interplay between different approaches (environmental, chemical, epidemiological, genetic) of our work provides new insights and methodology to the comprehension of the disease etiology.

2020 - Nutritional safety and suitability of a specific protein hydrolysate derived from whey protein concentrate and used in an infant and follow-on formula manufactured from hydrolysed protein by Danone Trading ELN B.V [Articolo su rivista]
Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Castle, L.; Fewtrell, M.; Przyrembel, H.; Dumas, C.; Titz, A.; Turck, D.
abstract

The European Commission asked EFSA to deliver an opinion on the nutritional safety and suitability of a specific protein hydrolysate. It is derived from whey protein concentrate and used in an infant and follow-on formula by Danone Trading ELN B.V, which submitted a dossier to the European Commission to request an amendment of Regulation (EU) 2016/127 with respect to the protein sources that may be used in the manufacture of infant and/or follow-on formula. This opinion does not cover the assessment of the safety of the food enzymes used in the manufacture of the protein hydrolysate. The protein hydrolysate under evaluation is sufficiently characterised with respect to the fraction of the hydrolysed protein. In the pertinent intervention study provided, an infant formula manufactured from the protein hydrolysate with a protein content of 2.3 g/100 kcal and consumed as the sole source of nutrition by infants for 3.5 months led to growth equivalent to a formula manufactured from intact cow's milk protein (2 g protein/100 kcal). No experimental data have been provided on the nutritional safety and suitability of this protein source in follow-on formula. However, given that it is consumed with complementary foods and the protein source is considered nutritionally safe and suitable in an infant formula that is the sole source of nutrition of infants, the Panel considers that the protein hydrolysate is also a nutritionally safe and suitable protein source for use in follow-on formula. The Panel concludes that the protein hydrolysate under evaluation is a nutritionally safe and suitable protein source for use in infant and follow-on formula, as long as the formula in which it is used contains a minimum of 2.3 g/100 kcal protein and complies with the compositional criteria of Commission Delegated Regulation (EU) 2016/127 and the amino acid pattern in its Annex IIIA.

2020 - Orodispersible lozenges containing a combination of Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 5289 and normal gum function: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Ildico Hirsch-Ernst, K.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Sanz, Y.; Siani, A.
abstract

Following an application from BioGaia AB submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Sweden, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to orodispersible lozenges containing a combination of Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 5289 and normal gum function. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The Panel considers that orodispersible lozenges containing L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289 are sufficiently characterised. Maintenance of normal gum function is a beneficial physiological effect. Out of the two studies from which conclusions could be drawn and that investigated the effect of lozenges containing L. reuteri at the proposed conditions of use (i.e. consumption twice daily) on appropriate gingival outcomes (bleeding on probing (PoB) and gingival index (GI)) in subjects with gingivitis, but without periodontitis, one showed a large effect on BoP and other gingival outcomes and one showed no effect. No effect was found in one study with the use of one lozenge daily. The three studies that investigated, at the proposed conditions of use, modified GI (and not BoP or GI) in subjects with gingivitis, but without periodontitis, or were conducted in patients with periodontitis support an effect of lozenges with L. reuteri on gum function. Some evidence has been provided for mechanisms by which consumption of lozenges containing L. reuteri could improve outcomes of gingivitis in patients with chronic periodontitis but the relevance of such mechanisms for the target population of the claim (i.e. subjects without periodontitis) is unclear. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of orodispersible lozenges containing a combination of L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289 and maintenance of normal gum function.

2020 - Pesticides, cognitive functions and dementia: A review [Articolo su rivista]
Aloizou, A. -M.; Siokas, V.; Vogiatzi, C.; Peristeri, E.; Docea, A. O.; Petrakis, D.; Provatas, A.; Folia, V.; Chalkia, C.; Vinceti, M.; Wilks, M.; Izotov, B. N.; Tsatsakis, A.; Bogdanos, D. P.; Dardiotis, E.
abstract

Pesticides are widely-used chemicals commonly applied in agriculture for the protection of crops from pests. Depending on the class of pesticides, the specific substances may have a specific set of adverse effects on humans, especially in cases of acute poisoning. In past years, evidence regarding sequelae of chronic, low-level exposure has been accumulating. Cognitive impairment and dementia heavily affect a person's quality of life and scientific data has been hinting towards an association between them and antecedent chronic pesticide exposure. Here, we reviewed animal and human studies exploring the association between pesticide exposure, cognition and dementia. Additionally, we present potential mechanisms through which pesticides may act neurotoxically and lead to neurodegeneration. Study designs rarely presented homogeneity and the estimation of the exposure to pesticides has been most frequently performed without measuring the synergic effects and the possible interactions between the toxicants within mixtures, and also overlooking low exposures to environmental toxicants. It is possible that a Real-Life Risk Simulation approach would represent a robust alternative for future studies, so that the safe exposure limits and the net risk that pesticides confer to impaired cognitive function can be examined. Previous studies that evaluated the effect of low dose chronic exposure to mixtures of pesticides and other chemicals intending to simulate real life exposure scenarios showed that hermetic neurobehavioral effects can appear after mixture exposure at doses considered safe for individual compounds and these effects can be exacerbated by a coexistence with specific conditions such as vitamin deficiency. However, there is an overall indication, derived from both epidemiologic and laboratory evidence, supporting an association between exposure to neurotoxic pesticides and cognitive dysfunction, dementia and Alzheimer's disease.

2020 - Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials [Articolo su rivista]
Filippini, T.; Naska, A.; Kasdagli, M. -I.; Torres, D.; Lopes, C.; Carvalho, C.; Moreira, P.; Malavolti, M.; Orsini, N.; Whelton, P. K.; Vinceti, M.
abstract

Background Epidemiologic studies, including trials, suggest an association between potassium intake and blood pressure (BP). However, the strength and shape of this relationship is uncertain. Methods and Results We performed a meta-analysis to explore the dose-response relationship between potassium supplementation and BP in randomized-controlled trials with a duration ≥4 weeks using the recently developed 1-stage cubic spline regression model. This model allows use of trials with at least 2 exposure categories. We identified 32 eligible trials. Most were conducted in adults with hypertension using a crossover design and potassium supplementation doses that ranged from 30 to 140 mmol/d. We observed a U-shaped relationship between 24-hour active and control arm differences in potassium excretion and BP levels, with weakening of the BP reduction effect above differences of 30 mmol/d and a BP increase above differences ≈80 mmol/d. Achieved potassium excretion analysis also identified a U-shaped relationship. The BP-lowering effects of potassium supplementation were stronger in participants with hypertension and at higher levels of sodium intake. The BP increase with high potassium excretion was noted in participants with antihypertensive drug-treated hypertension but not in their untreated counterparts. Conclusions We identified a nonlinear relationship between potassium intake and both systolic and diastolic BP, although estimates for BP effects of high potassium intakes should be interpreted with caution because of limited availability of trials. Our findings indicate an adequate intake of potassium is desirable to achieve a lower BP level but suggest excessive potassium supplementation should be avoided, particularly in specific subgroups.

2020 - RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies [Articolo su rivista]
Di Castelnuovo, Augusto; Costanzo, Simona; Antinori, Andrea; Berselli, Nausicaa; Blandi, Lorenzo; Bonaccio, Marialaura; Cauda, Roberto; Gialluisi, Alessandro; Guaraldi, Giovanni; Menicanti, Lorenzo; Mennuni, Marco; Mussinelli, Roberta; My, Ilaria; Parruti, Giustino; Patti, Giuseppe; Perlini, Stefano; Santilli, Francesca; Signorelli, Carlo; Stefanini, Giulio G; Vergori, Alessandra; Abete, Paolo; Ageno, Walter; Agostoni, Piergiuseppe; Aiello, Luca; Al Moghazi, Samir; Arboretti, Rosa; Aucella, Filippo; Barbieri, Greta; Barchitta, Martina; Bartoloni, Alessandro; Bonfanti, Paolo; Cacciatore, Francesco; Caiano, Lucia; Carrozzi, Laura; Cascio, Antonio; Castiglione, Giacomo; Cianfrone, Stefania; Ciccullo, Arturo; Cingolani, Antonella; Cipollone, Francesco; Colomba, Claudia; Colombo, Crizia; Cozzi, Ottavia; Crisetti, Annalisa; Crosta, Francesca; Danzi, Gian Battista; D'Ardes, Damiano; de Gaetano Donati, Katleen; Di Gennaro, Francesco; Di Tano, Giuseppe; D'Offizi, Gianpiero; Fusco, Francesco Maria; Gentile, Ivan; Graziani, Emauele; Guarnieri, Gabriella; Larizza, Giovanni; Leone, Armando; Lio, Veronica; Lucia, Mothanje Barbara; Maccagni, Gloria; Madaro, Ferruccio; Maitan, Stefano; Mancarella, Sandro; Manuele, Rosa; Mapelli, Massimo; Maragna, Riccardo; Marcucci, Rossella; Maresca, Giulio; Marongiu, Silvia; Marotta, Claudia; Marra, Lorenzo; Mastroianni, Franco; Mazzitelli, Maria; Mengozzi, Alessandro; Menichetti, Francesco; Meschiari, Marianna; Milic, Jovana; Minutolo, Filippo; Molena, Beatrice; Mussini, Cristina; Musso, Maria; Odone, Anna; Olivieri, Marco; Palimodde, Antonella; Pasi, Emanuela; Pesavento, Raffaele; Petri, Francesco; Pinchera, Biagio; Pivato, Carlo A; Poletti, Venerino; Ravaglia, Claudia; Rossato, Marco; Rossi, Marianna; Sabena, Anna; Salinaro, Francesco; Sangiovanni, Vincenzo; Sanrocco, Carlo; Scoppettuolo, Giancarlo; Scorzolini, Laura; Sgariglia, Raffaella; Simeone, Paola Giustina; Trecarichi, Enrico Maria; Vettor, Roberto; Vianello, Andrea; Vinceti, Marco; Virano, Alexandra; Vocciante, Laura; Iacoviello, Licia; Caterina, Null
abstract

OBJECTIVE: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID-19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID-19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies.METHODS: We analyzed 4,069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method.RESULTS: Out of 4,069 COVID-19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID-19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR=0.89, 0.67-1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N=2,057) patients (HR=1.00, 0.78-1.26 and HR=0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID-19 adult patients, 9,700 with hypertension) confirmed the absence of association.CONCLUSIONS: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID-19 patients.

2020 - Reply to comment on “environmental and occupational risk factors of amyotrophic lateral sclerosis: A population-based case-control study” [Articolo su rivista]
Filippini, T.; Tesauro, M.; Fiore, M.; Malagoli, C.; Consonni, M.; Violi, F.; Iacuzio, L.; Arcolin, E.; Conti, G. O.; Cristaldi, A.; Zuccarello, P.; Zucchi, E.; Mazzini, L.; Pisano, F.; Gagliardi, I.; Patti, F.; Mandrioli, J.; Ferrante, M.; Vinceti, M.
abstract

We much appreciate the positive comments and interest concerning our study on the environmental and occupational risk factors of amyotrophic lateral sclerosis (ALS) [...].

2020 - Safety of 3’-Sialyllactose (3’-SL) sodium salt as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3’-Sialyllactose (3’-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human identical milk oligosaccharide (HiMO) 3’-SL but also containing D-lactose, sialic acid and a small fraction of other related oligosaccharides resulting in a fully characterised mixture of carbohydrates. The NF is produced by fermentation with a genetically modified strain of Escherichia coli K-12 DH1. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of 3’-SL from the NF at the maximum proposed use levels is unlikely to exceed the intake level of naturally occurring 3’-SL in breastfed infants on a body weight basis. The intake of 3’-SL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 3’-SL is also considered of no safety concern. Food supplements are not intended to be used if other foods with added NF (as well as breast milk, milk, fermented milk-based products and selected cheeses retaining milk sugar (e.g. curd cheese) for infants and young children) are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use for the proposed target populations.

2020 - Safety of 6′-Sialyllactose (6′-SL) sodium salt as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 6′-Sialyllactose (6′-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 6′-SL but also contains D-lactose, sialic acid and a small fraction of other related oligosaccharides. The NF is produced by fermentation with a genetically modified strain of Escherichia coli K-12 DH1. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements. The target population is the general population. The anticipated daily intake of 6′-SL from the NF at the maximum proposed use levels is unlikely to exceed the intake level of naturally occurring 6′-SL in breastfed infants on a body weight basis. The intake of 6′-SL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 6′-SL is also considered of no safety concern. Food supplements are not intended to be used if other foods with the added NF or breast milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

2020 - Safety of Schizochytrium sp. oil as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Ferreira, L.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Schizochytrium sp. oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Schizochytrium sp. is a single-cell microalga. The strain WZU477, used by the applicant (Progress Biotech bv), was found to belong to the species Schizochytrium limacinum and was obtained in a marine environment from rotted mangrove forest leaves. The NF, an oil rich in docosahexaenoic acid (DHA), is isolated from the microalgae by mechanical extraction. The applicant proposed to use the NF in infant formulae (IF) and follow-on formulae (FOF). The use level defined by the applicant was derived from Regulation (EU) 2016/127, which states the mandatory addition of DHA to IF and FOF at the level of 20–50 mg/100 kcal. The intake of DHA resulting from the use of the NF in IF and FOF is not expected to pose safety concerns. The composition of the NF indicates the absence of marine biotoxins in the NF. Furthermore, Schizochytrium limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Based on the information provided, the microalga is not expected to survive the manufacturing process. Toxicological tests conducted with the NF were not performed. However, based on the available toxicological data on various forms of oils derived from Schizochytrium sp., the QPS status of the source of the NF, the production process and the composition of the NF, the Panel considers there are no concerns with regard to toxicity of the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

2020 - Safety of a botanical extract derived from Panax notoginseng and Astragalus membranaceus (AstraGin™) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on a botanical extract derived from both Panax notoginseng and Astragalus membranaceus (AstraGin™) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a combination of an ethanol extract of the roots of A. membranaceus and a hot water extract of the roots of P. notoginseng. The NF contains 1.5–5% total saponins, 0.1–0.5% ginsenoside Rb1 and 0.01–0.1% astragaloside I. Both plants that are used to produce the NF have a long history of use, especially in traditional Chinese medicine. Information on the production process and the composition of the NF is sufficient and does not raise safety concerns. The applicant proposed to use the NF as a food supplement for the general adult population, excluding pregnant women, at a maximum daily amount of 350 mg. Taking into account these conditions of use, the Panel considers that the consumption of the NF is not nutritionally disadvantageous. The provided genotoxicity studies do not raise concerns for genotoxicity of the NF. Based on the findings of a subchronic toxicity study, supported by a subacute toxicity study, the Panel identified the overall no observed adverse effect level (NOAEL) of the NF at 100 mg/kg body weight (bw) per day. By applying an uncertainty factor of 200, the Panel concludes that the NF is safe at an intake level of 0.5 mg/kg bw per day, corresponding to a maximum daily intake of 35 mg of the NF for the target population, i.e. adults excluding pregnant women.

2020 - Safety of astaxanthin for its use as a novel food in food supplements [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Gelbmann, W.; Steinkellner, H.; Knutsen, H. K.
abstract

Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of astaxanthin when used as a novel food in food supplements at maximum levels of 8 mg/day, taking into account the overall cumulative intake of astaxanthin from all food sources. In 2014, the NDA Panel assessed the safety of the novel astaxanthin-rich ingredient derived from microalgae Haematococcus pluvialis in the context of an application submitted under Regulation (EC) No 258/1997. In that opinion, the NDA Panel considered that the acceptable daily intake (ADI) for astaxanthin was 0.034 mg/kg body weight (bw) set by the EFSA FEEDAP Panel in 2014. In 2019, the FEEDAP Panel adopted an opinion which concerned the renewal of the authorisation of dimethyldisuccinate-astaxanthin and a new use of the additive for crustaceans and other fish than salmonids. In that assessment, the FEEDAP Panel derived a new ADI of 0.2 mg astaxanthin/kg bw which replaced the ADI of 0.034 mg/kg bw established in 2014. By taking into account an updated exposure assessment for astaxanthin from the background diet (fish and crustaceans) in combination with 8 mg from food supplements, the NDA Panel concludes that (i) such combined exposure to astaxanthin is safe for adults, (ii) 14 to < 18 years old adolescents reach the ADI, and (iii) the ADI is exceeded by 28% in children aged 10 to < 14 years and up to 524% in infants aged 4–6 months.

2020 - Safety of chia seeds (Salvia hispanica L.) subject to thermal processing in relation to the formation of process contaminants as a novel food for extended uses [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Matijevic, L.; Romero, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of chia seeds in foods subject to thermal processing which may result in the formation of process contaminants. The safety assessment of this novel food (NF) is based on previous assessments of chia seeds by the EFSA NDA Panel, information received from a public call for data by EFSA and information retrieved from an extensive literature search performed by EFSA. In 2019, during the overall safety assessment of chia seeds, the NDA panel retrieved one reference which, among others, investigated the formation of process contaminants, i.e. acrylamide, hydroxymethylfurfural and furfural, in wheat flour-based biscuits with added chia seeds flour. Based on this study, the Panel considers that there is a potential for substantial acrylamide formation in biscuits with 10–20% added chia seeds flour with low residual moisture contents (≤ 2%). The Panel is not aware of further scientific evidence corroborating these findings. The extensive new literature searches performed by EFSA did not show any relevant articles regarding either asparagine content or formation of process contaminants in chia seeds and products thereof. Information received from the call for data were either limited or inconclusive. The available evidence does not provide a basis to conclude whether or not the addition of chia seeds to foods undergoing heat treatment (at temperatures above 120°C) results in increased formation of acrylamide as compared to these foods without chia seeds. Reported concentrations of hydroxymethylfurfural and furfural in heat-treated chia seeds do not pose a safety concern. No information on other process contaminants in chia seeds was found.

2020 - Safety of chromium-enriched biomass of Yarrowia lipolytica as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on chromium-enriched biomass of Yarrowia lipolytica as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is the dried and heat-killed chromium-enriched biomass of Y. lipolytica. This yeast species is widespread in nature, can be found in the environment and in foods, and was attributed the qualified presumption of safety (QPS) status for production purposes in 2018, including food and feed products based on biomass of the yeast. The production process, fermentation in the presence of chromium chloride, includes a heat-killing step of the yeast, resulting in the absence of viable Y. lipolytica in the NF. The maximum total chromium content of the NF is 23 μg Cr/g, with the chromium present as Cr(III). The applicant proposed to use the NF as a food supplement. The target population proposed by the applicant is the general population from 3 years of age onwards, with maximum proposed use levels of 2 g/day for children from 3 to 9 years of age and 4 g/day thereafter. At the proposed use levels of the NF, the combined intake of chromium provided by the NF, in addition to a background diet high in chromium, would result in total chromium intakes well below the tolerable daily intake (TDI) for chromium(III) for all target population groups. The Panel concludes that the NF, chromium-enriched biomass of Y. lipolytica, is safe under the proposed conditions of use.

2020 - Safety of dried whole cell Euglena gracilis as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of dried whole cell Euglena gracilis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. E. gracilis is a single-cell microalga which occurs widely in nature and is commonly found in freshwater habitats. The NF, the dried biomass of E. gracilis, is produced by fermentation and its major constituent (> 50%) is a β-glucan polysaccharide. The applicant proposed to use the NF in food supplements, in foods for total diet replacement for weight control and as a food ingredient added to a number of food products. The target population proposed by the applicant is the general population, except for food supplements and for foods for total diet replacement for which the target population is the general population from 12 months of age onwards. In 2019, E. gracilis was attributed the qualified presumption of safety (QPS)-status with the qualification ‘for production purposes only’, which includes food products based on microbial biomass of the microalga. Based on the information provided, E. gracilis is not expected to survive the manufacturing process. The submitted toxicity studies did not raise safety concerns. No adverse effects were observed in the subchronic toxicity study, up to the highest dose tested, i.e. 3,300 mg NF/kg body weight, considered as the no observed adverse effect level (NOAEL). The margins of exposure between this dose and the high (95th percentile) intake estimates, range from 33 for infants to 192 for adults. The Panel considers that in view of the QPS status of the source of the NF, supported by the compositional data and lack of toxicity observed in the 90-day study, the margins of exposure are sufficient. The Panel considers that the NF, i.e. dried whole cell Euglena gracilis, is safe at the proposed uses and use levels.

2020 - Safety of hot water extract of fruits and peduncles of Hovenia dulcis as a novel food pursuant to Regulation 1(EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of ‘Hovenia dulcis fruit extract’ as a novel food (NF) for its use in food supplements. The NF concerns a hot water extract of sliced and dried fruits and peduncles of Hovenia dulcis Thun. The production process is described in sufficient detail but contains contradictory information regarding the mixing with another ingredient of the NF. The NF is comprised of mostly carbohydrates (about 90%), about 2% proteins, 5% moisture, less than 1% fat and about 2% ash. In addition, the NF contains small amounts of flavonoids such as dihydromyricetin, myricetin and quercetin. The Panel notes limitations of the data provided from the batch testing regarding proximate analyses and plant secondary metabolites. Given these limitations, the Panel considers that the data provided by the applicant do not demonstrate that different batches produced with the described production process meet the proposed specifications. The target population is the general adult population excluding pregnant and lactating women and people with a chronic disease, such as liver malfunction. Limited information was provided on a history of consumption of Hovenia dulcis fruits and on an extract approved in South Korea. A number of toxicological studies were performed. However, the study reports did not allow to verify that the test item was representative of the NF. The same applied to a human study provided by the applicant. The Panel concludes that the safety of the NF has not been established.

2020 - Safety of lacto-N-neotetraose (LNnT) produced by derivative strains of E. coli BL21 as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Maradona, M. P.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the change in the production process and specifications of lacto-N-neotetraose (LNnT) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) LNnT but also contains lactose, lacto-N-triose II (LNT II), para-lacto-N-neo-hexaose (para-LNnH) and other related carbohydrates. The NF is produced by fermentation with two genetically modified strains of Escherichia coliBL21. LNnT when chemically synthesised or produced by microbial fermentation using another E. coli strain (K-12) is already authorised and included in the EU list of NFs. This application is limited to a change in the manufacturing process and specifications while target population, uses and use levels and consequently the anticipated intake do not change. The information provided on the manufacturing process, including the absence of DNA from the producing microorganisms, composition, identity and specifications of the NF do not raise safety concerns. Particularly, the proposed changes in the specifications are limited to a slightly higher ash content and limits for the presence of yeast and moulds, while specifications for methanol and LNnT fructose isomer have been removed. Food supplements are not intended to be used if other foods with the added NF or breast milk for young children are consumed on the same day. The Panel concludes that lacto-N-neotetraose (LNnT) as a NF when produced by fermentation with two genetically modified strains of E. coliBL21 is safe under the proposed conditions of use.

2020 - Safety of rapeseed powder from Brassica rapa L. and Brassica napus L. as a Novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Dumont, A. F.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of rapeseed powder from Brassica rapa L. and Brassica napus L. as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Rapeseed powder will be produced from the seeds of non-genetically modified double low (00) cultivars that are varieties with a low content of erucic acid and reduced content of glucosinolates compared to older varieties. The applicant developed a production process designed to further reduce the content of glucosinolates and other undesirable compounds such as phytates. The NF will be used as a food ingredient added to a number of food products. The target population is the general population from 1 year of age. The maximum estimated intake of the NF is 18–21 g/day in adolescents, adults and elderly (corresponding to 0.35, 0.23 and 0.25 g/kg body weight (bw) per day, respectively). The levels of undesirable compounds in this NF, such as erucic acid, glucosinolates and phytates, are below levels which would raise concerns. The EFSA NDA Panel has previously assessed the safety of similar products for human consumption and there is extensive experience on the use of rapeseed in animal feed. The applicant provided a human study on the safety and tolerability of the NF and no safety concerns were identified. The Panel considers that the NF, i.e. rapeseed powder from Brassica rapa L. and Brassica napus L., is safe at the proposed conditions of use.

2020 - Safety of selenium-enriched biomass of Yarrowia lipolytica as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Ackerl, R.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on selenium-enriched biomass of Yarrowia lipolytica as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is the dried and heat-killed selenium-enriched biomass of Y. lipolytica. This yeast species is widespread in nature, can be found in the environment and in foods, and was attributed the qualified presumption of safety (QPS) status for production purposes in 2018, including food and feed products based on biomass of the yeast. The production process, fermentation in the presence of sodium selenite, includes a heat-killing step of the yeast, resulting in the absence of viable Y. lipolytica in the NF. The maximum total selenium content in the NF is 200 μg Se/g, mainly present as organic selenium compounds. The applicant proposed to use the NF as a food supplement. The target population proposed by the applicant is the general population from 3 years of age onwards, with maximum proposed use levels of 0.2 g/day for children from 3 to 9 years of age and 1 g/day thereafter. The Panel considers that the yeast biomass is not of safety concern at the proposed use levels. The Panel also considers that the selenium provided by the NF is as safe as selenium from other dietary sources. However, the Panel notes that, at the use levels proposed by the applicant, the intake of the NF could, in combination with a background diet high in selenium, lead to total selenium intakes exceeding the UL for selenium in all target population groups, except for children from 7 to 9 years. Furthermore, the Panel considers that newly emerging data warrant a reassessment of the UL for selenium.

2020 - Safety of the extension of use of plant sterol esters as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of the novel food ‘plant sterol esters’ when added to vegetable fat spreads and to liquid vegetable fat-based emulsions for cooking and baking purposes pursuant to Regulation (EU) 2015/2283. Member States expressed concerns in relation to plant sterol oxidation products (POP) and consumption by non-target population groups. The median (0.5%) and P90 (2.28%) value of the oxidation rates of plant sterols determined by a wide range of cooking experiments were used together with exposure estimates for plant sterol when added and cooked with vegetable fat spreads and liquids. The no-observed adverse effect level (NOAEL) of a subchronic rat study and an applied default uncertainty factor of 200 served to derive levels (i.e. 0.64 mg POP/kg body weight (bw) per day) considered safe for humans. This safe level of exposure would be exceeded at the P95 by all age groups when considering the P90 oxidation rate and using EFSA's comprehensive food consumption database for assessing the potential exposure. When considering the median oxidation rate, the safe level of 0.64 mg POP/kg bw per day would be exceeded at the highest P95 intake estimates in children below 9 years of age. When considering an intake of the maximum authorised use level of 3 g plant sterols/person per day and oxidation rates of 0.5% and 2.28%, the resulting daily POP intakes per kg bw by an adult weighing 70 kg would be 0.21 and 0.98 mg/kg bw per day, respectively, the latter value exceeding 0.64 mg/kg bw per day. The Panel concludes that the safety of the intended extension of use of plant sterol esters under the proposed conditions of use has not been established.

2020 - Safety of vitamin D2 mushroom powder as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Roldan-Torres, R.; Steinkellner, H.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on vitamin D2 mushroom powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an ingredient produced from Agaricus bisporus mushrooms that have been exposed to ultraviolet (UV) light to induce the conversion of provitamin D2 (ergosterol) to vitamin D2 (ergocalciferol). The NF contains concentrations of vitamin D provided by vitamin D2 in the ranges of 1,000–1,300 μg/g. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods and beverages, including food for special medical purposes and food supplements. The target population is the general population except for food supplements, for which the target population is individuals above seven months of age. The Panel concludes that the NF, used as an ingredient, is safe for the general population at the proposed condition of use in foods and beverages and that the NF used as a food supplement, is safe for individuals above 1 year. The Panel, however, notes that the UL for infants aged 0–6 months may be exceeded in high consumers of infant formula (IF) and/or follow-on formula (FoF) that may also be high consumers of foods fortified with the NF and for infants aged 7–12 months consuming a daily vitamin D oral supplementation of 10 μg. However, the Panel considers this scenario unlikely as complementary feeding in high consumers of IF and/or FoF may be limited. Furthermore, the combined consumption of vitamin D via fortified foods and supplements does not specifically concern this NF application. The Panel concludes that the NF is safe under the proposed conditions of use for the proposed target populations.

2020 - Satellite-detected tropospheric nitrogen dioxide and spread of SARS-CoV-2 infection in Northern Italy [Articolo su rivista]
Filippini, T.; Rothman, K. J.; Goffi, A.; Ferrari, F.; Maffeis, G.; Orsini, N.; Vinceti, M.
abstract

Following the outbreak of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) last December 2019 in China, Italy was the first European country to be severely affected, with the first local case diagnosed on 20 February 2020. The virus spread quickly, particularly in the North of Italy, with three regions (Lombardy, Veneto and Emilia-Romagna) being the most severely affected. These three regions accounted for >80% of SARS-CoV-2 positive cases when the tight lockdown was established (March 8). These regions include one of Europe's areas of heaviest air pollution, the Po valley. Air pollution has been recently proposed as a possible risk factor of SARS-CoV-2 infection, due to its adverse effect on immunity and to the possibility that polluted air may even carry the virus. We investigated the association between air pollution and subsequent spread of the SARS-CoV-2 infection within these regions. We collected NO2 tropospheric levels using satellite data available at the European Space Agency before the lockdown. Using a multivariable restricted cubic spline regression model, we compared NO2 levels with SARS-CoV-2 infection prevalence rate at different time points after the lockdown, namely March 8, 22 and April 5, in the 28 provinces of Lombardy, Veneto and Emilia-Romagna. We found little association of NO2 levels with SARS-CoV-2 prevalence up to about 130 μmol/m2, while a positive association was evident at higher levels at each time point. Notwithstanding the limitations of the use of aggregated data, these findings lend some support to the hypothesis that high levels of air pollution may favor the spread of the SARS-CoV-2 infection.

2020 - Scientific Opinion related to a notification from Lyckeby Starch AB on barley starch to be used in the manufacturing of several foods as ingredient, of the food additive modified starch and of glucose syrups pursuant to Article 21(2) of Regulation (EU) No 1169/2011 – for permanent exemption from labelling [Articolo su rivista]
Turck, D.; Castenmiller, J.; Hirsch Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Marchelli, R.; van Loveren, H.; Martinez, S. V.; de Henauw, S.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on barley starch to be used in the manufacturing of several foods as ingredient, of the food additive modified starch and of glucose syrups pursuant to Article 21(2) of Regulation (EU) No 1169/2011, as notified by Lyckeby Starch AB. The applicant provided information on the manufacturing process and data on the content of total protein, gluten and allergenic proteins in barley starch. The applicant also performed IgE-binding in vitro tests, which were considered inconclusive by the Panel. No human intervention studies with barley starch or food products thereof were provided by the applicant, except for a DBPCFC with barley starch hydrolysate in cereal allergic individuals. The Panel notes that glucose syrups based on barley have been already exempted from allergen labelling as per Annex II of Regulation (EU) No 1169/2011 and that the current application is for the exemption from labelling of all foods manufactured from barley starch. In all the scenarios considered for the anticipated intake, the calculated total protein intake from barley starch was above the MED/MOED for wheat (expressed in mg of wheat protein) in adults (10 mg) and children (2 mg). The Panel concludes that the data available are insufficient to conclude on the likelihood of adverse allergic reactions in cereal-allergic individuals upon consumption of barley starch under the conditions of use proposed by the applicant, and that the consumption of foodstuffs produced from barley starch as starting (raw) material or foodstuffs containing barley starch as an ingredient is unlikely to cause an adverse reaction in individuals with coeliac disease who are not allergic to cereals, provided that the value of gluten for ‘gluten-free’ foods (20 mg/kg) is not exceeded.

2020 - Scientific opinion on the safety of selenite triglycerides as a source of selenium added for nutritional purposes to food supplements [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Schlatter, J. R.; van Loveren, H.; Germini, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on selenite triglycerides as a novel food (NF) pursuant to Regulation (EU) 2015/2283, their safety when added for nutritional purposes to food supplements as a source of selenium and the bioavailability of selenium from this source, in the context of Directive 2002/46/EC. The proposed NF is the first lipophilic organic form of selenium so far described in the literature. It is composed by a mixture of individual Se-containing lipids which do not occur in nature. The Panel considers that the information provided on the composition of the NF does not allow a complete characterisation of the product. From the data provided to characterise the absorption, distribution, metabolism and excretion of the NF, it cannot be established in which chemical form Se is systemically available and if it can enter the functional Se body pool to fulfil Se physiological functions. The Panel considers that, since it is not demonstrated that the NF is converted to a known form of Se following ingestion and absorption, the NF is to be treated as a xenobiotic with unknown properties in the body. From a subchronic toxicity study in rats, the Panel derives a lowest observed adverse effect level (LOAEL) for general toxicity of 2 mg Se/kg body weight (bw) per day based on findings indicating liver as a target organ, as it has been shown for other studies on dietary Se. The Panel concludes that the NF is absorbed and provides Se, but in an unknown form of which the bioavailability has not been determined. The Panel also concludes that the safety of the NF under the intended conditions of use cannot be established.

2020 - Selenium and Other Trace Elements in the Etiology of Parkinson's Disease: A Systematic Review and Meta-Analysis of Case-Control Studies [Articolo su rivista]
Adani, G.; Filippini, T.; Michalke, B.; Vinceti, M.
abstract

Background: Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's dementia. Whereas the exact etiology of PD remains unknown, risk of developing PD seems to be related to a combination of genetic and environmental factors. This also includes abnormal exposure to trace elements of nutritional and toxicological interest. Objectives: In this systematic review and meta-Analysis, we summarized the results of case-control studies comparing levels of selenium, copper, iron, and zinc in PD patients and controls in either blood (whole blood, serum/plasma) or cerebrospinal fluid (CSF). Methods: We performed a systematic PubMed search selecting studies reporting trace element levels in different specimens of patients and controls. We performed a meta-Analysis using a random-effect model to compute the weighted mean differences (WMD) and corresponding 95% CI of selenium, copper, iron, and zinc levels in the blood or CSF of patients and their matched controls. Results: We retrieved 56 papers reporting data for selenium (cases/controls: 588/721), copper (2,190/2,522), iron (2,956/3,469), and zinc (1,798/1,913) contents in CSF and blood. Cases showed considerably higher levels of selenium in CSF compared with controls (+51.6%; WMD 5.49; 95% CI 2.82 to 8.15), while levels in serum were similar (-0.2%; WMD-0.22; 95% CI-8.05 to 7.62). For copper, cases showed slightly higher levels in CSF and slightly lower concentrations in serum (+4.5%; WMD 1.87; 95% CI-3.59 to 7.33, and-4.5%; WMD-42.79; 95% CI-134.35 to 48.76, respectively). A slight increase was also found for CSF iron-levels (+9.5%; WMD 9.92; 1.23 to 18.61), while levels were-decreased in serum/plasma (-5.7%; WMD-58.19; 95% CI-106.49 to-9.89) and whole blood (-10.8%; WMD-95.69; 95% CI-157.73 to-33.65). Conversely, for zinc cases exhibited lower levels both in CSF (-10.8%; WMD-7.34; 95% CI-14.82 to 0.14) and serum/plasma (-7.5%; WMD-79.93; 95% CI-143.80 to-16.06). A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood. Conclusions: Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones, this meta-Analysis suggests that overexposure in the central nervous system to selenium, and possibly to copper and iron, may be a risk factor of the disease, while zinc might have a protective-effect.

2020 - Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity [Articolo su rivista]
Tinkov, Alexey A; Ajsuvakova, Olga P; Filippini, Tommaso; Zhou, Ji-Chang; Lei, Xin Gen; Gatiatulina, Eugenia R; Michalke, Bernhard; Skalnaya, Margarita G; Vinceti, Marco; Aschner, Michael; Skalny, Anatoly V
abstract

Selenium (Se) homeostasis is tightly related to carbohydrate and lipid metabolism, but its possible roles in obesity development and in adipocyte metabolism are unclear. The objective of the present study is to review the current data on Se status in obesity and to discuss the interference between Se and selenoprotein metabolism in adipocyte physiology and obesity pathogenesis. The overview and meta-analysis of the studies on blood Se and selenoprotein P (SELENOP) levels, as well as glutathione peroxidase (GPX) activity in obese subjects, have yielded heterogenous and even conflicting results. Laboratory studies demonstrate that Se may modulate preadipocyte proliferation and adipogenic differentiation, and also interfere with insulin signaling, and regulate lipolysis. Knockout models have demonstrated that the selenoprotein machinery, including endoplasmic reticulum-resident selenoproteins together with GPXs and thioredoxin reductases (TXNRDs), are tightly related to adipocyte development and functioning. In conclusion, Se and selenoproteins appear to play an essential role in adipose tissue physiology, although human data are inconsistent. Taken together, these findings do not support the utility of Se supplementation to prevent or alleviate obesity in humans. Further human and laboratory studies are required to elucidate associations between Se metabolism and obesity.

2020 - Selenium and other trace elements in the etiology of Parkinson’s disease: a systematic review and meta-analysis of case-control studies [Abstract in Rivista]
Adani, G.; Filippini, T.; Michalke, B.; Vinceti, M.
abstract

.INTRODUCTION Parkinson’s disease (PD) is a neurodegenerative illness recognised as the most common neurological disorder after Alzheimer’s dementia. Whereas the exact PD etiology remains unknown, risk of developing PD seems to be related to an interrelation of genetic and environmental factors, including also altered exposure to trace elements. In this systematic review and meta-analysis, we updated and summarized the results of epidemiologic case-control studies comparing levels of selenium, copper, iron and zinc in PD patients with healthy subjects in either blood (as whole blood, serum or plasma) and cerebrospinal fluid (CSF). MATERIALS AND METHODS We performed a systematic PubMed search and we included in our assessment only studies reporting demographic and disease-related characteristics, as well as trace element levels in different specimens (whole blood, serum/plasma and CSF). We then performed a meta-analysis of mean differences of trace element levels between cases and controls, using a random-effect model computing the weighted mean differences (WMD) and corresponding 95% confidence intervals (CI) to assess the association between serum/plasma, whole blood, CSF and selenium, copper, iron and zinc with Parkinson’s disease. RESULTS We retrieved 55 papers reporting data for selenium (588 cases and 721 controls), copper (2190 and 2522), iron (2843 and 3434), and zinc (1798 and 1913). Cases showed higher levels of selenium in CSF compared with controls (WMD=5.49; 95%CI 2.82 to 8.15), while levels in serum were similar (WMD=-0.22; -8.05 to 7.62). For copper cases showed higher levels in CSF and lower in serum compared to controls (WMD=1.87; -3.59 to 7.33, and -42.79, -134.35 to 48.76 respectively). Same results were found for iron in CSF (WMD=6.54; -1.97 to 15.04) and in serum/plasma (WMD=-58.19; -106.49 to -9.89 and whole blood (WMD=-95.69; 157.73 to -33.65). On the converse, cases had lower levels of zinc both in CSF (WMD=-7.34; -14.82 to 0.14) and serum/plasma (WMD=-79.93; -143.80 to -16.06). CONCLUSIONS Results of this systematic review and meta-analysis suggests that overexposure to environmental selenium, copper and iron may be risk factors for PD onset or progression. Alternatively, some variation in levels of these trace elements may occur as a consequence of the disease. Considering the burden of PD in the world population, further investigation of trace element exposure in this disease is therefore warranted, especially to plan possible prevention measures.

2020 - The association between seafood intake and fecundability: Analysis from two prospective studies [Articolo su rivista]
Wise, L. A.; Willis, S. K.; Mikkelsen, E. M.; Wesselink, A. K.; Sorensen, H. T.; Rothman, K. J.; Tucker, K. L.; Trolle, E.; Vinceti, M.; Hatch, E. E.
abstract

Background: Seafood is an important source of omega‐3 fatty acids, which have been associated with improved oocyte quality and embryo morphology in some studies. However, seafood is also a source of persistent organic pollutants and heavy metals, which may adversely affect fecundity. Previous studies of seafood intake and fecundity have generated inconsistent results. Methods: In two prospective cohort studies of 7836 female pregnancy planners from Denmark (Snart Foraeldre, n = 2709) and North America (PRESTO, n = 5127), we evaluated the association of dietary intake of total seafood and marine‐sourced long‐chain omega‐3 fatty acids (eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid) with fecundability. Participants completed a baseline questionnaire on sociodemographics, behavioral factors, anthropometrics, and medical history, and a food frequency questionnaire. Pregnancy status was updated bimonthly for up to 12 months or until reported conception. We estimated fecundability ratios (FRs) and 95% confidence intervals (CIs) using proportional probabilities regression models, adjusted for energy intake and other potential confounders. We restricted analyses to women with ≤6 menstrual cycles of attempt time at enrollment. Results: Intake of total seafood or marine‐sourced long‐chain omega‐3 fatty acids was not appreciably associated with fecundability in either cohort (≥200 vs. <50 g/week total seafood: FR = 0.94, 95% CI: 0.79–1.10 in Snart Foraeldre; FR = 1.00, 95% CI: 0.90–1.13 in PRESTO; marine fatty acids: ≥90th vs. <25th percentile: FR = 1.00, 95% CI: 0.85–1.18 in Snart Foraeldre; FR = 0.97, 95% CI: 0.86–1.09 in PRESTO). In PRESTO, where we collected additional data on seafood preparation, we observed an inverse association between fecundability and fried shellfish (≥10 g/week vs. none: FR = 0.77, 95% CI: 0.61–0.98), but not unfried shellfish (≥20 g/week vs. none: FR = 0.98, 95% CI: 0.89–1.07); in Snart Foraeldre, there was no association with total shellfish intake. Conclusions: We found little association between seafood intake and fecundability overall, but greater intake of fried shellfish was associated with reduced fecundability among North American participants.

2020 - The study of levels from redox-active elements in cerebrospinal fluid of amyotrophic lateral sclerosis patients carrying disease-related gene mutations shows potential copper dyshomeostasis [Articolo su rivista]
Violi, F.; Solovyev, N.; Vinceti, M.; Mandrioli, J.; Lucio, M.; Michalke, B.
abstract

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by a loss of function of motor neurons. The etiology of this disorder is still largely unknown. Gene-environment interaction arises as a possible key factor in the development of amyotrophic lateral sclerosis. We assessed the levels of trace metals, copper (Cu), iron (Fe), and manganese (Mn), of 9 amyotrophic lateral sclerosis cases and 40 controls by measuring their content in cerebrospinal fluid. The following trace element species were quantified using ion chromatography-inductively coupled plasma mass spectrometry: univalent copper (Cu-I), divalent Cu (Cu-II), divalent Fe (Fe-II), trivalent Fe (Fe-III), divalent Mn (Mn-II), trivalent Mn (Mn-III), and also unidentified Mn species (Mn-unknown) were present in some samples. When computing the relative risks for amyotrophic lateral sclerosis through an unconditional logistic regression model, we observed a weak and imprecise positive association for iron (Fe III, adjusted odds ratio 1.48, 95% CI 0.46-4.76) and manganese (total-Mn and Mn-II; adjusted odds ratio 1.11, 95% CI 0.74-1.67, and 1.13, 95% CI 0.79-1.61, respectively). Increased risk for copper was found both in the crude analysis (odds ratio 1.14, 95% CI 0.99-1.31) and in multivariable analysis after adjusting for sex, age, and year of storage (1.09, 95% CI 0.90-1.32). Our results suggest a possible positive association between Cu and genetic amyotrophic lateral sclerosis, while they give little indication of involvement of Fe and Mn in disease, though some correlations found also for these elements deserve further investigation.

2020 - Towards effective COVID‑19 vaccines: Updates, perspectives and challenges (Review) [Articolo su rivista]
Calina, D.; Docea, A. O.; Petrakis, D.; Egorov, A. M.; Ishmukhametov, A. A.; Gabibov, A. G.; Shtilman, M. I.; Kostoff, R.; Carvalho, F.; Vinceti, M.; Spandidos, D. A.; Tsatsakis, A.
abstract

In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS‑COV‑2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID‑19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.

2020 - Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study [Articolo su rivista]
Castelnuovo, A. D.; Costanzo, S.; Antinori, A.; Berselli, N.; Blandi, L.; Bruno, R.; Cauda, R.; Guaraldi, G.; Menicanti, L.; My, I.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Spinoni, E.; Stefanini, G. G.; Vergori, A.; Ageno, W.; Agodi, A.; Aiello, L.; Agostoni, P.; Moghazi, S. A.; Astuto, M.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bonaccio, M.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Cannata, F.; Carrozzi, L.; Cascio, A.; Ciccullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Crosta, F.; Pra, C. D.; Danzi, G. B.; D'Ardes, D.; Donati, K. D. G.; Giacomo, P. D.; Gennaro, F. D.; Tano, G. D.; D'Offizi, G.; Filippini, T.; Fusco, F. M.; Gentile, I.; Gialluisi, A.; Gini, G.; Grandone, E.; Grisafi, L.; Guarnieri, G.; Lamonica, S.; Landi, F.; Leone, A.; Maccagni, G.; Maccarella, S.; Madaro, A.; Mapelli, M.; Maragna, R.; Marra, L.; Maresca, G.; Marotta, C.; Mastroianni, F.; Mazzitelli, M.; Mengozzi, A.; Menichetti, F.; Meschiari, M.; Minutolo, F.; Montineri, A.; Mussinelli, R.; Mussini, C.; Musso, M.; Odone, A.; Olivieri, M.; Pasi, E.; Petri, F.; Pinchera, B.; Pivato, C. A.; Poletti, V.; Ravaglia, C.; Rinaldi, M.; Rognoni, A.; Rossato, M.; Rossi, I.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinicci, M.; Trecarichi, E. M.; Venezia, A.; Veronesi, G.; Vettor, R.; Vianello, A.; Vinceti, M.; Vocciante, L.; De Caterina, R.; Iacoviello, L.
abstract

Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective: We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods: In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results: Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions: HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

2020 - [The Health Examination Survey at regional level: the Emilia-Romagna Region (Northern Italy) example] [Articolo su rivista]
Salvia, Chiara; Donfrancesco, Chiara; Palmieri, Luigi; Lo Noce, Cinzia; Vanuzzo, Diego; Vinceti, Marco; Bargellini, Annalisa; Borella, Paola; Giampaoli, Simona
abstract

to assess time trend of lifestyles, cardiovascular risk factors, and prevalence of high-risk conditions in random samples of the general adult population residing in Emilia-Romagna, examined in two cross-sectional surveys conducted within the Epidemiological Cardiovascular Observatory (OEC 1998-2002) and the Epidemiological Cardiovascular Observatory/Health Examination Survey (OEC/HES 2008-2012).

2019 - A combination of beta-sitosterol and beta-sitosterol glucoside and normal function of the immune system: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from Essential Sterolin Products (Pty) Ltd., submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the European Food Safety Authority (EFSA) Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to a combination of beta-sitosterol and beta-sitosterol glucoside and normal function of the immune system. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is a combination of beta-sitosterol and beta-sitosterol glucoside in a ratio 100:1. The Panel considers that a combination of beta-sitosterol and beta-sitosterol glucoside in a ratio 100:1 is sufficiently characterised. The claimed effect proposed by the applicant is ‘normal function of the immune system by restoring balance between TH1-TH2 mediated immunity’. The Panel notes that the claimed effect ‘normal function of the immune system by restoring balance between TH1- and TH2-mediated immunity’ does not refer to a specific function of the body which can be assessed in vivo in humans by generally accepted methods, but rather to a mechanism of action by which the food/constituent could exert the claimed effect. The Panel considers that the claimed effect does not refer to any specific health claim as required by Regulation (EC) No 1924/2006. The Panel concludes that a cause and effect relationship cannot be established between the consumption of a combination of beta-sitosterol and beta-sitosterol glucoside in a ratio 100:1 and a beneficial physiological effect.

2019 - A risk of bias instrument for non-randomized studies of exposures: A users' guide to its application in the context of GRADE [Articolo su rivista]
Morgan, Rebecca L; Thayer, Kristina A; Santesso, Nancy; Holloway, Alison C; Blain, Robyn; Eftim, Sorina E; Goldstone, Alexandra E; Ross, Pam; Ansari, Mohammed; Akl, Elie; Filippini, Tommaso; Hansell, Anna; Meerpohl, Joerg J; Mustafa, Reem A; Verbeek, Jos; Vinceti, Marco; Whaley, Paul; Schünemann, Holger J
abstract

The objective of this paper is to explain how to apply, interpret, and present the results of a new instrument to assess the risk of bias (RoB) in non-randomized studies (NRS) dealing with effects of environmental exposures on health outcomes. This instrument is modeled on the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) instrument. The RoB instrument for NRS of exposures assesses RoB along a standardized comparison to a randomized target experiment, instead of the study-design directed RoB approach. We provide specific guidance for the integral steps of developing a research question and target experiment, distinguishing issues of indirectness from RoB, making individual-study judgments, and performing and interpreting sensitivity analyses for RoB judgments across a body of evidence. Also, we present an approach for integrating the RoB assessments within the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess the certainty of the evidence in the systematic review. Finally, we guide the reader through an overall assessment to support the rating of all domains that determine the certainty of a body of evidence using the GRADE approach.

2019 - Alimentazione, ambiente e malattie cronico-degenerative: nuove metodologie di valutazione del rischio [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Malavolti, Marcella
abstract

Introduzione La valutazione del rischio sanitario associato a fattori di interesse nutrizionale e/o tossicologico (risk assessment) rappresenta un ambito di grande interesse per la popolazione generale, la comunità scientifica e gli operatori di sanità pubblica. Tale processo mira a definire adeguate misure ed indicazioni di sicurezza alimentare, ambientale e occupazionale, e favorire un’appropriata comunicazione del rischio ed efficaci interventi di medicina preventiva. Alla valutazione dei rischi sanitari attribuibili ai diversi fattori di tipo chimico e fisico presenti negli alimenti e negli ambienti di vita e di lavoro (‘fattori ambientali’ in senso lato) contribuiscono da un lato i singoli ricercatori attraverso i loro lavori originali di ricerca o meta-analisi, dall’altro gli enti e le istituzioni specificatamente deputati al processo di risk assessment, quali nello specifico per l’Unione Europea la European Food Safety Authority (EFSA), con sede nel nostro Paese a Parma. La valutazione del rischio attribuibile ai fattori ambientali e nutrizionali prevede diverse fasi metodologiche, tre delle quali sono state soggette a profonde innovazioni nel corso degli ultimi anni e sono di seguito brevemente analizzate: 1) l’identificazione e la valutazione metodologica della letteratura epidemiologica; 2) l’analisi ed interpretazione dei risultati di tale letteratura; 3) la formulazione di valutazioni finali condivise, superando eventuali differenze di opinione tra gli esperti. Identificazione e valutazione della letteratura pertinente al risk assessment Non vi è dubbio come ogni processo di valutazione del rischio sanitario debba basarsi in primo luogo sull’identificazione della letteratura scientifica pertinente. A tal fine, è naturalmente necessario effettuare una ricerca bibliografica rigorosa, completa ed infine illustrata in modo ‘trasparente’. In questa prospettiva, la metodologia adottata dai processi di valutazione del rischio sanitario si avvicina molto a quella adottata per le rassegne sistematiche, caratterizzandosi per una scelta il più possibile estensiva delle ‘parole chiave’ per identificare la letteratura di interesse, e per una strategia di ricerca e selezione degli studi facilmente riproducibile da chiunque. Ciò comporta l’uso di archivi bibliografici quali PubMed e la nota banca dati da esso contenuta Medline, EMBASE, Scopus e Web of Science (anche quest’ultimi contenenti Medline), ed eventualmente Google Scholar (in realtà più motore di ricerca che archivio bibliografico in senso proprio). Viene talora utilizzata per il risk assessment anche la letteratura ‘grigia’, ritrovabile però mediante ricerche complesse e non facilmente riproducibili attraverso archivi quali Conference Proceedings Citation Indexes di WoS, ERIC, PsycINFO, CINHAL, ProQuest Dissertations & Theses Global, International Guideline Library, e l’URL http://www.opengrey.eu/. L’appropriatezza dell’uso di tale letteratura grigia è tuttavia controversa, trattandosi di materiale bibliografico talora di limitata qualità e non sottoposto a valutazione ‘tra pari’. Dopo aver identificato gli articoli di interesse, occorre valutarne la pertinenza mediante l’esame del loro testo integrale, ed infine compiere una valutazione della qualità metodologica (critical appraisal o risk of bias assessment). Quest’ultimo processo è estremamente delicato ed influenza in modo sostanziale l’intero processo di valutazione del rischio. Esso prevede la valutazione delle principali distorsioni metodologiche degli studi, quali errori nella stima espositiva, presenza di confondimento, distorsione di selezione e di classificazione degli esiti sanitari, descrizione incompleta dei risultati e improprietà dell’elaborazione statistica. Valutazioni di questo tipo vengono frequentemente effettuate mediante l’uso di ‘griglie’ precodificate (quali il Risk of Bias della Cochrane Coll

2019 - Aluminum and tin: Food contamination and dietary intake in an Italian population [Articolo su rivista]
Filippini, Tommaso; Tancredi, Stefano; Malagoli, Carlotta; Cilloni, Silvia; Malavolti, Marcella; Violi, Federica; Vescovi, Luciano; Bargellini, Annalisa; Vinceti, Marco
abstract

Aluminum and tin are ubiquitous in the environment. In normal biological systems, however, they are present only in trace amounts and have no recognized biological functions in humans. High exposure to these metals can result in adverse health effects such as neurodegenerative diseases. In non-occupationally exposed subjects, diet is the primary source of exposure. In this study, we aimed at estimating dietary aluminum and tin intake in an Italian adult population. We measured aluminum and tin concentrations through inductively-coupled plasma mass spectrometry in 908 food samples. We also estimated dietary intake of these two metals, by using a validated semi-quantitative food-frequency questionnaire administered to 719 subjects (319 men and 400 women) recruited from the general population of the Emilia Romagna region, Northern Italy. We found the highest aluminum levels in legumes, sweets, and cereals, while the highest tin levels were in sweets, meat and seafood. The estimated median daily dietary intake of aluminum was 4.1 mg/day (Interquartile range – IQR: 3.3–5.2), with a major contribution from beverages (28.6%), cereals (16.9%), and leafy vegetables (15.2%). As for tin, we estimated a median intake of 66.8 μg/day (IQR: 46.7–93.7), with a major contribution from vegetables (mainly tomatoes) (24.9%), fruit (15.5%), aged cheese (12.2%), and processed meat (10.4%). This study provides an updated estimate of the dietary intake of aluminum and tin in a Northern-Italy adult population, based on data from a validated food-frequency questionnaire. The intake determined for this population does not exceed the established thresholds of tolerable intake.

2019 - Amyotrophic lateral sclerosis incidence following exposure to inorganic selenium in drinking water [Abstract in Atti di Convegno]
Vinceti, M; Filippini, T; Malagoli, C; Violi, F; Mandrioli, J; Consonni, D; Rothman, Kj; Wise, La
abstract

Background and aim. Some laboratory and epidemiologic studies have documented an association between high intake of the trace element selenium and risk of amyotrophic lateral sclerosis (ALS), a degenerative disease of the motor neurons. There have been few epidemiologic studies of the association. Methods. From 1986 through 2015, we followed a community cohort in northern Italy that had been inadvertently exposed in the 1974-86 period to drinking water with unusually high levels of selenium, around 8 µg/ml, in its inorganic hexavalent form (selenate). In this cohort, we previously identified a high incidence of ALS during 1986-94. Here we report extended follow-up of this exposed cohort, as well as of an unexposed cohort including over 95,000 municipal residents, for an additional 21 years. We identified incident cases through administrative sources and a specialized registry. Results. During follow-up, 7 and 112 ALS cases were newly diagnosed in the exposed and unexposed cohorts, respectively, yielding incidence rates of 14 and 5 per 100,000 person-years. A Poisson regression analysis adjusting for age, sex, and calendar year produced an overall rate ratio (RR) for ALS of 2.8 (95% confidence interval (CI) 1.3 - 6) in the entire period of follow-up. The association was stronger earlier than later in follow-up (1986-1994 vs. 1994-2015), and among women than men. All exposed cases were of the sporadic, non-familial form for the disease. Conclusion. Overall, results from this ‘natural experiment’ indicate a positive association between chronic exposure to inorganic selenium and ALS incidence, with rates in the exposed cohort declining over time after cessation of exposure. Also taking into account the recognized neurotoxicity of selenium, particularly its selective toxicity on motor neurons observed in animal studies, the present study provides additional support for the hypothesis that selenium in its inorganic form increases ALS risk.

2019 - Amyotrophic lateral sclerosis incidence following exposure to inorganic selenium in drinking water: A long-term follow-up [Articolo su rivista]
Vinceti, M.; Filippini, T.; Malagoli, C.; Violi, F.; Mandrioli, J.; Consonni, D.; Rothman, K. J.; Wise, L. A.
abstract

Some studies have reported an association between overexposure to selenium and risk of amyotrophic lateral sclerosis (ALS), a rare degenerative disease of motor neurons. From 1986 through 2015, we followed a cohort in Northern Italy that had been inadvertently consuming tap water with unusually high concentrations of inorganic hexavalent selenium from 1974 to 1985. We had previously documented an excess incidence of ALS in this cohort during 1986-1994. Here, we report extended follow-up of the cohort for an additional 21 years, encompassing 50,100 person-years of the exposed cohort and 2,233,963 person-years of the unexposed municipal cohort. We identified 7 and 112 incident ALS cases in the exposed and unexposed cohorts, respectively, yielding crude incidence rates of 14 and 5 cases per 100,000 person-years. A Poisson regression analysis, adjusting for age, sex and calendar year, produced an overall incidence rate ratio (IRR) for ALS of 2.8 (95% confidence interval (CI) 1.3, 6), with a substantially stronger IRR in 1986-1994 (8.2, 95% CI 2.7, 24.7) than in 1995-2015 (1.5, 95% CI 0.5, 4.7), and among women (5.1, 95% CI 1.8, 14.3) than men (1.7, 95% CI 0.5, 5.4). Overall, these results indicate an association between high exposure to inorganic selenium, a recognized neurotoxicant, and ALS incidence, with declining rates after cessation of exposure and stronger effects among women.

2019 - Appropriate age range for introduction of complementary feeding into an infant's diet [Articolo su rivista]
Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Fewtrell, M.; Kersting, M.; Przyrembel, H.; Dumas, C.; Titz, A.; Turck, D.
abstract

Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) revised its 2009 Opinion on the appropriate age for introduction of complementary feeding of infants. This age has been evaluated considering the effects on health outcomes, nutritional aspects and infant development, and depends on the individual's characteristics and development. As long as foods have an age-appropriate texture, are nutritionally appropriate and prepared following good hygiene practices, there is no convincing evidence that at any age investigated in the included studies (< 1 to < 6 months), the introduction of complementary foods (CFs) is associated with adverse health effects or benefits (except for infants at risk of iron depletion). For nutritional reasons, the majority of infants need CFs from around 6 months of age. Infants at risk of iron depletion (exclusively breastfed infants born to mothers with low iron status, or with early umbilical cord clamping (< 1 min after birth), or born preterm, or born small-for-gestational age or with high growth velocity) may benefit from earlier introduction of CFs that are a source of iron. The earliest developmental skills relevant for consuming pureed CFs can be observed between 3 and 4 months of age. Skills for consuming finger foods can be observed in some infants at 4 months, but more commonly at 5–7 months. The fact that an infant may be ready from a neurodevelopmental perspective to progress to a more diversified diet before 6 months of age does not imply that there is a need to introduce CFs. There is no reason to postpone the introduction of potentially allergenic foods (egg, cereals, fish and peanut) to a later age than that of other CFs as far as the risk of developing atopic diseases is concerned. Regarding the risk of coeliac disease, gluten can be introduced with other CFs.

2019 - Association between Outdoor Air Pollution and Childhood Leukemia: A Systematic Review and Dose-Response Meta-Analysis [Articolo su rivista]
Filippini, T.; Hatch, E. E.; Rothman, K. J.; Heck, J. E.; Park, A. S.; Crippa, A.; Orsini, N.; Vinceti, M.
abstract

BACKGROUND: A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose-response relation. OBJECTIVE: We investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia. METHODS: We searched all case-control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose-response curve using a restricted cubic spline regression model. RESULTS: We found 29 studies eligible to be included in our review. In the dose-response analysis, we found little association between disease risk and traffic indicators near the child's residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels. DISCUSSION: Overall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381.

2019 - Blood pressure levels and hypertension prevalence in a high selenium environment: results from a cross-sectional study [Articolo su rivista]
Vinceti, M.; Chawla, R.; Filippini, T.; Dutt, C.; Cilloni, S.; Loomba, R.; Bargellini, A.; Orsini, N.; Dhillon, K. S.; Whelton, P.
abstract

Background and aims: Recent human and laboratory studies have suggested the possibility that selenium overexposure may increase blood pressure. We sought to ascertain whether adults living in a seleniferous area exhibit an association between selenium exposure and both blood pressure levels as well as prevalence of hypertension. Methods and results: We measured selenium levels in blood (serum), hair and nail samples obtained from 680 adult volunteers (267 men and 413 women), living in seven Punjabi villages in a seleniferous area and related them to health outcomes, including systolic and diastolic blood pressure and presence of hypertension. In a multivariable restricted cubic spline regression model, adjusted for age, sex and history of hypertension, we found a positive association between systolic blood pressure and both serum (P = 0.004) and hair (P = 0.058) selenium levels, but not with nail selenium content. Little association emerged between the three selenium biomarkers and diastolic blood pressure. Hypertension prevalence was positively associated with the three exposure indicators (P < 0.001). The associations we found were generally stronger in women than in men. Conclusions: Overall, these findings suggest that chronic overexposure to environmental selenium may increase blood pressure, though there were inconsistencies for this association according to the choice of exposure indicator, the study endpoint and the sex.

2019 - Cadmium exposure and breast cancer risk: a systematic review and dose-response meta-analysis of cohort studies [Abstract in Atti di Convegno]
Filippini, T; Kasdagli, Mi; Naska, A; Torres, D; Lopes, C; Carvalho, C; Moreira, P; Malavolti, M; Orsini, N; Vinceti, M
abstract

Background and aim: Cadmium is a heavy metal which has been implicated in breast cancer etiology because of its toxic properties such as endocrine disruption. The general population is exposed to cadmium through dietary intake, cigarette smoking, emissions of motorized traffic and industrial facilities. We carried out a systematic review and dose-response meta-analysis of the cohort studies investigating the association between cadmium exposure and breast cancer risk, for which inconsistent results have been reported in the literature. Methods: Following online database search up to January 2019, we carried out a dose-response meta-analysis to identify the relation between cadmium exposure and disease risk. We used a restricted cubic spline model and the ‘one-stage’ approach, stratifying for exposure assessment method and menopausal status. Results: We identified 12 studies, 9 using breast cancer incidence and 3 mortality as an outcome. In six studies cadmium exposure was assessed through dietary questionnaires, in five through urinary excretion levels, and in one based on environmental air levels. Seven studies included post-menopausal women only. Overall, we observed a positive linear relation between breast cancer risk and dietary cadmium intake (relative risk (RR) 1.04, 95% confidence interval (CI) 0.81-1.33 at 10 µg/day, and RR 1.12, 95% CI 0.80-1.56 at 20 µg/day). On the converse, risk was not associated with urinary excretion. Analysis restricted to post-menopausal women showed a positive association between cadmium exposure assessed through either dietary intake and urinary excretion, for levels higher than 20 µg/day and 1.65 µg/g creatinine, respectively.

2019 - Cadmium exposure and risk of breast cancer: a dose-response meta-analysis of cohort studies [Abstract in Atti di Convegno]
Filippini, T; Torres, D; Lopes, C; Carvalho, C; Moreira, P; Naska, A; Kasdagli, M-I; Malavolti, M; Orsini, Nicola; Vinceti, M
abstract

Background: Cadmium is a toxic heavy metal that has been implicated in breast cancer etiology, albeit with inconsistent results. The general population is exposed to cadmium through dietary intake, cigarette smoking, emissions of motorized traffic and industrial facilities. We carried out a systematic review and dose-response meta-analysis of the cohort studies investigating the association between cadmium exposure and breast cancer risk. Methods: Following a literature search through September 10, 2019, we carried out a systematic review and a dose-response meta-analysis to investigate the relation between cadmium exposure and disease risk. We used a restricted cubic spline model and the ‘one-stage’ approach, stratifying for exposure assessment method and menopausal status. Results: We identified eleven studies on breast cancer risk, six based on cadmium dietary intake, and five on urinary excretion levels. In dose-response analysis, we observed a positive, statistically imprecise linear relation between dietary cadmium intake and disease risk. The risk ratio at 20 µg/day compared with no intake was 1.12 (95% confidence interval 0.80-1.56). Conversely, we detected a very imprecise negative association between urinary cadmium excretion and risk (risk ratio=0.89, 95% confidence interval 0.37-2.14 at 2 µg/g creatinine of cadmium excretion). Analysis restricted to post-menopausal women showed substantially no association, as was true for all meta-analyses carried out by comparing the highest versus the lowest exposure category. Conclusions: Overall, we found scant evidence of positive association between cadmium and breast cancer. Available data were too limited to carry out stratified analyses according to age, smoking and hormone receptor status. Therefore, possible associations between cadmium exposure and breast cancer risk in selected subgroups cannot be entirely ruled out. Keywords: cadmium, breast cancer, dietary intake, urine excretion, dose-response meta-analysis

2019 - Capitolo 3: Determinanti di salute e malattia [Capitolo/Saggio]
Vinceti, M; Balzarini, F; Filippini, T; Malagoli, C; Bossi, E
abstract

2019 - Compliance with Tuberculosis Screening in Irregular Immigrants [Articolo su rivista]
Bonvicini, Francesca; Cilloni, Silvia; Fornaciari, Rossano; Casoni, Carmen; Marchesi, Cristina; Greci, Marina; Monici, Lucia; Nicolini, Fausto; Vinceti, Marco
abstract

Tuberculosis (TB) is a serious public health problem in many regions of the world, especially in the poorest areas. For this reason, screening for active and latent forms must be considered when dealing with high-risk groups such as irregular immigrants in Western countries. We conducted a retrospective cohort study by recruiting subjects aged ≥15 years who underwent a tuberculin skin test at a dedicated National Health Service Centre in a northern Italian province between 1 January 2012 and 31 December 2013. These participants were followed up until 31 December 2016. We aimed at evaluating an experimental protocol for active and latent tuberculosis screening, focusing on patient compliance, feasibility, and capability to detect clinical forms of the disease. We enrolled 368 irregular immigrants, i.e., immigrants not having a valid residence permit and who were therefore not entitled to choose a general practitioner. In total, 90.22% of these completed all the steps for the screening of active TB, while 87.33% also undertook screening for the latent form of the disease. Homelessness, self-reported prostitution, female sex, and employment status adversely affected compliance. Chronic alcohol consumption was associated with increased risk of no beginning or interruption of the procedures. All of the five patients with active TB successfully completed the treatment. Overall, adherence to the screening program was high compared to other studies in immigrants, possibly owing to organizational factors such as the availability of cultural mediators, the network between the different health services, the presence of dedicated nursing staff and a free-of-charge service. In addition, selected vulnerable subgroups should be targeted using tailored screening and follow-up programs.

2019 - Deficient calcium, zinc, and iron intake on absorption of cadmium from diet [Abstract in Atti di Convegno]
Upson, K; Filippini, T; Vinceti, M; Wegienka, G; Wise, LAUREN ANNE; Tokar, Ej; Baird, Dd
abstract

Background/Aim: In vitro and in vivo studies have demonstrated that deficient calcium, zinc, and iron dietary intake upregulates metal ion transporters to increase intestinal absorption. However, these gut transporters are not specific and bind to other metals, including cadmium. Few human studies have investigated whether deficient calcium, zinc, and iron intake increases intestinal absorption of dietary cadmium. Methods: We used enrollment data (2010-2012) from the Study of Environment, Lifestyle & Fibroids, a cohort of 1693 African American women ages 23-35 who reside in the Detroit, Michigan area. Whole blood cadmium concentrations (proxy for cadmium absorption) were measured in 1548 participants. Dietary and supplemental calcium, zinc, and iron intake was estimated using Block 2005 Food Frequency Questionnaire data; deficient intake was defined as <80% of the recommended daily allowance. Daily dietary intake of total grains was used as the proxy for dietary cadmium intake as grains are a major source of cadmium exposure in U.S. diet. We estimated the percent difference in blood cadmium concentrations per median daily intake of total grains (4.55 ounce equivalents) using multivariable linear regression, stratified by deficient and sufficient calcium, zinc, and/or iron intake. We restricted the analyses to never smokers with plausible values for total energy intake (>400 and <5000 kcal/day) (n=1087). We adjusted for age at enrollment, total energy intake, body mass index, height, education, and natural log-transformed blood lead concentrations. Results: The observed percent difference in blood cadmium concentrations in relation to intake of total grains was stronger among those with deficient intake of calcium, zinc, and/or iron (28%, 95% CI; 6, 53%) than among those with sufficient intake of all 3 essential nutrients (5%, 95% CI: -7, 19%). Conclusions: Our preliminary findings suggest that women with deficient calcium, zinc, and/or iron intake have increased absorption of cadmium from the diet.

2019 - Dietary cadmium and risk of breast cancer subtypes defined by hormone receptor status: a prospective cohort study [Articolo su rivista]
Grioni, Sara; Agnoli, Claudia; Krogh, Vittorio; Pala, Valeria; Rinaldi, Sabina; Vinceti, Marco; Contiero, Paolo; Vescovi, Luciano; Malavolti, Marcella; Sieri, Sabina
abstract

Diet is the primary source of cadmium - a proven Group 1 human carcinogen - for non-smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have produced inconsistent results. We examined the association between dietary cadmium and risk of breast cancer defined by estrogen receptor (ER), progesterone receptor (PR) and HER2 status, in 8,924 women recruited to a prospective study between 1987 and 1992. Dietary cadmium intake was estimated using a semi-quantitative food frequency questionnaire at baseline. During a median of 22 years of follow-up, 451 incident cases of breast cancer were identified through the Varese Cancer Registry. Multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for breast cancer and receptor-defined breast cancer subtypes were estimated for quintiles of dietary cadmium intake, adjusting for confounding factors. Mean dietary cadmium intake was 7.8 (standard deviation 1.4) μg/day. Women with highest quintile of cadmium intake had a greater risk of breast cancer (HR 1.54; 95% CI, 1.06 - 2.22; p-trend = 0.028) than those with lowest quintile of intake. Women premenopausal at recruitment had HR = 1.73 (95% CI, 1.10 - 2.71, highest vs. lowest quintile); postmenopausal women had HR = 1.32 (95% CI, 1.05 - 1.66 for each standard deviation increase in cadmium). Cadmium-related risk of breast cancer did not vary with ER, PR or HER2 status (p-heterogeneity not significant). These findings support the hypothesis that dietary cadmium is a risk factor for breast cancer. This article is protected by copyright. All rights reserved.

2019 - Dietary cadmium exposure and risk of melanoma: an Italian population-based case-control study [Abstract in Atti di Convegno]
Filippini, T; Malagoli, C; Malavolti, M; Vinceti, M
abstract

Background and aim. The heavy metal cadmium could be highly toxic to humans, and its environmental exposure has been linked to many adverse health effects, such as atherosclerosis, diabetes, and cancer, including melanoma. Although the underlying mechanisms need yet to be clearly identified, recent findings suggested that cadmium can specifically promote the malignant transformation of melanoma cells through the aberrant DNA methylation inducing dysregulation of specific gene expression. Since in the non-occupationally exposed population, in addition to smoking, food intake is the major source of cadmium exposure, we aimed at assessing the risk of cutaneous melanoma in relation to dietary cadmium intake. Methods. Using a population-based study design, we recruited 380 incident cases of newly-diagnosed melanoma and 719 sex- and age-matched controls in the Emilia-Romagna Region, Northern Italy. We evaluated their dietary habits through a semi-quantitative food frequency questionnaire and we computed the odds ratio (OR) and its 95% confidence interval (CI) for melanoma according to quintile distribution of cadmium intake, using a conditional logistic regression model, matching by sex, age and province of residence, and adjusting also for phototype, non-alcoholic energy intake, body mass index, and Italian Mediterranean Diet Index. Results: Median intake of cadmium was 5.81 µg/day (interquartile range 4.46-7.59) in cases, and 5.63 µg/day (4.46-7.34) in controls. OR of melanoma associated with 1-unit increase in cadmium intake was 1.11 (95% CI 1.00-1.24). Melanoma risk increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99-2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12-2.75), and 1.65 (95% CI 1.05-2.61) in the second to the highest quintile compared to the lowest quintile. Sex-stratified analysis showed substantially comparable results and a generally higher risk in female population, with continuous ORs of 1.10 (95% CI 0.93-1-29), and 1.15 (95% CI 0.99-1.33) in men and women, respectively. Conclusions: Our results suggest a positive association between cadmium exposure through diet and risk of cutaneous melanoma in a Northern Italy population. Such association started to occur at a level of exposure lower than the tolerable intake established by the World Health Organization, and considered to be safe for humans.

2019 - Dietary cadmium intake and fecundability in a North American preconception cohort study [Abstract in Rivista]
Filippini, Tommaso; Willis, Sydney K.; Wesselink, Amelia K.; Hatch, Elizabeth E.; Rothman, Kenneth J.; Vinceti, Marco; Wise, Lauren A.
abstract

Objective To evaluate the association between dietary cadmium intake (D-Cd) and fecundability. Diet is one of the main sources of cadmium, and D-Cd is often used as indicator of cadmium exposure, particularly in non-smoking populations. In a previous preconception cohort study of 501 couples,1 high female cadmium concentrations measured in whole blood were associated with reduced fecundability. Design Prospective cohort study (2013-2018). Materials and Methods Pregnancy Online Study (PRESTO) is a North American prospective preconception cohort of pregnancy planners. At baseline, female participants aged 21-45 years completed a web-based questionnaire on demographic, lifestyle, medical and reproductive factors. Ten days after enrollment, participants completed the National Cancer Institute Dietary History Questionnaire II, a validated food frequency questionnaire (FFQ) of average intake during the previous year. D-Cd (μg/day) was estimated by combining FFQ responses with US Food and Drug Administration data on food cadmium content. Participants were then followed for up to 12 months or until reported pregnancy, whichever came first. The analysis included 4,768 women attempting to conceive for ≤6 cycles at study entry and not using fertility treatment. We used a proportional probabilities regression model to estimate fecundability ratios (FR) and 95% confidence intervals (CI), adjusted for age, body mass index (BMI), smoking history, parity, physical activity, last method of contraception, daily use of multivitamins, race/ethnicity, education, income, geographic region, and the 2010 healthy eating index score. We used the nutrient residual approach to adjust for energy intake. Results Median D-Cd was 8.0 μg/day (interquartile range: 7.0-9.1 μg/day). The top 5 contributors to D-Cd were nuts and seeds; fried potatoes; dark green lettuce; cooked greens; and white potatoes. Compared with an average D-Cd of <6.8 μg/day, FRs for D-Cd quintiles of 6.8-7.6, 7.7-8.4, 8.5-9.5, and ≥9.6 μg/day were 1.03 (CI: 0.92-1.14), 1.07 (CI: 0.96-1.18), 1.07 (CI: 0.96-1.19), and 1.08 (0.97-1.20), respectively. Results were not appreciably different among never smokers with no current passive smoke exposure, for whom cadmium exposure from other sources (e.g., cigarettes) would be lower (respective FRs: 1.02, 1.05, 1.06 and 1.02). Results did not differ materially by age (<30 vs. ≥30 years), BMI (<30 vs. ≥30 kg/m2), total fiber intake (<25 vs. ≥25 g/day), geographic region of residence (West, Midwest, Northeast, South, Canada), or attempt time at study entry (<3 vs. ≥3 cycles). Conclusions Dietary intake of cadmium was not appreciably associated with fecundability, though exposure misclassification and confounding could explain the null results. References 1 Buck Louis GM, Sundaram R, Schisterman EF, Sweeney AM, Lynch CD, Gore-Langton RE, Chen Z, Kim S, Caldwell KL, Barr DB. Heavy metals and couple fecundity, the LIFE Study. Chemosphere. 2012 Jun;87(11):1201-7. https://doi.org/10.1016/j.chemosphere.2012.01.017. Epub 2012 Feb 4. PubMed PMID: 22309709; PubMed Central PMCID: PMC3327819.

2019 - Dietary cadmium intake and risk of cutaneous melanoma: An Italian population-based case-control study [Articolo su rivista]
Filippini, T.; Malagoli, C.; Wise, L. A.; Malavolti, M.; Pellacani, G.; Vinceti, M.
abstract

Introduction: Exposure to the heavy metal cadmium has been associated with many adverse health effects, such as atherosclerosis, diabetes, and cancer, possibly melanoma. In non-occupationally exposed individuals, food intake is a major source of cadmium exposure, after smoking. We aimed to assess the risk of melanoma in relation to dietary cadmium intake. Methods: Using a population-based case-control study design, we recruited 380 incident cases of newly-diagnosed cutaneous melanoma and 719 matched controls in the Emilia-Romagna Region, Northern Italy in the years 2005-2006. We evaluated dietary intake using a semi-quantitative food frequency questionnaire. We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) for melanoma according to quintiles of dietary cadmium intake, adjusting for several potential confounders, and we modeled the association non-parametrically, using restricted cubic splines. Results: Median energy-adjusted intake of cadmium was 6.11 μg/day (interquartile range 5.38–6.91) among cases and 5.97 μg/day (5.15–6.79) among controls. For each 1 μg/day-increase in cadmium intake, the OR for melanoma was 1.11 (95% CI 1.00–1.24). Melanoma risk generally increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99–2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12–2.75), and 1.65 (95% CI 1.05–2.61) for the second through fifth quintiles, compared with the lowest quintile. Sex-stratified analysis showed ORs per 1 μg/day-increase in cadmium intake of 1.10 (95% CI 0.93-1-29) among men and 1.15 (95% CI 0.99–1.33) among women. Using spline regression analysis, we observed a generally linear increase in melanoma risk up to 6 μg/day of cadmium intake, after which the risk appeared to plateau. Conclusions: We observed a positive non-linear association between dietary cadmium intake and risk of cutaneous melanoma in a Northern Italy population. However, further studies are needed to elucidate this association, due to concerns about exposure misclassification, unmeasured confounding, and the limited and conflicting evidence from epidemiological findings.

2019 - Dietary cadmium intake and risk of cutaneous melanoma: a population-based case-control study in Northern Italy [Abstract in Rivista]
Filippini, T; Malagoli, C; Malavolti, M; Vinceti, M
abstract

BACKGROUND AND AIM. Cadmium is a toxic heavy metal for humans, and its environmental exposure has been linked to many adverse health effects, including cancer, atherosclerosis and diabetes. In particular, recent findings suggest that cadmium may increase risk of cutaneous melanoma, possibly through the promotion of the malignant transformation of melanoma cells through aberrant DNA methylation and by inducing gene expression dysregulation. Since in non-occupational exposed and non-smoking subjects dietary exposure is the major source of cadmium exposure, we aimed to assess melanoma risk in relation to dietary cadmium intake. METHODS. We recruited 380 newly-diagnosed incident cases of cutaneous melanoma and 719 sex- and age-matched population controls in four North Italian provinces (Parma, Reggio Emilia, Modena, and Bologna) of Emilia-Romagna Region. We estimated their dietary habits using a semi-quantitative food frequency questionnaire and we evaluated melanoma risk by computing the odds ratio (OR) and its 95% confidence interval (CI) according to quintile distribution of cadmium intake. We used a conditional logistic regression model to compute ORs, matching by sex, age and province of residence, and adjusting also for phototype, non-alcoholic energy intake, body mass index, and Italian Mediterranean Diet Index. Also a spline regression model was used in order to evaluated possible dose-response relation. RESULTS: Median cadmium intake was 5.81 µg/day (interquartile range 4.46-7.59) in cases, and 5.63 µg/day (4.46-7.34) in controls. OR of melanoma associated with 1-unit increase in cadmium intake was 1.11 (95% CI 1.00-1.24). Melanoma risk increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99-2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12-2.75), and 1.65 (95% CI 1.05-2.61) from second to highest quintile compared to lowest quintile. Sex-stratified analysis showed substantially comparable results and a generally higher risk in women, with continuous ORs of 1.10 (95% CI 0.93-1-29), and 1.15 (95% CI 0.99-1.33) in men and women, respectively. Spline regression analysis showed a non-linear risk increase, with possible plateau at 5-6 µg/day of cadmium intake. Slightly higher risk estimates in women and older subjects were detected. CONCLUSIONS: Our results seem to point out a positive association between dietary cadmium exposure and melanoma risk in the study population. Such association started to occur at a level of exposure lower than the tolerable intake established for food safety by international authorities.

2019 - Dietary exposure estimates to fifteen trace elements in an adult population of Emilia Romagna region, Northern Italy [Abstract in Atti di Convegno]
Filippini, T; Tancredi, S; Malagoli, C; Malavolti, M; Vescovi, L; Bargellini, A; Vinceti, M
abstract

The health effects and the exposure levels of trace elements in humans are important public health topics. Assessing their dietary intake is fundamental to evaluate the long-term risks for public health and for food safety assessment. Since a priority of food safety regulatory agencies is to ensure the protection of consumers and to assess the health risks for the general population, to estimate the actual dietary intake of trace elements for comparison with the upper and lower tolerable levels is very important. In this study, we aimed to evaluate the dietary intake of several trace elements in an Italian community, namely of antimony, barium, beryllium, boron, cobalt, lithium, molybdenum, nickel, silver, strontium, tellurium, thallium, titanium, uranium, and vanadium. To do that, in 2016-2017 we collected a total of 908 food samples available in Italian markets and groceries from two Northern Italy provinces (Modena and Reggio Emilia), and we measured their trace element content through inductively-coupled plasma mass spectrometry. We also administered a validated semi-quantitative food frequency questionnaire to 708 residents (300 men and 48 women) in the Emilia-Romagna Region, to assess their dietary habits and eventually to estimate their dietary intake of the aforementioned trace elements. Overall, study results showed that in our population the dietary exposure levels to selected trace elements could be considered similar to that observed in other European and non-European populations. Though we cannot rule out the possibility that the dietary exposure estimates in the present study may not be representative of the population as a whole, our results provide a good and updated assessment of trace elements far frequently evaluated in a sample of Italian adult consumers from the Emilia Romagna region. Our findings finally suggest that our population should not be at risk of adverse health effects in relation to excess or deficiency of the investigated trace elements since the estimated dietary intake generally point out exposure levels within the safe range as far as indicated by recommendations of international agencies.

2019 - Dietary intake of acrylamide and risk of breast, endometrial and ovarian cancer: a systematic review and dose-response meta-analysis [Poster]
Filippini, T; Adani, G; Wise, La; Vinceti, M
abstract

Background: Acrylamide is probable human carcinogen that occurs naturally in starchy foods during cooking processes at high temperatures. Aside from occupational exposures and smoking, main source of human exposure is diet, particularly consumption of potatoes, grain products, and coffee. High acrylamide intake has been associated with altered sex-steroid hormone concentrations and increased risk of hormone-dependent gynecologic neoplasms. Objective: We performed a systematic review of the papers investigating the association between acrylamide intake and risk of breast, endometrial and ovarian cancer. We also examined a possible dose-response relation by carrying out a dose-response meta-analysis of these studies. Methods: We searched in PubMed up to September 10, 2019 the non-experimental human studies investigating risk of breast, endometrial, or ovarian cancer in relation to dietary intake of acrylamide. We also carried out a dose-response meta-analysis using a restricted cubic spline model. Results: We retrieved 18 studies: 11 cohort, 5 case-cohort, and 2 case-control studies. Since some studies assessed more than one cancer type, we found a total of ten studies on risk of breast cancer, seven on endometrial cancer, and seven on ovarian cancer. In the dose-response meta-analysis, acrylamide intake was associated with slightly increased risks of endometrial and ovarian cancers, with a stronger and almost linear increased risk among never smokers. Conversely, for breast cancer we found no evidence to support an increased risk following acrylamide exposure, except for a positive association among premenopausal women exposed to at least 20 µg/day of acrylamide. Conclusions: Based on the relatively small number of studies published to date, acrylamide intake was associated with increased risk of endometrial and ovarian cancer in a dose-response fashion, with a slightly stronger association observed among never smokers. Acrylamide intake was associated with an increased risk of breast cancer only among premenopausal women and at intakes greater than 20 µg/day.

2019 - Dietary intake of acrylamide and risk of breast, endometrial and ovarian cancer: a systematic review and dose-response meta-analysis. [Abstract in Atti di Convegno]
Filippini, T; Adani, Giorgia; Wise, LAUREN ANNE; Vinceti, M
abstract

Background: Acrylamide is a probable human carcinogen that occurs naturally in starchy foods during cooking processes at high temperatures. Aside from occupational exposures and smoking, the main source of human exposure is diet, particularly consumption of potatoes, grain products, and coffee. High acrylamide intake has been associated with altered sex-steroid hormone concentrations and increased risk of hormone-dependent gynecologic neoplasms. Objective: We performed a systematic review of the papers investigating the association between acrylamide intake and risk of breast, endometrial and ovarian cancer in humans. We also examined a possible dose-response relation by carrying out a dose-response meta-analysis of these studies. Methods: We searched in PubMed up to September 10, 2019 the non-experimental human studies investigating risk of breast, endometrial, or ovarian cancer in relation to dietary intake of acrylamide. We also carried out a dose-response meta-analysis using a restricted cubic spline model. Results: We retrieved 18 studies: 11 cohort, 5 case-cohort, and 2 case-control studies. Since some studies assessed more than one cancer type, we found a total of ten studies on risk of breast cancer, seven on endometrial cancer, and seven on ovarian cancer. In the dose-response meta-analysis, acrylamide intake was associated with slightly increased risks of endometrial and ovarian cancers, with a stronger and almost linear increased risk among never smokers. Conversely, for breast cancer we found no evidence to support an increased risk following acrylamide exposure, except for a positive association among premenopausal women exposed to at least 20 µg/day of acrylamide. Conclusions: Based on the relatively small number of studies published to date, acrylamide intake was associated with increased risk of endometrial and ovarian cancer in a dose-response fashion, with a slightly stronger association observed among never smokers. Acrylamide intake was associated with an increased risk of breast cancer only among premenopausal women and at intakes greater than 20 µg/day. Keywords: acrylamide; dietary intake; breast cancer; endometrial cancer; ovarian cancer.

2019 - Dietary reference values for chloride [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aggett, P.; Fairweather-Tait, S.; Martin, A.; Przyrembel, H.; de Sesmaisons-Lecarre, A.; Naska, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) has derived dietary reference values (DRVs) for chloride. There are no appropriate biomarkers of chloride status, no balance studies and no adequate evidence on the relationship between chloride intake and health outcomes that can be used to set DRVs for chloride. There is a close relationship between sodium and chloride balances in the body. Sodium chloride is the main source of both electrolytes in European diets and similar urinary excretion levels of sodium and chloride (on a molar basis) are typically observed in Western populations. Hence, the Panel considered that reference values for chloride can be set at values equimolar to the reference values for sodium for all population groups, and are as follows: 1.7 g/day for children aged 1–3 years, 2.0 g/day for children aged 4–6 years, 2.6 g/day for children aged 7–10 years, 3.1 g/day for children aged 11–17 years and 3.1 g/day for adults including pregnant and lactating women. Consistent with the reference values for sodium, these levels of chloride intake are considered to be safe and adequate for the general EU population, under the consideration that the main dietary source of chloride intake is sodium chloride. For infants aged 7–11 months, an adequate intake of 0.3 g/day is set.

2019 - Dietary reference values for sodium [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Aggett, P.; Fairweather-Tait, S.; Martin, A.; Przyrembel, H.; Ciccolallo, L.; de Sesmaisons-Lecarre, A.; Valtuena Martinez, S.; Martino, L.; Naska, A.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) derived dietary reference values (DRVs) for sodium. Evidence from balance studies on sodium and on the relationship between sodium intake and health outcomes, in particular cardiovascular disease (CVD)-related endpoints and bone health, was reviewed. The data were not sufficient to enable an average requirement (AR) or population reference intake (PRI) to be derived. However, by integrating the available evidence and associated uncertainties, the Panel considers that a sodium intake of 2.0 g/day represents a level of sodium for which there is sufficient confidence in a reduced risk of CVD in the general adult population. In addition, a sodium intake of 2.0 g/day is likely to allow most of the general adult population to maintain sodium balance. Therefore, the Panel considers that 2.0 g sodium/day is a safe and adequate intake for the general EU population of adults. The same value applies to pregnant and lactating women. Sodium intakes that are considered safe and adequate for children are extrapolated from the value for adults, adjusting for their respective energy requirement and including a growth factor, and are as follows: 1.1 g/day for children aged 1–3 years, 1.3 g/day for children aged 4–6 years, 1.7 g/day for children aged 7–10 years and 2.0 g/day for children aged 11–17 years, respectively. For infants aged 7–11 months, an Adequate Intake (AI) of 0.2 g/day is proposed based on upwards extrapolation of the estimated sodium intake in exclusively breast-fed infants aged 0–6 months.

2019 - Does outdoor air pollution cause childhood leukemia? A systematic review and dose-response meta-analysis [Poster]
Filippini, Tommaso; Orsini, Nicola; Vinceti, Marco
abstract

A causal link between outdoor air pollution from motorized traffic and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks and no analyses have examined the dose-response relation. In this review, we investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia. We performed online database search up to October 10, 2019, including also snowballing methods to retrieve all possible case-control and cohort eligible studies. We carried out a meta-analysis, whenever possible with a dose-response approach using a restricted cubic spline regression model, our intent being to investigate the extent to which air pollution, especially in regard to traffic-related contaminants, affects the risk of childhood leukemia. We found 30 studies eligible to be included in our review. Exposure assessment either to motorized traffic and related contaminants was based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or on measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. In the dose-response analysis, we found an indication of increased but imprecise association between disease risk and traffic indicators, measured as number of vehicles in the closest roads, road density, and distance from major roads near the child’s residence, only at the highest levels of exposure. Similarly, exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels. Conversely, we found that benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 years of age, and when exposure assessment at the time of diagnosis was used. Overall, the summarized epidemiologic literature appears to support an association between benzene emissions from traffic exhausts and childhood leukemia risk, especially the myeloid subtype and in the youngest children, with no indication of any threshold.

2019 - Effect modification of smoking status and menopausal status on the association between die- tary intake of acrylamide and risk of breast cancer [Abstract in Rivista]
Adani, Giorgia; Filippini, Tommaso; Vinceti, Marco
abstract

Introduction Acrylamide is a probable human carcinogen 1 that occurs natu- rally in starchy foods during cooking processes at high tempera- tures 2. Aside from occupational exposures and smoking 3, main source of human exposure is diet, particularly consumption of potatoes, grain products, and coffee 4 5. High acrylamide intake has been associated with altered sex-steroid hormone concen- trations and increased risk of hormone-dependent cancers, such breast neoplasm with inconsistent findings 6-9. Since this cancer type represent a major cause of death among both premenopau- sal and postmenopausal women 10, investigating its environmen- tal and life-style risk factors, including for instance acrylamide intake, is of key relevance under a public health perspective. Materials and methods We performed a systematic review of the association between estimated dietary intake of acrylamide and risk of female breast cancer. Using PubMed, we performed a systematic search for non-experimental studies published through October 20, 2019 and we first performed a meta-analysis of the overall measure of association. Subsequently, we carried out a dose-response meta- analysis of these associations using restricted cubic spline models which allow to estimate the summary relative risk (sRR) across a large exposure range of acrylamide intake alongside with their approximate pointwise 95% confidence interval (CI) 11 12. Results We identified 10 papers covering 8 different study populations: 9 cohorts and 1 case-control studies, with a total of 18100 cases of breast cancer. Acrylamide dietary intake ranged from 3.6 μg/ day to 44 μg/day, with both mean and median values of 21 μg/ day (range 6.3 to 29.8 μg/day). In the meta-analysis summarizing the RR in the highest category of exposure versus the lowest, we found no evidence of cancer risk at any levels of acrylamide ex- posure. After restricting the analysis to never smokers, we found similar results, if not a reverse correlation. In analyses stratified by menopausal status, we found no appreciable association be- tween exposure and risk of breast cancer among premenopau- sal women, and an inverse association in postmenopausal par- ticipants. Results among never-smoking premenopausal women was available only for one study, which reported a positive as- sociation between acrylamide intake and breast cancer risk. Con- versely, among postmenopausal women, we found no associa- tion for breast cancer in never-smokers. In the dose-response me- ta-analysis, we found evidence of a null or even inverse relation between exposure to dietary acrylamide and breast cancer risk, particularly in never smokers and in post-menopausal women. Interestingly, in subgroup analysis limited to pre-menopausal women, breast cancer risk linearly increased starting from 20 μg/ day of acrylamide intake. Conclusions In conclusion, there was limited evidence for an association between acrylamide intake and breast cancer risk, with the ex- ception of increased risks at the highest levels of acrylamide exposure among premenopausal women, which warrants further investigation.

2019 - Environment and health: Risk perception and its determinants among Italian university students [Articolo su rivista]
Carducci, A.; Fiore, M.; Azara, A.; Bonaccorsi, G.; Bortoletto, M.; Caggiano, G.; Calamusa, A.; De Donno, A.; De Giglio, O.; Dettori, M.; Di Giovanni, P.; Di Pietro, A.; Facciola, A.; Federigi, I.; Grappasonni, I.; Izzotti, A.; Libralato, G.; Lorini, C.; Montagna, M. T.; Nicolosi, L. K.; Paladino, G.; Palomba, G.; Petrelli, F.; Schiliro, T.; Scuri, S.; Serio, F.; Tesauro, M.; Verani, M.; Vinceti, M.; Violi, F.; Ferrante, M.
abstract

Among the determinants of environmental health risk perception, health literacy and social media messages have been generally neglected. This study details the environmental health risk perception and its determinants in Italian university students, including a measure of functional health literacy and an analysis of newspapers and social media. A cross sectional survey was carried out among students from 15 Italian universities and different disciplines (grouped into Scientific-Health and Humanistic-Legal-Social sectors) using a self-administered anonymous questionnaire, divided into six sections: socio-demographic characteristics, information on health and environment, environmental health risk perception, trust, attitudes and behaviors and functional health literacy. Local newspapers and tweets in the same areas and period were analyzed in relation to quantity and topics. The study population included 4778 students (65.1% female) aged 21 ± 4.3 years, and functional health literacy was low (below the cutoff value) for 44.4% of students. A new outcome of the survey is that the detected association between high functional health literacy a higher global health risk perception and trust in institutions both as sources of information and as actors for protection against environmental risks. The internet and social networks were the most frequently consulted sources of information (77.7%), which was predictive of a higher risk perception. The possible relation between environmental health risk perception and tweet communication was highlighted by a comparison between the risk perception in the city with the highest number of tweets (Modena) and another one similar for socio-demographic characteristics (Pisa). In conclusion, the results of our study may be of help to strengthen information and education programs: functional health literacy should be taken into account in school programs, to produce a basic knowledge for a better understanding of health and environment. Moreover, mass and social media should be included in planning communication intervention and in verifying their results.

2019 - Epidemiology and social impact of early onset dementia in the province of Modena, Northern Italy [Abstract in Atti di Convegno]
Fiondella, Luigi; Galli, C.; Tondelli, M.; Vinceti, G.; Filippini, T.; Garuti, Caterina; Vinceti, M.; Chiari, A.; Zamboni, G.; Molinari, MARIA ANGELA; COSTA (Modena), M.
abstract

Aims of the study. Early onset dementia (EOD), defined as onset of dementia <65 years, has a much higher social impact compared to the more common late onset dementia. EOD epidemiologic data in Italy are extremely scarce, and international estimates of prevalence are considerably variable, ranging between 15.1 and 153/100.000 in the age 45-65. We present data from an ongoing study aimed at establishing EOD epidemiology in a Northern Italy community (Modena province, around 700.000 inhabitants). Materials. We retrospectively recruited all patients residing in Modena province referred to the Modena Baggiovara Hospital Neurologic Clinic CDCD (Centro disturbi cognitivi e demenze), by family practitioners and geriatricians of the province. Eligible patients were those affected by EOD from 2012 to January 2019. EOD was diagnosed in patients <65 years presenting with cognitive/behavioral symptoms, following a comprehensive neurological examination by a cognitive neurologist, as well as brain MRI, FDG PET scanning and CSF analyses when appropriate. Methods. We collected clinical data such as age at onset, disease severity at time of diagnosis, time delay from onset to diagnosis, and epidemiologic data including residence and occupational status. Results. We identified 223 patients with an EOD diagnosis from 2012 to January 2019. Of these, 103 are males (46,2%). 97 patients have AD (21 lvPPA, 13 PCA, 2 frontal variant), 47 have FTD (33 bvFTD, 14 svPPA), 6 have leucoencephalopathy. Mean onset age was 58,6 years (SD 5,1). Median time from symptoms onset to diagnosis was 3.1 years (SD 29,83). Mean MMSE score at diagnosis was 22,63/30 (SD 5,2). 24 patients were working at time of diagnosis (10,76%) and had to quit working due to the cognitive impairment. Two patients (0,89%) had young children (<18) at time of diagnosis. Discussion. We provide the first epidemiological data on EOD in Italy. These are consistent with the estimates calculated by transposing European data to the population of Modena province (estimated prevalence=200 patients, detected prevalence=223 patients)1. Our data show a higher percentage of atypical AD phenotypes and FTD in the EOD group compared to late onset disease2. Also, CAA and leucoencephalopaties were over-represented compared to LOD. From a social perspective, EOD has significant impacts on patients and their families: patients are generally forced to leave work, and their children are expected to need psychological support, currently not routinely available. Conclusions. Our population study provides the first data regarding EOD epidemiology and social impact in Italy.

2019 - Exposure to inorganic selenium in drinking water and incidence of amyotrophic lateral sclerosis: a long-term follow-up of a natural experiment [Poster]
Vinceti, Marco; Filippini, Tommaso; Malagoli, Carlotta; Violi, Federica; Mandrioli, Jessica; Consonni, Dario; Rothman, Kenneth; Wise, LAUREN ANNE
abstract

Background: Some studies have reported an association between overexposure to selenium and risk of amyotrophic lateral sclerosis (ALS), a rare degenerative disease of motor neurons. From 1986 through 2015, we followed a cohort in Northern Italy that had been inadvertently consuming tap water with unusually high concentrations of inorganic hexavalent selenium from 1974 to 1985. Methods: We had previously documented an excess incidence of ALS in this cohort during 1986-1994. Here, we report extended follow-up of the cohort for an additional 21 years, encompassing 50,100 person-years of the exposed cohort and 2,233,963 person-years of the unexposed municipal cohort. We assessed ALS risk using a Poisson regression analysis, adjusting for age, sex and calendar year. Results: We identified 7 and 112 incident ALS cases in the exposed and unexposed cohorts, respectively, yielding crude incidence rates of 14 and 5 cases per 100,000 person-years. The Poisson regression analysis produced an overall incidence rate ratio (IRR) for ALS of 2.8 (95% confidence interval (CI) 1.3, 6), with a substantially stronger IRR in 1986-1994 (8.2, 95% CI 2.7, 24.7) than in 1995-2015 (1.5, 95% CI 0.5, 4.7), and among women (5.1, 95% CI 1.8, 14.3) than men (1.7, 95% CI 0.5, 5.4). Conclusions: Overall, these results indicate an association between high exposure to inorganic selenium, a recognized neurotoxicant, and ALS incidence, with declining rates after cessation of exposure and stronger effects among women.

2019 - Food and beverage consumption and melanoma risk: a population-based case-control study in Northern Italy [Articolo su rivista]
Malagoli, C; Malavolti, M; Agnoli, C; Farnetani, F; Longo, C; Filippini, T; Pellacani, G; Vinceti, M
abstract

It has been suggested that diet may influence the risk of melanoma, but few studies are available on this topic. We assessed the relation between food consumption and the risk of cutaneous melanoma in a Northern Italy population. We carried out a population-based case-control study involving 380 cases of melanoma and 719 age- and sex-matched controls. Dietary habits were established through a self-administered semi-quantitative food frequency questionnaire. We computed the odds ratios (ORs) of melanoma and the corresponding 95% confidence intervals (CIs) according to tertiles of daily intake of each food item, using multiple logistic regression models adjusted for major confounding factors. We observed an indication of a positive association between melanoma risk and consumption of cereals and cereal products (OR = 1.32; 95% CI 0.89–1.96, higher vs. lowest tertile), sweets (OR = 1.22; 95% CI 0.84–1.76), chocolate, candy bars. etc., (OR = 1.51; 95% CI 1.09–2.09) and cabbages (OR = 1.51; 95% CI 1.09–2.09). Conversely, an inverse association with disease risk was found for the intake of legumes (OR = 0.77; 95% CI 0.52–1.13), olive oil (OR = 0.77; 95% CI 0.51–1.16), eggs (OR = 0.58; 95% CI 0.41–0.82), and onion and garlic (OR = 0.80; 95% CI 0.52–1.14). No relationship was observed with beverage consumption. Our results suggest potentially adverse effects on melanoma risk of foods characterized by high contents of refined flours and sugars, while suggesting a protective role for eggs and two key components of the Mediterranean diet, legumes and olive oil. These associations warrant further investigation and, if confirmed, they might have important public health implications for the reduction of melanoma incidence through dietary modification.

2019 - GlycoLite™ and helps to reduce body weight: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from analyze & realize GmbH submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to GlycoLite™. The Panel considers that the food, an aqueous extract from white kidney bean (Phaseolus vulgaris L.) standardised by its in vitro α-amylase inhibitory activity (GlycoLite™) which is the subject of the health claim, is sufficiently characterised. The claimed effect proposed by the applicant is ‘helps to reduce body weight’. The proposed target population is ‘overweight people from the age of 18 years who want to lose or manage their weight’. The Panel considers that a reduction in body weight is a beneficial physiological effect for overweight individuals. Two human intervention studies, carried out in the same centres and by the same research group, showed an effect of 3 g of GlycoLite™ on body weight when consumed daily for 12 weeks in the context of an energy restricted diet. The results have not been replicated in a different setting. One study of short duration and methodological limitations showed an effect of GlycoLite™ on body weight when eating ad libitum. No evidence for a plausible mechanism by which GlycoLite™ could exert a reduction in body weight in vivo in humans has been provided. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of an aqueous extract from white kidney bean (P. vulgaris L.) standardised by its in vitro α-amylase inhibitory activity (GlycoLite™) and a reduction of body weight either under energy restriction or when eating ad libitum.

2019 - Green tea consumption and risk of cancer: a systematic review and meta-analysis of observational studies [Abstract in Rivista]
Filippini, Tommaso; Malavolti, Marcella; Vinceti, Marco
abstract

Introduction Tea is one of the most highly consumed drink in the world after water. Between 2007 and 2016, world tea production grew by an average annual rate of 4.4%. Global tea consumption was 5.53 million tonnes in 2016 with an annual growth rate of 4.5 percent between 2007 and 2016 1. Brewed tea is obtained from the infu- sion of leaves and buds of Camellia sinensis. The most common- ly consumed type of tea varies cross-culturally, but green and black tea are the main ones. It has been described that Camellia sinensis contains polyphenols, particularly green tea that contain a high amount of catechins, powerful antioxidants. Laboratory studies have suggested that these compounds may inhibit cancer cell proliferation and 2 and some experimental and nonexperi- mental epidemiologic studies have suggested that green tea may have cancer-preventative effects 3 4. We aimed to assess associa- tions between green tea consumption and the risk of cancer incidence and mortality. Materials and methods We searched eligible studies up to January 2019 online databases as well as from reference lists of previous reviews and included studies. We included all observational epidemiological stud- ies (both cohort and case-control studies), that investigated the association of green tea consumption with cancer risk. Two or more authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We also per- formed a meta-analysis using a random effects model comparing the highest category of green tea intake with the lowest, and us- ing the most adjusted multivariable model. We summarized the results according to cancer type diagnosis Results In this review update, we included 131 studies, including 46 co- hort and 85 case-control studies with over 1,100,000 participants., we found a lower overall cancer incidence. Regarding overall cancer mortality we found no difference in risk For most of the site-specific cancers we observed a decreased sRR. However, af- ter stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: esophageal, prostate and urinary tract cancer showed an increased sRR in co- hort studies and a decreased/null sRR in case-control studies. Conclusions Overall, findings from observational epidemiological studies yielded inconsistent and even contrasting results for the effect of green tea consumption on cancer risk. In addition, since observa- tional studies generally suffered from the inherent limitation of this study design, potential unmeasured confounding and expo- sure misclassification, well conducted and adequately powered experimental studies are clearly needed to elucidate the possible beneficial effects of green tea consumption on cancer risk in hu- mans.

2019 - High‐frequency motor rehabilitation in amyotrophic lateral sclerosis: a randomized clinical trial [Articolo su rivista]
Zucchi, Elisabetta; Vinceti, Marco; Malagoli, Carlotta; Fini, Nicola; Gessani, Annalisa; Fasano, Antonio; Rizzi, Romana; Sette, Elisabetta; Cavazza, Stefano; Fiocchi, Alena; Buja, Sergio; Faccioli, Tiziana; Storani, Simone; Mandrioli, Jessica
abstract

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2019 - Influence of selenium on the emergence of neuro tubule defects in a neuron-like cell line and its implications for amyotrophic lateral sclerosis [Articolo su rivista]
Maraldi, T.; Beretti, F.; Anselmi, L.; Franchin, C.; Arrigoni, G.; Braglia, L.; Mandrioli, J.; Vinceti, M.; Marmiroli, S.
abstract

Impairment of the axonal transport system mediated by intracellular microtubules (MTs) is known to be a major drawback in neurodegenerative processes. Due to a growing interest on the neurotoxic effects of selenium in environmental health, our study aimed to assess the relationship between selenium and MTs perturbation, that may favour disease onset over a genetic predisposition to amyotrophic lateral sclerosis. We treated a neuron-like cell line with sodium selenite, sodium selenate and seleno-methionine and observed that the whole cytoskeleton was affected. We then investigated the protein interactome of cells overexpressing αTubulin-4A (TUBA4A) and found that selenium increases the interaction of TUBA4A with DNA- and RNA-binding proteins. TUBA4A ubiquitination and glutathionylation were also observed, possibly due to a selenium-dependent increase of ROS, leading to perturbation and degradation of MTs. Remarkably, the TUBA4A mutants R320C and A383 T, previously described in ALS patients, showed the same post-translational modifications to a similar extent. In conclusion this study gives insights into a specific mechanism characterizing selenium neurotoxicity.

2019 - Intake of Mediterranean Foods [Capitolo/Saggio]
Siotos, C.; Vinceti, M.; Naska, A.
abstract

The traditional Mediterranean diet is characterized by: (a) high consumption of cereals, vegetables, fruit, nuts, legumes, fish, and seafood; (b) the use of olive oil as the main, if not the only, added lipid; (c) moderate consumption of milk and dairy products; (d) moderate intake of alcohol, in the form of wine and preferably during meals; and (e) low consumption of meat and meat products. The prevalent consumption of olive oil and the low consumption of animal products are reflected in the high ratio of monounsaturated to saturated fat intake, typical of the dietary pattern in the region. There is increasing evidence from observational and experimental epidemiological studies, further enriched by the conclusions of their systematic reviews and meta-analyses, that adherence to the Mediterranean dietary pattern promotes health and reduces the risk of premature death from chronic degenerative diseases. Mediterranean countries and especially the European ones have experienced a “westernization” process of their food habits, and have increased the per capita supply of non-Mediterranean foods (animal fats, vegetable oils other than olive oil, sugar, and meat) and decreased the supply of legumes and alcoholic beverages, including wine. The evidence that Mediterraneans are gradually departing from their traditional eating habits does not only refer to the adult population in the region, but it has also been reproduced in large-scale nutritional surveys among children, adolescents, and young adults – the trend-setters for future generations. Next to the effect on people’s health, the gradual abandoning of the traditional Mediterranean diet cannot support sustainable development in the way the Mediterranean diet does. Being adjusted to the cultural, climatic, and other environmental characteristics of the region, the Mediterranean diet is protective and helpful to biodiversity, accessible and economically affordable, and contributes to food and nutrition security.

2019 - Iron consumption is not consistently associated with fecundability among north American and danish pregnancy planners [Articolo su rivista]
Hahn, K. A.; Wesselink, A. K.; Wise, L. A.; Mikkelsen, E. M.; Cueto, H. T.; Tucker, K. L.; Vinceti, M.; Rothman, K. J.; Sorensen, H. T.; Hatch, E. E.
abstract

Background: Infertility is an important public health problem with few known modifiable risk factors. Dietary factors including folic acid have been associated with improved fertility, but the association between iron and fertility is understudied. One study among US nurses found a 40% lower risk of ovulatory infertility with higher intake of nonheme iron and iron supplements. Objectives: The aim of this study was to determine the extent to which iron intake from diet and supplements reported on structured questionnaires is associated with fecundability. Methods: We conducted parallel analyses that used data from 2 prospective cohort studies of pregnancy planners from Denmark (Snart Foraeldre; n = 1693) and North America (PRESTO; n = 2969) during 2013-2018. Follow-up comprised menstrual cycles at risk until pregnancy or censoring for fertility treatment, stopped trying to conceive, withdrawal, loss to follow-up, or 12 cycles of attempt. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusting for confounders. Results: We found little association between dietary heme iron intake and fecundability in either cohort. The FR for nonheme iron intake (≥11 mg/d compared with <9 mg/day) was 1.11 for Snart Foraeldre participants (95% CI: 0.92, 1.34) and 1.01 for PRESTO participants (95% CI: 0.89, 1.14). The FR for iron-containing supplements was 1.01 in Snart Foraeldre (95% CI: 0.90, 1.13) and 1.19 in PRESTO (95% CI: 1.03, 1.38). In PRESTO, but not Snart Foraeldre, stronger positive associations were found for nonheme iron intake and iron supplement use among women with heavy menses or short menstrual cycles. Conclusions: Overall, dietary intake of iron was not consistently associated with fecundability, although there was some evidence for a positive association among women with risk factors for iron deficiency. We also found a small positive association between supplemental iron intake and fecundability among North American, but not Danish, pregnancy planners.

2019 - Maternal pregestational diabetes and risk of acute lymphoblastic leukemia in the offspring: A population-based study in Northern Italy [Articolo su rivista]
Borsari, L.; Malagoli, C.; Della Torre, F.; Cellini, M.; Rodolfi, R.; Pession, A.; Vinceti, M.
abstract

Introduction: This population-based study aims to evaluate the association between maternal pregestational diabetes and risk of acute lymphoblastic leukemia (ALL) in the offspring. Methods: All 241,958 children born in three Northern Italy provinces 1998–2010 were followed from birth until first cancer diagnosis (National Childhood Cancer Register), age 15 years, or 31 December 2017. We computed hazard ratio (HR) and 95% CI of ALL in relation to the presence of maternal diabetes through Cox proportional regression models. Results: We observed 145 cases of ALL, with a higher incidence in children born to women with pregestational diabetes compared to the others (12.4 vs 4.6). Adjusted hazard ratio of ALL was 2.6 (CI, 0.6–10.5) for maternal diabetes. Discussion: We estimated higher risks of ALL in the offspring of women with pregestational diabetes. These results are consistent with previous findings and compatible with a role of prenatal glycaemic environment in childhood cancer aetiology.

2019 - Nutrimune and immune defence against pathogens in the gastrointestinal and upper respiratory tracts: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Knutsen, H. K.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Thies, F.; Tsabouri, S.; Vinceti, M.; Bresson, J. -L.; Siani, A.
abstract

Following an application from H.J. Heinz Supply Chain Europe B.V. submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Nutrimune and immune defence against pathogens in the gastrointestinal (GI) tract and upper respiratory tract (URT). The food Nutrimune (a pasteurised cow's skim milk fermented with Lactobacillus paracasei CBA L74) which is the subject of the health claim is sufficiently characterised. The Panel considers that immune defence against pathogens in GI tract and URT is a beneficial physiological effect. Two human intervention studies were submitted as being pertinent to the claim, which were evaluated by the Panel in the previous application. One human intervention study from which conclusions could be drawn showed an effect of Nutrimune on immune defence against pathogens in the GI tract and the URT. The post hoc re-analysis of the two human studies combined does not address the methodological limitations of the second study raised in the previous opinion, i.e. that the study was not planned, designed, randomised and analysed as a multicentre study, and that the large disparity of subjects in the three centres was not duly justified. The results from one animal study could support an effect of Nutrimune on defence against pathogens in the GI tract. No evidence was provided for a plausible mechanism by which Nutrimune could exert the claimed effect in vivo in humans. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of Nutrimune and immune defence against pathogens in the GI tract and URT.

2019 - Occupational risk factors for early onset dementia (EOD) in the Modena population: a case-control study [Abstract in Rivista]
Adani, Giorgia; Filippini, Tommaso; Garuti, Caterina; Vinceti, Giulia; Chiara, Galli; Zamboni, Giovanna; Tondelli, Manuela; Manuela, Costa; Malavolti, Marcella; Vinceti, Marco; Chiari, Annalisa
abstract

Introduction Dementia is a clinical condition generally affecting subjects in the elderly. However, it may occur also at younger age, yielding a condition called early-onset dementia (EOD) characterized by an onset before 65 years 1 2. Despite the limited epidemiological data and the paucity of information regarding possible risk fac- tors 3 4, there is a general agreement that clinical presentation and consequences on daily life are different than late-onset demen- tia, due to the occurrence when subjects are still involved within occupational activities as well as familiar responsibilities 5. The aim of this work is to assess the epidemiological, clinical and prognostic role of occupational risk factors in EOD. Materials and methods Using a case-control design, we recruited newly-diagnosed EOD cases from the two Centers of Cognitive Disease of the Neurol- ogy Units of Modena-Baggiovara and Carpi Hospitals, as well as from the community health centers and general practitioners, October 1, 2016 to May 31, 2019. Referent population have been recruited from care-givers of EOD and LOD (late onset demen- tia) subjects. We investigated as possible risk factors of the dis- ease the occupational history, by administering a questionnaire collecting information about personal characteristics, family his- tory of diseases, clinical history and comorbidities, occupation activities, hobbies and other leisure activities, residential history, domestic use of pesticides, and dental care. We computed the odds ratios (ORs) of EOD risk, and the corresponding 95% con- fidence intervals (CIs), according to exposure to the investigated risk factors using an unconditional logistic regression model ad- justing for sex, age, and educational attainment. Results Fifty-six cases and fifty-three controls agreed to participate, with generally higher number of women (60% cases and 55% controls) and people over 65 (60% cases compared to 49% con- trols). About occupational factors, working in the agricultural sector seemed to be only slightly associated with risk of EOD (OR 1.31, 95% CI 0.26-6.59), while an increased risk was found for industrial sector (OR 2.23, 95% CI 0.85-5.88). Occupational exposure to contaminants showed positive association for occupational exposure to selenium (OR 2.23, 95% CI 0.11-46.42), aluminum (OR 2.75, 95% CI 0.42-18.11), pesticides (OR 2.10, 95% CI 0.60-7.36), dyes, paints or thinners (OR 2.07, 95% CI 0.70-6.05), while no association was found for exposure to or use of electric and electronic system or electromagnetic fields. Conclusions Results of this study suggest that some occupational factors, namely use of pesticides, dyes/paints, and metalloids such as alu- minum and selenium, could be associated with increased disease risk. Despite study limitations due to case-control design, includ- ing possible occurrence of selection and recall bias, our findings support the hypothesis of an environmental etiology of EOD.

2019 - Proximity to petrol station and risk of childhood leukemia: systematic review and meta-analysis [Poster]
Filippini, Tommaso; Malagoli, Carlotta; Vinceti, Marco
abstract

Motorized traffic exposure and particularly benzene have been associated to childhood leukemia. In particular, living next to a petrol station or repair garage may increase the opportunity for benzene exposure. In this review, we investigated the extent to which living in proximity to petrol stations is associated with risk of childhood leukemia. We searched all observational studies that have investigated the risk of childhood leukemia in relation to exposure to petrol station using either proximity of children residence or modelled exposure. We performed online database search up to October 10, 2019, including also snowballing methods to retrieve all possible eligible studies. We carried out a meta-analysis of all eligible studies using a random effect model. We found six studies eligible to be included in our review published from 1999 to 2019 and all with all with a case-control design. We identified two additional studies compared to the last published systematic review, including one conference abstract. Exposure assessment was performed using questionnaire or face-to-face interview asking for distance of residence to petrol station in three studies (in one case with external validation), while georeferencing method was used using either distance (two studies) or petrol station density (one study). We eventually included 3632 cases and 21874 controls in the analysis. Summary relative risk (sRR) was 1.63 (95% CI 1.11 to 2.50). After exclusion of one study in which exposure to either petrol station and automotive repair was considered, we still found an increased sRR of 1.48 (95% CI 1.03 to 2.12). Comparable risk was reported after stratification of exposure assessment method. Estimates were slightly higher for ALL (sRR=3.31, 95% CI 0.92 to 11.86) compared with AML (sRR=2.06, 95% CI 0.90 to 4.70), although based on only two studies. Overall, the epidemiologic literature appears to support an association between living in proximity to petrol station and childhood leukemia risk, particularly ALL, supporting previous findings regarding motorized traffic and particularly benzene.

2019 - Risk of early onset dementia (EOD) in relation to fruit and vegetable consumption: a case-control study [Abstract in Rivista]
Filippini, Tommaso; Garuti, Caterina; Adani, Giorgia; Vinceti, Giulia; Chiara, Galli; Zamboni, Giovanna; Tondelli, Manuela; Manuela, Costa; Malavolti, Marcella; Vinceti, Marco; Chiari, Annalisa
abstract

Introduction Early onset dementia (EOD) is a condition characterized by the onset of severe cognitive impairment before 65 year 1. There is a general agreement that clinical presentation and conse- quences on daily life are different than late-onset dementia, due to the occurrence when subjects are still involved within occupational activities as well as familiar responsibilities 2. Previous studies have raised the possibility that the risk factors may also differ between the two forms, including the role of environmental and life-style determinants such as diet 3. There is some epidemiologic evidence of an association between dietary habits and protective relations to cognitive decline and incident dementia 4 5. The aim of this study is to evaluate, for the first time to our knowledge, the association between diet and EOD risk. Materials and methods Using a case-control design, we recruited newly-diagnosed EOD cases from 2016 to 2019 in Modena province, Northern Italy. We recruited controls from care-givers of dementia patients referring the Neurology Units of Modena-Baggiovara and Carpi Hospi- tals. We investigated dietary habits through a self-administered semi-quantitative food frequency questionnaire, designed and validated to capture eating behaviors in Italy, and specifically developed as part of the European Prospective Investigation into Cancer and Nutrition (EPIC) study for the Northern Italy pop- ulation 6. Participants were asked to respond to 248 questions about 188 different food items, in order to assess frequency and quantity of daily consumption for each food item. We specifically focused on consumption of fruits and vegetables that were categorized into major and sub-group categories as previously reported 7. We computed the odds ratios (ORs) of EOD risk, and the corresponding 95% confidence intervals (CIs), according to increasing tertile of intake using an unconditional logistic regres- sion model and we also modeled the relation using restricted cu- bic splines with three knots (10, 50 and 90%). We implemented a model adjusted for sex, age (years), educational attainment (years), and total energy intake (kcal/day). Results We recruited 56 (men/women: 22/34) and 53 (men/women: 24/29) controls who agreed to participate and returned study ma- terial. Regarding food intake, cases showed a lower intake than controls of vegetables (119 g/day versus 148 g/day), pulses (19 g/day versus 22 g/day), potatoes (15 g/day versus 23 g/day), and dry fruits (2.6 g/day versus 4.0 g/day). Conversely cases showed a higher intake than controls of fresh fruits (256 g/day versus 240 g/day). In the analysis of EOD risk according to increasing tertile we found an inverse association with all vegetables overall considered and also for individual subgroup, particularly leafy vegetables and other vegetables (e.g. eggplant, zucchini or sweet pepper). Also, an inverse association was found for potatoes and slightly for legumes. Conversely, the higher tertile of intake of fresh fruits was associated with no difference in EOD risk, but in the stratified analysis for non-citrus and citrus fruits we found inverse association for the latter. Interestingly, for non-citrus fruits we found inverse association in the second tertile of consumption, and an opposite positive association in the third tertile. Finally, with increasing tertile of dry fruits intake, we found a strong inverse association with EOD risk. Similarly in the spline analysis, the increasing consumption of vegetables, particularly leafy vegetables showed a strong inverse association, as simi- larly also increased pulse intake. Regarding fruit consumption, fresh fruit overall considered showed ambivalent relation, while higher consumption of citrus fruits only, as well as dry fruits, showed a negative association with EOD risk. Conclusions In this study, we found an association of consumption of vegeta- bles and to some extent fruit with EOD risk in an Italian popula- tio

2019 - Safety of 2’-fucosyllactose/difucosyllactose mixture as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Sun, Q.; Turla, E.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2’-fucosyllactose/difucosyllactose (2’-FL/DFL) mixture as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a powdered mixture mainly composed of two oligosaccharides, 2’-FL and DFL, which are produced together by fermentation with a genetically modified strain of Escherichia coli K12. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and young children, foods for special medical purposes and food supplements. The target population is the general population except for food supplements, for which the target population is individuals above 1 year of age. Since the intake of 2’-FL and DFL from the NF at the proposed use levels is unlikely to exceed the intake level of naturally occurring 2’-FL and DFL in breastfed infants per kilogram body weight, the Panel concludes that the NF, a mixture of 2’-FL and DFL, is safe under the proposed conditions of use for the proposed target population.

2019 - Safety of Yarrowia lipolytica yeast biomass as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; de Henauw, Stefaan; Hirsch‐ernst, Karen‐ildico; Kearney, John; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Cubadda, Francesco; Engel, Karl‐heinz; Frenzel, Thomas; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser‐berthold, Monika; Pöting, Annette; Poulsen, Morten; Sanz, Yolanda; Schlatter, Josef Rudolf; van Loveren, Henk; Ackerl, Reinhard; Knutsen, Helle Katrine
abstract

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2019 - Safety of betaine as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Turla, E.; Knutsen, H. K.
abstract

In 2017, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) concluded that betaine as a novel food (NF) is safe to be used at a maximum intake level of 6 mg/kg body weight per day in addition to the intake from the background diet. Following the present request from the European Commission, the EFSA NDA Panel was asked to deliver a scientific opinion on betaine by carrying out the assessment for the revised uses and use levels of betaine as proposed by the applicant. Thus, EFSA performed an intake assessment based on individual data from the EFSA Comprehensive European Food Consumption Database and the new proposed uses of the NF for the general population. The resulting ranges for the mean and high-level estimated intakes of betaine for the general population do not exceed the safe level of intake previously established. The Panel concludes that the NF, betaine, is safe under the new proposed conditions of use.

2019 - Safety of chia seeds (Salvia hispanica L.) as a novel food for extended uses pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Gelbmann, W.; Matijevic, L.; Romero, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel foods and Food Allergens (NDA) was asked to deliver an opinion on overall safety assessment for chia seeds (Salvia hispanica L.) as a novel food (NF) pursuant to Regulation (EU) 2015/2283 in the light of the increasing dietary intake from the growing number of authorised uses in recent years. The safety assessment of this NF is based on data supplied in seven applications, previous safety assessments of chia seeds and information retrieved from an extensive literature search done by EFSA. Since none of the applications addressed the possible formation of process contaminants, the present assessment is limited to those proposed extended uses which do not raise safety concerns regarding the formation of such contaminants. These include the use of whole and ground chia seeds added to chocolate, fruit spreads, fruit desserts, mixed fruit with coconut milk in twin pot, fruit-preparations to underlay a dairy product, fruit-preparations to be mixed with dairy products, confectionary (excluding chewing gums), dairy products and analogues, edible ices, fruit and vegetables products, non-alcoholic beverages and compotes from fruit and/or vegetables and/or with cereals. In addition, this assessment also concerns uses of chia seeds without specific restrictions and precautions regarding their use levels in other foods which usually do not include heat treatment during processing and cooking. Apart from allergenicity, the Panel did not identify any hazard which causes safety concerns. Lacking the basis and need to establish safe maximum intake levels for chia seeds, no exposure assessment was conducted. The Panel concludes that chia seeds are safe under the assessed conditions of use.

2019 - Safety of chia seeds (Salvia hispanica L.) powders, as novel foods, pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Matijevic, L.; Katrine Knutsen, H.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel foods and Food Allergens (NDA) was asked to deliver an opinion on chia seeds (Salvia hispanica L.) powders as novel foods (NFs) pursuant to Regulation (EU) 2015/2283. The NFs are partially defatted chia seed powders, obtained by extrusion of whole seeds of S. hispanica L. with the main differences between two powders in particle sizes and the content of some macronutrients. The information provided on the production processes, composition, batch-to-batch variability, stability and specifications of the NFs is sufficient and does not raise safety concerns. The applicant proposed to market the NFs as food supplements and as ingredients in a variety of foods. The target population for the NFs is the general population. Noting that no hazard raising safety concerns (except for allergenicity) could be identified from the information available on the source (i.e. chia seeds), the production processes, composition, specifications and proposed uses of the NFs, irrespectively of the maximum use levels at the proposed uses, the Panel considers that intake estimates and additional toxicological data for the NFs are not needed for this assessment. The Panel concludes that the NFs, partially defatted powders of whole chia seeds, are safe under the assessed conditions of use.

2019 - Safety of heat-killed Mycobacterium setense manresensis as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Sun, Q.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on heat-killed Mycobacterium setense manresensis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is an encapsulated ingredient composed of 200 mg mannitol and ≤ 105 heat-killed, freeze-dried M. setense manresensis. The information provided on the efficacy of the heat inactivation process demonstrates that the applied thermal process effectively kills all M. setense manresensis. The Panel considers that the NF is sufficiently described and characterised. The NF is intended by the applicant to be marketed exclusively in food supplements (gelatine capsules) for the general adult population excluding, children, pregnant and lactating women. The NF is not intended to be an alternative to standard treatment against tuberculosis. The applicant proposed an intake of one capsule (with ≤ 105 heat-killed, freeze-dried M. setense manresensis) for 14 consecutive days and a minimum of 6 months with no consumption of the NF, before another intake for fourteen days may follow. M. setense is not considered to be a suitable microorganism species for the qualified presumption of safety (QPS). Genetic analyses of the genome indicate the absence of the ability to produce exotoxins. The Panel considers that consumption of heat-killed M. setense manresensis would not contribute to the pool of transmissible antimicrobial resistance genes already present in the intestinal microbiota. The Panel concludes that the NF is safe under the proposed conditions of use.

2019 - Safety of lacto-N-tetraose (LNT) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Colombo, P.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on lacto-N-tetraose (LNT) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a powdered mixture mainly composed by LNT, but also containing d-lactose and other oligosaccharides such as para-lacto-N-hexaose-2 (para-LNH-2), lacto-N-triose II and a small fraction of other carbohydrates. It is produced by fermentation with a genetically modified strain of Escherichia coli K-12. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements. The target population is the general population except for food supplements, for which the target population is individuals above 1 year of age. The intake of LNT from the NF at the proposed use levels is unlikely to exceed the intake level of naturally occurring LNT in breastfed infants on a body weight basis. The intake of other carbohydrate-type compounds structurally related to LNT is considered of no safety concern. The Panel concludes that the NF is safe under the proposed conditions of use for the proposed target populations.

2019 - Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; McArdle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren Agnes de Sesmaisons-Lecarre, H.; Germini, A.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Allergens (NDA) was asked to deliver an opinion on nicotinamide riboside chloride as a novel food (NF) pursuant to Regulation (EU) 2015/2283, including an evaluation of the safety of its use in food supplements as a source of niacin, and the bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. The NF, a synthetic form of nicotinamide riboside, is proposed to be used in food supplements for the healthy adult population at levels up to 300 mg/day. The production process, composition, specifications, batch-to-batch variability and stability of the NF do not raise safety concerns. Animal and human data indicate that the NF contributes to the nicotinamide body pool. There are no concerns regarding genotoxicity. Human studies do not raise safety concerns. The proposed maximum use level corresponds to an amount of nicotinamide, which is sixfold lower than the tolerable upper intake level (UL) set for adults, excluding pregnant and lactating women. The margin of exposure (MoE) of 70 derived from repeated dose toxicity studies with rats and dogs is considered sufficient for the adult population, excluding pregnant and lactating women. Regarding these two population groups, the MoE of 76 derived from a developmental toxicity study in rats is considered insufficient in the absence of data which could justify accepting a MoE lower than 100. The Panel concludes that the NF is safe under the proposed conditions of use for the healthy adult population, excluding pregnant and lactating women, and that an intake of the NF up to 230 mg/day is safe for pregnant and lactating women. The Panel also concludes that the NF is a source from which nicotinamide, a form of niacin, is bioavailable.

2019 - Safety of phenylcapsaicin as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Amundsen, M.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on phenylcapsaicin as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Phenylcapsaicin is a chemically synthesised analogue of capsaicin intended to be marketed in food supplements and in foods for special medical purposes to the general population above the age of 11 years old at a maximum level of 2.5 mg/day. The highest intake of the NF is 2.5 mg/day which corresponds to 36 μg/kg body weight (bw) per day for adults, and 58 μg/kg bw per day for adolescents (10–14 years). The Panel considers that there is no concern with respect to genotoxicity of the NF. The reference point derived based on a 13-week rat study was the lowest of the model averaged BMDL20 values of 37.2 mg/kg bw per day in females for increased plasma alanine aminotransferase (ALAT) levels. The Panel concludes that the NF, phenylcapsaicin, is safe under the proposed uses and use levels.

2019 - Safety of viable embryonated eggs of the whipworm Trichuris suis as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; De Henauw, S.; Hirsch-Ernst, K. I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Fernandez Dumont, A.; Gelbmann, W.; Knutsen, H. K.
abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on viable embryonated eggs of the whipworm Trichuris suis as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The applicant proposes to use the NF as a food supplement in the format of a 15-mL bottle containing 250 viable embryonated eggs of T. suis. The target population for the NF is the general population. Considering the compositional data and proposed conditions of use, the consumption of the NF is considered of no nutritional relevance. Available data suggest that most larvae of T. suis after hatching in the intestinal tract of humans remain immature and live for several weeks in the gastrointestinal tract of the human host. Nevertheless, under certain circumstances, T. suis can be invasive in human, being able to mature into adult size and reproduce in humans. Human studies have also shown that administration of T. suis ova may increase the incidence of adverse gastrointestinal reactions. The Panel considers that there are no studies available that demonstrate the safety of this NF intended for the general population at a proposed intake of 250 viable embryonated eggs of T. suis ova per day. Based on the available information, the Panel cannot establish a safe dose at which no safety concerns would be expected. The Panel concludes that the safety of the NF has not been established.

2019 - Safety of whey basic protein isolate for extended uses in foods for special medical purposes and food supplements for infants pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, D.; Castenmiller, J.; de Henauw, S.; Hirsch-Ernst, K. -I.; Kearney, J.; Maciuk, A.; Mangelsdorf, I.; Mcardle, H. J.; Naska, A.; Pelaez, C.; Pentieva, K.; Siani, A.; Thies, F.; Tsabouri, S.; Vinceti, M.; Cubadda, F.; Engel, K. -H.; Frenzel, T.; Heinonen, M.; Marchelli, R.; Neuhauser-Berthold, M.; Poting, A.; Poulsen, M.; Sanz, Y.; Schlatter, J. R.; van Loveren, H.; Amundsen, M.; Knutsen, H. K.
abstract

In 2018, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) concluded that whey basic protein isolate obtained by ion exchange chromatography from skimmed cow's milk is safe for human consumption under the proposed conditions of use as infant and follow on formula, meal replacement beverages, foods for special medical purposes and food supplements. Following a request from the European Commission, the EFSA NDA Panel was asked to deliver a scientific opinion on whey basic protein isolate for extended uses in foods for special medical purposes and food supplements for infants as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The applicant seeks to extend the conditions of use to infant (powder 30 mg/100 g and reconstituted 3.9 mg/100 mL) and follow on formulae (powdered 30 mg/100 g and reconstituted 4.2 mg/100 mL) as foods for special medical purposes as well as in food supplements for infants (25 mg/day). The Panel considers that the proposed extended uses would not increase the potential intake of the NF compared to that assessed in its 2018 opinion. The Panel concludes that whey basic protein isolate is safe at the extended uses and use levels.

2019 - Selenium and selenium species in the etiology of Alzheimer's dementia: The potential for bias of the case-control study design [Articolo su rivista]
Vinceti, Marco; Michalke, Bernhard; Malagoli, Carlotta; Eichmüller, Marcel; Filippini, Tommaso; Tondelli, Manuela; Bargellini, Annalisa; Vinceti, Giulia; Zamboni, Giovanna; Chiari, Annalisa
abstract

Several human studies imply that the trace element selenium and its species may influence the onset of neurological disease, including Alzheimer's dementia (AD). Nevertheless, the literature is conflicting, with reported associations between exposure and risk in opposite direction, possibly due to biases in exposure assessment. After conducting a cohort study that detected an excess AD risk associated with higher levels of inorganic-hexavalent selenium in subjects with mild cognitive impairment (MCI), we investigated the relation between selenium and AD using a case-control study design. We determined cerebrospinal fluid levels of selenium species in 56 MCI participants already included in the cohort study, considered as referents, and in 33 patients with established AD. AD risk was inversely correlated with inorganic selenium species and with the organic form bound to selenoprotein P. Selenium bound to other organo-selenium species was positively correlated with AD risk, suggesting compensatory selenoprotein upregulation following increased oxidative stress. The finding of an increased AD risk associated with inorganic-hexavalent selenium from the cohort study was not replicated. This case-control study yielded entirely different results than those generated by a cohort study with a partially overlapping participant population, suggesting that case-control design does not allow to reliably assess the role of selenium exposure in AD etiology. This inability appears to be due to exposure misclassification, falsely indicating an etiologic role of selenium deficiency likely due to reverse causation, and involving most selenium species. The case-control design may instead lend insights into the pathologic process underlying disease progression.

2019 - [The dose-response relationship between potassium intake and blood pressure levels. Results of meta-analysis of randomized clinical trials] [Abstract in Rivista]
Kasdagli, Μι; Filippini, T; Lopes, C; Carvalho, C; Moreira, P; Malavolti, M; Orsini, N; Vinceti, M; Naska, A
abstract

2018 - A GIS-based atmospheric dispersion model for pollutants emitted by complex source areas [Articolo su rivista]
Teggi, Sergio; Costanzini, Sofia; Ghermandi, Grazia; Malagoli, Carlotta; Vinceti, Marco
abstract

Gaussian dispersion models are widely used to simulate the concentrations and deposition fluxes of pollutants emitted by source areas. Very often, the calculation time limits the number of sources and receptors and the geometry of the sources must be simple and without holes. This paper presents CAREA, a new GIS-based Gaussian model for complex source areas. CAREA was coded in the Python language, and is largely based on a simplified formulation of the very popular and recognized AERMOD model. The model allows users to define in a GIS environment thousands of gridded or scattered receptors and thousands of complex sources with hundreds of vertices and holes. CAREA computes ground level, or near ground level, concentrations and dry deposition fluxes of pollutants. The input/output and the runs of the model can be completely managed in GIS environment (e.g. inside a GIS project). The paper presents the CAREA formulation and its applications to very complex test cases. The tests shows that the processing time are satisfactory and that the definition of sources and receptors and the output retrieval are quite easy in a GIS environment. CAREA and AERMOD are compared using simple and reproducible test cases. The comparison shows that CAREA satisfactorily reproduces AERMOD simulations and is considerably faster than AERMOD.

2018 - Adverse pregnancy outcomes in women with changing patterns of exposure to the emissions of a municipal waste incinerator [Articolo su rivista]
Vinceti, Marco; Malagoli, Carlotta; Werler, Martha M.; Filippini, Tommaso; De Girolamo, Gianfranco; Ghermandi, Grazia; Fabbi, Sara; Astolfi, Gianni; Teggi, Sergio
abstract

Municipal solid waste incinerators emissions contain pollutants that, despite their low concentration, might adversely affect reproductive health. In the present study, we examined rates of miscarriage and birth defects among women who resided or were employed in the vicinity of a municipal solid waste incinerator plant from 2003-2013. In 2009, a progressive shutdown of the old incineration lines and operation of a new line caused considerably higher atmospheric release of polycyclic aromatic hydrocarbons, particularly of dioxins, due to these irregular operating conditions, technological renovation, and increased capacity. We used dioxin emission levels, based on a dispersion model, as a marker of air pollution due to waste incineration. In women who resided in areas characterized by higher emission exposures compared with a referent area, the relative risk (RR) of miscarriage was 1.04 (95% confidence interval (CI) 0.80-1.32) based on 62 cases overall, with little evidence of a dose-response relation. RRs were similarly null for both 2003-2008 and 2010-2013 periods (RR 1.12 (95% CI 0.80-1.53) and 0.98 (95% CI 0.63-1.48), respectively). Concerning birth defects in the offspring of women residing in the exposed area, no evidence of increased risk emerged, since the prevalence ratio at birth was 0.64 (95% CI 0.29-1.26), with comparable results in the 2003-2008 and 2010-2013 period. Corresponding analyses carried out in municipal residents who worked in the exposed area confirmed these findings. We also did not detect abnormally high rates of miscarriage and birth defects in the exposed cohorts in the single year 2009. Overall, these results do not suggest an effect of exposure to the emissions of the municipal solid waste incinerator we investigated on two indicators of reproductive health. However, the limited statistical stability of the estimates and the absence of individual-based information on some potential confounders suggest caution in the interpretation of study findings.

2018 - Assessment of food contamination and dietary intake of lead and thallium in a Northern Italy population. [Abstract in Atti di Convegno]
Filippini, T; Malavolti, M; Cilloni, S; Violi, F; Malagoli, C; Vescovi, L; Vinceti, M.
abstract

Lead and thallium are heavy metals released in the environment after natural and anthropogenic activities. Food and water intake are the major sources of human exposure to these elements. In this study, we aimed at characterizing lead and thallium content in foods consumed in Northern Italy population, in order to estimate the dietary intake of these metals. To do that we bought food samples in markets and groceries collected during the period from October 2016 to February 2017 in the Emilia Romagna region, and we measured their element content using inductively coupled plasma-mass spectrometry. Finally, after assessing dietary habits of an Emilia-Romagna community by using a validated food frequency questionnaire, we eventually estimated dietary intake of these metals in that community. In the 890 analyzed food samples, the highest lead contamination levels were found in seafood, vegetables, sweets and beverages. The estimated dietary intake of lead was 5.758 (interquartile range-IQR: 4.547-7.427) µg/day, corresponding to 0.089 (IQR: 0.069-0.113) µg/kg of body weight per day, with cereals, beverages and vegetables as major contributors. About thallium, one third of specimens showed very low levels below the limit of detection, with the highest contamination levels in vegetables, dry fruits and sweets. The dietary intake of thallium was 0.236 (IQR: 0.183-0.312) µg/day, mainly from vegetables, beverages, cereals and sweets. In conclusion, our study provides an estimation of lead and thallium intake in a Northern Italian community and shows a generally low exposure levels from dietary sources.

2018 - Assessment of residential exposure to pesticides and risk of amyotrophic lateral sclerosis: methodological issue in the use of different versions of Land Use Chart. [Abstract in Atti di Convegno]
Filippini, T; Fiore, M; Violi, F; Malagoli, C; Cilloni, S; Odone, A; Signorelli, C; Ferrante, Michele; Vinceti, M.
abstract

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2018 - Atmospheric Dispersion Modelling and Spatial Analysis to Evaluate Population Exposure to Pesticides from Farming Processes [Articolo su rivista]
Costanzini, Sofia; Teggi, Sergio; Bigi, Alessandro; Ghermandi, Grazia; Filippini, Tommaso; Malagoli, Carlotta; Nannini, Roberta; Vinceti, Marco
abstract

This work originates from an epidemiological study aimed to assess the correlation between population exposure to pesticides used in agriculture and adverse health effects. In support of the population exposure evaluation two models implemented by the authors were applied: a GIS-based proximity model and the CAREA atmospheric dispersion model. In this work, the results of the two models are presented and compared. Despite the proximity analysis is widely used for these kinds of studies, it was investigated how meteorology could affect the exposure assessment. Both models were applied to pesticides emitted by 1519 agricultural fields and considering 2584 receptors distributed over an area of 8430 km2. CAREA output shows a considerable enhancement in the percentage of exposed receptors, from the 4% of the proximity model to the 54% of the CAREA model. Moreover, the spatial analysis of the results on a specific test site showed that the effects of meteorology considered by CAREA led to an anisotropic exposure distribution that differs considerably from the symmetric distribution resulting by the proximity model. In addition, the results of a field campaign for the definition and planning of ground measurement of concentration for the validation of CAREA are presented. The preliminary results showed how, during treatments, pesticide concentrations distant from the fields are significantly higher than background values.

2018 - Black tea and improvement of attention: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (JJ); Siani, Alfonso
abstract

Following an application from Unilever NV, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to black tea and improvement of attention. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is black tea. The Panel considers that black tea characterised by its content of tea solids, caffeine and l-theanine, which is the subject of the health claim, is sufficiently characterised in relation to the claimed effect. The claimed effect proposed by the applicant is ‘improves attention’. The Panel considers that improvement of attention is a beneficial physiological effect. Three human intervention studies provided by the applicant show an effect of black tea on attention under the conditions of used proposed by the applicant. The applicant proposed that the claimed effect depends on the concerted action of two substances, caffeine and l-theanine, both of which are present in black tea. The Panel considers that the effect of black tea on attention observed in the three human intervention studies provided by the applicant can be explained by its caffeine content. The Panel concludes that a cause and effect relationship has been established between the consumption of black tea and improvement of attention. The Panel considers that the effect of black tea on attention can be explained by its caffeine content. The following wording reflects the scientific evidence: ‘Owing to its caffeine content, black tea improves attention’. In order to obtain the claimed effect, 2–3 servings of black tea providing at least 75 mg of caffeine in total should be consumed within 90 min.

2018 - Black tea and maintenance of normal endothelium‐dependent vasodilation: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdor, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (J. J. ); Siani, Alfonso
abstract

ollowing an application from Unilever NV, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Ireland, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to black tea and maintenance of normal endothelium-dependent vasodilation. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is black tea beverages, either freshly prepared or reconstituted from water extract powders of black tea, characterised by the content of flavanols (expressed as catechins plus theaflavins) of at least 30mg per 200mL serving. The Panelconsiders that black tea characterised by the content of flavanols (expressed as catechins plus theaflavins) is sufficiently characterised. The claimed effect proposed by the applicant is improvement of endothelium-dependent vasodilation'. The Panelconsiders that maintenance of normal endothelium-dependent vasodilation is a beneficial physiological effect. Of the five human intervention studies provided on the chronic effect of black tea consumption on endothelium-dependent vasodilation, two investigated the effect after regular consumption of black tea for a sufficiently long time period (i.e. at least 4weeks). These two studies did not allow an effect of black tea on endothelium-dependent vasodilation to be established. The Panelconcludes that a cause and effect relationship has not been established between the consumption of black tea and maintenance of normal endothelium-dependent vasodilation.

2018 - Cadmium and atherosclerosis: A review of toxicological mechanisms and a meta-analysis of epidemiologic studies [Articolo su rivista]
Tinkov, Alexey A; Filippini, Tommaso; Ajsuvakova, Olga P; Skalnaya, Margarita G; Aaseth, Jan; Bjørklund, Geir; Gatiatulina, Eugenia R; Popova, Elizaveta V; Nemereshina, Olga N; Huang, Pai-Tsang; Vinceti, Marco; Skalny, Anatoly V
abstract

Cadmium has been proposed to be the one of the factors of atherosclerosis development, although the existing data are still controversial. The primary objective of the present study is the review and the meta-analysis of studies demonstrating the association between Cd exposure and atherosclerosis as well as review of the potential mechanisms of such association. We performed a systematic search in the PubMed-Medline database using the MeSH terms cadmium, cardiovascular disease, atherosclerosis, coronary artery disease, myocardial infarction, stroke, mortality and humans up through December 20, 2017. Elevated urinary Cd levels were associated with increased mortality for cardiovascular disease (HR = 1.34, 95% CI: 1.07-1.67) as well as elevated blood Cd levels (HR = 1.78, 95% CI: 1.24-2.56). Analysis restricted to never smokers showed similar, though more imprecise, results. Consistently, we also observed an association between Cd exposure markers (blood and urine) and coronary heart disease, stroke, and peripheral artery disease. Moreover, Cd exposure was associated with atherogenic changes in lipid profile. High Cd exposure was associated with higher TC levels (OR = 1.48, 95% CI: 1.10-2.01), higher LDL-C levels (OR = 1.31, 95% CI 0.99-1.73) and lower HDL-C levels (OR = 1.96, 95% CI: 1.09-3.55). The mechanisms of atherogenic effect of cadmium may involve oxidative stress, inflammation, endothelial dysfunction, enhanced lipid synthesis, up-regulation of adhesion molecules, prostanoid dysbalance, as well as altered glycosaminoglycan synthesis.

2018 - Cancer incidence following long-term consumption of drinking water with high inorganic selenium content [Articolo su rivista]
Vinceti, Marco; Vicentini, Massimo; Wise, Lauren A.; Sacchettini, Claudio; Malagoli, Carlotta; Ballotari, Paola; Filippini, Tommaso; Malavolti, Marcella; Rossi, Paolo Giorgi
abstract

Selenium, a trace element to which humans are exposed mainly through diet, has been involved in the etiology of human cancer. We investigated the long-term effects of selenium exposure on cancer incidence using data from a natural experiment in Northern Italy. During the 1970s–1980s, in a part of the Italian municipality of Reggio Emilia, residents were inadvertently exposed to unusually high levels of inorganic hexavalent selenium (selenate) through drinking water. We followed the exposed residents for 28 years, generating data on incidence (when available) and mortality rates for selected cancer sites; the remaining municipal residents comprised the unexposed (reference) group. We observed no substantial difference in overall cancer incidence comparing exposed and unexposed cohorts. We detected, however, a higher incidence of cancer at some sites, and for a few of them, namely cancers of the buccal cavity and pharynx, melanoma, urinary tract and lymphoid tissue, the excess incidence was particularly evident in the first period of follow-up but decreased over time. Overall, these results suggest that consumption of water with levels of selenium in its inorganic hexavalent form close to the European standard, 10 μg/L, may have unfavourable effects on cancer incidence.

2018 - Carbohydrate solutions and contribute to the improvement of physical performance during a high‐intensity and long‐lasting physical exercise: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (JJ); Siani, Alfonso
abstract

Following an application from Specialised Nutrition Europe (SNE), submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to carbohydrate solutions and contribute to the improvement of physical performance during a high-intensity and long-lasting physical exercise. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is carbohydrate solutions containing glucose, mixtures of glucose and fructose, sucrose and/or maltodextrins. The Panel considers that carbohydrate solutions are sufficiently characterised in relation to the claimed effect. The claimed effect proposed by the applicant is 'contribute to the improvement of physical performance during a high-intensity and long-lasting physical exercise', which is considered by the Panel as a beneficial physiological effect. The Panel concludes that a cause and effect relationship has been established between the consumption of carbohydrate solutions and the improvement of physical performance during high-intensity and long-lasting physical exercise. The target population is healthy trained adults performing high-intensity (at least at 65% of the VO2max) and long-lasting (at least 60 min) physical exercise. (c) 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

2018 - Cerebrospinal Fluid Neurofilaments May Discriminate Upper Motor Neuron Syndromes: A Pilot Study [Articolo su rivista]
Zucchi, Elisabetta; Bedin, Roberta; Fasano, Antonio; Fini, Nicola; Gessani, Annalisa; Vinceti, Marco; Mandrioli, Jessica
abstract

Patients presenting with upper motor neuron (UMN) signs may widely diverge in prognosis, ranging from amyotrophic lateral sclerosis (ALS) to primary lateral sclerosis (PLS) and hereditary spastic paraplegia (hSP). Neurofilaments are emerging as potential diagnostic and prognostic biomarkers for ALS, but the diagnosis of UMN syndromes still relies mostly on clinical long-term observation and on familiarity or genetic confirmation.

2018 - Comparison of two alternative methodologies to estimate the weekly intake of cadmium in an italian population [Abstract in Rivista]
Filippini, Tommaso; Malagoli, Carlotta; Michalke, Bernhard; Vinceti, Marco
abstract

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2018 - Congenital anomalies and risk of childhood leukemia: a pooled analysis from the childhood leukemia international consortium (clic) [Abstract in Atti di Convegno]
Lupo, Pj; Mueller, Ba; Clavel, J; Dockerty, Jd; Ezzat, S; Hansen, J; Heck, Je; Infante-Rivard, C; Magnani, C; Metayer, C; Milne, E; Mora, Am; Petridou, Et; Malagoli, C; Pombo-de-Oliveira, Ms; Roman, E; Schüz, J; Vinceti, M; Spector, Lg; Scheurer, Me
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2018 - Contaminazione alimentare da piombo e stima dell’assunzione giornaliera in una popolazione del Nord Italia. [Abstract in Atti di Convegno]
Cilloni, S; Filippini, T; Violi, F; Malavolti, M; Malagoli, C; Ferrari, A; Vescovi, L; Vinceti, M.
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2018 - Correlation between dietary cadmium exposure with biochemical and metabolic parameters: A cross-sectional study in Northern Italy population [Abstract in Atti di Convegno]
Filippini, T; Lasagni, D; Bruzziches, F; Baraldi, C; Malagoli, C; Grioni, S; Sieri, S; Santachiara, A; De Luca, T; Pertinhez, T; Baricchi, R; Vinceti, M.
abstract

Background and aim: Cadmium is a heavy metal classified as carcinogen for humans. It accumulates in the organism, especially in kidney and liver. Recent findings suggested that cadmium could influence human metabolism acting as endocrine disruptor and high cadmium exposure has been associated with impairment of cardiovascular and endocrine systems. This study aims at assessing the dietary intake of cadmium in an Italian community of Northern Italy and to evaluate its correlation with endocrine and metabolic factors. Methods: In a sample adult population of ever smokers from Reggio Emilia Province we estimated dietary cadmium intake through a food frequency questionnaire, validated for the Northern Italy population. From each participant we collected a fasten blood sample for determination of biochemical parameters and hormones levels, including alanine transaminase, blood glucose, total cholesterol, high-density lipoproteins (HDL), and thyroid-stimulating hormone (TSH). All subjects who participated to this study signed a written informed consent. Results: We eventually recruited 104 participants (men/women: 46/58), with mean (standard deviation) dietary intake of cadmium of 16.0 (8.5) μg/day. Correlation between cadmium intake and biochemical factors demonstrated a positive association with total cholesterol levels, blood glucose and TSH. Adjustment for main confounders, including sex, age, and bass index did not substantially alter the results. No clear correlation emerged with other parameters under investigation. Discussion: The results show that in our sampled population, dietary intake of cadmium is similar with other Italian and European populations. They also suggest that cadmium intake could influence the levels of metabolic and other biochemical factor which are important risk factors for chronic cardiovascular and endocrine system diseases. Acknowledgements We acknowledge the collaboration of the personnel of Transfusion Medicine Unit of AUSL-IRCCS of Reggio Emilia, staff and volunteers of AVIS – Section of Reggio Emilia, and all blood donors who participated to this study.

2018 - Correlation between dietary selenium exposure with biochemical and metabolic parameters: a cross-sectional study in Northern Italy population. [Abstract in Atti di Convegno]
Vinceti, M; Lasagni, D; Bruzziches, F; Baraldi, C; Malagoli, C; Grioni, S; Sieri, S; Santachiara, A; De Luca, T; Pertinhez, T; Baricchi, R; Filippini, T.
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2018 - Diagnostic medical radiation exposure and risk of childhood leukaemia: results from an Italian population-based case-control study. [Abstract in Atti di Convegno]
Cilloni, S; Arcolin, E; Malagoli, C; Filippini, T; Violi, F; Borsari, L; Vinceti, M.
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2018 - Diagnostic medical radiation exposure and risk of childhood leukemia: results from an Italian population-based case-control study. [Abstract in Atti di Convegno]
Filippini, T; Arcolin, E; Malagoli, C; Cilloni, S; Violi, F; Borsari, L; Vinceti, M.
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2018 - Diet composition and serum levels of selenium species: A cross-sectional study [Articolo su rivista]
Filippini, Tommaso; Michalke, Bernhard; Wise, Lauren A.; Malagoli, Carlotta; Malavolti, Marcella; Vescovi, Luciano; Salvia, Chiara; Bargellini, Annalisa; Sieri, Sabina; Krogh, Vittorio; Ferrante, Margherita; Vinceti, Marco
abstract

Selenium is a trace element of both nutritional and toxicological interest, depending on its dose and chemical form. Diet is the primary source of exposure for most individuals. We sought to investigate the influence of food intake on serum levels of selenium species. Among fifty subjects randomly selected from a Northern Italian population, we assessed dietary habits using a validated semi-quantitative food frequency questionnaire. We also measured circulating levels of selenium species in serum using high pressure liquid chromatography associated with inductively-coupled plasma dynamic reaction cell mass spectrometer. Circulating levels of inorganic selenium, the most toxic selenium species, were positively associated with intake of fish, legumes and dry fruits, and inversely associated with intake of dairy products and mushrooms. Concerning the organic selenium species, selenoproteinP-bound selenium was inversely associated with intake of fish, fresh fruits, vegetables, and legumes, while selenocysteine-bound selenium positively associated with intake of fresh fruit, potato, legume and mushroom. In the present study, intakes of different foods were correlated with different types of selenium species. These results have important public health implications when assessing the nutritional and toxicological potential of diet composition with reference to selenium exposure.

2018 - Dietary intake of cadmium, chromium, copper, manganese, selenium and zinc in a Northern Italy community [Articolo su rivista]
Filippini, T; Cilloni, S; Malavolti, M; Violi, F; Malagoli, C; Tesauro, M; Bottecchi, I; Ferrari, A; Vescovi, L; Vinceti, M
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This study provides the dietary intakes of six trace elements (cadmium, chromium, copper, manganese, selenium and zinc), generally characterized by both nutritional and toxicological features depending on their exposure. Being diet the most relevant source of exposure to trace elements in non-professionally exposed subjects, we measured content of these trace elements in foods composing the typical Italian diet using inductively coupled plasma-mass spectrometry, and assessing dietary habits using a validated semi-quantitative food frequency questionnaire we eventually estimated dietary daily intake of trace elements in a Northern Italian community. In the 890 analyzed food samples, the main contributors to cadmium intake are cereals, vegetables and sweets, while cereals, beverages and vegetable are to primary source of manganese. The primary contributors for copper are cereals, fresh fruits and vegetables, while for chromium are beverages, cereals and meat. The main source of selenium intake are cereals and meat, followed by fish, seafood and milk and dairy products, while of zinc intake are meat, cereals, milk and dairy products. In our Italian population sample, the estimated median (interquartile range) dietary daily intakes are 5.00 (3.17-7.65), 56.70 (36.08-86.70) and 66.53 (40.04-101.32) µg/day for cadmium, chromium and selenium, and corresponding figures are 0.98 (0.61-1.49), 2.34 (1.46-3.52) and 8.50 (5.21-12.48) mg/day for copper, manganese and zinc. The estimated intakes are generally within the average intake reported in other European populations, and in such cases well above the daily dietary intakes recommended by national international agencies, avoiding the risk of excess or deficiency. The present estimated intake data can be used to examine a specific trace element of interest and would afford enhanced health protection from those trace elements characterized by both nutritional and toxicological effects.

2018 - Dietary intake of calcium, phosphorus and magnesium in a Northern Italian community. [Abstract in Atti di Convegno]
Malavolti, M; Filippini, T; Malagoli, C; Cilloni, S; Violi, F; Vescovi, L; Vinceti, M.
abstract

Minerals are essential micronutrients for growth, development, and maintenance of healthy tissues, the long term insufficient intake of minerals may lead to bone demineralization and often requires the use of food supplements. The ratios of certain minerals intake like calcium and phosphorus are also proved to can affect the bioavailability of calcium and even lead to adverse health consequence. This study was designed to explore the dietary sources of calcium (Ca), phosphorus (P), and magnesium (Mg) and the ratios between different minerals (Ca/P). We measured the content of these elements in foods composing typical Italian diet using inductively coupled plasma-mass spectrometry and we estimated their daily dietary intakes assessing through a semi-quantitative food frequency questionnaire specifically developed within the European Prospective Investigation into Cancer and Nutrition (EPIC) study in a Northern Italian Community. In 890 analyzed food samples the main contributors to calcium are milk and dietary products, dry fruits, legumes and sweet products. Important sources of phosphorus are represented by dry fruits, legumes, milk and dairy products and meat. While dry fruits, legumes, cereals and fish symbolized the most important sources for magnesium. In our Italian population sample, the estimated median (interquartile range) dietary daily intakes are 786.3 (592.2-1062.7) μg/day for calcium; 1291.7 (1017.2-1591.4) mg/day for phosphorus and 323.2 (260.3-396.6) mg/day for magnesium. The calcium-phosphorus (Ca/P) ratio in this study was 0.63 (0.52-0.73). These values are in agreement with those suggested by European and International recommended intake for adult population, with the exception of calcium which is slightly lower than recommended values and suggest that this population does not present nutritional deficiencies requiring any supplementation.

2018 - Environmental Selenium and Human Health: an Update [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Wise, Lauren A
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Selenium, a trace element, is ubiquitous in the environment. The main source of human exposure is diet. Despite its nutritional benefits, it is one of the most toxic naturally occurring elements. Selenium deficiency and overexposure have been associated with adverse health effects. Its level of toxicity may depend on its chemical form, as inorganic and organic species have distinct biological properties.

2018 - Exposure to electromagnetic fields and risk of childhood leukemia: a population-based case-control study in two Italian provinces. [Abstract in Atti di Convegno]
Malagoli, C; Filippini, T; Storani, S; Violi, F; Fabbi, S; Teggi, S; Ballotti, E; Zanichelli, P; Poli, M; Bruni, M; Sesti, D; Notari, B; Palazzi, G; Vinceti, M.
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2018 - Exposure to high voltage power lines and risk of childhood leukaemia: an Italian population-based case-control study. [Abstract in Atti di Convegno]
Violi, F; Malagoli, C; Filippini, T; Fabbi, S; Teggi, S; Ballotti, E; Zanichelli, P; Poli, M; Bruni, M; Sesti, D; Notari, B; Vinceti, M.
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2018 - Food contamination from the food packaging metals aluminum and tin: estimation of their dietary exposure in an Italian adult community. [Abstract in Atti di Convegno]
Filippini, T; Tancredi, Stefano; Malagoli, C; Cilloni, S; Malavolti, M; Violi, F; Vescovi, L; Bargellini, A; Vinceti, M.
abstract

2018 Scientific meeting Italian Association for the Study of Trace Elements in living Organisms – AISETOV. Ozzano Emilia, Bologna, October 12, 2018 (ISBN: 9788894309812)

2018 - Genetic polymorphisms in amyotrophic lateral sclerosis: Evidence for implication in detoxification pathways of environmental toxicants [Articolo su rivista]
Dardiotis, Efthimios; Siokas, Vasileios; Sokratous, Maria; Tsouris, Zisis; Michalopoulou, Amalia; Andravizou, Athina; Dastamani, Metaxia; Ralli, Styliani; Vinceti, Marco; Tsatsakis, Aristidis; Hadjigeorgiou, Georgios M.
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2018 - Guidance for the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Heng, Leng; Valtueña Martínez, Silvia; Siani, Alfonso
abstract

EFSA asked the Panelon Dietetic Products, Nutrition and Allergies (NDA) to update the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. The update takes into accounts experiences gained with evaluation of additional health claim applications related to antioxidants, oxidative damage and cardiovascular health, and the information collected from a Grant launched in 2014. This guidance is intended to assist applicants in preparing applications for the authorisation of health claims related to the antioxidants, oxidative damage and cardiovascular health. The document was subject to public consultation (from 12 July to 3 September 2017). This document supersedes the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. It is intended that the guidance will be further updated as appropriate in the light of experience gained from the evaluation of health claims.

2018 - Guidance on the scientific requirements for health claims related to muscle function and physical performance: (Revision 1) [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Willatts, Peter; Martin, Ambroise; Strain, John Joseph; Heng, Leng; Valtueña Martínez, Silvia; Siani, Alfonso
abstract

EFSA has asked the Panel on Nutrition, Novel Foods and Food Allergens (NDA) to update the guidance on the scientific requirements for health claims related to physical performance published in 2012. The update takes into account the experience gained by the NDA Panel with the evaluation of additional health claim applications, changes introduced to the general scientific guidance for stakeholders for health claims applications and information collected from a grant launched in 2014 which aimed at gathering information in relation to claimed effects, outcome variables and methods of measurement in the context of the scientific substantiation of health claims. The guidance is intended to assist applicants in preparing applications for the authorisation of health claims related to muscle function and physical performance. The draft guidance was subject to public consultation from 16 July to 2 September 2018. This document supersedes the guidance on the scientific requirements for health claims related to physical performance published in 2012. It is intended that the guidance will be further updated as appropriate in the light of experience gained from the evaluation of health claims.

2018 - I fattori ambientali di rischio delle malattie neurodegenerative: prospettive e metodologie di ricerca epidemiologica. [Abstract in Atti di Convegno]
Vinceti, M; Malagoli, C; Filippini, T
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2018 - Impact of referral sources and waiting times on the failure to quit smoking: One-year follow-up of an italian cohort admitted to a smoking cessation service [Articolo su rivista]
Borsari, Lucia; Storani, Simone; Malagoli, Carlotta; Filippini, Tommaso; Tamelli, Marco; Malavolti, Marcella; Nicolini, Fausto; Vinceti, Marco
abstract

In Italy, the National Health Service offers specialized evidence-based support to smokers who would like to quit through smoking cessation (SC) services. We conducted a two-year prospective study, involving all 288 subjects treated for smoking cessation at the SC service of Reggio Emilia, to assess the association of referral sources and waiting times with the risk of treatment failure, by following participants up to one year after the quit date. We performed Cox-regression analysis, including demographic and smoking-related characteristics as confounding variables. The treatment failure rate at 12 months was 59.4% (171/288), including only 12 subjects lost to follow-up. The main mode of entry was self-referral (42.4%), followed by 32.6% from general practice, 17.4% from hospital and 7.6% from other sources. Only 27.8% participants were involved in the SC-program within 60 days of the first contact, as the guidelines suggest. The risk of treatment failure at 12 months showed little association with the type of referral source, while it correlated with waiting times ≥ 60 days (hazard ratio = 1.59; 95% confidence interval 1.10-2.29). This study provides evidence of long-term high quit rates from a SC service, with few subjects lost to follow-up and biochemical verification of almost all abstinent subjects. Timeliness in care provision could further improve the outcome.

2018 - Intake of arsenic and mercury from fish and seafood in a Northern Italy community [Articolo su rivista]
Filippini, Tommaso; Malavolti, Marcella; Cilloni, Silvia; Wise, Lauren A.; Violi, Federica; Malagoli, Carlotta; Vescovi, Luciano; Vinceti, Marco
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Regular consumption of fish is generally recommended by authorities because fish is an important source of essential nutrients. However, the presence of potentially toxic contaminants in fish has raised many concerns about the food's safety for human health. In the present study, we used a validated semi-quantitative food frequency questionnaire to assess the dietary habits of a representative sample of 719 individuals (319 males and 400 females) aged 18–87 years residing in Northern Italy. We estimated weekly dietary intakes of Arsenic (As) and Mercury (Hg), and we compared them with safety standards set by the European Food Safety Authority. In this population, fish was the main contributor to As and Hg intake. The highest levels of As were in sardine, sole/flounder and cephalopods, and of Hg in the biggest, predatory fish. About the other foods, cereals were the second contributor to the intake of these elements, especially rice for As and bread for Hg, and high levels of As and Hg were also found in mushrooms, coffee and wine. Average weekly intake of both contaminants was below recommended safety limits.

2018 - Investigating the environmental risk factors for childhood leukaemia: the research activity at the University of Modena and Reggio Emilia, Northern Italy. [Abstract in Atti di Convegno]
Vinceti, M; Malagoli, C; Filippini, T; Violi, F; Cilloni, S; Malavolti, M; Borsari, L; Storani, S; Arcolin, E; Palazzi, G; Teggi, S; Fabbi, S; Costanzini, Sofia; Ghermandi, G; Bagni, Enrico
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2018 - Is there a relation between birth of month and risk of childhood leukaemia? A case-control study in two Italian provinces. [Abstract in Atti di Convegno]
Malavolti, M; Filippini, T; Malagoli, C; Cilloni, S; Borsari, L; Vinceti, M.
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2018 - Joint Effect of Maternal Tobacco Smoking and Pregestational Diabetes on Preterm Births and Congenital Anomalies: A Population-Based Study in Northern Italy [Articolo su rivista]
Borsari, Lucia; Malagoli, Carlotta; Werler, Martha M.; Rothman, Kenneth J.; Malavolti, Marcella; Rodolfi, Rossella; De Girolamo, Gianfranco; Nicolini, Fausto; Vinceti, Marco
abstract

Smoking and pregestational diabetes (PGD) are recognized risk factors for adverse pregnancy outcomes, but to date, no population-based study has investigated their joint effects. Using hospital discharges, we identified all women with PGD delivering in Emilia-Romagna region during 2007-2010 matched 1: 5 with parturients without diabetes. Our study endpoints were preterm births and congenital anomalies. We measured interaction between PGD and maternal smoking, by calculating excess prevalence and prevalence ratio due to interaction, relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (S). Analyses were performed in the overall study population and in the subgroup whose PGD was validated through diabetes registers. The study included 992 women with PGD (10.5% smokers) and 4788 comparison women (11.9% smokers). The effects of PGD and maternal tobacco smoking were greater than additive for both preterm birth (excess prevalence due to interaction = 11.7%, excess ratio due to interaction = 1.5, RERI = 2.39, AP = 0.51, S = 2.82) and congenital anomalies (excess prevalence due to interaction = 2.2%, excess ratio due to interaction = 1.3, RERI = 1.33, AP = 0.49, S = 5.03). Joint effect on both endpoints was confirmed in the subgroup whose PGD status was validated. In conclusion, we found that maternal tobacco smoking and PGD intensify each other's effect on preterm birth and congenital anomalies.

2018 - Livelli di assunzione di selenio in un campione di popolazione italiana e correlazione con parametri metabolici ed ormonali: uno studio trasversale in Emilia Romagna. [Abstract in Atti di Convegno]
Vinceti, M; Lasagni, D; Bruzziches, F; Baraldi, C; Malagoli, C; Grioni, S; Sieri, S; Santachiara, Alessia; De Luca, T; Pertinez, T; Baricchi, R; Filippini, T.
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2018 - Livelli di esposizione alimentare a cadmio e correlazione con parametri metabolici ed ormonali: uno studio cross-sectional in una popolazione emiliana. [Abstract in Atti di Convegno]
Filippini, T; Lasagni, D; Bruzziches, F; Baraldi, C; Malavolti, M; Grioni, S; Sieri, S; Santachiara, A; De Luca, T; Pertinez, T; Baricchi, R; Vinceti, M
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2018 - L‐carnitine and contribution to normal lipid metabolism: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (J. J. ); Siani, Alfonso
abstract

Following an application from Lonza Ltd., submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No1924/2006 via the Competent Authority of Germany, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to L-carnitine and normal lipid metabolism. The food that is proposed as the subject of the health claim is L-carnitine. The Panelconsiders that L-carnitine is sufficiently characterised. The claimed effect proposed by the applicant is normal lipid metabolism'. The target population proposed by the applicant is the general population. The Panelconsiders that contribution to normal lipid metabolism is a beneficial physiological effect. The applicant proposes that the claim submitted with this application is based on the essentiality of a nutrient. The Panelconsiders that the evidence provided does not establish that dietary L-carnitine is required to maintain normal lipid metabolism in the target population, for which the claim is intended. The Panelconcludes that a cause and effect relationship has not been established between the consumption of L-carnitine and contribution to normal lipid metabolism in the target population.

2018 - Magnesium citrate malate as a source of magnesium added for nutritional purposes to food supplements [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Dean, Tara; Engel, Karl-Heinz; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Pöting, Annette; Sanz, Yolanda; Schlatter, Josef Rudolf; Germini, Andrea; van Loveren, Henk
abstract

The present scientific opinion deals with the assessment of the bioavailability of magnesium, from the proposed nutrient source, magnesium citrate malate (MgCM), when added for nutritional purposes to food supplements. MgCM is a mixed salt consisting of magnesium cations and citrate and malate anions, and with a magnesium content of 12–15%. MgCM is proposed to be used in food supplements that are intended to provide up to 300–540 mg/day magnesium. The data provided demonstrate that the production process results in batches of MgCM that comply with the product specifications and that the product is stable throughout its proposed shelf life. The human studies provided demonstrate that magnesium from MgCM is bioavailable. However, the extent of its bioavailability per se or compared to other magnesium sources cannot be established due to the lack of an appropriate magnesium source as a comparator in the studies provided or relevant kinetic data for magnesium. One publication provided in the dossier reported that supplementation with MgCM decreases calcium absorption, but this finding was not supported by publications on different magnesium salts and therefore the Panel could not draw conclusions from this finding. The Panel concludes that MgCM is a source from which magnesium is bioavailable, but the extent of its bioavailability cannot be established. The Panel notes that at the proposed maximum use levels of MgCM, the existing tolerable upper intake level for magnesium in nutritional supplements, water, or added to food and beverages (250 mg/day) is exceeded.

2018 - Maternal pregestational diabetes and risk of childhood leukaemia in the offspring: a population-based study in Northern Italy. [Abstract in Atti di Convegno]
Borsari, L; Malagoli, C; della Torre, F; Palazzi, G; Rodolfi, R; Filippini, T; Violi, F; Cilloni, S; Malavolti, M; Nicolini, F; Vinceti, M.
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2018 - NWT‐02, a fixed combination of lutein, zeaxanthin and docosahexaenoic acid in egg yolk and reduction of the loss of vision: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (J. J. ); Siani, Alfonso
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Following an application from Newtricious R&D B.V., submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panelon Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to NWT-02 and a reduction of the loss of vision. The food proposed by the applicant as the subject of the health claim is NWT-02. NWT-02 is standardised by its content in lutein (>= 1.10 mg), zeaxanthin (>= 0.20 mg) and docosahexaenoic acid (DHA) (>= 170 mg). The Panel considers that the food/constituent that is the subject of the health claim, NWT-02, a fixed combination of lutein, zeaxanthin and docosahexaenoic acid in egg yolk, is sufficiently characterised. The claimed effect proposed by the applicant is 'reduces loss of vision'. The target population proposed by the applicant is 'healthy adults over 50 years of age'. The Panel considers that a reduction of the loss of vision is a beneficial physiological effect. The applicant provided two human intervention studies for the scientific substantiation of the claim. The Panel considers that the only study from which conclusions can be drawn for the scientific substantiation of the claim did not show an effect of NWT-02 on vision. The Panel concludes that a cause and effect relationship has not been established between the consumption of NWT-02, a fixed combination of lutein, zeaxanthin and docosahexaenoic acid in egg yolk, and a reduction of the loss of vision.

2018 - Non-chromosomal congenital anomalies and risk of childhood leukaemia: An Italian population-based case-control study [Abstract in Atti di Convegno]
Malagoli, C; Filippini, T; Malavolti, M; Volpato, S; Astolfi, G; Palazzi, G; Vinceti, M
abstract

Introduction: The association between chromosomal conditions such as Down syndrome and increased CL risk of childhood leukemia (CL) is well established, while the association between non-chromosomal birth defects is far less clear. We conducted a population-based case-control study in two provinces of Northern Italy to evaluate CL risk in children born with non-chromosomal anomalies. Methods: We identified all leukemia cases diagnosed in children (<15 years) in the Modena and Reggio Emilia provinces through the Italian National Childhood Cancer Register in the period 1998-2013. For each case, we randomly selected four population controls matched by age, sex, province of residence and calendar year. Through the Emilia-Romagna Region population-based Birth Defects Registry, we retrieved information about occurrence and type of congenital malformations for each study subject. We computed the odds ratio (OR) of CL for children affected by non-chromosomal birth defects using a multivariable conditional logistic regression model. Results: We eventually included 132 cases and 528 controls, 5 of which (2 cases and 3 controls) were affected by a non-chromosomal congenital malformation. We found an increased risk of CL in children born with non-chromosomal anomalies, with an OR of 2.7 (95% confidence interval 0.4–16.0). Conclusions: Despite the limited stability of the risk estimates and the risk of unmeasured and residual confounding, our study appears to suggest an association between non-chromosomal birth defects and risk of childhood leukemia.

2018 - Non-chromosomal congenital anomalies and risk of childhood leukaemia: a Italian population-based case-control study. [Abstract in Atti di Convegno]
Malagoli, C; Filippini, T; Malavolti, M; Volpato, S; Astolfi, G; Palazzi, G; Vinceti, M.
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2018 - Outdoor air pollution and risk of conversion from mild cognitive impairment to dementia: a cohort study. [Abstract in Atti di Convegno]
Filippini, T; Chiari, A; Zamboni, G; Tondelli, M; Vinceti, G; Maffeis, G; Cherubini, A; Malagoli, C; Vinceti, M.
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2018 - Proximity to Overhead Power Lines and Childhood Leukemia: An International Pooled Analysis [Abstract in Atti di Convegno]
Amoon, A; Crespi, Cm; Ahlbom, A; Bhatnagar, M; Bray, I; Bunch, K; Clavel, J; Feychting, M; Hemon, D; Johansen, C; Kreis, C; Malagoli, C; Marquant, F; Pedersen, C; Raaschou-Nielsen, O; Roosli, M; Spycher, B; Sudan, M; Swanson, J; Tittarelli, A; Tuck, D; Tynes, T; Vergara, X; Vinceti, M; Wünsch-Filho, V; Kheifets, L.
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2018 - Proximity to overhead power lines and childhood leukemia: an international pooled analysis [Articolo su rivista]
Amoon, Aryana; Crespi, Catherine; Ahlbom, Anders; Bhatnagar, Megha; Bray, Issy; Bunch, Kathryn; Clavel, Jacqueline; Feychting, Maria; Hemon, Denis; Johansen, Christoffer; Kreis, Christian; Malagoli, Carlotta; Marquant, Fabienne; Pedersen, Camilla; Raaschou-Nielsen, Ole; Roosli, Martin; Spycher, Ben; Sudan, Madhuri; Swanson, John; Tittarelli, Andrea; Tuck, Dierdre; Tynes, Tore; Vergara, Ximena; Vinceti, Marco; Wunsch Filho, Victor; Kheifets, Leeka
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2018 - Residence near electrical transformer rooms and risk of childhood leukaemia: an Italian population-based case-control study. [Abstract in Atti di Convegno]
Filippini, T; Storani, S; Malagoli, C; Fabbi, S; Teggi, S; Sesti, D; Notari, B; Zanichelli, P; Poli, M; Palazzi, G; Vinceti, M.
abstract

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2018 - Riluzole and other prognostic factors in ALS: a population-based registry study in Italy [Articolo su rivista]
Mandrioli, Jessica; Malerba, Sara Angela; Beghi, Ettore; Fini, Nicola; Fasano, Antonio; Zucchi, Elisabetta; De Pasqua, Silvia; Guidi, Carlo; Terlizzi, Emilio; Sette, Elisabetta; Ravasio, Alessandro; Casmiro, Mario; Salvi, Fabrizio; Liguori, Rocco; Zinno, Lucia; Handouk, Yasmin; Rizzi, Romana; Borghi, Annamaria; Rinaldi, Rita; Medici, Doriana; Santangelo, Mario; Granieri, Enrico; Mussuto, Vittoria; Aiello, Marina; Ferro, Salvatore; Vinceti, Marco
abstract

In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS cases in Emilia Romagna Region (ERR), Italy.

2018 - Risk of amyotrophic lateral sclerosis and passive residential exposure to pesticides: comparison of questionnaire-based with gis-based exposure assessment methods [Abstract in Rivista]
Filippini, Tommaso; Malagoli, Carlotta; Costanzini, Sofia; Violi, Federica; Cilloni, Silvia; Teggi, Sergio; Fiore, Maria; Ferrante, Margherita; Vinceti, Marco
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2018 - Safety of Allanblackia seed oil for extended uses in vegetable oils and milk and in yellow fat and cream-based spreads up to 30% (w/w) [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; McArdle, Harry J; Naska, Androniki; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl-Heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef; Gelbmann, Wolfgang; van Loveren, Henk
abstract

In 2007, the EFSA NDA Panel concluded that Allanblackia seed oil obtained from the seeds of Allanblackia trees is safe for human consumption under the proposed conditions of use. Due to its high contents of stearic-oleic-stearic and stearic-oleic-oleic triglycerides, which made the oil suitable as a ‘hardstock’ component, the applicant applied for its use as a novel food (NF) ingredient in yellow fat and cream-based spreads at a level of 20% (w/w). In this application, the applicant seeks (1) to increase the authorised maximum use level (i.e. 20% w/w) in yellow fat spreads and cream-based spreads to 30% (w/w) and (2) the use of this NF in mixes of vegetable oils and milk up to a maximum use level of 30% (w/w). (3) The applicant proposes also some changes in the specifications of the NF, although he noted that the oil is collected, extracted and refined using the same processes that are currently used for other edible vegetable oils and which have been evaluated in the original application assed by EFSA in 2007. According to the information provided by the applicant, the production process and the composition of the NF do not change. The Panel notes that the revised specification limits on trans-fatty acid (TFA), unsaponifiable matter, peroxide value are similar to those for other edible oils and fats. The applicant also indicated that he had performed an updated comprehensive literature search using several different databases, but no preclinical studies or human studies on Allanblackia seed oil were identified which have not been provided for the previous EFSA assessment in 2007. The Panel notes that the proposed extended uses would increase the potential intake of the NF, which is considered not to be nutritionally disadvantageous. The Panel concludes that Allanblackia seed oil is safe at the extended uses and use level.

2018 - Safety of Whey basic protein isolates as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl–heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Amundsen, Mathias; van Loveren, Henk
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2018 - Safety of d-ribose as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry; Naska, Androniki; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl-Heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Germini, Andrea; Van Loveren, Henk
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on D-ribose as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The applicant intends to market the NF as ingredient in a variety of foods, food supplements and in certain foods for specific groups. The NF is produced by fermentation using a transketolase-deficient strain of Bacillus subtilis and marketed as Bioenergy Ribose™. The information provided on the batch-to-batch variability, specifications, stability, production process and history of the organism used as a source of the NF is sufficient and does not raise safety concerns. The Panel considers that the effects observed in a subchronic toxicity study in rats could be the consequence of nutritional imbalances, but toxicological effects could not be ruled out; from this study, the Panel derived a No observed adverse effect level (NOAEL) of 3.6 g/kg body weight (bw) per day. From the human studies indicating a potential decrease in glucose levels and/or the occurrence of transient symptomatic hypoglycaemia at intakes of 10 g of d-ribose, the Panel defined 70 mg/kg bw per day as the NOAEL with respect to hypoglycaemia that can be considered applicable for adults. For children, the Panel acknowledges the lack of human data directly relevant for this population group. Based on the NOAEL derived from the subchronic toxicity study in rats, an acceptable level of intake of 36 mg/kg bw per day was defined that would also take into account the potentially increased sensitivity of certain population groups to hypoglycaemia. The Panel concludes that the NF is safe for the general population at intake levels up to 36 mg/kg bw per day and considers that the safety of the NF at the intended uses and use levels as proposed by the applicant has not been established.

2018 - Safety of egg membrane hydrolysate as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl‐heinz; Marchelli, Rosangela; Pöting, Annette; Schlatter, Josef Rudolf; Ackerl, Reinhard; van Loveren, Henk
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2018 - Safety of shrimp peptide concentrate as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara Ann; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; McArdle, Harry J; Naska, Androniki; Neuhäuser-Berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl-Heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Matijević, Leonard; van Loveren, Henk
abstract

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on shrimp peptide concentrate as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a peptide mixture obtained by an enzymatic proteolysis from northern shrimp (Pandalus borealis) shells and heads. The information provided on the composition, specifications, batch-to-batch variability, stability and production process of the NF is sufficient and does not raise safety concerns. The intention of the applicant is to use this NF as an ingredient in food supplements and to market it to adult consumers at a maximum proposed level of intake of 1,200 mg/day (corresponding to 17 mg/kg body weight (bw) per day for a 70 kg person). There are no concerns with regard to genotoxicity. The available human data do not raise safety concerns. Considering the no observed adverse effect level (NOAEL) of 2,000 mg/kg bw per day from a 90-day repeated-dose oral toxicity study, the maximum proposed level of intake and the nature of the NF, the Panel concludes that the margin of exposure (of 117) is sufficient. The Panel concludes that the NF, shrimp peptide concentrate, is safe to be used as a food supplement at the proposed maximum dose of 1,200 mg/day. The target population is adults. The Panel considered that the conclusion on the safety of the NF could not have been reached without the data from the unpublished study report on repeated-dose 90-day oral toxicity and from the unpublished study reports on two human studies.

2018 - Safety of xylo‐oligosaccharides (XOS) as a novel food pursuant to Regulation (EU) 2015/2283 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Vinceti, Marco; Willatts, Peter; Engel, Karl‐heinz; Marchelli, Rosangela; Pöting, Annette; Poulsen, Morten; Schlatter, Josef Rudolf; Turla, Emanuela; van Loveren, Henk
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2018 - Selenium Neurotoxicity and Amyotrophic Lateral Sclerosis: An Epidemiologic Perspective [Capitolo/Saggio]
Filippini, Tommaso; Michalke, Bernhard; Mandrioli, Jessica; Tsatsakis, Aristidis M.; Weuve, Jennifer; Vinceti, Marco
abstract

.Selenium exposure has been proposed as possible risk factor for amyotrophic lateral sclerosis (ALS), due to the selective toxicity of the trace element, especially in its inorganic forms, toward motor neurons. The epidemiological evidence, in association with laboratory and veterinary findings, linking selenium exposure and ALS risk was originally suggested by the increased ALS mortality in an area characterized by high selenium content in soil, and subsequently confirmed in an Italian community. The latter was unintentionally exposed to high levels of inorganic hexavalent selenium through drinking water, and subsequently showed an increased incidence for neurodegenerative diseases, including ALS and Parkinson’s disease. Review of the epidemiological studies addressing the association between selenium exposure and ALS risk points out important lessons that should be considered in future research, in order to avoid misleading and biased evaluations of selenium’s effects. These include the use of central nervous system indicator of exposure such as cerebrospinal fluid, and the implementation of speciation analysis, due to the different toxic and nutritional properties of the various selenium compounds.

2018 - Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Rothman, Kenneth J
abstract

In 2007, supplementation with the trace element selenium in a trial was unexpectedly found to be associated with an excess risk of type 2 diabetes. Given the concerns raised by these findings and the large number of recent studies on this topic, we reviewed the available literature with respect to this possible association. In this paper, we assessed the results of both experimental and nonexperimental epidemiologic studies linking selenium with type 2 diabetes incidence. Through a systematic literature search, we retrieved 50 potentially eligible nonexperimental studies and 5 randomized controlled trials published through June 11, 2018. To elucidate the possible dose-response relation, we selected for further analysis those studies that included multiple exposure levels and serum or plasma levels. We computed a pooled summary risk ratio (RR) of diabetes according to selenium exposure in these studies. We also computed a RR for diabetes incidence following supplementation with 200 µg/day of selenium compared with placebo in trials. In the nonexperimental studies, we found a direct relation between selenium exposure and risk of diabetes, with a clear and roughly linear trend in subjects with higher plasma or serum selenium levels, with RR at 140 µg/L of selenium exposure compared with a referent category of < 45 µg/L equal to 3.6 [95% confidence interval (CI) 1.4-9.4]. A dose-response meta-analysis focusing on studies with direct assessment of dietary selenium intake showed a similar trend. In experimental studies, selenium supplementation increased the risk of diabetes by 11% (RR 1.11, 95% CI 1.01-1.22) compared with the placebo-allocated participants, with a higher RR in women than in men. Overall, results from both nonexperimental and experimental studies indicate that selenium may increase the risk of type 2 diabetes across a wide range of exposure levels. The relative increase in risk is small but of possible public health importance because of the high incidence of diabetes and the ubiquity of selenium exposure.

2018 - Selenium for preventing cancer [Articolo su rivista]
Vinceti, Marco; Filippini, Tommaso; Del Giovane, Cinzia; Dennert, Gabriele; Zwahlen, Marcel; Brinkman, Maree; Zeegers, Maurice P. A.; Horneber, Markus; D'Amico, Roberto; Crespi, Catherine M.
abstract

Background: This review is the third update of the Cochrane review "Selenium for preventing cancer". Selenium is a naturally occurring element with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancer. Objectives: To gather and present evidence needed to address two research questions: 1. What is the aetiological relationship between selenium exposure and cancer risk in humans?2. Describe the efficacy of selenium supplementation for cancer prevention in humans. Search methods: We updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6), as well as searches of clinical trial registries. Selection criteria: We included randomised controlled trials (RCTs) and longitudinal observational studies that enrolled adult participants. Data collection and analysis: We performed random-effects (RE) meta-analyses when two or more RCTs were available for a specific outcome. We conducted RE meta-analyses when five or more observational studies were available for a specific outcome. We assessed risk of bias in RCTs and in observational studies using Cochrane's risk assessment tool and the Newcastle-Ottawa Scale, respectively. We considered in the primary analysis data pooled from RCTs with low risk of bias. We assessed the certainty of evidence by using the GRADE approach. Main results: We included 83 studies in this updated review: two additional RCTs (10 in total) and a few additional trial reports for previously included studies. RCTs involved 27,232 participants allocated to either selenium supplements or placebo. For analyses of RCTs with low risk of bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95% confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high-certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80 to 1.30; 1 study, 17,444 participants). For the most frequently investigated site-specific cancers, investigators provided little evidence of any effect of selenium supplementation. Two RCTs with 19,009 participants indicated that colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69 to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2 studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2 studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1 study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2 studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14; 4 studies, 18,942 participants). Certainty of the evidence was high for all of these cancer sites, except for breast cancer, which was of moderate certainty owing to imprecision, and non-melanoma skin cancer, which we judged as moderate certainty owing to high heterogeneity. RCTs with low risk of bias suggested increased melanoma risk. Results for most outcomes were similar when we included all RCTs in the meta-analysis, regardless of risk of bias. Selenium supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to 1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to 1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers showed limited changes compared with estimates from high-quality studies alone, except for liver cancer, for which results were reversed. In the largest trial, the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks of alopecia and dermatitis, and for participants with highest background selenium status, supplementation also increased risk of high-grade prostate cancer. RCTs showed a slightly increased risk of type 2 diabetes associated with supplementation. A hypothesis generated by the Nutritional Prevention of Cancer Trial - that individu

2018 - Statement on the safety of d-ribose [Articolo su rivista]
Turck, Dominique; Castenmiller, Jacqueline; De Henauw, Stefaan; Hirsch-Ernst, Karen Ildico; Kearney, John; Knutsen, Helle Katrine; Maciuk, Alexandre; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Pelaez, Carmen; Pentieva, Kristina; Siani, Alfonso; Thies, Frank; Tsabouri, Sophia; Vinceti, Marco; Dean, Tara; Engel, Karl Heinz; Heinonen, Marina; Marchelli, Rosangela; Neuhäuser-Berthold, Monika; Poulsen, Morten; Pöting, Annette; Sanz, Yolanda; Schlatter, Josef Rudolf; Germini, Andrea; van Loveren, Henk
abstract

In 2018, the EFSA NDA Panel adopted the Scientific Opinion on the safety of d-ribose as a novel food pursuant to Regulation (EU) 2015/2283 when used in a variety of food, concluding that d-ribose is safe for the general population at intake levels up to 36 mg/kg body weight (bw) per day, but that its safety at the intended uses and use levels as proposed by the applicant could not be established. Following a request from the European Commission, the EFSA NDA Panel was asked to carry out a supplementary safety assessment for d-ribose by considering the new proposed uses and use levels submitted by the applicant. In order to address the present mandate, an intake assessment was carried out based on individual data from the EFSA Comprehensive European Food Consumption Database. Intakes were estimated for all age groups of the general population. The resulting ranges for the mean and high-level estimated intakes of d-ribose for all the population groups, including the target population groups, did not exceed the acceptable level of intake for the general population previously defined, i.e. 36 mg/kg bw per day, except for one survey on adolescents where the mean and 95th percentile of the intake estimates were 8.6 and 39.4 mg/kg bw per day, respectively. The Panel concludes that the novel food, d-ribose, is safe under the new proposed conditions of use.

2018 - Symbiosal® and lowering of blood pressure and reduced risk of hypertension: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (J. J. ); Siani, Alfonso
abstract

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2018 - The new-old exposure to lead: assessment of food contamination and estimation of dietary intake in a Northern Italy population. [Abstract in Atti di Convegno]
Filippini, T; Malavolti, M; Cilloni, S; Violi, F; Malagoli, C; Vescovi, L; Vinceti, M.
abstract

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2018 - Traffic-related air pollution and risk of childhood leukaemia: A systematic review and dos-response meta-analysis [Abstract in Atti di Convegno]
Vinceti, M; Filippini, T
abstract

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2018 - Traffic-related air pollution and risk of childhood leukaemia: A systematic review and dose-response meta-analysis. [Abstract in Atti di Convegno]
Vinceti, M; Filippini, T
abstract

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2018 - Update of the tolerable upper intake level for vitamin D for infants [Articolo su rivista]
Turck, Dominique; Bresson, Jean-Louis; Burlingame, Barbara; Dean, Tara; Fairweather-Tait, Susan; Heinonen, Marina; Hirsch-Ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Siani, Alfonso; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Loveren, Henk Van; Vinceti, Marco; Willatts, Peter; Fewtrell, Mary; Lamberg-Allardt, Christel; Przyrembel, Hildegard; Arcella, Davide; Dumas, Céline; Fabiani, Lucia; Martino, Laura; Tomcikova, Daniela; Neuhäuser-Berthold, Monika
abstract

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to revise the tolerable upper intake level (UL) for vitamin D for infants (≤ 1 year) set in 2012. From its literature review, the Panel concluded that the available evidence on daily vitamin D intake and the risk of adverse health outcomes (hypercalciuria, hypercalcaemia, nephrocalcinosis and abnormal growth patterns) cannot be used alone for deriving the UL for infants. The Panel conducted a meta-regression analysis of collected data, to derive a dose–response relationship between daily supplemental intake of vitamin D and mean achieved serum 25(OH)D concentrations. Considering that a serum 25(OH)D concentration of 200 nmol/L or below is unlikely to pose a risk of adverse health outcomes in infants, the Panel estimated the percentage of infants reaching a concentration above this value at different intakes of vitamin D. Based on the overall evidence, the Panel kept the UL of 25 μg/day for infants aged up to 6 months and set a UL of 35 μg/day for infants 6–12 months. The Panel was also asked to advise on the safety of the consumption of infant formulae with an increased maximum vitamin D content of 3 μg/100 kcal (Commission Delegated Regulation (EU) 2016/127 repealing Directive 2006/141/EC in 2020). For infants aged up to 4 months, the intake assessment showed that the use of infant formulae containing vitamin D at 3 μg/100 kcal may lead some infants to receive an intake above the UL of 25 μg/day from formulae alone without considering vitamin D supplemental intake. For infants aged 4–12 months, the 95th percentile of vitamin D intake (high consumers) estimated from formulae and foods fortified or not with vitamin D does not exceed the ULs, without considering vitamin D supplemental intake.

2018 - Xanthohumol in XERME®, a xanthohumol‐enriched roasted malt extract, and protection of DNA from oxidative damage: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 [Articolo su rivista]
Turck, Dominique; Bresson, Jean‐louis; Burlingame, Barbara; Dean, Tara; Fairweather‐tait, Susan; Heinonen, Marina; Hirsch‐ernst, Karen Ildico; Mangelsdorf, Inge; Mcardle, Harry J; Naska, Androniki; Neuhäuser‐berthold, Monika; Nowicka, Grażyna; Pentieva, Kristina; Sanz, Yolanda; Sjödin, Anders; Stern, Martin; Tomé, Daniel; Van Loveren, Henk; Vinceti, Marco; Willatts, Peter; Martin, Ambroise; Strain, Sean (JJ); Siani, Alfonso
abstract

Following an application from TA-XAN AG, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Germany, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to xanthohumol in XERME (R), a xanthohumol-enriched roasted malt extract, and protection of DNA from oxidative damage. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The food proposed by the applicant as the subject of the health claim is xanthohumol in XERME (R), a xanthohumol-enriched roasted malt extract. The Panel considers that xanthohumol in XERME (R), a xanthohumol-enriched roasted malt extract, is sufficiently characterised. The claimed effect proposed by the applicant is helps to maintain the integrity of DNA and protects against oxidative damage in the cells of the body'. The Panel considers that protection of DNA from oxidative damage is a beneficial physiological effect. The only human study from which conclusions can be drawn for the scientific substantiation of the claim did not show an effect of xanthohumol in XERME (R) on the protection of DNA from oxidative damage. In the absence of evidence for an effect of xanthohumol in XERME (R) on the protection of DNA from oxidative damage, the studies provided by the applicant on the proposed mechanisms by which the food/constituent could exert the claimed effect were not considered by the Panel for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of xanthohumol in XERME (R), a xanthohumol-enriched roasted malt extract, and protection of DNA from oxidative damage.

2017 - 112. Bonvicini F, Fornaciari R, Casoni C, Marchesi C, Monici L, Cilloni S, Malagoli C, Greci M, Vinceti M. Epidemiologia della forma attiva e latente di tubercolosi in un gruppo di immigrati irregolari visitati presso il centro della salute per la famiglia straniera (CSFS) dell’azienda Ausl di Reggio Emilia. 50° Congresso Nazionale SItI. Torino 20-22 Novembre 2017 [Abstract in Atti di Convegno]
Bonvicini, F; Fornaciari, R; Casoni, C; Marchesi, C; Monici, L; Cilloni, S; Malagoli, C; Greci, M; Vinceti, M.
abstract

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2017 - A fixed carbohydrate: protein ratio <= 1.8 on an energy basis consumed in the context of an energy-restricted diet and reduction of body weight: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006. [Articolo su rivista]
Turck, D; Bresson, Jl; Burlingame, B; Dean, T; Fairweather Tait, S; Heinonen, M; Hirsch Ernst, Ki; Mangelsdorf, I; Mcardle, Hj; Naska, A; Neuhauser Berthold, M; Nowicka, G; Pentieva, K; Sanz, Y; Sjodin, A; Stern, M; Tome, D; Van Loveren, H; Vinceti, Marco; Willatts, P; Martin, A; Joseph, J; Siani, A.
abstract

Following an application from Marks and Spencer PLC, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to a CHO:P ratio &lt;= 1.8 on an energy basis in the context of an energy-restricted diet and body weight. The Panel considers that the food/constituent that is the subject of the health claim is sufficiently characterised. The Panel also considers that reduction of body weight in the context of an energy-restricted diet is a beneficial physiological effect. The target population proposed by the applicant is 'adults between the ages of 18 and 70 years with excess body weight'. No conclusions could be drawn from two unpublished studies investigating the effect of ready-to-eat meals with a CHO: P ratio &lt;= 1.8 on body weight. The remaining 14 human intervention studies investigated the effect of diets targeting a CHO: P ratio &lt;= 1.8 as compared to diets targeting a CHO: P ratio &gt;= 3.0 on overweight and obese adults in the context of energy restriction. Four out of seven studies lasting &lt; 12 weeks reported an effect of a CHO: P ratio &lt;= 1.8 on body weight in overweight/obese subjects, whereas no significant effect was observed in six out of the seven studies lasting 12 weeks or more. The Panel considers that these studies do not provide evidence for a sustained effect of the food/constituent on body weight. The Panel concludes that a cause and effect relationship has not been established between the consumption of a fixed CHO: P ratio &lt;= 1.8 on an energy basis consumed in the context of an energy-restricted diet and reduction of body weight. (C) 2017 European Food Safety Authority.

2017 - A selenium species in cerebrospinal fluid predicts conversion to Alzheimer's dementia in persons with mild cognitive impairment [Articolo su rivista]
Vinceti, Marco; Chiari, Annalisa; Eichmüller, Marcel; Rothman, Kenneth J; Filippini, Tommaso; Malagoli, Carlotta; Weuve, Jennifer; Tondelli, Manuela; Zamboni, Giovanna; Nichelli, Paolo F; Michalke, Bernhard
abstract

Little is known about factors influencing progression from mild cognitive impairment to Alzheimer's dementia. A potential role of environmental chemicals and specifically of selenium, a trace element of nutritional and toxicological relevance, has been suggested. Epidemiologic studies of selenium are lacking, however, with the exception of a recent randomized trial based on an organic selenium form.

2017 - Air dispersion modelling for the evaluation of population exposure to pollutants emitted by complex areal sources. [Abstract in Atti di Convegno]
Costanzini, Sofia; Teggi, Sergio; Bigi, Alessandro; Ghermandi, Grazia; Filippini, Tommaso; Malagoli, Carlotta; Vinceti, Marco; Nannini, R.
abstract

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2017 - Assessment of selenium levels and risk factors for stroke and other cardiovascular disease: a cross sectional study in a seleniferous area of Punjab, India [Abstract in Atti di Convegno]
Chawla, R; Cilloni, S; Loomba, R; Rohit, C; Chander, D; Dhillon, Ks; Filippini, T; Vinceti, M
abstract

Background and aims: Rural areas of Punjab in India have been found to have soil rich in selenium (Se); about 2160 hectare area is seleniferous and is populated by about 10,000 inhabitants. Selenium concentrations in these villages were reported to be as high as 65 times over non-seleniferous areas. The aim of this cross-sectional study was to evaluate selenium levels in blood, hair and nails in a group of subjects living in this area, and to evaluate the correlation between selenium exposure levels and a relevant cardiovascular risk factor and blood pressure. Methods: In a random sample of rural residents in three districts of a seleniferous area of Punjab, we determined selenium concentration in hair, nail clippings and serum samples. Analyses were carried out using atomic absorption spectrophotometry at National Dairy Research Institute (NDRI), Karnal, India. Data analysis was performed using the STATA 15.0 software (STATA Corp. TX). Results: A total of 680 human subjects were recruited in this study, with a male/female ratio of 0.6