Scientific opinion on the tolerable upper intake level for selenium.

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 µg/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 µg/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 weight0.75). 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.

Evidence to Underpin Vitamin A Requirements and Upper Limits in Children Aged 0 to 48 Months: A Scoping Review.

Vitamin A deficiency is a major health risk for infants and children in low- and middle-income countries. This scoping review identified, quantified, and mapped research for use in updating nutrient requirements and upper limits for vitamin A in children aged 0 to 48 months, using health-based or modelling-based approaches. Structured searches were run on Medline, EMBASE, and Cochrane Central, from inception to 19 March 2021. Titles and abstracts were assessed independently in duplicate, as were 20% of full texts. Included studies were tabulated by question, methodology and date, with the most relevant data extracted and assessed for risk of bias. We found that the most recent health-based systematic reviews and trials assessed the effects of supplementation, though some addressed the effects of staple food fortification, complementary foods, biofortified maize or cassava, and fortified drinks, on health outcomes. Recent isotopic tracer studies and modelling approaches may help quantify the effects of bio-fortification, fortification, and food-based approaches for increasing vitamin A depots. A systematic review and several trials identified adverse events associated with higher vitamin A intakes, which should be useful for setting upper limits. We have generated and provide a database of relevant research. Full systematic reviews, based on this scoping review, are needed to answer specific questions to set vitamin A requirements and upper limits.

Guidance on safety evaluation of sources of nutrients and bioavailability of nutrient from the sources (Revision 1).

[Table: see text] This guidance describes the scientific data required to allow an evaluation of the safety of new substances that are proposed for use as sources of nutrients in food supplements, foods for the general population or foods for specific groups and an assessment of the bioavailability of the nutrient from the proposed source. This guidance describes the scientific data required to allow an evaluation of the safety of the source within the established framework for risk assessment of food additives and novel food ingredients and the bioavailability of the nutrient from this source. This document is arranged in five main sections: one on technical data aimed at characterising the proposed source and at identifying potential hazards resulting from its manufacture and stability in food; one on existing authorisations and evaluation, providing an overview of previous assessments on the proposed source and their conclusions; one on proposed uses and exposure assessment section, allowing an estimate of the dietary exposure to the source and the nutrient based on the proposed uses and use levels; one on toxicological data, describing approaches which can be used to identify (in conjunction with data on manufacture and composition) and to characterise hazards of the source and any relevant breakdown products; the final section on bioavailability focuses on determining the extent to which the nutrient from the proposed source is available for use by the body in comparison with one or more forms of the same nutrient that are already permitted for use on the positive lists. This guidance was adopted by the Panel on Food Additives and Nutrient Sources added to Food (ANS Panel) on 16 May 2018. Upon request from EFSA, the present guidance has been revised to inform applicants of new provisions set out in 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.

Safety of orthosilicic acid-vanillin complex (OSA-VC) as a novel food ingredient to be used in food supplements as a source of silicon and bioavailability of silicon from the source.

The present scientific opinion deals with the safety of orthosilicic acid-vanillin complex (OSA-VC) as a novel food ingredient for use as a source of silicon (Si) in food supplements and with the bioavailability of Si from this source. OSA-VC is stable in liquid solution at low pH values. OSA from OSA-VC was available as revealed by the increase in plasma Si concentrations after oral ingestion in human volunteers. The toxicological data provided in support of the current application were not in accordance with the Tier 1 requirement of the 'Guidance for submission for food additive evaluations'; however, this was considered justified by the Panel given that OSA-VC at pH 6.8 dissociates into orthosilicic acid and vanillin. The daily consumption of OSA-VC at the dose recommended by the applicant would provide a supplemental intake of Si of approximately 10-18 mg Si/day which would result in an estimated total intake of roughly 30-70 mg Si/day. The maximum vanillin intake resulting from the consumption of OSA-VC would be less than 5% of the acceptable daily intake (ADI) value for vanillin of 10 mg/kg body weight (bw) per day established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2002. The Panel concluded that there would be no safety concern with the proposed use and use level of OSA-VC as a novel food ingredient intended to be used as a source of Si in food supplements for the adult population. The Panel concluded that OSA, measured as Si, is bioavailable following ingestion of OSA-VC and appears similar to values reported in the literature for other established sources of OSA.

Evaluation of di-calcium malate, used as a novel food ingredient and as a source of calcium in foods for the general population, food supplements, total diet replacement for weight control and food for special medical purposes.

The present scientific opinion deals with the evaluation of the safety of di-calcium malate (DCM) proposed as a novel food ingredient and as a source of calcium for use in foods for the general population, food supplements, total diet replacement for weight control and food for special medical purposes (FSMP), and with the bioavailability of calcium from this source. The structural formula of the proposed complex is based on expert judgement and not supported by any analytical data. On the basis of the available data, the Panel concluded that there was insufficient scientific evidence of a difference between the proposed novel food ingredient named as di-calcium malate (DCM) and calcium malate already authorised as a source of calcium included in Annex II to Directive 2002/46/EC. Accordingly, the Panel was unable to assess the safety of DCM as a novel food ingredient. On the basis of the results provided, the Panel considered that DCM does not completely dissociate into calcium and malic acid. The Panel concluded that when DCM dissociates, calcium would be available following ingestion of DCM and the bioavailability would appear similar to values reported for other sources of calcium already permitted. Furthermore, the Panel concluded that on the basis of the information available it was not possible to calculate the exposure to DCM as a source of calcium to foods for the general population, food supplements, total diet replacement for weight control and FSMP.

Evaluation of di-magnesium malate, used as a novel food ingredient and as a source of magnesium in foods for the general population, food supplements, total diet replacement for weight control and food for special medical purposes.

The present scientific opinion deals with the evaluation of the safety of di-magnesium malate (DMM) proposed as a novel food ingredient and as a source of magnesium for use in foods for the general population, food supplements, total diet replacement for weight control and food for special medical purposes (FSMP), and with the bioavailability of magnesium from this source. Additional information was sought from the applicant during the assessment process. However, despite several requests, the applicant did not provide the additional data. Consequently, the Panel performed this assessment on the basis of the available data and concluded that there was insufficient scientific evidence of a difference between the proposed novel food ingredient named as DMM and magnesium malate already authorised as a source of magnesium included in Annex II to Directive 2002/46/EC. Accordingly, the Panel was unable to assess the safety of DMM as a novel food ingredient. The Panel concluded that based on the data provided it was not possible to assess the dissociation of DMM into magnesium and malic acid. The Panel further concluded that if DMM dissociates, magnesium would be available following ingestion of DMM and the availability would appear similar to values reported for other sources of magnesium already permitted. Finally, the Panel noted that the proposed use levels could result in exposures to magnesium greater than its upper level (UL) (250 mg/day) for food supplements and for food for special medical purposes.

Guidance on safety evaluation of sources of nutrients and bioavailability of nutrient from the sources.

Whenever new substances are proposed for use as sources of nutrients in food supplements, foods for the general population or foods for specific groups, EFSA is requested by the European Commission to perform an assessment of their safety and of the bioavailability of the nutrient from the proposed source. This guidance describes the scientific data required to allow an evaluation of the safety of the source within the established framework for risk assessment of food additives and novel food ingredients and the bioavailability of the nutrient from this source. This document is arranged in five main sections: one on technical data aimed at characterising the proposed source and at identifying potential hazards resulting from its manufacture and stability in food; one on existing authorisations and evaluation, providing an overview of previous assessments on the proposed source and their conclusions; one on proposed uses and exposure assessment section, allowing an estimate of the dietary exposure to the source and the nutrient based on the proposed uses and use levels; one on toxicological data, describing approaches which can be used to identify (in conjunction with data on manufacture and composition) and to characterise hazards of the source and any relevant breakdown products; the final section on bioavailability focuses on determining the extent to which the nutrient from the proposed source is available for use by the body in comparison with one or more forms of the same nutrient that are already permitted for use on the positive lists. This guidance document should replace the previous guidance issued by the Scientific Committee for Food and published in 2001.

Re-evaluation of calcium silicate (E 552), magnesium silicate (E 553a(i)), magnesium trisilicate (E 553a(ii)) and talc (E 553b) as food additives.

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of calcium silicate (E 552), magnesium silicate (E 553a) and talc (E 553b) when used as food additives. In 1991, the Scientific Committee on Food (SCF) established a group acceptable daily intake (ADI) 'not specified' for silicon dioxide and silicates. The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) recently provided a scientific opinion re-evaluating the safety of silicon dioxide (E 551) when used as a food additive. The Panel noted that the absorption of silicates and talc was very low; there was no indication for genotoxicity or developmental toxicity for calcium and magnesium silicate and talc; and no confirmed cases of kidney effects have been found in the EudraVigilance database despite the wide and long-term use of high doses of magnesium trisilicate up to 4 g/person per day over decades. However, the Panel considered that accumulation of silicon from calcium silicate in the kidney and liver was reported in rats, and reliable data on subchronic and chronic toxicity, carcinogenicity and reproductive toxicity of silicates and talc were lacking. Therefore, the Panel concluded that the safety of calcium silicate (E 552), magnesium silicate (E 553a(i)), magnesium trisilicate (E 553a(ii)) and talc (E 553b) when used as food additives cannot be assessed. The Panel considered that there is no mechanistic rationale for a group ADI for silicates and silicon dioxide and the group ADI established by the SCF is obsolete. Based on the food supplement scenario considered as the most representative for risk characterisation, exposure to silicates (E 552-553) for all population groups was below the maximum daily dose of magnesium trisilicate used as an antacid (4 g/person per day). The Panel noted that there were a number of approaches, which could decrease the uncertainties in the current toxicological database. These approaches include - but are not limited to - toxicological studies as recommended for a Tier 1 approach as described in the EFSA Guidance for the submission of food additives and conducted with an adequately characterised material. Some recommendations for the revision of the EU specifications were proposed by the Panel.

Nutrition issues in Codex: health claims, nutrient reference values and WTO agreements: a conference report.

BACKGROUND: Codex documents may be used as educational and consensus materials for member governments. Also, the WTO SPS Agreement recognizes Codex as the presumptive international authority on food issues. Nutrient bioavailability is a critical factor in determining the ability of nutrients to provide beneficial effects. Bioavailability also influences the quantitative dietary requirements that are the basis of nutrient intake recommendations and NRVs. HEALTH CLAIMS: Codex, EFSA and some national regulatory authorities have established guidelines or regulations that will permit several types of health claims. The scientific basis for claims has been established by the US FDA and EFSA, but not yet by Codex. Evidence-based nutrition differs from evidence-based medicine, but the differences are only recently gaining recognition. Health claims on foods may provide useful information to consumers, but many will interpret the information to mean that they can rely upon the food or nutrient to eliminate a disease risk. NUTRIENT REFERENCE VALUES: NRVs are designed to provide a quantitative basis for comparing the nutritive values of foods, helping to illustrate how specific foods fit into the overall diet. The INL-98 and the mean of adult male and female values provide NRVs that are sufficient when used as targets for individual intakes by most adults. WORLD TRADE ORGANIZATION AGREEMENTS: WTO recognizes Codex as the primary international authority on food issues. Current regulatory schemes based on recommended dietary allowances are trade restrictive. A substantial number of decisions by the EFSA could lead to violation of WTO agreements.

Criteria for substantiating claims.

Claims are used to support public health advocacy and marketing. Their evidence base is variable. Claims are made on (i) nutrient content, (ii) comparative merits, (iii) health benefits, and (iv) medical benefits. Experience with therapeutic agents has aided the development of recommendations for the substantiation of health claims for foods and food components, with which dietary supplements would be included. An EU Concerted Activity, Functional Food Science in Europe, suggested that such claims should be based on the general outcomes of 'enhanced function' and 'reduced risk of disease'. A further EU Concerted Activity, The Process for the Assessment of Scientific Support for Claims on Foods, proposed that the evidence base should provide: a characterization of the food or food component to which the claimed effect is attributed; human data, primarily from intervention studies that represent the target populations for the claim; a dose-response relationship: evidence of allowing for confounders including lifestyle, consumption patterns, background diet and food matrix; an appropriate duration for the study; a measure of compliance; and have adequate statistical power to test the hypothesis. When ideal endpoints are not easily accessible for measurement, validated and quality assured markers of the intermediate or final outcomes could be used, as long as their relationship is well characterized. Overall, the totality and coherence of published and unpublished evidence should be considered. Assessments for substantiation need expert judgement, weighting of the strength of the claim, and intelligent use of the criteria applied on an individual basis with respect both to gaps in knowledge and to any need for new knowledge and data.

Feeding preterm infants after hospital discharge: a commentary by the ESPGHAN Committee on Nutrition.

Survival of small premature infants has markedly improved during the last few decades. These infants are discharged from hospital care with body weight below the usual birth weight of healthy term infants. Early nutrition support of preterm infants influences long-term health outcomes. Therefore, the ESPGHAN Committee on Nutrition has reviewed available evidence on feeding preterm infants after hospital discharge. Close monitoring of growth during hospital stay and after discharge is recommended to enable the provision of adequate nutrition support. Measurements of length and head circumference, in addition to weight, must be used to identify those preterm infants with poor growth that may need additional nutrition support. Infants with an appropriate weight for postconceptional age at discharge should be breast-fed when possible. When formula-fed, such infants should be fed regular infant formula with provision of long-chain polyunsaturated fatty acids. Infants discharged with a subnormal weight for postconceptional age are at increased risk of long-term growth failure, and the human milk they consume should be supplemented, for example, with a human milk fortifier to provide an adequate nutrient supply. If formula-fed, such infants should receive special postdischarge formula with high contents of protein, minerals and trace elements as well as an long-chain polyunsaturated fatty acid supply, at least until a postconceptional age of 40 weeks, but possibly until about 52 weeks postconceptional age. Continued growth monitoring is required to adapt feeding choices to the needs of individual infants and to avoid underfeeding or overfeeding.