Scientific opinion on the tolerable upper intake level for vitamin B6.

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.

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.

Conversion of calcium-l-methylfolate and (6S)-5-methyltetrahydrofolic acid glucosamine salt into dietary folate equivalents.

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.

Scientific opinion on the relationship between intake of alpha-lipoic acid (thioctic acid) and the risk of insulin autoimmune syndrome.

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.

Statement on additional scientific evidence in relation to the essential composition of total diet replacement for weight control.

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.

Appropriate age range for introduction of complementary feeding into an infant's diet.

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.