Upper Intake Level For Vitamin Research Articles

Preparatory work for the update of the tolerable upper intake levels for vitamin A

Preparatory work for the update of the tolerable upper intake levels for vitamin A

Scientific and technical assistance to the evaluation of the safety of calcidiol monohydrate as a novel food.

EFSA was asked by the European Commission to provide scientific assistance with respect to the EFSA adopted scientific opinion on 'Safety of calcidiol monohydrate produced by chemical synthesis as a novel food pursuant to Regulation (EU) 2015/2283', including its bioavailability as a metabolite of vitamin D3 when added for nutritional purposes to food supplements. On 5 July 2023, EFSA adopted the 'Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate'. This opinion concerns an updated exposure assessment for vitamin D and proposes a conversion factor for calcidiol monohydrate into vitamin D3 of 2.5 for labelling purposes. In addition, in reference to the EFSA opinion on the safety of calcidiol monohydrate, the Commission had received a letter from the pharmaceutical company EirGen Pharma Ltd requesting a revision of this opinion based on new data concerning calcidiol. Based on the information and data considered in this scientific technical report, EFSA concludes that the novel food calcidiol monohydrate proposed for use in food supplements is a bioavailable source of the biologically active metabolite of vitamin D, i.e. 1,25-dihydroxyvitamin D, that a conversion factor of 2.5 reflects the relative bioavailability of calcidiol vs vitamin D3 under the proposed conditions of use and use levels, and that it is safe under the proposed conditions of use and use levels, i.e. up to 10 μg/day for children ≥ 11 years old and adults, including pregnant and lactating women, and up to 5 μg/day for children 3-10 years of age.

Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate.

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.

Preparatory work for the update of the tolerable upper intake levels for vitamin D

Preparatory work for the update of the tolerable upper intake levels for vitamin D

Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude.

There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intakeestimates across a range of 25(OH)D thresholds. To maintain serum 25(OH)D concentrations ≥ 25 and 30nmol/L in 97.5% of individuals, 23.9 and 27.3µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50nmol/L was 66.8µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).

Evaluation of Tolerable Upper Intake Levels for Vitamin D in Children and Adolescents

In 2012, the European Food Safety Authority (EFSA) suggested a tolerable upper intake level (UL) for vitamin D at 100 µg/day for adults based on the risk of hypercalcaemia. EFSA concluded that consumption of up to 50 µg/day does not lead to hypercalcaemia in children and adolescents (10-17 years). Furthermore, EFSA stated that there is no reason to assume that children and adolescents in the phase of rapid bone formation and growth have a lower tolerance for vitamin D compared to adults, and a UL of 100 µg/day for adolescents aged 11-17 years and 50 µg/day in children 1-10 years, taking the smaller body size into account, was proposed.
 The Norwegian Food Safety Authority (NFSA) is currently revising the national regulation of maximum limits in food supplements (not yet harmonised in the European Economic Area (EEA)), including maximum limits for vitamin D. NFSA has therefore requested the Norwegian Scientific Committee for Food Safety (VKM) to evaluate the assumption in the EFSA opinion that children and adolescents can tolerate the same amount of vitamin D as adults due to rapid bone formation and growth. In children and adolescents with lower weight than adults, this assumption actually implies that adolescents can tolerate more vitamin D per kg body weight than adults. VKM is therefore requested to evaluate if there is scientific evidence that a UL at 50 µg/day for children (1-10 years) and 100 µg/day for adolescents (11-17 years) is safe.
 The present statement is prepared by members of the Panel on Nutrition, Dietetic Products and Novel Food and Allergy in VKM.
 Three literature searches were performed to find new relevant studies investigating high intakes of vitamin D in children and adolescents and the role of vitamin D in bone formation and growth.
 No studies supporting a higher tolerance to vitamin D in children and adolescents due to rapid bone formation and growth were retrieved in the literature search. Moreover, there is apparently no firm association between bone formation and vitamin D levels in children during their growth period into adolescence and adulthood. 
 No studies investigating high intakes of vitamin D in children 1-10 years were found. Furthermore, no studies that have examined safety issues and/or adverse effects of vitamin D supplementation in doses above 50 µg/day in adolescents were identified. It can therefore not be concluded that the UL at 50 µg/day in children (1-10 years) and 100 µg/day in adolescents (11-17 years) is safe.
 In the 2002 report from European Scientific Committee on Food (SCF), a UL was set at 25 µg/day for children aged 2-10 years, and 50 µg/day for adolescents aged 11-17 years (corresponding to the UL for adults at that time). To the best of knowledge no serious, harmful effects have been reported for these doses of vitamin D.

Update of the tolerable upper intake level for vitamin D for infants.

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.

Outcome of a public consultation on the Draft Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the update of the tolerable upper intake level for vitamin D for infants

Outcome of a public consultation on the Draft Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on the update of the tolerable upper intake level for vitamin D for infants

Estimation of Usual Intake and Assessment of Nutrient Intake for Korean Adolescents: Analysis of the 2010-2012 Korea National Health and Nutrition Examination Survey

This study assessed the nutrient intake for Korean adolescents using the estimated usual intake. The usual intake of 1,763 adolescents aged 12-17 years old was estimated from one-day 24-hour recall data in the 2010-2012 Korean National Health and Nutrition Survey. The nutrient intakes of four groups according to sex (male and female) and age (12-14 and 15-17 years old) were then assessed in reference to the 2015 Dietary Reference Intakes for Koreans. For macronutrients, the proportions of subjects below and above the Acceptable Macronutrient Distribution Ranges (AMDR) were calculated. The Estimated Average Requirement (EAR) cut-point method was used to assess insufficient intakes of protein, vitamin C, thiamin, riboflavin, niacin, calcium, phosphorus, and iron; the full probability approach was used to assess the insufficient intake for iron among females. The proportions of subjects over the Tolerable Upper Intake Levels for vitamin C, niacin, calcium, phosphorus, and iron and the proportions over the Intake Goal for sodium were calculated to assess excessive intake. The proportions of subjects above AMDR for carbohydrates ranged from 22.5% to 38.0% by group. The proportions of subjects by group with insufficient intake for vitamin C, riboflavin, calcium, phosphorus, and iron ranged 29.1-39.7%, 22.5-34.3%, 73.1-89.3%, 14.3-43.6%, and 23.2-55.5%, respectively. The proportions of subjects by group with excessive intake for sodium ranged from 91.5% to 99.3%. The results of this study represent important basic information to establish nutritional standards for school lunches as well as to decide on relevant nutrition policies for adolescents. Keywords: nutrition survey, nutrition assessment, Dietary Reference Intakes, adolescent health

ビタミンDの耐用上限量の引き上げをEU食品安全機関(EFSA)が提案

ビタミンDの耐用上限量の引き上げをEU食品安全機関(EFSA)が提案

Scientific Opinion on the safety of UV‐treated bread as a novel food EFSA Panel on Dietetic Products, Nutrition and Allergies

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA Panel) was asked to carry out the additional assessment for UV-treated bread as a novel food (NF) in the context of Regulation (EC) No 258/97, taking into account the comments and objections of a scientific nature raised by Member States. The NF is bread to which a treatment with UV radiation is applied after baking in order to convert ergosterol, which is present in bread as a result of yeast fermentation, to vitamin D2. The provided compositional data, the specifications (i.e. vitamin D2 content of 0.75–3 μg/100 g in the UV-treated bread, 1–5 g/100 g of yeast in the dough) and the data from batch testing do not give rise to safety concerns. The data provided on the production process are sufficient and do not give rise to safety concerns. The Panel considers that even if it is conservatively assumed that all consumed breads are UV-treated and contain the maximum proposed amount of 3 µg vitamin D2/100 g, it is highly unlikely that tolerable upper intake levels for vitamin D, established by EFSA for various age groups, will be exceeded. The NF is not nutritionally disadvantageous. Under certain conditions, UV treatment may result in reactions of biomolecules. However, the levels of potential reaction products that may be formed under the employed conditions are low compared with the reactions induced by the baking process. Therefore, the Panel considers that it is not necessary to perform additional analyses and that the absence of toxicological studies with the novel food is acceptable. The risk of allergic reactions to the NF is not dissimilar to that associated with conventional bread. The Panel considers that bread enriched with vitamin D2 through UV treatment is safe under the conditions of use as specified by the applicant.

Vitamin Intake from Food Supplements in a German Cohort - Is there a Risk of Excessive Intake?

Food supplements, if not properly used, may lead to potentially harmful nutrient intake. The purpose of this survey was to examine vitamin intake from food supplements. Taking into account the intake from food, as obtained from the National Nutrition Survey, it was determined whether the tolerable upper intake levels (ULs) were exceeded via supplements alone, or in combination with food. Data from 1070 supplement users (18-93 years) was available. The dietary and supplemental vitamin intakes of three groups were analyzed: average intake (50th percentile food+50th percentile supplements), middle-high intake (50th+95th) and high intake (95th+95th). Vitamin C (53%), vitamin E (45%) and B vitamins (37-45%) were consumed most frequently. Few subjects (n=7) reached or exceeded the ULs through supplements alone. The UL for vitamin A and folate was reached by a few men in the middle-high group, and by a few men and women in the high intake group. Otherwise, even in the high intake group, the recommended vitamin D intake of 20 µg/day (in case of insufficient endogenous synthesis) could not be achieved. The use of food supplements was not associated with excessive vitamin intake in this survey, except in a small number of cases. Vitamin A intake above the UL was the result of high dietary intake which also included the intake of β-carotene, rather than the result of overconsumption of food supplements. Diets mainly included folate from natural sources, which has no associated risk.

Scientific Opinion on the Tolerable Upper Intake Level of vitamin D

Scientific Opinion on the Tolerable Upper Intake Level of vitamin D

New proposal for the Safe Tolerable Upper Intake Level of Vitamin D

New proposal for the Safe Tolerable Upper Intake Level of Vitamin D

Inability to assess the safety of vitamin D‐enriched yeast added for nutritional purposes as a source of vitamin D in food supplements and the bioavailability of vitamin D from this source, based on the supporting dossier

EFSA JournalVolume 7, Issue 6 1148 StatementOpen Access Inability to assess the safety of vitamin D-enriched yeast added for nutritional purposes as a source of vitamin D in food supplements and the bioavailability of vitamin D from this source, based on the supporting dossier European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author First published: 23 June 2009 https://doi.org/10.2903/j.efsa.2009.1148 Panel members: F. Aguilar, U.R. Charrondiere, B. Dusemund, P. Galtier, J. Gilbert, D.M. Gott, S. Grilli, R. Guertler, G.E.N. Kass, J. Koenig, C. Lambré, J-C. Larsen, J-C. Leblanc, A. Mortensen, D. Parent-Massin, I. Pratt, I.M.C.M. Rietjens, I. Stankovic, P. Tobback, T. Verguieva, R.A. Woutersen. Acknowledgement: The European Food Safety Authority wishes to thank the members of Working Group B on Food Additives and Nutrient Sources added to Food for the preparation of this opinion: D. Boskou, U.R. Charrondiere, B. Dusemund, D. Gott, T. Hallas-Møller, K.F.A.M. Hulshof, J. König, C. Le Donne, D. Parent-Massin, I.M.C.M. Rietjens, G.J.A. Speijers, P. Tobback, T. Verguieva, R.A. Woutersen. Adoption date: 5 June 2009 Published date: 23 June 2009 Question number: EFSA-Q-2005-198 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References EFSA (European Food Safety Authority), 2008. Opinion of the Scientific Panel on Biological Hazards on the maintenance of the list of QPS microorganisms intentionally added to food or feed. The EFSA Journal (2008) 923, 1– 48. SCF (Scientific Committee on Food), 2002. Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Vitamin D. Available at: ec.europa.eu/food/fs/sc/scf/out157_en.pdf. Volume7, Issue6June 20091148 ReferencesRelatedInformation

Effect of storage on retinol concentration of Cobb and Ross strain chicken livers

Liver is an important item in the human diet. The present study examined the retinol concentration in the fresh livers of Cobb and Ross chicken strains, after freezing at −18°C for 90 days. The retinol dosage in the liver was determined by high-performance liquid chromatography. The poultry strain significantly influenced liver retinol levels. The mean retinol value in the fresh samples was 6,678.0±1,337.7 and 8,324.1±1,158.5 µg/100 g in the Cobb and Ross strains, respectively. These values decreased significantly with liver storage time and reached levels that were 44.1% lower than those of fresh liver after 90 days. The results showed a high concentration of retinol in the chicken livers and demonstrated that more than 30 days of storage causes decreased retinol. Despite the losses resulting from freezing, the ingestion of a typical 100 g portion of liver, regardless of the chicken strain analyzed, exceeds the tolerable upper intake level of vitamin A (3,000 µg/day) for adults.

Calcium and vitamin D and bone strength ‐ Scientific substantiation of a health claim related to calcium and vitamin D and bone strength pursuant to Article 14 of Regulation (EC) No 1924/2006 ‐ Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies

Calcium and vitamin D and bone strength ‐ Scientific substantiation of a health claim related to calcium and vitamin D and bone strength pursuant to Article 14 of Regulation (EC) No 1924/2006 ‐ Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies

Are low tolerable upper intake levels for vitamin A undermining effective food fortification efforts?

Vitamin A deficiency (VAD) is a major health problem, particularly in low-resource countries, putting an estimated 125-130 million preschool-aged children at increased risk of morbidity and mortality from infectious diseases. Vitamin A supplementation reduces VAD and increases child survival; it is complemented by fortifying foods with vitamin A. Concern over increased risk of bone fracture associated with vitamin A intakes below the tolerable upper intake level (UL) among populations in affluent countries conflicts with the need to increase intakes in less developed countries, where populations are at greater risk of VAD and intakes are unlikely to reach the UL as diets include fewer foods containing retinol while vitamin A from carotenoids poses no risk of overdose. With the implementation of recently developed risk management tools, vitamin A can be used safely in food fortification, including point-of-use fortification in the context of supplementation among specific target groups in low-resource countries.

Vitamin D in Health and Disease

Vitamin D functions in the body through both an endocrine mechanism (regulation of calcium absorption) and an autocrine mechanism (facilitation of gene expression). The former acts through circulating calcitriol, whereas the latter, which accounts for more than 80% of the metabolic utilization of the vitamin each day, produces, uses, and degrades calcitriol exclusively intracellularly. In patients with end-stage kidney disease, the endocrine mechanism is effectively disabled; however, the autocrine mechanism is able to function normally so long as the patient has adequate serum levels of 25(OH)D, on which its function is absolutely dependent. For this reason, calcitriol and its analogs do not constitute adequate replacement in managing vitamin D needs of such patients. Optimal serum 25(OH)D levels are greater than 32 ng/mL (80 nmol/L). The consequences of low 25(OH)D status include increased risk of various chronic diseases, ranging from hypertension to diabetes to cancer. The safest and most economical way to ensure adequate vitamin D status is to use oral dosing of native vitamin D. (Both daily and intermittent regimens work well.) Serum 25(OH)D can be expected to rise by about 1 ng/mL (2.5 nmol/L) for every 100 IU of additional vitamin D each day. Recent data indicate that cholecalciferol (vitamin D(3)) is substantially more potent than ergocalciferol (vitamin D(2)) and that the safe upper intake level for vitamin D(3) is 10,000 IU/d.

Vitamin D Toxicity, Policy, and Science

The serum 25-hydroxyvitamin D [25(OH)D] concentration that is the threshold for vitamin D toxicity has not been established. Hypercalcemia is the hazard criterion for vitamin D. Past policy of the Institute of Medicine has set the tolerable upper intake level (UL) for vitamin D at 50 mug (2000 IU)/d, defining this as "the highest level of daily nutrient intake that is likely to pose no risks of adverse health effects to almost all individuals in the general population." However, because sunshine can provide an adult with vitamin D in an amount equivalent to daily oral consumption of 250 mug (10,000 IU)/d, this is intuitively a safe dose. The incremental consumption of 1 mug (40 IU)/day of vitamin D(3) raises serum 25(OH)D by approximately 1 nM (0.4 ng/ml). Therefore, if sun-deprived adults are to maintain serum 25(OH)D concentrations >75 nM (30 ng/ml), they will require an intake of more than the UL for vitamin D. The mechanisms that limit vitamin D safety are the capacity of circulating vitamin D-binding protein and the ability to suppress 25(OH)D-1-alpha-hydroxylase. Vitamin D causes hypercalcemia when the "free" concentration of 1,25-dihydroxyvitamin D is inappropriately high. This displacement of 1,25(OH)(2)D becomes excessive as plasma 25(OH)D concentrations become higher than at least 600 nM (240 ng/ml). Plasma concentrations of unmetabolized vitamin D during the first days after an acute, large dose of vitamin D can reach the micromolar range and cause acute symptoms. The clinical trial evidence shows that a prolonged intake of 250 mug (10,000 IU)/d of vitamin D(3) is likely to pose no risk of adverse effects in almost all individuals in the general population; this meets the criteria for a tolerable upper intake level.