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

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 D 3 for labelling purposes. Vitamin D refers to ergocalciferol (vitamin D 2 ), cholecalciferol (vitamin D 3 ), and calcidiol monohydrate. Systematic reviews of the literature were conducted to assess the relative bioavailability of calcidiol monohydrate versus vitamin D 3 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.

Association between vitamin D status, physical performance, sex, and lifestyle factors: a cross-sectional study of community-dwelling Kosovar adults aged 40 years and older

“…However, the most recent data from the European Food Saferty Agency (EFSA), based on European dietary surveys, show that vitamin D intake (from food sources) ranges from 2.48 to 4.34 µg/day in adult and older adult men and from 1.84 to 3.53 µg/day in women. In addition, the EFSA recommends an adequate intake (AI) of 15 µg/day for adults [ 1 ]. The low dietary intake of vitamin D among the Kosovar population compared to the recommendations highlights the urgent need for interventions, including even food fortification strategies as a potential way to improve the prevalence of vitamin D deficiency in Kosovo.…”

“…MyAssays.com was used to generate a four-parameter logistic curve fit to calculate the vitamin D concentration in the samples. Among the discrepancies between cut-offs, it is generally accepted that the appropriate target for serum 25(OH)D concentration is 50 nmol/L, which we used as the cut-off between sufficiency and deficiency [ 1 ].…”

“…Vitamin D is a topic of global interest to the scientific and clinical communities as well as the general public. Vitamin D deficiency has often been described as a growing concern for people of all ages, particularly following evidence of its potential health effects [ 1 ]. Low levels of vitamin D have been reported worldwide leading to the classification of vitamin D deficiency as a pandemic [ 2 ].…”

“…This can be achieved through sun exposure, dietary sources of vitamin D such as oily fish, eggs, meat, and some vitamin D fortified food products [ 13 ]. However, other factors such as age, skin pigmentation, clothing style, sunscreen use, air pollution, latitude and finally genetic profile may be important contributors to vitamin D deficiency [ 1 , 4 , 14 ], possibly impacting the wide range of vitamin D deficiency data in different countries.…”

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

“… The EFSA scientific opinion on the safety of calcidiol monohydrate produced by chemical synthesis as a novel food (NF) pursuant to Regulation (EU) 2015/2283 (EFSA NDA Panel, 2021 ). The EFSA scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate (EFSA NDA Panel, 2023 ). The letter sent by EirGen Pharma Ltd to the European Commission dated 13 April 2023 .…”