Turck Dominique, Bohn Torsten, Castenmiller Jacqueline, de Henauw Stefaan, Hirsch-Ernst Karen-Ildico, Knutsen Helle Katrine, Maciuk Alexandre, Mangelsdorf Inge, McArdle Harry J, Pentieva Kristina, Siani Alfonso, Thies Frank, Tsabouri Sophia, Vinceti Marco, Lanham-New Susan, Passeri Giovanni, Craciun Ionut, Fabiani Lucia, De Sousa Rita Ferreira, Martino Laura, Martínez Silvia Valtueña, Naska Androniki
EFSA J. 2023 Aug 8;21(8):e08145. doi: 10.2903/j.efsa.2023.8145. eCollection 2023 Aug.
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 for labelling purposes. Vitamin D refers to ergocalciferol (vitamin D), cholecalciferol (vitamin D), and calcidiol monohydrate. Systematic reviews of the literature were conducted to assess the relative bioavailability of calcidiol monohydrate versus vitamin D 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.
应欧盟委员会（EC）的两项请求，欧洲食品安全局（EFSA）的营养、新型食品和食品过敏原专家小组（NDA）被要求就维生素D可耐受最高摄入量（UL）的修订提供科学意见，并为标签目的提出单水钙化二醇转化为维生素D的转换系数（CF）。维生素D是指麦角钙化醇（维生素D₂）、胆钙化醇（维生素D₃）和单水钙化二醇。开展了文献系统综述，以评估单水钙化二醇与维生素D₂和D₃相比对血清25(OH)D浓度的相对生物利用度，以及过量摄入维生素D的主要不良健康影响，即持续性高钙血症/高钙尿症以及与肌肉骨骼健康相关的终点指标（即跌倒、骨折、骨量/密度及其指数）。基于现有证据，专家小组建议用于标签目的的单水钙化二醇的CF为2.5。持续性高钙尿症可能是维生素D过量的比持续性高钙血症更早的迹象，被选为确定维生素D UL的关键终点指标。从两项人体随机对照试验中确定了最低观察到有害作用水平（LOAEL）为250μg/天，应用2.5的不确定性系数以考虑未观察到有害作用水平（NOAEL）的缺失。为成年人（包括孕妇和哺乳期妇女）以及11至17岁的青少年确定了100μg维生素D当量（VDE）/天的UL，因为没有理由认为处于快速骨骼形成和生长阶段的青少年对维生素D的耐受性低于成年人。对于1至10岁的儿童，考虑到他们较小的体型，确定了50μg VDE/天的UL。根据现有摄入数据，欧洲人群不太可能超过UL，但经常使用高剂量维生素D食品补充剂的人群除外。
