Long-term vitamin D₃ supplementation is more effective than vitamin D₂ in maintaining serum 25-hydroxyvitamin D status over the winter months

Abstract

Public health recommendations do not distinguish between vitamin D 2 and vitamin D 3 , yet disagreement exists on whether these two forms should be considered equivalent. The objective of the present study was to evaluate the effect of a daily physiological dose of vitamin D 2 or vitamin D 3 on 25-hydroxyvitamin D (25(OH)D) status over the winter months in healthy adults living in Dunedin, New Zealand (latitude 468S). Participants aged 18-50 years were randomly assigned to 25 mg (1000 IU) vitamin D 3 (n 32), 25 mg (1000 IU) vitamin D 2 (n 31) or placebo (n 32) daily for 25 weeks beginning at the end of summer. A per-protocol approach, which included $90 % supplement compliance, was used for all analyses. (1 -10) . Vitamin D 3 , the form produced in the skin of humans after exposure of 7-dehydrocholesterol to sunlight, is found either naturally in animal products such as fatty fish and cod-liver oil, or added as a fortificant to foods. Commercial production of vitamin D 3 is performed by UV irradiation of 7-dehydrocholesterol extracted from the lanolin of sheep wool. Vitamin D 2 is made either naturally or synthetically from the UV irradiation of ergosterol obtained from yeast, and added to foods. Structurally, vitamin D 2 differs from vitamin D 3 in that its side chain has an added methyl group on carbon 24 and an additional double bond between carbons 22 and 23. These structural differences, however, do not prevent the metabolic activation of the two forms. Before exerting their biological effects, both vitamin D 2 and vitamin D 3 must undergo 25-hydroxylation to form 25-hydroxyvitamin D 2 (25(OH)D 2 ) or 25-hydroxyvitamin D 3 (25(OH)D 3 ), respectively, followed by 1a-hydroxylation to produce the respective biologically active metabolites 1,25-dihydroxyvitamin D (1,25(OH) 2 D).With the use of appropriate assay systems to detect the 25(OH)D 2 metabolite, several randomised trials using large oral dose preparations ranging from 1250 to 7500 mg (50 000-300 000 IU) have suggested that vitamin D 2 is less effective in elevating or maintaining total serum 25-hydroxyvitamin D (25(OH)D) levels in healthy adults (3,6,9,10) , whereas the few studies which have directly compared daily administered low-dose preparations of vitamin D 3 and vitamin D 2 have yielded inconsistent results (1,2,5,7 -9) . In addition to varying dose and dosing regimens, these latter studies have been

A vitamin D protocol post‐liver transplantation

“…Vitamin D supplementation using ergocalciferol was the current approach at project site among liver transplant providers. The move towards cholecalciferol was appropriate given the evidence that it has shown to improve serum levels more effectively than ergocalciferol (Logan et al, 2013;Mangoo-Karim et al, 2015;Osborn & Germann, 2011).…”

“…Although both pre and post transplanted patients receive supplementation, this study focused only on the post-transplanted patient's response to this dosing schedule. This protocol replaces the previously used vitamin D2 (ergocalciferol) dosing as evidence shows the superiority of cholecalciferol in improving serum 25(OH)D levels (Logan et al, 2013;Osborn & Germann, 2011).…”

25-Hydroxyvitamin D concentration and all-cause mortality: the Melbourne Collaborative Cohort Study

“…The lower affinity of 25(OH)D 2 for vitamin D binding protein relative to 25(OH)D 3 means its free fraction in blood is likely to be higher, consistent with the faster turnover of 25(OH) D 2 (8,27) . The shorter circulating half-life of ergocalciferol metabolites may lead to up-regulation of enzymes that not only metabolise ergocalciferol, but also concomitantly induce accelerated catabolism and clearance of 25(OH)D 3 (8,11) . Differential specificities of the various cytochrome P450 (CYP) enzymes that metabolise vitamin D may also help to explain the apparent effect of ergocalciferol on 25(OH)D 3 concentration.…”

Effect of vitamin d2 supplementation on serum 25 hydroxy-vitamin d3 levels: a systematic review and meta-analysis

“…However, recent research has indicated that vitamin D 2 has a lesser effect on raising total vitamin D (25(OH)D) status compared to vitamin D 3 and could result in a decrease in 25(OH)D 3 concentrations (2)(3)(4) . Furthermore, only vitamin D 3 and not vitamin D 2 has been found to decrease all-cause and cancer mortality (5) .…”

“…Furthermore, only vitamin D 3 and not vitamin D 2 has been found to decrease all-cause and cancer mortality (5) . The objective was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) that have supplemented with vitamin D 2 via a tablet/capsule or via a food fortification vehicle, and to compare concentrations of measured serum 25(OH)D 3 following supplementation.…”