Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial

Abstract

Context: Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism.

Objective: To compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3.

Methods: We measured baseline and 4-month serum concentrations of vitamin D3, 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2, 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], and 4β,25-dihydroxyvitamin D3 [4β,25(OH)2D3] in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 (n = 28) or vitamin D3 (n = 24) over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisons were made to evaluate effects of vitamin D2 and vitamin D3 on metabolism of vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups.

Results: Vitamin D2 was less effective than vitamin D3 in elevating total serum 25(OH)D concentration. Vitamin D2 suppressed mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and mean ratios of 25(OH)D3 to D3 and 1α,25(OH)2D3 to 25(OH)D3, while increasing the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Vitamin D3 increased mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Participants receiving vitamin D2 had lower mean postsupplementation ratios of 25(OH)D3 to vitamin D3 and 1α,25(OH)2D3 to 25(OH)D3 than those receiving vitamin D3. Mean postsupplementation ratios of 24R,25(OH)2D3 to 25(OH)D3 and 4β,25(OH)2D3 to 25(OH)D3 did not differ between groups.

Conclusions: Bolus-dose vitamin D2 is less effective than bolus-dose vitamin D3 in elevating total serum 25(OH)D concentration. Administration of vitamin D2 reduces 25-hydroxylation of vitamin D3 and 1-α hydroxylation of 25(OH)D3, while increasing 24R-hydroxylation of 25(OH)D3.

Figure 1.

Vitamin D₃ oxidation pathways. The monohydroxylated and dihydroxylated metabolites investigated in the current study are shown, with the cytochrome P450 enzymes catalyzing each conversion in capitals.

Figure 2.

Trial profile.

Figure 3.

Influence of oral administration of vitamin D₃ and vitamin D₂ on serum concentrations of (A) total 25(OH)D, (B) 25(OH)D₃, (C) 25(OH)D₂, and (D) 1α,25(OH)₂D₃. Baseline and 4-mo data are presented for 24 adults receiving four bolus doses of 2.5 mg vitamin D₃ at 0, 1, 2, and 3 mo postrandomization and 28 adults receiving an equivalent regimen of vitamin D₂. Lines link data points from the same individual; P values for within-group comparisons before vs after supplementation are from paired Student t tests. P values for intergroup comparisons of postsupplementation values in participants randomized to vitamin D₃ vs vitamin D₂ are from linear regression with adjustment for baseline values.