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

Context: Vitamin D-2 and vitamin D-3 have been hypothesized to exert differential effects on vitamin D metabolism. Objective: To compare the influence of administering vitamin D-2 vs vitamin D-3 on metabolism of vitamin D3. Methods: We measured baseline and 4-month serum concentrations of vitamin D-3, 25-hydroxyvitamin D-3 [25(OH)D-3], 25-hydroxyvitamin D-2, 24R,25-dihydroxyvitamin D-3 [24R,25(OH)(2)D-3], 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3], and 4 beta,25-dihydroxyvitamin D-3 [4 beta,25(OH)(2)D-3] in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 (n = 28) or vitamin D-3 (n = 24) over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisonsweremadeto evaluate effects of vitamin D-2 and vitamin D-3 on metabolismof vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups. Results: Vitamin D-2 was less effective than vitamin D-3 in elevating total serum 25(OH)D concentration. Vitamin D-2 suppressed mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)(2)D-3, 1a,25(OH)(2)D-3, and 4 beta,25(OH)(2)D-3 and mean ratios of 25(OH)D-3 to D-3 and 1 alpha,25(OH)(2)D-3 to 25(OH)D-3, while increasing the mean ratio of 24R,25(OH)(2)D-3 to 25(OH)D-3. Vitamin D-3 increased mean four-month serumconcentrations of 25(OH)D-3, 24R,25(OH)(2)D-3, 1 alpha,25(OH)(2)D-3, and 4 beta,25(OH)(2)D-3 and the mean ratio of 24R,25(OH)(2)D-3 to 25(OH)D-3. Participants receiving vitamin D-2 had lower mean postsupplementation ratios of 25(OH)D3 to vitamin D-3 and 1 alpha,25(OH)(2)D-3 to 25(OH)D-3 than those receiving vitamin D-3. Mean postsupplementation ratios of 24R,25(OH)2D3 to 25(OH)D-3 and 4b,25(OH)(2)D-3 to 25(OH)D-3 did not differ between groups. Conclusions: Bolus-dose vitamin D-2 is less effective than bolus-dose vitamin D-3 in elevating total serum 25(OH)D concentration. Administration of vitamin D-2 reduces 25-hydroxylation of vitamin D-3 and 1-alpha hydroxylation of 25(OH)D-3, while increasing 24R-hydroxylation of 25(OH)D-3.