Differential Effects of Oral Boluses of Vitamin D(2) vs Vitamin D(3) 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 D(3). 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)], 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)], and 4β,25-dihydroxyvitamin D(3) [4β,25(OH)(2)D(3)] in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D(2) (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 comparisons were made to evaluate effects of vitamin D(2) and vitamin D(3) on metabolism of 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)D(3), 24R,25(OH)(2)D(3), 1α,25(OH)(2)D(3), and 4β,25(OH)(2)D(3) and mean ratios of 25(OH)D(3) to D(3) and 1α,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 serum concentrations of 25(OH)D(3), 24R,25(OH)(2)D(3), 1α,25(OH)(2)D(3), and 4β,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)D(3) to vitamin D(3) and 1α,25(OH)(2)D(3) to 25(OH)D(3) than those receiving vitamin D(3). Mean postsupplementation ratios of 24R,25(OH)(2)D(3) to 25(OH)D(3) and 4β,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-α hydroxylation of 25(OH)D(3), while increasing 24R-hydroxylation of 25(OH)D(3).