Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: A randomized controlled trial in older adults

Abstract

Background & aims: Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D₂ or D₃ is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D₃ and assessed the dose which results in mean serum 25(OH)D₃ concentrations between 75 and 100 nmol/L.

Methods: This randomized, double-blind intervention study included men and women aged ≥65 years (n = 59). Participants received either 5, 10 or 15 μg calcifediol or 20 μg vitamin D₃ per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D₃, 25(OH)D₃, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) and 24,25-dihydroxyvitamin D₃ (24,25(OH)₂D₃). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated.

Results: Supplementation with 20 μg vitamin D₃ increased 25(OH)D₃ concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 μg calcifediol increased 25(OH)D₃ levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D₃ levels stabilizing between 84 and 89 nmol/L in the 10 μg calcifediol group. A significant association was observed between the changes in 25(OH)D₃ and 24,25(OH)₂D₃ (R² = 0.83, P < 0.01), but not between 25(OH)D₃ and 1,25(OH)₂D₃ (R² = 0.04, P = 0.18). No cases of hypercalcemia occurred in any treatment during the study period.

Conclusions: Calcifediol supplementation rapidly and safely elevates serum 25(OH)D₃ concentrations to improve vitamin D status in older adults. A daily dose of 10 μg calcifediol allows serum 25(OH)D₃ concentrations to be maintained between 75 and 100 nmol/L.

Trial registration number: NCT01868945.

Keywords: 25-Hydroxyvitamin D; Calcifediol; Dose–response; PTH; Supplementation; Vitamin D.