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

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 D or D 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 D and assessed the dose which results in mean serum 25(OH)D 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 D 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 D, 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)D). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated.

Results: Supplementation with 20 μg vitamin D increased 25(OH)D concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 μg calcifediol increased 25(OH)D levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D 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)D and 24,25(OH)D (R = 0.83, P < 0.01), but not between 25(OH)D and 1,25(OH)D (R = 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)D concentrations to improve vitamin D status in older adults. A daily dose of 10 μg calcifediol allows serum 25(OH)D concentrations to be maintained between 75 and 100 nmol/L.

Trial Registration Number: NCT01868945.