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 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.
['Vaes|Anouk M M|AMM|', 'Tieland|Michael|M|', 'de Regt|Margot F|MF|', 'Wittwer|Jonas|J|', 'van Loon|Luc J C|LJC|', 'de Groot|Lisette C P G M|LCPGM|']
D015650:24,25-Dihydroxyvitamin D 3 D000368:Aged D000369:Aged, 80 and over D002112:Calcifediol D002117:Calcitriol D002118:Calcium D002136:Calcium, Dietary D002762:Cholecalciferol D019587:Dietary Supplements D004305:Dose-Response Relationship, Drug D004311:Double-Blind Method D005260:Female D006801:Humans D008297:Male D009752:Nutritional Status D010281:Parathyroid Hormone D014807:Vitamin D
Supplementation Calcifediol 25-Hydroxyvitamin D Vitamin D Dose–response PTH