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

Anouk M. M. Vaes*, Michael Tieland, Margot F. de Regt, Jonas Wittwer, Luc J. C. van Loon, Lisette C. P. G. M. de Groot

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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-2 or D-3 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-3 and assessed the dose which results in mean serum 25(OH)D-3 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 mu g calcifediol or 20 mu g vitamin D-3 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-3, 25(OH)D-3, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) and 24,25-dihydroxyvitamin D-3 (24,25(OH)(2)D-3). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated.

Results: Supplementation with 20 jig vitamin 03 increased 25(OH)D-3 concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 mu g calcifediol increased 25(OH)D-3 levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D-3 levels stabilizing between 84 and 89 nmol/L in the 10 mu g calcifediol group. A significant association was observed between the changes in 25(OH)D-3 and 24,25(OH)(2)D-3 (R-2 = 0.83, P <0.01), but not between 25(OH)D-3 and 1,25(OH)(2)D-3 (R-2 = 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-3 concentrations to improve vitamin D status in older adults. A daily dose of 10 mu g calcifediol allows serum 25(OH)D-3 concentrations to be maintained between 75 and 100 nmol/L.

Trial registration number: NCT01868945. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Original languageEnglish
Pages (from-to)808-814
Number of pages7
JournalClinical Nutrition
Issue number3
Publication statusPublished - Jun 2018


  • Vitamin D
  • Calcifediol
  • Dose response
  • Supplementation
  • 25-Hydroxyvitamin D
  • PTH
  • D-3
  • 25(OH)D
  • FOOD
  • AGE

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