Effects of cholecalciferol vs. calcifediol on total and free 25-hydroxyvitamin D and parathyroid hormone

Research output: Contribution to journalArticle


  • Albert Shieh
  • Christina Ma
  • Rene F Chun
  • Sten Witzel
  • Brandon Rafison
  • Hannah Tm Contreras
  • Jonas Wittwer-Schegg
  • Leon Swinkels
  • Tonnie Huijs
  • John S Adams

Colleges, School and Institutes

External organisations

  • Department of Medicine, University of California, Los Angeles.
  • David Geffen School of Medicine at UCLA
  • Department of Orthopaedic Surgery, University of California, Los Angeles.
  • Future Diagnostics.
  • Institute of Metabolism and Systems Research, The University of Birmingham.


Context: Vitamin D deficiency (25-hydroxyvitamin D [25D] <20 ng/ml) disproportionately affects non-Caucasian individuals. Controversy persists over: 1) how to best restore low 25D levels; and 2) how to best define vitamin D status (total [protein-bound + free] vs. free 25D). Objective: To assess: 1) the effects of vitamin D3 (cholecalciferol, D3) vs. pharmacologic 25-hydroxyvitamin D3 (calcifediol, 25D3) on total and free 25D in a multi-ethnic cohort of adults; and 2) whether change in parathyroid hormone (PTH) is more strongly associated with total vs. free 25D. Design: 16-week randomized controlled trial. Biochemistries at 0, 4, 8, and 16 weeks. Intervention: 60 mcg (2,400 IU)/day of D3 or 20 mcg/day of 25D3. Setting: Academic medical center. Participants: 35 adults >18 years with 25D levels <20 ng/ml. Main Outcome Measures: Total and free 25D, PTH. Results: Baseline total (16.2 + 3.7 vs. 17.0 + 2.5 ng/ml, p=0.4) and free (4.2 + 0.8 vs. 4.7 + 1.0 pg/ml, p=0.2) 25D were similar between D3 and 25D3 groups, respectively. 25D3 increased total (+25.5 vs. +13.8 ng/ml, p=0.001) and free (+6.6 vs. +3.5 pg/ml, p=0.03) 25D more than D3. By 4 weeks, 87.5% of 25D3 participants had total 25D levels >30 ng/ml, compared to 23.1% of D3 participants (p=0.001). These trends were consistent across race/ethnicity. Change in PTH was similarly associated with both total (p=0.01) and free 25D (p=0.04). Conclusions: 25D3 increased total and free 25D levels more rapidly than D3, regardless of race/ethnicity. Free and total 25D were similarly associated with change in PTH.


Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Early online date10 Feb 2017
Publication statusE-pub ahead of print - 10 Feb 2017