Effects of Cholecalciferol vs Calcifediol on Total and Free 25-Hydroxyvitamin D and Parathyroid Hormone

Context Vitamin D deficiency disproportionately affects nonwhite individuals. Controversy persists over how to best restore low 25D levels, and how to best define vitamin D status [total (protein bound plus free) vs free 25D]. Objective To assess the effects of vitamin D3 (cholecalciferol, or D3) vs 25-hydroxyvitamin D3 (calcifediol, or 25D3) on total and free 25D in a multiethnic cohort of adults, and whether change in parathyroid hormone (PTH) is more strongly associated with total vs free 25D. Design Sixteen-week randomized controlled trial. Biochemistries at 0, 4, 8, and 16 weeks. Setting Academic medical center. Participants Thirty-five adults ≥18 years of age with 25D levels <20 ng/mL. Intervention Sixty micrograms (2400 IU)/d of D3 or 20 μg/d of 25D3. Main Outcome Measures Total and free 25D, and 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 with 23.1% of D3 participants (P = 0.001). Change in PTH was 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.