Dose response to vitamin D supplementation in African Americans: results of a 4-arm, randomized, placebo-controlled trial

Abstract

Background: Association studies have suggested that lower circulating 25-hydroxyvitamin D [25(OH)D] in African Americans may partially underlie higher rates of cardiovascular disease and cancer in this population. Nonetheless, the relation between vitamin D supplementation and 25(OH)D concentrations in African Americans remains undefined.

Objective: Our primary objective was to determine the dose-response relation between vitamin D and plasma 25(OH)D.

Design: A total of 328 African Americans in Boston, MA, were enrolled over 3 winters from 2007 to 2010 and randomly assigned to receive a placebo or 1000, 2000, or 4000 IU vitamin D₃/d for 3 mo. Subjects completed sociodemographic and dietary questionnaires, and plasma samples were drawn at baseline and 3 and 6 mo.

Results: Median plasma 25(OH)D concentrations at baseline were 15.1, 16.2, 13.9, and 15.7 ng/mL for subjects randomly assigned to receive the placebo or 1000, 2000, or 4000 IU/d, respectively (P = 0.63). The median plasma 25(OH)D concentration at 3 mo differed significantly between supplementation arms at 13.7, 29.7, 34.8, and 45.9 ng/mL, respectively (P < 0.001). An estimated 1640 IU vitamin D₃/d was needed to raise the plasma 25(OH)D concentration to ≥ 20 ng/mL in ≥ 97.5% of participants, whereas a dose of 4000 IU/d was needed to achieve concentrations ≥ 33 ng/mL in ≥ 80% of subjects. No significant hypercalcemia was seen in a subset of participants.

Conclusions: Within African Americans, an estimated 1640 IU vitamin D₃/d was required to achieve concentrations of plasma 25(OH)D recommended by the Institute of Medicine, whereas 4000 IU/d was needed to reach concentrations predicted to reduce cancer and cardiovascular disease risk in prospective observational studies. These results may be helpful for informing future trials of disease prevention.

Trial registration: ClinicalTrials.gov NCT00585637.

Figures

FIGURE 1.

Consolidated Standards of Reporting Trials diagram. 25(OH)D, 25-hydroxyvitamin D.

FIGURE 2.

Plasma 25(OH)D concentrations (ng/mL) at baseline and 3 and 6 mo according to vitamin D3 dose. 25(OH)D, 25-hydroxyvitamin D.

FIGURE 3.

Graphical display of plasma 25(OH)D concentrations (ng/mL) at 3 mo and dose of vitamin D3 supplementation (n = 67 for 1000 IU/d; n = 76 for 2000 IU/d; n = 78 for 4000 IU/d). The solid line is a quadratic fit to the observed mean plasma 25(OH)D concentration. The dashed line falls below the mean line by 1.96 SDs of the distribution of the estimated within-subject mean concentration (obtained from the random patient effect in the mixed model) and represents the empirical Bayesian prediction interval to bound 97.5% of future subjects’ mean plasma 25(OH)D concentrations. This prediction interval crosses the 20-ng/mL line at 1640 IU/d (95% CI: 1490, 2020 IU/d), indicating that an estimated dose of 1640 IU vitamin D3/d is required to achieve an individual mean plasma 25(OH)D concentration at ≥20 ng/mL in ≥97.5% of the study population. 25(OH)D, 25-hydroxyvitamin D.