Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults

Abstract

Background: Many factors have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in observational studies, with variable consistency. However, less information is available on factors affecting the magnitude of changes in serum 25(OH)D resulting from vitamin D supplementation.

Objective: This study aimed to identify factors associated with the serum 25(OH)D response to supplementation with 1000 IU cholecalciferol/d during the first year of a large, multicenter, randomized, placebo-controlled colorectal adenoma chemoprevention trial.

Methods: Eligible older adults who were not vitamin D-deficient [serum 25(OH)D ≥12 ng/mL] were randomly assigned in a modified 2 × 2 factorial design to 1 of 4 groups: daily 1000 IU cholecalciferol, 1200 mg Ca as carbonate, both, or placebo. Women could elect 2-group (calcium ± cholecalciferol) random assignment. In secondary analyses, we used multivariable models to assess factors associated with serum 25(OH)D concentrations in all enrollees (n = 2753) and with relative changes in serum 25(OH)D after 1 y cholecalciferol supplementation among those randomly assigned (n = 2187).

Results: In multivariable models, 8 factors accounted for 50% of the variability of proportional change in serum 25(OH)D after cholecalciferol supplementation. Larger increases were associated with being female (34.5% compared with 20.5%; P < 0.001) and with lower baseline serum 25(OH)D (P < 0.0001), optimal adherence to study pill intake (P = 0.0002), wearing long pants and sleeves during sun exposure (P = 0.0002), moderate activity level (P = 0.01), use of extra vitamin D-containing supplements during the trial (P = 0.03), and seasons of blood draw (P ≤ 0.002). Several genetic polymorphisms were associated with baseline serum 25(OH)D and/or serum response, but these did not substantially increase the models' R2 values. Other factors, including body mass index, were associated with serum 25(OH)D at baseline but not with its response to supplemental cholecalciferol.

Conclusions: The factors that most affected changes in serum 25(OH)D concentrations in response to cholecalciferol supplementation included sex, baseline serum 25(OH)D, supplement intake adherence, skin-covering clothes, physical activity, and season. Genetic factors did not play a major role. This trial was registered at www.clinicaltrials.gov as NCT00153816.

Keywords: 25-hydroxyvitamin D; calcium; cholecalciferol; dose response; randomized controlled trial; vitamin D3.

Conflict of interest statement

2 Author disclosures: JR Rees, LA Mott, EL Barry, JA Baron, RM Bostick, JC Figueiredo, RS Bresalier, DJ Robertson, and JL Peacock, no conflicts of interest.

© 2016 American Society for Nutrition.

Figures

FIGURE 1

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

FIGURE 2

Changes in serum 25-hydroxyvitamin D concentrations in older adults who received daily supplements containing cholecalciferol, calcium, both, or placebo. Values shown are the proportions achieving deficient, inadequate, or adequate status after 1 y in each of 4 baseline categories: 1) inadequate vitamin D status randomly assigned to placebo (n = 194), 2) inadequate vitamin D status randomly assigned to cholecalciferol (n = 181), 3) adequate vitamin D status randomly assigned to placebo (n = 267), and 4) adequate vitamin D status randomly assigned to cholecalciferol (n = 279). Individuals were excluded from analysis if they were vitamin D–deficient at baseline, had been taking vitamin D supplements before enrollment, or took personal vitamin D supplements during year 1. All measures are unadjusted.