Association of Body Weight With Response to Vitamin D Supplementation and Metabolism

Post hoc analysis of the Vitamin D and Omega-3 Trial (VITAL); randomized, double-blind, placebo-controlled 2x2 factorial design of vitamin D3 (2000 IU/d) and omega-3 fatty acids; participants were men aged ≥50 and women aged ≥55 without cancer or cardiovascular disease at baseline; baseline blood samples from 16,515 participants and year-2 samples from 2,742.

Vitamin D3 (cholecalciferol), 2000 IU/day, orally, for 2 years.

Vitamin D3 supplementation increased total 25-OHD, 25-OHD3, free vitamin D, and bioavailable vitamin D over 2 years vs placebo, but the increases were smaller in participants with higher baseline BMI. Baseline BMI was associated with lower levels of several vitamin D biomarkers; vitamin D–carrier proteins (VDBP, albumin) and calcium were largely unchanged, and PTH changes were minimal. Interpretation: adiposity may blunt vitamin D metabolism/availability, potentially partially explaining reduced health benefits of supplementation in overweight/obese individuals; higher or tailored dosing may be needed in this population.

Limitations include self-reported baseline BMI, potential residual confounding, and analysis limited to a subset with biomarker data and repeat measurements; adherence was high (94%), but postrandomization factors could bias results; generalizability to non-US populations may be limited.