Association of Body Weight With Response to Vitamin D Supplementation and Metabolism.
Level 2 - randomized trial
Secondary biomarker cohort analysis of a large randomized controlled trial
PubMed 36648947 · doi:10.1001/jamanetworkopen.2022.50681
What was done
In a secondary cohort analysis of the VITAL randomized, double-blind, placebo-controlled trial, researchers evaluated the effect of cholecalciferol (2000 IU/d) versus placebo on vitamin D metabolism across body mass index (BMI) categories. Blood samples were analyzed at baseline in 16,515 participants (mean age 67.7 years; 50.7% women; 76.9% non-Hispanic White) and at 2-year follow-up in a subset of 2,742 participants. Biomarkers measured included total 25-hydroxyvitamin D (25-OHD), 25-OHD3, free vitamin D (FVD), bioavailable vitamin D (BioD), vitamin D-binding protein (VDBP), albumin, parathyroid hormone (PTH), and calcium.
What was found
Baseline total 25-OHD was progressively lower with higher BMI (adjusted mean [SE]: underweight, 32.3 [0.7] ng/mL; normal weight, 32.3 [0.1] ng/mL; overweight, 30.5 [0.1] ng/mL; obesity class I, 29.0 [0.2] ng/mL; obesity class II, 28.0 [0.2] ng/mL; P < .001 for trend). Baseline 25-OHD3, FVD, BioD, VDBP, albumin, and calcium levels were also lower with higher BMI, whereas PTH was higher (all P < .001). At 2 years, vitamin D supplementation increased total 25-OHD, 25-OHD3, FVD, and BioD relative to placebo, but these increases were significantly blunted in higher BMI categories (all interaction P < .001). Supplementation did not substantially change VDBP, albumin, PTH, or calcium levels.
Why it matters
These findings show that individuals with overweight or obesity experience a diminished rise in circulating vitamin D biomarkers from fixed-dose supplementation, providing a metabolic explanation for why clinical trials often observe reduced health benefits in higher-weight groups.
Limits
Follow-up blood measurements were available for only 2,742 of the initial 16,515 participants. The population was predominantly older and non-Hispanic White, limiting generalizability to younger and more diverse cohorts, and direct clinical endpoints were not assessed in this biomarker analysis.
Cited by
- supports Vitamin D bioavailability is reduced in individuals with obesity compared to non-obese individuals.