Plasma 25-hydroxyvitamin D3 response to vitamin D supplementation in obese and non-obese men and women

Abstract

Context: Obese adults are more susceptible to poor vitamin D status and response to supplementation than lean adults, but explanatory mechanisms remain unclear. Proposed hypotheses include increased degradation or adipose tissue sequestration of vitamin D.

Objective: The purpose of this study was to investigate how plasma 25-hydroxyvitamin D₃ [25(OH)D₃] concentrations respond to vitamin D repletion relative to changes in plasma vitamin D ₃ and the major degradation metabolite, 24,25-dihydroxyvitamin D ₃ [24,25(OH)₂D₃]. We also investigated how obesity and obesity-related adipose tissue inflammation affects vitamin D status.

Methods: This was a randomized intervention pilot study that supplemented daily oral vitamin D₃ doses of either 2,000 IU or 4,000 IU to fifteen vitamin D-deficient, overweight to obese adults for three months. At baseline and 3-month visits, we measured concentrations of vitamin D₃, 25(OH)D₃, and 24,25(OH)₂D ₃ in plasma and adipose tissue using high performance liquid chromatography-tandem mass spectrometry. We also measured gene expression of the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNFα), in adipose tissue.

Results: Plasma concentration of 25(OH)D₃ significantly increased after supplementation (p < 0.001), and increased more in the 4,000 IU/d group than in the 2,000 IU/d group (p = 0.04). Change in plasma 25(OH)D₃ was positively associated with change in plasma 24,25(OH) ₂D₃ (β-coefficient 3.7, 95% CI 1.9-5.4, p = 0.001), but not associated with change in plasma vitamin D₃. We also computed a multivariable model that included change in plasma concentrations of both vitamin D₃ and 24,25(OH)₂D₃ as independent variables and adjusted for dose. In this analysis, the association between changes in plasma 25(OH)D₃ and 24,25(OH)₂D₃ remained significantly positive, but the association between changes in plasma 25(OH)D₃ and vitamin D₃ became significantly inverse (β-coefficient -0.4, 95% CI -0.8- -0.01, p = 0.046). BMI was not significantly associated with the changes in plasma 25(OH)D₃, 24,25(OH) ₂D₃, or vitamin D₃. Adipose tissue expression of TNFα was not associated with changes in plasma 25(OH)D₃ or 24,25(OH)₂D₃.

Conclusion: Our findings were inconclusive about the sequestration hypothesis and did not support the hypothesis that the obese degrade more vitamin D than the lean due to greater adipose tissue inflammation. Future studies should investigate how baseline vitamin D status affects vitamin D response in the obese population.