| 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 (TNFalpha), 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 (beta-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 (beta-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 TNFalpha 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. |
