Vitamin D 3 Supplementation Increases Long-Chain Ceramide Levels in Overweight/Obese African Americans: A Post-Hoc Analysis of a Randomized Controlled Trial.

Sphingolipid metabolism plays a critical role in cell growth regulation, lipid regulation, neurodevelopment, type 2 diabetes, and cancer. Animal experiments suggest that vitamin D may be involved in sphingolipid metabolism regulation. In this study, we tested the hypothesis that vitamin D supplementation would alter circulating long-chain ceramides and related metabolites involved in sphingolipid metabolism in humans. We carried out a post-hoc analysis of a previously conducted randomized, placebo-controlled clinical trial in 70 overweight/obese African-Americans, who were randomly assigned into four groups of 600, 2000, 4000 IU/day of vitamin D ₃ supplements or placebo for 16 weeks. The metabolites were measured in 64 subjects (aged 26.0 ± 9.4 years, 17% male). Serum levels of N -stearoyl-sphingosine (d18:1/18:0) (C18Cer) and stearoyl sphingomyelin (d18:1/18:0) (C18SM) were significantly increased after vitamin D ₃ supplementation ( p s < 0.05) in a dose-response fashion. The effects of 600, 2000, and 4000 IU/day vitamin D ₃ supplementation on C18Cer were 0.44 ( p = 0.049), 0.52 ( p = 0.016), and 0.58 ( p = 0.008), respectively. The effects of three dosages on C18SM were 0.30 ( p = 0.222), 0.61 ( p = 0.009), and 0.68 ( p = 0.004), respectively. This was accompanied by the significant correlations between serum 25-hydroxyvitamin D ₃ [25(OH)D] concentration and those two metabolites ( p s < 0.05). Vitamin D ₃ supplementations increase serum levels of C18Cer and C18SM in a dose-response fashion among overweight/obese African Americans.