Abstract P012: The Effect of Vitamin D Supplementation on Epigenetic Aging: A Randomized Placebo-Controlled Clinical Trial

Abstract

Background: Vitamin D deficiency is associated with age-related diseases, such as cardiovascular disease, diabetes and cancer. We have previously shown that vitamin D plays a role in regulating human epigenome. Moreover, we have demonstrated that vitamin D supplementation increases telomerase activity, suggesting an anti-aging property. Epigenetic age acceleration, an emerging marker of biological aging, predicts cardiovascular mortality, morbidity and cancer. In this study, we tested the hypothesis that vitamin D supplementation would decelerate epigenetic aging. Methods: We have previously completed a 16 week randomized placebo-controlled clinical trial of vitamin D3 supplementation in overweight/obese African-Americans (NCT01583621). The participants were randomly assigned into four groups of placebo, 600 IU/day, 2000 IU/day, and 4000 IU/day of vitamin D supplements. A genome-wide methylation scan was performed using the Illumina Human Methylation 480K Bead Chip on peripheral blood mononuclear cell DNA. DNA methylation age of 52 participants was determined based on 353 CpG sites using the statistical pipeline developed by Horvath. Epigenetic aging, methylation-based age acceleration index (Δage) was defined as the difference between DNA methylation age and chronological age in years. Mixed-effects models were used to evaluate the treatment effects. Results: DNAm age was significantly correlated with chronological age (r=0.9082, p-value < 0.001). The correlation was higher at baseline (r=0.9281, p-value < 0.001) than at 16 weeks (r=0.8887, p-value < 0.001), which implies that the 16 week treatment may drive the DNAm age deviated from the chronological age. Compared with placebo, vitamin D supplementation was also associated with decreased Δage after adjustment for sex, BMI, lymphocyte percentage, month and baseline 25(OH)D concentration (600 IU/day: β = 0.90, p-value = 0.325; 2000 IU/day: β= -1.21, p-value = 0.118; 4000 IU/day: β= -1.70, p-value = 0.035), but only the treatment effect of 4000 IU/day supplementation was significant. Conclusion: Our results suggest that vitamin D supplementation might decelerate epigenetic aging, further supporting the anti-aging effect of vitamin D supplementation in overweight/obese African Americans. Larger studies are needed to replicate the findings.