Effects of Vitamin D3 Supplementation on Epigenetic Aging in Overweight and Obese African Americans With Suboptimal Vitamin D Status: A Randomized Clinical Trial

J Gerontol A Biol Sci Med Sci. 2019 Jan 1;74(1):91-98. doi: 10.1093/gerona/gly223.


Background: We have previously shown that vitamin D supplementation increases telomerase activity, suggesting an anti-aging effect. In this study, we aim to test the hypothesis that vitamin D supplementation would slow down epigenetic aging, a new marker of biological aging.

Methods: A randomized clinical trial was previously conducted among 70 overweight/obese African Americans with serum 25-hydroxyvitamin D [25(OH)D] < 50 nmol/L, who were randomly assigned into four groups of 600 IU/d, 2,000 IU/d, 4,000 IU/d of vitamin D3 supplements or placebo followed by 16-week interventions. Whole genome-wide DNA methylation analysis was conducted in 51 participants. DNA methylation ages were calculated according to the Horvath and the Hannum methods. Methylation-based age acceleration index (∆Age) is defined as the difference between DNA methylation age and chronological age in years. Mixed-effects models were used to evaluate the treatment effects.

Results: Fifty-one participants (aged 26.1 ± 9.3 years, 16% are male) were included in the study. After the adjustment of multi-covariates, vitamin D3 supplementation of 4,000 IU/d was associated with 1.85 years decrease in Horvath epigenetic aging compared with placebo (p value = .046), and 2,000 IU/d was associated with 1.90 years decrease in Hannum epigenetic aging (p value = .044). Serum 25(OH)D concentrations were significantly associated with decreased Horvath ∆Age only (p values = .002), regardless of treatments.

Conclusions: Our results suggest that vitamin D supplementation may slow down Horvath epigenetic aging. But the effect on Hannum epigenetic aging is not conclusive. Large-scale and longer duration clinical trials are needed to replicate the findings.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • African Americans*
  • Aging
  • Cholecalciferol / therapeutic use*
  • DNA Methylation / drug effects
  • Dietary Supplements
  • Double-Blind Method
  • Epigenesis, Genetic*
  • Female
  • Follow-Up Studies
  • Georgia / epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Obesity / ethnology*
  • Obesity / genetics
  • Obesity / therapy
  • Overweight / ethnology*
  • Overweight / genetics
  • Overweight / therapy
  • Retrospective Studies
  • Telomerase / genetics*
  • Telomerase / metabolism
  • Vitamins / therapeutic use
  • Young Adult


  • Vitamins
  • Cholecalciferol
  • Telomerase