Effects of Vitamin D3 Supplementation on Epigenetic Aging in Overweight and Obese African Americans With Suboptimal Vitamin D Status: A Randomized Clinical Trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 30256915 · doi:10.1093/gerona/gly223
What was done
A 16-week randomized trial evaluated overweight or obese African Americans with baseline serum 25(OH)D < 50 nmol/L assigned to four parallel groups: placebo, 600 IU/d, 2,000 IU/d, or 4,000 IU/d of vitamin D3. Genome-wide DNA methylation was measured in 51 participants (mean age 26.1 ± 9.3 years, 16% male) out of 70 enrolled. Biological age was calculated using Horvath and Hannum epigenetic clocks, and methylation-based age acceleration (∆Age) was analyzed with mixed-effects models adjusting for multiple covariates.
What was found
Compared to placebo, 4,000 IU/d vitamin D3 was associated with a 1.85-year reduction in Horvath epigenetic aging (p = .046), while 2,000 IU/d was associated with a 1.90-year reduction in Hannum epigenetic aging (p = .044). Higher serum 25(OH)D concentrations correlated significantly with lower Horvath ∆Age (p = .002) regardless of treatment arm, but did not correlate with Hannum ∆Age.
Why it matters
This study provides preliminary human trial evidence that correcting suboptimal vitamin D status may influence DNA methylation biomarkers associated with biological aging.
Limits
The sample size was small (n = 51 analyzed) with an 84% female skew, limiting generalizability. Findings were inconsistent across clocks (Horvath showed an effect at 4,000 IU/d, whereas Hannum showed an effect only at 2,000 IU/d), the intervention duration was short (16 weeks), and clinical longevity or healthspan outcomes were not measured.
Cited by
- supports In severely vitamin D-deficient African Americans who are overweight or obese, supplementing with 4,000 IU of vitamin D daily for 16 weeks reverses epigenetic aging.