Effect of adding B-vitamins to vitamin D and calcium supplementation on CpG methylation of epigenetic aging markers

Nutr Metab Cardiovasc Dis. 2018 Apr;28(4):411-417. doi: 10.1016/j.numecd.2017.12.006. Epub 2017 Dec 29.

Abstract

Background and aim: B-vitamins may influence DNA methylation. We studied the effects of vitamin D + Ca + B versus D + Ca on epigenetic age markers and biological age.

Methods and results: Participants (mean ± SD of age = 68.4 ± 10.1 years) were randomized to receive 1200 IE vitamin D3 plus 800 mg Ca-carbonate alone (n = 31) or with 0.5 mg B9, 50 mg B6, and 0.5 mg B12 (n = 32). The CpG methylation of 3 genes (ASPA, ITGA2B, and PDE4C) and the changes in methylation were compared between the groups after 1 year. The changes of ASPA methylation from baseline were higher in the D + Ca + B than in the D + Ca group (1.40 ± 4.02 vs. -0.96 ± 5.12, respectively; p = 0.046, adjusted for age, sex, and baseline methylation). The changes in PDE4C from baseline were slightly higher in the D + Ca + B group (1.95 ± 3.57 vs. 0.22 ± 3.57; adjusted p = 0.062). Methylation of ITGA2B and its changes from baseline were not different between the intervention groups. Sex-adjusted odds ratio of accelerated aging (chronological age < biological age at 1 year) was 5.26 (95% confidence interval 1.51-18.28) in the D + Ca + B compared with the D + Ca group. Accelerated aging in both groups was associated with younger age. In the D + Ca + B group, it was additionally associated with lower baseline homocysteine.

Conclusions: Vitamin D + Ca + B and D + Ca differentially affected epigenetic age markers, although the effect size appeared to be small after 1 year. B-vitamins effect in young subjects with low homocysteine requires further investigation. ClinicalTrials.gov ID: NCT02586181.

Keywords: Aging; DNA-Methylation; Epigenetics; Supplementation; Vitamins.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / blood
  • Aging / genetics*
  • Calcium Carbonate / administration & dosage*
  • Cholecalciferol / administration & dosage*
  • CpG Islands / drug effects*
  • DNA Methylation / drug effects*
  • Dietary Supplements*
  • Double-Blind Method
  • Epigenesis, Genetic / drug effects*
  • Female
  • Folic Acid / administration & dosage
  • Germany
  • Homocysteine / blood
  • Humans
  • Male
  • Middle Aged
  • Time Factors
  • Treatment Outcome
  • Vitamin B 12 / administration & dosage
  • Vitamin B 6 / administration & dosage
  • Vitamin B Complex / administration & dosage*

Substances

  • Homocysteine
  • Vitamin B Complex
  • Cholecalciferol
  • Vitamin B 6
  • Folic Acid
  • Calcium Carbonate
  • Vitamin B 12

Associated data

  • ClinicalTrials.gov/NCT02586181