B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial

Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3503-3508. doi: 10.1073/pnas.1618545114. Epub 2017 Mar 13.


Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 μg/m3) under placebo, and PM2.5 (250 μg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4+ T-helper cells. PM2.5 induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM2.5 depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; P = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM2.5 effect by 102% (Pinteraction = 0.01). Our study indicates that individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM2.5 effects, with possible significant public health benefit in areas with frequent PM2.5 peaks.

Keywords: B vitamins; DNA methylation; air pollution; mitochondria.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Air Pollutants / toxicity*
  • Air Pollution
  • Cross-Over Studies
  • DNA Methylation / drug effects
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Epigenesis, Genetic / drug effects*
  • Epigenomics
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • Male
  • Particulate Matter / toxicity*
  • Pilot Projects
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 6 / administration & dosage*
  • Young Adult


  • Air Pollutants
  • DNA, Mitochondrial
  • Particulate Matter
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12