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

Acute exposure to fine particle (PM_2.5) 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, PM_2.5 (250 μg/m³) under placebo, and PM_2.5 (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. PM_2.5 induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM_2.5 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 PM_2.5 effect by 102% (P_interaction = 0.01). Our study indicates that individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM_2.5 effects, with possible significant public health benefit in areas with frequent PM_2.5 peaks.