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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/m 3 ) under placebo, and PM 2.5 (250 μg/m 3 ) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B 6 , and 1 mg/d vitamin B 12 ), 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.

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