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

Abstract

Acute exposure to fine particle (PM) 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 (250 μg/m) under placebo, and PM (250 μg/m) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B, and 1 mg/d vitamin B), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4 T-helper cells. PM induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM effect by 102% ( = 0.01). Our study indicates that individual-level prevention may be used to complement regulations and control potential mechanistic pathways underlying the adverse PM effects, with possible significant public health benefit in areas with frequent PM peaks.

Joint effects of prenatal air pollutant exposure and maternal folic acid supplementation on risk of autism spectrum disorder

“…A recent crossover study of 10 adults showed changes in DNA methylation in 10 loci following two hours of controlled PM2.5 exposure. These changes were not observed in the same 10 loci when PM2.5 exposure followed four weeks of B vitamin supplementation, including high doses of folic acid (2.5mg/d) and vitamin B6 (50 mg/d) (Zhong et al, 2017). …”

B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial

“…As previously described19, all volunteers (baseline characteristics described in Supplementary Table 1) completed three controlled exposure experiments (July 2013 to February 2014) (Fig. 1).…”

“…We recruited ten healthy, 18–60-year-old, non-smoking volunteers who were not on any form of B vitamin supplementation or other medication, from the University of Toronto St. George campus and surrounding area (downtown Toronto, Ontario, Canada)19. The number to recruit was determined through power calculation based on a 2-sided alternative at α = 0.05/6 = 0.0833 to reflect a Bonferroni correction for multiple testing (six HRV indexes).…”

“…1)19 with controlled exposure experiments (July 2013 to February 2014). A two-hour sham exposure experiment (exposure one, particle-free medical air) was included to provide baseline data.…”

“…After exposure two, we administered B vitamin supplements for four weeks before the next two-hour exposure experiment to PM 2.5 (exposure three, 250 μg/m 3 ). The four-week placebo or B vitamin treatment also served as washout periods between exposure experiments to diminish the carryover effect of PM 2.5 exposure1940, while minimizing the impact of seasonality and temporal trend on the source and composition of the concentrated ambient PM 2.5 . To ensure comparable conditions across all controlled exposure experiments to PM 2.5 , the present study could not randomize on the treatment (placebo vs B vitamins) sequence because vitamin B 12 has a biological half-life longer than four months41.…”