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

Mailman School of Public Health, Columbia University, New York, NY 10032; jiazhong@mail.harvard.edu. Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. Department of Pharmaceutical Biosciences, Uppsala University, 752 37 Uppsala, Sweden. Institute for Genomic Medicine, Columbia University, New York, NY 10032. Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, 430030. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China, 430030. Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115. Singapore Institute for Clinical Sciences, Singapore 117609. Department of Developmental Neurobiology, National Institute of Perinatology, Mexico City 11000, Mexico. Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115. Division of Occupational & Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada. Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada. Southern Ontario Centre for Atmospheric Aerosol Research, Toronto, ON M5S 3E5, Canada. Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115. Mailman School of Public Health, Columbia University, New York, NY 10032.

Proceedings of the National Academy of Sciences of the United States of America. 2017;(13):3503-3508
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Abstract

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.

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Publication Type : Clinical Trial

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