title: B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial.
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. PM2.5induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM2.5depleted 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 PM2.5effect 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 PM2.5effects, with possible significant public health benefit in areas with frequent PM2.5peaks.
authors.affiliation: Mailman School of Public Health, Columbia University, New York, NY 10032; jiazhong@mail.harvard.edu.
authors.forename: Jia
authors.identifier: 0000-0003-4582-6896
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.|Department of Pharmaceutical Biosciences, Uppsala University, 752 37 Uppsala, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Karlsson
authors.affiliation: Institute for Genomic Medicine, Columbia University, New York, NY 10032.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Singapore Institute for Clinical Sciences, Singapore 117609.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115.
authors.forename: Michele
authors.initials: M
authors.lastname: Zemplenyi
authors.affiliation: Department of Developmental Neurobiology, National Institute of Perinatology, Mexico City 11000, Mexico.
authors.forename: Marco
authors.initials: M
authors.lastname: Sanchez-Guerra
authors.affiliation: Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115.
authors.forename: Letizia
authors.initials: L
authors.lastname: Trevisi
authors.affiliation: 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.
authors.forename: Bruce
authors.initials: B
authors.lastname: Urch
authors.affiliation: Division of Occupational & Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Speck
authors.affiliation: Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115.
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115.
authors.forename: Petros
authors.initials: P
authors.lastname: Koutrakis
authors.affiliation: 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.
authors.forename: Frances
authors.initials: F
authors.lastname: Silverman
authors.affiliation: Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115.|Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
authors.affiliation: 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.
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.affiliation: Mailman School of Public Health, Columbia University, New York, NY 10032.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution; D018592:Cross-Over Studies; D019175:DNA Methylation / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D057890:Epigenomics; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D052638:Particulate Matter / Q000633:toxicity*; D010865:Pilot Projects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism; D014805:Vitamin B 12 / Q000008:administration & dosage*; D025101:Vitamin B 6 / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D004272:DNA, Mitochondrial; D052638:Particulate Matter; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12
keywords: B vitamins; DNA methylation; air pollution; mitochondria