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.

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Inhibition, one of the building blocks of executive function, is the ability to focus one’s attention despite interference from external stimuli. It undergoes substantial development during adolescence and may be susceptible to adverse impacts of prenatal exposure to chemical mixtures, yet few studies have explored this association. The New Bedford Cohort (NBC) is a birth cohort of residents living near the New Bedford Harbor Superfund site in Massachusetts. Among adolescents from the NBC, we investigated the association of biomarkers of prenatal exposure to organochlorines (DDE, HCB, PCBs) and metals (Pb, Mn) with inhibition, assessed with the Delis–Kaplan Executive Function System Design Fluency (non-verbal task) and Color–Word Interference (verbal task) subtests. An exploratory mixtures analysis using Bayesian kernel machine regression (BKMR) informed a traditional multivariable regression approach. NBC adolescents are diverse with 29% non-white and 31% in a low-income household at birth. Cord serum organochlorine concentrations and cord blood metals concentrations were generally similar to other birth cohorts. In BKMR models, we observed a suggestive adverse association of the chemical mixture with Color–Word Interference but not Design Fluency. In covariate-adjusted linear regression models including all five chemical exposure measures, a doubling of cord blood Mn was associated with poorer Color–Word Interference completion time scaled scores (difference = −0.74; 95% CI: −1.34, −0.14). This study provided evidence of an adverse joint association between prenatal exposure to a five-chemical mixture and verbal inhibition in adolescence with exposure to Mn potentially driving this overall association.

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