Abstract

Introduction: The US Environment Protection Agency has proposed National Primary Drinking Water Regulation for six per- and polyfluoroalkyl substances including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). The health effects of the two chemicals need to be thoroughly evaluated. In addition, few studies have investigated interventions that can help clear the two chemicals from the human body. Hypothesis: We hypothesize that the plasma metabolome reflects reactions of the human body to PFOA/PFOS exposures and dietary supplements can reduce PFOA/PFOS. Methods: In the Protein and Blood Pressure (ProBP) trial, 80 participants were randomly assigned to take 40 grams/day of soy protein, milk protein, or carbohydrate supplementation each for 8 weeks in a cross-over design. Plasma PFOA and PFOS levels were tracked from baseline to each of the three intervention phases. We analyzed the associations of serum PFOS and PFOA with a total of 964 known metabolites at baseline and each dietary intervention, respectively. Age, sex, and race were adjusted in all analyses. ProBP findings were evaluated for replication among 1261 participants of the Bogalusa Heart Study (BHS). Results: PFOA and PFOS were significantly reduced after phase I and were decreased further with intervention phases. Soy protein showed the strongest reduction on both PFOA (net change: -0.13, p=1.13х10 -5 ) and PFOS (net change: -0.18, p=4.32х10 -5 ) compared with carbohydrate and milk protein. After Bonferroni correction for 77 independent metabolite clusters (p<6.49х10 -4 ), PFOS was positively associated with 54 metabolites (47 at baseline, 9 at soy protein, 8 at milk protein, and 6 at carbohydrate, respectively). Of which, 20 associations were replicated in BHS ( Table ). PFOA was positively associated with 3-methyladipate at soy protein and bilirubin (E,E) at milk protein. Conclusions: Dietary intervention reduced serum PFOA and PFOS. Several metabolites may play important roles in PFOA/PFOS related health effects.

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