Associations between exposure to multiple environmental chemicals and metabolic syndrome: A mixture analysis

• Exposure to phenols, PAHs, metals, and phthalates was associated with higher MetS risk. • Strong associations observed for 2-PHE and MEHHP with MetS and its components. • The association between chemical exposure and MetS was stronger in current smokers. Exposure to environmental chemicals is prevalent. While previous studies reported associations between multiple chemical exposures and metabolic syndrome (MetS), they did not comprehensively account for correlations among exposures. We used machine learning methods including Boruta algorithm and least absolute shrinkage and selection operator (LASSO) regression, combined with weighted quartiles sum (WQS) regression to investigate the associations of phenols, polycyclic aromatic hydrocarbons (PAHs), metals, and phthalates with MetS and its components. Data were drawn from the 2005-2012 National Health and Nutrition Examination Survey (NHANES). The mean (standard deviation (SD)) age of 2596 participants was 48.4 (17.9) years. After adjusting for age, sex, body mass index, race/ethnicity, marital status, education, poverty income ratio, physical activity, smoking, and alcohol, higher 2-Phenanthrene (2-PHE) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) concentrations were associated with a higher odds of the MetS (odds ratio (OR) = 4.26, 95% confidence interval (CI) 2.40-7.58 per ng/mL, and 3.24, 1.75-6.02 per ng/L, respectively). WQS index for environmental chemicals was positively associated with the MetS (OR=1.31, 95% CI 1.09-1.57). Moreover, we observed consistent and stronger positive associations with MetS (OR=1.54, 95% CI 1.04-2.30) in current smokers. Exposure to phenols, PAHs, metals, and phthalates was positively associated with an increase in metabolic syndrome and its components, which was more pronounced in current smokers.