Associations between urine glyphosate levels and metabolic health risks: insights from a large cross-sectional population-based study

Background: Prevalence of the Metabolic Syndrome (MetS) in American adults has risen from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor. Methods: We employ three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and the MetS. We first created a MetS score using Exploratory Factor Analysis of 6 International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, Albumin to Creatinine Ratio. The score was validated via a machine-learning approach in predicting ACR score via binary classification, then used in multivariable regression to test association between quartile-categorized glyphosate exposure and the MetS score. Results: In adjusted multivariable regressions, quartile regressions between glyphosate exposure and MetS score show a significant inverted U-shaped or saturating dose-response profile, often with largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category shows significant differences by race and age, with older people (ages > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles. Conclusions: We find that urinary glyphosate is significantly associated with a statistical score designed to capture the MetS, and that dose-response is nonlinear, with advanced age and non-Hispanic African American and Mexican American and other Hispanic participants showing higher effect sizes.