Urinary Phthalate Metabolites Associated with Increased Prevalence of Gallstone Disease in U.S. Adults: Data from the NHANES Study

Background Phthalate exposure has been hypothesized to influence cholesterol metabolism and gallstone pathogenesis, but previous studies are limited. We aimed to examine the associations between urinary phthalate metabolites and prevalence of gallstone disease in a nationally representative sample. Methods We analyzed data on 1,696 adults aged ≥ 6 years from the National Health and Nutrition Examination Survey (NHANES) 2017–2018. Gallstone disease was defined based on self-reported physician-diagnosis. Exposure was measured by urinary concentrations of 10 phthalate metabolites. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) assessed metabolite mixtures in relation to gallstones. Results Elevated urinary concentrations of mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(3-carboxypropyl) phthalate (MCPP), mono-n-butyl phthalate (MnBP), and mono-carboxyoctyl phthalate (MCOP) were associated with 43–82% higher odds of gallstones compared to lower exposure groups. The WQS index exhibited a significant positive association with gallstone prevalence (OR: 1.49; 95%CI: 1.10, 2.02). BKMR identified exposure-response trends for MECPP, MCPP, and mono-benzyl phthalate (MBzP). Conclusion Higher urinary phthalate metabolite concentrations were associated with increased gallstone risk. These novel findings suggest phthalate exposure may contribute to lithogenic pathogenesis. Future prospective and mechanistic research is warranted.