Phthalate exposure and hyperuricemia: the mediating role of obesity.

Although epidemiological evidence links phthalate exposure to hyperuricemia development, the mediating role of obesity in this association remains unclear. We performed a cross-sectional study of 9194 eligible participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 cycles. Multivariate linear, logistic regression and restricted cubic splines were employed to assess dose-response relationships between ten phthalate metabolites (including monocarboxyoctyl phthalate (MCOP), monocarboxynonyl phthalate (MCNP), monobutyl phthalate(MBP), monoethyl phthalate(MEP), mono-isobutyl phthalate(MiBP), monobenzyl phthalate(MBzP), mono(3-carboxypropyl) phthalate (MCPP),mono(2-ethyl-5-hydroxyhexyl) phthalate(MEHHP),mono(2-ethyl-5-oxohexyl) phthalate(MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate(MECPP)) and both serum uric acid/ hyperuricemia risk. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models evaluated mixture effects, while causal mediation analysis quantified body mass index (BMI) 's mediating role. Interaction effects were examined through cross-product terms in linear regression models. All phthalate metabolites except MEP demonstrated positive dose-response associations with uric acid elevation and hyperuricemia. WQS and BKMR models identified significant mixture effects, MBzP being the primary contributor. BMI mediated 37.45%-62.67% of the total effect in the associations of individual phthalate metabolites and uric acid levels/hyperuricemia risk. Significant interaction was observed between BMI and MBzP. Our findings substantiate that both single and mixed phthalate metabolites exhibit significant uric acid dysregulation effects, mediated substantially through adiposity. This evidence highlights the clinical relevance of weight control strategies in phthalate-exposed populations.