ORIGINAL ABSTRACT

Glyphosate is the most widely used herbicide in the world. This study aimed to evaluate the relationships among urinary glyphosate, all-cause mortality and cardiovascular diseases (CVD)-related mortality in the general US population of adults, and to determine the role of alkaline phosphatase (ALP), an inflammation marker that is associated with glyphosate exposure, in these relationships. Subjects from the National Health and Nutrition Examination Survey (NHANES) 2013-2018 cycles were included. Survey-weighted Cox regression analysis was applied to estimate the relationship of glyphosate with overall and CVD mortalities. Restricted cubic spline (RCS) analysis was utilized to detect the linearity of associations. The intermediary role of ALP was explored by mediation analysis. Our results found consistent and positive associations of glyphosate with all-cause mortality (HR: 1.29, 95%CI: 1.05-1.59) and CVD mortality (HR: 1.32, 95%CI: 1.02-1.70). RCS curves further validated linear and positive dose-dependent relationships between glyphosate and mortality-related outcomes. Moreover, serum ALP was identified as a mediator in these associations and explained 12.1% and 14.0% of the total associations between glyphosate and all-cause death and CVD death risk, respectively. Our study indicated that glyphosate was associated with increased all-cause and CVD mortality in humans. Increased ALP may play an essential role in these associations.