Association of glyphosate exposure with frailty and all-cause mortality in general adults: A population-based cohort study

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Glyphosate is the most widely used herbicide globally. However, its association with frailty, an emerging public health concern, and mortality in the general population remains unclear. This cohort utilized the National Health and Nutrition Examination Survey (NHANES) 2013–2018 data, with follow-up through December 31, 2019. Weighted logistic regression, Cox regression, and restricted cubic splines analyses were performed to investigate the association of urinary glyphosate with frailty, defined using a 49-item frailty index at baseline, and all-cause mortality, respectively. Causal mediation analysis and sensitivity analysis were also employed. 4697 adults (mean age: 47.1 years; 48.9 % male) were included. Multivariable logistic regression showed that elevated urinary glyphosate correlated with increased frailty prevalence (log 2 -transformed, adjusted OR = 1.14, 95 % CI: 1.04–1.25; quartiles, P for trend = 0.002), with a linear dose-response relationship ( P value for nonlinearity = 0.568). During a median follow-up of 3.9 years, 238 total deaths occurred. Multivariable-adjusted Cox regression demonstrated that urinary glyphosate was positively related to all-cause mortality (log 2 -transformed, adjusted HR = 1.19, 95 % CI: 1.07–1.31; quartiles, P for trend = 0.005). Additionally, frailty significantly mediated the association between glyphosate and all-cause mortality, with mediation proportion of 30.3 %. Urinary glyphosate was positively associated with frailty and all-cause mortality in the general US adult population. Frailty also played a partial mediator role in this relationship. These findings provide new evidence of adverse health effects of glyphosate and imply that enhanced efforts should be made to mitigate exposure to glyphosate. • Urinary glyphosate demonstrated a positive and linear association with frailty. • Urinary glyphosate was also positively associated with all-cause mortality. • Frailty played a partial mediator role in this relationship. • These findings suggest the need for strict measures to reduce glyphosate exposure.

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