Associations Between Urinary Phthalate Metabolites and Decreased Serum α-Klotho Level: A Cross-Sectional Study Among US Adults in Middle and Old Age

Phthalates are widely used chemicals with ubiquitous human exposure. Evidence indicated that phthalate exposure was associated with an increased risk of aging-related diseases. Klotho is a transmembrane protein with anti-aging functions, and its association with phthalates remains unknown. To find the association between phthalate exposure and serum alpha-Klotho, a cross-sectional study was performed in 4482 adults (40-79 years old) who completed the National Health and Nutrition Examination Survey (NHANES) (2007-2016). As shown in the results of multivariable linear regression analyses, mono(carboxynonyl) phthalate (MCNP) and mono-n-butyl phthalate (MBP) were inversely associated with alpha-Klotho, and the regression coefficients of MCNP and MBP were -1.14 (95% confidence interval (CI): -2.00, -0.27) and -0.08 (95% CI: -0.14, -0.02). Subgroup analyses based on the quartiles of each phthalate metabolite showed that both MCNP and MBP were only inversely associated with alpha-Klotho in the subgroups of the highest levels. For mono-isobutyl phthalate (MIBP), the inverse association with alpha-Klotho was only statistically significant in the subgroup of the lowest level, and the regression coefficient was -26.87 (95% CI: -52.53, -1.21). Our findings suggest that alpha-Klotho might be involved in the association of phthalate exposure with aging-related diseases. Future research investigating the causality between phthalates and alpha-Klotho and its underlying mechanisms is encouraged.