Current marijuana use is associated with lower circulating α-Klotho levels in US adults even after adjusting for tobacco use: A national cross-sectional analysis of NHANES

INTRODUCTION: α-Klotho is a circulating protein linked to longevity and healthy aging. While tobacco use is known to reduce α-Klotho levels, the effects of marijuana use on this aging-related biomarker remain unclear. This study aimed to examine the association between marijuana use and serum α-Klotho levels in a nationally representative sample of US adults. METHODS: We conducted a secondary analysis of publicly available data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016, including 6601 adults aged 40-59 years with available serum α-Klotho levels and complete substance use data. Multivariable linear regression models were used to estimate the association between marijuana use and α-Klotho levels. RESULTS: Current marijuana use was significantly associated with lower serum α-Klotho levels compared to never use (β= -0.084; 95% CI: -0.126 - -0.041), independent of tobacco and illicit drug use. In the combined exposure model, those using both marijuana and tobacco exhibited the greatest reduction in α-Klotho (β= -0.112; 95% CI: -0.162 - -0.062). The inverse association persisted across most subgroups, including both current smokers (β= -0.078; 95% CI: -0.134 - -0.021) and non-smokers (β= -0.087; 95% CI: -0.151 - -0.002). CONCLUSIONS: Marijuana use was independently associated with lower circulating α-Klotho levels, suggesting a potential link between cannabis exposure and accelerated biological aging, even after adjusting for tobacco use. These findings highlight the need for further longitudinal studies to investigate the long-term impact of marijuana and tobacco use on systemic aging processes and health effects.