Association between volatile organic compounds exposure and frailty among adults in NHANES 2011–2018: the mediating role of oxidative stress and inflammation

Evidence regarding the cumulative impact of exposure to diverse volatile organic compounds (VOCs) on frailty remains limited. We aimed to explore the association between VOCs and frailty, and to investigate the mediating effects of oxidative stress and inflammation. Our study involved 4,677 participants aged ≥20 from the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were employed. We further conducted mediation analysis to explore the mediating role of oxidative stress and inflammation. Multivariable logistic regression revealed several VOCs were significantly correlated with frailty, particularly for N-Acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA), N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA), N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), mandelic acid (MA), N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-l-cysteine (MHBMA3) and N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (HPMMA). WQS regression confirmed synergistic effects of combined VOCs exposure on frailty (OR = 1.53, 95%CI: (1.28, 1.83)), with four mVOCs (DHBMA, CEMA, HPMMA and CYMA) contributing most substantially. BKMR analysis further identified this positive correlation, and the association was more significant in the older group. Mediation analysis showed these relationships were partially mediated by oxidative stress and inflammatory pathways. This study offers novel evidence for a positive correlation between VOCs and frailty, with DHBMA being the most significant contributor. Oxidative stress and inflammation potentially act as mediators.