ORIGINAL RESEARCH article
Front. Public Health
Sec. Aging and Public Health
Volume 13 - 2025 | doi: 10.3389/fpubh.2025.1655214
Urinary volatile organic compound metabolites and frailty in U.S. adults: NHANES 2011–2018
Provisionally accepted
- 1Jiangyin People's Hospital, Jiangyin, China
- 2Jiaying University, Meizhou, China
- 3Nanjing Medical University, Nanjing, China
- 4Jiangsu Province Geriatric Hospital, Nanjing, China
- 5Wuxi Huishan District Center for Disease Control and Prevention, Wuxi, China
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Background Whether environmentally relevant exposure to volatile organic compounds (VOCs) contributes to frailty remains unknown. We examined urinary VOC metabolites (VOCms) and their mixtures in relation to frailty in a nationally representative U.S. cohort. Methods We analysed 2 715 adults (≥20 y) from NHANES 2011–2018 in a cross-sectional design. Frailty was defined with a 48-item index. Sixteen creatinine-adjusted VOCms were quantified. Single metabolites were evaluated with survey-weighted logistic regression. Two-directional weighted-quantile-sum regression (WQS), grouped Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) characterised mixture effects, and sex-and age-stratified subgroup analyses were performed. Mediation by γ -glutamyl-transferase (GGT), bilirubin, albumin, the Dietary Oxidant/Antioxidant Balance Score (OBS), and high-sensitivity C-reactive protein (hs-CRP) was assessed. Results Four metabolites—DHBMA, CEMA, HPMMA and MHBMA3—were each positively associated with frailty (adjusted OR per log₁₀-unit 1.67–2.59). The positive WQS index increased frailty odds by 25 % (OR = 1.25, 95 % CI 1.17–1.33), whereas the negative index lowered odds by 17 % (OR = 0.83, 0.75– 0.91). Only the positive index remained significant in men and in adults ≥65 y; MHBMA3 dominated male weights (18 %), HPMMA female weights (16 %). BKMR confirmed a monotonic dose–response for the positive group, whereas qgcomp detected no overall effect. Bilirubin and albumin jointly mediated 5–20 % of the associations; GGT showed no significant mediation. Conclusions Urinary VOCm mixtures are linked to frailty at population exposure levels, with risk driven by four metabolites and most pronounced in men and older adults. Oxidative stress explains part—but not all— of the association, suggesting additional pathways. Reducing VOC exposure may help preserve physiological reserve; longitudinal studies are warranted to confirm causality.
Keywords: Volatile Organic Compounds, Frailty, Oxidative Stress, Mixture modelling, weighted quantile sum, NHANES
Received: 27 Jun 2025; Accepted: 01 Sep 2025.
Copyright: © 2025 Qu, Zhang, Huang, Chen and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ye Zhu, Wuxi Huishan District Center for Disease Control and Prevention, Wuxi, China
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