Dietary Factors Drive Volatile Organic Compound Exposure and Modulate Its Impact on Multi‐Dimensional Biological Aging

Volatile organic compound (VOC) exposure is ubiquitous and linked to aging, but dietary contributions and effects on multi-dimensional biological age (BA) indicators are unclear. This study investigated dietary drivers of urinary VOC metabolite (VOCM) concentrations, their association with multi-dimensional BA, and whether diet modifies this relationship. This study analyzed 4,976 U.S. adults (2011-2020), measuring 16 urinary VOC metabolites (VOCMs) and four BA indicators: Klemera-Doubal BA/phenotypic age acceleration (KDMAgeAccel/PhenoAgeAccel), allostatic load (AL), and homeostatic dysregulation (HD). Survey-weighted generalized linear and logistic regression models were used to examine associations between 16 VOCMs and four BA indicators, assessing interaction with dietary patterns. VOCM concentrations were influenced by dietary factors, including dietary patterns, food groups, and nutrients. Multiple VOCMs, and their mixture, were positively associated with BA (e.g., VOCM mixture on KDMAgeAccel > 0: OR = 1.235, 95% CI: 1.097, 1.391). Specifically, 4HBeMA exhibited significant positive associations with KDMAgeAccel, AL, and PhenoAgeAccel. KDMAgeAccel emerged as the most sensitive BA indicator, significantly associated with eight VOCMs, with DHBMA showing the strongest correlation (KDMAgeAccel > 0: OR = 1.393, 95% CI: 1.129, 1.718). Healthy dietary patterns have protective effects against VOCMs-related BA. Dietary factors are significant drivers of VOC exposure inequality. VOCM exposure is linked to multi-dimensional BA, for which KDMAgeAccel is a sensitive biomarker. Healthier dietary patterns may protect against VOC-related BA, suggesting a viable strategy for public health intervention.