Metabolic disruption associated with e-cigarette vaping and secondhand exposure: Urinary metabolomics evidence from a Thai population.

The increasing use of electronic cigarettes (e-cigarettes) has raised concerns regarding potential health effects associated with both direct use and secondhand exposure to e-cigarette aerosols. However, human evidence describing systemic metabolic alterations related to these exposures remains limited. In this study, metabolomics was applied to compare urinary metabolic profiles among active e-cigarette users, individuals exposed to secondhand e-cigarette aerosols, and unexposed control participants. Multivariate analyses were performed to identify exposure-related metabolic signatures, followed by pathway enrichment and evaluation of candidate biomarkers. Distinct metabolic differences were observed across exposure groups. Direct e-cigarette use was associated with alterations in amino acid metabolism, mitochondrial energy pathways, and redox-related processes, with glutathione metabolism identified as a key associated pathway and oxidized glutathione highlighted as a candidate urinary biomarker of redox-related metabolic alterations. Secondhand exposure was primarily associated with alterations in alanine, aspartate, and glutamate metabolism, with L-glutamic acid demonstrating discriminatory performance as a candidate metabolite associated with metabolic differences related to secondhand e-cigarette aerosol exposure. Comparative pathway analyses suggested that direct e-cigarette use was associated with more extensive metabolic alterations than secondhand exposure, particularly in pathways linking glutamine-glutamate metabolism, the tricarboxylic acid cycle, and glutathione metabolism, suggesting a possible graded biological response to aerosol exposure. In addition, nicotine metabolism-related metabolites and e-liquid constituents, including propylene glycol, glycerol, and cotinine