Background: The use of menthol in cigarettes and marketing is under consideration for regulation by the FDA. However, the effects of menthol on smoking behavior and carcinogen exposure have been inconclusive. We previously reported metabolomic profiling for cigarette smokers, and novelly identified a menthol-glucuronide (MG) as the most significant metabolite directly related to smoking. Here, MG is studied in relation to smoking behavior and metabolomic profiles. Methods: This is a cross-sectional study of 105 smokers who smoked two cigarettes in the laboratory one hour apart. Blood nicotine,MG, and exhaled carbon monoxide (CO) boosts were determined (the difference before and after smoking). Spearman correlation, c2, and ANCOVA adjusted for gender, race, and cotinine levels for menthol smokers assessed the relationship of MG boost, smoking behavior, and metabolic profiles. Multivariate metabolite characterization using supervised partial least squares-discriminant analysis (PLS-DA) was carried out for the classification of metabolomics profiles. Results: MG boost was positively correlated with CO boost, nicotine boost, average puff volume, puff duration, and total smoke exposure. Classification using PLS-DA, MG was the top metabolite discriminating metabolome of menthol versus nonmenthol smokers. Among menthol smokers, 42 metabolites were significantly correlated with MG boost, which linked to cellular functions, such as of cell death, survival, and movement. Conclusions: Plasma MG boost is a new smoking behavior biomarker that may provide novel information over self-reported use of menthol cigarettes by integrating different smoking measures for understanding smoking behavior and harm of menthol cigarettes. Impact: These results provide insight into the biological effect of menthol smoking.
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