High Wattage Vaping Shifts Urine Metabolome Toward A Healthier Profile: A Randomized Crossover Study

Objective: We previously demonstrated in young and healthy occasional tobacco smokers that acute exposure to high wattage vaping with and without nicotine decreases transiently transcutaneous oxygen tension and arterial oxyen tension. Propylene glycol and glycerol are e-cigarette constituents that facilitate liquid vaporization and nicotine transport. As these small hydrophilic molecules have a short serum/urine half-live, we hypothesized that short-term cessation of vaping in regular users would change urine metabolic signatures. Design and method: Thirty regular e-cigarette users were enrolled in this randomized, investigator-blinded, three-period crossover-study. The periods consisted of nicotine-vaping (nicotine-session), nicotine-free vaping (nicotine-free-session), and complete cessation of vaping (stop-session), all maintained for five days before the session began. Multiparametric metabolomic analyses on urine and serum were used to verify subjects’ protocol compliance. Metabolomic analysis was performed on urine samples by proton nuclear magnetic resonance. Results: Partial least squares discriminant analysis (PLS-DA) performed on baseline serum metabolome did not allow to split up any of the three experimental session. PLS-DA performed on baseline urine metabolome allowed to split up the nicotine and the stop sessions (Figure 1.C), the nicotine-free and the stop-sessions (Figure 1.D) but not the nicotine from the nicotine-free session (Figure 1.B) as well as all three sessions (Figure 1.A). Heatmap outlines the main metabolites with variables of importance values > 1 of both session as well as those identified by the PLS-DA. Baseline urine propylene glycol was lower in the stop-session compared to the nicotine-and nicotine-free sessions (all-p < 0.0001). Baseline urine 3-hydroxyisovalerate and urine-pyruvate were higher in the nicotine-session vs. the nicotine-free and the stop-sessions (all-p < 0.05). Compared to the stop-session, baseline urine trimethylamine-oxide and hippurate were lower in the nicotine-session (all-p < 0.05). Finally, baseline N-Phenylacetyl-glycine was lower in the nicotine-session when compared to the stop-session (p < 0.05).Conclusions: In conclusion, our study reveals that short-term e-cigarette cessation in regular users modified the urine metabolomic signature in a way signature in a way that suggests several modulations in hypoxia related pathways. This will need further researches focusing on cellular and molecular alterations (i.e., hypoxia-inducible Factors-1, nuclear factor-kappa B), in cell and animal models.