Metabolomics analysis identified reduced levels of oxidative stress and improved vitamin metabolism in smokers switching to an electronic nicotine delivery system (ENDS)
Switching to non-combustible tobacco products presents an opportunity for cigarette smokers to potentially reduce the harm associated with smoking. Electronic nicotine delivery systems (ENDS) are one type of non-combustible tobacco product that hold potential for harm reduction, since the vapor produced from ENDS contains far fewer toxicants than cigarette smoke. To investigate the biochemical effects of switching cigarette smokers to an ENDS, we assessed global metabolomic profiles of smokers in a seven-day clinical confinement study. In the first two days of this clinical study, the subjects used their usual brand of cigarettes and then switched to exclusive ENDS ad libitum use for five days. Urine and plasma samples were collected at baseline and five days after switching. The samples were analyzed using a mass spectrometry-based metabolomics platform. Random forest analyses of urine and plasma metabolomics data revealed excellent predictive accuracy (>97 %) of the 30-metabolite signatures that can differentiate the smokers before or after switching. In these signatures, most biomarkers are nicotine-derived metabolites or xenobiotics that were significantly reduced in urine and plasma after switching, suggesting a decreased xenobiotic load on consumers. Our results also show significantly decreased levels of plasma glutathione metabolites after switching, indicating reduced oxidative stress. In addition, increased urinary and plasma levels of vitamins and anti-oxidants were observed, suggesting enhanced bioavailability due to discontinuation of cigarette smoking and less interference from ENDS use. Together, our results suggest a less toxic chemical environment, reduced oxidative stress and potential beneficial changes in vitamin metabolism within a few days in combustible cigarette smokers after switching to an ENDS.