The e-cigarette seems to be a safer alternative to tobacco combustible cigarette and a valuable tool to reduce the tobacco harm caused by smoke. It is a battery-powered device that simulates smoking by heating an e-liquid to produce an aerosol that the user inhales. E-liquid typically contains a combination of propylene glycol (PG), vegetable glycerin (VG), nicotine, and chemical flavors. Flavors are generally recognized as safe (GRAS) for food applications, but little is known about their application in vaping. In this study the international Replica group investigated the effects of vanillin, one of the most widespread flavors in vaping, on the endothelium when vaporized from an e-cigarette. We vaped e-liquids containing PG, VG, and vanillin in two settings, regular and sub-ohm, to verify how vanillin behaves towards aortic endothelial cells, to replicate a study conducted by Fetterman and colleagues in 2018. We evaluated cytotoxicity, oxidative stress, and nitric oxide bioavailability, by covering some gaps reported in the original study by Fetterman. We observed a certain harmful effect mostly attributable to ethanol, mistakenly used to dilute vanillin in the original work by Fetterman and colleagues, but no harmful effect either on the viability of the cells or on their ability to produce nitric oxide. Even a certain protective effect against oxidative stress for vanillin has been observed. Our results confirm the endothelial cell dysfunction observed in the original paper but clarify that these observations are attributable to the ethanol and not to vanillin, which instead, in a more appropriate and realistic model of exposure, seems to exert a protective effect, particularly in a regular setting of the e-cigarette, compared to the most extreme setting (sub-ohm).
Competing Interest Statement
Riccardo Polosa is full tenured professor of Internal Medicine at the University of Catania (Italy) and Medical Director of the Institute for Internal Medicine and Clinical Immunology at the same University. He has received grants from U-BIOPRED and AIR-PROM Integral; Rheumatology & Immunology Specialists Network (IRIS); Foundation for a Smoke Free World; Pfizer; GlaxoSmithKline; CV Therapeutics; NeuroSearch A/S; Sandoz; Merk Sharp & Dohme; Boehringer Ingelheim; Novartis; Arbi Group Srl.; Duska Therapeutics; Forest Laboratories; Ministero dell Universita e della Ricerca (MUR) Bando PNRR 3277/2021 (CUP E63C22000900006) and 341/2022 (CUP E63C22002080006) funded by NextGenerationEU of the European Union (EU) and the ministerial grant PON REACT (EU 2021 GREEN) Bando 3411/2021 by Ministero dell Universita e (MUR) PNRR EU Community. He is founder of the Center for Tobacco Prevention and Treatment (CPCT) at the University of Catania and of the Center of Excellence for the Acceleration of Harm Reduction at the same university. He receives consultancy fees from Pfizer; Boehringer Ingelheim; Duska Therapeutics; Forest Laboratories; CV Therapeutics; Sermo Inc.; GRG Health; Clarivate Analytics; Guidepoint; Expert Network and GLG Group. He receives textbooks royalties from Elsevier. He is also involved in a patent application for ECLAT Srl. He is a pro bono scientific advisor for Lega Italiana Anti Fumo (LIAF) and the International Network of Nicotine Consumers Organizations (INNCO); and he is Chair of the European Technical Committee for Standardization on Requirements and test methods for emissions of electronic cigarettes (CEN/TC 437; WG4). Giovanni Li Volti is currently elected Director of the Center of Excellence for the acceleration of HArm Reduction (CoEHAR). The other authors have no relevant financial interests to disclose.
