Some e-cig flavors could be more toxic than others

Smoking flavored e-cigarettes can have a detrimental effect on endothelial function, leaving e-cig users prone to poor vascular health and heart disease, researchers report in the June edition of the Journal of the American College of Cardiology. According to the study, cinnamon-flavored products pose the greatest threat to cell viability.

Since e-cigarettes remain a relatively new phenomenon, there are still holes in our knowledge of how their use affects different physical systems, including the cardiovascular system, first author Won Hee Lee, PhD, and colleagues wrote in JACC. To date, most toxicological studies on the subject have been limited to cytotoxicity studies using established cell lines, leaving little room for generalization.

“Understanding the health effects of e-liquids, especially flavorings, is important for establishing the short- and long-term safety of e-cigarettes,” Lee et al. said. “In this study, we compared the biological effects of flavored e-liquids (both with and without nicotine) on human-induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and found that some flavorings had toxic effects on endothelial cell viability and function.”

The team drew iPSC-ECs from three healthy individuals and a study population of five non-smokers, five active cigarettes smokers, two dual users of e-cigarettes and cigarettes and two sole users of e-cigarettes. All subjects were healthy and free of major CV risk factors at the study’s baseline.

Lee and colleagues treated iPSC-ECs with a dilution of six commercially available e-liquids at varying concentrations of nicotine (0, 6 and 18 mg/ml). They found different flavors of e-liquid had different effects on cell survival—the fruit flavor, sweet tobacco with vanilla and caramel flavor, tobacco flavor and butterscotch flavor all showed moderate cytotoxic effects on iPSC-ECs, while the cinnamon and menthol tobacco flavors appeared to be more cytotoxic.

The authors said the cinnamon flavor, sold as “Marcado” by Johnson Creek, had the strongest cytotoxic effect, followed by the menthol tobacco-flavored “Tundra,” distributed by the same company. Marcado impaired endothelial function and enhanced the formation of reactive oxygen species, and Tundra exhibited strong cytotoxic effects even without nicotine.

Lee and co-authors wrote there were more than 450 e-cigarette products and nearly 8,000 unique flavors on the commercial market in 2014—numbers that are sure to have risen over the past half-decade. They said most flavoring chemicals in e-liquids meet the “generally recognized safe standard” for ingestion as food additives, but they haven’t been tested adequately as inhalants. Buttery and fruity flavors, in particular, have exhibited toxicity.

“The question as to the safety of e-cigarettes is not trivial,” Jane E. Freedman, MD, and Chinmay M. Trivedi, MD, PhD, wrote in a related JACC editorial. “Although touted as beneficial in smoking cessation, there is growing alarm at the rate of use amongst teens and adults and increasing concerns that e-cigarettes products are, in fact, a gateway to future tobacco use. Compounding the risk is the fact that, while standard cigarettes do not have flavoring, e-cigarette products often do and the hazards of these additives remain unclear.”

Freedman and Trivedi said oversight and regulation in the field are “clearly needed,” and Lee et al.’s study makes it clear that additional product and safety testing for e-cigs is another necessity.

“The results by Lee et al. clearly demonstrate that e-liquid flavorings had stronger effects on cytotoxicity, vascular dysfunction and angiogenesis than nicotine,” the editorialists wrote. “Thus, in addition to harm from the nicotine, the additives are a potential source of adverse vascular health and one that is being disproportionately placed on the young.

“These observations suggest that, even without the smoke of combustible cigarette products, there may be a smoldering fire of adverse health effects.”