Fire without smoke? E-cigarettes may impair blood vessel health even without nicotine

Jul 11

In 2015, the British Government issued a press release stating that electronic cigarettes or e-cigarettes were around 95% less harmful than smoking based on an independent Public Health England expert report. Recent groundbreaking research published by Stanford Diabetes Research Center (SDRC) member Dr. Joseph Wu and his colleagues, Dr. Won Lee, PhD and Dr. Sang-Ging Ong, PhD in the Journal of the American College of Cardiology (JACC) in June 2019 is the latest in a series of studies to challenge the claim that vaping is safer than smoking.

Vaping refers to the inhalation and exhalation of vapors produced by heating a flavored liquid containing nicotine in a device called an e-cigarette. Often, smokers who want to kick the habit take up vaping as it has been marketed as a safer alternative that has fewer toxic chemicals than regular cigarettes. Conventional cigarette sales and consumption have been on a steady decline in the US, whereas, e-cigarette use has been on the rise, especially among youth. While e-cigarettes do have a lower content of many of the chemicals found in traditional cigarettes, the current study suggests that certain flavoring liquids in e-cigarettes may severely damage the inner lining of blood vessels and increase cardiovascular disease risk even in the absence of nicotine.

Dr. Wu’s team studied the effect of 6 popular flavors of e-liquids on the health and integrity of endothelial cells which form the inner lining of blood vessels. Endothelial cells are vital for cardiovascular health and their degradation is associated with increased cardiovascular disease risk. Using a novel approach, the researchers generated endothelial cells for this first-of-its-kind study from induced pluripotent stem cells or iPS cells. Under the right laboratory conditions, iPS cells can be coaxed to become any cell type in the body including endothelial cells. This enabled the researchers to have a ready pool of endothelial cells on which to test e-liquids.

Dr. Wu found that all 6 flavors of e-liquids had detrimental effects to varying degrees on the endothelial cells, however, exposing the cells to menthol and cinnamon flavored e-liquids had the most dramatic effects in terms of decreasing their ability to survive, form vascular tubes and migrate. Surprisingly, these effects did not appear to be correlated with the presence or absence of nicotine in the e-liquids, suggesting that the flavoring chemicals themselves were toxic. In addition, the researchers found that exposing endothelial cells to blood taken from smokers or vapers after consuming a single e-cigarette or cigarette was sufficient to impair their function and increase the production of free radicals and molecules associated with cell death and inflammation.

The endothelial cells displayed other signs of damage as well, some of which were dependent on nicotine levels. The scientists noted that exposure of endothelial cells to nicotine containing e-liquids increased their uptake of inflammation-associated lipids and low-density lipoproteins and activated inflammatory immune cells called macrophages. Moreover, the team observed similar levels of nicotine in the blood of participants immediately after vaping or smoking.

“It is important for e-cigarette users to realize that these chemicals are circulating within their bodies and affecting their vascular health”, says Dr. Wu in a Stanford News Press Release. Dr. Wu and his colleagues acknowledge caveats in their study including the fact that they tested unheated e-liquids as opposed to the aerosols and their analyses being limited to just six of the hundreds of e-cigarette flavorings available in the market, precluding the universal extrapolation of their results to all e-cigarettes.

Describing the relevance of the study in an audio summary, JACC Editor-in-Chief Dr. Valentin Fuster said, “Although it has been portrayed that e-cigarettes can be beneficial in smoking cessation, there is growing alarm at the rate of use among teens and adults and increasing concerns that e-cigarette products are in fact a gateway to future tobacco use”. Moreover, he added, advertising promotes e-cigarette flavors targeting children and young adults – flavors that could be toxic as shown by Dr. Wu’s team.

Dr. Fuster concluded his remarks by citing an editorial comment on the study in the same issue of JACC by Drs. Freedman and Trivedi from the University of Massachusetts Medical School, Division of Cardiovascular Medicine, Worcester, Massachusetts in which they write “The results by Lee et al clearly demonstrate that e-liquid flavorings had stronger effects on cytotoxicity, vascular dysfunction and angiogenesis than nicotine. 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”. It appears, he said, that even without the smoke of combustible cigarette products, there may be a smoldering fire of adverse health effects.

Dr. Won Lee, now an assistant professor at the University of Arizona, was the recipient of a Pilot award from the SDRC from a grant sponsored by the National Institutes of Health. Dr. Sang-Ging Ong is an assistant professor at the University of Illinois-Chicago. Other Stanford coauthors include research assistant Yang Zhou, postdoctoral scholars Dr. Lei Tian, Dr. Hongchao Guo, graduate student Hye Ryeong Bae, undergraduate student Natalie Baker and Professor Kari Nadeau, MD, PhD, Department of Pediatrics, Stanford.