From the Journals

E-cigarette flavorings foster cardiovascular dysfunction



Flavorings used in e-cigarettes have a negative impact on endothelial cells that may play a role in cardiovascular toxicity.

Flavored tobacco products are popular among current smokers, including youth, and the flavorings have been deemed ingestible, but their impact on heart health has not been studied, wrote Jennifer Fetterman, PhD, of Boston University, and her colleagues. The report was published in Arteriosclerosis, Thrombosis, and Vascular Biology.

The researchers studied nine types of flavorings used in alternative tobacco products to assess their impact on cardiovascular health.

The first part of the study comprised a population of nine nonsmokers, six nonmenthol cigarette smokers, and six menthol cigarette smokers without cardiovascular disease. The researchers isolated venous endothelial cells from each participant.

Overall, cells from both nonmenthol and menthol cigarette smokers had significantly lower nitric oxide production compared with nonsmokers (P = .003 and P = .012, respectively). In addition, the flavoring compounds menthol and eugenol impaired nitric oxide production in the cells of healthy individuals.

“Increased inflammation and a loss of nitric oxide are some of the first changes to occur leading up to cardiovascular disease and events like heart attacks and stroke, so they are considered early predictors of heart disease,” Dr. Fetterman said in a statement, adding that the “findings suggest that these flavoring additives may have serious health consequences.”

e-cigarette Carpe89/ThinkStock
To characterize the acute effects of flavoring compounds, the researchers also acquired commercially available endothelial cells and exposed them to nine flavorings: eugenol (clove), vanillin (vanilla), cinnamaldehyde (cinnamon), menthol (mint), 2,5-dimethylpyrazine (strawberry), diacetyl (butter), isoamyl acetate (banana), eucalyptol (mint), and acetylpyridine (burnt).

All nine flavorings induced cell death at the highest concentration tested, ranging from 10 to 100 mmol/L).

The study findings were limited by several factors, primarily a lack of data on how heating the flavorings in the in vitro part of the study might have affected toxicity in the body, the researchers noted.

“Future studies will focus on how the toxicity of the flavorings is altered with heating and characterization of the levels obtained in the circulation after use of an e-cigarette,” they said.

However, data support the need for regulation and limits on the level of flavorings used in e-cigarettes and other tobacco products, they emphasized.
“These findings suggest that flavoring compounds induce endothelial cell dysfunction in human cells similarly to the abnormal function in active cigarette smokers,” the researchers noted.

The study was funded by the National Heart, Lung, and Blood Institute; Food and Drug Administration Center for Tobacco Products; and the American Heart Association. The researchers had no financial conflicts to disclose.

SOURCE: Fetterman J et al. Arterioscler Thromb Vasc Biol. 2018. doi: 10.1161/ATVBAHA.118.311156.

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