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Tobacco aside, e-cigarette flavorings may harm blood vessels

Flavoring chemicals widely used in e-cigarettes and other tobacco products may be toxic to the cells that line and regulate blood vessel function.

Flavor additives used in electronic cigarettes and related tobacco products could impair blood vessel function and may be an early indicator of heart damage, according to new laboratory research in Arteriosclerosis, Thrombosis and Vascular Biology, an American Heart Association journal.

Endothlium endangered

Nine chemical flavorings – menthol (mint), acetylpyridine (burnt flavor), vanillin (vanilla), cinnamaldehyde (cinnamon), eugenol (clove), diacetyl (butter), dimethylpyrazine (strawberry), isoamyl acetate (banana) and eucalyptol (spicy cooling) – which are widely used in e-cigarettes, hookah, little cigars and cigarillos were tested for their short-term effects on endothelial cells, the cells which line the blood vessels and the inside of the heart.

Researchers found all nine flavors were dangerous to cells in the laboratory at the highest levels tested and all the flavorings impaired nitric oxide production in endothelial cells in culture (outside of the body). Several of the flavorings – menthol, clove, vanillin, cinnamon and burnt flavoring – resulted in higher levels of an inflammatory marker and lower levels of nitric oxide, a molecule that inhibits inflammation and clotting, and regulates vessels’ ability to widen in response to greater blood flow.

Endothelial cells were collected from volunteers (nine non-smokers/non-e-cigarette users; six non-menthol and six menthol cigarette smokers) and tested in the lab. Researchers found that both groups of smokers had a similar deficit in nitric oxide production when stimulated by a chemical called A23187. Nonsmokers’ cells that were treated with menthol or a clove flavoring also had impaired nitric oxide production, suggesting those flavorings cause damage like that found in active smokers.

The team also exposed commercially-available human aortic endothelial cells to the flavorings. Burnt flavor, vanilla, cinnamon and clove flavors impaired nitric oxide production and boosted an inflammatory chemical called interleukin-6 (IL-6) at all concentrations tested, suggesting the endothelium is particularly sensitive to these flavors.

Nonsmokers’ cells that were treated with menthol or a clove flavoring also had impaired nitric oxide production
Increased oxidative stress

At the highest levels tested, all nine chemicals caused cell death, while at lower levels cinnamon, clove, strawberry, banana and spicy cooling flavor did. Dimethylpyrazine/strawberry flavor had that effect even at very low levels, suggesting endothelial cells are especially sensitive to it. Vanillin and eugenol also increased oxidative stress in the cells.

Three flavorings were tested when heated, to mimic what happens in e-cigarettes. Nitric oxide production was impaired with vanillin and eugenol, but not with menthol.

A key strength of the new research was that it directly tested effects of just the flavorings, at levels likely to be reached in the body. Limitations include the fact that testing did not heat all the flavorings or include other chemicals used in e-cigarettes. Also, the study gauged just the flavorings’ short-term effects and captured these with cells outside the body, not inside.

AHA cautions

The American Heart Association cautions against the use of e-cigarettes, stating that e-cigarettes containing nicotine are tobacco products that should be subject to all laws that apply to these products. The Association also calls for strong new regulations to prevent access, sales and marketing of e-cigarettes to youth, and for more research into the product’s health impact.

Fetterman JL et al. Flavorings in Tobacco Products Induce Endothelial Cell Dysfunction.  Arteriosclerosis, Thrombosis, and Vascular Biology. 2018.

https://doi.org/10.1161/ATVBAHA.118.311156