New independent research published today in Circulation: Arrhythmia and Electrophysiology, a peer-reviewed journal of the American Heart Association, has found that synthetic cooling ingredients added to e-cigarettes can cause abnormal heartbeats and increase cardiovascular risk measures in mice and lab-grown human heart cells. This is the first study to show that these synthetic cooling agents may negatively affect heart health.
The U.S. restricts the sale of many flavored e-cigarettes, such as cotton candy flavors, to reduce their appeal to children. However, most states allow menthol and other ingredients that produce a cooling sensation when inhaled. Synthetic coolants like WS-3 and WS-23 have become popular because they reduce harshness and make inhalation feel smoother, and they often fall outside flavor restrictions. According to a 2024 report from the CDC Foundation and Truth Initiative, sales of e-cigarettes with synthetic cooling ingredients increased by 872.1% between 2020 and 2023 in the U.S.
In the study, researchers exposed mice to aerosols from e-cigarettes containing nicotine with or without cooling agents and monitored their heart rhythm. They also exposed lab-grown human heart cells to cooling agents and noradrenaline to mimic the impact of nicotine on stress hormones. The results showed that all cooling ingredients affected heart rate variability, increasing the risk for mistimed heartbeats, high blood pressure, and other cardiovascular issues. Adding synthetic coolants to e-cigarettes with nicotine increased irregular heartbeats in mice, with WS-23 tripling the number of premature heartbeats compared to e-cigarettes with nicotine alone.
“Because synthetic coolants create a chilling sensation without flavor, they fall outside of e-cigarette restrictions that focus on ‘characterizing flavors,’” said Alex Carll, Ph.D., M.S.P.H., principal investigator of the study and an associate professor at the University of Louisville School of Medicine. “Coolants are added to e-cigarettes at very high levels, often more than nicotine or any other flavoring. Coolant levels in vapes should be considered for regulation, especially if further studies confirm that they increase the harmful effects of vaping on the heart.”
The study leaves several open questions for future research, including how coolants affect people with higher risk for heart rhythm conditions, such as pregnant women and those with hypertension, heart disease, obesity, or Type 2 diabetes. A 2023 scientific statement from the American Heart Association, Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products, called for more long-term research on e-cigarette use in people with pre-existing heart and lung disease.
“This research is timely since menthol and cooling flavors are becoming more popular,” said Jason J. Rose, M.D., M.B.A., an associate professor at the University of Maryland School of Medicine and volunteer chair of the 2023 scientific statement writing group, who was not involved in this research. “The study results are not surprising because ingredients in e-cigarettes, particularly synthetic flavoring agents, independently carry health risks. We just don’t know the long-term impact of vaping.”
Study limitations include that mice may respond differently than humans, and only male mice were used. Additionally, lab-grown human heart cells may not fully capture the complex interactions between the respiratory and cardiovascular systems. The short-term effects observed may underestimate or differ from products with more ingredients, and long-term exposure requires more research.
