A study published today in Circulation: Arrhythmia and Electrophysiology, a peer-reviewed journal of the American Heart Association, reveals that synthetic cooling ingredients added to e-cigarettes can cause abnormal heart rhythms and increase cardiovascular risk. The research, conducted in mice and lab-grown human heart cells, is the first to show that synthetic coolants like WS-3 and WS-23 may negatively affect heart health.
The U.S. restricts the sale of many flavored e-cigarettes to reduce appeal to children, but most states exempt menthol and other cooling ingredients. Synthetic coolants, which create a chilling sensation without flavor, fall outside these restrictions. According to lead investigator Alex Carll, Ph.D., M.S.P.H., associate professor at the University of Louisville School of Medicine, "Synthetic coolants WS-3 and WS-23 have become really popular in vapes, partly because they reduce harshness and make inhalation feel smoother."
In the study, mice inhaled aerosols from e-cigarettes containing nicotine with or without cooling agents. All cooling ingredients affected heart rate variability, indicating stress responses linked to mistimed heartbeats, high blood pressure, and other cardiovascular issues. Adding synthetic coolants to nicotine-laced e-cigarettes increased irregular heartbeats, with WS-23 tripling premature heartbeats compared to nicotine alone. Coolants also led to increased heart rate and slower electrical recharge between beats.
In lab-grown human heart cells, coolants did not alter normal resting rhythm but slowed rhythm and sped up recharge when cells were hormonally stressed. "These findings suggest coolants could cause arrhythmias by making the heart electrically ready too soon or too late for the next beat," Carll explained. "Coolants, especially WS-23, intensified the cardiovascular effects of e-cigarette exposures in the mice, causing more mistimed heartbeats and greater signs of fight-or-flight stress responses, which increase the risk of dangerous mis-timed heartbeats and sudden cardiac arrest."
The study also notes that sales of e-cigarettes with synthetic cooling ingredients increased 872.1% between 2020 and 2023 in the U.S., according to a 2024 report from the CDC Foundation and Truth Initiative. Carll suggests policymakers review current rules about coolants, as they are added at very high levels, often exceeding nicotine or other flavorings.
Limitations include that mice may respond differently than humans, and the study used male mice only. Additionally, lab-grown heart cells may not fully capture human cardiovascular complexities. The researchers emphasize that these results need confirmation in human studies. Jason J. Rose, M.D., M.B.A., of the University of Maryland School of Medicine, who was not involved in the study, commented, "The study results are not surprising because ingredients in e-cigarettes, particularly synthetic flavoring agents, independently carry health risks. It is important for parents to talk with their children to make sure they understand that no vaping or tobacco product is safe or risk-free."
The American Heart Association's 2023 scientific statement, Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products, called for more long-term research on e-cigarette use by people with pre-existing heart and lung disease.


