A new independent study 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 caused abnormal heartbeats (arrhythmias) and increased cardiovascular risk measures in mice and lab-grown human heart cells. This is the first study to show that synthetic cooling agents in e-cigarettes may negatively affect heart health.
The U.S. restricts the sale of many flavored e-cigarettes, such as cotton candy flavors, to reduce youth appeal. However, most states have exceptions allowing menthol and other ingredients that produce a cooling sensation when inhaled. These exceptions persist, and the FDA recently authorized certain flavored e-cigarettes for adults, highlighting ongoing questions about how flavorings, cooling agents such as WS-3 and WS-23, and product design affect cardiovascular health and youth use.
“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. “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, researchers conducted two types of laboratory tests. In the first, mice inhaled aerosols from e-cigarettes containing nicotine with or without cooling agents, and their heart rhythm and conduction patterns were monitored. In the second, lab-grown human heart cells were exposed to cooling agents and noradrenaline to mimic the impact of nicotine on stress hormones.
Key findings showed that all cooling ingredients affected heart rate variability, indicating stress responses that increase the risk for mistimed heartbeats, high blood pressure, and other cardiovascular issues. Adding synthetic coolants to e-cigarettes already containing nicotine and solvents increased irregular heartbeats in the mice, especially WS-23, which tripled the number of premature heartbeats compared to e-cigarettes with only nicotine and solvents. In human heart cells, coolants did not change normal resting rhythm but, when hormonally stressed, slowed their rhythm and sped up recharge between beats.
“Together, these findings suggest coolants could cause arrhythmias by making the heart electrically ready too soon or too late for the next beat,” Carll said. “Coolants, especially WS-23, intensified the cardiovascular effects, 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.”
Carll suggests policymakers review current rules about coolants used in vapes. “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 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 by people with pre-existing heart and lung disease.
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. This research is timely as menthol and cooling flavors become more popular. Jason J. Rose, M.D., M.B.A., volunteer chair of the 2023 scientific statement writing group, noted, “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, even if it has been authorized by the FDA.”
Study limitations include that mice may respond differently than humans, and only male mice were used. Additionally, lab-grown human heart cells may overlook complex interactions between respiratory and cardiovascular systems. The short-term effects observed may underestimate long-term impacts, which require more research.
