Adding synthetic cooling ingredients to e-cigarettes resulted in mis-timed heartbeats that could increase the risk for sudden cardiac arrest, according to a study published today in Circulation: Arrhythmia and Electrophysiology, a peer-reviewed journal of the American Heart Association. The research, conducted in mice and in lab-grown human heart cells, raises concern that people who use these products may have an increased risk of irregular heart rhythm and possibly sudden cardiac arrest.
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, but most states have exceptions allowing menthol and other ingredients that give a cooling sensation. These exceptions persist, and the FDA recently authorized certain flavored e-cigarettes for adults, underscoring ongoing questions about how flavorings and cooling agents affect cardiovascular health.
“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 and an associate professor of physiology 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.”
Researchers conducted two types of laboratory tests. In the first, mice inhaled aerosols from e-cigarettes containing nicotine with or without cooling agents. Their heart rhythm and conduction patterns were monitored during exposure. In the second test, lab-grown human heart cells were exposed to cooling agents and noradrenaline to mimic the impact of nicotine on stress hormones.
All of the 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 for WS-23, which tripled the number of premature heartbeats compared to e-cigarettes containing just nicotine and solvents.
“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 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.”
Carll suggests that policymakers review the 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,” he said. “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.”
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 since menthol and cooling flavors are becoming more popular,” said Jason J. Rose, M.D., M.B.A., an associate professor of medicine at the University of Maryland School of Medicine, who was not involved in the study. “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.”
The study has limitations, including that mice may respond differently than humans, and lab-grown heart cells may not capture complex interactions between respiratory and cardiovascular systems. The results need to be confirmed by research in people. The full manuscript is available online.
