Study: Cooling Agents in E-Cigarettes Linked to Irregular Heartbeats, Cardiac Arrest Risk

DALLAS - Synthetic cooling ingredients added to e-cigarettes caused abnormal heartbeats and increased cardiovascular risk measures in mice and lab-grown human heart cells, according to new independent research published today in Circulation: Arrhythmia and Electrophysiology, a peer-reviewed journal of the American Heart Association. This study is the first 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 make them less enticing to children. However, most states have exceptions allowing menthol and other ingredients that give a cooling sensation when inhaled. These exceptions persist, and the FDA recently authorized certain flavored e-cigarettes for adults, underscoring 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 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.”

In previous research, Carll and colleagues found that exposure to e-cigarette aerosols rapidly disrupted heart rhythm in mice. In this study, 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’s rhythm and conduction patterns were monitored during exposure. In the second test, lab-grown human heart cells were exposed to cooling agents and to noradrenaline to mimic the impact of nicotine on stress hormones.

All of the cooling ingredients in e-cigarettes affected heart rate variability, which indicate 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. With coolant exposures, these mistimed heartbeats corresponded with increased heart rate and a slower electrical recharge between beats.

In human heart cells, the coolants did not change normal resting heart rhythm or recharge rate. However, when the cells were hormonally stressed, coolants slowed their rhythm and also sped up their recharge between heartbeats. In the mice, coolants did not significantly increase the amount of nicotine absorbed into the bloodstream after inhalation.

“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. “In general, we’ve seen tobacco-flavored vapes do not disrupt cardiac conduction in mice as much as vapes with either menthol or synthetic coolants. Coolants, especially WS-23, intensified the cardiovascular effects of e-cigarette exposures, 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.”

The study leaves several open questions for future research. “It is still unclear how coolants in vapes affect people with higher risk for heart rhythm conditions. This includes pregnant women and those with hypertension, heart disease, obesity or Type 2 diabetes. We also don’t know if the short-term effects of coolants lead to long-term harm,” Carll said.

According to a 2024 report from the CDC Foundation and Truth Initiative, menthol-flavored e-cigarette sales increased by 175.8% between 2019 and 2023, and sales of e-cigarettes with synthetic cooling ingredients increased 872.1% between 2020 and 2023 in the U.S. 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.

“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. “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.”

The study's 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 complex interactions between the respiratory and cardiovascular systems. The short-term effects observed may underestimate or differ from products with more ingredients, and the potential impact of long-term exposure requires more research.