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 irregular heartbeats (arrhythmias) in mice and lab-grown human heart cells. This is the first research to show that these synthetic coolants, such as WS-3 and WS-23, may negatively impact heart health, potentially increasing the risk of sudden cardiac arrest.
The study comes as sales of e-cigarettes with synthetic cooling ingredients have surged 872.1% between 2020 and 2023, according to a 2024 report from the CDC Foundation and Truth Initiative. Meanwhile, menthol-flavored e-cigarette sales increased by 175.8% from 2019 to 2023. These products often fall outside flavor restrictions because synthetic coolants create a chilling sensation without a characterizing flavor.
“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 the study, researchers exposed mice to aerosols from e-cigarettes containing nicotine with or without cooling agents and monitored heart rhythm and conduction patterns. They also exposed lab-grown human heart cells to cooling agents and noradrenaline to mimic the impact of nicotine on stress hormones. The 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 mice. WS-23 tripled the number of premature heartbeats compared to e-cigarettes with just nicotine and solvents. In human heart cells, coolants did not change normal resting rhythm but slowed rhythm and sped up recharge between beats when hormonally stressed. Importantly, coolants did not significantly increase nicotine absorption into the bloodstream.
“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 in heart rhythm of fight-or-flight stress responses, which in turn increase the risk of dangerous mis-timed heartbeats and sudden cardiac arrest.”
The study leaves open questions, particularly for people with pre-existing conditions such as hypertension, heart disease, or diabetes. “It is still unclear how coolants in vapes affect people with higher risk for heart rhythm conditions,” Carll noted. 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.
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, commented on the 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. While the FDA’s Center for Tobacco Products authorizes some specific flavored e-cigarettes for adults, this does not mean they are safe to use.”
Carll suggests policymakers review current rules about coolants: “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 limitations include that mice may respond differently from humans, and only male mice were used. Additionally, lab-grown human heart cells may not fully capture interactions between respiratory and cardiovascular systems. The short-term effects observed may also underestimate long-term impacts, requiring more research.
