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 and increase cardiovascular risk. The research, conducted in mice and lab-grown human heart cells, is the first to show that synthetic cooling agents like WS-3 and WS-23 may negatively affect heart health.
According to the study, adding these coolants to e-cigarettes containing nicotine resulted in mis-timed heartbeats that could increase the risk for sudden cardiac arrest. The findings raise concern that people using these products may have an increased risk of arrhythmias and possibly sudden cardiac arrest, though the results need to be confirmed by research in humans.
“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.”
The study involved 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 show 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, especially WS-23, which 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 heart rhythm but slowed rhythm and sped up recharge between beats when hormonally stressed.
“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 notes that menthol-flavored e-cigarette sales increased by 175.8% between 2019 and 2023, while 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.
Jason J. Rose, M.D., M.B.A., an associate professor of medicine at the University of Maryland School of Medicine and volunteer chair of the 2023 American Heart Association scientific statement on e-cigarettes, commented, “This research is timely since menthol and cooling flavors are becoming more popular. 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 leaves several 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. Carll suggests that policymakers review current rules about coolants used in vapes, as “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.”
Study limitations include that mice may respond differently than humans, and only male mice were used, so results cannot be generalized to female mice. Additionally, lab-grown human heart cells may overlook complex interactions between respiratory and cardiovascular systems. The short-term effects observed may underestimate or differ from products with more ingredients, and long-term exposure effects require more research.
For more information, the manuscript is available online.
