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 induced abnormal heartbeats and heightened cardiovascular risk measures in mice and lab-grown human heart cells. This marks the first investigation demonstrating that synthetic cooling agents may adversely affect heart health.
While the U.S. restricts the sale of many flavored e-cigarettes to curb youth appeal, most states permit menthol and other cooling ingredients. The FDA recently authorized certain flavored e-cigarettes for adults, underscoring ongoing questions about how flavorings and cooling agents influence 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 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. In a separate test, lab-grown human heart cells were exposed to cooling agents and noradrenaline to mimic nicotine’s stress effects. All cooling ingredients affected heart rate variability, indicating stress responses that increase risk for mistimed heartbeats and high blood pressure. Adding synthetic coolants to e-cigarettes increased irregular heartbeats in mice, with WS-23 tripling premature heartbeats compared to e-cigarettes with only nicotine and solvents.
In human heart cells under hormonal stress, coolants slowed rhythm and sped up electrical recharge between beats. “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 cardiovascular effects, causing more mistimed heartbeats and signs of fight-or-flight stress responses, which increase the risk of sudden cardiac arrest.”
The study notes that 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. Menthol-flavored e-cigarette sales rose 175.8% between 2019 and 2023.
“This research is timely since menthol and cooling flavors are becoming more popular,” said Jason J. Rose, M.D., M.B.A., associate professor at the University of Maryland School of Medicine and volunteer chair of the 2023 American Heart Association scientific statement on e-cigarettes. “The study results are not surprising because ingredients in e-cigarettes, particularly synthetic flavoring agents, independently carry health risks.”
Carll suggests policymakers review rules about coolants in vapes, as coolant levels are often higher than nicotine or other flavorings. The study leaves open questions for future research, including effects on people with pre-existing heart conditions, pregnant women, and long-term harm from short-term effects.
