Researchers have found that synthetic cooling ingredients added to e-cigarettes can cause irregular heartbeats and increase the risk of sudden cardiac arrest, according to a study published today in Circulation: Arrhythmia and Electrophysiology, a peer-reviewed journal of the American Heart Association. The study, conducted in mice and lab-grown human heart cells, is the first to demonstrate that synthetic cooling agents like WS-3 and WS-23 may negatively affect heart 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 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 U.S. restricts the sale of many flavored e-cigarettes to reduce youth appeal, but most states exempt menthol and other cooling ingredients, leading to a surge in their use.
The study involved two sets of experiments. In the first, mice inhaled aerosols from e-cigarettes containing nicotine with or without cooling agents, and their heart rhythms were monitored. In the second, lab-grown human heart cells were exposed to cooling agents and noradrenaline to mimic nicotine’s stress effects. Key findings revealed that all cooling ingredients affected heart rate variability, indicating stress responses that increase the risk for mistimed heartbeats and high blood pressure. Notably, WS-23 tripled the number of premature heartbeats compared to e-cigarettes with only nicotine and solvents. In human heart cells, coolants slowed rhythm and sped up electrical recharge 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 of fight-or-flight stress responses, which increase the risk of dangerous mis-timed heartbeats and sudden cardiac arrest.” The study also noted that coolants did not significantly increase nicotine absorption into the bloodstream in mice.
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 by 175.8% over the same period. Jason J. Rose, M.D., M.B.A., an associate professor at the University of Maryland School of Medicine and volunteer chair of a 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. We just don’t know the long-term impact of vaping.”
Carll urged policymakers to review current rules: “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 leaves open questions about the effects on high-risk populations, including pregnant women and those with heart disease, and whether short-term effects lead to long-term harm. The American Heart Association’s 2023 scientific statement called for more long-term research on e-cigarette use by people with pre-existing heart and lung disease. The full study is available online.
