A study suggests that cooling agents in vaping could increase the risk of arrhythmias or cardiac arrest.

Adding cooling agents like menthol, WS-3, or WS-23 to e-cigarettes could increase their effects on heart rhythm and the risk of arrhythmia, according to a study from the University of Louisville, Kentucky, School of Medicine, conducted on mice and on human heart cells derived from stem cells.[1]. The authors show that some of these additives, particularly the synthetic agents WS-3 and WS-23, exacerbate the proarrhythmic effects of vaping by altering the balance of the autonomic nervous system and cardiac repolarization.

Context and methodology of the study

The study begins with the observation that e-cigarettes often contain, in addition to nicotine, flavorings and additives designed to make inhalation more appealing. Among these, cooling agents have gained popularity, particularly in "ice" or mentholated products, while their specific health effects remained poorly understood. The authors note that previous studies had already linked certain mentholated e-liquids to heart rhythm disturbances, but without precisely isolating the role of each synthetic cooling agent.

Researchers exposed mice to e-cigarette aerosols containing either only the nicotine-solvent vehicle or the same mixture enriched with menthol, WS-3, or WS-23, at different concentrations. They continuously monitored heart rate, heart rate variability, electrocardiographic changes, and the occurrence of premature ventricular contractions. Simultaneously, they tested the effects of these same substances on human cardiomyocytes derived from pluripotent stem cells to observe a possible direct effect on the electrical activity of cardiac cells.

Main results

In mice, all cooling agents accentuated the autonomic imbalance caused by e-cigarette aerosol, but the most pronounced effects were observed with the synthetic coolants WS-3 and WS-23. These substances increased the frequency of spontaneous ventricular arrhythmias, with an even stronger association for WS-23. The authors also show that these arrhythmias were linked to signs of sympathetic dominance and a transient slowing of cardiac repolarization.

Higher concentrations of WS-3 and WS-23 produced the most pronounced effects, suggesting a dose-response relationship. Menthol also altered the autonomic balance, but in a more variable and less systematic way than the synthetic agents. The researchers further note that these effects were not explained by a greater increase in nicotine exposure, nor by a significant change in its metabolism.

Cellular data

In laboratory-cultured human cardiomyocytes, synthetic coolants had little effect under basal conditions. However, in the presence of norepinephrine—used by researchers to replicate a sympathetic stimulation comparable to that induced by nicotine—menthol and WS-3 reduced heart rate and shortened certain repolarization markers. The authors conclude that these additives can also act directly on the electrophysiology of cardiac cells, and not only via the autonomic nervous system.

This research, which still needs to be explored further, could shed light on the regulation of additives and flavorings.

The authors believe their results provide strong evidence for considering cooling agents as potentially proarrhythmic compounds in e-cigarettes. They emphasize that this effect could be particularly problematic in individuals already susceptible to arrhythmias or slowed ventricular repolarization.

The study is limited, however, by the fact that it relies on animal and cellular models and cannot, on its own, draw conclusions about the exact effects in humans. The researchers therefore call for further clinical studies to verify whether these results translate into findings for e-cigarette users, particularly young adults who are heavily exposed to these flavored products.

They nevertheless believe that this data could be of interest to health authorities and regulators in the regulation of additives used in vaping, given that, according to figures cited by the American Heart Association, US sales of menthol e-cigarettes increased by nearly 176 million between 2019 and 2023, and those of products containing synthetic cooling agents increased by more than 870 million between 2020 and 2023.« Cooling agents are often present in electronic cigarettes at higher concentrations than nicotine or other flavorings. »,« said Alex Carll, professor of physiology at the University of Louisville School of Medicine.« It is necessary to consider regulatory limits regarding the concentration of these cooling agents in electronic cigarettes. »[2]

Let us remember that Despite scientific evidence of limited benefit for smoking cessation, the US FDA has just relaxed its regulations on fruity flavors in electronic cigarettes..

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[1]Kucera C., Ramalingam A., Raph S., Paily R., Srivastava S., Lorkiewicz P., Bhatnagar A., Nystoriak M., Carll P., Influence of Cooling Agents on the Arrhythmogenic and Autonomic Effects of Electronic Cigarettes in an in vivo Model,Circulation, Arrhythmia and Electrophysiology, American Heart Association, published June 15, 2026, accessed June 18, 2026

[2]Seyoung Moon, Louisville cardiology team links e-cigarette cooling additives to cardiac arrhythmia, DongA Science, published June 15, 2026, accessed June 18, 2026

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