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Popular Vape Flavor Chemicals May Carry Their Own Heart Risk
In A Nutshell
- Synthetic cooling chemicals called WS-3 and WS-23, common in “ice”-flavored vapes, significantly increased irregular heartbeats in mice beyond what nicotine alone caused.
- The heart risk grew worse at higher concentrations, and WS-23 showed the strongest link to dangerous rhythm changes.
- Nicotine levels in the blood did not differ between groups, suggesting these coolants affect the heart through their own mechanism rather than by boosting nicotine intake.
- WS-3 and WS-23 are officially considered flavorless, a distinction that has left them outside some e-cigarette flavor restrictions, even though a majority of kids who vape in the U.S. use ice-labeled products containing them.
Cooling agents that make e-cigarettes feel smooth and refreshing, the same ingredients behind popular “ice” flavors, may be doing something alarming to the heart. A new study in Circulation: Arrhythmia and Electrophysiology found that two synthetic cooling chemicals tested in mice significantly increased irregular heartbeats beyond what nicotine vapor alone produced, with effects that worsened at higher concentrations.
For millions of vapers who reach for mint- or ice-labeled products, the cooling sensation makes inhaling easier and more pleasant. But that smoothness comes at a cost only now coming into focus: the chemicals responsible, called WS-3 and WS-23 (the “WS” stands for Wilkinson Sword), turn up in some commercial ice-labeled e-liquids at concentrations up to about 4%, among the highest levels reported for either chemical. Some e-cigarette flavor restrictions have targeted menthol while overlooking WS-3 and WS-23 because they are treated as nonflavorant additives rather than flavorings.
This research arrives amid growing clinical concern. Recent reports have described cases of sudden cardiac arrest in young adults associated with vaping. More than 30% of Americans ages 19 to 22 reported using nicotine e-cigarettes within the past year, according to the study, and a majority of children who vape in the United States use ice-labeled products containing these chemicals.
Ice Vape Chemicals Tested in Mice and Human Heart Cells
Researchers at the University of Louisville School of Medicine used two experimental approaches to test how cooling agents affect the heart.
Male mice were fitted with internal devices that continuously tracked heart electrical activity, essentially a miniature heart monitor implanted under the skin. The animals inhaled e-cigarette vapor from a standard nicotine base liquid with different cooling agents added at increasing concentrations. Eight male mice took part in the heart-monitoring experiment, with the same animals undergoing different exposures on separate days at concentrations designed to mirror commercially available products. Researchers tracked heart rate, the natural variation between heartbeats, and extra, out-of-sequence heartbeats known as irregular beats.
In a second approach, the team tested the cooling agents directly on human heart muscle cells grown in a lab dish. These cells were derived from human stem cells and engineered to beat like real heart cells, giving researchers a window into how the chemicals interact with human cardiac tissue.
Synthetic Coolants in Ice Vapes Triggered More Irregular Heartbeats
Irregular heartbeat events rose significantly in mice that inhaled vapor containing WS-3 or WS-23, and the effect was strongest at the highest concentration tested, where WS-23 produced more irregular beats than clean air, nicotine-only vapor, and even the menthol group. Menthol alone did not significantly increase irregular beats, though it did influence the body’s nervous system balance.
Irregular heartbeats were strongly linked to a shift toward the body’s “fight-or-flight” state. During rest periods between puffing sessions, mice exposed to synthetic coolants showed heart rates rising and heartbeat-to-heartbeat variation dropping sharply, both recognized markers of heart risk. This relationship was strongest, by a wide margin, in the WS-23 group. The arrhythmias also tracked with brief delays in how quickly the heart’s lower chambers reset electrically between beats, a pattern that showed up most strongly with WS-23.
Researchers also checked whether the coolants simply caused mice to absorb more nicotine. They found no significant differences in nicotine levels or its breakdown products across coolant groups, making increased nicotine exposure an unlikely explanation for the added effects, though the study was not designed to rule out every possible interaction between nicotine and the coolants.
In the lab-dish experiments, the cooling agents had little effect on heart cells under normal resting conditions. But when researchers added a stress hormone, the cooling agents slowed the cells’ beating rate overall, and menthol and WS-3 also altered how quickly the cells electrically reset between beats, pointing to a direct effect on heart cells under chemical stress.
Flavor Bans Overlook These Common Ice Vape Additives
Perhaps the most pointed finding concerns regulation. WS-3 and WS-23 are described in the paper as flavorless, providing a cooling sensation without technically tasting like anything, a distinction that has left them outside some flavor restrictions aimed at making vaping products less appealing to young users.
Study authors caution that their findings come from animal and lab models, and that human studies are needed to confirm the effects. Mice and humans differ meaningfully in how their hearts and lungs work, and the lab-grown heart cell results pointed in a somewhat different direction than the whole-animal results, suggesting the full picture is still being assembled.
Taken together, the mouse findings and the cell findings suggest these popular cooling additives carry a cardiac risk of their own, separate from nicotine. Confirming that risk in humans is the logical next step, one regulators and vape makers may not be able to ignore much longer.
Disclaimer: This article is intended for general informational purposes only and does not constitute medical advice. Anyone with concerns about vaping, nicotine use, or heart health should consult a licensed physician.
Paper Notes
Limitations
Study authors acknowledge several limitations. The study relied on male mice only, based on prior observations that male mice are more susceptible to e-cig-induced heart effects than females, meaning the findings may not fully represent effects in females. The numerous differences between mouse and human cardiovascular and respiratory systems require caution when applying these findings to people, and the authors call for confirmation through human studies. Mice used for blood-level testing were not the same animals used for the heart-monitoring experiments, and were not previously exposed to e-cigarette vapor, introducing some uncertainty about direct comparisons. Baseline heart rate and variability did not differ between treatment sessions, suggesting no major carryover effects from the crossover design. The whole-animal findings and the lab-cell findings also diverged in places, most notably in how menthol and WS-3 affected the heart’s repolarization timing differently in cells than in living mice, a discrepancy that leaves the precise mechanisms unresolved.
Funding and Disclosures
This research was funded by the National Heart, Lung, and Blood Institute, the National Institute of General Medical Sciences, and the National Institute of Environmental Health Sciences, all part of the National Institutes of Health, along with the U.S. Food and Drug Administration’s Center for Tobacco Products. The authors reported no disclosures.
Publication Details
Authors: Cory Kucera, Anand R. Ramalingam, Sean M. Raph, Romith Paily, Shweta Srivastava, Pawel K. Lorkiewicz, Aruni Bhatnagar, Matthew A. Nystoriak, and Alex P. Carll, all affiliated with the University of Louisville School of Medicine, Louisville, Kentucky, per the correspondence information provided in the paper. | Journal: Circulation: Arrhythmia and Electrophysiology (American Heart Association) | Paper Title: “Influence of Cooling Agents on the Arrhythmogenic and Autonomic Effects of Electronic Cigarettes in an in vivo Model” | DOI: 10.1161/CIRCEP.125.014253 | Published: June 2026
