For years, flavour additives in e-cigarettes have been largely viewed as a secondary concern compared with nicotine. Research and regulation have focused on addiction, nicotine delivery and, more recently, the respiratory effects of vaping. But as evidence accumulates researchers are increasingly asking whether certain flavouring ingredients have health effects of their own.
Among the compounds attracting attention are menthol and synthetic cooling agents that create the refreshing sensation associated with popular "ice" flavours . These additives now appear in everything from mint-flavoured products to fruit and confectionery blends - and research suggests they may be doing more than simply enhancing the vaping experience.
The cooling sensation is often created by menthol or menthol-inspired synthetic compounds such as WS-3 and WS-23. These substances do not actually cool the air entering the lungs. Instead, they activate a receptor called TRPM8 - the body's cold sensor - tricking the brain into registering cold even though the temperature of the inhaled aerosol is unchanged. The effect can make vaping feel smoother and less irritating, potentially encouraging deeper inhalation and more frequent use.
Scientists once assumed these compounds acted only within the sensory system, but TRPM8 receptors are found throughout the body. A recent study in mice found that menthol-containing e-cigarette aerosols raised heart rate and blood pressure and increased the occurrence of ventricular premature beats - usually harmless irregular heartbeats that can signal stress on the heart's electrical system.
The study also found higher levels of epinephrine, the hormone behind the fight-or-flight response . Some of these effects persisted after exposure ended, with changes in heart rhythm regulation still detectable weeks later.
Researchers are now asking whether similar effects extend to the blood vessels themselves.
Blood vessels are lined with cells that help control blood flow, inflammation and clotting. Laboratory studies suggest that some chemicals used to flavour e-cigarettes can damage these cells , increasing inflammation and other forms of cellular stress while making the cells more likely to die . Some of these effects have been seen even in the absence of nicotine.
Damage to the cells that line blood vessels is considered one of the earliest signs of cardiovascular disease. This suggests that cooling agents could affect not just the heart but the entire circulatory system.
A market moving faster than science
The concern is growing as manufacturers increasingly use synthetic cooling chemicals that create a strong cooling sensation without a minty taste. This allows fruit-, candy- and beverage-flavoured vapes to deliver the icy feeling many users enjoy, even though the health effects of some of these compounds remain poorly understood.
Being safe to eat does not mean something is safe to inhale. Chemicals absorbed through the lungs reach the bloodstream far more directly, and new formulations can reach the market long before comprehensive safety studies are completed.
This does not mean cooling flavours have been proved to cause heart disease - that would require larger studies in humans. But growing evidence suggests these compounds are not biologically inactive, as was once assumed. What started as research into flavour has become a wider effort to understand how these additives affect the body, and the findings are more complex than expected.
Keith Rochfort receives funding from Research Ireland.
