A new study published in the Journal of the American Medical Association (JAMA) has raised concerns over the widespread use of the artificial sweetener neotame in disposable e-cigarettes, calling for further research into its health implications when inhaled.

Conducted by researchers at Yale University and led by Dr. Hanno C. Erythropel, the study analyzed 73 e-cigarette devices currently available in the U.S. market—including FDA-approved products, zero-nicotine options, and those containing nicotine analogues—to determine the prevalence and concentration of neotame. The team also included a reference mint candy to benchmark levels of the sweetener.

The findings revealed that neotame was present in 57 out of 73 e-cigarette samples, with an average concentration nearly 4.6 times higher than that found in the mint candy (1.75 μg/mg versus 0.38 μg/mg). Notably, none of the FDA-approved cartridges or JUUL products contained neotame, while the sweetener was found across all tested popular disposable devices, nicotine-free products, and those with synthetic nicotine analogues.

The study also highlighted that devices containing 6-methylnicotine—a synthetic nicotine substitute—had the highest levels of neotame. In addition to the sweetener, WS-23, a synthetic cooling agent, was detected in the majority of devices (50 of 63), while menthol and another synthetic coolant (WS-3) were present in fewer products.

Interestingly, in zero-nicotine and 6-methylnicotine products, no actual nicotine was detected, suggesting these products may appeal to a broader, possibly younger, demographic due to their sweet taste and cooling effects—despite being marketed as nicotine alternatives.

Although neotame is FDA-approved for use in food, its inhalation safety remains unknown. The study authors cautioned that more research is urgently needed to understand neotame's potential health effects when heated and inhaled through vaping, including its impact on respiratory function and overall toxicity.

“More information on neotame’s contribution to disposable cigarette appeal, abuse liability, and toxicity is needed to determine whether regulatory intervention is necessary,” the authors wrote.

Given the rising popularity of flavored disposable e-cigarettes, especially among youth, these findings could intensify regulatory scrutiny and reignite debates about flavor additives and synthetic sweeteners in vaping products. Some study authors disclosed ties to industry organizations, underscoring the need for independent research in this emerging area of public health concern.