PITTSBURGH — A paper published Tuesday in the journal Respiratory Research adds to a growing body of research that shows menthol flavoring added to electronic cigarette liquid worsens lung damage. The study represents the first time, to the authors' knowledge, that these effects have been seen with aerosolized menthol vapor.
Menthol is added to many products, such as chewing gum and pain patches. But researchers at the University of Pittsburgh, who ran a series of experiments using a "vaping robot," found when it is added to e-liquid, it increases the number of particles inhaled into the lungs.
Previous research has found that particle inhalation is not incidental. Fine particles can get caught in the respiratory tract and lung tissue, leading to inflammation, constriction of the bronchioles and reduced lung function.
Jennifer Folkenroth, the national senior director of tobacco programs for the American Lung Association, said the study results were "not surprising and incredibly concerning."
The results have been published during a contentious time for vaping devices, which encompass many forms of inhalation products, like cannabis vapes and e-cigarettes. Once seen as a Hail Mary for helping chronic smokers quit cigarettes, e-cigarettes and the companies that market them have faced scrutiny for their apparent targeting of minors and the highly addictive nature of the products.
One company, Juul, sold 14 million vape devices between 2016 and 2017, and its net worth skyrocketed to $38 billion when the tobacco company Altria invested $12.5 billion. That same year, cigarette smoking among teens had hit a historic low, according to a Business Insider report on Juul's rise and fall.
Juul continued to profit as vaping, or "Juuling," became a teen status symbol and mouth-watering vape flavors — such as mint, mango, menthol, fruit medley, vanilla and creme brulee — rose in popularity. Middle and high school students kept vaping from Juul's (and other brand's) sleek and discrete devices, which have disposable and interchangeable pods more miniscule than a flash drive.
Then in late 2019, when Juul's CEO Ken Burns stepped down and a new leader took over, the company banned the sale of mint-flavored pods. The Trump administration subsequently banned the sale of almost all flavored pods, citing what the FDA had coined a teen vaping epidemic a couple years earlier. But the federal ban did not include mint or menthol, and it only encompassed the flavored cartridges, not disposable e-cigarettes like Puff Bars.
"As these regulatory policies happen, there are certain loopholes," said Alayna Tackett, a researcher with the Center for Tobacco Research at the Ohio State University Comprehensive Cancer Center.
In June 2022, the FDA banned Juul devices in the U.S. in their entirety, but many states and organizations that sued the company felt the announcement was too little too late, as Juul marketed its products in an unregulated market for years before any regulatory body stepped in.
Vaping is still rampant among both teens and adults, even with the void Juul has left in the market. A 2022 National Youth Tobacco Survey, co-authored by the FDA and CDC, found that one in four middle and high schoolers use e-cigarettes daily, with 85% puffing on flavored products. A recent survey study by California researchers found that respondents ages 14 to 20 years old preferred sweet and fruit flavors most, with menthol and fruit-ice "hybrids" coming next.
And while a Penn State study of both teens and adults found that the popularity of menthol flavoring in e-cigarettes has dropped, it still sits at around a fifth of preferred consumption for those surveyed.
At Pitt's School of Medicine, Kambez Benam, associate professor in the Division of Pulmonary, Allergy and Critical Care Medicine, and his colleagues targeted menthol flavor as one culprit for what makes vapes so hazardous to lung health. Benam's lab receives partial funding through the FDA for its vaping robot.
The lab began the study by creating its own e-liquid based on standard commercial e-liquids used in vape devices, which are typically a 50/50 combination of propylene glycol and vegetable glycerin.
Then they tested the effect on adding menthol at increasing doses. The vaping robot is engineered to mimic the mechanics of human breathing, with a complex design that measures everything from particle count and lung function.
The researchers found that even at the small concentration of 0.1%, the addition of menthol led to more particles inhaled by the robot.
The second phase of the study was to measure the impact of real commercial products: Vuse Alto. The researchers tested both standard tobacco and menthol Vuse flavoring and found again that the menthol let in more particles.
The third and last phase was to validate their findings with clinical data to gain an understanding of how real people have been affected. The team pored over a vast database called the COPDGene Study, which gathers long-term data from more than 10,000 patients. The final cohort for this specific study involved 25 menthol vapers and 69 users of other flavored vaping products.
After controlling for the confounding variables of age, gender, race, total years smoking and the use of vaping products (nicotine, cannabis or otherwise), the Pitt team discovered that patients who had reported vaping with menthol flavoring fared worse in various lung function tests than those who did not use menthol.
"This is likely associated with lung injury in the clinic," said Benam.
Folkenroth, of the American Lung Association, said the organization is seeing continued use of vaping products despite regulations. The 2022 National Youth Tobacco Survey stated that e-cigarette use was the most common form of tobacco consumption. Another study, with senior author Alayna Tackett, found that many students reported they would continue to use menthol products as long as the flavor was available. And the 2020 Penn State study found that nearly half of all participants said they would "find a way" to access their preferred flavor if it was banned.
"E-cigarettes have created a new pattern of use," said Folkenroth.
Nicotine by itself is incredibly addictive — some research reveals that it's even harder to quit than heroin. In the developing adolescent brain, the hijacking of addiction circuitry can feel even more potent, with teens reporting stark behavioral changes, restlessness, irritability and nausea.
That's why an additional finding in Benam's study is of note: that when the team measured the actual nicotine concentration of the commercially available Vuse Alto menthol product, it was triple what was marked on the package.
Using a technique called gas chromatography, they found the nicotine concentration to be between 5.9 and 6.1%, while the package displayed a 1.8% nicotine concentration. Benam said he was shocked to discover this, and that the issue is not isolated to the Vuse product.
"This is a bigger problem," he said.
In addition to the presence of menthol allowing a user to take in more fine particles, menthol's cooling properties can suppress the harshness of nicotine vapor inhalation, said Folkenroth. This can make naive users more susceptible to getting hooked.
Menthol also has pain-relieving properties and can reduce airway irritation, hiding early signs of harm. Folkenroth said that in her work with youth, many have anecdotally reported one downside of vaping is a diminished breathing capacity during athletics.
"We know that when you can't breathe, nothing else matters," she said.
Tackett said Benam and his colleagues' study was "really interesting" and an important contribution to the field.
"This is a great foundational paper that paves the way for other researchers to look for similar patterns," she said.
In her own work, she's found that the fruit-ice hybrid flavors seem to be most popular among youth. "Ice" refers to some type of cooling agent added to the e-liquid — sometimes it's menthol, but other times companies use a different chemical additive that doesn't fall into the "categorizing flavor," allowing them to skirt regulatory limits on menthol content.
"These companies seem to find any way to make these products appealing and addictive," said Benam.
Tackett wonders if different flavor profiles might present different respiratory risks — something Benam's study has opened the door for researchers to look into.
Benam said his lab does want to measure different vape flavors eventually. They chose to study menthol first, he said, due to its popularity.
"This study highlights the importance of testing the toxicity of novel additives to e-vapor products before they become commercially available," said Josh Kaplan, an associate professor of behavioral neuroscience at Western Washington University and whose lab studies the therapeutic effects of vapor inhalation of cannabis oils and terpenes. (Full disclosure: This story's reporter previously worked in Kaplan's lab.)
"Just because something is safely consumed in one manner, such as oral consumption of menthol in chewing gum, doesn't make it safe when consumed through other routes, like inhalation," he went on. "The way in which we take chemicals into our bodies matters."
