Cigarette smoking remains the leading cause of preventable death in the United States, even though cigarette smoking rates will fall to an all-time low of about 10% by 2024. Some research suggests that electronic cigarettes (e-cigarettes) can help people quit smoking and reduce exposure to harmful chemicals, but products are changing rapidly and it’s unclear whether these benefits still apply.
A new study led by researchers at Penn State College of Medicine found that switching to pod-based salt nicotine e-cigarettes, one of the most popular types of e-cigarettes on the market, may improve chances of quitting smoking while significantly reducing exposure to harmful chemicals. This study was announced today (May 19th). JAMA network openfound that smokers who started using nicotine-containing e-cigarettes daily were three times more likely to quit smoking within six weeks compared to smokers who used the same-looking e-cigarettes without nicotine. They also had lower levels of several tobacco-related toxic substances in their bodies.
This study suggests that for smokers who are unable to stop using approved medications, switching to nicotine e-cigarettes is associated with a substantial reduction in exposure to harmful toxicants, supporting smoking cessation. This is a finding with implications for public health. ”
Jessica Yingst, associate professor of public health sciences and first author of the paper
To the researchers’ knowledge, this is the first randomized, placebo-controlled trial conducted in the United States to measure the effects of completely switching from cigarettes to pod-based salt nicotine e-cigarettes, the researchers said.
Although addictive, nicotine is not the main cause of cancer and heart disease associated with smoking. Rather, burning cigarettes produces byproducts that can be harmful to your health. Because long-term smoking cessation is difficult, health officials have long sought mitigation measures to transition people from traditional combustible cigarettes (the most commonly used tobacco product) to less harmful products. Previous research in this area suggests that e-cigarettes reduce people’s exposure to tobacco-related toxicants and may provide a less harmful alternative for people who have been unable to quit using other means, Yingst said.
In the current study, researchers wanted to understand the short-term effects on toxic exposure, smoking patterns, and health when adults who smoke daily switch to pod-based salt nicotine e-cigarettes. These pod-based devices use a nicotine salt formulation that delivers nicotine more smoothly and efficiently compared to older e-cig designs.
Researchers enrolled 104 people who smoked four or more cigarettes a day and who expressed interest in completely switching from cigarettes to e-cigarettes. Participants were randomly assigned to use either an e-cigarette with 5% nicotine content or an identical e-cigarette with zero nicotine (52 people per group). Neither the researchers nor the participants knew which group the participants were assigned to.
Participants were instructed to completely switch from cigarettes to e-cigarettes and were followed for six weeks, with an additional check-in at week 10. The nicotine-free e-cigarette served as a placebo, delivering vapor to participants and allowing them to make the familiar hand-to-mouth motion of smoking without nicotine.
To understand whether and how tobacco-related harms change over the course of the study, researchers measured biomarkers indicating the presence of toxic substances associated with tobacco use in participants’ urine and breath at the beginning of the study, three weeks later, and six weeks later. The study’s primary endpoint was NNAL, a marker for a potent lung carcinogen derived exclusively from tobacco leaves. Professor Yingst explained that this measurement can help researchers understand tobacco exposure, as the presence of NNAL in the body can be an indicator that a person has smoked. The researchers also measured changes in blood pressure, lung function, and heart rate, and assessed tobacco use as well as craving and withdrawal symptoms through questionnaires.
At the end of six weeks, 69 participants completed the study. Of these, 35 were in the 5% nicotine group and 34 were in the 0% nicotine group. Yingst said this dropout rate is typical in smoking cessation studies because people tend to drop out of studies if they try to quit and are unsuccessful.
Overall, both groups had reduced exposure to toxic substances that cause respiratory and cardiovascular disease, particularly NNAL, at the end of the study compared to baseline. The presence of NNAL indicates that participants were still smoking cigarettes, but the lower levels suggest that e-cigarettes are helping to reduce regular smoking levels, with the 5% nicotine group seeing a significant reduction in exposure. However, after adjusting for key baseline variables, the difference between groups fell just below statistical significance.
Researchers also found that switching to e-cigarettes containing nicotine increased the likelihood of quitting smoking. At the end of the six-week study period, 36.5% of the 5% nicotine group had completely quit smoking, compared with 11.5% of the no-nicotine group, a difference that remained the same at the 10-week follow-up.
Dr. Inst explained that this finding is consistent with the decreased NNAL levels seen in the 5% nicotine group, suggesting that fewer people in that cohort continued to smoke during the study and thus had less exposure to tobacco-related toxicants. People who used the 5% nicotine device also had fewer withdrawal symptoms and fewer cravings for cigarettes, which may have helped them stay off the habit.
“The way the nicotine is delivered is important,” says Yingst. “Nicotine e-cigarettes deliver the same levels of nicotine as cigarettes, satisfying cravings and making the switch easier, but with significantly reduced overall exposure to toxic chemicals.”
In contrast, the non-nicotine group wasn’t taking nicotine replacements, which may have made it harder to quit smoking completely, Yingst said.
Penn State is a Tobacco Center for Regulation and Science (TCORS) site designated by the Federal Drug Administration (FDA) and the National Institutes of Health. Under the current TCORS grant, a team at the Penn State Tobacco and Health Research Center is conducting a similar study to assess whether the use of oral nicotine pouches can reduce tobacco-related harms in people who currently smoke cigarettes.
The study’s principal investigator was Jonathan Falls, professor of public health, psychiatry, and behavioral health. Other Penn State School of Medicine authors on the paper include Sophia Allen, assistant professor of public health sciences; Zachary Bitzer, assistant professor of public health sciences; Junjia Zhu, Associate Professor of Public Health Sciences. Christopher Sciamanna, professor of medicine and public health; Nicole Krebs, Research Project Manager. Candice Bordner, Research Project Manager. Neil Trusin, Senior Researcher; Craig Livelesberger, human research engineer. Vicki Peters, Research Technician; Alison Salkin, research engineer; Lisa Reinhart, research engineer; Courtney Zimmerman, research engineer; Sitasunu Dahal, Postdoctoral Researcher. Laraib Mazar, PhD scholar. And Kavitha Hassan. Research engineer.
Funding from the National Institute on Drug Abuse, National Center for the Advancement of Translational Sciences, National Cancer Institute, and FDA supported this research.
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Reference magazines:
Engst, J.M.; Others. (2026) Toxic exposure after switching from cigarettes to pod-based electronic cigarettes: a randomized clinical trial. JAMA network open. DOI: 10.1001/jamanetworkopen.2026.13292. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2849145
