Despite cigarette smoking having dropped to all-time low (10%) in 2024, smoking is still the leading preventable cause of death in the United States, but recent research now suggests that smoking nicotine vapes could improve the odds of quitting.
Various studies have suggested that electronic cigarettes (e-cigarettes) may have helped habitual smokers stub out while exposing them to fewer harmful chemicals — however, products have changed rapidly, and it’s unclear whether these benefits still hold true.
This latest study, led by researchers from Penn State College of Medicine, found that switching to a pod-based salt-nicotine e-cigarette, one of the most popular types of e-cigarettes on the market, could boost the chances of quitting cigarette smoking while meaningfully lowering exposure to harmful chemicals.
The study, published in JAMA Network Open, found that daily smokers who started using a nicotine e-cigarette were three times more likely to quit smoking within six weeks than those who used an identical-looking e-cigarette containing no nicotine. They also had lower levels of several tobacco-related toxicants in their body.
“For people who smoke and haven’t been able to quit using approved medications, this research suggests that switching to a nicotine e-cigarette is associated with real reductions in harmful toxicant exposures and does support smoking cessation,” said Jessica Yingst, associate Professor of Public Health Sciences and lead author on the paper. “That’s a meaningful finding for public health.”
The researchers said that to their knowledge, this was the first randomised placebo-controlled trial conducted in the United States to measure the effects of switching completely from cigarettes to pod-based salt-nicotine e-cigarettes.
Nicotine, while addictive, isn’t the primary cause of smoking-related cancers and heart disease. Rather, burning tobacco yields by-products that can be harmful to health.
Since quitting smoking long-term is difficult, health officials have long sought off-ramps to move people away from traditional combustible cigarettes – the most commonly used tobacco product – to less harmful products.
Previous studies in the field have suggested that e-cigarettes could expose people to fewer tobacco-related toxicants and serve as a less harmful alternative for those who have been unable to quit cigarette smoking through other means, Yingst said.
In the current study, the researchers wanted to know the short-term effects on toxicant exposure, cigarette smoking patterns and health when adults who smoke daily switch over to a pod-based salt-nicotine electronic cigarette.
These pod-based devices use a nicotine salt formulation, which delivers nicotine more smoothly and efficiently than older e-cigarette designs.
The researchers enrolled 104 people who smoked more than four cigarettes a day and who expressed interest in switching completely from cigarettes to an e-cigarette. Participants were randomly assigned to use either a 5% nicotine e-cigarette or an identical device with zero nicotine – 52 per group.
Neither the researchers nor the participants knew to which group the participants were assigned.
Participants were instructed to switch completely from cigarettes to the e-cigarette and were followed for six weeks, with an additional check-in at 10 weeks. The no-nicotine e-cigarette acted as the placebo, providing vapour and allowing participants the familiar hand-to-mouth motion of smoking without the nicotine.
Researchers measured biomarkers signalling the presence of toxicants associated with tobacco use in the participants’ urine and breath at the beginning of the study, at three weeks, and at six weeks to understand if and how tobacco-related harms change over the course of the study.
The primary outcome measure for the study was NNAL – a marker for a potent lung carcinogen that only comes from the tobacco leaf.
Yingst said this measure can help researchers understand cigarette exposure, as the presence of NNAL in the body can be an indicator that a person has smoked. The researchers also measured blood pressure, lung function and heart rate variability and assessed cigarette use as well as cigarette craving and withdrawal symptoms through questionnaires.
At the end of six weeks, 69 participants completed the study – 35 in the 5%-nicotine group and 34 in the 0%-nicotine group. The drop-out rate is typical for a smoking cessation study, Yingst said, since people tend to drop out of studies if they try to quit smoking and aren’t successful.
Overall, both groups experienced lower exposure to toxicants – including those who contribute to respiratory and cardiovascular disease, specifically NNAL – at the end of the study compared with baseline.
While the presence of NNAL at all indicated that participants still smoked cigarettes, the lower levels suggest that the e-cigarettes assisted in cutting back on their normal smoking levels, with the 5%-nicotine group experiencing greater reductions in exposure. However, the difference between the groups fell just short of statistical significance after controlling for key baseline variables.
The researchers also found that switching to a nicotine-containing e-cigarette is associated with a greater likelihood of quitting smoking. At the end of the six-week study period, 36.5% of the 5%-nicotine group stopped smoking entirely compared with 11.5% in the no-nicotine group, a gap that held up at the 10-week follow-up point.
Yingst said this finding corresponds with the lower level of NNAL found in the 5%-nicotine group, which suggests that fewer people in that cohort continued to smoke during the study and were exposed to fewer tobacco-related toxicants.
Those who used the 5%-nicotine device also experienced less withdrawal and fewer cravings, which may have also helped them stay off cigarettes.
“The way nicotine is delivered matters,” Yingst said. “The nicotine e-cigarette provides a similar level of nicotine as a cigarette, satisfying cravings and making the switch easier, but their overall toxic chemical exposure dropped substantially.”
The no-nicotine group, in contrast, weren’t getting any nicotine replacement, which may have made it harder to stop smoking completely, Yingst said.
Penn State is a designated Tobacco Centres for Regulatory Science (TCORS) site by the US Federal Drug Administration (FDA) and National Institutes of Health. Under the current TCORS grant, the team at the Penn State Centre for Research on Tobacco and Health is conducting a similar study to evaluate whether the use of oral nicotine pouches can reduce tobacco-related harms among those who currently smoke cigarettes.
Funding from the National Institutes on Drug Abuse, the National Centre for Advancing Translational Sciences, the National Cancer Institute and the FDA supported this work.
Study details
Toxicant Exposures After Switching From Cigarettes to a Pod-Based Electronic Cigarette: A Randomised Clinical Trial
Jessica Yingst, Nicolle Krebs, Sitasnu Dahal, et al.
Published in JAMA Open Network on 19 May 2026
Key Points
Question What are the short-term effects of switching from cigarettes to a pod-based salt nicotine electronic cigarette (EC) among adults who smoke cigarettes daily?
Findings In this randomised clinical trial of 104 participants, switching from cigarettes to a 5% nicotine EC for 6 weeks was associated with reduced levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, a tobacco-specific lung carcinogen biomarker, compared with the 0% nicotine EC. The difference was not statistically significant when controlling for several key baseline variables
Meaning These findings suggest that EC nicotine delivery plays an important role in facilitating reduction in toxicant exposure from cigarettes.
Abstract
Importance
Electronic cigarettes (EC) have been shown to expose users to fewer tobacco-related toxicants compared with combustible cigarettes. The current generation of ECs has rapidly shifted toward pod-based nicotine salt formulation ECs, and more research is needed to understand the impacts of using these EC products among those who smoke.
Objective
To determine the short-term effects of switching from cigarettes to a pod-based 5% nicotine EC, compared with a 0% nicotine EC.
Design, Setting, and Participants
This double-blind, parallel-arm, randomised, placebo-controlled trial with follow-up at 6 weeks (randomised phase) and 10 weeks (post-randomised phase) was conducted at a single-site academic medical centre in Pennsylvania from April 22, 2022, to December 12, 2023. Participants included adults who smoked more than 4 cigarettes per day (CPD) and expressed interest in switching completely to an EC. Data were analysed from August 23, 2024, to December 1, 2025.
Interventions
Participants were allocated 1:1 to the standardised research EC (SREC) with 5% nicotine or 0% nicotine for 6 weeks.
Main Outcomes and Measures
The primary outcome was concentration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine corrected for creatinine level at 6 weeks. Secondary outcomes included exhaled carbon monoxide (CO), cotinine level, CPD, CO-verified cigarette abstinence, and levels of volatile organic compounds.
Results
A total of 104 participants (52 per group) were randomised, of whom 68 (65.4%) were female, with a mean (SD) age of 50.9 (10.0) years. At 6 weeks, the 5% SREC group did not have significantly lower NNAL levels (mean difference [MD], −116.6 [95% CI, −245.4 to 12.2] pg/mg; P = .08). However, a greater proportion of participants in the 5% SREC group were abstinent from cigarettes (19 of 52 [36.5%] vs 6 of 52 [11.5%]; P = .005), compared with the 0% SREC group. The 5% SREC group had greater cotinine levels (MD, 2367.8 [95% CI, 407.5-4328.2] ng/mg; P = .02); however, there were no differences in CPD (MD, −0.9 [95% CI, −3.9 to 2.1] CPD; P = .55) or exhaled CO levels (MD, −5.1 [95% CI, −12.9 to 2.6] ppm; P = .19) between groups. Levels of cyanoethyl mercapturic acid (CYMA) (MD, −49.0 [95% CI, −90.4 to −7.6] ng/mg; P = .02) and 3-hydroxypropyl mercapturic acid (3HPMA) (MD, −290.8 [95% CI, −514.0 to −67.6] ng/mg; P = .01), biomarkers of acrylonitrile (a carcinogen) and acrolein (a cardiac toxicant) exposure (both of which are respiratory toxicants), were lower in the 5% SREC group compared with the 0% SREC group.
Conclusions and Relevance
In this randomised clinical trial of adults who smoke, switching from cigarettes to a 5% SREC vs a 0% SREC resulted in reduced exposure to some toxicants delivered by cigarette smoking and an increased rate of smoking cessation. ECs that deliver nicotine like a cigarette may have an important role in reducing the harmful toxicant exposure caused by cigarette smoking.
See more from MedicalBrief archives:
Nicotine vapes help smokers quit, but long-term effects still unclear – Cochrane Review
Major independent evidence review: vaping ‘a small fraction’ of the risk of smoking
Nicotine vaping linked to lung cancer – Australian analysis