In a study comparing toxic exposures among smokers and long-term users of e-cigarettes and nicotine replacement therapy (NRT), analysis of salivary and urinary biomarkers of smoking exposure suggested a low risk for harm associated with long-term use of e-cigarettes, reported Lion Shahab, PhD, of the University College London, and colleagues.

Significant reductions in exposures were seen in regular, long-term use of e-cigarettes and NRT, but not dual users of traditional cigarettes and e-cigarettes or cigarettes and NRT, they wrote in the Annals of Internal Medicine.

“Former smokers who used e-cigarettes long term as a replacement for cigarettes dramatically reduced their risk, compared to continuing to smoke,” Shahab told MedPage Today, adding that the few human studies that have examined toxic exposures associated with e-cigarette use have looked at short-term exposure to the products, and did not include real-world control groups.

Shahab’s group compared metabolite levels of nicotine, carcinogens, and toxin exposures among five groups:

• Cigarette smokers
• Former smokers using e-cigarettes daily for at least 6 months
• Former smokers using NRT daily for at least 6 months
• Dual users of cigarettes and e-cigarettes
• Dual users of cigarettes and NRT

All participants (n=181) provided urine and saliva samples, which were analyzed for biomarkers of nicotine, tobacco-specific N-nitrosamines (TSNAs), and volatile organic compounds (VOCs).

Sociodemographic characteristics (age, sex, ethnicity, education, and marital status) were assessed in addition to other relevant potential confounders.

The analysis revealed that compared with smokers or dual users, e-cigarette and NRT users had significantly lower levels of the VOCs acrolein, acrylamide acrylonitrile, 1,3-butadiene, and Ethylene oxide.

E-cigarette-only users also had significantly lower levels of the tobacco-specific N-nitrosamine carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL).

But e-cigarette-only and NRT-only use was associated with roughly similar nicotine intake as combustible-cigarette only use, suggesting that, “users seek a particular level of nicotine intake, regardless of the delivery system and adjust product use accordingly,” the researchers wrote.

“This finding is consistent with more recent, but not older, studies on nicotine delivery from e-cigarettes, which may reflect the improved design of newer generations of e-cigarettes, and highlights the importance of focusing on experienced, long-term users rather than naive, short-term users,” they noted.

The findings did not suggest a significant difference in exposure to carcinogens and toxins in users of e-cigarettes and NRT, nor a significant difference in exposures among cigarette smokers and dual users of cigarettes and e-cigarettes or NRT.

“E-cigarettes are likely to be beneficial only if complete cessation of combustible cigarette smoking is achieved,” the authors noted. “Thus, dual users should be encouraged to cease using combustible products to reduce long-term health risks.”

Study limitations included the small sample size and the lack of information on specific e-cigarette types and NRT used. Indirect exposures were also not assessed, and the analysis was limited by the number of biomarkers available and spot sampling, “which can only provide a snapshot of exposure,” they wrote.

“However, given the lack of long-term data, we chose this pragmatic design to quickly evaluate potentially important associations of e-cigarette use with intake of carcinogens and toxins to inform further longitudinal work,” the researchers wrote.

Shahab said the findings add to the growing body of research suggesting that e-cigarettes may be as effective and safe as widely used NRT pharmacotherapies.

Cancer Research UK, which was the primary funding source for the newly published research, has publicly recognized the potential role of e-cigarettes in smoking harm reduction.

Most anti-smoking public health groups in the U.S., as well as the FDA and the Surgeon General of the U.S., have not accepted this view to date. In a December 2016 report, the Surgeon General called the dramatic increase in e-cigarette use among children and teens a “major public health concern.”

“The vast majority of smokers find it very, very difficult to stop smoking without some kind of help, and nicotine replacement therapy is what most people turn to,” Shahab told MedPage Today.

But Alan Blum, MD, of the University of Alabama Center for the Study of Tobacco and Society in Tuscaloosa, told MedPage Today the debate about whether e-cigarettes should be considered a smoking cessation tool is misguided.

“The fact is, the rate of smoking cessation for all nicotine replacement therapy is not that great,” said Blum, who was not involved in the study. “As good as e-cigarettes may prove to be for nicotine replacement, by far the least expensive and most proven method for stopping smoking is doing it on your own. But nobody makes any money off that.”

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner