The introduction of low-nicotine cigarettes has been proposed as a potential method to reduce cigarette use; however, no significant clinical trial to date has provided evidence to support this hypothesis. A recent study published in The Lancet Regional Health compares the effects of low-nicotine cigarettes in a setting where regular cigarettes and non-combusted alternative nicotine delivery systems (ANDS) are freely available.
Study: Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial. Image Credit: Clari Massimilliano / Shutterstock.com
Nicotine and addiction
Reducing the nicotine content in cigarettes to very low levels could make them less addictive for smokers. Previous studies have demonstrated that this type of reduction from the standard 16 mg/g content of nicotine to 2.4 mg/g is associated with fewer cigarettes smoked daily.
By reducing dependence on cigarettes and the satisfaction obtained from smoking, the addictiveness of cigarettes will subsequently decline. In fact, nicotine reduction to 0.4 mg/g, which is the nicotine concentration in very low nicotine content cigarettes (VLNC), is associated with more frequent efforts to quit, smoke-free days, and a higher proportion of successful quitters as compared to the use of regular nicotine content (NNC) cigarettes.
Previously, an abrupt shift to VLNC was associated with a significant increase in these beneficial health effects compared to attempts to gradually reduce NNC cigarette use. Nevertheless, it is crucial to determine how potential customers would benefit from transitioning from VLNC to NNC in the presence of ANDS in the marketplace, as is the case in the real world.
Recently, the United States Food and Drug Administration (FDA) tentatively proposed a nicotine reduction standard for all combusted tobacco products. This initiative follows a New Zealand study modeling the notable benefits of reducing the nicotine content of cigarettes.
About the study
The current study involved six sites where smokers were randomly assigned to smoke either NNC or VLNC that were purchased from an online experimental marketplace. E-cigarettes and medical nicotine were also available.
All study participants were adults above 21 years of age, smoked between five and 40 cigarettes each day, and were physically and mentally sound without alcohol or drug abuse histories.
Study participants were exposed to the marketplace for 12 weeks. At the end of this period, the number of cigarettes smoked each day and total no-smoking days were evaluated.
What did the study show?
The study comprised 438 participants, most of whom were white and with a mean age of 45. Over 77% of the study cohort completed the 12-week trial.
Participants in the VLNC group smoked fewer cigarettes each day by the end of the study period at seven cigarettes as compared to 13 cigarettes for the NNC group.
After adjusting for confounding factors, VLNC consumers used an average of six cigarettes less each day than NNC users by the 12th week, with this effect increasing with time. The VLNC group had a mean of 19 smoke-free days compared to five days in the NNC group.
The availability of ANDS failed to improve the likelihood of quitting cigarettes compared to an earlier study without ANDS. Nevertheless, 20% of study participants in the VLNC group quit smoking for at least seven days, compared to 7% of the NNC group.
Thus, the likelihood of quitting was three-fold higher with VLNC use. Interestingly, this occurred in a population of smokers who were not interested in quitting in the near future.
The levels of 2-cyanoethyl mercapturic acid (CEMA), a biomarker for acrylonitrile, reduced to a greater extent at week 12 in the VLNC group, thus indicating reduced exposure to toxins and carcinogens in these individuals. Non-combusted tobacco use was lower at baseline but increased in the VLNC group over time as combusted tobacco use declined.
Cigarette dependence scores were significantly lower at week 12 with VLNC as compared to NNC use. During the first week of VLNC use, withdrawal symptoms were higher until eventually declining to those reported in the NNC group by week two. Smoking urges were also significantly lower with VLNC use as compared to NNC use by the end of the study period.
Conclusions
The availability of VLNC cigarettes improved smoking-related outcomes. Non-combusted ANDS were more likely to be used in this group by the end of the study.
Smoking-related toxicant exposure was also reduced, with CEMA and other toxicant levels comparable in combusted tobacco users as compared to users of both combusted and non-combusted tobacco. Thus, VLNC use is preferable to e-cigarette use among would-be quitters, considering the significantly reduced exposure risk.
The study findings demonstrate that reduced-nicotine cigarettes could be an essential public health measure to reduce tobacco addiction. Thus, these products should be made standard in the marketplace, along with non-combusted ANDS.
A policy that establishes a nicotine reduction standard for combusted products is likely to accelerate smoking cessation.”
The availability of non-combusted ANDS in the marketplace will benefit smokers who are not ready to quit. Most VLNC users who quit used ANDS, thus emphasizing their value in these individuals.
ANDS also helps VLNC users abstain from smoking, as demonstrated by their use by most individuals who stopped smoking for seven days. Thus, both smoking cessation support and a policy that leads to the enforcement of nicotine reduction standards are essential to reduce smoking-related harms.
Journal reference:
- Hatsukami, D. K., Jensen, J. A., Carroll, D. M., et al. (2024). Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial. The Lancet Regional Health. doi:10.1016/j.lana.2024.100796.