Research Summary

Systematic Review Finds Minimal Compensatory Smoking With Very Low Nicotine Cigarettes

Anthony Calabro, MA

Key Highlights

  • None of the 17 included RCTs reported increased mean cigarette consumption or exhaled carbon monoxide exposure with very low nicotine content cigarettes compared with normal nicotine content cigarettes.
  • At 6 weeks, an estimated 0.8% of participants could be expected to smoke more cigarettes when assigned to very low nicotine content cigarettes.
  • An estimated 8.1% of participants could experience increased carbon monoxide exposure at 6 weeks, with a maximum expected increase of 4.2 ppm.

Very low nicotine content cigarettes were not associated with widespread compensatory smoking during extended use, according to a systematic review and pooled meta-analysis published in JAMA Network Open. The findings address concerns that reducing the nicotine content of cigarettes could cause people to smoke more cigarettes or alter their smoking behavior in ways that increase smoke exposure.

Very low nicotine content cigarettes contain approximately 95% less nicotine than standard cigarettes. The researchers analyzed this data as the FDA pursues a product standard that would establish a maximum nicotine level for cigarettes and other combusted tobacco products.

Investigators searched PubMed MEDLINE, Embase, Web of Science, the Cochrane Library, and CINAHL through July 5, 2024, for randomized clinical trials evaluating very-low-nicotine-content cigarettes. Eligible trials assigned participants to smoke the cigarettes for 3 to 20 weeks and reported daily cigarette consumption, exhaled carbon monoxide exposure, or both.

The systematic review included 17 RCTs published between 2010 and 2024, representing 5,500 adolescent and adult participants. Sixteen trials were conducted in the United States, and 1 was conducted in New Zealand. A pooled meta-analysis included 2,454 participants from 7 US trials and used individual-level treatment-effect modeling to estimate the proportion of participants who might compensate for reduced nicotine exposure.

Study Findings

No included trial reported an increase in mean cigarettes smoked per day or carbon monoxide exposure among participants assigned to very low nicotine content cigarettes compared with normal nicotine content cigarettes.

Sixteen of the 17 trials found significantly fewer cigarettes smoked per day with very-low- nicotine-content cigarettes, with between-group differences ranging from approximately 1.6 to 14.9 fewer cigarettes per day. Among the 13 trials reporting carbon monoxide outcomes, 9 found significant reductions, and 4 found no significant between-group differences.

In the pooled analysis, participants assigned to very-low-nicotine-content cigarettes smoked an estimated mean of 5.7 fewer cigarettes per day at 6 weeks. Approximately 0.8% could be expected to increase their cigarette consumption, with a maximum expected increase of 3.3 cigarettes per day.

Exhaled carbon monoxide levels were an estimated mean of 2.7 ppm lower at 6 weeks. An estimated 8.1% of participants could experience increased carbon monoxide exposure, with a maximum expected increase of 4.2 ppm.

Although estimated compensation was more common after 1 week, the increases were generally not sustained at 6 weeks. The researchers also found no subgroups, based on sociodemographic or tobacco-use characteristics, that were more likely to increase cigarette consumption or carbon monoxide exposure.

Clinical Implications

According to the study authors, the findings suggest that widespread compensatory smoking is unlikely if the FDA implements a low-nicotine product standard for cigarettes and other combusted tobacco products. The authors noted that some individuals may initially increase their smoking while transitioning to very-low-nicotine-content cigarettes. Still, the pooled findings indicated that such changes were unlikely to persist.

The study limitations included reliance on self-reported cigarette consumption and exhaled carbon monoxide measurements, which may be affected by smoking recency or other exposures. The pooled trial population was also not representative of the overall US population of people who smoke, limiting interpretation of the estimates at the national level.

Expert Commentary

“In this systematic review and pooled meta-analysis of VLNC RCTs, we observed minimal evidence of compensatory smoking when people smoked VLNCs for extended periods,” the researchers concluded.

Reference
Denlinger-Apte RL, Ji Z, Harwood EA, et al. Compensatory smoking with very low nicotine content cigarettes: a systematic review and meta-analysis. JAMA Netw Open. 2026;9(7):e2622543.. doi:10.1001/jamanetworkopen.2026.2254