Compensatory Smoking With Very Low Nicotine Content Cigarettes: A Systematic Review and Meta-Analysis.

Importance: The US Food and Drug Administration (FDA) is pursuing a low-nicotine product standard for cigarettes and other combusted tobacco. Very low nicotine content cigarettes (VLNCs) contain approximately 95% less nicotine than standard cigarettes. A key concern is that people who smoke may increase their smoking to compensate for the reduced nicotine levels, which would be a major unintended consequence of the regulation. Objective: To examine whether people who smoke increase their smoking behavior and/or smoke exposure when smoking VLNCs for extended periods. Data Sources: A comprehensive search was performed across multiple databases (eg, PubMed Medline, Embase, Web of Science, Cochrane Library, and CINAHL) on July 5, 2024, to identify randomized clinical trials (RCTs) evaluating VLNCs. Study Selection: Eligible RCTs reported treatment conditions comprising smoking VLNCs for 3- to 20-week periods. Control conditions varied but typically included smoking normal nicotine content cigarettes (NNCs). Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Two investigators performed the data extraction. Main Outcomes and Measures: Outcomes included the total number of cigarettes smoked per day and exhaled breath carbon monoxide (CO) exposure at the end of the intervention. Results: Seventeen RCTs (16 from the US and 1 from New Zealand) published between 2010 and 2024 met inclusion criteria, representing 5500 adolescents and adults who smoked cigarettes daily or nondaily, with or without quit interest. The pooled meta-analysis included a subset of 2454 participants from 7 US trials. No trials reported increases in the mean number of cigarettes smoked per day or CO exposure at the end of the intervention among participants assigned to VLNCs vs NNCs. It was estimated that 0.8% of participants could expect an increase in smoking, with a maximum expected increase of 3.3 cigarettes smoked per day, and 8.1% could expect an increase in CO exposure, with a maximum expected increase of 4.2 parts per million 6 weeks after randomization if assigned VLNCs vs NNCs. Conclusions and Relevance: This systematic review and meta-analysis of VLNC RCTs found minimal evidence of compensation among people assigned to smoke VLNCs. The findings suggest that widespread compensatory smoking is unlikely to occur if the FDA implements a low-nicotine product standard for cigarettes and other combusted tobacco.