Low-nicotine Cigarette Use May Not Lead to Compensatory Smoking

PHILADELPHIA – The use of cigarettes with low nicotine content did not result in compensatory smoking, according to results from two studies published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

“Smoking is the number one preventable cause of death in the United States and worldwide,” said Tracy Smith, PhD, assistant professor at the Medical University of South Carolina and Hollings Cancer Center and the lead author on both studies. “The U.S. Food and Drug Administration (FDA) is considering a policy that would require the nicotine content in cigarettes to be reduced to a minimally addictive level. It is important to understand how such a policy might impact the smoking behaviors of current smokers.”

One of the concerns associated with lowering the nicotine content of cigarettes is that this may lead to compensatory smoking, such as smoking more cigarettes and/or smoking differently to acquire more nicotine. “If using low-nicotine cigarettes results in compensatory smoking, there could be a negative impact on public health due to increased exposure to harmful constituents in the smoke,” said Smith. “The purpose of our studies was to determine if smokers engaged in compensatory smoking when using low-nicotine cigarettes.”

In the first study, Smith and colleagues asked whether smokers using low-nicotine cigarettes changed the way they smoked, such as increasing intensity of their puffs, to obtain more nicotine. Prior studies examining smoking intensity have not found evidence of compensatory smoking with low-nicotine cigarettes after the first few cigarettes; however, those studies were performed in laboratory settings. “The laboratory setting may not represent real-world behavior, so we wanted to examine smoking intensity in a more natural setting outside of the lab,” said Smith.

For this study, Smith and colleagues utilized data from a larger clinical trial in which participants were randomly assigned to receive either cigarettes with normal nicotine content – containing 15.8 mg nicotine per 1 g of tobacco – or one of four different low-nicotine content cigarettes – ranging from 0.4 to 5.2 mg nicotine per 1 g of tobacco. Participants were asked to smoke only the provided cigarettes and to collect and return their used cigarette butts for analysis. The study duration was six weeks, and cigarette butts were collected during weeks two and six.

Analyses were performed on week-six cigarette butts from 378 participants, representing 51 to 70 participants from each group. The amount of a chemical called solanesol was measured in each cigarette butt to estimate the amount of nicotine taken into the mouth. The estimated nicotine intake from each cigarette butt was then compared to the level of nicotine intake that would be expected if the cigarette were smoked with normal intensity and without compensation. The expected nicotine intake for each type of study cigarette had been previously determined using a laboratory machine. The machine determined expected nicotine intake by smoking a cigarette and measuring the nicotine exposure, explained Smith.

Consistent with previous laboratory studies, the authors found no significant differences between the observed nicotine intakes and the expected intakes, suggesting that participants using low-nicotine cigarettes most likely had not increased the intensity of their puffs to obtain more nicotine. “The data from this study are important because they suggest that smokers do not engage in compensatory smoking by smoking each cigarette more intensely when switching to low-nicotine cigarettes,” said Smith.

A limitation of the study is that participants still had access to commercially available cigarettes with normal nicotine content. “We know that some participants smoked non-study cigarettes with normal nicotine levels, even though we asked them to smoke only the cigarettes we provided,” said Smith. “Since we were only able to analyze the butts of the provided study cigarettes, we don’t know the nicotine intake or smoke exposure from these other cigarettes.” It is possible that participants smoked non-study cigarettes more intensely.

Another limitation is that cigarette butts were not collected from the first week of the study, when compensatory smoking may be more likely. However, data collected from week six is more likely to be representative of long-term smoking behaviors and therefore more informative, explained Smith. A third limitation is that the expected nicotine intake determined by the laboratory machine may not be representative of how some individuals smoke cigarettes.

In the second study, Smith and colleagues asked whether smoking low-nicotine cigarettes would impact the number of cigarettes that participants smoked per day. Unlike the previous study, participants in this study did not have access to non-study cigarettes since all 16 participants were isolated to a hotel where they could only purchase the cigarettes provided by the study. All study subjects participated in two four-night hotel stays, separated by one week. During the first stay, the study cigarettes had a normal nicotine content (15.8 mg nicotine per g of tobacco), while the study cigarettes during the second stay had a low nicotine content (0.4 mg nicotine per g of tobacco). Participants were aware of the nicotine content of their cigarettes during all portions of the study. Participants collected and returned used cigarette butts, which were counted to determine the number of cigarettes smoked per day.

Smith and colleagues found that there were no significant changes in the number of cigarettes smoked per day when participants switched to low-nicotine cigarettes. Analysis of urine samples demonstrated that most of the biomarkers of smoke exposure – which correlate with both number of cigarettes smoked and smoking intensity – did not increase with low-nicotine cigarettes. One biomarker, a metabolite of the toxicant acrolein, was significantly increased for the first day of using low-nicotine cigarettes but not for subsequent days, indicating that any increase in smoking intensity was transient.

Limitations of the second study include the small sample size, the limited racial diversity of the participants, and the somewhat artificial hotel setting.

“Together, these studies show that when smokers switch to low-nicotine cigarettes, there is no evidence of stable compensatory smoking,” said Smith. “These data provide critical information about the effects we might observe if the FDA were to implement a policy mandating the reduction of nicotine in cigarettes to a minimally addictive level.” Both studies were supported by the National Institute on Drug Abuse, the National Institutes of Health, and the Food and Drug Administration Center for Tobacco Products (R03DA045197, U54DA031659). The discarded filter analysis and analyses of urinary biomarkers were supported by the Centers for Disease Control and Prevention. The statistical analyses were supported by a shared core at the Masonic Cancer Center and University of Minnesota funded by the National Cancer Institute. Smith reports no conflicts of interest. Smith’s comments are her own and do not necessarily represent the official views of the National Institutes of Health.