Study examined impact on fast nicotine metabolizers All smokers, including fast nicotine metabolizers, are likely to benefit if the FDA follows through on a proposal to reduce nicotine levels in cigarettes to minimally addictive or non-addictive levels, new research suggests. It has been a year since FDA Commissioner Scott Gottlieb, MD, announced plans to consider the move, and in March of this year the agency issued an advanced notice of proposed rulemaking (ANPRM) asking for public comment on the proposal. According to an FDA model, reducing nicotine levels to very low levels would prevent more than eight million premature deaths from tobacco in the U.S. by the year 2100. But it is not clear if capping nicotine levels would benefit smokers who metabolize nicotine rapidly, either due to genetic predisposition or for some other reason, said Andrew Strasser, PhD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia. "Fast metabolizers tend to smoke more cigarettes per day and they puff more intensely when they smoke commercially available cigarettes," Strasser told MedPage Today. "But with the low-nicotine content cigarette the FDA is proposing, puffing more intensely would not be rewarding because there is no additional nicotine to extract." Nevertheless, he said it made sense to examine whether federally mandated nicotine restrictions would in some way adversely affect smokers who are fast nicotine metabolizers. In the study, published online in JAMA Network Open, Strasser and colleagues examined the association between reduced nicotine content cigarette use and smoking behaviors and biomarkers of exposure in fast and slow nicotine metabolizers. A total of 100 daily, non-treatment-seeking, non-menthol cigarette smokers, including 59 fast and 41 slow metabolizers, were included in the study. Use of reduced nicotine content cigarettes for two 15 day periods (5.2 mg [RNC1] and 1.3 mg [RNC2] of nicotine per gram of tobacco) was the intervention, and the main outcomes and measures included smoking behaviors (number of cigarettes smoked per day, total puff volume) and biomarkers of exposure (carbon monoxide, urine total nicotine equivalents, and 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol.) Use of both reduced nicotine content cigarettes were associated with decreased puffing and urinary biomarkers of exposure, but not with decreased daily cigarette consumption of carbon monoxide levels, the researchers noted. Nicotine-metabolite ratio was not associated with moderation at the nicotine levels tested. "Contrary to our hypothesis, the nicotine-metabolite ratio did not moderate these associations, suggesting that fast metabolizers are not at greater risk of increasing use or exposure with these products," the researchers wrote. "The findings are consistent with those of prior reduced nicotine content studies, although these smokers have greater conventional cigarette use and exposure." The study's lead author, Melissa Mercincavage, PhD, also of the University of Pennsylvania, told MedPage Today: "Importantly, there were not differences based on how smokers metabolized nicotine. These findings suggest that if the FDA moves forward in deciding to set a maximum level of nicotine content in cigarettes, nicotine metabolism is not a factor that needs to be considered." Source
