Mentholated Cigarette Smoking Inhibits Nicotine Metabolism

Abstract

Smoking mentholated cigarettes has been suggested to convey a greater cancer risk compared with smoking nonmentholated cigarettes. Two of the possible mechanisms by which mentholated cigarette smoking could increase risk are by increasing systemic exposure to tobacco smoke toxins and by affecting the metabolism of nicotine or tobacco smoke carcinogens. To examine these possibilities, we performed a crossover study in 14 healthy smokers, one-half of whom were African-Americans and one-half whites. Subjects were randomly assigned to smoke mentholated or nonmentholated cigarettes for 1 week, then to cross over to the other type of cigarettes for another week. Subjects were confined to a Clinical Research Center for 3 days of each week, during which time blood levels of nicotine and carbon monoxide were measured throughout the day and an intravenous infusion of deuterium-labeled nicotine and cotinine was administered to determine the rate and pathways of nicotine metabolism. The systemic intake of nicotine and carbon monoxide was, on average, not affected by mentholation of cigarettes. Mentholated cigarette smoking did significantly inhibit the metabolism of nicotine (clearance: 1289 versus 1431 ml/min, two sided, p ϭ 0.02). Inhibition of nicotine metabolism occurred both by slower oxidative metabolism to cotinine and by slower glucuronide conjugation. Our data do not support the hypothesis that mentholated cigarette smoking results in a greater absorption of tobacco smoke toxins. Our finding of impaired metabolism of nicotine while mentholated cigarette smoking suggests that mentholated cigarette smoking enhances systemic nicotine exposure.

Smokers of Menthol and Nonmenthol Cigarettes Exhibit Similar Levels of Biomarkers of Smoke Exposure

“…The present biomarkers findings are consistent with the weight of extant epidemiologic evidence (22,24) and prior biomarkers studies (36,40) suggesting that exposures and consequent risks attending the smoking of mentholated cigarettes are not substantially different from those of nonmentholated cigarettes. …”

“…The estimate of 0.625 mg menthol delivery to the smoker per cigarette smoked that was developed by Benowitz and colleagues (36) is in fair agreement with an estimated systemic delivery that might be developed from the 0.34 mg menthol per cigarette smoke yield reported here from standardized machine smoking. The recent development of improved methods to measure the lung deposition and retention of individual cigarette smoke constituents in human smokers (41,42) suggests that better estimates of both local and systemic exposures to menthol or to other smoke constituents of greater toxicologic interest may soon be attainable.…”

Racial Differences in Serum Cotinine Levels of Smokers

“…Although there have been reports of higher cotinine levels among menthol smokers [14,16], most studies are not in accord with these findings [18][19][20][21][22][23], and we observed adjusted cotinine levels non-significantly lower in this group. White female menthol smokers in fact had the highest intensity of smoking but the lowest average cotinine levels (Fig.…”

“…1). It has been hypothesized that menthol cigarettes may intensify smokingrelated lung cancer risk through a variety of physiological mechanisms or by altering smoking behavior (e.g., by facilitating deeper inhalation) [5,21]. A recent investigation measuring smoking topography, however, reported slightly lower puff volume among menthol compared with non-menthol smokers [24].…”

Inhibition of Morphine Glucuronidation in the Liver Microsomes of Rats and Humans by Monoterpenoid Alcohols

“…It has been reported that smoking cigarettes containing menthol interferes with nicotine glucuronidation 49) the catalysts of which are assumed to be UGT2B10 and UGT1A4. 50,51) Monoterpenoid alcohols interfere with propofol glucuronidation catalyzed by UGT1A9.…”