Does menthol cigarette use moderate the effect of nicotine metabolism on short-term smoking cessation?

Abstract

The nicotine metabolite ratio (NMR) has been shown to predict response to the transdermal nicotine patch, such that faster nicotine metabolism is associated with a lower abstinence rate. Menthol cigarette use, vs. non-menthol cigarette use, slows nicotine metabolism and therefore may attenuate the effect of NMR on smoking abstinence. In this study, we evaluated whether cigarette type (menthol vs. non-menthol) modified the association between NMR and short-term abstinence. This was a secondary analysis examining treatment in the first 8 weeks of 21 mg/day nicotine patch therapy in a completed clinical trial (n=474). Menthol cigarette use was based on self-report. NMR was defined dichotomously (0=fast, 1=slow) to distinguish between fast (≥0.47) versus slow NMR. Using logistic regression analysis, we tested whether cigarette type moderated the association between NMR and bioverified 7-day point prevalence abstinence at week 8. Covariates include nicotine dependence, age, race, and sex. 302 participants reported smoking menthol cigarettes, of which 234 (77%) were classified as slow NMR. Among the 172 non-menthol smokers, 136 were classified as slow NMR (79%). Contrary to our expectations, the NMR by cigarette type interaction effect on abstinence was not significant (Odds Ratio [OR]=0.91, p=.86). Excluding the interaction variable, fast NMR was associated with decreased likelihood of abstinence (OR=0.55, p=.03), but menthol cigarette use was not (OR=1.15, p=.56). Further exploration of risk factors among menthol cigarette smokers, especially among racially diverse and light smokers, could clarify the association between menthol cigarette use and poorer smoking outcomes.

Brief Report: HIV Infection Does Not Explain Higher Nicotine Metabolism in People Living With HIV

“…This is notable as White smokers are less likely to smoke menthol cigarettes, which have been shown to inhibit nicotine metabolism and thus may lower the NMR. 26,27 However, previous work by Jao et al 28 suggests that menthol cigarette use was not associated with short-term smoking abstinence, and there was no evidence of an interaction between cigarette type and NMR on the effect of short-term abstinence.…”

Use of Mentholated Cigarettes and Likelihood of Smoking Cessation in the United States: A Meta-Analysis

“…Of these, 22 met all study inclusion criteria. 8,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][40][41][42][43][44] In three instances, two published articles analyzed data from the same underlying study; therefore, our meta-analysis included information from 19 data sources representing 147 584 cigarette smokers. Although we did not intentionally exclude non-US studies, all identified studies except for one were conducted exclusively in the United States, and the one exception included smokers from both the United States and Canada.…”

Peripheral Biomarkers of Tobacco-Use Disorder: A Systematic Review

“…Longitudinal studies of exposure markers have primarily been secondary analyses of randomized controlled clinical trials (RCTs) or non-randomized studies of smoking cessation, and thus offer an opportunity to look at potential predictive relationships with treatment response. One such secondary analysis of a 8-week RCT of nicotine replacement therapy (NRT), in the form of a 21mg/day transdermal nicotine patch, measured the impact of NMR at baseline on treatment response in 474 smokers (22). Those with a lower NMR (i.e.…”

“…This systematic review yielded many study studies revealing associations between peripheral biomarkers and clinical outcomes, most notably: severity of dependence, treatment response, and risk of relapse after cessation. Biomarkers of exposure such as cotinine, beyond indicating smoking status, showed robust associations with severity of dependence (30-32, 40), and low NMR showed an association with increased risk of relapse during cessation (22, 35). Cotinine showed less consistent associations with CPD, suggesting expired CO as a superior status marker and cotinine/NMR a superior dependence marker.…”

“…Expired CO is increased acutely (6-9 hours) after combustible tobacco use, whereas cotinine, the primary metabolite of nicotine, has a longer half life (5-7 days) thus giving a longer-term measure of exposure to nicotine, regardless of the route of administration (21). However, growing evidence suggests that these, other exposure markers, are associated with dependence severity and risk of relapse (22, 23). Biomarkers not directly related to nicotine metabolism have been increasingly studied in TUD, such as markers of cardiovascular disease (CVD), inflammation, oxidative stress, and hypothalamic-pituitary-adrenal (HPA) axis reactivity (24-26).…”