Non-menthol Cigarette Smokers Research Articles

Improving Prediction of Tobacco Use Over Time: Findings from Waves 1-4 of the Population Assessment of Tobacco and Health Study.

First-order Markov models assume future tobacco use behavior is dependent on current tobacco use and are often used to characterize patterns of tobacco use over time. Higher-order Markov models that assume future behavior is dependent on current and prior tobacco use may better estimate patterns of tobacco use. This study compared Markov models of different orders to examine whether incorporating information about tobacco use history improves model estimation of tobacco use and estimated tobacco use transition probabilities. We used data from four waves of the Population Assessment of Tobacco and Health Study. In each Wave, a participant was categorized into one of the following tobacco use states: never smoker, former smoker, menthol cigarette smoker, non-menthol cigarette smoker, or e-cigarette/dual user. We compared first-, second-, and third-order Markov models using multinomial logistic regression and estimated transition probabilities between tobacco use states. The third-order model was the best fit for the data. The percentage of former smokers, menthol cigarette smokers, non-menthol cigarette smokers, and e-cigarette/dual users in Wave 3 that remained in the same tobacco use state in Wave 4 ranged from 63.4% to 97.2%, 29.2% to 89.8%, 34.8% to 89.7%, and 20.5% to 80.0%, respectively, dependent on tobacco use history. Individuals who were current tobacco users, but former smokers in the prior two years, were most likely to quit. Transition probabilities between tobacco use states varied widely depending on tobacco use history. Higher-order Markov models improve estimation of tobacco use over time and can inform understanding of trajectories of tobacco use behavior. Findings from this study suggest that transition probabilities between tobacco use states vary widely depending on tobacco use history. Tobacco product users (cigarette or e-cigarette/dual users) who were in the same tobacco use state in the prior two years were least likely to quit. Individuals who were current tobacco users, but former smokers in the prior two years, were most likely to quit. Quitting smoking for at least two years is an important milestone in the process of cessation.

Comparison of urine heavy metals in exclusive menthol and non-menthol cigarette users by race/ethnicity: The 2015-2016 National Health and Nutrition Examination Survey Special Sample.

The objective of this study was to investigate the differences in urine concentrations of heavy metals (uranium, cadmium, and lead) between exclusive menthol and non-menthol cigarette smokers across three racial/ethnic groups using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 Special Sample. Data from NHANES 2015-2016 Special Sample were analyzed to assess the association between menthol smoking and heavy metal biomarkers in urine across three racial/ethnic groups (N=351), including Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic/Other (HISPO). Multivariable linear regression models were used to estimate adjusted geometric means (GMs) and ratio of GMs (menthol/non-menthol smokers) (RGMs) for urine biomarkers of heavy metals between menthol and non-menthol smokers by race/ethnicity. Among the 351 eligible participants, 34.4% (n=121) were NHW, 33.6% (n=118) were NHB, and 32.0% (n=112) were HISPO exclusive cigarette smokers. The analysis revealed significantly higher concentrations of urine uranium in NHB menthol smokers compared to NHB non-menthol smokers (RGMs=1.3; 95% CI: 1.0-1.6; p=0.04). NHW menthol smokers appeared to have higher levels of urine uranium than non-menthol smokers, but the difference was not statistically significant (9.0 vs 6.3; RGMs=1.4; 95% CI: 1.0-2.2; p=0.08). There were no significant differences in urine metals (cadmium and lead) by menthol status among NHW, NHB, or HISPO cigarette smokers (p>0.05). The research findings regarding the higher levels of urine uranium among Non-Hispanic Black (NHB) menthol cigarette smokers raise questions about the claims suggesting that additives in cigarettes do not contribute to increased toxicity.

Commentary: Cigarette dependence in menthol and non-menthol young adult cigarette smokers

FDA’s Proposed Final Rule to ban menthol cigarettes asserts that “menthol cigarettes contribute to greater nicotine dependence in youth and young adults than non-menthol cigarettes.” However, none of the publications referenced included young adults. To provide empirical evidence on the subject, we examine smoking frequency and Heaviness of Smoking Index (HSI) dependence among 2,194 young adult (ages 18–25 years) menthol and non-menthol smokers from 31 online survey samples. Unpaired t-tests examined if daily smoking or the proportion of daily smokers who are low or high dependence on the HSI vary by menthol cigarette smoking status. Young adult menthol smokers were less likely to be daily smokers than young adult non-menthol smokers. There were no differences in the percentages of daily menthol and non-menthol smokers categorized as low or high dependence on the HSI. Smoking menthol cigarettes, therefore, does not appear to be associated with greater cigarette dependence among young adults than smoking non-menthol cigarettes.

Assessing the Evidence on the Differential Impact of Menthol versus Non-menthol Cigarette Use on Smoking Dependence in the US Population: A Systematic Review and Meta-analysis.

Background: Menthol's effect on cigarette smoking behaviors is an intensely scrutinized US public health issue. This systematic review and meta-analysis examined the question: Does menthol cigarette use have a differential impact on smoking dependence compared with non-menthol cigarette use? Methods: We consulted 6 databases from inception to October 15, 2021. We included articles comparing menthol versus non-menthol cigarette smokers against predefined smoking dependence outcomes. Risk of bias was assessed using the AHRQ Evidence-Based Practice Center approach. We applied a random-effects model to pool adjusted odds ratios. Results: We synthesized 37 demographically adjusted studies. Meta-analytic results suggested non-menthol smokers were equally/more likely to report daily versus non-daily smoking; menthol use was associated with needing a cigarette within one hour; cigarettes per day was not associated with menthol use; menthol use was associated with a low (vs high) Heaviness of Smoking Index score; and results were either non-significant or associated menthol use with lower TTFC. Conclusions: Despite consistently good or fair quality adjusted studies across several measures, results were discordant depending on measures used and means of measurement. Overall, the evidence is insufficient to draw clear conclusions on a differential association between menthol (vs non-menthol) cigarette use and smoking dependence.

Comparison of Carcinogen Biomarkers in Smokers of Menthol and Nonmenthol Cigarettes: The 2015-2016 National Health and Nutrition Examination Survey Special Sample.

The US FDA announced its commitment to prohibiting menthol as a characterizing flavor in tobacco. The relationship between cigarette menthol and exposure to toxic substances in mainstream tobacco smoke is not well characterized. Data from the National Health and Nutrition Examination Survey (NHANES) 2015 to 2016 special sample were used to study markers of 26 harmful and potentially harmful constituents (HPHC) in tobacco smoke. These include urine metabolites of polycyclic aromatic hydrocarbons (PAH), volatile organic compounds (VOC), and heavy metals in exclusive menthol (n = 162) and nonmenthol (n = 189) cigarette smokers. Urine metabolites of 7 PAHs, 15 VOCs, and 4 heavy metal biomarkers were compared by menthol status. Multivariable analyses were conducted on creatinine-adjusted concentrations. There were no significant differences in cotinine levels or in 22 of 26 HPHCs. Among the urine metabolites of PAHs, the levels of 1-hydroxyphenanthrene were about 16% lower in menthol smokers. Among the urine metabolites of VOCs, menthol cigarette smokers presented significantly lower concentrations of acrylamide, N,N-dimethylformamide, and acrylonitrile. Menthol and nonmenthol smokers presented similar levels of heavy metals. Menthol did not affect the levels of cotinine and the nicotine metabolite ratio in urine. Menthol and nonmenthol cigarettes deliver similar levels of most HPHCs. Findings on toxicity are similar for menthol and nonmenthol cigarettes.

Differences in Cognitive Task Performance, Reinforcement Enhancement, and Nicotine Dependence Between Menthol and Nonmenthol Cigarette Smokers.

Menthol has been shown to target similar brain regions and neural receptors as nicotine, yet the association between menthol cigarette use and cognitive performance remains unknown. This study examined differences in cognitive task performance between menthol (MS) and nonmenthol (NMS) cigarette smokers after acute cigarette consumption. Sixty white and black and/or African American, nonabstinent, MS (n = 30) and NMS (n = 30) were assessed presmoking and postsmoking their preferred cigarette on four computerized tasks: Continuous Performance Task (CPT; alerting attention), N-Back Task (working memory), Finger Tapping Task (motor control), and Apple Picker Task (reinforcement enhancement). Self-reported nicotine dependence and objective smoking topography measures were also compared between groups. Initial unadjusted analyses showed a significant effect of cigarette type × time on CPT speed (p = .042), where MS improved while NMS group worsened in CPT speed after smoking. After controlling for baseline cigarette craving and cigarette nicotine levels, the effect of cigarette type × time for all cognitive outcomes was statistically nonsignificant (ps > .05). However, there remained a significant effect of cigarette type, where MS versus NMS had poorer CPT (p = .046) and N-Back Task accuracy (p = .006) but faster N-Back speed (p = .039). There were no statistically significant differences between groups on reinforcement enhancement, nicotine dependence, or smoking behavior outcomes (ps > .05). Contrary to our hypotheses, results did not find a significant effect of cigarette type on the change in cognitive performance after acute smoking in nonabstinent smokers. Further studies are needed to clarify the specific pharmacological effects of nicotine and menthol on cognitive functioning. The current study is the first to compare the potential enhancement of cognitive task performance after acute cigarette smoking between satiated menthol and nonmenthol cigarette smokers. Study results suggest that acute menthol cigarette use may not enhance cognitive function above and beyond nonmenthol cigarettes to increase dependence among menthol smokers. However, the contribution of other psychological factors (eg, craving, mood) and cigarette characteristics (eg, nicotine content) may be involved in cognitive function enhancement to perpetuate dependence and smoking persistence for menthol smokers.

Utilizing Reach Ratios to Assess Menthol Cigarette Smoker Enrollment in Quitline Services

Increasing the reach of evidence-based cessation services is a longstanding public health priority, especially for subgroups who may be most at risk. Little research has examined whether quitlines are reaching menthol cigarette smokers who may have increased difficulty quitting compared with nonmenthol cigarette smokers. This study aims to understand whether quitline services are reaching menthol cigarette smokers. The study sample included adult smokers enrolled in Minnesota's quitline program, QUITPLAN Services, between May 2017 and April 2018 (N=10,999). Cigarette smokers were asked about the usual cigarette type (menthol versus nonmenthol). Reach ratios were calculated by dividing the percentage of program enrollees who are menthol smokers by the percentage of Minnesota smokers who are menthol smokers. Differences in demographic, tobacco use, and utilization characteristics between menthol and nonmenthol smokers were assessed using chi-square and t-tests. Analyses were conducted in March 2019. Among QUITPLAN Services enrollees, 30.7% of smokers reported using menthol cigarettes. The reach ratio was 1.12 (95% CI=0.99, 1.25). Menthol smokers were more likely to be younger, be female, be Black/African American, be Hispanic, and live in an urban area than nonmenthol smokers. Although menthol smokers were more likely than nonmenthol smokers to enroll in text messaging, no other significant differences in service utilization were found. The findings suggest that menthol smokers are proportionately represented among quitline enrollees. State quitlines should assess menthol smoking status at intake and allocate resources to reach and better serve menthol smokers.

A Longitudinal Examination of Behavioral Transitions among Young Adult Menthol and Non-Menthol Cigarette Smokers Using a Three-State Markov Model.

Young adult cigarette smoking behaviors are complex and dynamic. Emerging research suggests a growing rate of switching from non-menthol to menthol cigarettes. Transitions across cigarette smoking states are not well understood. This research longitudinally explores transitions in cigarette smoking behaviors among 18-29 year olds. We applied a Markov model to data collected biannually for 1542 initially 18-29 year old young adults (mean age: 20.9 years; SD = 2.6) in Texas, who provided 7021 total observations from Fall 2014 to Spring 2017. All participants were past 30 day menthol or non-menthol cigarette smokers at first observation. We examined transitions across three states of cigarette smoking (menthol, non-menthol, and nonsmoking) and compared predictors of each transition, during young adulthood. Descriptively, 22.2% of menthol and 14.3% of non-menthol smokers switched products while 25.6% of menthol and 26.0% of non-menthol smokers quit smoking. Among quitters, 20.0% relapsed via menthol and 28.2% relapsed via non-menthol cigarettes. Results from Markov model indicated that Hispanic/Latinos (Hazard Ratio [HR]: 3.69) and Asians (HR: 2.85) were significantly more likely to switch from non-menthol to menthol cigarettes, relative to non-Hispanic whites. Among recent quitters, the use of non-cigarette products was associated with increased risk of relapse via menthol (HR: 1.54) and non-menthol (HR: 1.85) cigarettes. A substantial proportion of young adult cigarette smokers transitioned across cigarette smoking states over the course of 2.5 years. Other tobacco use and nicotine dependence were impediments to becoming and remaining a non-smoker. Hispanic/Latinos and Asians, relative to non-Hispanic whites, had greater odds of transitioning from non-menthol smoking to both non-smoking and to menthol smoking. Findings suggest racial/ethnic differences in cigarette smoking transitions during young adulthood. This paper examined multidirectional transitions across cigarette smoking, including switching between menthol and non-menthol cigarettes, among young adults. Results indicate that Hispanic/Latino and Asian young adults are at increased risk of transition to menthol cigarette smoking compared with non-Hispanic white young adults. Findings highlight need for further study of Hispanic/Latino and Asian young adult smoking behaviors.

National Support for a Menthol Cigarette Sales Ban.

The US Food and Drug Administration (FDA) and local jurisdictions have different authorities to regulate menthol cigarettes, and a growing number of localities and the FDA are considering these policy options. The objective of this study was to update previous research on public support for a menthol ban, including examining differences in support by demographic factors, geographic region, and smoking status. We assessed policy support among a cross-sectional sample of 2871 adults aged 18-64 from a nationally representative online panel. We calculated weighted estimates of support by demographic factors, political ideology, region (Northeast, Midwest, South, West), and smoking status (never, former, current nonmenthol, current menthol). We used weighted adjusted logistic regression analysis to examine correlates of support for a menthol ban. Overall, 56.4% (95% CI, 54.4%-58.3%) of participants supported a government policy to ban menthol cigarette sales. Support was significantly higher among women than among men (62.5% vs 50.1%; P < .001); among Hispanic/Latino (69.3%), non-Hispanic African American (60.5%), and non-Hispanic other (65.8%) people than among non-Hispanic White people (50.4%; P < .001); and among never (64.8%) and former (47.0%) smokers than among current nonmenthol cigarette smokers (30.1%; P < .001). A significant proportion (28.5%; P < .001) of current menthol cigarette smokers supported a ban. After controlling for other factors, geographic region was not significantly associated with support for a ban. Efforts are needed to further increase support for a ban among current menthol cigarette smokers. These findings can be used to assist policy makers and communities in efforts to ban menthol cigarettes in their jurisdictions.

The Relationship Between Menthol Cigarette Use, Smoking Cessation, and Relapse: Findings From Waves 1 to 4 of the Population Assessment of Tobacco and Health Study.

Some, but not all, studies suggest that menthol cigarette smokers have more difficulty quitting than non-menthol cigarette smokers. Inconsistent findings may be a result of differences in smoker characteristics (eg, daily vs. non-daily smokers) across studies. This study examines the relationship between menthol cigarette use, cessation, and relapse in a longitudinal, nationally representative study of tobacco use in the United States. Data come from four waves of the Population Assessment of Tobacco and Health Study. Waves 1-4 were conducted approximately annually from September 2013 to January 2018. Generalized estimating equation models were used to prospectively examine the relationship between menthol cigarette use, cessation, and relapse in non-daily and daily adult (18+) smokers. Cessation was defined as smokers who had not used cigarettes within the past 30 days at their subsequent assessment. Relapse was defined as cessation followed by past 30-day smoking in the next assessment. Among daily smokers (n = 13 710), 4.0% and 5.3% of menthol and non-menthol smokers quit after 1 year, respectively. In an adjusted model, menthol smokers were less likely to quit compared with non-menthol smokers (odds ratio [OR] = 0.76 [0.63, 0.91]). When the sample was stratified by race/ethnicity, African American (OR = 0.47 [0.24, 0.91]) and White (OR = 0.78 [0.63, 0.97]) daily menthol users were less likely to have quit. Among non-daily smokers (n = 3608), there were no significant differences in quit rates. Among daily and non-daily former smokers, there were also no differences in relapse rates between menthol and non-menthol smokers. Menthol cigarette use is associated with lower odds of cessation. Findings from this study suggest that menthol cigarette use is associated with lower odds of cessation, but not relapse. Removing menthol cigarettes from the market may improve cessation rates.

Health Care Utilization of Menthol and Non-menthol Cigarette Smokers.

To study the association between health care utilization and menthol cigarette use and whether the association differed between African American (AA) and non-AA smokers. We analyzed the three most recent 2005, 2010, and 2015 National Health Interview Survey Cancer Control Supplements. After incorporating propensity score weights adjusting for observed differences between menthol and non-menthol users, we estimated Zero-Inflated Poisson models on hospital nights, emergency department visits, doctor visits, and home visits as a function of menthol use status and other covariates separately for current cigarette smokers and recent quitters (former smokers quitting cigarette smoking ≤ 4 years). Although current menthol smokers smoked fewer cigarettes per day than current non-menthol smokers, they did not differ from current non-menthol smokers in health care utilization. Among recent quitters, those who used to smoke menthol cigarettes had higher odds of having hospital nights than those who used to smoke non-menthol cigarettes. However, we did not find any significant association between menthol use and other health care utilization-emergency department visits, doctor visits, and home visits-among recent quitters. Moreover, compared with non-AA recent quitters, AA recent quitters had higher odds of having home visits, but fewer home visits, if they used to smoke menthol cigarettes. Menthol use was associated with greater hospitalization among recent quitters, and the association between home visits and menthol use differed between AA and non-AA recent quitters. This is the first study that used econometric models to study the association between health care utilization and menthol cigarette use and examine whether the association differed between AA and non-AA smokers. Our study found health care utilization did not differ by menthol use status for current smokers, although current menthol smokers smoked fewer cigarettes per day than current non-menthol smokers. However, we found menthol use was associated with higher odds of having hospital nights for recent quitters. We also found AA recent quitters had a different association between home visits and menthol use compared with non-AA recent quitters.

Gender Differences in the Association between Marijuana and Menthol Cigarette Use among African American Adult Cigarette Smokers

Introduction: Despite the strong relationship between marijuana and tobacco use, especially among African American individuals and males, very few studies have examined the association between marijuana and menthol cigarette use. This study was designed to identify the prevalence of past month, past year and lifetime marijuana use and marijuana dependence among menthol and non-menthol cigarette smokers, as well as the association between marijuana and menthol cigarette use among African American female and male cigarette smokers. Methods: Data were drawn from 1,173 African American adult cigarette smokers in the 2017 National Survey on Drug Use and Health. Results: Overall, 8.8%, 13.9% and 44.7% of African American menthol and non-menthol cigarette smokers reported past month, past year and lifetime marijuana use, respectively. Weighted multivariable logistic regression models revealed a significant interaction between gender and past month marijuana use on menthol cigarette use (AOR = 1.49, 95% CI: 1.21-2.42, p < .05). Past month marijuana use was associated with an increased odds of past month menthol cigarette use (relative to non-menthol cigarette use) among females, but a decreased odds of past of past month menthol cigarette use among males. Conclusions: When stratified by gender, marijuana use is differentially related to menthol cigarette use among African American adults. Given the prevalence of menthol cigarette use among this population, it is important to examine factors such as marijuana use that could be targeted in prevention and treatment interventions for African Americans, especially females, who are at risk for smoking or are currently smoking menthol cigarettes. Implications: This study found that marijuana use was associated with an increased odds of menthol cigarette use among African American females, while marijuana use was associated with a decreased odds of menthol cigarette use among their male counterparts. The impact of marijuana use on menthol cigarette smoking differs among females and males, highlighting the need for gender-tailored interventions that target marijuana use among African American individuals, especially females, who are at risk for smoking or are currently smoking menthol cigarettes.

Effects of Very Low Nicotine Content Cigarettes on Smoking Behavior and Biomarkers of Exposure in Menthol and Non-menthol Smokers.

IntroductionBecause 30% of cigarettes sold in the United States are characterized as menthol cigarettes, it is important to understand how menthol preference may affect the impact of a nicotine reduction policy.MethodsIn a recent trial, non-treatment-seeking smokers were randomly assigned to receive very low nicotine cigarettes (VLNC; 0.4 mg nicotine/g tobacco) or normal nicotine cigarettes (NNC; 15.5 mg/g) for 20 weeks. On the basis of preference, participants received menthol or non-menthol cigarettes. We conducted multivariable regression analyses to examine whether menthol preference moderated the effects of nicotine content on cigarettes per day (CPD), breath carbon monoxide (CO), urinary total nicotine equivalents (TNE), urinary 2-cyanoethylmercapturic acid (CEMA), and abstinence.ResultsAt baseline, menthol smokers (n = 346) reported smoking fewer CPD (14.9 vs. 19.2) and had lower TNE (52.8 vs. 71.6 nmol/mg) and CO (17.7 vs. 20.5 ppm) levels than non-menthol smokers (n = 406; ps < .05). At week 20, significant interactions indicated that menthol smokers had smaller treatment effects than non-menthol smokers for CPD (–6.4 vs. –9.3), TNE (ratio of geometric means, 0.22 vs. 0.10) and CEMA (ratio, 0.56 vs. 0.37; ps < .05), and trended toward a smaller treatment effect for CO (–4.5 vs. –7.3 ppm; p = .06). Odds ratios for abstinence at week 20 were 1.88 (95% confidence interval [CI] = 0.8 to 4.4) for menthol and 9.11 (95% CI = 3.3 to 25.2) for non-menthol VLNC smokers (p = .02) relative to the NNC condition.ConclusionsAlthough menthol smokers experienced reductions in smoking, toxicant exposure, and increases in quitting when using VLNC cigarettes, the magnitude of change was smaller than that observed for non-menthol smokers.ImplicationsResults of this analysis suggest that smokers of menthol cigarettes may respond to a nicotine reduction policy with smaller reductions in smoking rates and toxicant exposure than would smokers of non-menthol cigarettes.

Role of l- and d-Menthol in the Glucuronidation and Detoxification of the Major Lung Carcinogen, NNAL.

Menthol, which creates mint flavor and scent, is often added to tobacco in both menthol and nonmenthol cigarettes. A potent tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is extensively metabolized to its equally carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) as (R)- or (S)-NNAL enantiomers. NNAL is detoxified by UDP-glucuronosyltransferase (UGT) enzymes, with glucuronidation occurring on either NNAL's pyridine ring nitrogen (NNAL-N-Gluc) or the chiral alcohol [(R)- or (S)-NNAL-O-Gluc]. To characterize a potential effect by menthol on NNAL glucuronidation, in vitro menthol glucuronidation assays and menthol inhibition of NNAL-Gluc formation assays were performed. Additionally, NNAL and menthol glucuronides (MG) were measured in the urine of smokers (n = 100) from the Southern Community Cohort Study. UGTs 1A9, 1A10, 2A1, 2A2, 2A3, 2B4, 2B7, and 2B17 all exhibited glucuronidating activity against both l- and d-menthol. In human liver microsomes, both l- and d-menthol inhibited the formation of each NNAL-Gluc, with a stereospecific difference observed between the formation of (R)-NNAL-O-Gluc and (S)-NNAL-O-Gluc in the presence of d-menthol but not l-menthol. With the exception of three nonmenthol cigarette smokers, urinary MG was detected in all menthol and nonmenthol smokers, with l-MG comprising >98% of total urinary MG. Levels of urinary NNAL-N-Gluc were significantly (P < 0.05) lower among subjects with high levels of total urinary MG; no significant changes in free NNAL were observed. These data suggest that the presence of menthol could lead to increases in alternative, activating metabolic pathways of NNAL in tobacco target tissues, increasing the opportunity for NNAL to damage DNA and lead to the development of tobacco-related cancers. SIGNIFICANCE STATEMENT: High levels of the major menthol metabolite, menthol-glucuronide, was observed in the urine of smokers of either menthol or nonmenthol cigarettes. The fact that a significant inverse correlation was observed between the levels of urinary menthol-glucuronide and NNAL-N-glucuronide, a major detoxification metabolite of the tobacco carcinogen, NNK, suggests that menthol may inhibit clearance of this important tobacco carcinogen.

Ban on menthol-flavoured tobacco products predicts cigarette cessation at 1 year: a population cohort study

ObjectivesThe province of Ontario, Canada, banned the use of menthol-flavoured tobacco products as of 1 January 2017. The long-term impact of a menthol ban on smoking behaviour has not been...

Menthol Inhibits UGT2B10‐catalyzed Detoxification of the Potent Tobacco‐carcinogen, NNAL

Menthol may be added to tobacco products as either naturally occurring L‐menthol or synthesized racemic DL‐menthol and is excreted as a menthol glucuronide (MG). The most potent tobacco carcinogen is 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK). NNK is extensively metabolized to enantiomers [(R) or (S)] of the equally carcinogenic chiral 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL). Both (R)‐ and (S)‐NNAL have been shown to be carcinogenic. Detoxification of (R)‐ and (S)‐NNAL through glucuronidation on NNAL's pyridine ring nitrogen (NNAL‐N‐gluc) is primarily mediated by UGT2B10. Menthol has been shown to inhibit NNAL‐N‐gluc formation in human liver microsomes (HLM). The goal of the present study was to elucidate the impact of menthol on NNAL‐N‐gluc formation in vivo. In vitro inhibition assays using HLM or microsomes from UGT2B10 over‐expressing HEK293 cells were performed with racemic (R/S)‐NNAL as substrate with each menthol enantiomer added separately as inhibitor. In vivo data were gathered from analysis of MG, NNAL, and NNAL metabolites from 50 menthol smokers and 50 non‐menthol smokers. Samples were obtained from the Southern Community Cohort Study. Both L‐ and D‐menthol enantiomers were inhibitors of UGT2B10 in vitro with IC50 values of 236 and 202 μM, respectively. In vivo D‐MG levels, when present, were far below the levels of L‐MG observed in smokers of both menthol or non‐menthol cigarettes, with D‐MG comprising an average of 1.3% of total MG. Urinary L‐MG was detectable in 98 subjects and levels were not significantly different between menthol and non‐menthol smokers (p=0.50). When stratified by tertiles of urinary MG levels, NNAL‐N‐gluc levels were highest in smokers with the lowest MG levels, with NNAL‐N‐gluc levels inversely associated with MG levels in smokers (p&lt;0.05). These data suggest that menthol inhibits a major detoxification pathway of the tobacco carcinogen, NNK. The relatively high levels of urinary menthol in smokers of both menthol and non‐menthol cigarettes raise the possibility that menthol branding may not be the best approach to studying the impact of menthol as a tobacco additive.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Stroke risk among menthol versus non-menthol cigarette smokers in the United States: Analysis of the National Health and Nutrition Examination Survey (NHANES)

Though available evidence is relatively consistent in showing no additional health effects among smokers due to menthol in cigarettes, two studies reported conflicting results for stroke risk using different subsets of NHANES data. We investigated reasons for the differences in these reports by analyzing NHANES cycles conducted between 1999 and 2012, combined and in subsets. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) from three different survey logistic regression models compare risk of reported stroke diagnoses among menthol and non-menthol cigarette smokers. Depending on timeframe, about 1150 to 8000 U.S. adults (aged ≥ 20 years) who smoked on ≥ 1 of the last 30 days had complete data for cigarette type and all covariates included in each model. Results were not much affected by which covariates were included in the models, but depended strongly on the NHANES cycles included in the analysis. Using NHANES 1999–2012 data combined, AORs and 95% CIs for stroke comparing menthol with non-menthol cigarette smokers were 0.95 (95% CI: 0.65, 1.37), 0.85 (95% CI: 0.59, 1.23) or 0.86 (95% CI: 0.59, 1.25). Collectively, findings illustrate the need for fully reporting research and analytical methods, especially when analyses are meant to develop evidence intended for regulatory decision-making.

Determining non-cigarette tobacco, alcohol, and substance use typologies across menthol and non-menthol smokers using latent class analysis

BackgroundSubstance use and mental health are robustly associated with smoking and poor cessation outcomes, but not often examined in combination with menthol cigarette smoking, which is also associated with lower quit rates. This study identified classes of Black and White menthol and non-menthol cigarette smokers based on demographics, alcohol, drug, and other tobacco use behaviors.MethodsUsing screening data from two studies, latent class analysis (LCA) was conducted to classify n = 1177 menthol and non-menthol cigarette smokers on demographic characteristics, heavy smoking, alcohol and drug use, desire to quit smoking, other tobacco product use, and use of psychotropic medication.ResultsThree latent classes were identified that differentiated smokers on substance use, menthol cigarette smoking, and other tobacco use behavior. One class consisted primarily of young adults who used a wide array of other tobacco products, reported the highest prevalence of other drug use, and showed the lowest desire to quit smoking cigarettes in the next 6-months. Class 2 comprised primarily of Black male menthol smokers, all of whom used cigarillos in addition to cigarettes, and who displayed moderate drug use. The third class was categorized as primarily older cigarette smokers, who engaged in very little other tobacco use or drug use, but who were most likely to self-report being prescribed psychotropic medication.ConclusionsLCA allowed for the identification of distinct classes of smokers based on factors related to poor cessation outcomes, including menthol use, that have not previously been examined in combination. Interventions should target specific groups of smokers, rather than take a “one size fits all” approach.

Menthol Cigarettes, Time to First Cigarette, and Smoking Cessation

Summary The goal of the present work is to determine if menthol and non-menthol cigarette smokers differ with respect to time to first cigarette (TTFC) and successful smoking cessation via a meta-analysis of published results. For 13 independent estimates, menthol smokers were slightly but statistically significantly more likely to exhibit TTFC ≤ 5 min (random-effects odds ratio (OR) = 1.12; 95% confidence interval (CI), 1.04–1.21), while 17 independent estimates provided a non-significant difference for TTFC ≤ 30 min (random-effects OR = 1.06; 95% CI, 0.96–1.16). For cessation studies, meta-analysis of 30 published estimates indicated a decreased likelihood for menthol cigarette smokers to quit (random-effects OR = 0.87; 95% CI, 0.80–0.96). There was no difference between cessation rates for Caucasian menthol and non-menthol cigarette smokers, but the results support that African American menthol cigarette smokers find it more difficult to quit. Adjustment of cessation for socioeconomic status eliminated any statistically significant advantage for smoking cessation in non-menthol smokers. In conclusion, these results suggest that the observed differences in cessation rates between menthol and non-menthol cigarette smokers are likely explained by differences in socioeconomic status and also suggest that TTFC may not be a robust predictor of successful smoking cessation.

Menthol and Nonmenthol Cigarette Smoking: All-Cause Deaths, Cardiovascular Disease Deaths, and Other Causes of Death Among Blacks and Whites.

In contrast to whites, black smokers prefer menthol cigarettes over nonmenthol cigarettes by a large margin and tend to have higher mortality from several smoking-related diseases than whites, raising the possibility that menthol cigarettes contribute to racial disparities in risk. Evidence for differential associations between menthol and nonmenthol cigarettes indicates lower cancer risk for menthol smokers, but for cardiovascular disease (CVD) mortality, evidence has been inconsistent. Cox proportional hazards models were used to compute hazard ratios and accompanying 95% confidence intervals for all-cause and CVD mortality for menthol compared with nonmenthol cigarette smokers among 65 600 participants in the Southern Community Cohort Study, an ongoing community-based cohort with the largest number of menthol smokers being traced. Among the 27 619 current cigarette smokers, 4224 died during follow-up, with 1130 deaths attributed to CVD. Both all-cause (hazard ratio=0.93; 95% confidence interval=0.86-1.01; P=0.10) and CVD (hazard ratio=0.88; 95% confidence interval=0.76-1.03; P=0.10) mortality risks were similar in menthol compared with nonmenthol cigarette smokers. Smoking regardless of cigarette type is hazardous to health, but these results do not indicate that menthol cigarettes are associated with greater CVD risks than nonmenthol cigarettes.