The effect of menthol containing cigarettes on adult smokers’ exposure to nicotine and carbon monoxide
Introduction
Mentholated cigarettes were introduced into the market in the 1920’s and since then represent a distinct “brand style” of cigarettes. Mentholated cigarette brands may be found in all categories of tar and nicotine yields ranging from Ultra Lights (1–3 mg tar) to Full flavor (15 mg tar) brands. In the lower tar categories (Lights and Ultra lights), mentholated styles account for about 25% of the US sales volume. In the full flavor category, about 60% of cigarettes consumed are regular (non-mentholated), and approximately 40% are mentholated (US DHHS, 2007a). Currently, approximately 34% of all smokers use mentholated brands (SAMHSA, OAS, 2009). The latest National Survey on Drug Use and Health (US DHHS, 2007a) comprehensive dataset of more than 55,000 subjects and their use of tobacco products shows that menthol cigarette smoking is significantly higher in non-Hispanic African-American males (74.4%) and females (83.9%), compared to non-Hispanic White males (19.8%) and females (29.1%), respectively. Menthol has been approved as a food or flavor ingredient by the US Food and Drug Administration (21 CFR § 182.20 and 21 CFR § 172.515), and the Joint FAO/WHO Expert Committee on Food Additives (JECFA), and is generally recognized as safe (GRAS) by the Flavor and Extract Manufacturers Association (FEMA).
Menthol in cigarette smoke and its effects on in vitro and in vivo biological endpoints has been studied and reported on repeatedly in the scientific literature (Carmines, 2002, Coggins et al., 1990, Gaworski et al., 1997, Gaworski et al., 1999). Extensive clinical and epidemiological studies have also been reported (Brooks et al., 2003, Carpenter et al., 1999, Friedman et al., 1998, Hebert, 2003, Kabat and Hebert, 1991; Murray et al., 2007; Sidney et al., 1995, Stellman et al., 2003). The overwhelming weight of evidence provided by these studies indicates that use of menthol cigarettes does not increase smoking-related health risks in menthol cigarette smokers compared to non-mentholated cigarette smokers (Heck, 2009, Hebert, 2003, Werley et al., 2007). However, the observation that lung cancer incidence in African-American smokers is higher than in White smokers, and the fact that African-American males predominantly smoke mentholated cigarettes has led some researchers to hypothesize that smoking menthol cigarettes may increase exposure to toxic cigarette smoke constituents compared to smoking non-menthol cigarettes (Clark et al., 2004). Relatively little has been reported on human exposure to smoke constituents in smokers smoking mentholated cigarettes compared to smokers of non-mentholated cigarettes. Previous papers including some comparative menthol and non-menthol biomarkers include Richie et al., 1997, Rosenblatt et al., 1998, Patterson et al., 2003, Benowitz et al., 2004, Mustonen et al., 2005, Moolchan et al., 2006, Williams et al., 2007, Muscat et al., 2009 and the cited paper of Heck (2009). One way of addressing this issue is to determine whether mentholation over a wide range of tar categories might impact smoker behaviors and exposure by measuring biomarkers of exposure in smokers using mentholated and non-mentholated cigarettes. The analyses on exposure to cigarette smoke in a subpopulation of African-American and White menthol and non-menthol cigarette smokers from the Total Exposure Study (Mendes et al., 2009, Roethig et al., 2009) are presented and also discussed in the context of epidemiological data related to the question of whether menthol contributes to the disparity in lung cancer risks between African-American and White smokers.
The purpose of this study was to investigate the effects of smoking menthol cigarettes on the biomarkers of exposure, urinary nicotine equivalents per day (NE/24) and adjusted for the number of cigarettes smoked (NE/cig), serum cotinine, urinary trans-3′-hydoxycotinine (3OHC) to cotinine ratio and carboxyhemoglobin (COHb). NE was selected because it is considered a surrogate for exposure to smoke constituents in general and especially for particulate phase constituents (Mendes et al., 2008, Mendes et al., 2009) whereas COHb is considered a surrogate for the gas–vapor phase constituents. Effects of various demographic and other parameters on biomarker levels were also examined. The data for these analyses was generated from the Total Exposure Study (Mendes et al., 2009, Roethig et al., 2009) that was conducted in 2002–2003 with the main objective being the estimation of exposure to cigarette smoke in a representative sample of adult smokers in the US population.
Section snippets
Study design, subjects and conduct
The 3341 African-American and White adult cigarette smokers included in this analysis were from the TES study, which was a cross-sectional, observational, ambulatory, multi-centered study. Adult males and females, 21 years old or older, in generally good health, from 31 states (39 investigative sites across the United States), were enrolled into one of 4 parallel groups based on the smoking machine derived tar categories (i.e., ⩽2.9 mg tar; 3.0–6.9 mg tar; 7.0–12.9 mg tar; and ⩾13.0 mg tar) of the
Results
Demographic data for the menthol and non-menthol cigarette smokers are summarized in Table 1. Of the 3341 smokers included in the analysis, 1044 (31.3%) were menthol cigarette smokers. The mean age was 42 years in both groups. The proportion of female smokers was higher in the menthol group (64%) than in the non-menthol group (55%) whereas the proportion of male smokers was higher in the non-menthol group (45%) compared to the menthol group (36%). Approximately 35% of females and 27% of males
Discussions
This cross-sectional study included more than 3000 African-American and White adult menthol and non-menthol cigarette smokers who smoked more than 300 different cigarette brands. The study population with 31% of menthol smokers is representative of the US smoking population (Giovino et al., 2004, Heck, 2009). The demographics in this study are consistent with the 1986 survey by the US Department of Health and Human Services (Giovino et al., 2004, US DHHS, 1989). Menthol smokers on average smoke
Acknowledgments
The authors thank Management Science Associates, Pittsburgh, Pennsylvania for data analysis, Dr. Qiwei Liang for statistical review and Dr. Mohamadi Sarkar for his review and helpful suggestions.
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2015, Preventive Medicine ReportsCitation Excerpt :Furthermore, prior studies did not examine the relationship between BMI and nicotine metabolism. Menthol inhibits nicotine metabolism in the liver (Benowitz et al., 2004; MacDougall et al., 2003) and menthol smokers have slower metabolism than non-menthol smokers as indicated by the nicotine metabolite ratio (NMR = ratio of trans 3' hydroxycotinine to cotinine) (Chenoweth et al., 2014; Mwenifumbo et al., 2007; Wang et al., 2010). Nicotine metabolism is primarily mediated by the enzyme cytochrome P450 2A6 (CYP2A6), and studies suggest that the NMR is a valid phenotypic marker of CPY2A6 activity (Dempsey et al., 2004; Nakajima et al., 1996; Zhu et al., 2013).
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