THE INDUSTRY 

MENTHOL REPORT
 

Menthol Cigarettes:

No Disproportionate Impact on Public Health
 

Submitted to FDA by the Non-Voting Industry Representatives on TPSAC 

and Other Tobacco Industry Stakeholders 

March 23, 2011 

Available for Public Disclosure without Redaction 

Under the Family Smoking Prevention and Tobacco Control Act (the Act), the Tobacco Products 

Scientific Advisory Committee (TPSAC) must issue a report and recommendation to the Food and Drug

Administration (FDA) on “the issue of the impact of the use of menthol in cigarettes on the public 

health, including such use among children, African-Americans, Hispanics, and other racial and ethnic 

minorities” (Act at § 907(e)). 
 

 

Report Title: Menthol Cigarettes: No Disproportionate Impact on Public Health 

Dated: March 23, 2011 

The Industry Menthol Report is submitted to the Food and Drug Administration at its request by: 

Non-Voting Industry Representatives of the Tobacco Products Scientific Advisory Committee: 

Jonathan Daniel Heck, Ph.D., DABT, Representative of the tobacco manufacturing industry 

Luby Arnold Hamm, Jr., Representative of the interests of tobacco growers 

John H. Lauterbach, Ph.D., DABT, Representative of the interests of small business tobacco 

manufacturing industry 

Industry Stakeholders: Lorillard Tobacco Company 

R. J. Reynolds Tobacco Company 

The following industry stakeholders support filing the report but did not participate in its 

drafting: 

Burley Tobacco Growers Cooperative Assn. Liggett Group LLC 

Commonwealth Brands, Inc. North Carolina Farm Bureau 

Dosal Tobacco Corporation Shamrock Specialty Papers, Ltd. 

Fair Products, Inc. Sherman’s 1400 Broadway, NYC Ltd. 

(D/B/A Nat Sherman) IOTA USA, LLC
 

Swisher International, Inc.
 JT International U.S.A., Inc. 

Tobacco Rag Processors 

Kentucky Farm Bureau 

U.S. Tobacco Cooperative Association King Maker Marketing Inc. 

Vector Tobacco Inc. 

i 
 

 

 

 

 

 

 

 

 

 

EXECUTIVE SUMMARY
 

Under the Family Smoking Prevention and Tobacco Control Act (the Act), the Tobacco Products 

Scientific Advisory Committee (TPSAC) must issue a report and recommendation to the Food and 

Drug Administration (FDA) on “the issue of the impact of the use of menthol in cigarettes on the 

public health, including such use among children, African-Americans, Hispanics, and other racial 

and ethnic minorities” (Act at § 907(e)). 

THE INDUSTRY MENTHOL REPORT 

The Industry Menthol Report is submitted to FDA, at its request, by the non-voting Industry 

Representatives on TPSAC and other tobacco industry stakeholders.1 Consistent with FDA’s 

commitment to science-based regulatory decisions that rely on the best available data, the Industry 

Menthol Report provides FDA with a complete and thorough evaluation and assessment of the best 

available scientific data. 

The only appropriate focus for FDA is to assess whether menthol cigarettes have a disproportionate 

public health effect when compared to nonmenthol cigarettes. The Industry Menthol Report adopts 

this focus. All cigarettes are hazardous to health. It does not require a scientific analysis by TPSAC 

or FDA to conclude that removal of menthol cigarettes from the market plausibly would have some 

public health benefit. It is axiomatic that removing any type of cigarette preferred by a substantial 

number of American smokers – whether that be menthol, nonmenthol, lower tar, higher tar, filtered 

or unfiltered – might result in some smokers quitting when their preferred type of cigarette is taken 

away by the government. However, this is a very different issue than that contemplated in the Act. 

The Industry Menthol Report takes into account the statutory considerations that TPSAC must 

address in its report and recommendation and that FDA must consider before deciding whether to 

propose any regulatory action. One of the issues Congress specifically recognized was the need to 

address the countervailing effects resulting from any regulatory decision, particularly “the creation of 

a significant demand for contraband.” The illicit sale of cigarettes is a well-documented problem 

that poses significant threats to both the public health and the public safety. 

The Industry Menthol Report outlines the demographics of menthol cigarette smoking and assesses 

whether menthol cigarettes have any impact over that of nonmenthol cigarettes on disease 

occurrence, as well as smoking behavior. The Industry Menthol Report also responds to speculative 

hypotheses that have been advanced with respect to menthol in cigarettes. In addition, the Industry 

Menthol Report pulls together numerous studies and reports, many from government agencies, 

along with written submissions and public comments to TPSAC on the likely countervailing effects 

resulting from an overly restrictive regulation of menthol cigarettes. 

1 See the list of non-voting Industry Representatives and other tobacco industry stakeholders on Page i. 

Executive Summary ii 
 

 

 

 

 

 

 

PROVEN FRAMEWORK TO ASSESS THE WEIGHT OF THE EVIDENCE 

In systematically evaluating the studies and data on menthol in cigarettes, both study methodology 

and ability to support inferences with respect to menthol were assessed using a scientifically rigorous 

approach. The scientific standards and processes used in the Surgeon General’s Reports (SGRs) 

guided the conclusions reached in the Industry Menthol Report. The four categories adopted by the 

2004 SGR to classify the strength of causal inferences, with modifications required to address the 

specific menthol topics, are used in the Industry Menthol Report to describe the weight of evidence 

with respect to any impact of menthol cigarettes on public health above the impact of nonmenthol 

cigarettes. The Surgeon General’s causality framework has been applied for many decades to 

questions of smoking and health, and has also been adopted by other major public health authorities 

such as the Institute of Medicine (IOM) and the International Agency for Research on Cancer. The 

Surgeon General’s categories include: 

•	 “Evidence is sufficient to infer a causal relationship” (Sufficient) 

•	 “Evidence is suggestive but not sufficient to infer a causal relationship” (Suggestive) 

•	 “Evidence is inadequate to infer the presence or absence of a causal relationship” 

(Inadequate) 

•	 “Evidence is suggestive of no causal relationship” (No Causal Relationship) 

SGR 2004 also noted that “[t]here is no category beyond ‘suggestive of no causal relationship’ as it is 

extraordinarily difficult to prove the complete absence of a causal association” (USDHHS 2004). If 

an assessment falls into the category of “Suggestive,” it may be appropriate for FDA to recommend 

further study of the issues. However, if an assessment of the totality of available scientific evidence 

falls into either of the final two categories (“Inadequate” or “No Causal Relationship”), no 

regulatory action on menthol is warranted by FDA. 

This approach contrasts sharply with TPSAC’s adoption of an unorthodox standard using the 

amorphous concept of equipoise, which historically has been used to address issues not relevant 

here – such as how to ethically conduct randomized clinical trials or award veterans’ benefits. The 

IOM has used equipoise to evaluate veterans’ benefits, but TPSAC does not adhere to the IOM 

equipoise categories. Most importantly, TPSAC’s approach omits a category used by the IOM to 

encompass the conclusion of “Against: The evidence suggests the lack of a causal relationship.” 

Ironically, that is the category into which the majority of the evidence regarding menthol falls. 

MAJOR CONCLUSIONS OF THE REPORT 

The conclusions of the Industry Menthol Report comply with FDA’s mandate to “follow the 

science.” 

Using the Surgeon General’s framework for assessing causality, a synthesis of the reliable data on the 

use of menthol in cigarettes, including data relating to its impact on disease and smoking behavior, 

leads to the conclusion that the “evidence is suggestive of no causal relationship” between 

menthol cigarettes and any disproportionate impact on the public health as a whole or for any 

Executive Summary iii 
 

 

 

 

 

 

 

 

 

 

 

 

 

demographic group when compared to nonmenthol cigarettes. As a result, there is no scientific 

basis to support the regulation of menthol cigarettes any differently than nonmenthol cigarettes. 

Demographics of Menthol Cigarette Preference and Current Trends in Smoking Prevalence 

Smoking prevalence refers to estimates of cigarette use among the overall population, whereas 

smoking preference refers to the percentage of smokers who smoke a particular type of cigarette 

(e.g., menthol versus nonmenthol). An increase in smoking prevalence in the population could 

represent an adverse population-level effect, while higher preference for a particular cigarette type 

that does not provide any increased risk for disease or adversely impact smoking behavior among a 

declining smoking population would not. Cigarette smoking in the overall population (prevalence) 

has steadily declined during the last two decades, irrespective of race/ethnicity, sex and age category. 

Menthol cigarettes are used by only a quarter of the smoking population (preference). The majority 

of all menthol smokers are White. The vast majority of African American smokers prefer menthol 

cigarettes, and it is reported that female smokers prefer menthol more than male smokers. Some 

studies appear to suggest that menthol cigarette preference is also higher among younger as 

compared to older smokers. During the last two decades, declines in smoking prevalence have 

generally been more pronounced for minorities (including African Americans), females and 

adolescents, despite their preference for menthol. Also, prevalence of African American adolescent 

smoking is far below that of White adolescent smoking. 

Menthol in Cigarettes Does Not Change the Inherent Health Risks of Cigarette Smoking 

The available epidemiologic studies clearly demonstrate that smokers of menthol cigarettes are at no 

greater risk of developing chronic smoking-related diseases than are nonmenthol smokers. The 

number of studies and their consistency make it possible to draw this conclusion with confidence. 

While all epidemiology studies have limitations, the available studies are well-designed and wellanalyzed. The diseases studied include lung cancer (the most common smoking-related cancer), 

cancers of the upper aerodigestive tract (esophagus, larynx, oropharynx), and other cardiac and lung 

outcomes. The studies provide data on risks specific to both sexes and to both Whites and African 

Americans, and do not find that there is any subpopulation of menthol smokers who incur increased 

risks compared to nonmenthol smokers. Thus, it can be concluded that, according to the Surgeon 

General’s framework for assessing causality, the “evidence is suggestive of no causal 

relationship” between the use of menthol cigarettes and increased smoking-related disease risk 

above that caused by use of nonmenthol cigarettes. 

Menthol in Cigarettes Has No Meaningful Effect on Smoking Biomarkers 

The vast majority of studies of biomarkers of exposure to smoke constituents and biomarkers of 

potential harm have found no meaningful differences between menthol and nonmenthol smokers. 

The body of available scientific evidence from biomarker studies leads to the conclusion that the 

“evidence is suggestive of no causal relationship” between the use of menthol cigarettes and 

increases in biomarkers of exposure and potential harm over and above those caused by the 

smoking of nonmenthol cigarettes. 

Executive Summary iv 
 

 

 

 

 

 

 

 

 

 

Evidence on Menthol and Smoking Topography is Inadequate to Support a Conclusion that 

Menthol Cigarettes are Smoked More Intensely 

The available studies on menthol cigarettes and smoking topography differ in the ways that they 

attempt to measure smoking variables such as puffing, depth, volume and frequency; and many have 

weaknesses (e.g., small numbers of subjects, use of cigarettes differing in yield and menthol content, 

etc.). This makes it difficult to compare the studies and to reach definitive overall conclusions 

regarding these aspects of smoking topography. Although the findings are somewhat inconsistent, 

the majority of studies find no significant differences between menthol and nonmenthol smokers in 

smoking topography variables. These data provide no support for the presence of a clear and 

consistent association between menthol smoking and an adverse impact on smoking topography and 

provide no convincing support for the suggestion that menthol increases the exposure to smoke 

constituents through effects on smoking behavior. However, given the inconsistencies that exist, 

the “evidence is inadequate to infer the presence or absence of a causal relationship” 

between use of menthol cigarettes and adverse impacts on smoking topography. When placed in the 

context of the epidemiology and biomarker evidence referenced above, there is no reason to 

conclude that smoking topography differences, if any, lead to any increased health risks over those 

of nonmenthol cigarettes. 

Menthol in Cigarettes Does Not Adversely Impact the Toxicologic Properties of 

Mainstream Smoke 

Toxicology studies show that menthol has no notable effects at exposures spanning the ranges 

typical for its flavor application in cigarettes. Additionally, the weight of the evidence on the 

toxicologic properties of the mainstream smoke from menthol cigarettes compared with 

nonmenthol cigarettes provides no indications of increased toxicity, consistent with a broader 

conclusion that menthol has no causal relationship to adverse impacts on public health. This leads 

to the conclusion that the “evidence is suggestive of no causal relationship” between menthol 

added to cigarettes and increases in the toxicity of cigarette smoke. 

Menthol in Cigarettes Does Not Meaningfully Alter the Chemical Composition of 

Mainstream Smoke 

The weight of the evidence clearly shows that the chemical compositions of the mainstream smoke 

from menthol and nonmenthol cigarettes are very similar, apart from the presence of menthol itself. 

Thus, the “evidence is suggestive of no causal relationship” between the use of menthol in 

cigarettes and potentially harmful changes in mainstream smoke chemistry. 

Evidence is Inadequate to Conclude that Menthol in Cigarettes Influences Smoking 

Initiation 

Smoking initiation rates have not changed significantly over the past decade. In addition, menthol 

smokers report later onset of initiation as compared to nonmenthol smokers. While some studies 

report that younger smokers have a higher preference for menthol cigarettes than older smokers, 

there are no studies that directly examine cigarette type (menthol versus nonmenthol) at the time of 

initiation. Although these data are suggestive of no causal relationship between menthol cigarette 

use and adverse smoking initiation behaviors, they do not directly address the cigarette type used to 

initiate smoking. Thus, using the Surgeon General’s framework for assessing causality, it must be 

Executive Summary v 
 

 

 

 

 

 

concluded that the “evidence is inadequate to infer the presence or absence of a causal 

relationship” between menthol cigarette use and adverse smoking initiation behaviors, including 

higher or earlier smoking initiation by the general population or by subpopulations. 

Menthol in Cigarettes Has No Meaningful Impact on Smoking Cessation 

Review of the methodologically sound literature on menthol smoking and cessation demonstrates 

that the most relevant studies – those that address successful long-term quitting – do not indicate 

that smokers of menthol cigarettes are less likely to quit than smokers of nonmenthol cigarettes. 

There are a sufficient number of high-quality studies that consistently find that menthol has no 

meaningful impact on smoking cessation. A few studies (three cross-sectional studies and one of a 

smoking cessation clinic) reported some lower cessation rates among non-White menthol smokers 

only. However, if menthol is a factor that affects the ability to quit smoking, one would expect to 

see consistency among White and non-White subjects. This race-associated inconsistency suggests 

that some other factor, possibly related to socioeconomic status or genetics, affects the ability to 

quit, rather than menthol itself. Given the number of high-quality studies that consistently find that 

menthol cigarette use has no meaningful impact on smoking cessation, using the Surgeon General’s 

framework for assessing causality leads to the conclusion that the “evidence is suggestive of no 

causal relationship.” 

Menthol in Cigarettes Has No Meaningful Impact on Nicotine Dependence 

Review of the methodologically sound literature on menthol smoking and measures of nicotine 

dependence demonstrates that menthol smokers are not any more dependent on nicotine than 

nonmenthol smokers, as assessed by a variety of measures including cigarettes per day (CPD), time 

to first cigarette (TTFC), and Fagerström Test for Nicotine Dependence (FTND). There are a 

sufficient number of studies, and they are consistent in their results. Menthol smokers do not 

smoke significantly more CPD than nonmenthol smokers; in fact, half of the studies reported that 

menthol cigarette smokers report significantly fewer CPD than nonmenthol smokers. Similarly, 

menthol and nonmenthol smokers do not differ significantly on composite measures of dependence. 

With respect to the studies that evaluated TTFC, half found no difference between menthol and 

nonmenthol smokers and about half found that menthol smokers had significantly shorter TTFC 

than nonmenthol smokers, but this was true only among limited subgroups of subjects. Given both 

the number of high-quality studies and their overall consistent findings, it is reasonable to conclude 

that the “evidence is suggestive of no causal relationship” between smoking menthol cigarettes 

and significantly increased levels of nicotine dependence. 

Numerous Hypotheses Put Forth by TPSAC are Speculative and Cannot Serve as the Basis 

for Regulatory Policy 

From review of meeting transcripts and presentations given at TPSAC meetings, it is apparent that 

committee members are concerned about a number of unfounded hypotheses. For example, 

TPSAC has addressed whether menthol cigarettes are perceived by menthol smokers as less harmful 

than nonmenthol cigarettes. The data show that this is not true. This and other speculative 

hypotheses are addressed in Chapter 6. 

Executive Summary vi 
 

 

A Ban on Menthol Cigarettes Will Result in Significant Countervailing Effects 

If a ban were imposed on menthol cigarettes, despite the scientific evidence that does not support 

regulating menthol cigarettes differently than nonmenthol cigarettes, the evidence unequivocally 

shows that the result would be a dramatically larger illegal cigarette market than currently exists. As 

a result, there also would be severe negative impacts on public health, including exposure of 

smokers to more harmful contraband cigarettes, increased access of youth to tobacco, increased 

criminal activity particularly in urban communities, reduced government revenues and loss of jobs. 

Executive Summary vii 
TABLE OF CONTENTS 

INTRODUCTION ................................................................................................................... 1
 

THE INDUSTRY MENTHOL REPORT...................................................................................................1
 

Organization of the Industry Menthol Report .........................................................................................2
 

REFERENCES..................................................................................................................................................4
 

CHAPTER 1.	 APPROACH TO DATA ANALYSIS AND DECISION MAKING............5
 

STUDIES AND DATA EVALUATED.......................................................................................................5
 

APPROACH FOR ANALYZING THE STRENGTH OF EVIDENCE.............................................6
 

APPLICATION OF THE 2004 SGR CATEGORIES REGARDING CAUSAL INFERENCES
 

RELATED TO MENTHOL CIGARETTES COMPARED TO NONMENTHOL
 

CIGARETTES...................................................................................................................................................8
 

EQUIPOISE ......................................................................................................................................................9
 

PROPER INTERPRETATION OF DATA .............................................................................................12
 

REFERENCES................................................................................................................................................14
 

CHAPTER 2.	 DEMOGRAPHICS OF MENTHOL CIGARETTE PREFERENCE 

AND CURRENT TRENDS IN SMOKING PREVALENCE ................. 15
 

DEMOGRAPHICS DATA FOR MENTHOL CIGARETTE PREFERENCE................................15
 

National Health and Nutrition Examination Survey (NHANES).......................................................16
 

National Health Interview Survey (NHIS)..............................................................................................16
 

National Survey on Drug Use and Health (NSDUH)...........................................................................17
 

National Youth Tobacco Survey (NYTS) ...............................................................................................17
 

Tobacco Use Supplement to the Current Population Survey (TUS-CPS) .........................................17
 

EXAMINATION OF AVAILABLE DATA ON SMOKING DEMOGRAPHICS.........................18
 

Cross-sectional Studies Based on Nationally Representative Populations of Smokers....................19
 

National Health Interview Survey (NHIS)..........................................................................................19
 

Tobacco Use Supplement to the Current Population Survey (TUS-CPS).....................................20
 

National Survey on Drug Use and Health (NSDUH).......................................................................21
 

National Youth Tobacco Survey (NYTS)...........................................................................................21
 

Studies Based on Specific Populations of Smokers ...............................................................................22
 

UNPUBLISHED ANALYSES PRESENTED TO TPSAC ...................................................................23
 

CIGARETTE PREFERENCE IS NOT INDICATIVE OF SMOKING PREVALENCE ............24
 

Table of Contents viii 
SMOKING PREVALENCE IS DECLINING REGARDLESS OF RACE/ETHNICITY, 

SEX OR AGE CATEGORY........................................................................................................................26 

CONCLUSION...............................................................................................................................................28 

REFERENCES................................................................................................................................................30 

CHAPTER 2 TABLES 

Table 2-1. National Surveys Examining the Demographics of Menthol Cigarette Preference 

Table 2-2. Additional Studies Examining the Demographics of Menthol Cigarette Preference 

Table 2-3. Menthol Smoking Prevalence (by demographic characteristics; Giovino unpublished) 

Chapter 2 Appendix Tables 

Table 2-4. Higher Quality Studies on Menthol Preference Demographics (N=6) 

CHAPTER 2 FIGURES 

Figure 2-1. Smoking Prevalence and Cigarette Preference
 

Figure 2-2. Smoking Prevalence among US Adults (by race/ethnicity, 1991-2008)
 

Figure 2-3. Smoking Prevalence among U.S. Adolescents and Adults (1997-2007)
 

CHAPTER 3A.	 MENTHOL IN CIGARETTES DOES NOT CHANGE THE 

INHERENT HEALTH RISKS OF SMOKING....................................... 38 

SUFFICIENT EPIDEMIOLOGY DATA ARE AVAILABLE TO DRAW CONCLUSIONS .....39 

PROPER INTERPRETATION OF EPIDEMIOLOGY FINDINGS IS ESSENTIAL..................40 

EPIDEMIOLOGY SHOWS NO DIFFERENCE IN RISK OF TOBACCO-RELATED 

DISEASE BETWEEN MENTHOL AND NONMENTHOL SMOKERS .......................................40
 

Lung Cancer.................................................................................................................................................41
 

Esophageal Cancer......................................................................................................................................44
 

Oropharyngeal Cancer................................................................................................................................44
 

Other Smoking-Related Cancers...............................................................................................................44
 

Coronary Calcification and Lung Function .............................................................................................45
 

Mortality Due to Cardiovascular Disease ................................................................................................45
 

ADDITIONAL UNPUBLISHED EPIDEMIOLOGY STUDIES.......................................................46 

EPIDEMIOLOGY STUDIES ARE SUPPORTED BY ECOLOGICAL DATA .............................47 

EPIDEMIOLOGY ALSO SHOWS NO SEX-SPECIFIC OR RACE-SPECIFIC 

ASSOCIATIONS ............................................................................................................................................47
 

Sex-Specific Associations...........................................................................................................................48
 

Race-Specific Associations.........................................................................................................................49
 

Table of Contents ix 
CONCLUSION...............................................................................................................................................51
 

CHAPTER 3B. MENTHOL IN CIGARETTES HAS NO MEANINGFUL 

EFFECT ON BIOMARKERS OF EXPOSURE AND POTENTIAL 

HARM......................................................................................................... 52
 

SUFFICIENT DATA ON BIOMARKERS EXIST TO DRAW CONCLUSIONS..........................52
 

MENTHOL SMOKERS DO NOT HAVE HIGHER SYSTEMIC CARBON MONOXIDE
 

EXPOSURE.....................................................................................................................................................53
 

Conclusion about Exposure to Systemic Carbon Monoxide ...............................................................54
 

MENTHOL SMOKERS DO NOT HAVE HIGHER EXPOSURE TO NICOTINE OR
 

NICOTINE METABOLITES......................................................................................................................54
 

Conclusion about Exposure to Nicotine and Nicotine Metabolites ...................................................57
 

MENTHOL DOES NOT INHIBIT THE METABOLISM OF TOBACCO SMOKE
 

COMPONENTS.............................................................................................................................................58
 

Conclusion about Effects on Metabolism of Tobacco Smoke Components ....................................59
 

MENTHOL DOES NOT INCREASE EXPOSURE TO CARCINOGENS ....................................59
 

Conclusion about Exposure to Carcinogens...........................................................................................61
 

LACK OF EFFECT OF MENTHOL CONFIRMED BY TOTAL EXPOSURE STUDY ............61
 

CONCLUSION...............................................................................................................................................63
 

CHAPTER 3C. EVIDENCE IS INADEQUATE TO CONCLUDE THAT
 

MENTHOL IN CIGARETTES ADVERSELY IMPACTS 

SMOKING TOPOGRAPHY...................................................................... 64
 

METHODS OF MEASURING SMOKING TOPOGRAPHY PARAMETERS..............................64
 

EXHALED BREATH CARBON MONOXIDE AS AN INDICATOR OF PUFFING
 

INTENSITY ....................................................................................................................................................65
 

PUFF VOLUME.............................................................................................................................................67
 

PUFFS PER CIGARETTE...........................................................................................................................68
 

OTHER TOPOGRAPHY VARIABLES ...................................................................................................69
 

CONCLUSION...............................................................................................................................................69
 

CHAPTER 3D. MENTHOL IN CIGARETTES DOES NOT ADVERSELY 

IMPACT THE TOXICOLOGIC PROPERTIES OF 

MAINSTREAM SMOKE........................................................................... 71
 

NEAT MENTHOL HAS NO NOTABLE TOXICOLOGIC PROPERTIES...................................71
 

In Vitro Genotoxicity ................................................................................................................................. 72
 

Menthol Added to Experimental Cigarettes Has No Adverse Impact on Smoke Toxicology .......73
 

CONCLUSION...............................................................................................................................................76
 

Table of Contents x 
CHAPTER 3E.	 MENTHOL DOES NOT MEANINGFULLY ALTER THE 

CHEMICAL COMPOSITION OF MAINSTREAM SMOKE................. 77 

CONCLUSION...............................................................................................................................................79
 

REFERENCES................................................................................................................................................80
 

CHAPTER 3 TABLES 

Table 3-1. Comparison of Carboxyhemoglobin between Menthol and Nonmenthol Smokers 

(N=4) 

Table 3-2. Comparison of Nicotine or Nicotine Metabolites Between Menthol and 

Nonmenthol Smokers (N=17) 

Table 3-3. Comparison of NNAL and NNAL Metabolites Between Menthol and Nonmenthol 

Smokers (N=4) 

Table 3-4 Summary of Results of TES 

Table 3-5. Comparison of CO concentrations between menthol and nonmenthol smokers 

(N=8) 

Table 3-6. Comparison of Puff Volume Between Menthol and Nonmenthol Smokers (N=8) 

Table 3-7. Comparison of Puffs Per Cigarette Between Menthol and Nonmenthol Smokers 

(N=8) 

Table 3-8. Comparison of Mainstream Analyte Concentrations in Menthol and Nonmenthol 

Cigarettes 

Chapter 3 Appendix Tables 

Table 3-9.	 Comparative Risk of Lung Cancer Associated with Menthol Cigarettes vs. that 

Associated with Nonmenthol Cigarettes (N=9) 

Table 3-10.	 Comparative Risk of Esophageal Cancer Associated with Menthol Cigarettes vs. that 

Associated with Nonmenthol Cigarettes (N=2) 

Table 3-11.	 Comparative Risk of Oropharyngeal Cancer Associated with Menthol Cigarettes vs. 

that Associated with Nonmenthol Cigarettes (N=1) 

Table 3-12.	 Comparative Risk of Other Smoking-Related Cancers Associated with Menthol 

Cigarettes vs. that Associated with Nonmenthol Cigarettes (N=1) 

Table 3-13.	 Comparative Risk of Other Cardiac/Lung Outcomes Associated with Menthol 

Cigarettes vs. that Associated with Nonmenthol Cigarettes (N=2) 

Table 3-14.	 Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) 

CHAPTER 4. EVIDENCE IS INADEQUATE TO CONCLUDE THAT 

MENTHOL IN CIGARETTES ADVERSELY IMPACTS 

SMOKING INITIATION BEHAVIORS................................................. 117
 

FACTORS ASSOCIATED WITH SMOKING INITIATION BEHAVIORS ................................118
 

Table of Contents xi 
DIFFICULTIES IN ASSESSING SMOKING INITIATION BEHAVIORS .................................119
 

Ideal Study for Assessing Role of Menthol Cigarette Use During Smoking Initiation ................. 120
 

BEST AVAILABLE SCIENCE WAS DETERMINED THROUGH A RIGOROUS
 

PROCESS.......................................................................................................................................................120
 

Tier 1 Studies on Menthol Smoking and Initiation Behaviors .......................................................... 122
 

Tier 3 Studies on Menthol Smoking and Initiation Behaviors .......................................................... 123
 

Studies Not Designed to Address Initiation Behaviors...................................................................... 123
 

Recent Publications of Data from National Cross-Sectional Surveys.............................................. 124
 

Unpublished Analyses Presented to TPSAC........................................................................................ 125
 

TREND DATA FOR SMOKING INITIATION RATES ..................................................................126
 

MENTHOL MARKET SHARE COMPARED TO YOUTH SMOKING RATES .......................129
 

SWITCHING BETWEEN MENTHOL AND NONMENTHOL ....................................................130
 

CONCLUSIONS...........................................................................................................................................131
 

REFERENCES..............................................................................................................................................133
 

CHAPTER 4 TABLES 

Table 4-1.	 Studies of Menthol Smoking and Initiation Behaviors (N=6) Quality Ratings by 

Covance 

Table 4-2.	 Analysis of time trends for smoking initiation (NHANES, 1999-2008) 

Chapter 4 Appendix Tables 

Table 4-3.	 Higher Quality Studies on Menthol Cigarette Smoking and Initiation Behaviors (N=4) 

Table 4-4.	 Distribution of Menthol versus Nonmenthol Current Cigarette Smoking (NHANES, 

1999-2008); Demographic Characteristics for New Smokers (Smoking for 1 year or 

less) 

CHAPTER 4 FIGURES 

Figure 4-1. Annual smoking initiation rate as percent of respondents (NSDUH, 2002-2008)
 

Figure 4-2. Menthol Market Share Compared to Youth Smoking Rates (2009)
 

Figure 4-3. Menthol Market Share Compared to Youth and Adult Smoking Rates - International
 

CHAPTER 5A.	 MENTHOL IN CIGARETTES HAS NO MEANINGFUL
 

IMPACT ON SMOKING CESSATION ................................................. 142
 

FACTORS ASSOCIATED WITH SMOKING CESSATION............................................................142
 

DIFFICULTIES IN ASSESSING SMOKING CESSATION.............................................................143
 

BEST AVAILABLE SCIENCE WAS DETERMINED THROUGH A RIGOROUS
 

Table of Contents xii 
PROCESS.......................................................................................................................................................144
 

Tier 1 Studies on Menthol Cigarette Smoking and Cessation Behaviors......................................... 145
 

Prospective and Cross-Sectional Studies that Examined Long-Term Cessation............................ 146
 

Cross-Sectional Studies of Nationally Representative Populations .................................................. 147
 

Tobacco Use Supplement to the Current Population Survey (TUS-CPS).................................. 147
 

National Health Interview Survey (NHIS)....................................................................................... 148
 

Studies from Smoking Cessation Clinics with Short-Term Cessation Measures............................ 149
 

Tier 2 Studies on Menthol Smoking and Cessation Behaviors ......................................................... 150
 

Unpublished Analyses Presented to TPSAC........................................................................................ 151
 

MENTHOL CIGARETTES AND CESSATION BY RACE..............................................................152
 

MENTHOL CIGARETTES AND CESSATION AMONG YOUNG PEOPLE...........................153
 

CONCLUSION.............................................................................................................................................153
 

CHAPTER 5B.	 MENTHOL IN CIGARETTES HAS NO MEANINGFUL
 

IMPACT ON NICOTINE DEPENDENCE ......................................... 154
 

BEST AVAILABLE SCIENCE WAS DETERMINED THROUGH A RIGOROUS
 

PROCESS.......................................................................................................................................................154
 

Tier 1 Studies on Menthol Smoking and Nicotine Dependence ...................................................... 155
 

Tier 2 and 3 Studies of Menthol Smoking and Nicotine Dependence ............................................ 158
 

Unpublished Analyses Presented to TPSAC........................................................................................ 159
 

MENTHOL CIGARETTES AND DEPENDENCE AMONG ADOLESCENTS .......................161
 

CONCLUSIONS...........................................................................................................................................163
 

REFERENCES..............................................................................................................................................165
 

CHAPTER 5 TABLES 

Table 5-1.	 Studies of Menthol Smoking and Cessation Behaviors (N=25) Quality Ratings by 

Covance 

Table 5-2.	 Studies of Menthol Smoking and Nicotine Dependence (N=22) Quality Ratings by 

Covance 

Chapter 5 Appendix Tables 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15)
 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10)
 

CHAPTER 6.	 SEVERAL HYPOTHESES POSED BY TPSAC ARE 

SPECULATIVE........................................................................................ 196
 

Table of Contents xiii 
HYPOTHESIS: SMOKERS PERCEIVE MENTHOL CIGARETTES AS BEING LESS 

HARMFUL.....................................................................................................................................................196
 

HYPOTHESIS: MENTHOL INCREASES HARM THROUGH CHEMOSENSORY
 

EFFECTS .......................................................................................................................................................198
 

HYPOTHESIS: MENTHOL “MAKES THE POISON GO DOWN EASIER”...........................202
 

HYPOTHESIS: MENTHOL INCREASES POTENTIAL FOR ABUSE .......................................203
 

HYPOTHESIS: MENTHOL SMOKERS WHO SMOKE 6-10 CIGARETTES/DAY ARE 

UNIQUELY AFFECTED ..........................................................................................................................203
 

HYPOTHESIS: VARIATIONS IN MENTHOL LEVEL DRIVE BRAND POPULARITY .....204
 

Introduction of Fire Standards Compliant (FSC) Cigarette Regulations......................................... 205
 

HYPOTHESIS: MANUFACTURERS MARKET MENTHOL CIGARETTES
 

DIFFERENTLY THAN NONMENTHOL CIGARETTES ..............................................................206
 

No Health Claims in Menthol Advertising........................................................................................... 208
 

Menthol Cigarettes Are More Expensive Than Nonmenthol Cigarettes ........................................ 208
 

REFERENCES..............................................................................................................................................209
 

CHAPTER 6 FIGURES 

Figure 6-1.	 Percentage of Menthol vs. Nonmenthol Smokers Who Believe Smoking Presents a 

Great Risk of Harm (NSDUH) 

Figure 6-2.	 Percentage of Menthol vs. Nonmenthol Smokers (Age 12-17) Who Believe Smoking 

Presents a Great Risk of Harm (NSDUH) 

Figure 6-3.	 Percentage of Menthol Smokers by Race/Ethnicity Who Believe Smoking Presents a 

Great Risk of Harm (NSDUH) 

Figure 6-4.	 Newport Full Flavor 80mm Menthol Level (1993-2010) 

CHAPTER 7.	 A BAN ON MENTHOL CIGARETTES WILL RESULT IN 

SIGNIFICANT COUNTERVAILING EFFECTS................................. 213
 

BANNING MENTHOL CIGARETTES WOULD INCREASE BLACK MARKET 

CIGARETTE SALES AND PRODUCE A RANGE OF PUBLIC HEALTH PROBLEMS .......213
 

A Large-Scale Illegal Market in Cigarettes Has Been Well Documented ........................................ 214
 

Estimating the Size of an Expanded Black Market if Menthol is Banned....................................... 215
 

Countervailing Effects on the Public Health from an Expanded Black Market ............................ 217
 

Negative impact on public health with unregulated contraband cigarettes................................. 217
 

Illicit tobacco markets undermine efforts to prevent underage smoking.................................... 219
 

Expansion of criminal enterprises, requiring increased spending by law enforcement............. 220
 

Impact on urban communities........................................................................................................... 221
 

Table of Contents xiv 
Foregone government revenue.......................................................................................................... 222
 

Loss of jobs dependent in whole or part on the legal sale of menthol cigarettes...................... 223
 

Building the Knowledge Base................................................................................................................. 224
 

CONCLUSION.............................................................................................................................................226
 

REFERENCES..............................................................................................................................................228
 

CHAPTER 7 TABLES 

Table 7-1.	 Potential impacts of menthol cigarette volume moving to the U.S. illicit cigarette 

market 

Table 7-2.	 Estimated fiscal 2009 cigarette revenue by category, based on the assumption that 

menthol cigarettes made up 27% of the U.S. taxed cigarette market that year ($ billion) 

Table 7-3.	 Summary of employment across the tobacco value chain 

CHAPTER 7 FIGURES 

Figure 7-1.	 Many Toxic Metals are in Higher Concentrations in Counterfeit Cigarettes (NY) 

CHAPTER 8. CONCLUSIONS...................................................................................... 231
 

MAJOR CONCLUSIONS OF THE REPORT ......................................................................................231
 

Demographics of Menthol Cigarette Preference and Current Trends in Smoking Prevalence.... 231
 

Menthol in Cigarettes Does Not Change the Inherent Health Risks of Cigarette Smoking ........ 232
 

Menthol in Cigarettes Has No Meaningful Effect on Smoking Biomarkers .................................. 232
 

Evidence on Menthol and Smoking Topography is Inadequate to Support a Conclusion 

that Menthol Cigarettes are Smoked More Intensely.......................................................................... 232
 

Menthol in Cigarettes Does Not Adversely Impact the Toxicologic Properties of 
 

Mainstream Smoke................................................................................................................................... 233
 

Menthol in Cigarettes Does Not Meaningfully Alter the Chemical Composition of 
 

Mainstream Smoke................................................................................................................................... 233
 

Evidence is Inadequate to Conclude that Menthol in Cigarettes Influences Smoking
 

Initiation .................................................................................................................................................... 233
 

Menthol in Cigarettes Has No Meaningful Impact on Smoking Cessation .................................... 233
 

Menthol in Cigarettes Has No Meaningful Impact on Nicotine Dependence ............................... 234
 

Numerous Hypotheses Put Forth by TPSAC are Speculative and Cannot Serve as the
 

Basis for Regulatory Policy ..................................................................................................................... 234
 

A Ban on Menthol Cigarettes Will Result in Significant Countervailing Effects ........................... 234
 

Table of Contents xv 
 

 

 

 

 

 

 

 

 

INTRODUCTION
 

Under the Family Smoking Prevention and Tobacco Control Act (the Act), the Tobacco Products 

Scientific Advisory Committee (TPSAC) must issue a report and recommendations to the Food and 

Drug Administration (FDA) on “the issue of the impact of the use of menthol in cigarettes on the 

public health, including such use among children, African-Americans, Hispanics, and other racial 

and ethnic minorities” (Act at § 907(e)). 

THE INDUSTRY MENTHOL REPORT 

While FDA had invited all members of the TPSAC to participate in developing the menthol report 

and recommendation, FDA allowed only the voting members to participate in writing the report. 

FDA invited the three non-voting members representing industry interests to collaborate in 

providing an industry perspective. This report (Industry Menthol Report) provides the industry 

perspective on the use of menthol in cigarettes. 

The hallmark of FDA regulation long has been a commitment to science-based decisions that rely 

on the best available data. Consistent with the FDA’s commitment, the purpose of the Industry 

Menthol Report is to provide the FDA with a complete and thorough evaluation and assessment of 

the best available scientific data to determine whether the use of menthol in cigarettes 

disproportionately impacts public health compared to nonmenthol cigarettes. 

The focus of the Industry Menthol Report on the assessment of any disproportionate public health 

effects of menthol cigarettes over nonmenthol cigarettes is the only appropriate focus for FDA. All 

cigarettes are hazardous to health. A conclusion that removal of menthol cigarettes from the market 

plausibly would have some public health benefit does not require any scientific analysis by TPSAC 

or FDA. It is axiomatic that removal of the segment of any cigarette taste preference – whether that 

be menthol, nonmenthol, lower tar, higher tar, filtered or unfiltered cigarettes – may result in some 

smokers quitting and thus some public health benefit. However, that is a very different question 

than that posed in the Act. Failing to examine the public health impact in terms of any 

disproportionate harm from menthol cigarettes when compared to nonmenthol cigarettes inevitably 

leads first to a removal of menthol cigarettes from the market and eventually could lead to a 

complete ban of all cigarettes, which would violate §907(d)(3) of the Act. 

The Industry Menthol Report takes into account the statutory considerations that TPSAC and FDA 

must consider: (1) “the risks and benefits to the population as a whole, including users and nonusers 

of tobacco products” (Act at § 907(a)(3)(B)(i)); (2) “the increased or decreased likelihood that 

existing users of tobacco products will stop using such products” ((Act at § 907(a)(3)(B)(i)); (3) “the 

increased or decreased likelihood that those who do not use tobacco products will start using such 

products.” (Act at § 907(a)(3)(B)(i)); and (4) “information concerning the countervailing effects of 

the proposed standard [or recommendation] . . ., such as the creation of a significant demand for 

contraband.” (Act at § 907(b(3)(B)). 

Introduction 

1
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Any decision by FDA regarding menthol must be grounded in accurate and reliable scientific data. 

The Industry Menthol Report is a complete and thorough scientific review that FDA can use in 

determining whether to take any action with respect the use of menthol in cigarettes. 

A strict scientific standard was applied in the Industry Menthol Report to evaluate the studies and 

data relating to the impact of the use of menthol in cigarettes on the public health. The standard 

included objectivity and inclusiveness in evaluation of the scientific literature and data, as well as 

consideration for the full spectrum of worthy scientific interpretations of the data. The Industry 

Menthol Report is science-based and data-driven and includes an evaluation of the totality of the 

scientific data regarding the use of menthol in cigarettes, including data presented in published 

studies, as well as data provided to FDA by the Industry1 and others. Studies that were properly 

designed and provide direct measurable data and outcomes which have been evaluated with 

statistical precision and rigor form the basis for the conclusions in the Industry Menthol Report. 

Organization of the Industry Menthol Report 

The Industry Menthol Report is designed to address whether the use of menthol in cigarettes 

disproportionately impacts public health compared to nonmenthol cigarettes, including such use 

among children, African American, Hispanics and other racial and ethnic minorities. Mindful of the 

requirements of the Act, the Industry Menthol Report specifically considers: 

1.	 The risks and benefits to the population as a whole of smoking menthol cigarettes 

compared to smoking nonmenthol cigarettes; 

2.	 The increased or decreased likelihood that existing smokers of menthol cigarettes 

will have disproportionate rates of quitting compared to smokers of nonmenthol 

cigarettes; 

3.	 The increased or decreased likelihood that non-smokers will have disproportionate 

rates of initiation with menthol cigarettes compared to nonmenthol cigarettes; and 

4.	 The countervailing effects of any recommendation on the public health including the 

creation of a significant demand for contraband menthol cigarettes. 

Therefore, the Industry Menthol Report assesses the disproportionate impact, if any, that menthol 

cigarettes have over nonmenthol cigarettes on disease occurrence, initiation, cessation and 

1 Tobacco product manufacturers and other stakeholders have expended extraordinary efforts to provide TPSAC, as 

well as FDA, with relevant information regarding menthol. Since the enactment of the Act in 2009, Lorillard Tobacco 

Company, R.J. Reynolds Tobacco Company and Altria Client Services Inc. on behalf of Philip Morris USA, Inc., and 

possibly others (collectively Tobacco Manufacturers) have cooperated with FDA in implementing the provisions of the 

Act and have invested significant time and resources to provide TPSAC and FDA with relevant science and 

information so that TPSAC can meets its statutory charge of evaluating the science on menthol and provide FDA with 

its report and recommendation. Tobacco Manufacturers have submitted numerous written submissions and made 

numerous presentations to TPSAC during the course of its menthol review. Tobacco Manufacturers and possibly 

others have spent hundreds of hours collecting, reviewing and submitting documents to FDA in order to respond to 

specific requests from TPSAC about the use of menthol in cigarettes. Additionally, Tobacco Manufacturers have 

provided written comments to numerous regulatory proposals or other notices for information posted in the Federal 

Register relating to tobacco products, many of which have relevance to the use of menthol in cigarettes. 

Introduction 

2
 

 

 

 

 

 

 

dependence while considering the countervailing effects that a ban on the use of menthol cigarettes 

(considered only in order to fully assess the countervailing effects) would have on the public health. 

The chapters included in the Industry Menthol Report are: 

• Chapter 1.	 APPROACH TO DATA ANALYSIS AND DECISION MAKING 

•	 Chapter 2. DEMOGRAPHICS OF MENTHOL CIGARETTE PREFERENCE 

AND CURRENT TRENDS IN SMOKING PREVALENCE 

•	 Chapter 3. 3A. MENTHOL IN CIGARETTES DOES NOT CHANGE THE 

INHERENT HEALTH RISKS OF SMOKING 

3B.	 MENTHOL IN CIGARETTES HAS NO MEANINGFUL 

EFFECT ON BIOMARKERS OF EXPOSURE AND 

POTENTIAL HARM 

3C.	 EVIDENCE IS INADEQUATE TO CONCLUDE THAT 

MENTHOL IN CIGARETTES ADVERSELY IMPACTS 

SMOKING TOPOGRAPHY 

3D.	 MENTHOL IN CIGARETTES DOES NOT ADVERSELY 

IMPACT THE TOXICOLOGIC PROPERTIES OF 

MAINSTREAM SMOKE 

3E.	 MENTHOL DOES NOT MEANINGFULLY ALTER THE 

CHEMICAL COMPOSITION OF MAINSTREAM SMOKE 

•	 Chapter 4. EVIDENCE IS INADEQUATE TO CONCLUDE THAT MENTHOL 

IN CIGARETTES ADVERSELY IMPACTS SMOKING INITIATION 

BEHAVIORS 

•	 Chapter 5. 5A. MENTHOL IN CIGARETTES HAS NO MEANINGFUL 

IMPACT ON SMOKING CESSATION 

5B.	 MENTHOL IN CIGARETTES HAS NO MEANINGFUL 

IMPACT ON NICOTINE DEPENDENCE 

• Chapter 6.	 SEVERAL HYPOTHESES POSED BY TPSAC ARE SPECULATIVE 

•	 Chapter 7. A BAN ON MENTHOL CIGARETTES WILL RESULT IN
 

SIGNIFICANT COUNTERVAILING EFFECTS
 

• Chapter 8. CONCLUSIONS 

Introduction 

3
REFERENCES 

Family Smoking Prevention and Tobacco Control Act. 2009. Pub. L. No. 111-31. 22 June. 

Introduction 

4
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

CHAPTER 1. 

APPROACH TO DATA ANALYSIS AND DECISION MAKING
 

STUDIES AND DATA EVALUATED 

The conclusions of the Industry Menthol Report are based on a comprehensive and inclusive review 

of the available literature and data related to the use of menthol in cigarettes. The Industry Menthol 

Report is science-based and data-driven and includes an evaluation of the totality of the scientific 

data regarding the use of menthol in cigarettes, including data presented in published studies, as well 

as data provided to FDA by the Industry1 and others. Scientific data were examined from 

observational epidemiology, experimental and clinical studies, as well as large, nationally 

representative surveys and individual studies of specific populations. 

The available literature and reported data on epidemiology, biomarkers of exposure and harm, 

smoking topography, toxicology and analytical chemistry studies comparing menthol cigarettes to 

nonmenthol cigarettes were evaluated using well-established procedures that have been used by 

public health authorities, such as the U.S. Surgeon General, the International Agency for Research 

on Cancer (IARC) and the National Academy of Sciences Institute of Medicine (IOM), to determine 

the weight of evidence for or against causal inferences with respect to menthol. 

Data regarding the use of menthol and nonmenthol cigarettes have also been collected by large, 

nationally representative surveys that typically capture only self-reported statements of behavior and 

subjective intent. Survey data have not been considered in prior deliberations by FDA Advisory 

Committees, Surgeon General’s Report authors or IARC Working Groups in developing causal 

inferences or assessing the strength of causal relationships because survey instruments are, by nature, 

less controlled in terms of taking into account or correcting for confounding or mediating factors. 

Data related to the demographics of smoking prevalence and the preference of smokers for menthol 

and nonmenthol cigarettes can be obtained primarily from two major sources: nationally 

representative surveys and individual studies of specific populations. Demographic data from 

studies based on national surveys were generally determined to be more informative because the 

sample populations have been weighted to reflect nationally representative estimates aligned with the 

U.S. population; hence, study findings are considered to be representative of the entire smoking 

population. This was not always the case for individual studies based on specific populations. 

Findings from individual studies were only considered to be representative of the entire smoking 

population if external validity was demonstrated through appropriate comparisons. 

Data and studies of smoking behaviors such as initiation, cessation and dependence comparing 

menthol and nonmenthol cigarette smokers were also primarily derived from nationally 

representative surveys and individual studies of specific populations. Published studies of these 

types of smoking behaviors were given an additional level of review. The published literature in the 

1 The written comments, submissions and presentations to TPSAC or to FDA by Lorillard Tobacco Company 

(Lorillard), R.J. Reynolds Tobacco Company (RJRT) and Altria Client Services Inc. (Altria) on behalf of Philip Morris 

USA, Inc. regarding the use of menthol in cigarettes and the marketing of cigarettes, generally, are incorporated herein 

by this reference. 

Chapter 1 

5
 

 

 

 

 

 

 

 

 

 

 

areas of smoking initiation, cessation and dependence was independently identified and was 

systematically evaluated by an independent organization (Covance Market Access Services Inc. 

(Covance)) for methodologic quality (using criteria developed by the Agency for Healthcare 

Research and Quality (Ranney et al. 2006)), and for ability to support inferences related to menthol. 

Rating categories included: “good,” “good to fair,” “fair,” “fair to poor,” and “poor.” Based on the 

review, the studies were categorized into three tiers:

2 

•	 Tier 1 studies were those rated by Covance as fair or better with respect to both overall 

quality and ability to support inferences related to menthol cigarette use; 

•	 Tier 2 studies were those rated by Covance as fair or better with respect to overall quality, 

but lower than fair with respect to ability to support inferences related to menthol cigarette 

use; and 

•	 Tier 3 studies were those rated by Covance as lower than fair with respect to both categories. 

APPROACH FOR ANALYZING THE STRENGTH OF EVIDENCE 

Scientific standards for determining the strength of evidence regarding any health effects related to 

menthol have guided the conclusions reached in the Industry Menthol Report. The approach taken 

by the Surgeon General’s Reports (SGR) provides a reasonable basis to develop conclusions and 

determine the weight of scientific evidence in regard to any effect of the use of menthol in cigarettes 

on the public health. 

Beginning in 1964, the Office of the Surgeon General periodically has issued reports on smoking 

and health, which have included syntheses of epidemiologic and other evidence supporting 

inferences of causation and evaluating the strength of those inferences for a number of smokingrelated diseases (USPHS 1964). The scientific standards and processes employed by the SGR 

authors in support of inferences of causation have continued to evolve over the course of the series 

of SGRs as increasingly diverse data accumulated. This evolution culminated in a major report 

issued in 2004 (USDHHS 2004) that formalized and delineated the standards and processes 

employed in determinations of causal inferences for diseases and conditions associated with 

smoking, as well as specific categorization of the strengths of any causal inferences (USDHHS 

2004). 

The causal inference paradigm and categories describing the strength of the inference advanced in 

the 2004 SGR were not novel; they represented the essence of standards and terminology that had 

already been established by the IOM and IARC. The 2004 SGR sought to provide clarity regarding 

judgments of the strength and weight of available evidence for or against a given causal inference 

between smoking and a specific disease. 

The authors of the original 1964 SGR on smoking and health had offered a similar philosophy and 

process for judgments of causal inference at a time when the available biomedical and epidemiologic 

2 Covance Market Access Services Inc., “The Role of Menthol Flavoring in Smoking Initiation, Cessation and other 

Smoking Behaviors: A Search and Methodological Evaluation of the Literature” Final Study Report Version 3.1, 

March 16, 2011. An earlier version of this report was provided to TPSAC and a summary of the findings was 

presented to TPSAC on February 10, 2011. Analysis of recent additional studies was added in the Final Study Report 

Version 3.1. 

Chapter 1 

6
 

 

 

 

 

 

 

 

 

 

 

 

information on smoking was at a far less advanced state of maturity. The process for the 

development of causal inferences for smoking and disease that were set forth by the 1964 SGR 

authors included considerations later specified by A. Bradford Hill in 1965 (Hill 1965), as well as a 

component of scientific judgment beyond those criteria (USPHS 2004). 

The Bradford Hill criteria comprise an itemization of the qualities of available scientific data and of 

the process of reasoning required to develop a defensible scientific judgment in regard to whether an 

established association between an exposure and a health outcome may be inferred to be causal. As 

recognized in the 2004 SGR “[a]ll of these criteria were meant to be applied to an already established 

statistical association; if no association has been observed, then these criteria are not relevant” 

(USDHHS 2004). 

The quality and quantity of available data determine the degree of strength of the final judgment and 

the ultimate conclusion of whether a causal inference is (1) confirmed with high confidence, 

(2) suspected but not confirmed in the face of substantive remaining uncertainties, (3) equivocal in 

the face of sparse or conflicting data, or (4) rebutted by substantial contrary data. The nine Bradford 

Hill criteria have been frequently distilled and represented as the qualities of consistency, strength, 

specificity, temporality, and coherence that characterize the strength of the available data for a potential 

cause and effect relationship (Hill 1965). Each of these dimensions of overall data quality is 

encompassed in the Surgeon General’s 2004 guidance for evaluating the existence and strength of 

causality in regard to smoking. As recognized in the 2004 SGR, “[t]hese criteria, which were just 

emerging into public health [in 1964], have since become widely accepted and used in epidemiology 

and public health” (USDHHS 2004). 

The statistical significance of thoughtfully designed and well-executed scientific or epidemiologic 

investigations into a potential cause and effect relationship is a starting point in assessing the 

consistency and strength of the data. The magnitude of measurable study outcomes and the consistency 

of findings developed from multiple independent investigations build confidence in the 

development (or refutation) of causal inferences (Hill 1965). In the 2004 SGR, consistency refers to 

“the persistent finding or an association between exposure and outcome in multiple studies of 

adequate power [emphasis added], and in different persons, places, circumstances, and time” and its 

purpose “is to make the hypothesis of a chance effect unlikely...” (USDHHS 2004). Strength of an 

association refers to “the magnitude of the association and its statistical strength” (USDHHS 2004). 

The specificity of the relationships between smoking and a disease can be an important consideration 

because all smoking-related diseases are known to occur in nonsmokers as well, reflecting other 

environmental or genetic causes or spontaneous disease occurrence. The coherence of data derived 

from diverse areas of study may be evaluated by an inclusive consideration of all available 

information on a given topic or subtopic. 

Importantly, however, both Hill and the SGR 2004 authors recognized that neither exposure and 

effect associations nor the statistical significance of those associations are in themselves sufficient to 

warrant an inference of causation (Hill 1965, USDHHS 2004). As stated in the 2004 SGR, although 

inferences, whether about causality or statistical associations, are always uncertain to a degree, the 

goal of the SGR approach “is to explain and communicate scientific judgments as to whether 

observed associations ... are likely to be causal, based on the totality of scientific evidence.” The 

2004 SGR was also careful to separate causal conclusions from public health recommendations 

(USDHHS 2004). 

Chapter 1 

7
 

 

 

 

 

 

 

 

The 2004 SGR adopted a four-level hierarchy of categories (2004 SGR Categories) to classify the 

strength of causal inferences between smoking and diseases, based on available evidence:

3 

•	 Evidence is sufficient to infer a causal relationship (i.e., smoking is proven to cause the 

disease). 

•	 Evidence is suggestive but not sufficient to infer a causal relationship. (i.e., smoking more 

likely than not causes the disease). 

•	 Evidence is inadequate to infer the presence or absence of a causal relationship (i.e., there is 

not enough proof that smoking does or does not cause the disease). 

•	 Evidence is suggestive of no causal relationship (i.e., smoking probably does not cause the 

disease) (USDHHS 2004). 

Importantly, SGR 2004 noted that “[t]here is no category beyond ‘suggestive of no causal 

relationship’ as it is extraordinarily difficult to prove the complete absence of a causal association” 

(USDHHS 2004). The general and inherent limitation of the scientific method in providing absolute 

proof of the absence of an effect must be borne in mind in the present consideration of menthol. 

APPLICATION OF THE 2004 SGR CATEGORIES REGARDING CAUSAL 

INFERENCES RELATED TO MENTHOL CIGARETTES COMPARED TO 

NONMENTHOL CIGARETTES 

In the present question of whether the use of menthol in cigarettes may adversely affect the public 

health, FDA must consider the potential of menthol to adversely impact the disease risks to the 

individual smoker; to the smoking population, generally; or to subpopulations of smokers. Wellestablished, proven general guidance and scientific principles for such a consideration are provided 

in the 2004 SGR, with some modifications required to address the specific menthol topics delineated 

in the text of the Act and reiterated in FDA’s charge to the TPSAC. 

The possible four conclusions relative to the review of the scientific literature on menthol expressed 

in terms of the four 2004 SGR categories are stated as follows: 

•	 Evidence is sufficient to infer a causal relationship between the use of menthol in cigarettes 

and an adverse impact on public health (i.e., smoking menthol cigarettes is proven to cause 

disease in the smoker, in the general population, or in subpopulations over and above that 

caused by smoking nonmenthol cigarettes; or smoking menthol cigarettes is proven to cause 

increased or earlier smoking initiation or reduced smoking cessation over and above that 

caused by smoking nonmenthol cigarettes). (Sufficient) 

•	 Evidence is suggestive but not sufficient to infer a causal relationship between the use of 

menthol in cigarettes and an adverse impact on public health (i.e., smoking menthol 

cigarettes is more likely than not to cause disease in the smoker, in the general population, or 

in subpopulations over and above that caused by smoking nonmenthol cigarettes; or 

3 Similar hierarchical approaches have also been used by the Institute of Medicine committees (IOM 1999) to classify 

causal conclusions and by the International Agency for Research on Cancer (IARC 1986) to classify conclusions 

regarding whether substances are carcinogenic. 

Chapter 1 

8
 

 

 

 

 

 

 

 

 

smoking menthol cigarettes is more likely than not to cause increased or earlier smoking 

initiation or reduced smoking cessation over and above that caused by smoking nonmenthol 

cigarettes). (Suggestive) 

•	 Evidence is inadequate to infer the presence or absence of a causal relationship between the 

use of menthol in cigarettes and an adverse impact on public health (i.e., there is not enough 

proof that smoking menthol cigarettes does or does not cause disease in the smoker, in the 

general population, or in subpopulations over and above that caused by smoking 

nonmenthol cigarettes; or there is not enough proof that smoking menthol cigarettes does or 

does not cause increased or earlier smoking initiation or reduced smoking cessation over and 

above that caused by smoking nonmenthol cigarettes). (Inadequate) 

•	 Evidence is suggestive of no causal relationship between the use of menthol in cigarettes and 

an adverse impact on public health (i.e., the evidence does not suggest that smoking menthol 

cigarettes causes disease in the smoker, in the general population, (or in subpopulations) 

over and above that caused by smoking nonmenthol cigarettes; or the evidence does not 

suggest that smoking menthol cigarettes causes increased or earlier smoking initiation or 

reduced smoking cessation over and above that of caused by smoking nonmenthol 

cigarettes). (No Causal Relationship) 

As noted above, because it is difficult to prove the complete absence of a causal relationship, the 

SGR 2004 does not provide a category beyond the final category -- “evidence is suggestive of no 

causal relationship.” 

In terms of the evaluation of menthol, if an assessment falls into the category of “Suggestive,” it may 

be appropriate for FDA to recommend further study of the issues. However, if an assessment of 

the totality of available scientific evidence falls into either of the final two categories (“Inadequate” 

or “No Causal Relationship”), no regulatory action on menthol is warranted by FDA. Also, as Hill 

pointed out, his criteria were to be used only if an association was “perfectly clear-cut and beyond 

what we would care to attribute to the play of chance” (Hill 1965). This indicates that if a 

statistically significant association cannot be established between menthol and a given health effect, 

the “evidence is suggestive of no causal relationship.” 

EQUIPOISE 

The use of the categories adopted by the U.S. Surgeon General in the Industry Menthol Report 

differs from the report to be issued by TPSAC, which uses the concept of equipoise. Equipoise has 

been used historically to provide an ethical basis for conducting medical research involving 

treatments of patients in clinical trials and more recently to evaluate veterans’ eligibility for certain 

medical benefits. Although the concept of equipoise has been used to express the “strength of 

overall evidence” [emphasis in original] for or against a causal relationship between exposure and 

disease (IOM 2008), TPSAC applied the concept in a framework very different from IOM (TPSAC 

2011). It is important to consider whether or not equipoise, as used by TPSAC, is the best approach 

for determining causation issues and questions related to any public health impact of the use of 

menthol as a cigarette ingredient above and beyond that for nonmenthol cigarettes. The simple 

answer is that it is not. 

Chapter 1 

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To understand why TPSAC’s unique application of the equipoise concept is inappropriate, a short 

discussion of the background use of equipoise is necessary. The use of equipoise in determining 

causation was employed in the IOM 2008 report on determining veterans’ benefits (IOM 2008). 

First, the IOM report described equipoise “to refer to the point at which the evidence is in balance 

between favoring and not favoring causation” (IOM 2008). Freedman, however, in his seminal 

article on equipoise and clinical research noted that this type of “theoretical equipoise” is near 

unattainable: 

Theoretical equipoise exists when, overall, the evidence on behalf of two alternative 

treatment regimens is exactly balanced. This evidence may be derived from a variety 

of sources, including data from the literature, uncontrolled experience, 

considerations of basic science and fundamental physiological processes, and 

perhaps a “gut feeling” or “instinct” resulting from (or superimposed on) other 

considerations.... Theoretical equipoise is overwhelmingly fragile; that is, it is 

disturbed by a slight accretion of evidence favoring one arm of the trial.... 

Theoretical equipoise is also highly sensitive to the vagaries of the investigator’s 

attention, and perception. Because of its fragility, theoretical equipoise is disturbed 

as soon as the investigator perceives a difference between the alternatives – whether 

or not any genuine difference exists.... Finally, as described by several authors, 

theoretical equipoise is personal and idiosyncratic. It is disturbed when the clinician 

has, in Shafer’s words, what “might be labeled as bias or a hunch,” a preference of a 

“merely intuitive nature.” (Freedman 1987). 

As noted in the 2008 IOM report, equipoise is based on the underlying scientific data. Discussing 

the evidence necessary for an association between an agent and a disease, the IOM report states 

“[a]lthough it is not sufficient for establishing causation, association is nevertheless prima facie 

evidence for causation, and the lack of association is prima facie evidence for lack of causation” 

(IOM 2008). Much like the Hill criteria, the lack of an association must certainly stop the analysis. 

As described earlier, Hill notes in introducing his criteria “[o]ur observations reveal an association 

between two variables, perfectly clear-cut and beyond what we would care to attribute to the play of 

chance” (Hill 1965). 

Similar to the 2004 SGR, the 2008 IOM Report also proposed “a four-level categorization of the 

strength of the overall evidence for or against a causal relationship between exposure and disease: 

1.	 Sufficient: The evidence is sufficient to conclude that a causal relationship exists. 

2.	 Equipoise and Above: The evidence is sufficient to conclude that a causal relationship is at 

least as likely as not, but not sufficient to conclude that a causal relationship exists. 

3.	 Below Equipoise: The evidence is not sufficient to conclude that a causal relationship is at 

least as likely as not, or is not sufficient to make a scientifically informed judgment. 

4.	 Against: The evidence suggests a lack of a causal relationship. 

The term “equipoise” is used to refer to the point at which the evidence is in balance between 

favoring and not favoring causation (IOM 2008). 

The 2008 IOM report provides valuable insight into the lack of rigor the equipoise method employs 

as compared to the Surgeon General’s Criteria. For example, the equipoise concept seemingly 

Chapter 1 

10
 

 

 

 

 

 

 

 

 

 

rejects the consistency requirement. The Surgeon General’s consistency requirement seeks 

“persistent finding of an association between exposure and outcome in multiple studies of adequate 

power, and in different persons, places, circumstances, and times” (USDHHS 2004 at 21). 

The IOM’s description and application of the equipoise concept is in stark contrast to the approach 

adopted by TPSAC. Although TPSAC adopts a “hierarchical classification for the strength of 

evidence,” the categories adopted by TPSAC can be contrasted with those used by the 2008 IOM 

Report: 

TPSAC - “The evidence is sufficient to conclude that a relationship is more likely than not” 

(contrasted to IOM 2008 - “Sufficient: The evidence is sufficient to conclude that a causal 

relationship exists”). 

TPSAC - “The evidence is sufficient to conclude that a relationship is at least as likely as 

not” (contrasted to IOM 2008 – “Equipoise and Above: The evidence is sufficient to conclude 

that a causal relationship is at least as likely as not, but not sufficient to conclude that a 

causal relationship exists”). 

TPSAC - “The evidence is insufficient to conclude that a relationship is more likely than 

not” (contrasted to IOM 2008 – “Below Equipoise: The evidence is not sufficient to conclude 

that a causal relationship is at least as likely as not, or is not sufficient to make a scientifically 

informed judgment’). 

TPSAC – “There is insufficient evidence to determine whether a relationship exists” 

(contrasted to IOM 2008 - Below Equipoise: The evidence is not sufficient to conclude that a 

causal relationship is at least as likely as not, or is not sufficient to make a scientifically 

informed judgment”). 

Most important, TPSAC completely eliminates the fourth category adopted by IOM: “Against: The 

evidence suggests the lack of a causal relationship.” This omission alone means that TPSAC cannot 

conclude that there is evidence that the use of menthol in cigarettes suggest no impact on public 

health, even though, as described in the following Chapters of the Industry Menthol Report, this is 

the appropriate category for the majority of the scientific evidence on menthol. This omission is a 

serious flaw in TPSAC’s approach. 

In addition to this critical omission, the equipoise concept as described by TPSAC lacks specific 

common assessment criteria to be followed in evaluating the evidence. As opposed to the specific 

criterion set forth in the Surgeon General’s Criteria, TPSAC did not propose specific criteria that 

would be applied uniformly. The absence of uniform, specified criteria severely limits conclusions 

that can be drawn from such a methodology. The scientific underpinning of reproducibility is cast 

to the wind because no one, other than the two-to-three person subcommittee for each chapter, 

could review the evidence and come to the same or similar conclusions based on the described 

method. As a result, the methodology TPSAC has reported also lacks the type of scientific rigor 

envisioned by Congress and expressed by FDA, particularly when the result of a recommendation 

from TPSAC could result in a consumer product being permanently removed from the market. 

The modified equipoise concept adopted by TPSAC is, therefore, an inappropriate tool to be used 

in an objective, data-driven, science-based evaluation due to the critical omission of a complete 

category of causal inference, along with the susceptibility of any determination to be impacted by 

instinct, bias, and hunches of the evaluator. 

Chapter 1 

11
 

 

 

 

 

 

 

 

 

 

PROPER INTERPRETATION OF DATA 

When determining the weight that should be given to any scientific research or data, it is essential to 

interpret the research findings and data appropriately and objectively. Many of the studies related to 

cigarette mentholation are observational studies that examine whether an association exists between 

the use of menthol in cigarettes and specific public health issues such as disease incidence, smoking 

initiation, dependence or smoking cessation. The existence of an association is a necessary 

condition of any eventual causal inference; however, variables may be associated without there being 

any causal relationship. Thus, the existence of an association does not prove causation and in many 

instances does not even support a causal inference. 

Often, the magnitude of an association is expressed by a comparative risk estimate (such as a relative 

risk, odds ratio, or hazard ratio), with a 1.0 risk estimate representing no increased risk. A risk 

estimate, however, is just that: an estimate of the strength of an association. Generally, the greater 

the risk estimate, the more likely that association is real (i.e., not due to bias or confounding). 

Confounding refers to the distortion of an observed association between two variables by a third 

factor associated with both the exposure and the outcome, but not considered in the analysis. 

Potential confounding factors must be considered in any reported association between the use of 

menthol in cigarettes and the outcome being examined. Examples of potential confounding factors 

in many studies of menthol cigarettes include race, sex, body mass index, socioeconomic status, 

residence of study participants, and tar, nicotine and carbon monoxide levels of the cigarettes 

studied, among other things. Caution must be exercised when inferring any causal relationship when 

risk estimates are below 2.0, because risk estimates of this magnitude can be produced by bias or 

confounding. Many respected epidemiologists believe that risk estimates below 2.0 are too weak to 

support a causal inference, especially when the related body of literature is inconsistent or even 

shows a non-significant reduced risk (e.g., Wynder 1996). 

Statistical significance of research results, including risk estimates, is an important consideration with 

respect to the scientific weight accorded those results. The confidence interval of a statistical 

estimate of the strength of an association between two variables is an indication of whether the 

association is likely to be due to chance. The confidence interval is the range within which the true 

mean value is believed to be contained, with a given probability (typically 95%). The statement that 

a given result is statistically significant (usually at the α=0.05 level, or below) means that it has a low 

probability of being due to chance. However, chance or sampling variability can never be completely 

ruled out as an explanation for a result. 

A risk estimate is judged to be statistically significant if the 95% confidence interval does not contain 

1.0. Further, although a risk estimate may be greater or lower than 1.0, if the confidence interval 

includes 1.0, the risk estimate is not considered to be statistically significant. A risk estimate that is 

not statistically significant means that chance or sampling variability cannot be ruled out as an 

explanation for the observed association. Importantly, a statistically non-significant elevated or 

reduced risk estimate (one that is greater or lower than 1.0, respectively) with a confidence interval 

that includes 1.0 cannot be interpreted as indicating a trend toward an increased risk or as being 

suggestive of an increased risk. In addition, statistically significant scientific findings are the essential 

foundation of any defensible causal inference, but may not in themselves be sufficient to infer 

Chapter 1 

12
 

causation, particularly for complex associations such as those between multidimensional smoking 

behaviors and multifactorial disease conditions. 

Note that in the Industry Menthol Report when study results or data are discussed as being 

“significant” or “non-significant,” those terms mean “statistically significant” or “statistically nonsignificant,” respectively. 

Chapter 1 

13
 

 

 

 

 

 

REFERENCES 

Family Smoking Prevention and Tobacco Control Act. 2009. Pub. L. No. 111-31. 22 June. 

Freedman B. 1987. Equipoise and the ethics of clinical research. New England J Med. 317(3):141-

145. 

Hill AB. 1965. The environment and disease: association or causation? Proceedings of the Royal 

Society of Medicine. 58(5):295-300. 

Institute of Medicine (IOM). 1999. Veterans and Agent Orange: Update 1998. Washington: 

National Academy Press. 

Institute of Medicine (IOM). 2008. Improving the Presumptive Disability Decision-Making Process 

for Veterans 2007. Washington: National Academy Press. 

International Agency for Research on Cancer (IARC). 1986. IARC Monographs on the Evaluation 

of the Carcinogenic Risk of Chemicals to Man: Tobacco Smoking. Vol. 38. Lyon (France): 

International Agency for Research on Cancer. 

Ranney L, Melvin C, Lux L, McClain E, Morgan L, Lohr KN. 2006. Tobacco use: Prevention, 

Cessation and Control. Evidence Report/Technology Assessment No. 140. AHRQ Publication 

No. 06-E015. 

TPSAC. 2011. Menthol cigarettes and public health: Review of the scientific evidence and 

recommendations. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM247689.pdf 

U.S. Department of Health and Human Services (USDHHS). 2004. The Health Consequences of 

Smoking: A Report of the Surgeon General. 

U.S. Public Health Service (USPHS). 1964. Smoking and Health: Report of the Advisory 

Committee to the Surgeon General of the Public Health Service. 

Wynder EL. 1996. Invited commentary: Response to Science article “Epidemiology faces its 

limits”. Am J Epidemiol. 143:747–749. 

Chapter 1 

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CHAPTER 2. 

DEMOGRAPHICS OF MENTHOL CIGARETTE PREFERENCE AND CURRENT 

TRENDS IN SMOKING PREVALENCE
 

It has been suggested that individuals that smoke menthol cigarettes may be more likely to transition 

from cigarette experimentation to established smoking (i.e., initiate smoking), may be more likely to 

exhibit evidence of nicotine dependence and/or may be less likely to successfully quit smoking. 

This chapter reviews what is known about current smokers and the demographic characteristics that 

may be associated with higher menthol compared to nonmenthol cigarette preference. Properly 

interpreted, such demographic data can provide the necessary context for subsequent examinations 

of potential population-level effects (i.e., smoking initiation, dependence and/or cessation) that may 

be associated with higher menthol cigarette preference. 

The available data indicates that menthol compared to nonmenthol cigarette preference is 

significantly higher among current smokers that are African American1 and, to a lesser extent, 

female. Some studies appear to suggest a higher menthol cigarette preference among younger 

compared to older smokers; however, these data are less consistent than for African American and 

female smokers. 

Also discussed are current trends in smoking prevalence, i.e., the proportion of the overall 

population (or subpopulation) that smoke cigarettes. Evidence that a specific group of smokers 

reports a higher preference for menthol cigarettes, or that preference among a group of smokers is 

increasing over time must not be interpreted as evidence of increased smoking prevalence. The 

reality is that smoking prevalence for the U.S. population has been steadily declining for the past two 

decades, regardless of demographic characteristics associated with race/ethnicity, sex or age 

category. 

DEMOGRAPHICS DATA FOR MENTHOL CIGARETTE PREFERENCE 

Information on the demographics of menthol compared to nonmenthol cigarette preference is 

available from nationally representative surveys and from individual studies of specific populations. 

Demographic data from studies based on national surveys are generally more informative due to the 

fact that the sample populations have been weighted to reflect nationally representative estimates 

aligned with the U.S. population; hence, study findings are considered to be representative of the 

entire smoking population. This is not the case for individual studies based on specific populations; 

findings from these studies would only be considered representative of the entire smoking 

population if external validity was demonstrated though appropriate comparisons. 

1 Studies refer to racial/ethnic subgroups in different ways. When citing specific studies, this Industry Menthol Report 

uses the terms used by the study authors. When discussing race/ethnicity in general terms, the term African Americans 

is used and includes African Americans, Blacks, and non-Hispanic Blacks. The term Whites is used to refer to Whites, 

Caucasians, European Americans and non-Hispanic Whites. The term Hispanics is used to refer to Hispanics and 

Latinos. 

Chapter 2 

15
 

 

 

 

 

 

Demographics data on menthol compared to nonmenthol cigarette preference among nationally 

representative populations of smokers are provided by five nationally representative surveys, as 

follows: 

• National Health and Nutrition Examination Survey (NHANES), 

• National Health Interview Survey (NHIS), 

• National Survey on Drug Use and Health (NSDUH), 

• National Youth Tobacco Survey (NYTS), and 

• Tobacco Use Supplement to the Current Population Survey (TUS-CPS). 

A brief description for each of the surveys is provided. 

National Health and Nutrition Examination Survey (NHANES) 

The NHANES is a major program of the National Center for Health Statistics (NCHS) that is 

designed to assess the health and nutritional status of adults and children. This nationally 

representative survey provides samples of the U.S. civilian, non-institutionalized population (~5,000 

persons/year), completed in two-year cycles. Information on smoking is collected in similar fashion 

for older and younger participants, using computer aided self-reports and not direct interviews. For 

adult respondents (aged ≥20 years), interviews are completed prior to a physical examination, in the 

home, using the Computer-Assisted Personal Interviewing system. For respondents aged 12-19 

years, smoking information is obtained during a physical examination, at the Mobile Examination 

Center (MEC), in the MEC Interview Room; respondents used audio computer-assisted, selfinterviews. To estimate menthol cigarette use, current adult smokers are asked, “What brand of 

cigarettes [do you] usually smoke?” Brand is visually confirmed, but in the absence of visual 

confirmation adult smokers are asked, “Is the cigarette product mentholated or nonmentholated?” 

Youth respondents (aged 12-19 years) are asked to indicate the specific brand name cigarettes in 

response to the question, “During the past 30 days, on the days that you smoked, which brand of 

cigarettes did you usually smoke?” For Marlboro, Winston, Benson and Hedges, and “other,” 

respondents are asked, “Was the [brand] cigarettes menthol or nonmenthol?” 

National Health Interview Survey (NHIS) 

The NHIS is a cross-sectional survey conducted by the NCHS that collects information on a variety 

of health indicators. This continuing nationwide sample survey collects data using personal 

household interviews with individuals aged ≥18 years. The NHIS includes an Adult Health 

Behavior section that contains questions related to cigarette smoking. All adults that indicate that 

they currently or formerly smoked are asked whether their usual cigarette brand is or was 

mentholated, whether they had ever tried to quit smoking, and the method(s) they used the last time 

they tried to stop smoking. To estimate menthol cigarette use, current adult smokers are asked the 

following question, “Earlier you said you smoke cigarettes. Is your usual cigarette brand menthol or 

nonmenthol?” 

Chapter 2 

16
 

 

 

 

 

 

 

 

 

National Survey on Drug Use and Health (NSDUH) 

The NSDUH, formerly called the National Household Survey on Drug Abuse (NHSDA), was 

initiated in 1971 as a result of legislation enacted in 1970 that created the Commission on Marijuana 

and Drug Abuse. This survey is sponsored by the Substance Abuse and Mental Health Services 

Administration (SAMHSA), and has grown in size and complexity from its initial sample size of 

~3,000 to its current sample of nearly 70,000 persons. Participants of the survey represent the U.S. 

civilian, non-institutionalized population, aged ≥12 years. The survey is currently conducted via 

computer-assisted interviewing. To estimate menthol cigarette use, respondents are asked the 

following questions, “During the past 30 days, what brand of cigarettes did you smoke most often?” 

and “Were the [FILL] cigarettes you smoked during the past 30 days menthol?” Menthol status is 

typically assigned based on response to the latter question only, as many leading cigarette brands 

have menthol and nonmenthol sub-brands and these details are not collected in the survey. 

National Youth Tobacco Survey (NYTS) 

In collaboration with the Centers for Disease Control and Prevention (CDC), the American Legacy 

Foundation developed the NYTS to measure the tobacco-related beliefs, attitudes and behaviors of 

youth. This survey is a self-administered, school-based survey that targets students in grades 6 

through 12 (aged 9-21 years). Surveys are completed anonymously, in a group setting, during the 

school day and on school property. The 1996, 1998 and 2000 surveys used passive parental consent, 

while the 2002 and 2004 surveys used active parental consent. In contrast, the 2006 and 2008 

surveys used a mixed parental consent procedure. The NYTS uses a multi-stage sampling design to 

produce a nationally representative sample of students. The survey questions used to assess menthol 

cigarette smoking changed slightly from survey to survey between 1999 and 2006, but have 

consistently attempted to determine cigarettes usually smoked; for example, respondents were asked 

the following question during the 2004 and 2006 surveys, “Are the cigarettes you usually smoke 

menthol cigarettes?” 

Tobacco Use Supplement to the Current Population Survey (TUS-CPS) 

The Tobacco Use Supplement of the Current Population Survey (TUS-CPS) is a survey of tobacco 

use that is co-sponsored by the National Cancer Institute (NCI) and the CDC. TUS-CPS has been 

conducted approximately every three years, and uses a nationally representative sample that contains 

information on ~240,000 individuals within a survey period. Smoking information is collected for a 

U.S. civilian, non-institutionalized population aged ≥15 years. Approximately 70% of the 

respondents complete the survey by telephone, and ~30% complete the survey in person. The 

survey contains mostly self-reported data, although ~20% of the data for a few measures of tobacco 

use are collected by proxy (i.e., data are collected about others in the household indirectly from the 

survey respondent). To estimate menthol cigarette use in 2003 and 2006/07, current smokers were 

asked the following question, “Is your usual cigarette brand menthol or nonmenthol?” 

Chapter 2 

17
Chapter 2 

 

EXAMINATION OF AVAILABLE DATA ON SMOKING DEMOGRAPHICS 

As noted above, there are two sources for data on the demographics of menthol compared to 

nonmenthol cigarette preference: nationally representative surveys and individual studies of specific 

populations. 

Eleven publications were identified that provided data on the demographics of menthol compared 

to nonmenthol cigarette preference. Of these studies, six analyses were based on data from four 

national surveys, appropriately weighted to be representative of the overall smoking population, 

including: 

Table 2-1.	 National Surveys Examining the Demographics of Menthol Cigarette 

Preference 

National Survey Citation Target Population Size 

2005 NHIS 

Cubbin et al. 2010 Adult smokers 

(aged 25-64 years) 3,902 

Mendiondo et al. 2010 Adult smokers 

(aged ≥18 years) 6,055 

2003, 2006/07 TUS- Fernander et al. 2010 Adult smokers 

(aged ≥18 years) 66,145 

CPS Lawrence et al. 2010 Adult smokers 

(aged ≥18 years) 63,193 

2004-2008 NSDUH Rock et al. 2010 Adult smokers 

(aged ≥12 years) 71,605 

2006 NYTS Hersey et al. 2010 Adolescent smokers 

(aged 9-21 years) 3,281 

Five additional studies provide data on the demographics of menthol compared to nonmenthol 

cigarette preference among specific populations not necessarily representative of the overall smoking 

population, including those listed in Table 2-2 below: 

18
Chapter 2 

 

 

 

 

 

 

Table 2-2. Additional Studies Examining the Demographics of Menthol Cigarette 

Preference 

Citation Study Target Population Size 

Hyland et al. 2002 COMMIT (1988) Adult smokers 

(aged 25-64 years) 13,268 

Murray et al. 2007 Lung Health Study, 1986-

1989 

Adult smokers 

(aged 35-60 years) 5,887 

Muscat et al. 2002 Case-control study of lung 

cancer, 1981-1999 Adult smokers 19,545 

Pletcher et al. 2006 CARDIA (1985) Adults 

(aged 18-30 years) 1,535 

Stahre et al. 20101 2005 NHIS Adult smokers 

(aged ≥18 years) 6,055 

1 Although Stahre et al. 2010 provides an analysis of data from the NHIS, which is a nationally representative survey, 

their sample population did not appear to be weighted to provide nationally representative estimates, likely limiting the 

generalizability of study findings to the overall population of smokers. 

Cross-sectional Studies Based on Nationally Representative Populations of Smokers 

Six studies are considered to be the “best available science” for examining the demographics of 

current menthol compared to nonmenthol cigarette preference. These studies are listed in Appendix 

Table 2-4, and are summarized below based on data source: 

National Health Interview Survey (NHIS) 

Analyses from both studies examining data from the 2005 NHIS indicated that African American 

and female smokers were significantly more likely to report current menthol versus nonmenthol 

cigarette preference compared to White and male smokers, respectively. None of the analyses based 

on NHIS data suggested that young adult smokers were more likely than older adult smokers to 

report menthol cigarette preference. These studies are described below: 

Cubbin et al. (2010) reported findings for menthol versus nonmenthol cigarette preference among 

current daily smokers (aged 18-64 years; N=3,902). The proportion of smokers that reported using 

menthol cigarettes was highest for African Americans; after adjusting for age, education and income, 

69.7% (99% CI:61.5-77.8%) of males and 77.9% (99% CI:71.1-84.7%) of females reported current 

use of menthol cigarettes; for Hispanics, 16.5% (99% CI:9.2-23.8%) of male and 35.6% (99% 

CI:25.6-45.7%) of female smokers reported using menthol cigarettes; and, the proportions of White 

male and female smokers that reported using menthol cigarettes were 14.6% (99% CI:11.9-17.3%) 

and 24.5% (99% CI:21.4-27.7%), respectively. Based on non-overlapping confidence intervals, 

African American smokers were significantly more likely to smoke menthol cigarettes than Whites 

(for both sexes) (p<0.01); and, female smokers were significantly more likely to smoke menthol 

cigarettes than males among both Hispanics and Whites (p<0.01). 

19
 

 

 

 

 

 

 

 

 

 

 

 

Mendiondo et al. (2010) reported findings for menthol cigarette preference among current 

smokers (aged ≥18 years; N=6,055). The proportion of current smokers that reported using 

menthol cigarettes was estimated to be ~25%. After controlling for race/ethnicity, sex and age 

category, current smokers of menthol cigarettes were significantly more likely to be female than male 

(OR=1.74; 95% CI:1.30-2.33), and African American (OR=11.52; 95% CI:8.86-14.98) or Hispanic 

(OR=1.85; 95% CI:1.35-2.55) than White. There were no significant differences based on age 

category (OR=0.99; 95% CI:0.99-1.00). 

Tobacco Use Supplement to the Current Population Survey (TUS-CPS)

2 

Analyses from both studies examining data from the 2003 and 2006/07 TUS-CPS indicated that 

African American and female smokers were significantly more likely to report current menthol 

cigarette preference compared to White and male smokers, respectively. Unlike findings from the 

NHIS, both analyses of TUS-CPS data suggested that younger smokers were significantly more 

likely to report menthol versus nonmenthol cigarette preference than older smokers, i.e. aged ≥65 

years. These studies are described below: 

Fernander et al. (2010) reported findings from descriptive analyses and logistic regression models 

examining menthol versus nonmenthol cigarette preference among current smokers (aged ≥18 

years). Descriptive analyses suggested that ~28% of current smokers reported using menthol 

cigarettes (17,441/63,193). Results from regression models that controlled for demographic 

characteristics, age at smoking initiation and purchasing unit suggested the odds of using menthol 

cigarettes were 11-fold higher for African American smokers compared to Whites (OR=11.10; 95% 

CI:10.01-12.31). Other sociodemographic categories were associated with relatively smaller 

magnitude differences in the odds of smoking menthol versus nonmenthol cigarettes. For example, 

male smokers had a 42% lower odds of using menthol cigarettes than females (OR=0.58; 95% 

CI:0.55-0.61); Hispanic smokers had 55% higher odds of using menthol cigarettes than Whites 

(OR=1.55; 95% CI:1.40-1.71); and, smokers aged 18-24 years had 66% higher odds of using 

menthol cigarettes compared to smokers aged ≥65 years (OR=1.66; 95% CI:1.47-1.88). 

Lawrence et al. (2010) examined sociodemographic correlates of using menthol cigarettes based on 

analyses of current smokers who participated in the TUS-CPS (N=63,193). Descriptive analyses 

suggested that ~28% of current smokers reported using menthol cigarettes (95% CI:27.14-28.10%). 

The proportions of current smokers that reported using menthol cigarettes were similar (i.e., 20-30% 

range) for all categories of race/ethnicity, except for African Americans, who were much more likely 

to prefer menthol to nonmenthol cigarettes (73.6%; 95% CI:71.97-75.16%). Stratifying by sex, 

female current smokers (32.4%; 95% CI:31.7-32.99%) were more likely than males (23.5%; 95% 

CI:22.86-24.06%) to report using menthol cigarettes, and this pattern was repeated within strata 

defined by each of the race/ethnicity groups. Findings from regression models suggested that 

African American smokers were approximately 11-fold more likely to prefer menthol cigarettes 

compared with Whites (OR=10.92; 99% CI:9.58-12.44). White females were more likely to report 

menthol cigarette preference than males (OR 1.67; 99% CI:1.53-1.82), as were African American 

2 Taures et al. (2010) examined the differential effect of price structures and indoor air quality regulations on smokers of 

menthol versus nonmenthol cigarettes, but did not provide any additional demographic data beyond that provided by 

cited analyses from the TUS-CPS. 

Chapter 2 

20
Chapter 2 

 

 

females (OR=1.57; 99% CI:1.26-1.96). The odds of reporting menthol cigarette preference were 

2.5- to 3-fold higher (p<0.01) among younger African American smokers compared to those aged 

≥65 years; no age-related differences were suggested for White smokers. For Hispanic smokers, 

differences were limited to females being more likely to report menthol cigarette preference 

compared to males (OR=1.51; 99% CI:1.19-1.91). 

National Survey on Drug Use and Health (NSDUH) 

A single study examining data from the 2004-2008 NSDUH suggested that significantly higher
 

percentages of African American and female smokers report menthol versus nonmenthol cigarette
 

preference compared to White and male smokers. Moreover, the percentage of current smokers
 

reporting menthol versus nonmenthol cigarette preference was significantly higher among
 

adolescent and younger adult smokers compared to older adults. This study is described below:
 

Rock et al. (2010) reported findings for menthol versus nonmenthol cigarette preference among
 

past-month smokers (aged ≥12 years; N=71,605). The proportion of past-month smokers that
 

reported using menthol cigarettes was estimated to be ~36%. Among female smokers, a 

significantly larger proportion smoked menthol compared to nonmenthol cigarettes (52.2% vs. 

43.0%; p<0.01). African American smokers were almost 10 times more likely to smoke menthol
 

than nonmenthol cigarettes (29.4% vs. 3.0%; p<0.01). For Hispanics, 11.7% (95% CI:10.9–12.5%)
 

smoked menthol cigarettes, while 11.5% (95% CI:11.0–12.1%) smoked nonmenthol cigarettes.
 

Preference for past-month menthol cigarette preference was highest in smokers aged
 

12-17 years (44.7%; 95% CI:43.2-46.2%), and lower among young smokers aged 18-25 years (36.1%; 

95% CI:35.3–36.9%) and aged ≥26 years (30.2%; 95% CI:29.4–31.1%). 

It has been suggested that estimates of menthol cigarette preference from the NSDUH are based on
 

an overly inclusive question that may misclassify smokers whose usual brand is nonmenthol but
 

have smoked any menthol cigarette(s) in the past month. Estimates of menthol preference among
 

current smokers from the NSDUH are typically higher (e.g., ~36%, as suggested by Rock et al.
 

above) than those from surveys that base estimates of menthol preference on usual cigarette (or
 

brand) smoked (~28%, as suggested by Lawrence et al. 2010 using the TUS-CPS; ~25%, as
 

suggested by Mendiondo et al. 2010 using the NHIS). Additionally, current smokers in the NSDUH
 

estimates were defined as having smoked all or part of a single cigarette in the last 30 days, a much
 

more inclusive definition of smoking compared to that used by other surveys (i.e., having smoked 

≥100 cigarettes lifetime and currently smoking on some days or every day). Hence, the potential
 

exists that estimates provided by the NSDUH are somewhat exaggerated, particularly among
 

younger, less experienced smokers.
 

National Youth Tobacco Survey (NYTS) 

A single study examining data from the 2006 NYTS suggested that African American adolescent 

smokers were significantly more likely to report current menthol versus nonmenthol cigarette 

preference compared to White smokers; no sex differences were reported. This study is described 

below: 

21
 

 

 

 

 

 

 

Hersey et al. (2010) reported that among middle school students, there were no significant 

differences in the proportions of smokers using menthol versus nonmenthol cigarettes by sex. 

African American smokers were significantly more likely to report using menthol cigarettes (80.6%; 

95% CI:72.0–89.3%), and significantly more likely to prefer menthol cigarettes compared to Whites 

(43.1%; 95% CI:36.2-50.0%). Among high school students, there were no sex differences for 

menthol versus nonmenthol cigarette preference (39.4%; 95% CI:33.6- 45.2% for males; and, 46.9%; 

95% CI:38.9-54.9% for females). However, there were significant differences for menthol cigarette 

preference between African American smokers (84.8%; 95% CI:77.3-92.3%) and White smokers 

(37.6%; 95% CI:31.0-44.3%) 

The NYTS differs from the other surveys with regard to both target population (i.e., restricted to 

adolescents enrolled in public and private schools, grades 6-12) and data collection methodology 

(i.e., survey is completed in a group versus private setting). The potential for a group versus private 

survey setting to impact data collection is suggested by a comparison of adolescent responses to 

identically worded items from the school-based (group setting) Youth Risk Behavior Surveillance 

System (YRBSS) and household-based (private setting) NHIS (Kann et al. 2002). Published findings 

indicated that 39 of the 42 identically worded items produced higher risk estimates for the YRBSS 

compared to the NHIS. For 24 of the items, comparisons yielded significant differences, including 

higher estimates for ever tried cigarette smoking, smoked a whole cigarette prior to age 13, ever 

smoked regularly and smoked regularly prior to age 13. Estimates may likewise be exaggerated due 

to the fact that current smokers were identified based on smoking all or part of a single cigarette in 

the past month, which overestimates established smoking particularly among younger, less 

experienced smokers. 

Studies Based on Specific Populations of Smokers 

Five studies examined the demographics of menthol compared to nonmenthol cigarette preference 

among current smokers, but have significant weaknesses that preclude drawing sound conclusions 

regarding demographic information. They are mentioned here briefly because they have been 

discussed at TPSAC meetings. 

•	 Hyland et al. (2002) analyzed baseline characteristics from a randomized community-based 

intervention trial (N=13,286) for smoking cessation; controlling for covariates suggested that 

menthol cigarette preference was more common among female compared to male smokers, 

African American compared to White smokers, and among smokers aged 25-34 years 

compared to aged 35-64 years. 

•	 Murray et al. (2007) analyzed baseline characteristics from a smoking cessation study of 

adults (N=5,887) with early evidence of obstructive lung impairment; African American 

smokers were more likely to prefer menthol versus nonmenthol cigarettes at baseline. 

•	 Muscat et al. (2002) reported cross-sectional analyses of baseline characteristics for current 

smokers (N=19,545) participating in a case-control study of tobacco-related cancers; 

smokers of menthol cigarettes were significantly more likely to be African American, female 

and aged <55 years. 

Chapter 2 

22
 

 

 

 

 

•	 Pletcher et al. (2006) reported analyses of baseline characteristics for current smokers 

(N=5,115) participating in a longitudinal study of pulmonary disease; menthol cigarette 

preference was reported to be strongly related to being African American, female and 

younger aged (estimated means). 

•	 Stahre et al. (2010) reported findings for menthol cigarette preference among current 

smokers in the NHIS (aged ≥18 years; N=6,055); African American smokers reported a 

significantly higher preference for menthol cigarettes compared to White smokers (76.0% vs. 

20.2%; p<0.001); female smokers likewise reported a significantly higher preference for 

menthol cigarettes compared to male smokers (33.1% vs. 22.0%; p<0.001); and, preference 

for menthol cigarettes was highest among smokers aged 18-24 years (31.6%), but was not 

significantly different compared to older age groups. 

The data from these five studies likewise indicate that menthol cigarette preference is higher among 

African American smokers compared to White smokers, and to a lesser extent, female smokers 

compared to male smokers. Some studies appear to suggest that menthol cigarette preference is also 

higher among younger compared to older smokers, although the data are less consistent than for 

African American and female smokers. 

UNPUBLISHED ANALYSES PRESENTED TO TPSAC 

In July 2010 and January 2011, a number of unpublished analyses that addressed the demographics 

of menthol versus nonmenthol cigarette preference were presented to TPSAC. Although these 

analyses have not undergone peer review, the authors’ conclusions are mentioned here briefly: 

•	 Curtin (unpublished) analyzed data from several large nationally representative surveys and 

reported that: 

o	 According to data from the 2005/06 and 2007/08 NHANES (aged ≥12 years), menthol 

cigarette preference among current smokers overall was ~26%; significantly higher 

proportions of African American and female smokers reported menthol cigarette 

preference compared to White and male smokers (by ~49% and ~9%, respectively), with 

no significant differences between younger and older smokers (26.4%, 31.7%, 25.5% and 

24.5% for aged 12-17, 18-24, 25-29 and ≥30 years, respectively). 

o	 According to data from the 2005 NHIS (aged ≥18 years), menthol cigarette preference 

among current smokers overall was ~27%; significantly higher proportions of African 

American and female smokers reported menthol cigarette preference compared to White 

and male smokers (by ~57% and ~11%, respectively), with no significant differences 

between younger and older smokers (31.5%, 27.4% and 25.9% for aged 18-24, 25-29 and 

≥30 years, respectively). 

Chapter 2 

23
 

 

 

 

 

 

o	 According to data from the 2007 NSDUH (aged ≥12 years), menthol cigarette 

preference among currents smokers overall was ~32%; a significantly higher proportion 

of African American smokers reported menthol cigarette preference compared to White 

smokers (by ~58%), with no significant difference for female compared to male 

smokers; smokers aged 12-17 and 18-23 reported significantly higher preferences for 

menthol cigarettes compared to smokers aged 24-29 and >30 years (46.7%, 40.8%, 

35.1% and 29.5% for aged 12-17, 18-23, 24-29 and ≥30 years, respectively). 

o	 According to data from the 2007 NYTS (aged 9-21 years), menthol cigarette preference 

among current smokers overall was ~43%; a significantly higher proportion of African 

American smokers reported menthol cigarette preference compared to White smokers 

(by ~41%), with no significant differences based on sex. 

•	 Delnevo et al.(unpublished) analyzed ever-smoker data from the 2003 and 2006/07 TUSCPS; controlling for covariates, menthol cigarette preference was suggested to be higher for 

African American compared to White smokers, female compared to male smokers, and 

young adult (aged 18-24 years) compared to older adult smokers. 

•	 Giovino (unpublished) analyzed data from the 2004-2008 NSDUH (aged ≥12 years), and 

reported that menthol cigarette preference among past-month smokers overall was ~33%; 

higher proportions of African American and female smokers reported menthol cigarette 

preference compared to White and male smokers (by ~62% and ~8%, respectively), with 

evidence of an age gradient for menthol cigarette preference (49.3%, 37.5%, 29.9%, 31.4% 

and 30.2% for aged 12-17, 18-25, 26-34, 35-49 and ≥50 years, respectively). 

•	 Hyland and Rivard (unpublished) analyzed adult smoker data from the 2002-2008 

International Tobacco Control Four Country Survey (aged ≥18 years), and reported that 

menthol cigarette preference among currents smokers overall was ~27%; higher proportions 

of African American and female smokers reported menthol cigarette preference compared 

to White and male smokers, with no reported analyses based on age category. 

In addition, Thorne et al. (2010) (researchers from the CDC) presented an analysis from the 2001-

2006 NHANES at the 2010 American Public Health Association meeting (on behalf of the FDA). 

They reported that menthol cigarette preference among past month smokers overall was ~25%; 

higher proportions of African American and female smokers reported menthol cigarette preference 

compared to White and male smokers (by ~59% and ~10%, respectively), with no differences 

between younger and older smokers (28.9%, 26.1%, 23.6%, 25.3% and 23.7% for aged 20-24, 24-34, 

35-44, 45-64 and ≥65 years, respectively). 

CIGARETTE PREFERENCE IS NOT INDICATIVE OF SMOKING PREVALENCE 

Data indicating that specific groups of smokers (e.g., African Americans) report a higher preference 

for menthol versus nonmenthol cigarettes or that menthol preference is increasing over time must 

not be interpreted as evidence of increased smoking prevalence. Researchers have, in some instance, 

confused cigarette “preference” with smoking “prevalence,” which in turn has led to inappropriate 

conclusions related to population-level harm. 

Chapter 2 

24
 

 

 

 

 

 

Smoking prevalence provides an estimate of cigarette use among the overall population, i.e., the 

proportion of individuals in the population (or subpopulation) that currently smoke cigarettes. 

According to a recent report by the National Cancer Institute (NCI 2010), estimates provided by the 

NHIS indicate that smoking prevalence (i.e., established smoking) among all U.S. adults in 2008 was 

~20.5%; stratifying by race/ethnicity, ~22.5% of Whites and ~19% of African Americans reported 

having smoked ≥100 cigarettes lifetime and currently smoking on some days or every day (Figure 

2.1). 

In contrast, estimates of cigarette preference provide information on the percentage of current 

smokers that choose to smoke a particular type of cigarette, such as higher versus lower tar or 

menthol versus nonmenthol. Estimates provided by the 2005 NHIS indicate that ~20% of White 

smokers report using menthol cigarettes, while ~76.5% of African American smokers report using 

menthol cigarettes (Curtin unpublished). As is clearly indicated in Figure 2-1, the disproportionate 

preference for menthol versus nonmenthol cigarettes estimated for African American compared to 

White smokers does not translate to a higher smoking prevalence for African Americans compared 

to Whites; in fact, smoking prevalence among African Americans is similar or slightly lower than 

that for Whites. 

Figure 2-1. Smoking Prevalence and Cigarette Preference Smoking Prevalence (%) 

100 

80 

60 

40 

20 

0 

Smoking Prevalence: Menthol Cigarette Preference: 

Overall, 20.5% Overall smokers, 27% 

Whites, 22.5% White smokers, 20% 

African Americans, 19.0% African American smokers, 76.5% 

Overall 

Prevalence 

Whites African Americans 

menthol cigarette preference nonmenthol cigarette preference 

Smoking prevalence data based on 2008 NHIS (NCI 2010); cigarette preference data based on 2005 NHIS (Curtin 

unpublished). Nationally representative surveys indicate that the majority (>50%) of menthol smokers are White; there 

are approximately two times more White menthol smokers than African American smokers (based on menthol smoking 

prevalence and census data for White and African American populations). 

Chapter 2 

25
 

 

 

 

 

 

 

 

 

SMOKING PREVALENCE IS DECLINING REGARDLESS OF RACE/ETHNICITY, 

SEX OR AGE CATEGORY 

An increase in smoking prevalence in the population could represent an adverse population-level 

effect, while higher preference for a particular cigarette type that does not provide any increased risk 

for disease or adversely impact smoking behavior among a declining smoking population would not. 

Recent estimates for the proportion of the U.S. population reporting established smoking (i.e., 

having smoked ≥100 cigarettes lifetime, and currently smoking some days or every day) indicate that 

smoking prevalence has been steadily declining during the last two decades, regardless of 

race/ethnicity, sex or age category. 

As shown in Figure 2-2, smoking prevalence has declined among adults (aged ≥18 years) of all races 

from 1991 to 2008. The prevalence of smoking among African Americans and Hispanics declined 

more dramatically than smoking prevalence among Whites. Additionally, smoking prevalence 

among Hispanics, and to a lesser extent, African Americans tends to be lower than for Whites. 

Smoking prevalence among both adult males and females (aged ≥18 years) has steadily declined

since 1991 (from ~26% to ~21%), with a more pronounced reduction for females compared to 

males during the period of 2000 to 2006. Among adults aged 18-24 years, smoking prevalence 

initially increased but began declining in 1997 among males and in 1999 among females. Smoking 

prevalence among males and females aged ≥25 years steadily declined over the entire period. 

Figure 2-2. Smoking Prevalence among US Adults (by race/ethnicity, 1991-2008) 

 

35
 

30
 

25
 

20
 

15
 

10
 

5 

0 

1991 1994 1998 2001 2004 2007 

Non-Hispanic White Non-Hispanic Black Hispanic 

Figure reproduced from NCI 2010 

Smoking Prevalence (%) 

Figure 2-3 depicts trends in smoking prevalence among adolescents (past month smoking, grades 

9-12) and adults (established smoking, aged ≥18 years) over the period of 1997 to 2007. For 

Chapter 2 

26
 

adolescents, smoking prevalence initially increased from 1991 to 1997 but was followed by a 

dramatic decline (from ~37% to ~19%) from 1997 to 2007. Comparatively, smoking prevalence 

among adults declined from ~24% to ~20.5% from 1997 to 2007. 

Figure 2-3. Smoking Prevalence among U.S. Adolescents and Adults (1997-2007) 

 

 

Smoking Prevalence (%) 

40 

35 

30 

25 

20 

15 

10 

5 

0 

1997 1999 2001 2003 2005 2007 

Adults (aged ≥ 18 years) Adolescents (grades 9-12) 

Figure reproduced from NCI 2010 

 

 

 

 

 

Thus, estimates from a nationally representative sampling of the U.S. population indicate that 

cigarette smoking prevalence has steadily declined for all demographic groups, regardless of 

race/ethnicity, sex or age category; and, that these declines have been more pronounced for 

minorities (including African Americans), females and adolescents, despite their higher preference 

for menthol versus nonmenthol cigarettes. 

Corresponding trends analyses of smoking prevalence based on menthol versus nonmenthol 

cigarette preference are not currently available from the published literature. Nonetheless, original 

trend analysis data from the NSDUH (aged 12-25 years) were provided to the TPSAC during the 

November 2010 meeting. Findings suggested that menthol smoking prevalence among African 

Americans, females and adolescents had generally declined from 2004 to 2008 (Table 2-3; derived 

from Giovino unpublished). Similar to findings from the NCI 2010 report, these data indicate that 

higher menthol cigarette preference among demographic groups that report higher menthol versus 

nonmenthol cigarette preference has not translated to an increased smoking prevalence. 

Chapter 2 

27
Chapter 2 

 

 

 

 

 

 

 

 

 

 

 

Table 2-3. Menthol Smoking Prevalence (by demographic characteristics; Giovino 

unpublished) 

Non-Hispanic Black Female Aged 12-17 years 

% 95% CI % 95% CI % 95% CI 

2004 5.3 4.20-6.34 6.0 5.32-6.63 5.3 4.82-5.76 

2005 6.1 4.69-7.53 5.2 4.46-6.03 4.8 4.23-5.31 

2006 5.7 4.39-6.97 5.3 4.87-5.79 4.8 4.43-5.18 

2007 5.8 4.44-7.11 5.0 4.44-5.61 4.9 4.46-5.42 

2008 4.9 3.80-5.92 4.7 4.19-5.28 4.6 4.12-4.99 

CONCLUSION 

This review of the best available literature on the demographics of menthol cigarette preference 

indicates that substantially higher proportions of African American smokers report using menthol 

cigarettes compared to White smokers. While the difference is decidedly less pronounced, the 

available data consistently suggest that higher proportions of female compared to male smokers 

report using menthol cigarettes. 

The available literature on the existence of an age gradient, whereby youth and younger adult 

smokers report higher menthol cigarette preference compared to older smokers, are inconsistent. 

Descriptive analyses based on data from the NHIS and NHANES consistently suggest no 

significant age-related differences for current menthol cigarette preference, while data from the 

NSDUH and, to a lesser extent, the TUS-CPS appear to suggest an age gradient for menthol 

cigarette preference. It bears mentioning that menthol status for respondents to the NSDUH is 

assigned based on any past month menthol cigarette use and not necessarily based on usual brand, 

leading to somewhat higher estimates of menthol cigarette preference relative to other nationally 

representative surveys. Moreover, interpretation of published findings from the TUS-CPS is 

complicated, to some extent, by use of the ≥65 years age category (i.e., those with the lowest 

preference for menthol cigarettes) as the reference group for comparative analyses. Regardless of 

whether the available data support the existence of an age gradient, the reality is that youth and 

young adult smokers will likely continue to be viewed as groups of particular interest during 

subsequent analyses of potential population-level effects associated with menthol cigarette 

preference. 

Evidence that a specific group of smokers reports a higher preference for menthol cigarettes, or that 

preference among a group of smokers is increasing over time must not be interpreted as evidence of 

increased smoking prevalence. Current cigarette type preference is not informative with regard to 

the use of menthol versus nonmenthol cigarettes during experimentation with cigarettes or 

transitioning from cigarette experimentation to established smoking. The NCI recently reported 

that smoking prevalence has steadily declined during the past two decades for all demographic 

groups, and that these declines have been more pronounced for minorities (including African 

Americans), females and adolescents – the same groups that report higher menthol cigarette 

preference. Demographic data detailed in this chapter are most appropriately used to inform 

28
 

subsequent examinations of potential population-level effects (i.e., smoking initiation, dependence 

and/or cessation) that may be associated with menthol cigarette preference. 

Chapter 2
 29
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

REFERENCES 

Cubbin C, Soobader J-J, LeClere FB. 2010. The intersection of gender and race/ethnicity in 

smoking behaviors among menthol and non-menthol smokers in the United States. Addict. 105:32-

38. 

Curtin GM. [unpublished]. Epidemiological analysis of menthol cigarette use: demographics and 

population-level effects. Presented at: TPSAC, 16 Jul 2010. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM220050.pdf 

Delnevo CD, Gunderson DA, Hrwyna M. [unpublished]. Examining the relationship between 

menthol smoking and cessation using data from the 2003 and 2006/7 Tobacco Use Supplement. 

Paper presented to: TPSAC, 10-11 Jan 2011. 

Fernander A, Rayens MK, Zhang M, Adkins S. 2010. Are age of smoking initiation and purchasing 

patterns associated with menthol smoking? Addict. 105:39-45. 

Giovino GA. [unpublished]. Patterns of and recent trends in the use of mentholated cigarettes in 

the United States. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM234658.pdf 

Hersey JC, Nonnemaker JM, Homsi G. 2010. Menthol cigarettes contribute to the appeal and 

addiction potential of smoking for youth. Nicotine Tob Res. 12:S136-S146. 

Hyland A, Garten S, Giovino GA, Cummings KM. 2002. Mentholated cigarettes and smoking 

cessation: findings from COMMIT. Community Intervention Trial for Smoking Cessation. Tob. 

Control. 11:135-139. 

Hyland A, Rivard C. [unpublished]. Analysis of mentholated cigarettes using the COMMIT Data. 

Paper presented to: TPSAC, 10-11 Jan 2011. 

Kann L, Brener ND, Warren CW, Collins JL, Giovino GA. 2002. An assessment of the effect of 

data collection setting on the prevalence of health risk behaviors among adolescents. J. Adolesc. 

Health. 31:327-335. 

Lawrence D, Rose A, Fagan P, Moolchan ET, Gibson JT, Backinger CL. 2010. National patterns 

and correlates of mentholated cigarette use in the United States. Addict. 105:13-31. 

Mendiondo MS, Alexander LA, Crawford T. 2010. Health profile differences for menthol and nonmenthol smokers: findings from the national health interview survey. Addict. 105:124-140. 

Murray RP, Connett JE, Skeans MA, Tashkin DP. 2007. Menthol cigarettes and health risks in 

Lung Health Study data. Nicotine Tob Res. 9:101-107. 

Chapter 2 

30
 

 

 

 

 

 

 

 

 

 

 

 

Muscat JE, Richie JP, Stellman SD. 2002. Mentholated cigarettes and smoking habits in whites and 

blacks. Tob Control. 11:368-371. 

National Cancer Institute. 2010. Cancer trends progress report – 2009/2010 update. Bethesda, 

MD. Available at: http://progressreport.cancer.gov/index.asp 

Pletcher MJ, Hulley BJ, Houston T, Kiefe CI, Benowitz N, Sidney S. 2006. Menthol cigarettes, 

smoking cessation, atherosclerosis, and pulmonary function: the Coronary Artery Risk Development 

in Young Adults (CARDIA) Study. Arch Intern Med. 166:1915-1922. 

Rock VJ, Davis SP, Thorne SL, Asman KJ, Caraballo RS. 2010. Menthol cigarette use among racial 

and ethnic groups in the United States, 2004-2008. Nicotine Tob Res. 12:S117-S124. 

Stahre M, Okuyemi KS, Joseph AM, Fu SS. 2010. Racial/ethnic differences in menthol cigarette 

smoking, population quit ratios and utilization of evidence-based tobacco cessation treatments. 

Addict. 105:75-83. 

Taures JA, Levy D, Chaloupka FJ, Villanti A, Niaura RS, Vallone D, Abrams DB. 2010. Menthol 

and non-menthol smoking: the impact of prices and smoke-free air laws. Addict. 105:115-123. 

Thorne S, Davis S, Caraballo R. 2010. Menthol use and nicotine dependence among US adults, 

2001-2006. Presented at: American Public Health Association Meeting; 9 Nov; Denver, CO. 

Chapter 2 

31
Chapter 2 – Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2-4. Higher Quality Studies on Menthol Preference Demographics (N=6) 

CITATION STUDY TYPE GROUPS RESULTS CONCLUSIONS 

Cubbin et al. 

2010 

The intersection 

of sex and 

race/ethnicity in 

smoking 

behaviors 

among menthol 

and nonmenthol 

smokers in the 

United States 

Cross-sectional data 

from the 2005 National 

Health Interview 

Survey (NHIS) linked 

with the Cancer 

Control Supplement 

Analytical sample 

included 21,196 

subjects aged 25–64; 

included current 

(N=3,902), former 

(N=3,786) and never 

(N=13,508) smokers 

who reported menthol 

status. 

Data adjusted by 

race/ethnicity, age, 

income and education; 

imputed income from 

the National Center for 

Health Statistics was 

used for subjects whose 

income was unknown. 

Every Day Smokers 

Black 

Women 

Men 

Hispanic 

Women 

Men 

White 

Women 

Men 

Menthol Smoking Preference

Percent (99% CI) 

77.9 (71.1–84.7) 

69.7 (61.5–77.8) 

35.6 (25.6–45.7)* 

16.5 (9.2–23.8) 

24.5 (21.4–27.7)* 

14.6 (11.9–17.3) 

Adjusted for age, income and 

education. 

Black every day smokers, both men and women, 

were significantly (p<0.01) more likely to smoke 

menthol cigarettes than nonmenthol cigarettes 

compared to White or Hispanic every day 

smokers. 

Hispanic or White female smokers were 

significantly (p<0.01) more likely to smoke 

menthol cigarettes than Hispanic or White men; 

no significant differences were reported for Black 

female and male smokers. 

This study used 99% confidence intervals for 

statistical tests. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

32
Chapter 2 – Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2-4. Higher Quality Studies on Menthol Preference Demographics (N=6) (Continued) 

CITATION STUDY TYPE GROUPS RESULTS CONCLUSIONS 

Fernander et al. 

2010 

Age of smoking 

initiation and 

purchasing 

patterns and 

associations with 

menthol 

smoking 

Cross-sectional data 

from the 2003 and the 

2006/07 Tobacco Use 

Supplement to the 

Current Population 

Survey (TUS CPS) 

Analytical sample 

included 66,145 

subjects, selfresponders only, aged 

18 years or older; 

included respondents 

that smoked menthol 

(N=16,294) or 

nonmenthol 

(N=46,899) cigarettes, 

or were unresponsive 

(2,952). 

Proxy respondents 

were excluded from 

this study because it 

was assumed that 

certain items pertaining 

to smoking would be 

less accurate when 

answered by a proxy 

respondent. 

Current Smokers 

(every or some days) 

Sex 

Male 

Female 

Ethnicity 

Black 

Hispanic 

Other 

White non-Hispanic 

Age Cohorts

18-24 

25-44 

45-64 

65+ 

Odds Ratio Associated with 

Menthol Smoking (95% CI) 

0.58 (0.55–0.61)** 

1.00 (reference) 

11.10 (10.01-12.31)* 

1.55 (1.40-1.71) 

1.35 (1.19-1.54) 

1.00 (reference) 

1.66 (1.47-1.88)* 

1.20 (1.07-1.34)* 

1.36 (1.22-1.51)* 

1.00 (reference) 

Female current smokers were significantly 

(p<0.05) more likely to smoke menthol cigarettes 

than males. 

Black current smokers were significantly (p<0.05) 

more likely than any other ethnic group to smoke 

menthol cigarettes, followed by Hispanic smokers. 

Current smokers aged 18-24, 25-44 and 45-64 

years were significantly (p<0.05) more likely to 

smoke menthol cigarettes than smokers aged 65+ 

years. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

33
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2-4. Higher Quality Studies on Menthol Preference Demographics (N=6) (Continued) 

CITATION STUDY TYPE GROUPS RESULTS CONCLUSIONS 

Hersey et al. 

2010 

Menthol 

cigarettes and 

the appeal and 

addiction 

potential of 

smoking for 

youth 

Cross-sectional data 

from the 2006 National 

Youth Tobacco Survey 

(NYTS) 

Sample included 27,038 

subjects in Grades 6-

12; analyses were 

restricted to those who 

had smoked in the past 

30 days and could 

identify whether the 

usual brand was 

menthol or 

nonmenthol (N=3,281; 

771 middle school and 

2,510 high school). 

Past Month Smokers 

Middle school 

All youth smokers 

Sex 

Male 

Female 

Race/ethnicity

Black 

Asian American 

Hispanic 

White (non-Hispanic) 

High school

All youth smokers 

Sex 

Male 

Female 

Race/ethnicity 

Black 

Asian American 

Hispanic 

White (non-Hispanic) 

Menthol Smoking Preference

Percent (95% CI) 

51.7 (45.8-57.5) 

55.1 (43.9-54.7) 

48.1 (28.1-51.6) 

80.6 (72.0-89.3) 

57.4 (27.7-87.1) 

57.9 (48.8-67.0) 

43.1 (36.2-50.0) 

43.1 (37.0-49.1) 

39.4 (33.6-45.2) 

46.9 (38.9-54.9) 

84.8 (77.3-92.3) 

43.6 (24.3-63.0) 

56.4 (48.7-64.2) 

37.6 (31.0-44.3) 

There were no significant differences in menthol 

smoking preference between males and females in 

either age group (middle school or high school). 

Black middle school and high school students 

reported the highest menthol smoking preference 

among the race/ethnicity groups, and Whites 

reported the lowest. 

Among middle school students, menthol 

preference among Blacks was significantly higher 

than White (non-Hispanic) and Hispanic 

participants. Among high school students, 

preference for menthol among Blacks was 

significantly higher than any other race/ethnicity. 

Only 6.3% (95% CI, 5.1-7.5) of middle school 

smokers and 19.7% (95% CI, 18.1-21.4) of high 

school smokers reported a usual brand of 

cigarette. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

Chapter 2 – Appendix 

34
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2-4. Higher Quality Studies on Menthol Preference Demographics (N=6) (Continued) 

CITATION STUDY TYPE GROUPS RESULTS CONCLUSIONS 

Lawrence et al. 

2010 

National 

patterns and 

correlates of 

mentholated 

cigarette use in 

the United 

States 

Cross-sectional data 

from the 2003 and 

2006/07 Tobacco Use 

Supplement to the 

Current Population 

Survey (TUS CPS) 

Analytical sample 

included 63,193 

subjects aged 18 years 

or older; 16,294 

(25.8%) smoked 

menthol and 46,899 

(74.2%) smoked 

nonmenthol cigarettes. 

Regular Smokers 

Sex 

Male 

Female 

Age Cohorts 

18-24 

25-44 

45-64 

65+ 

Ethnicity 

White (non-Hispanic) 

Black (non-Hispanic) 

Hispanic 

A. Indian/ Alaskan Native 

(non-Hispanic) 

Asian/Pacific Islander 

(non-Hispanic) 

Multiple races 

Age by Sex 

Males 

18-24 

25-44 

45-64 

65+ 

Female 

18-24 

25-44 

45-64 

65+ 

Adjusted Odds Ratio Associated 

with Menthol Smoking (99% CI) 

1.00 (reference) 

1.64 (1.53-1.76)* 

1.39 (1.12-1.73)* 

1.07 (0.89-1.28) 

1.29 (1.09-1.53)* 

1.00 (reference) 

1.00 (reference) 

10.92 (9.58-12.44)* 

1.92 (1.66-2.21)* 

1.19 (0.87-1.63) 

2.07 (1.57-2.73)* 

1.61 (1.29-2.01)* 

1.46 (1.05-2.02)* 

0.92 (0.69-1.23) 

1.08 (0.82-1.44) 

1.00 (reference) 

1.31 (0.98-1.75) 

1.21 (0.97-1.52) 

1.48 (1.19-1.84)* 

1.00 (reference) 

Menthol cigarette smoking among regular smokers 

was significantly associated with race/ethnicity, 

sex and age. 

The most significant factor was race/ethnicity, 

with Black smokers being nearly 11 times more 

likely to use menthol cigarettes than White 

smokers; Hispanic and API smokers were 

approximately twice as likely. 

Female smokers were 1.6 times more likely to 

smoke menthol cigarettes than were males 

smokers. 

Smokers aged 18-24 and 45-64 years were 

approximately 1.4 and 1.3 times as likely, 

respectively, to use menthol cigarettes than 

smokers aged 65 years. 

Chapter 2 – Appendix 

35
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2-4. Higher Quality Studies on Menthol Preference Demographics (N=6) (Continued) 

CITATION STUDY TYPE GROUPS RESULTS CONCLUSIONS 

Lawrence et al. 

2010 

(continued) 

Adjusted for socio-demographic and 

smoking behavior variables that were 

associated significantly with 

mentholated cigarette smoking in 

bivariate logistic regression models. 

Mendiondo et 

al. 2010 

Health profile 

differences for 

menthol and 

nonmenthol 

smokers: 

findings from 

the national 

health interview 

survey 

Cross-sectional data 

from the 2005 National 

Health Interview 

Survey (NHIS) linked 

with the Cancer 

Control Supplement 

Analytical sample 

included 12,004 

subjects aged 18 years 

and older who were 

either current 

(N=6,055) or former 

(N=5,949) smokers and 

reported menthol 

status. 

Reported use of 

menthol cigarettes was 

25.2% among current 

smokers. 

Post-stratification 

adjustments based on 

sex, race/ethnicity and 

age using the Census 

Bureau data were 

applied. 

Current Smokers 

(every or some days) 

Sex 

Male 

Female 

Ethnicity

Non-Hispanic White 

Black 

Hispanic 

Age 

Adjusted Odds Ratio Associated 

with Menthol Smoking (95% CI) 

1.00 (reference) 

1.74 (1.30-2.33)* 

1.00 (reference) 

11.52 (8.86–14.98)* 

1.85 (1.35–2.55)* 

0.99 (0.99-1.00) 

Adjusted for age, education, region, 

race/ethnicity, income and sex. 

African American and female smokers were 

significantly more likely to be menthol versus 

nonmenthol smokers compared to Whites and 

males, respectively. 

There were no significant differences based on 

age. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

Chapter 2 – Appendix 

36
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2-4. Higher Quality Studies on Menthol Preference Demographics (N=6) (Continued) 

CITATION STUDY TYPE GROUPS RESULTS CONCLUSIONS 

Rock et al. 

2010 

Menthol 

cigarette use 

among racial 

and ethnic 

groups in the 

United States, 

2004-2008 

Cross-sectional data 

from the 2004-2008 

National Survey on 

Drug Use and Health 

(NSDUH) 

Analytical sample 

included 71,605 

subjects (35.7% 

menthol smokers and 

64.3% nonmenthol 

smokers), aged 12 years 

or older, who reported 

and menthol smoking 

in the past 30 days. 

Data were adjusted for 

non-response and 

weighted to provide 

national estimates of 

smoking preference. 

Age Cohorts 

12-17 years 

Total 

Male 

Female 

White 

Black 

Hispanic 

Asian 

A. Indian/Alaska Native 

18-25 years 

Total 

Male 

Female 

White 

Black 

Hispanic 

Asian 

A. Indian/Alaska Native 

26+ years 

Total 

Male 

Female 

White 

Black 

Hispanic 

Asian 

Indian/Alaska Native 

Menthol Smoking Preference 

Percent (95% CI) 

44.7 (43.2–46.2) 

42.2 (40.3–44.2) 

47.3 (45.5–49.1)* 

41.0 (39.4–42.6) 

71.9 (67.1–76.2) 

47.0 (42.5–51.5) 

51.5 (39.2–63.6) 

34.7 (24.3–46.8) 

36.1 (35.3–36.9) 

33.9 (32.9–34.9) 

38.8 (37.9–39.8)* 

28.8 (28.0–29.6) 

85.0 (83.8–86.5) 

38.2 (36.1-40.4) 

35.8 (31.0–40.9) 

27.4 (22.7–32.8) 

30.2 (29.4–31.1) 

26.1 (25.1–27.2) 

35.0 (33.8–36.2)* 

21.9 (20.9–22.9) 

82.2 (80.1–84.1) 

29.5 (27.4–31.8) 

28.6 (23.2–34.7) 

23.0 (16.4–31.3) 

Preference for menthol cigarettes was higher 

among 12-17 year old smokers than among other 

age groups, for the overall sample, for males and 

females, and for Whites and Hispanics. 

Preference for menthol cigarettes was lower 

among Black smokers age 12-17 years compared 

to older age groups. 

In general, preference for menthol cigarettes was 

higher among Black smokers than among any 

other ethnic group. 

In general, preference for menthol cigarettes was 

higher among female smokers than males. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

Chapter 2 – Appendix 

37
 

 

 

CHAPTER 3A.
 

MENTHOL IN CIGARETTES DOES NOT CHANGE
 

THE INHERENT HEALTH RISKS OF SMOKING
 

Menthol is one of the most widely studied ingredients in cigarettes. This review of the scientific 

evidence, which includes epidemiology studies, as well as those of biomarkers of exposure and harm, 

smoking topography, and toxicology and chemistry, clearly demonstrates that smokers of menthol 

cigarettes are at no greater risk of developing smoking-related diseases than are nonmenthol 

smokers. 

The tobacco industry acknowledges that smoking any type of cigarette carries significant health risks. 

However, the science clearly shows that the addition of menthol to a cigarette does not affect the 

inherent health risks associated with smoking. FDA and the TPSAC must evaluate all available data 

in an impartial and comprehensive manner and base any recommendations or regulatory decisions 

on a rigorous evaluation of sound science. 

The associations between cigarette smoking and various chronic diseases have been studied by 

epidemiologists for decades. Studies conducted in a variety of different populations during the past 

60 years have given the same basic message: the risk of smoking-related diseases increases with 

amount and duration of smoking. Number of cigarettes smoked per day and years of smoking have 

been shown to be robust and reproducible predictors of the risks of developing smoking-related 

diseases. To the extent that smoking exposure is characterized accurately, well-conducted 

epidemiology studies are capable of measuring associated health risks. The epidemiology studies 

comparing smokers of menthol and nonmenthol cigarettes provide strong evidence that there is no 

difference between the two types of cigarettes with respect to health risks. 

Findings from epidemiology studies are consistent with the available data on biomarkers of exposure 

and harm (which provide quantitative measures of smokers’ systemic exposures and incorporate all 

aspects of smoking behavior), smoking topography, as well as studies of toxicology and chemistry. 

These studies indicate that menthol in cigarettes does not expose the smoker to any additional health 

risks over those associated with nonmenthol cigarettes. 

Using the framework for causal inferences set forth by the Surgeon General in 2004, a collective 

assessment of the available literature on epidemiology, biomarkers of exposure and harm, smoking 

topography, toxicology and chemistry leads to the conclusion that the “evidence is suggestive of 

no causal relationship” between the use of menthol in cigarettes and increased chronic disease risk 

above that of nonmenthol cigarettes. 

Chapter 3 

38
 

 

 

 

SUFFICIENT EPIDEMIOLOGY DATA ARE AVAILABLE TO DRAW CONCLUSIONS 

Chronic disease epidemiology provides an essential foundation for the Surgeon General’s 

conclusions on disease causation associated with smoking (e.g., USDHHS 20041). Most 

importantly, epidemiology studies integrate all aspects of cigarettes and smoking, including the 

composition and design of cigarettes, smoking duration, smoking behavior and intensity 

(topography), and smoking cessation on public health. The Institute of Medicine (2001) has stated: 

“Most of what is known about harmful tobacco products has resulted from epidemiology. ... 

[E]pidemiological studies can provide the most definitive data about tobacco harm.” The 

recognition by the Surgeon General, the National Academy of Sciences, and the Institute of 

Medicine that, of all disciplines, epidemiology provides the most important evidence concerning 

risks to public health, is particularly relevant to the evaluation of any health effects of menthol in 

cigarettes. 

Having sufficient, methodologically-sound epidemiology data is key to being able to draw reliable 

conclusions about the impact of menthol cigarettes on disease risk. While there may be debate 

about how many, and what type of, studies constitute the ideal dataset for any given public health 

problem, sufficient data exist to draw reliable conclusions about the health effects of menthol 

cigarettes compared to those of nonmenthol cigarettes, for the following reasons: 

•	 There are more than a dozen relevant individual epidemiology studies which are of 

reasonable methodologic quality 

•	 Most of these analyses were specifically designed to test hypotheses related to menthol’s 

health effects 

•	 These studies directly compared health risks between smokers of menthol and nonmenthol 

cigarettes 

•	 There are multiple studies of different designs, which were done by different researchers 

•	 Most of the studies had large sample sizes and good representation of menthol smokers 

•	 Most studies controlled for the most relevant potential confounding factors and many 

performed race-specific and sex-specific analyses 

•	 Several different health effects have been considered, most importantly, lung cancer and 

cancers of the upper aerodigestive tract; lung cancer is the most common smoking-related 

cancer, and cancers of the lung, esophagus, larynx, and oropharynx are the cancers most 

strongly associated with smoking 

•	 There is also a recent, high-quality meta-analysis that examined the outcome of lung cancer 

•	 Cardiovascular disease and respiratory disease have also been considered 

•	 Especially important is the fact that epidemiology studies effectively incorporate all aspects 

of smoking behavior, including those that are not easily quantified 

Given the number of studies and overall methodologic quality, there is adequate information to 

allow for a causal determination as outlined by the Surgeon General’s framework (USDHHS 2004). 

As noted previously, the “evidence is suggestive of no causal relationship” between menthol in 

cigarettes and chronic disease risk compared to nonmenthol cigarettes. 

1 Other Surgeon General reports that have relied on epidemiology include those published in 1964, 1967, 1968, 1969, 

1971, 1972, 1973, 1974, 1975, 1977-78, 1979, 1980, 1981, 1982, 1983, 1984, 1985, 1986, 1989, 1990, 1992, 1998, 2001, 

2006. 

Chapter 3 

39
 

As will be discussed in detail in the next section, these studies consistently show that the health risks 

associated with smoking menthol cigarettes are no greater than those associated with smoking 

nonmenthol cigarettes. The consistency of these studies is striking, and helps to rule out even small 

elevations in risk. This is important, as the only way to avoid drawing erroneous conclusions is to 

evaluate the overall pattern of study results, as well as individual study findings. 

Studies on the health risks of menthol cigarettes were first proposed in the late 1980s when 

epidemiologists noticed two striking facts. First, incidence rates of lung cancer were higher among 

African American men than White men, and incidence rates of esophageal cancer were much higher 

among African Americans of both sexes compared to Whites. Second, African American smokers 

strongly favored menthol cigarettes compared to Whites; by the mid-1980s, approximately 62% of 

African American smokers preferred menthol cigarettes compared to 23% of Whites (Hebert and 

Kabat 1988, 1989). However, as described above, large epidemiology studies that assessed the 

association between type of cigarette smoked (menthol versus nonmenthol) and risk of lung cancer 

(the most common smoking-related cancer) did not support this hypothesis. A smaller number of 

studies of other tobacco-related cancers with higher incidence among African Americans compared 

to Whites also did not provide evidence of a menthol effect. As will be demonstrated in the 

following section, higher rates of certain smoking-related diseases among African Americans 

compared to Whites cannot be explained by the greater preference for menthol cigarettes among 

African Americans. It is notable that the higher rate of lung cancer among African Americans, both 

men and women, is a phenomenon that has also been observed among those who have never 

smoked, suggesting that constitutional differences or factors other than cigarette preference underlie 

these differences (Thun et al. 2008). 

PROPER INTERPRETATION OF EPIDEMIOLOGY FINDINGS IS ESSENTIAL 

Because epidemiology serves as the foundation for understanding the health effects of menthol 

smoking, it is essential to interpret the findings of these studies properly and objectively. Review of 

TPSAC meeting minutes and FDA staff presentations to TPSAC suggests that epidemiology 

findings are sometimes not interpreted correctly. Thus, before discussing the relevant studies, it may 

be helpful to review the discussion of some of the most fundamental concepts provided in 

Chapter 1. 

EPIDEMIOLOGY SHOWS NO DIFFERENCE IN RISK OF TOBACCO-RELATED 

DISEASE BETWEEN MENTHOL AND NONMENTHOL SMOKERS 

The epidemiologic evidence provides a compelling basis to conclude that the risk of cancer and 

other smoking‐related diseases is not materially affected by the use of menthol in cigarettes. To 

date, 13 published studies, a meta-analysis, and two unpublished studies have directly compared the 

risk of smoking‐related diseases between menthol and nonmenthol cigarette smokers. These studies 

have addressed the following endpoints: lung cancer, esophageal cancer, oropharyngeal cancer, 

other smoking-related cancers (including those of the upper aerodigestive tract, pancreas, kidney, 

urinary tract and uterine cervix), as well as various other cardiac and lung conditions (coronary 

calcification, decline in pulmonary function, and mortality due to coronary heart disease, 

cardiovascular disease, and all causes). The overwhelming weight of the evidence shows no 

Chapter 3 

40
 

 

 

 

 

 

difference between the disease risks of smoking menthol cigarettes and nonmenthol cigarettes. 

Consequently, the claims that this literature is equivocal or mixed are scientifically invalid; according 

to the Surgeon General’s framework for assessing causality, the “evidence is suggestive of no 

causal relationship.” Each study is discussed briefly below, and summarized in detail in the 

attached Tables 3-9 through 3-13. 

Lung Cancer 

Lung cancer is the most common smoking-related cancer and the one most strongly associated with 

cigarette smoking. According to the American Cancer Society, there were an estimated 222,500 new 

cases of lung cancer in the U.S. in 2010 (ACS 2010). Eight individual epidemiology studies and one 

meta-analysis have addressed this endpoint (Kabat and Hebert 1991, Sidney et al. 1995, Carpenter 

et al. 1999, Brooks et al. 2003, Stellman et al. 2003, Jöckel et al. 2004, Murray et al. 2007, Etzel et al. 

2008, Lee 2011). All but one of these studies reported no significant differences between menthol 

versus nonmenthol smokers in risk of lung cancer. Only one study (Sidney et al. 1995) reported a 

statistically elevated risk (relative risk=1.45; 95% CI:1.03‐2.02) for lung cancer in a single subgroup 

(men but not women) who smoked menthol cigarettes compared those who smoked nonmenthol 

cigarettes. Because this finding was not replicated in other studies, the authors later stated that it 

may have been “merely a chance finding” (Friedman et al. 1998). 

While all epidemiology studies have limitations, the available studies of menthol smoking and lung 

cancer are well-designed and well-analyzed, for the most part have adequate numbers of lung cancer 

cases, and are able to detect effects of smoking parameters, including amount smoked, duration of 

smoking, and smoking cessation. This literature provides no evidence that smoking menthol 

cigarettes, as opposed to smoking nonmenthol cigarettes, increases the risk of lung cancer. The 

consistency of the studies is impressive. There is no consistent evidence of an effect of menthol in 

the study populations overall or in subgroups: males or females, or African Americans or Whites. 

Each study is described below and summarized in more detail in Table 3-1 (including all relevant risk 

estimates). 

Kabat and Hebert (1991) examined risk of lung cancer among current smokers of menthol or 

nonmenthol cigarettes in a hospital-based case-control study. The study involved a large number of 

subjects (1,044 cases, 1,324 controls), with a substantial number of menthol smokers (from 24-37%, 

depending on sex and race). The investigators obtained detailed information on types of tobacco 

products used throughout life, and considered many important confounders in their analysis 

(inhalation, race, body mass index (BMI), age, education, cigarettes/day, and duration of smoking). 

No statistically significant associations were observed between either short-term (1-14 years) or longterm (15+ years) menthol use and lung cancer for either men or women in logistic regression 

analyses adjusting for covariates. There was also no indication of any association with specific 

histological types of lung cancer. The authors concluded that “Use of mentholated cigarettes was 

not associated with increased risk of lung cancer or of specific histological types of lung cancer in 

this study.” 

Sidney et al. (1995) examined menthol cigarette use and lung cancer incidence among 11,761 

participants in the Kaiser Permanente Medical Care Program who were current smokers with a selfreported smoking history of 20 or more years. There were 93 cases of lung cancer among 3,654 

Chapter 3 

41
 

menthol smokers and 225 cases of lung cancer among 8,107 nonmenthol smokers over a mean of 

approximately 8 years of follow-up. There were no statistically significant elevations in risk 

associated with any duration of menthol smoking (1-9; 10-19; or ≥20 years). However, there was a 

modest elevation in the risk of lung cancer associated with menthol cigarette use by men only (all 

races combined) (RR=1.45; 95% CI:1.03-2.02) after adjustment for age, race, education, 

cigarettes/day, and smoking duration. A similar finding was not seen for women (RR=0.75; 95% 

CI:0.51-1.11), despite the greater preference for menthol among women as opposed to men (34.6% 

vs. 27.4%, respectively). The authors concluded that: “This study suggests that there is an increased 

risk of lung cancer associated with mentholated cigarette use in male smokers but not in female 

smokers.” 

Importantly, a later study by some of the same authors (including Sidney) acknowledged that the 

elevated risk of lung cancer seen in this study among male menthol smokers may have been merely a 

chance finding, since it was not seen in women and has not been replicated elsewhere (Friedman et 

al. 1998 discussed below). 

Carpenter et al. (1999) conducted a case-control study comparing 337 incident cases of lung cancer 

with 478 population controls who were current or former smokers. Among African American 

subjects, 85 men and 101 women had ever smoked menthols; among Caucasians, 66 men and 122 

women had ever smoked menthols. The adjusted odds ratio for exclusive menthol smokers was not 

different from that of nonmenthol smokers (OR=1.04; 95% CI:0.62-1.75), after adjustment for age, 

sex, race, total pack-years, and years since quitting smoking. Similarly, odds ratios calculated by sex, 

race, and duration of menthol cigarette smoking (up to 32+ pack-years) revealed no statistically 

significant differences between menthol and nonmenthol cigarette smokers. The authors concluded: 

“Our results suggest that the lung-cancer risk from smoking mentholated cigarettes resembles the 

risk from smoking non-mentholated cigarettes.” 

Brooks et al. (2003) examined data from a large, multi-hospital case-control study to examine 

whether smoking menthol cigarettes might be associated with higher lung cancer risk as compared 

to smoking nonmenthol cigarettes. The analysis was restricted to 643 cases and 4,110 controls for 

whom cigarette brand information could be identified for at least 60% of the total duration of 

smoking. There were 114 ever smokers of menthol cigarettes among the cases and 1,093 among the 

controls. Overall, menthol smokers did not have an elevated risk of lung cancer relative to 

nonmenthol smokers (OR=0.89; 95% CI:0.69-1.14), after adjustment for sex, age, race, year of 

interview, number years smoking, cigarettes/day, years since quitting, and proportion of years 

smoking filter cigarettes. Odds ratios were also close to 1.0 in separate analyses of male, female, 

Black, and White subjects that considered duration of smoking menthols (1-15 years >15 years). 

The authors concluded: “The results of this study do not support the hypothesis that smoking 

menthol cigarettes increases the risk of lung cancer relative to smoking nonmenthol cigarettes.” 

Stellman et al. (2003) conducted a hospital-based case-control study to investigate whether risk of 

lung cancer differs between Blacks and Whites for equivalent exposure to tobacco smoke. The 

study was large, including 3,031 White and 417 Black cases with lung cancer, and 8,151 control 

subjects. Smoking of menthol cigarettes was one of several variables examined; the prevalence of 

menthol smoking ranged from 13-24% among White subjects and was substantially higher (41-52%) 

among Black subjects. Among current smokers, the ORs associated with menthol smoking were 

almost the same as those associated with nonmenthol smoking for White men, Black men, White 

women, and Black women (after adjustment for age, education, BMI, and pack-years). The authors 

Chapter 3 

42
 

 

 

concluded: “Smokers of flavored cigarettes were at no greater risk for lung cancer than were 

smokers of unflavored brands.” 

Jöckel et al. (2004) provided a brief description (abstract only) of a hospital-based case-control 

study of menthol cigarette smoking and lung cancer in a White population in Germany (1,004 cases 

and 1,004 controls matched for region, sex, and age). After adjustment for total amount of tobacco 

smoking, smoking menthol cigarettes was not associated with increased risk of lung cancer. The 

authors stated: “The present study gives no indication for an additional risk [of lung cancer] of ever 

smoking menthol cigarettes if total amount of smoking is taken into account.” It should be noted 

that relatively few subjects had ever smoked menthol cigarettes (5% of cases and 4% of controls). 

Murray et al. (2007) described an analysis of data from the Lung Health Study, a clinical trial of 

smoking cessation that included 5,887 current or former smokers with mild to moderate airway 

obstruction. About 20% had smoked menthol cigarettes at baseline. Over 14 years of follow-up, 

there were 240 deaths due to lung cancer. The hazard ratio associated with smoking menthol 

cigarettes at baseline was not elevated (RR=0.96; 95% CI:0.70-1.32) compared to nonmenthol 

cigarettes. The authors concluded: “We found no evidence in our data that mentholation of 

cigarettes is an attribute that contributes to the health risks of smoking.” 

Etzel et al. (2008) developed and validated a lung cancer prediction model specific to African 

Americans using data from a case-control study of lung cancer (491cases, 497 controls). There was a 

high prevalence of menthol use among these African American subjects (41% of cases, 47% of 

controls), although it was just one of many factors evaluated. Risk of lung cancer was not elevated 

among current or former menthol smokers (ORs were 0.69 and 0.99, respectively) compared to 

smokers of nonmenthol cigarettes, after adjustment for age, sex, and smoking status. The authors 

reported that their data were consistent with a possible “protective” effect of menthol cigarettes 

relative to nonmenthol cigarettes for current smokers. The authors stated: “...we observed no 

significant risks of lung cancer among former or current smokers who reported smoking 

mentholated cigarettes . . .” 

This study is particularly important because it shows that when the range of risk factors is 

considered for inclusion in a “prediction equation” for lung cancer in African Americans, a number 

of factors make a significant contribution and are retained in the final equation (smoking status, 

pack-years of smoking, age at smoking cessation, exposure to asbestos or dusts, and history of 

COPD or hay fever); however, menthol did not contribute to risk of lung cancer in the prediction 

equation and was not retained in the equation. 

Lee (2011) recently conducted a meta-analysis that examined the relationship between smoking 

menthol cigarettes and risk of lung cancer. Meta-analysis is a technique for statistically combining 

the results of a number of individual studies to obtain a summary risk estimate that is more precise 

because of the larger sample size. 

A systematic search of the literature revealed only the eight studies of lung cancer described 

individually above. Lee (2011) described these studies as “...generally of good quality, with valid 

cases and controls, and appropriate adjustment made for age, gender, race and smoking habits.” 

Chapter 3 

43
 

 

 

Combining the data from the eight studies yielded an overall adjusted RR of 0.93 (95% CI:0.84­

1.02). In subgroup analyses, there was also no evidence of increased risk among men or women 

separately, among Blacks or Whites separately, among ever smokers, current smokers, or former 

smokers, or among long-term smokers of menthol cigarettes (15+ years). In fact, RRs were almost 

all 1.0 or less. Lee (2011) concluded: “The data do not suggest any effect of mentholation on lung 

cancer risk. While some study weaknesses exist, the epidemiological evidence is consistent with 

mentholation having no effect on the lung carcinogenicity of cigarettes.” 

Esophageal Cancer 

Two publications (one of which is a letter to the editor) describing the same hospital-based casecontrol study (Hebert and Kabat 1988, 1989) found no evidence that smoking menthol cigarettes is 

associated with increased risk of esophageal cancer (see Table 3-2). The study involved 303 cases 

and 453 controls, all of whom were current smokers. The number of subjects who had ever smoked 

menthol cigarettes was small: 45 among the cases and 66 among the controls. Logistic regression 

analyses revealed no significant increase in ORs associated with smoking menthol cigarettes (either 

for <10 years or for >10 years) among men, after adjustment for covariates (education, religion, 

alcohol consumption, race, cigarettes/day, and smoking duration). Among women who smoked 

menthol cigarettes, adjusted ORs were elevated (1.5 for <10 years, 2.3 for >10 years), but were not 

statistically significant. The authors concluded: “Our results do not support the hypothesized 

relationship between menthol cigarette smoking and oesophageal cancer.” Given the small number 

of cases (especially African Americans), the authors recommended that additional studies of 

adequate size be performed. 

Oropharyngeal Cancer 

A single study (a hospital-based case-control study conducted by Kabat and Hebert in 1994) found 

no evidence that smoking menthol cigarettes was associated with increased risk of oropharyngeal 

cancer (see Table 3-3). Detailed information on lifetime smoking habits and other variables was 

obtained for 276 cases and 1,256 controls, all of whom were current smokers. Menthol use was not 

common among these subjects; only 5% had smoked menthol cigarettes exclusively, and 24% had 

smoked both menthol and nonmenthol cigarettes. Odds ratios for smoking menthol cigarettes for 

either 1-14 or >15 years were not elevated either for men or for women, after adjustment for 

covariates of age, education, filter use, race, BMI, hospital, alcohol, and cigarettes/day. Additional 

analyses examined risk by anatomic site within the oropharynx; menthol use was positively 

associated only with pharyngeal cancer in men, but the elevation in risk was small and not 

statistically significant. The authors concluded: “These results indicate that the use of mentholated 

cigarettes is unlikely to be an important independent factor in oropharyngeal cancer.” 

Other Smoking-Related Cancers 

In a large prospective study of data from the Kaiser Permanente Medical Care Program in 

California, Friedman et al. (1998) investigated whether their previous finding of a higher risk of lung 

cancer among men who smoked menthol cigarettes compared to men who smoked nonmenthols 

(reported by Sidney et al. 1995) also applied to other smoking-related cancers (see Appendix Table 

3-12). The analysis involved 11,761 subjects who were current smokers with a smoking history of 

20 or more years. There were 69 cases of lung cancer among 3,654 menthol smokers and 212 cases 

of lung cancer among 8,106 nonmenthol smokers over more than 10 years of follow-up. 

Chapter 3 

44
 

 

 

 

 

Smoking menthol cigarettes was not associated with an increased rate of cancer in either sex or in 

any of the sites examined (upper aerodigestive, pancreas, renal adenocarcinoma, other urinary tract, 

and uterine cervix). In fact, for 9 of the 11 tumor sites examined, the point estimates associated with 

menthol use were below 1.0. For all smoking-related cancers combined, the menthol/nonmenthol 

rate ratio was 0.76 (95% CI:0.52-1.11) for men and 0.79 (95% CI:0.53-1.18) for women. The 

authors concluded: “Risk was not increased among persons who currently smoked mentholated 

compared with plain cigarettes for all of the non-lung smoking-related cancers combined or for 

most sites studied.” Referring to the Sidney et al. 1995 publication, they further stated: “...the 

association of mentholation with lung cancer in this study population may be merely a chance 

finding, particularly as it was absent in women and has not been replicated elsewhere.” 

Coronary Calcification and Lung Function 

Pletcher and colleagues (2006) investigated whether smoking menthol cigarettes had a greater effect 

on the development of atherosclerotic disease and changes in pulmonary function than did smoking 

nonmenthol cigarettes among subjects enrolled in the Coronary Artery Risk Development in Young 

Adults Study (CARDIA) (see Appendix Table 3-13). The prospective study followed 5,115 subjects 

for 15 years; of these, 972 smoked menthol cigarettes and 563 smoked nonmenthols at baseline. 

Smokers of menthol cigarettes and those of nonmenthol cigarettes did not differ in coronary 

calcification (p=0.75) or decline in pulmonary function (p=0.88); the authors stated that the two 

types of cigarettes seem to be equally harmful with respect to these endpoints. The authors 

concluded: “Mentholation of cigarettes does not seem to explain disparities in ischemic heart 

disease and obstructive pulmonary disease between African Americans and European Americans in 

the United States . . .” 

Mortality Due to Cardiovascular Disease 

Murray et al. (2007) reported on mortality due to various causes in the Lung Health Study, a clinical 

trial of smoking cessation that included 5,887 current or former smokers with mild to moderate 

airway obstruction (see Appendix Table 3-13). About 20% had smoked menthol cigarettes at 

baseline. Over 14 years of follow-up, there were 77 deaths due to coronary heart disease (CHD), 

163 deaths due to cardiovascular disease, and 731 deaths due to any cause. The authors reported no 

differences between menthol and nonmenthol smokers in risk of death due to CHD (HR=1.31; 

95% CI:0.77-2.22), cardiovascular disease (HR=1.03; 95% CI:0.70-1.52), or any cause (HR=0.99; 

95% CI:0.83-1.20). The authors concluded: “We found no evidence in our data that mentholation 

of cigarettes is an attribute that contributes to the health risks of smoking.” However, they 

speculated that the hazard ratio associated with smoking menthol cigarettes and CHD was of 

sufficient magnitude that it might reach statistical significance in a study with a larger sample size. 

Chapter 3 

45
 

 

 

 

ADDITIONAL UNPUBLISHED EPIDEMIOLOGY STUDIES 

In addition to the published, peer-reviewed articles described above, two unpublished analyses 

prepared at the request of the FDA and submitted to TPSAC are relevant. Because these have not 

been peer-reviewed, they must be considered to represent a lower level of evidence than the studies 

described above. 

Stellman and Neugut (unpublished) used existing data from a hospital-based, multi-center casecontrol study to evaluate the relationship between menthol smoking and risk of five tobacco-related 

cancers (including oral cavity, esophagus, larynx, lung, and bladder). Their analysis involved 5,771 

cases with various cancers and 7,906 controls. Menthol smoking was not associated with elevations 

in risk of any of these cancers, compared to nonmenthol smoking. In fact, all odds ratios associated 

with menthol smoking were 1.0 or lower. The authors concluded that their data “... do not provide 

evidence of increased risk of lung or other cancers in smokers of menthol cigarettes over and above 

the well-known risks of cigarette smoking.” While they suggested that the small numbers of cases of 

some of the cancers may have limited their ability to detect small effects due to menthol, they 

conceded that a menthol “effect,” if any, is unlikely to be of substantive magnitude in comparison to 

the effects of smoking, generally. 

Hyland and Kasza (unpublished) used data from two hospital-based case-control studies to 

evaluate the association between menthol smoking and lung diseases. One study involved 503 lung 

cancer cases and 1,081 controls from 1957-1965; the other involved 144 lung cancer cases, 238 cases 

of COPD/emphysema, and 58 cases of premalignant lung disease (defined as being at high risk for 

lung cancer, e.g., having long pack-year histories) from 2005-2010. The findings of the more recent 

cases are interesting, as their smoking behaviors and cigarette brand styles are most like those of the 

contemporary U.S. smoking population. 

Using the conventional statistical threshold of p=0.05, the authors did not find any main 

effects (i.e., menthol smoking was not associated with significantly elevated risk of the various 

diseases compared to nonmenthol smoking). For lung cancer, the odds ratio associated with 

menthol smoking (men and women combined) in the 2005-2010 sampling, adjusted for age, sex, 

race, smoking behaviors and smoking duration was 0.76 (95% CI:0.41-1.44). The authors stated 

that: “ . . . no clear pattern of risk was observed between menthol smokers in the populations and 

disease endpoints examined.” Although they found no main effect of menthol, the authors 

highlighted several second-order findings (i.e., among subgroups) that achieved statistical 

significance according to a more liberal p value of <0.10. They cited three odds ratios that gave 

“slight suggestions” of elevated risk, although all of the confidence intervals included 1.0, and thus 

are not statistically significant using traditional standards. Critical review of this unpublished study 

shows that it is another null study that is consistent with the vast majority of published studies in 

finding no significantly elevated risks associated with menthol cigarette smoking. 

Chapter 3 

46
 

 

 

EPIDEMIOLOGY STUDIES ARE SUPPORTED BY ECOLOGICAL DATA 

As noted above, it was noticeable differences between African Americans and White smokers in 

rates of certain tobacco-related cancers that first drew attention to the possible health effects of 

menthol cigarettes. Consequently, it is of interest to compare rates of these cancers over the past 20 

years (using NCI’s Surveillance Epidemiology and End Results (SEER) data) to trends in menthol 

preference. 

In 1989, the age-adjusted incidence rate of lung cancer per 100,000 was much higher in Black men 

than in White men (142.8 vs. 97.1, or a 47.1% excess in Blacks), but was only slightly higher in Black 

women compared to White women (51.4 vs. 47.2, or a 9% excess in Blacks) (Altekruse 2010). Rates 

had changed dramatically by 2007. At that time, age-adjusted incidence had decreased to 93.5 for 

Black men and to 69.1 for White men. In other words, there was a 35% decrease in the incidence 

rate among Black men and a 28% decrease in White men. In contrast, rates among women were 

slightly higher in 2007: 53.4 for Black women and 54.1 for White women. Thus, in spite of the 

higher preference for menthol cigarettes among smokers who are Black or female, the rate of lung 

cancer has decreased among Black men but remained stable among Black and White women. This 

fails to support a relationship between menthol cigarette smoking and lung cancer, especially among 

Black men. 

Examination of esophageal cancer incidence rates also fails to support an association with the use of 

menthol cigarettes. In 1989, the age-adjusted incidence rate of esophageal cancer per 100,000 was 

greater in Black men compared to White men (17.3 vs. 6.2) and in Black women compared to White 

women (5.4 vs. 2.0). By 2007, the rate had declined in Black men to 7.9, while the rate among White 

men had increased slightly to 8.2. Incidence of esophageal cancer also decreased dramatically in 

Black women (to 2.8), while the rate in White women remained unchanged. The dramatic decline in 

esophageal cancer among Black men and women, but not White men or women, provides no 

support for the notion that menthol plays any role in the etiology of this cancer. 

While the limitations of using ecologic data to make causal inferences are well-known, and while it 

would be desirable to distinguish between squamous cell cancer and adenocarcinoma of the 

esophagus, one can still conclude that the SEER data cited above comparing changes in the rates of 

lung and esophageal cancer among Blacks and Whites over the past 20 years are not suggestive of 

any contribution of menthol to the risk of these diseases. 

EPIDEMIOLOGY ALSO SHOWS NO SEX-SPECIFIC OR RACE-SPECIFIC 

ASSOCIATIONS 

Despite the fact that the substantial body of epidemiology studies has consistently found that 

menthol cigarette smoking is not associated with increased risk of any of the diseases evaluated, 

there appears to be the perception that, if one looks hard enough, one may find an elevated risk 

among a specific subgroup (either race or sex) of the population. The data do not support this 

notion, as described below. 

It is important to remember that to avoid drawing erroneous conclusions, it is essential to evaluate 

the overall pattern of study findings, their consistency, and study quality. Isolated elevated risk 

estimates, especially when not statistically significant, should not be given undue weight. When 

Chapter 3 

47
 

 

 

 

 

 

 

 

 

many analyses are conducted, statistically significant associations can arise by chance (i.e., it is to be 

expected that, on average, 1 in 20 results (or 5%) could be statistically significant due to chance 

alone, when the conventional criterion for statistical significance of 5% is used) (Fleiss 2003). The 

only safeguard against giving isolated results undue weight is to focus on the overall pattern of 

results. Doing so leads to the conclusion that there are no subgroups of smokers that have 

increased disease risks due to menthol in cigarettes. 

Sex-Specific Associations 

Much has been made of the single statistically significant finding in this literature: that by Sidney 

et al. (1995) in an analysis of the Kaiser Permanente cohort. As discussed above, those investigators 

found a modest elevation in risk of lung cancer (RR=1.45; 95% CI:1.03-2.02) among men (all races 

combined) who smoked menthol cigarettes, but not women (RR=0.75; 95% CI:0.51-1.11), despite 

the greater preference for menthol use among women. The authors considered this a suggestive 

finding, but a later analysis of smoking-related cancers in this cohort by some of the same 

investigators did not support this suggestion. 

That later study (Friedman et al. 1998) examined the relationship between menthol smoking and 

other smoking-related cancers. It found that menthol smokers did not have a significantly increased 

risk of all of the non-lung smoking related cancers combined, or of any of the individual sites 

studied. The authors (including Sidney) concluded that the earlier finding by Sidney et al. may have 

been merely a chance finding, since it was not seen in women and has not been replicated elsewhere. 

Numerous studies have examined risks among men and women menthol and nonmenthol smokers 

and found that neither sex had elevated risk of several important outcomes (i.e., Kabat and Hebert 

1991, Kabat and Hebert 1994, Carpenter et al. 1999, Brooks et al. 2003, Stellman et al. 2003, 

Friedman et al. 1998). 

Information presented to TPSAC2 has suggested that there might be a menthol x disease x sex 

interaction, citing some point estimates that were >1.0, although not statistically significant. 

Specifically, the supporting evidence cited included: 

•	 The finding by Carpenter et al. (1999) of an odds ratio of 1.48 (95% CI:0.71-3.05) for lung 

cancer associated with 32+ pack-years of menthol smoking among men; 

•	 The finding by Kabat and Hebert (1994) of an odds ratio of 1.7 (0.8-3.4) for pharyngeal 

cancer associated with ever menthol smoking among men; and 

•	 The finding by Hebert and Kabat (1989) of an odds ratio of 2.30 (95% CI:0.93-5.72) for 

esophageal cancer associated with >10 years of smoking menthols among women. 

This suggestion of an interaction is unfounded for a number of reasons. First, none of the results is 

statistically significant. Second, there is no consistent pattern. In the first two instances, it appears 

that males have a higher risk, whereas in the third instance, females appear to have a higher risk. 

Third, if certain selected elevated risks are highlighted, similar focused discussion of reports of 

relative risks that are below 1.0 (and there are many in this literature) must also be considered. 

2 This information was provided to TPSAC in a presentation made in March 2010 and a white paper submitted in 

October 2010 (both by Dr. Allison Hoffman, NIDA/NIH). 

Chapter 3 

48
 

Rather than cherry-picking individual results, it is more appropriate to conduct a meta-analysis to 

determine the overall association based on all available studies and to look at consistency of results 

in subgroups. As noted previously, none of the ORs reported in the meta-analysis on lung cancer by 

Lee (2011) associated with menthol smoking (by race, sex, and length of menthol smoking) were 

statistically significant, and virtually all were less than 1.0. 

Race-Specific Associations 

TPSAC has been specifically charged with evaluating the impact of menthol cigarettes on African 

Americans, Hispanics, and other racial and ethnic minorities. With respect to smoking-related 

diseases, the epidemiology literature mainly provides risk estimates among African American and 

White smokers. This has been the focus of interest for two reasons: African Americans have higher 

rates of certain smoking-related cancers than Whites, and the percentage of African American 

smokers who prefer menthol cigarettes (69%) is much higher than that of White smokers who 

prefer menthols (22%) (Giovino et al. 2004). As was noted in Chapter 2 of this report on the 

demographics of menthol use, the number of White menthol smokers greatly exceeds the number of 

African American menthol smokers. According to NSDUH (2004-2008), 53% of menthol smokers 

are White and 30% are African American (Caraballo unpublished). 

However, not a single study has shown that African Americans who smoke menthols have 

statistically significant elevations in risk of any of the diseases examined (compared to African 

Americans who smoke regular cigarettes), as detailed in Appendix Tables 3-9 to 3-13. The bulk of 

the data on race come from studies that examined the endpoint of lung cancer. These studies drew 

the following conclusions: 

•	 Carpenter et al. (1999): In this case-control study, odds ratios for lung cancer associated 

with menthol smoking among African Americans (either >1-15, 16-31, or 32+ pack years) 

were all less than 1.0. The authors concluded: “The lung-cancer risk associated with 

menthol smoking was similar to that for exclusive nonmentholated cigarette smoking both in 

the total sample and within ethnic groups.” 

•	 Brooks et al. (2003): In this case-control study, odds ratios for lung cancer associated with 

menthol smoking among Blacks (1-15 and >15 years) relative to nonmenthol smoking were 

not statistically significant. The authors stated: “In separate analyses of men, women, 

Blacks, and Whites, long-term use of menthol cigarettes was not associated with an increase 

in lung cancer relative to exclusive use of nonmenthol cigarettes.” 

•	 Stellman et al. (2003): Odds ratios for lung cancer associated with menthol smoking were 

1.34 (95% CI:0.79-2.29) for Black men and 0.79 (95% CI:0.41-1.54) for Black women. The 

authors noted: “While Black smokers in our study were more likely to choose menthol than 

nonmenthol brands, our data provide no evidence that menthol cigarettes per se produce 

greater lung cancer risk than do nonmenthol brands.” 

•	 Etzel et al. (2008): In a case-control study of only African American subjects, neither current 

nor former smokers of menthol cigarettes had increased risk of lung cancer (odds ratios were 

0.69 and 0.99). They concluded: “We observed no significant risks of lung cancer among 

former or current smokers who reported smoking mentholated cigarettes and our data 

suggested a possible protective effect of mentholated cigarettes for current smokers.” 

Chapter 3 

49
 

•	 Lee (2011): This recent analysis found no significantly increased risk of lung cancer among 

Blacks who had ever smoked menthol cigarettes (OR=0.96; 95% CI:0.80-1.15) or those who 

had long-term use (15+ years) of menthol cigarettes (OR=1.08; 95% CI:0.79-1.47). Lee 

(2011) concluded: “The data do not suggest any effect of mentholation on lung cancer risk.” 

He also stated: “There is also no evidence of an increase in men or women separately, in 

Blacks or Whites separately, or in estimates for ever smokers, current smokers, or former 

smokers.” And finally: “Higher lung cancer rates in Black men cannot be due to their 

greater preference for mentholated cigarettes.” 

Two studies provide some data on other health outcomes; again, these did not find any significant 

elevations in risks for African American menthol smokers: 

•	 Friedman et al. (1998) did not present much race-specific information in their analysis of the 

Kaiser Permanente cohort, but they did discuss prostate cancer because of its higher 

incidence rate among African Americans. They found no statistically significant excess risk 

associated with mentholation in analyses not controlled for race (rate ratio=1.15; 95% 

CI:0.82-1.62), and in Cox proportional hazards regression controlling for age and race (rate 

ratio=1.12; 95% CI:0.80-1.58). 

•	 Pletcher et al. (2006): In the CARDIA longitudinal cohort study, there was no association 

between menthol exposure and coronary calcification among either European Americans or 

African Americans. With respect to pulmonary function, European Americans tended to 

have larger declines associated with menthol cigarettes than did African Americans. The 

authors concluded: “Mentholation of cigarettes does not seem to explain disparities in 

ischemic heart disease and obstructive pulmonary disease between African Americans and 

European Americans in the United States . . .” 

TPSAC panel members are concerned that it may be difficult to interpret studies of menthol 

smoking and lung cancer, given that baseline rates of lung cancer differ by race, sex, and smoking 

status. This concern is unfounded, as every study of menthol smoking and lung cancer has 

considered race in some way. Some studies have been limited to only one race; for example, some 

compared African American menthol smokers to African American nonmenthol smokers (e.g., Etzel 

et al. 2008). In those studies that had adequate numbers of subjects of each race, separate analyses 

were conducted among Whites and African Americans (e.g., Brooks et al. 2003, Carpenter et al. 

1999, Stellman et al. 2003). Other studies combined races but adjusted for race (e.g., Kabat and 

Hebert 1991, Murray et al. 2007, Sidney et al. 1995). This adjustment can be made through the study 

design (i.e., by matching cases and controls on race) or through statistical adjustment (by including a 

term for race in the multivariate model). 

Differences in incidence of lung cancer by sex have been handled in the same manner (either sexspecific analyses, matching or statistical adjustment). Finally, all of these studies are limited to 

smokers (current or former). This analytic approach avoids any baseline difference in lung cancer 

risk among never smokers of different races. By focusing on menthol versus nonmenthol, the 

studies appropriately isolate the potential effect of menthol. 

TPSAC members have pointed out that African American menthol smokers smoke fewer cigarettes 

per day than nonmenthol smokers, but have contended that those smokers do not have lower 

biomarker levels or reduced incidence of smoking-related diseases. TPSAC members have theorized 

Chapter 3 

50
 

 

 

that African American smokers smoke their fewer cigarettes more intensely, thus increasing their 

exposure. However, a review of the biomarker studies (discussed in Chapter 3B) and epidemiology 

studies do in fact suggest lower levels of exposure and lower levels of disease risk, although these 

findings are not statistically significant. For example, Etzel et al. (2008) studied lung cancer rates 

among African American smokers and found that current menthol smokers had lower odds ratio 

(OR=0.69; 95% CI:0.46-1.03) for lung cancer compared to current nonmenthol smokers, which is 

what one would expect with smoking fewer cigarettes per day. 

CONCLUSION 

This review of available epidemiology studies clearly demonstrates that smokers of menthol 

cigarettes are at no greater risk of developing chronic smoking-related diseases than are nonmenthol 

smokers. Importantly, with more than a dozen published studies as well as a meta-analysis of the 

eight studies on lung cancer, there are sufficient data available to draw this conclusion with 

confidence. Furthermore, the literature is very consistent, which rules out the possibility that there 

are even small elevations in risk associated with menthol cigarettes. While all epidemiology studies 

have limitations, the available studies are well-designed and well-analyzed, for the most part have 

adequate numbers of cases, and are able to detect effects of smoking parameters. The diseases 

studied include lung cancer (the most common smoking-related cancer), cancers of the upper 

aerodigestive tract (esophagus, larynx, oropharynx), and other cardiac and lung outcomes. The 

studies provide data on risks specific to both sexes and to both Whites and African Americans, and 

do not find that there is any subpopulation that is especially susceptible to effects from menthol 

smoking. Thus, it can be concluded that, according to the Surgeon General’s framework for 

assessing causality, the “evidence is suggestive of no causal relationship” between the use of 

menthol cigarettes and increased smoking-related disease risk above that caused by use of 

nonmenthol cigarettes. 

Chapter 3 

51
 

 

 

CHAPTER 3B. 

MENTHOL IN CIGARETTES HAS NO MEANINGFUL EFFECT ON BIOMARKERS 

OF EXPOSURE AND POTENTIAL HARM 

As described above, epidemiology studies show no significant difference in the risk of smokingrelated disease among menthol smokers as compared to nonmenthol smokers. Consistent with the 

epidemiology, biomarker studies show that menthol in cigarettes does not increase exposure of 

smokers to smoke constituents, including some constituents that are believed to cause disease. 

A considerable number of soundly-designed and well-conducted studies comparing biomarkers of 

exposure and potential harm among menthol smokers and nonmenthol smokers have been 

conducted. Sensitive methods are currently available to measure biomarkers of smoke constituent 

exposures in body fluids (e.g., saliva, blood, urine) of smokers, primarily as metabolites of those 

constituents. A number of biomarkers of potential harm that may be related to chronic disease risk 

have also been investigated and reported, although they are at a lesser state of development and 

validation. 

To evaluate the hypothesis that menthol in cigarettes affects exposure to smoke constituents, either 

directly or by influencing the manner in which cigarettes are smoked, various researchers have 

examined the relationship between menthol cigarettes and biomarkers of exposure, metabolism and 

potential harm. Overwhelmingly, the data show that biomarkers of exposure are not significantly 

different among menthol smokers compared with nonmenthol smokers. Similarly, menthol does 

not appear to meaningfully impact exposure to putative biomarkers of potential harm. These 

biomarker studies integrate and reflect the combined impacts of all the diverse elements of complex 

human smoking behaviors, including cigarettes smoked per day, puffing intensity (puff number, 

volume, interval and duration), amount of smoke inhalation, the percent of the cigarette smoked and 

the amount of filter ventilation hole blocking, if any. According to the Surgeon General’s 

framework for assessing causality, a thorough assessment of the available scientific evidence from 

biomarkers studies leads to the conclusion that the “evidence is suggestive of no causal 

relationship” between smoking menthol cigarettes and increases in biomarkers of exposure to 

smoke constituents or their metabolites or biomarkers of potential harm as compared to smoking 

nonmenthol cigarettes. The rationale for reaching this conclusion on each biomarker endpoint is 

provided in the appropriate section below. 

SUFFICIENT DATA ON BIOMARKERS EXIST TO DRAW CONCLUSIONS 

Included in the vast body of literature evaluating tobacco smoke biomarkers are 19 studies that 

compare biomarkers between menthol and nonmenthol smokers. These comparisons have been 

made on a wide variety of endpoints, some of which reflect acute exposures (e.g., exhaled carbon 

monoxide (CO) or increases (“boosts”) in plasma nicotine from the smoking of a single cigarette) 

and others which provide far more meaningful representations of daily exposures (e.g., a midafternoon sampling of blood providing a near steady-state assessment of systemic exposure to CO 

(as blood carboxyhemoglobin) and nicotine (as plasma cotinine)). Those studies that have assessed 

acute pre- and post-smoking “boosts” in breath CO and plasma nicotine are considered primarily in 

Chapter 3 

52
 

 

 

 

Chapter 3C on smoking topography, since these measures are intended to evaluate exposures 

resulting from the last cigarette smoked rather than systemic exposures integrated over the course of 

daily smoking. The volume of the literature available for each of the endpoints considered in the 

following biomarkers section varies. The breakdown of the 19 studies and a summary of their 

findings are as follows: 

•	 4 of 4 studies comparing systemic carbon monoxide exposure found no significant
 

differences
 

•	 12 of 17 studies comparing levels of nicotine or its metabolites found no significant
 

differences
 

•	 4 of 4 studies comparing levels of carcinogens found no significant differences3 

Details of these studies are provided in Appendix Table 3-14. 

MENTHOL SMOKERS DO NOT HAVE HIGHER SYSTEMIC CARBON MONOXIDE 

EXPOSURE 

Carbon monoxide (CO), a combustion product of cigarette tobacco and other organic materials, can 

be estimated through measurement of expired-air carbon monoxide (expressed as parts per million) 

or as blood carboxyhemoglobin (as the percent of hemoglobin saturation). Breath CO 

measurements are readily influenced by short-term changes in smoke inhalation and reflect very 

recent smoking since the half-life for CO elimination in the breath is approximately 1-4 hours 

(Scherer 2006). Exhaled breath CO has been reported to correlate relatively poorly with daily 

cigarette consumption (Rosenblatt et al. 1998; Ho et al. 2009). Blood carboxyhemoglobin 

measurement is more reflective of daily systemic exposures to CO from smoking than is exhaled 

breath analysis, since CO has a very high affinity for stably-circulating hemoglobin and 

carboxyhemoglobin accumulates over the course of the smoker’s day to attain a near steady-state 

level, typically by mid-afternoon (Smith et al. 1998). Blood carboxyhemoglobin level is not as 

sensitive to the time since the last cigarette and is a preferred biomarker to assess daily or chronic 

CO exposures from smoking. Studies reporting exhaled breath CO measurements are therefore 

discussed primarily in the following section (Chapter 3C) on smoking topography, while those 

reporting blood carboxyhemoglobin as a biomarker of smoke exposure are discussed in the present 

biomarkers section. 

Four studies have compared blood carboxyhemoglobin between menthol and nonmenthol smokers. 

As shown in Table 3-1, none of these studies found a statistically significant difference between 

menthol and nonmenthol smokers. Importantly, Wang et al. (2010) evaluated carboxyhemoglobin 

levels in more than 3,000 smokers as part of the Total Exposure Study (discussed in more detail 

below). Given the size of the study population and inclusion of a significant number of menthol 

and nonmenthol smokers (1,044 and 2,297, respectively), any meaningful difference that existed 

between the groups should have been detected. 

3 One study found a small difference in a carcinogen metabolite ratio (i.e., NNAL-glucuronide/NNAL); the relevance of 

this finding to disease risk is unknown. 

Chapter 3 

53
 

 

 

 

 

Table 3-1. Comparison of Carboxyhemoglobin between Menthol and Nonmenthol Smokers (N=4) 

Nonmenthol > Menthol No significant difference Menthol > Nonmenthol 

- No Studies - Benowitz et al. 2004 - No Studies ­

Heck 2009 

Jarvik et al. 1994 

Wang et al. 2010 

Conclusion about Exposure to Systemic Carbon Monoxide 

The four studies that have compared blood carboxyhemoglobin are consistent in finding no 

significant difference between menthol and nonmenthol smokers in carboxyhemoglobin, a sensitive 

measure of systemic carbon monoxide exposure. Wang et al. (2010) included an adequate sample 

size to detect a meaningful difference. Thus, according to the Surgeon General’s framework for 

assessing causality, the “evidence is suggestive of no causal relationship” between the use of 

menthol in cigarettes and elevated levels of systemic carbon monoxide above those caused by 

smoking nonmenthol cigarettes. 

MENTHOL SMOKERS DO NOT HAVE HIGHER EXPOSURE TO NICOTINE OR 

NICOTINE METABOLITES 

Nicotine and its metabolites are perhaps the most-studied among the available biomarkers employed 

in smoking research. Seventeen studies4 have reported on comparisons of exposure to nicotine or 

nicotine metabolites in menthol and nonmenthol cigarette smokers; details of each study are 

provided in Appendix Table 3-14. The measures of exposure in these studies include nicotine; acute 

“nicotine boost;” nicotine/cigarette; unlabeled nicotine in plasma; salivary and plasma cotinine; 

cotinine/cigarette ratio; urinary recovery of nicotine, nicotine-glucuronide, cotinine, cotinineglucuronide, 3’-hydroxycotinine and 3’-hydroxycotinine-glucuronide; urinary nicotine equivalents; 

and cotinine/3’-hydroxycotinine ratio. 

Nicotine is a major tobacco and cigarette smoke constituent which is absorbed in the lungs and 

rapidly metabolized in the liver, with a half-life of only about 2 hours. Acute measures of “nicotine 

boost” before and after the laboratory smoking of an experimental cigarette are intended to assess 

nicotine exposure from the last cigarette smoked and are considered a correlate of puffing intensity 

(smoking topography). Studies reporting “nicotine boost” are therefore discussed in the subsequent 

section, Chapter 3C, on smoking topography. 

The main metabolite of nicotine is cotinine, which has a much longer half-life of 16-18 hours 

(Roethig et al. 2009). This longer half-life of cotinine makes it a more practical biomarker of 

systemic tobacco smoke exposure than nicotine. Cotinine can be measured in saliva, blood or urine. 

Salivary cotinine has been reported to have a relatively stable and predictable relationship to plasma 

cotinine and offers a relatively convenient means to assess systemic nicotine exposure. 

4 Ahijevych and Parsley 1999, Ahijevych and Wewers 1994, Ahijevych et al. 2002, Allen and Unger 2007, Benowitz et al. 

2004, Benowitz et al. 2010, Clark et al. 1996, Gan et al. 2008, Heck 2009, Ho et al. 2009, Muscat et al. 2009, Mustonen 

et al. 2005, Patterson et al. 2003, Signorello et al. 2009, Strasser et al. 2011, Wang et al. 2010, Williams et al. 2007. 

Chapter 3 

54
Chapter 3 

 

 

Cotinine is further metabolized into 3’-hydroxycotinine and other minor metabolites. Nicotineglucuronide and cotinine-glucuronide are the primary conjugated metabolites of nicotine and 

cotinine that can be measured in excreted urine to assess exposure, as well as the efficiency of 

glucuronide conjugation. Some studies report urinary nicotine equivalents, typically as the molar 

sum of nicotine and the five principal metabolites that account for a majority of nicotine clearance 

(sum of nicotine, cotinine, trans-3’-hydroxycotinine and their respective glucuronides) (Roethig et al. 

2009). The ratio of cotinine/3’-hydroxycotinine represents a measure of cytochrome P450 2A6 

activity, the primary hepatic enzyme responsible for nicotine metabolism in humans. 

Of these seventeen studies, twelve found no elevation in nicotine or any of its metabolites in 

menthol smokers as compared to nonmenthol smokers. Included among these are seven studies 

that included more than 100 to 500 smokers, two studies of more than 500 to 1,000 smokers and 

two studies with sample sizes exceeding 1,000 smokers. Table 3-2 below lists the studies according 

to their overall results: those in which subjects who smoked nonmenthols had significantly greater 

levels of nicotine or nicotine metabolites than those who smoked menthols; those in which there 

was no significant difference, and those in which subjects who smoked menthols had significantly 

greater levels of nicotine or nicotine metabolites than those who smoked nonmenthols. 

Table 3-2.	 Comparison of Nicotine or Nicotine Metabolites Between Menthol and Nonmenthol 

Smokers (N=17) 

Nonmenthol > Menthol No significant difference Menthol > Nonmenthol 

- No Studies - Ahijevych and Wewers 19941 Ahijevych and Parsley 19992 

Allen and Unger 20071 Ahijevych et al. 20022 

Benowitz et al. 2004 Clark et al. 19962 

Benowitz et al. 20101 Mustonen et al. 20053 

Gan et al. 20081 Williams et al. 20074 

Heck 20091 

Ho et al. 20091 

Muscat et al. 20091 

Patterson et al. 20031 

Signorello et al. 20091 

Strasser et al. 2011 

Wang et al. 20101 

1 No significant difference in cotinine, cotinine/cigarette or cotinine/CPD 2 Significantly higher cotinine in menthol smokers 3 Significantly higher cotinine/CPD in menthol smokers 4 Significantly higher serum cotinine and serum nicotine 

Wang et al. (2010) published analyses of the Total Exposure Study (TES) dataset, which is discussed 

in more detail below. This study is important to consider due to its substantial size (3,341 smokers) 

and its inclusion of a substantial number of menthol, as well as nonmenthol smokers (1,044 and 

2,297, respectively). Additionally, the study evaluated a broad number of biomarkers and subject 

characteristics, including extensive demographic and physical traits, CPD, nicotine equivalents, 

nicotine equivalents per cigarette and serum cotinine. Analysis of unadjusted data found statistically 

significantly higher nicotine equivalents per cigarette in menthol smokers while CPD and nicotine 

equivalents per 24 hours were found to be significantly lower in menthol smokers as compared to 

nonmenthol smokers. There was no reported difference in serum cotinine between smokers of the 

two cigarette types. After adjustment for variables which were found to be statistically significant in 

55
 

 

 

the initial model5, there were no longer any statistically significant effects of menthol cigarettes on 

nicotine equivalents per 24 hours, serum cotinine or nicotine equivalents per cigarette. 

Similarly, the findings of Gan et al. (2008), a study of 840 men and 680 women among the large 

1999-2000 NHANES sampling which evaluated the effect of sex on cotinine levels, showed 

significantly higher plasma cotinine in menthol smokers as compared to nonmenthol smokers, but 

only in the univariate analysis. After adjustment for sex, CPD, age, race, BMI, poverty status and 

nicotine content per cigarette, the difference was no longer significant. 

In addition to Wang et al. (2010) and Gan et al. (2008), eight studies found no significant differences 

between menthol and nonmenthol smokers in levels of cotinine (Table 3-2, footnote 1) and five 

studies reported higher cotinine levels in menthol smokers compared to nonmenthol smokers 

(Table 3-2, footnotes 2-4). 

One of the five studies that reported higher cotinine levels in menthol smokers, Mustonen et al. 

(2005), collected salivary samples for cotinine analysis from 307 smokers (28.7% menthol smokers) 

recruited for a clinical smoking cessation trial. Although there was no difference observed in CPD 

or measures of salivary cotinine, the authors observed a significantly higher cotinine/CPD ratio 

among menthol smokers as compared to nonmenthol smokers (p=0.004). It should be noted that 

these analyses were unadjusted. Given that Mustonen et al. (2005) reported a significant effect of 

the interaction between sex, race and cigarette type on salivary cotinine and cotinine/CPD, the 

differences observed in cotinine/CPD may have been due to these factors, which were not 

accounted for in the univariate analysis. 

However, Williams et al. (2007), in a study of 89 schizophrenic smokers and 53 control smokers 

(comprising 79 menthol smokers), found no significant difference in cotinine/CPD but found 

significantly elevated serum cotinine levels in menthol smokers as compared to nonmenthol smokers 

after adjustment for schizophrenic status, race and CPD. In addition to the differences observed in 

serum cotinine, Williams et al. (2007) found significant elevations in serum nicotine, but not in 

nicotine/CPD in menthol smokers as compared to nonmenthol smokers. The discrepancies in 

these results depending on the method used to adjust for CPD imply that some other variable is 

responsible for the difference. 

Clark et al. (1996) collected samples from 161 smokers following a 1-hour smoking abstention for 

determination of serum cotinine. Serum cotinine levels were found to be significantly elevated in 

menthol smokers versus nonmenthol smokers (84.5 ng/ml increase in menthol smokers after 

adjustment for race, CPD and mean amount of cigarette smoked). However, the question of 

whether differences in the mainstream smoke nicotine yields of the subjects’ preferred cigarettes 

may at least partially account for the reported cotinine differences limits the conclusions that can be 

drawn from this study with respect to menthol. 

Two additional studies (Ahijevych and Parsley 1999 and Ahijevych et al. 2002) of all female smokers 

reported increased cotinine/cigarette ratios at baseline among menthol smokers as compared to 

nonmenthol smokers. Neither of these studies considered the machine-measured mainstream 

smoke nicotine yields of the cigarettes smoked by the study subjects, an adjustment that is lacking 

5 Those tested included menthol, age, sex, BMI, race, smoking machine derived tar category, CPD, U.S. Census region, 

annual household income, education and the two-way and three-way interactions of the factors. 

Chapter 3 

56
 

 

 

 

 

 

from the majority of biomarkers studies. For example, in Williams et al. (2007), subjects reported 

smoking a variety of different full-flavor, lights and ultra-lights brands. The most frequently smoked 

menthol brand among study subjects was Newport, which at the time of the study delivered 9% 

more machine-determined (FTC) nicotine and 13% more carbon monoxide than did the most 

frequently-reported nonmenthol brand (Marlboro) in the study. Thus, attribution of reported 

differences to the presence of menthol cannot be scientifically justified. In Heck (2009), in which 

112 smoking subjects were provided with designated menthol and nonmenthol brands closely 

matched for machine-determined “tar,” nicotine and CO yields, the two groups of smokers did not 

have significantly different levels of cotinine or urinary nicotine equivalents. 

The few differences reported between menthol and nonmenthol smokers in these measures of 

nicotine and nicotine metabolites in body fluids, especially differences that remain when taking into 

account cigarettes per day, may reflect differences in the ways that the two types of cigarettes are 

smoked. However, whether this can be attributed to the inclusion of menthol in cigarettes is 

unclear. Another important consideration when evaluating a measure of exposure per cigarette is 

the accuracy of the cigarette per day data. For many of these studies, data on cigarette consumption 

were self-reported, and as shown by Ahijevych and Wewers (1994), this method of data collection 

can be subject to substantial underreporting of cigarette consumption. 

Benowitz et al. 2004, Benowitz et al. 2010, Heck 2009 and Patterson et al. 2003 found no differences 

in any measures of nicotine exposure. One study (Muscat et al. 2009) also compared levels of 

thiocyanate, a metabolite of hydrogen cyanide, in menthol smokers versus nonmenthol smokers and 

reported no difference. 

Conclusion about Exposure to Nicotine and Nicotine Metabolites 

In drawing conclusions about type of cigarette smoked and nicotine and nicotine metabolites, it 

must be remembered that there are a good number of studies (N=17) and many endpoints assessed 

among those studies. It is not surprising that there might be a few significant findings when doing 

this number of analyses; however, it is important to focus on the overall pattern of results. Of the 

17 studies that compared exposure to nicotine or nicotine metabolites between menthol and 

nonmenthol smokers, the majority (N=12) showed no significant differences in any of the endpoints 

measured. This includes the two largest studies (Wang et al. 2010, Gan et al. 2008), which presented 

data on nationally representative populations (TES and NHANES). 

Among the five studies that found significant differences between menthol and nonmenthol 

smokers, all observed differences in cotinine levels. Two of these involved only relatively small 

groups of female smokers. Additionally, results were not internally consistent, with discrepant 

findings in cotinine and cotinine/CPD in two of the studies (Mustonen et al. 2005, Williams et al. 

2007) that could not be easily explained. Thus, the combined weight of available published, peerreviewed studies of biomarkers of systemic nicotine exposure clearly supports a conclusion that the 

“evidence is suggestive of no causal relationship” between the use of menthol in cigarettes and 

elevated systemic nicotine exposure above that caused by smoking nonmenthol cigarettes. 

Chapter 3 

57
 

 

 

 

 

 

 

 

 

MENTHOL DOES NOT INHIBIT THE METABOLISM OF TOBACCO SMOKE 

COMPONENTS 

The studies discussed above that evaluated measures of nicotine metabolites provide information 

both on systemic nicotine exposure and on the impact of menthol on the metabolism of certain 

tobacco smoke components. With the majority showing no significant difference between menthol 

and nonmenthol smokers in levels of nicotine metabolites, it can be concluded that menthol does 

not meaningfully affect the metabolism of tobacco smoke components. Benowitz et al. (2004), 

discussed in further detail below, suggested that menthol may affect the metabolism of nicotine, and 

these authors explored the potential of such an effect to influence smoke constituent exposures 

accompanying menthol cigarette smoking. An earlier report by MacDougall et al. (2003) had 

reported inhibitory effects of menthol and similar compounds on the in vitro oxidation of nicotine 

by human microsomes, but the rather modest potency of menthol in affecting these enzyme 

activities (Ki value for inhibition of cotinine formation by menthol = 69.7 μM vs. systemic menthol 

from smoking ~1 μM or less) does not suggest a likelihood of a meaningful effect in vivo at 

exposure levels resulting from menthol’s use in cigarettes. Indeed, a number of subsequent studies 

in humans have not observed metabolic interactions between menthol and a number of drugs that 

are well-characterized as human cytochrome P450 substrates (Gelal et al. 2003, 2005). 

Benowitz et al. (2004), was a forced crossover study of 14 smokers, half African American and half 

White. Each subject was randomly assigned to smoking either a menthol or nonmenthol cigarette of 

similar FTC smoke yield (Kool Kings or Marlboro Kings) for a one-week period. Following the 

treatment period, subjects were administered an intravenous dose of deuterated nicotine and 

cotinine and deuterated nicotine metabolites were analyzed in collected urine to assess nicotine and 

metabolite clearance. Subjects’ menthol and nonmenthol group assignments were then switched for 

another week of smoking followed by another intravenous administration of deuterated nicotine and 

urinary metabolite collection and analysis. 

The disposition kinetics of nicotine and cotinine were evaluated through a number of measures 

including clearance, half-life and volume of distribution at steady state. The only significant 

differences that were observed were slower total and nonrenal clearance of nicotine among menthol 

smokers and a lower nicotine-glucuronide/nicotine ratio in menthol smokers. These differences 

were not found for cotinine. There were also no significant differences in urinary recovery of 

nicotine, nicotine-glucuronide, cotinine, cotinine-glucuronide, 3’-hydroxycotinine or 

3’-hydroxycotinine-glucuronide when comparing the menthol group to the nonmenthol group. 

These results led the authors to conclude that menthol inhibits nicotine, but not cotinine, 

metabolism. However, given the lack of consistent evidence of an effect of menthol on the 

metabolism of tobacco smoke components (e.g., Heck 2009, Ho et al. 2009, Benowitz et al. 2010, 

Wang et al. 2010, Strasser et al. 2011, Williams et al. 2007), the practical implications of this as-yet 

unconfirmed observation that menthol may affect the metabolism of intravenously-administered 

nicotine are not readily apparent. 

The extremely large study of Wang et al. (2010), in particular, addressed the discrepancy in their 

results versus those observed by Benowitz et al. (2004). As stated above, Wang et al. (2010), along 

with nine other studies, found no difference in serum cotinine levels between menthol and 

nonmenthol smokers; the authors also reported no significant differences in nicotine metabolite 

ratios, suggesting that menthol has no effect on the metabolism of nicotine derived from smoking. 

This is in contrast to the conclusion of Benowitz et al. (2004) that menthol cigarettes significantly 

Chapter 3 

58
 

 

 

 

inhibit nicotine metabolism by slower oxidative metabolism to cotinine and slower glucuronide 

conjugation. Wang et al. (2010) explained that the reason for the discrepancy between the two 

studies could be due to the differences in the study designs (i.e., Benowitz et al. 2004) compared 

urine cotinine levels collected for eight hours after an intravenous infusion of deuterium-labeled 

nicotine and cotinine in a controlled setting, whereas Wang et al. (2010) compared serum cotinine 

levels taken at a single time-point from smokers in an ambulatory setting. Furthermore, the sample 

sizes between the two studies are vastly different (N=14 vs. N=3,341). The absence of statistically 

significant differences in serum cotinine levels or any other nicotine metabolites measured in the 

large Wang et al. (2010) study suggests that an effect, if any, of menthol on nicotine metabolism is 

most likely small since it could not be detected in such a large study. 

Heck (2009) was a parallel-arm study of 112 smokers who were assigned to specific brands of 

menthol or nonmenthol cigarettes with similar machine-measured tar yields. Smokers were assigned 

either to menthol or nonmenthol cigarettes based on their stated preference and smoked commercial 

cigarettes of similar machine-measured ‘‘tar” yields (~9-10 mg) ad libitum for a 2-week study 

interval. Measures of metabolism included nicotine-glucuronide, cotinine-glucuronide, 

trans-3’-hydroxycotnine and trans-3’-hydroxycotinine-glucuronide; there were no significant 

differences between the menthol and nonmenthol group in any of these measures. In addition, 

Strasser et al. (2011) and Williams et al. (2007) reported 3’-hydroxycotinine to cotinine ratios, a 

measure of CYP2A6-mediated nicotine metabolism, that did not show significant differences 

between menthol and nonmenthol smokers. 

Conclusion about Effects on Metabolism of Tobacco Smoke Components 

Of the four studies most relevant to this topic, there was only a single significant finding, which 

suggested that menthol inhibits metabolism. This finding came from a study of only 14 subjects and 

it has not been confirmed in three subsequent analyses (one of which was an analysis of the 

extremely large TES dataset). Thus, there is no clear and consistent association between menthol 

smoking and an effect on nicotine metabolism. This conclusion is supported by the lack of 

significant differences in studies that have compared levels of nicotine metabolites, as discussed in 

the previous section. The combined weight of available published, peer-reviewed studies comparing 

levels of nicotine metabolites and other measures of metabolism supports a conclusion that the 

“evidence is suggestive of no causal relationship” between the use of menthol in cigarettes and 

altered nicotine metabolism when compared the use of nonmenthol cigarettes. 

MENTHOL DOES NOT INCREASE EXPOSURE TO CARCINOGENS 

Tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) are among 

the carcinogens present in measurable quantities in tobacco smoke. Prominent among the TSNAs is 

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and a urinary metabolite of this compound, 

4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAL) that has been broadly employed as a 

sensitive and specific urinary biomarker for NNK exposures resulting from tobacco use. 

Chapter 3 

59
Chapter 3 

 

 

 

 

Urinary levels of excreted NNAL and its glucuronide conjugates (NNAL-gluc) have been measured 

in several studies to compare the relative NNK exposures resulting from the smoking of menthol 

and nonmenthol cigarettes. Although NNAL has itself been classified by IARC as a Group 2B 

carcinogen (i.e., possibly carcinogenic to humans), the relatively efficient urinary clearance of the 

glucuronide conjugate of NNAL has led some authors to propose that a higher urinary NNALgluc/NNAL ratio may be indicative of a metabolic detoxification capacity that is consistent with 

lower cancer risks. Notably, this speculation that NNAL-gluc/NNAL ratio may determine smokers’ 

lung cancer risks has not been borne out in studies of populations having substantially different 

metabolite profiles and lung cancer risks (Derby et al. 2008). 

Four studies have evaluated concentrations of NNAL and its metabolites among menthol smokers 

and nonmenthol smokers, and none of these have reported higher total NNAL excretion by 

menthol cigarette smokers (see Table 3-3). One of these studies reported menthol-related 

differences in NNAL-gluc/NNAL ratio, as discussed below. 

Table 3-3.	 Comparison of NNAL and NNAL Metabolites Between Menthol and Nonmenthol 

Smokers (N=4) 

Nonmenthol > Menthol No significant difference Menthol > Nonmenthol 

- No Studies - Benowitz et al. 2010 - No Studies ­

Heck 2009 

Muscat et al. 2009 

Xia et al. 2010 

One of the studies which measured NNAL concentrations (Xia et al. 2010) included an analysis of 

1,373 tobacco users who participated in the 2007-2008 NHANES. Urinary total NNAL 

concentrations were determined from analysis of urine samples of all participants aged 6 years or 

older. The authors reported no significant difference between menthol and nonmenthol smokers 

(285 vs. 331 pg/ml, respectively) in this analysis. Likewise, Heck (2009), discussed in more detail 

above, found no difference in total NNAL concentrations between menthol and nonmenthol 

smokers nor any difference in its metabolite, NNAL-glucuronide. Benowitz et al. (2010) included a 

comparison of urine NNAL in menthol smokers to that measured in nonmenthol smokers and 

reported that there was no significant difference. 

The study reported by Muscat et al. (2009) found no significant difference between menthol and 

nonmenthol smokers in total urinary NNAL, but these authors reported a significantly higher 

NNAL-glucuronide/NNAL ratio for nonmenthol smoking subjects than for the menthol smokers. 

This finding was in contrast to the analysis reported in a prior publication by this group for the same 

study population, which had concluded African American race, but not menthol preference, 

appeared to be associated with apparent reduced glucuronidation efficiency for NNAL (Richie et al. 

1997). The authors hypothesized that the 2009 finding could be due to inhibition of UDPglucuronosyltransferase enzymes responsible for glucuronidation of nicotine and NNAL. The 

authors offered the findings of a single in vitro experimental incubation of human S-9 in support of 

their hypothesis. However, this experiment used menthol levels roughly equivalent to those that 

would result from smoking several hundred cigarettes, and the experimental NNAL level used was 

approximately 5 million times greater than what is measured in human smokers. The authors 

acknowledged that the levels of menthol and substrate in the in vitro enzyme incubation were not 

representative of those from actual smoking. No prior or subsequent studies in human smokers 

60
 

 

 

 

have confirmed the speculation of Muscat et al. (2009) that menthol in cigarettes may affect NNAL 

metabolism. The alternate explanation offered by Ritchie et al. (1997) (i.e., metabolic differences 

between Black and White smokers as opposed to an effect by menthol), is also supported by the 

findings of the large Total Exposure Study. 

One study, Benowitz et al. (2010), compared urine total PAHs, the molar sum of all PAH 

metabolites, in menthol smokers to those of nonmenthol smokers. In this analysis of 127 smokers 

(60 menthol and 62 nonmenthol), nonmenthol smokers were found to have significantly higher 

levels of total PAH in the urine than menthol smokers. The authors conducted various statistical 

analyses to understand the relationship between measures of menthol exposure and other variables, 

including nicotine equivalents, NNAL and total PAHs. They concluded that menthol exposure does 

not add to the predictive value of nicotine exposure in determining exposure to TSNAs or PAHs 

from cigarette smoking. 

Conclusion about Exposure to Carcinogens 

None of the four studies that compared levels of NNAL or PAH found significant differences 

between menthol and nonmenthol smokers. One of these (Xia et al. 2010) included an analysis of 

data collected as part of a nationally representative survey, NHANES. The only study that reported 

a significant finding was Muscat et al. (2009), which reported a significantly lower NNALglucuronide/NNAL ratio among menthol smokers compared to nonmenthol smokers (but no 

difference in total urinary NNAL). This finding conflicted with earlier studies by the same group 

that attributed the difference to race. The combined weight of available published, peer-reviewed 

studies of biomarkers of potential harm support the conclusion that the “evidence is suggestive of 

no causal relationship” between the use of menthol in cigarettes and increased levels of TSNAs 

and PAHs above that caused by smoking nonmenthol cigarettes. 

LACK OF EFFECT OF MENTHOL CONFIRMED BY TOTAL EXPOSURE STUDY 

The largest dataset measuring a variety of biomarkers was generated from PM USA’s Total 

Exposure Study (TES). The TES was a stratified, multi-center, cross-sectional study specifically 

designed to estimate exposure to selected cigarette smoke constituents in a population of U.S. adult 

smokers (Roethig et al. 2009). The study included 3,585 evaluable adult smokers (1,104 menthol 

smokers and 2,481 nonmenthol smokers) and 1,077 evaluable non-smokers from 39 investigative 

sites located in 31 states across the U.S. Various biomarkers were measured in blood and urine 

samples and comparisons were made between menthol and nonmenthol smokers, and also between 

Black and White smokers. Wang et al. (2010) is the only available publication to date reporting these 

data with regard to menthol and focuses on biomarkers of exposure. The study findings have been 

presented to TPSAC and to the broader scientific community at the 2010 meeting of the Society for 

Research on Nicotine and Tobacco. Given its size and the comprehensive measurements made in 

this study, additional details from further analyses of the dataset are presented in Table 3-4 below. 

Chapter 3 

61
Chapter 3 

 

The results of TES found: 

•	 Overall, no statistically significant differences (p>0.05) in biomarkers of exposure were 

observed between menthol and nonmenthol smokers 

•	 Overall, no statistically significant differences (p>0.05) in metabolite ratios were observed 

between menthol and nonmenthol smokers 

•	 Menthol had no statistically significant effect (p>0.05) on the biomarkers of potential harm 

investigated; there were no statistically significant menthol-related interaction terms 

Table 3-4 Summary of Results of TES 

Measure Menthol 

(N=1044) 

Nonmenthol 

(N=2297) 

Biomarkers of Exposurea 

CPD 15.0 (8.7) 16.8 (9.0) 

Tar yield (mg) 10.6 (6.2) 8.5 (4.9) 

NE (mg/24 h) 12.8 (7.8) 13.5 (7.9) 

Total NNAL (ng/24 h) 399.9 (294.8) 436.7 (309.5) 

Serum cotinine (ng/ml) 188.9 (108.4) 183.4 (105.4) 

Carboxyhemoglobin (% saturation) 5.2 (2.27) 5.4 (2.23) 

Metabolite Ratiosb 

3OHC/cotinine 2.67 2.52 

Nicotine gluc./nicotine 1.12 1.09 

Cotinine gluc./cotinine 2.85 2.59 

3OHC gluc./3OHC 1.07 1.09 

NNAL gluc./NNAL 3.16 3.06 

Biomarkers of Potential Harmc 

HDL cholesterol (mg/dl) 52.6 (15.3) 51.0 (16.3) 

LDL cholesterol (mg/dl) 114 (36.4) 116 (36.3) 

Oxidized LDL (U/L) 73.5 (21.4) 74.5 (21.0) 

Total cholesterol (mg/dl) 194 (42.3) 198 (41.6) 

Triglycerides (mg/dl) 142 (106) 164 (141) 

hs C-Reactive Protein (mg/L) 2.91 (2.69) 2.69 (2.55) 

FEV1 (% predicted) 83.5 (19.0) 84.1 (18.0) 

8-epi-Prostaglandin-F2-α (ng/24h) 1882 (1082) 1893 (1040) 

11-dehydrothromboxane-B2 (ng/24h) 1397 (1016) 1310 (1045) 

White blood cells (x100/uL) 7.74 (2.33) 8.05 (2.27) a Data shown as unadjusted mean (SD)
 b Data shown as LSMeans
 c Data shown as Mean (SD)
 

No statistically significant differences
 

CPD=cigarettes per day; NE=nicotine equivalents; 3OHC=3’-hydroxycotinine; HDL=high-density lipoprotein;
 

LDL=low-density lipoprotein; FEV1=forced expiratory volume in 1 second
 

62
 

 

CONCLUSION 

Overall, the vast majority of studies comparing biomarkers of exposure to tobacco smoke 

constituents and their metabolites and biomarkers of potential harm have found no difference 

between menthol and nonmenthol smokers. Sporadic findings of differences have been reported in 

smaller studies, but substantive differences in biomarkers of exposure are not seen in analyses of 

body fluids from large study populations. According to the Surgeon General’s framework for 

assessing causality, the “evidence is suggestive of no causal relationship” between the use of 

menthol in cigarettes and increases in biomarkers of exposure and potential harm over and above 

those caused by the smoking of nonmenthol cigarettes. 

Chapter 3 

63
 

 

CHAPTER 3C.
 

EVIDENCE IS INADEQUATE TO CONCLUDE THAT
 

MENTHOL IN CIGARETTES ADVERSELY IMPACTS SMOKING TOPOGRAPHY
 

Some researchers have attempted to measure the effect of menthol in cigarettes on human smoking 

behavior. These studies have attempted to measure differences between menthol and nonmenthol 

smokers in puff volume, number and frequency of puffs; depth of inhalation; duration of smoke 

retention in the lungs; percentage of cigarette smoked and other variables. These variables are 

typically referred to as elements of “smoking topography.” The results of the studies are mixed in 

regard to whether they find a significant difference between menthol and nonmenthol smokers and 

also, among the studies that do report differences, the results are mixed with regard to the direction 

of the change observed. Any differences reported between menthol and nonmenthol smokers may 

be dependent on the method of measurement used and the lack of specificity of the outcome 

measured. Despite the somewhat contradictory results of the studies, overall the studies are 

consistent with the studies on biomarkers of exposure, discussed above, which report that menthol 

does not affect exposure of smokers to smoke constituents. In addition, any clinically meaningful 

differences in smoking topography among smokers of menthol and nonmenthol cigarettes would be 

reflected in the epidemiology studies discussed above which show no increase in tobacco-related 

disease risk due to menthol. According to the Surgeon General’s framework for assessing causality, 

the “evidence is inadequate to infer the presence or absence of a causal relationship” 

between the use of menthol cigarettes and adverse impacts on smoking topography. 

METHODS OF MEASURING SMOKING TOPOGRAPHY PARAMETERS 

A variety of methodologies are used to capture data on smoking behavior, and have been applied in 

experimental comparisons of menthol and nonmenthol cigarettes. Each of the available methods 

has distinct shortcomings that have contributed to the mixed and inconsistent findings in published 

work to date. 

Some investigators have reported acute changes in exposure biomarkers (e.g., exhaled CO or plasma 

nicotine “boosts”) as indirect indices of smoking topography. Although CO accumulation and 

elimination from the body has been well characterized, the kinetics of these processes are complex 

due to physiological variables such as lean body mass, the partitioning of CO into myoglobin and 

cytochrome protein sinks, and the endogenous production of CO by heme catabolism (Lloyd and 

Rowe 1999). Smoking-related exposures to CO are also influenced by the design and mainstream 

smoke yields of specific cigarettes. Cigarette filter ventilation and paper porosity both have a 

marked effect in lowering mainstream smoke CO yield and the smoker’s consequent CO exposure. 

Other available methods to assess smoking topography have included the smoking of cigarettes 

through pressure and flow-sensing mouthpiece devices that to varying degrees influence the 

experimental smoker’s normal manner of smoking since the test cigarette is not held in the smoker’s 

lips or hands in the normal way. The more the methods of data collection interfere with a subject’s 

ability to smoke normally, the less meaningful the data. A less intrusive approach to the estimation 

Chapter 3 

64
 

of inhaled puff volumes, inspiratory flow rates and puff retention times uses chest band transducers 

to record chest expansion patterns during the smoking process (Nil and Bättig 1989, St. Charles et 

al. 2009). 

An emerging method to compare at least some aspects of the differences in smoking topography 

among smokers or between different types of cigarettes uses chemical analyses of segments of the 

expended filter butt as an indication of the quantity of mainstream smoke that has been drawn from 

the cigarette by the normal smoking process. This “mouth level exposure” method offers the 

advantage of allowing completely naturalistic smoking. An international effort to develop and 

validate standard methods for mouth level exposure is underway (under the auspices of the 

Cooperation Centre for Research Relative to Tobacco (CORESTA)). 

Several of the studies that have sought to determine whether there may be differences in smoking 

topography between menthol and nonmenthol cigarettes have applied some combination of 

pressure and/or flow transducer-equipped mouthpieces, plethysmography/spirometry, laboratory 

smoke-delivery devices, and modified rapid smoking procedures. The lack of standardized methods 

in this area of study has contributed to the mixed and inconsistent nature of this literature. Only a 

few of the studies that present comparisons of menthol and nonmenthol smokers have gathered 

data on subjects during natural smoking (Pickworth et al. 2002, St. Charles et al. 2009). In general, 

the topography studies have yielded inconsistent results, which could be attributable to variation in 

the data collection methods and the ability of participants to smoke naturally in a clinical setting. 

Although differences in various smoking topography parameters may be measured in the laboratory 

setting, it is not always clear that these differences are present or meaningful in real-life smoking 

scenarios. 

EXHALED BREATH CARBON MONOXIDE AS AN INDICATOR OF PUFFING 

INTENSITY 

Exhaled breath CO may be reported as a measure of smoking intensity as either a single exhaled 

breath concentration or as a change in that concentration (“CO boost”) after smoking a cigarette 

under laboratory conditions. The transient nature of increases in breath carbon monoxide level and 

the relatively short half-life for CO elimination by exhalation render exhaled CO measurements 

informative in assessing the topography of cigarette smoking rather than cumulative daily systemic 

exposures. 

Among the eight studies comparing exhaled CO concentrations, five found no significant 

differences between menthol and nonmenthol smokers (see Table 3-5). While three studies found 

significant differences, the results were inconsistent in that two found higher CO concentrations 

among menthol smokers while a third study found the opposite, i.e., higher CO concentrations 

among nonmenthol smokers. 

Chapter 3 

65
Chapter 3 

 

 

 

 

 

Table 3-5. Comparison of CO concentrations between menthol and nonmenthol smokers (N=8) 

Nonmenthol > Menthol No significant difference Menthol > Nonmenthol 

Rosenblatt et al. 1998: 10 

smokers; 50% menthol; race not 

provided 

Allen and Unger 2007: 432 smokers; 

68.5% menthol; 100% African 

American 

Miller et al. 1994: 12 smokers; 

50% menthol; 100% African 

American 

Clark et al. 1996: 161 smokers; 

47.2% menthol; 40.4% Black, 59.6% 

White 

Williams et al. 2007: 142 smokers; 

55.6% menthol; 53.1% Black, 

28.1% White, 18.8% 

Hispanic/Latino1 

Ho et al. 2009: 700 smokers; 81.3% 

menthol; 100% African American 

Jarvik et al. 1994: 20 smokers; 50% 

menthol; 50% Black, 50% White 

McCarthy et al. 1995: 29 smokers; 

38% menthol; 55.2% Black, 44.8% 

White 1 Race breakdown provided for menthol smokers only 

It should be noted that the studies that included the largest sample sizes (Allen and Unger 2007, Ho 

et al. 2009) found no differences in exhaled breath CO measurements. 

The study of Rosenblatt et al. (1998) was designed to compare olfactory thresholds for nicotine and 

menthol between menthol and nonmenthol smokers. Among the 10 smokers included in the study, 

menthol smokers were found to have significantly lower exhaled carbon monoxide levels than 

nonmenthol smokers and this was not correlated with CPD as there was no difference in CPD 

between the two groups. 

Two studies that have applied exhaled breath CO measurements as a measure of smoking/puffing 

intensity have reported that menthol smokers had statistically significantly higher levels of CO as 

compared to nonmenthol smokers (Miller et al. 1994, Williams et al. 2007). 

Miller et al. (1994) evaluated the effect of increasing menthol concentrations (0 mg, 4 mg, 8 mg per 

cigarette) on carbon monoxide boost after subjects had inhaled a specific volume of smoke through 

an experimental apparatus from the test cigarettes. The authors concluded that this study 

demonstrated that adding menthol to cigarettes causes a significant increase in exhaled carbon 

monoxide despite a constant volume of smoke exposure. 

The analyses in Williams et al. (2007) were designed to compare the effect of menthol smoking in 

smokers with and without schizophrenia and found statistically significantly higher exhaled carbon 

monoxide levels in menthol smokers. It should be noted that the measures of carbon monoxide 

levels in this study resulted from the smoking of a variety of cigarette types (full-flavor, as well as 

low tar brands). Adjustments were made for group (schizophrenic versus control), CPD and race 

but not for cigarette brand or FTC yield. 

66
Chapter 3 

 

 

PUFF VOLUME 

Several studies have examined the relationship between mentholation of cigarettes and inhaled puff 

volume. Although it has been suggested that menthol in cigarettes could allow for greater inhalation 

of cigarette smoke (i.e., increased puff volume), there is little support for this hypothesis as shown in 

Table 3-6 below. In fact, only one of eight studies found a significantly increased puff volume 

among menthol smokers as compared to nonmenthol smokers. The table below lists the studies 

according to their overall results: those in which subjects who smoked nonmenthols had 

significantly greater puff volumes than those who smoked menthols; those in which there was no 

significant difference; and those in which subjects who smoked menthols had significantly greater 

puff volumes than those who smoked nonmenthols. 

Table 3-6. Comparison of Puff Volume Between Menthol and Nonmenthol Smokers (N=8) 

Nonmenthol > Menthol No significant difference Menthol > Nonmenthol 

Jarvik et al. 1994: 20 

smokers; 50% menthol; 50% 

Black, 50% White 

Ahijevych et al. 1996: 37 smokers; 48.6% 

menthol; 48.4% Black, 51.4% White 

Ahijevych and Parsley 1999: 

95 smokers; 53% menthol; 

50.5% Black, 49.5% White 

McCarthy et al. 1995: 29 

smokers; 38% menthol; 

55.17% Black, 44.83% White 

Miller et al. 1994: 12 smokers; 50% 

menthol; 100% African American 

Nil and Bättig 19891: 15 

smokers; menthol preference 

not provided2; race not 

provided 

St. Charles 2009: 74 smokers; 24.3% 

menthol; race not specified 

Strasser 2007: 119 smokers; 38% menthol; 

62% White, 31% African American, 2.5% 

Hispanic or Latino 1 Significant difference between high yield menthol and: low yield menthol, high and low yield blond tobacco (aka fluecured bright tobacco), own brand. 2 All subjects smoked 6 experimental cigarettes including 1 high smoke yield and 1 low smoke yield menthol, and 1 

cigarette of their own brand. 

Note that three of these studies (Jarvik et al. 1994, McCarthy 1995, Nil and Bättig 1989) found that 

menthol smokers had a significantly decreased puff volume compared to nonmenthol smokers. The 

majority of studies (4 of 8) found no statistically significant effect of menthol on puff volume and 

only one study (Ahijevych and Parsley 1999) reported a significantly increased (by 8 mL) puff 

volume among menthol smokers compared to nonmenthol smokers. 

These studies represent a broad range of study designs and smoking conditions. The study 

conducted by Ahijevych and Parsley (1999) assessed smoking parameters in a laboratory setting and 

found significantly larger puff volumes in menthol compared to nonmenthol smokers ( 45.8 vs. 37.8 

ml, p=0.03). However, it was unclear whether these values were adjusted for potential confounding 

factors, such as race or body physiology. Ahijevych et al. (1996) used the same laboratory setting 

and data collection procedures and found no significant difference in puff volume; however, the 

sample size was much smaller in this earlier study (37 vs. 95). 

67
Chapter 3 

 

 

 

 

PUFFS PER CIGARETTE 

It has also been hypothesized that menthol could contribute to taking more puffs per cigarette. 

Eight studies compared this parameter and none found that menthol smokers took more puffs per 

cigarette than nonmenthol smokers (see Table 3-7 below). Three studies found that nonmenthol 

smokers took significantly more puffs per cigarette than menthol smokers and five studies found no 

difference between the two groups. The table below lists the studies according to their overall 

results: those in which subjects who smoked nonmenthols had significantly greater puffs per 

cigarette than those who smoked menthols; those in which there was no significant difference; and 

those in which subjects who smoked menthols had significantly greater puffs per cigarette than 

those who smoked nonmenthols. 

Table 3-7. Comparison of Puffs Per Cigarette Between Menthol and Nonmenthol Smokers (N=8) 

Nonmenthol > Menthol No significant difference Menthol > Nonmenthol 

Jarvik et al. 1994: 20 smokers; 

50% menthol; 50% Black, 50% 

White 

Ahijevych et al. 1996: 37 smokers; 

48.6% menthol; 48.4% Black, 51.4% 

White 

- No studies -

McCarthy et al. 1995: 29 

smokers; 38% menthol; 55.17% 

Black, 44.83% White 

Caskey et al. 1993: 28 smokers; 43% 

menthol; 61% Black, 39% White 

Nil and Bättig 19891: 15 

smokers; menthol preference not 

provided2; race not provided 

Miller et al. 1994: 12 smokers; 50% 

menthol; 100% African American 

Pickworth et al. 2002: 36 smokers; 

50% menthol; 55.6% African 

America, 44.4% Caucasian 

Strasser 2007: 119 smokers; 38% 

menthol; 62% White, 31% African 

American, 2.5% Hispanic or Latino 1 Significant difference between high yield menthol and: low yield menthol, low yield dark tobacco (aka air-cured 

European-style tobacco), high and low yield blond tobacco, own brand. 2 All subjects smoked 6 experimental cigarettes including 1 high smoke yield and 1 low smoke yield menthol, and 1 

cigarette of their own brand. 

Contrary to the suggestion that the menthol smokers have greater exposure to smoke constituents 

from taking more puffs per cigarette, those studies that found a significant difference between 

menthol and nonmenthol smokers in puffs per cigarette reported significantly more puffs per 

cigarette among nonmenthol smokers. While the results across the eight studies are inconsistent, 

there are none that suggest that menthol smokers take more puffs per cigarette. 

68
 

 

 

 

 

 

 

OTHER TOPOGRAPHY VARIABLES
 

Some of the studies noted above also examined a number of other smoking topography measures, 

but found few differences between menthol and nonmenthol smokers. For example, although 

Jarvik et al. (1994) found significant increased puff volume and puffs per cigarette among 

nonmenthol smokers, the study found no significant differences between menthol and nonmenthol 

smokers in puff duration, peak puff flow, interpuff interval, inhaled volume and lung retention time. 

St. Charles (2009) compared total lung exposure time between menthol and nonmenthol smokers 

and found no difference. In addition to finding no differences in puff volume and number of puffs, 

Ahijevych et al. (1996) compared puff duration, interpuff interval, inhalation duration and exhalation 

duration between menthol and nonmenthol smokers and found no significant differences. Nil and 

Bättig (1989) found that postpuff inspiratory times (the time during which the subject continues to 

inhale following a cigarette puff) increased across cigarette taste categories from menthol to dark 

tobacco to blond tobacco. The inconsistencies within these studies argue that one must be cautious 

about placing too much importance on the finding of a significant difference in any single measure, 

as no single measure has yet been proven and validated as an adequate representation of the 

complexities of human smoking behavior. Rather the findings from all measures of topography 

should be assessed as a whole. 

A few studies have evaluated the relationship between menthol, nicotine, and tar yield to smoking 

topography (e.g., Miller et al. 1994, Nil and Bättig 1989, Pickworth et al. 2002). However, these 

studies were not able to clearly delineate the relative importance of smoke taste (menthol) or smoke 

yield (e.g., nicotine, smoke condensate, CO) on measures of smoking topography. The one study 

that measured mouth level exposures to tar and nicotine resulting from natural smoking found no 

significant differences between menthol and nonmenthol cigarettes (Nelson et al. 2010). This study 

included six menthol brand styles among the total of 26 brands and styles smoked by a sampling of 

1,330 smokers at multiple nationwide study sites. 

CONCLUSION 

There is a reasonable body of literature on menthol cigarette smoking and smoking topography. 

The available studies are quite different in the ways that they measure smoking topography variables, 

and many have significant weaknesses, including differences in study design, small study sizes, use of 

only men or women in a study, and use of cigarettes differing in yield and menthol content. These 

differences make it difficult to compare the studies and to reach definitive overall conclusions 

regarding these aspects of smoking topography. Although the findings are somewhat inconsistent, 

overall the majority of studies find no significant differences between menthol and nonmenthol 

smokers in smoking topography variables. Many of the studies that do find significant differences 

report smoking behaviors that would lead to greater exposures among nonmenthol smokers as 

compared to menthol smokers. These data provide no support for the presence of a clear and 

consistent association between menthol smoking and an adverse impact on smoking topography and 

provide no convincing support for the suggestion that menthol increases the exposure to smoke 

constituents through effects on smoking behavior. However, given the inconsistencies that exist, 

according to the Surgeon General’s framework for assessing causality, the “evidence is inadequate 

to infer the presence or absence of a causal relationship” between use of menthol cigarettes and 

Chapter 3 

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adverse impacts on smoking topography. Moreover, topography studies purport to be proxies for 

exposure and risk that are more directly measured by biomarker and epidemiology studies. The 

biomarker and epidemiology studies summarized above show that menthol cigarettes are not 

associated with increased risk of exposure or disease as compared to nonmenthol cigarettes. 

Chapter 3 

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CHAPTER 3D.
 

MENTHOL IN CIGARETTES DOES NOT ADVERSELY IMPACT
 

THE TOXICOLOGIC PROPERTIES OF MAINSTREAM SMOKE
 

Since menthol and nonmenthol cigarettes are very similar in design characteristics (such as tobacco 

blend, paper characteristics, and filter design), they have been shown to produce mainstream smoke 

(MSS) that is also very similar (except of course, for the differential presence of menthol) (see Table 

A1 in (Heck 2010)). Therefore, it would be expected that the toxicologic profile for menthol and 

nonmenthol MSS would be very similar. The relevant data show that to be the case. 

The toxicologic properties of the mainstream smoke (MSS) from menthol cigarettes have received 

considerable attention, and there are recent reviews on the subject (Werley et al. 2007, Heck 2010). 

These reviews describe three ways in which toxicologic assessments have been performed: 

• On the neat compound 

• On menthol added as a single ingredient to experimental cigarettes 

• On menthol added as one of several ingredients to experimental cigarettes 

NEAT MENTHOL HAS NO NOTABLE TOXICOLOGIC PROPERTIES 

As reviewed below, the toxicity of menthol has been extensively evaluated. Menthol does not burn 

at the temperatures seen in cigarettes: rather, it sublimes at approximately 212 °C and is carried 

nearly quantitatively into smoke as the intact parent molecule. There are repeated cycles of 

sublimation and condensation that take place as the cigarette is smoked, but in none of these cycles 

is the menthol pyrolyzed or combusted (Jenkins et al. 1970a, 1970b; Wilson 1993). Because menthol 

in cigarettes is transferred to the smoker as the intact parent molecule, and may be recovered 

primarily as urinary metabolites identical to those resulting from oral exposures (Benowitz 2010), the 

literature on the safety of the neat compound is in fact quite relevant to the present consideration. A 

total of twelve such analyses, representative of a larger literature on the safety of menthol in 

flavoring applications, are briefly reviewed below. 

Belsito et al. (2008). This general toxicology review considered the various toxicologic 

characteristics of menthol that have been published elsewhere. The broad conclusion was that there 

were no safety concerns regarding the use of menthol. 

National Toxicology Program (1979). Menthol was tested for carcinogenicity by the National 

Cancer Institute in the predecessor to the National Toxicology Program, using lifetime feeding 

studies in male and female Fischer 344 rats and B6C3F1 mice. The details of the test were: 

“Groups of 50 rats of each sex and 50 mice of each sex were administered d,l-menthol at one of the 

following doses, either 3,750 [0.375%] or 7,500 ppm [0.75%] for the rats and either 2,000 [0.2%] or 

4,000 ppm [0.4%] for the mice, for 103 weeks, then observed for 1 or 2 additional weeks. Matched 

controls consisted of 50 untreated rats of each sex and 50 untreated mice of each sex. All surviving 

rats were killed at 105 weeks and all surviving mice at 104 weeks. Mean body weights of dosed rats 

and mice were only slightly lower than those of corresponding controls. No other clinical signs 

Chapter 3 

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related to administration of the d,l-menthol were noted in the dosed groups of animals. A doserelated trend in mortality was observed only in the female mice. Survival at the end of the bioassay 

was at least 62% in all dosed and control groups of animals of each species, and sufficient numbers 

of animals were at risk for the development of late-appearing tumors. In male rats, no tumors 

occurred at incidences which were considered to be related to the administration of d,l-menthol. In 

female rats, no tumors occurred at higher incidences in the dosed groups than in the control groups. 

Fibroadenomas of the mammary gland occurred at lower incidences in the low-dose (10/49) and 

high-dose (7/49) groups than in the control group (20/50), and alveolar/bronchiolar adenomas or 

carcinomas of the lung occurred only in the controls (3/50). In mice of either sex, no tumors 

occurred in dosed groups at incidences that were significantly different from those for 

corresponding control groups. It is concluded that under the conditions of this bioassay, d,lmenthol was not carcinogenic for either Fischer 344 rats or B6C3F1 mice.” Subsequently, several 

genetic toxicology tests were performed to confirm the results of this study (see below). 

In Vitro Genotoxicity 

Most of the remaining studies with the neat compound involve in vitro genotoxicity, with menthol 

being evaluated in several different types of cell cultures. 

Ishidate et al. (1984). One of the first studies used six different strains of Salmonella typhimurium in 

the presence and absence of the S9 metabolic activation mix: this procedure is known as the “Ames 

test.” These authors also evaluated chromosomal aberrations using a Chinese hamster fibroblast cell 

line. Menthol was negative in all tests performed. 

Andersen and Jensen (1984). This study replicated the results of Ishidate et al. (1984) (Ames test 

only), and again no mutagenic activity was noted for menthol. 

Zeiger et al. (1988). Menthol was one of 300 chemicals tested for mutagenicity using the Ames 

test. This work was part of the evaluation by the NTP to correlate results in genetic toxicology 

testing with those obtained in the long-term rodent carcinogenicity studies described above. The 

authors described the results as “negative.” 

Ivett et al. (1989). Menthol was one of 15 individual compounds tested in Chinese Hamster Ovary 

(CHO) cells, using the endpoints chromosomal aberrations and sister chromatid exchange (SCE), in 

the presence and absence of the S9 metabolic mix. This work was part of the evaluation by the 

NTP to correlate results in genetic toxicology testing with those obtained in the long-term rodent 

carcinogenicity studies described above. In both assays menthol was tested “up to toxic or neartoxic levels as evidenced by the reduction of cell confluence at the highest doses.” The authors 

considered menthol to be negative in both assays. 

Myhr and Caspary (1991). Menthol was one of 31 compounds tested for mutagenesis at the 

thymidine kinase locus in L5178Y mouse lymphoma cells (the “mouse lymphoma” assay) in the 

presence and absence of the S9 metabolic mix. This work was part of the evaluation by the NTP to 

correlate results in genetic toxicology testing with those obtained in the long-term rodent 

carcinogenicity studies described above. The authors reported that “no evidence for mutagenicity 

was found.” 

Chapter 3 

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Shelby et al. (1993). Menthol was one of 49 chemicals tested in a mouse bone marrow 

micronucleus test that involved three daily exposures by intraperitoneal injection. This work was 

part of the evaluation by the NTP to correlate results in genetic toxicology testing with those 

obtained in the long-term rodent carcinogenicity studies described above. The authors noted that 

the “The initial test was negative to 1000 mg/kg and was not repeated.” 

Murthy et al. (1991). Tests were performed using in vitro exposures of human lymphocytes, the 

aim being to determine whether menthol had any effect in these cells on chromosome aberration 

and SCE. The authors concluded that “menthol does not have a chromosome-damaging effect in 

human lymphocytes.” 

Foureman et al. (1994). The last of the five comparisons with the results of the NTP long-term 

rodent carcinogenicity studies used the sex-linked recessive lethal assay in Drosophila. Administration 

of menthol to flies was by either feeding (up to 50,000 ppm, 5.0%) or injection (10,000 ppm, 1.0%). 

The lethality rate was very low for both routes of administration, and the authors termed the 

response “negative.” 

Gomes-Carneiro et al. (1998). Menthol was one of a group of essential oils again tested using the 

Salmonella assay (only four strains, tested with and without S9). The authors compared other 

published data with their own and concluded that “menthol is not mutagenic in the Ames test.” 

Additional studies on menthol metabolism and other properties in toxicology test systems are 

available, and these have been considered in extensive reviews of the menthol literature (Adams et 

al. 1996, Belsito et al. 2008). 

Menthol has also been studied as a potential modifier of the speed of permeation of exogenous 

compounds across biological tissues, particularly in topical applications, but also in porcine oral and 

esophageal preparations (Kitagawa and Li 1999, Azzi et al. 2006, Squier et al. 2010). Speculation 

that such effects may promote the speed or efficiency of penetration of tobacco smoke constituents 

is not substantiated as biologically consequential when considered in light of the extensive body of 

smoke biomarkers data showing no significant differences between menthol and nonmenthol 

cigarette smokers (discussed previously in this report). 

Menthol Added to Experimental Cigarettes Has No Adverse Impact on Smoke Toxicology 

Several experiments have evaluated menthol as a single ingredient added to experimental cigarettes 

or as a component of ingredient mixtures (e.g., minor top flavorings, humectants, casings) that 

reflect typical commercial manufacturing practice. These published reports and their underlying data 

have been provided to the FDA and presented to the TPSAC, and are briefly listed and summarized 

below. 

Gaworski et al. (1997). “A 13-wk comparative nose-only smoke inhalation toxicity study was 

conducted using an American-style, cellulose acetate-filtered, non-menthol reference cigarette and a 

similarly blended test cigarette containing 5000 ppm [0.5%] synthetic l-menthol tobacco. Male and 

female Fischer 344 rats were exposed for 1 hr/day, 5 days/wk for 13 weeks at target mainstream 

smoke particulate concentrations of 200, 600 or 1200 mg/m3, while control rats were exposed to 

filtered air. Internal dose biomarkers (blood carboxyhemoglobin, serum nicotine and serum 

cotinine) indicated equivalent exposures were obtained for the two cigarettes. Effects typically noted 

Chapter 3 

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in rats exposed to high levels of mainstream tobacco smoke were similar for both cigarette types and 

included reduced body weights (males slightly more affected than females), increased heart-to-body 

weight ratios and lung weights, and histopathological changes in the respiratory tract. Rats exposed 

to reference cigarette smoke displayed a dose-related increase in nasal discharge that was not 

observed in menthol smoke exposed rats. All smoke-related effects diminished significantly during a 

6-week non-exposure recovery period. The results of this 13-week smoke inhalation study indicated 

that the addition of 5000 ppm (0.5%) menthol to tobacco had no substantial effect on the character 

or extent of the biological responses normally associated with inhalation of mainstream cigarette 

smoke in rats.” 

Previously unpublished work performed by the R. J. Reynolds Tobacco Company and appearing as 

Appendix B in a recent review (Heck 2010) used a comparative approach to assess the mutagenic 

activity of menthol addition in experimental cigarettes. Two types of cigarettes were used, identical 

except for the addition of 1.03% menthol to one of them. This addition rate is about twice as high 

as that typically used commercially. The cigarettes contained a standard commercial blend of 

tobaccos. Ames testing was done on cigarette smoke condensate with 5 bacterial strains, both with 

and without the S9 mix. The authors concluded that “there was no evidence that the addition of 

menthol increases the mutagenicity of smoke particulate material.” 

The same experimental cigarettes as mentioned above were used to make a comparative evaluation 

of the cytotoxicity of the smoke condensates (Heck 2010), using the neutral red uptake (NRU) assay. 

This cytotoxicity assay is among the tests specified by Health Canada for comparative assessments 

of cigarette smoke condensates and is widely used elsewhere for that purpose. These workers used 

CHO cells to assess the proportion of cells killed by the treatment (and therefore unable to 

accumulate the vital dye neutral red). The authors concluded that “there was no evidence that 

menthol addition increases the cytotoxic potential of cigarette smoke condensate” of menthol versus 

nonmenthol cigarettes. 

The same experimental cigarettes as mentioned above were used to generate data on chromosomal 

aberrations, using the sister chromatid exchange (SCE) assay in CHO cells treated with different 

concentrations of cigarette total particulate matter (TPM) (Heck 2010). The SCE assay is not a 

common component of batteries of genotoxicity assays, probably because interpretations of the data 

obtained are considered to be difficult. Smokers have been reported however to have elevated 

numbers of SCEs in circulating lymphocytes in a number of studies, so this in vitro assay may reflect 

processes occurring in smokers. The authors stated that “cigarette smoke TPM from menthol 

cigarettes was not significantly different from that of nonmenthol cigarettes either in the presence or 

absence of S9 activation under conditions of this study.” 

There are several major studies that have examined the toxicologic properties of menthol as one of 

several ingredients added to experimental cigarettes (Gaworski et al. 1998, Gaworski et al. 1999, 

Carmines 2002, Baker et al. 2004); these studies report in vitro and in vivo toxicology data. These 

studies of combinations of commonly-used cigarette ingredients model potential interactions that 

may exist among ingredients used in commercial cigarettes. 

Carmines (2002). The Carmines work used menthol added at a target concentration of 18,000 ppm 

(1.8%) to experimental cigarettes (as part of Ingredient Group 3); the other components added in 

this group were cocoa shells, licorice extract, and corn syrup sugar. Toxicology endpoints included 

the Ames mutagenesis test and the NRU cytotoxicity assay (Roemer et al. 2002), plus a standard 

Chapter 3 

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battery of endpoints classically used in 90-day inhalation studies with cigarette smoke 

(Vanscheeuwijck et al. 2002). None of the in vitro or in vivo toxicology endpoints were significantly 

elevated in the groups with added menthol when compared with no added menthol. 

Baker et al. (2004). The Baker work used menthol added at a target concentration of 23,400 ppm 

(2.34%) to experimental cigarettes, with five other compounds (cocoa, ethanol, licorice, propylene 

glycol, and raisin juice) added in the “B4” group (plus water). Toxicology endpoints included the 

Ames test, the in vitro micronucleus assay of disruption to chromosomal segregation, and the NRU 

cytotoxicity assay, plus a standard battery of classically used endpoints in 90-day inhalation studies. 

The response due to tobacco smoke exposure was not distinguishable between the test and control 

cigarettes, indicating that the presence of the ingredients had made no discernable differences to the 

type and severity of the treatment-related changes. 

Gaworski et al. (1998). The experimental design used in a 90-day smoke inhalation study reported 

by Gaworski used 172 added ingredients allocated to one of four different experimental cigarettes, 

including menthol at a concentration of 5,000 ppm (0.5%) (Gaworski et al. 1998). “Male and female 

Fischer 344 rats were exposed 1 h/day, 5 days/wk, for 13 week to smoke from cigarettes containing 

mixtures of flavor ingredients at target mainstream smoke particulate concentrations between 150 

and 1200 mg/m3. For comparison, separate groups of rats were exposed to smoke from nonflavored reference cigarettes of similar construction and tobacco blend, or to filtered air. Internal 

dose biomarkers (carboxyhemoglobin, serum nicotine, and serum cotinine) were measured during 

the studies to monitor smoke exposure. Effects typically noted in rats exposed to mainstream 

tobacco smoke were similar for both flavored and non-flavored cigarette types. Dose-related 

reductions in body weights, increased organ-to-body weight ratios for the heart and lungs, and a 

trend toward decreased blood glucose concentrations in males were noted in the smoke-exposed 

groups. Exposure-related histopathologic changes occurred only in the respiratory tract. These 

changes were primarily associated with epithelial tissue, and presented as hyperplasia and/or 

metaplasia in the nose and larynx. The anterior sections of the nose were more severely affected 

than were the more posterior regions. Macrophages and areas of epithelial hyperplasia were 

observed in the lungs of smoke-exposed animals. All smoke-related histopathologic effects 

diminished significantly during a 6-week post-exposure recovery period. The results indicate that 

the addition of these flavoring ingredients to cigarette tobacco had no discernible effect on the 

character or extent of the biologic responses normally associated with inhalation of mainstream 

cigarette smoke in rats.” 

Gaworski et al. (1999). A similar approach as in the previous section was used in a 26-week mouse 

skin painting study of cigarette smoke condensate (CSC) using female SENCAR mice: there were 

150 added ingredients allocated to one of six different experimental cigarettes, including menthol at 

a concentration of 5,000 ppm (0.5%). “Groups of 30-50 female SENCAR mice each were initiated 

topically with 50 μg of 7,12-dimethylbenz(a)anthracene (DMBA), and promoted thrice weekly for 26 

weeks with either 10 or 20 mg of CSC from test cigarettes containing ingredient mixtures. For 

comparison, separate groups of mice received concurrent treatment with CSC from reference 

cigarettes prepared without added ingredients. Negative and positive controls were treated with 

acetone or 12-0-tetradecanoyl-phorbol-13-acetate (TPA) as a promoter, respectively. CSC-only 

groups served as promotion controls. Tumors developed in >80% of the TPA-treated mice by 

study week 11, with a <3% background tumor formation in the acetone treated controls at 

termination. Tumor incidence in CSC-only promotion control groups was <20%, with no apparent 

difference between reference and test CSC groups. Approximately 70% of the DMBA-initiated 

Chapter 3 

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mice promoted with 20 mg CSC developed tumors. Tumors first appeared around week 9, with 

about five tumors per tumor bearing animal. Tumor incidence, latency and multiplicity were CSC 

dose related, with a lower tumor incidence (approximately 50%), longer latency (12 weeks), and 

reduced tumor burden (four tumors/tumor bearing animal) at the 10 mg CSC dose level. While 

tumor incidence, latency and multiplicity data occasionally differed between test and comparative 

reference CSC groups, all effects appeared to be within normal variation for the model system. 

Furthermore, none of the changes appeared to be substantial enough to conclude that the tumor 

promotion capacity of CSC obtained from cigarettes containing tobacco with ingredients was 

discernibly different from the CSC obtained from reference cigarettes containing tobacco processed 

without ingredients.” 

As a result of the inclusion of several other compounds in the experimental menthol-containing 

cigarettes, compared with controls, it is difficult to make definitive statements on the role of 

menthol per se in the overall toxicologic responses noted in the studies of ingredient combinations 

reviewed here. Nevertheless, no meaningful increases in biological activity were noted in any study 

involving the addition of menthol to cigarettes. These results further suggest that menthol does not 

participate in chemical interactions with other ingredients that are commonly used in commercial 

cigarettes. 

CONCLUSION 

Among a broad range of toxicologic endpoints evaluated with respect to the neat compound 

menthol, including several different genotoxicity assays (e.g., Salmonella mutagenicity using 5 

different bacterial strains, cytotoxicity (using the NRU), different measures of chromosomal 

aberrations, micronucleus testing, the mouse lymphoma assay, and the sex-linked recessive lethal 

assay in Drosophila), menthol did not show any positive toxicologic findings. These in vitro tests 

broadly support the results of the NTP rat and mouse chronic feeding studies, which unequivocally 

showed no carcinogenic activity of menthol. Neat menthol clearly has very low toxicologic activity. 

In studies with menthol added to experimental cigarettes (either on its own or as part of a mixture), 

including a 26-week dermal carcinogenicity study in mice and multiple nose-only 90-day smoke 

inhalation studies in rats, the addition of menthol did not modify the toxicologic profile in any way 

when the results obtained were compared with those produced by comparable nonmenthol 

cigarettes. 

Overall, the weight of the evidence on wide-ranging toxicology testing of the neat material shows 

that menthol has no notable effects at exposures spanning the ranges typical for its flavor 

applications. Additionally, the weight of the evidence on the toxicologic properties of the 

mainstream smoke from menthol cigarettes compared with nonmenthol cigarettes provides no 

indications of increased toxicity, consistent with a broader conclusion that menthol has no causal 

relationship to adverse impacts on public health. According to the Surgeon General’s framework 

for assessing causality, “the evidence is suggestive of no causal relationship” between menthol 

added to cigarettes and increases in the toxicity of cigarette smoke. 

Chapter 3 

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CHAPTER 3E.
 

MENTHOL DOES NOT MEANINGFULLY ALTER THE
 

CHEMICAL COMPOSITION OF MAINSTREAM SMOKE
 

The chemical composition of the mainstream smoke (MSS) from nonmenthol cigarettes has 

received considerable attention, and there are many publications on the subject (Rodgman and 

Perfetti 2009). In contrast, the MSS from menthol cigarettes has been of much less interest 

scientifically, and consequently publications are sparse. Comparisons of the two data sets reveal 

that, apart from menthol itself, the MSS from menthol cigarettes is very similar to that from 

nonmenthol cigarettes. The main reason for this common MSS composition is that the design 

characteristics (e.g., tobacco blends, paper, filter, to name just a few) of the two cigarette types are 

very comparable, except for the addition of small amounts of menthol. Because the formulations 

are broadly similar, the combustion products of the cigarettes are broadly similar. 

A brief technical note from 1968 (Schmeltz and Schlotzhauer 1968) indicated that neat menthol 

when heated to 800 °C produced small amounts of benzo[a]pyrene (BAP). At 800 °C, 

approximately 400 μg of BAP were calculated to be produced per gram of menthol, with no BAP 

produced at 600 °C. Identification and quantification of BAP was made using (by today’s standard) 

a very crude analytical technology (paper chromatography), and the results do not seem to have been 

confirmed by other workers. In any case, “the correlation of pyrolysis products formed this way 

with those formed during the burning of a cigarette is extremely difficult, if not impossible, without 

knowing the quantitative relationship between the precursor and its products in the cigarette smoke” 

(Jenkins et al. 1970a, 1970b). In a review of pyrolysis work on cigarette components, more recent 

authors commented that “unless they are performed under dynamic conditions that are relevant to 

those that occur during tobacco burning, results can be obtained which have little resemblance to 

those obtained during cigarette smoking” (Baker and Bishop 2004). 

A subsequent study used menthol that was universally-labeled with 14C (Jenkins et al. 1970a, 1970b) 

and clearly showed that in the matrix of MSS there is “very little, if any, pyrolysis and combustion of 

menthol during the puffing of the cigarette,” with approximately 99% of the labeled material 

recovered being in the form of unchanged menthol. Thus, menthol itself does not add to or 

otherwise modify MSS composition, because menthol does not burn at the temperatures seen in 

cigarettes; rather, it sublimes, at approximately 212 °C. The menthol in the tobacco near the burning 

cone of the cigarette (at about 850 °C, see Figure 7 in Wilson 1993) is (1) converted from a solid to 

gaseous menthol and (2) drawn downstream into adjacent cooler tobacco, where (3) it condenses 

back into a solid. There are repeated cycles of sublimation and condensation that take place as the 

cigarette is smoked, but in none of these is the menthol itself pyrolyzed or combusted (Jenkins et al. 

1970a, 1970b; Wilson 1993). A variety of other processes that occur in menthol cigarettes (e.g., in 

the filter) has been described elsewhere (Wilson 1993). 

A recent review (Heck 2010) described the MSS composition of directly comparable cigarettes 

whose only difference was the addition of menthol (at a target rate of 1.03%). A total of 25 analytes 

in MSS were measured in each pair, and the results are presented in Table 3-8 as the ratio (percent) 

of the concentration in the menthol cigarettes to the concentration in the nonmenthol cigarettes. In 

general, the chemical composition of the smoke from the menthol cigarettes was very similar to the 

Chapter 3 

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Chapter 3 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

smoke from nonmenthol cigarettes, with the exception of menthol itself. The lowest ratio was 

69.2% (nitrogen), and the highest was 124% (formaldehyde). This difference in mainstream smoke 

formaldehyde yield achieved statistical significance for these carefully matched experimental 

cigarettes, but the levels of this constituent for the menthol cigarette were well within the ranges 

reported for many contemporary nonmenthol commercial cigarettes. Concentrations of BAP were 

not significantly different between the two cigarettes, confirming other independent work 

(Rustemeier et al. 2002) which indicates that the evolution from menthol upon furnace pyrolysis 

under inert atmosphere that was reported in the very early study by Schmeltz and Schlotzhauer 

(1968) has no relevance to the burning and distillation processes that occur in an actual cigarette. 

Table 3-8.	 Comparison of Mainstream Analyte Concentrations in Menthol and Nonmenthol 

Cigarettes 

Component Menthol Nonmenthol M/NM (%) 

Menthol (mg/cig) 0.41 0 -­

Ammonia (μg/cig) 4.6 4.49 102 

Benzo[a]pyrene (BAP) (ng/cig) 2.65 2.87 92.3 

Puffs 9 8.8 102 

Formaldehyde (μg/cig) 4.2 3.4 124* 

Acetaldehyde (μg/cig) 284.6 275.8 103 

Acetone (μg/cig) 114.8 117.1 98.0 

Acrolein (μg/cig) 22.1 21.4 103 

Hydrogen cyanide (μg/cig) 40.8 43.3 94.2 

Carbon (%) 69 65.25 106* 

Hydrogen (%) 9.71 8.57 113* 

Nitrogen (%) 3.7 5.35 69.2* 

Total particulate matter (mg/cig) 4.6 4.1 112 

Nicotine (mg/cig) 0.35 0.35 100 

Water (mg/cig) 0.3 0.3 100 

Tar (mg/cig) 3.9 3.5 111 

Carbon monoxide (mg/cig) 5.2 5.3 98.1 

Carbon dioxide (mg/cig) 22.1 22.5 98.2 

Hydroquinone (μg/cig) 17.36 17.56 98.9 

Catechol (μg/cig) 20.98 21.38 98.1 

Phenol (μg/cig) 2.56 2.42 106 

Cresol (μg/cig) 2.5 2.34 107 

N-nitrosonornicotine (NNN) (ng/cig) 29 35 82.9 

N-nitrosoanatabine (NAB) (ng/cig) 30 33 90.9 

4-(methylnitrosamino)­

1-(3-pyridyl)-1-butanone (NNK) (ng/cig) 22 28 78.6 

Data obtained from Heck (2010). 

* Statistically significant difference between menthol and nonmenthol (p<0.05); (N=6 cigarettes). 

78
CONCLUSION 

The weight of the evidence clearly shows that the chemical compositions of the MSS from menthol 

and nonmenthol cigarettes are very similar, apart from the presence of menthol itself. Thus, 

according to the Surgeon General’s framework for assessing causality, the “evidence is suggestive 

of no causal relationship” between the use of menthol in cigarettes and harmful changes in 

mainstream smoke chemistry. 

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Chapter 3 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-9. Comparative Risk of Lung Cancer Associated with Menthol Cigarettes vs. that Associated 

with Nonmenthol Cigarettes (N=9) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Brooks et al. 

2003 

United States 

Lung cancer 

Case-control study (643 

cases, 4,110 controls) 

Subjects were current 

or former smokers with 

>20 yrs smoking. 

Among the cases, 61 

men and 53 women 

had ever smoked 

menthols; among the 

controls, 453 men and 

640 women had ever 

smoked menthols. 

Tobacco Use 

Nonmenthol only 

Ever menthol 

Current menthol (>15 yrs) 

1-15 yrs smoking menthol 

>15 yrs smoking menthol 

Subgroups 

Men 

Nonmenthol only 

1-15 yrs smoking menthol 

>15 yrs smoking menthol 

Women 

Nonmenthol only 

1-15 yrs smoking menthol 

>15 yrs smoking menthol 

Whites 

Nonmenthol only 

1-15 yrs smoking menthol 

>15 yrs smoking menthol 

Blacks 

Nonmenthol only 

1-15 yrs smoking menthol 

>15 yrs smoking menthol 

Adjusted Odds Ratios (95% CI) 

1.0 (reference) 

0.89 (0.69-1.14) 

0.90 (0.62-1.31) 

0.80 (0.57-1.13) 

0.97 (0.79-1.34) 

1.0 (reference) 

0.67 (0.43-1.05) 

0.91 (0.57-1.46) 

1.0 (reference) 

1.14 (0.66-1.95) 

1.00 (0.63-1.60) 

1.0 (reference) 

0.86 (0.59-1.28) 

1.01 (0.68-1.51) 

1.0 (reference) 

0.60 (0.27-1.35) 

1.21 (0.64-2.26) 

Adjusted for sex, age, race, year of 

interview, number years smoking, 

cigarettes/day, years since quitting, 

proportion of years smoking filter 

cigarettes. 

The lung cancer risk for long-term smokers of 

menthol cigarettes was similar to that for smokers 

of nonmenthol cigarettes. 

The results of this study do not support the 

hypothesis that smoking menthol cigarettes 

increases the risk of lung cancer relative to 

smoking nonmenthol cigarettes. 

In separate analyses of men, women, Blacks, and 

Whites, long-term use of menthol cigarettes was 

not associated with an increase in lung cancer 

relative to exclusive use of nonmenthol cigarettes. 

* denotes statistically significant increase in risk 

88
 

Chapter 3 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-9. Comparative Risk of Lung Cancer Associated with Menthol Cigarettes vs. that Associated 

with Nonmenthol Cigarettes (N=9) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Carpenter et al. 

1999 

United States 

Lung cancer 

Case-control study (337 

cases, 478 population 

controls) 

Subjects were eversmokers (current or 

former). Among the 

cases, 85 African 

Americans and 66 

Caucasians had ever 

smoked menthols; 

among the controls, 

101 African Americans 

and 122 Caucasians had 

ever smoked menthols. 

Entire Population 

Exclusive regular 

Exclusive menthol 

Mixed menthol/regular 

Subgroups 

Caucasians 

Exclusive regular 

>1-15 pk-yrs menthol 

16-31 pk-yrs menthol 

32+ pk-yrs menthol 

African Americans 

Exclusive regular 

>1-15 pk-yrs menthol 

16-31 pk-yrs menthol 

32+ pk-yrs menthol 

Men 

Exclusive regular 

>1-15 pk-yrs menthol 

16-31 pk-yrs menthol 

32+ pk-yrs menthol 

Women 

Exclusive regular 

>1-15 pk-yrs menthol 

16-31 pk-yrs menthol 

32+ pk-yrs menthol 

Adjusted Odds Ratios (95% CI) 

1.0 (reference) 

1.04 (0.62-1.75) 

1.01 (0.71-1.42) 

1.0 (reference) 

1.01 (0.61-1.68) 

1.01 (0.41-2.47) 

1.06 (0.47-2.36) 

1.0 (reference) 

0.96 (0.54-1.70) 

0.69 (0.30-1.60) 

0.90 (0.38-2.12) 

1.0 (reference) 

0.87 (0.57-1.37) 

1.21 (0.56-2.62) 

1.48 (0.71-3.05) 

1.0 (reference) 

1.58 (0.77-3.22) 

0.51 (0.19-1.34) 

0.41 (0.15-1.11) 

Adjusted for age, sex, race, total packyears, and years since quitting. 

Our results suggest that the lung-cancer risk from 

smoking mentholated cigarettes resembles the risk 

from smoking non-mentholated cigarettes. 

The lung-cancer risk associated with menthol 

smoking was similar to that for exclusive 

nonmentholated cigarette smoking both in the 

total sample and within ethnic groups. 

Our data does not support the hypothesis that the 

increased risk of lung cancer among African 

Americans is due to the increased prevalence of 

menthol smoking. 

* denotes statistically significant increase in risk 

89
 

Chapter 3 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-9. Comparative Risk of Lung Cancer Associated with Menthol Cigarettes vs. that Associated 

with Nonmenthol Cigarettes (N=9) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Etzel et al. 2008 Lung cancer Current Smokers 

Nonmenthol smokers 

Adjusted Odds Ratios (95% CI) 

1.0 (reference) 

We observed no significant risks of lung cancer 

among former or current smokers who reported 

United States Case-control study (491 

cases, 497 population 

controls; all African 

Americans). 

Prevalence of menthol 

smoking was 41% 

among cases and 47% 

among controls. 

Subjects were never, 

current, or former 

smokers. 

Menthol smokers 

Former Smokers 

Nonmenthol smokers 

Menthol smokers 

0.69 (0.46-1.03) 

1.0 (reference) 

0.99 (0.62-1.56) 

Adjusted for age, sex, and smoking 

status (current vs. former). 

smoking mentholated cigarettes and our data 

suggested a possible protective effect of 

mentholated cigarettes for current smokers. 

Existing lung cancer prediction models may not 

be appropriate for predicting risk for African 

Americans. 

Jöckel et al. 2004 Lung cancer Tobacco Use Adjusted Odds Ratios (95% CI) The present study gives no indication for an 

(abstract) 

Case-control study (839 

Not defined 

Ever menthol smoking 

1.0 (reference) 

1.12 (0.68-1.83) 

additional risk of ever smoking menthol cigarettes 

if total amount of smoking is taken into account. 

Germany male and 165 female 

cases; 839 male and 165 

female population 

controls). It appears 

that all subjects were 

White. 

It appears that subjects 

were ever-smokers. 

Adjusted for total amount of tobacco 

smoking. 

However, the number of exposed subjects is small 

hindering definitive conclusions with respect to 

dose. 

* denotes statistically significant increase in risk 

90
 

Chapter 3 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-9. Comparative Risk of Lung Cancer Associated with Menthol Cigarettes vs. that Associated 

with Nonmenthol Cigarettes (N=9) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Kabat and 

Hebert 1991 

United States 

Lung cancer 

Case-control study (588 

male and 456 female 

cases; 914 male and 410 

female hospital 

controls). Prevalence 

of menthol smokers 

ranged from 24-37%, 

depending on age and 

sex. 

All were current 

smokers. 

Men 

Nonmenthol smokers 

1-14 yrs smoking menthol 

15+ yrs smoking menthol 

Women 

Nonmenthol smokers 

1-14 yrs smoking menthol 

15+ yrs smoking menthol 

Adjusted Odds Ratios (95% CI) 

1.0 (reference) 

1.14 (0.82-1.19) 

0.98 (0.70-1.38) 

1.0 (reference) 

0.82 (0.52-1.28) 

0.76 (0.53-1.16) 

Adjusted for inhalation, race, BMI, 

age, education, cigarettes/day, and 

duration of smoking, 

Use of mentholated cigarettes was not associated 

with increased risk of lung cancer or of specific 

histological types of lung cancer in this study. 

If our results are confirmed by other researchers, 

the implication would be that use of mentholated 

cigarettes does not explain black-white differences 

in lung cancer incidence rates or time trends. 

Other hypotheses need to be formulated to 

explain these differences. 

Lee [submitted] Lung cancer 

Meta-analysis of 8 

Use of Menthol 

Cigarettes Among Ever 

Smokers (or Current if 

The data do not suggest any effect of 

mentholation on lung cancer risk. There is also 

no evidence of an increase in men or women 

studies: not Available) Adjusted Relative Risks (95% CI) separately, in Blacks or Whites separately, or in 

Sidney et al. 1995 Overall 0.93 (0.84-1.02) estimates for ever smokers, current smokers, or 

Brooks et al. 2003 Men 1.01 (0.88-1.15) former smokers. 

Murray et al. 2007 Women 0.80 (0.67-0.95) 

Kabat & Hebert 1991 Whites 0.87 (0.75-1.03) While some study weaknesses exist, the 

Carpenter et al. 1999 

Stellman et al. 2003 

Jockel et al. 2004 

Etzel et al. 2008 

Blacks 

Long-Term Use (15+ 

Yrs) of Menthol 

Cigarettes

0.90 (0.73-1.10) epidemiological evidence is consistent with 

mentholation having no effect on the lung 

carcinogenicity of cigarettes. 

Higher lung cancer rates in Black men cannot be 

Overall 0.95 (0.80-1.13) due to their greater preference for mentholated 

Men 1.11 (0.88-1.39) cigarettes. 

Women 0.78 (0.60-1.01) 

Whites 1.02 (0.71-1.46) 

Blacks 1.09 (0.66-1.81) 

* denotes statistically significant increase in risk 

91
Chapter 3 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-9. Comparative Risk of Lung Cancer Associated with Menthol Cigarettes vs. that Associated 

with Nonmenthol Cigarettes (N=9) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Murray et al. Lung cancer Tobacco Exposure Adjusted Hazard Ratios (95% CI) We found no evidence in our data that 

2007 

Clinical trial of smoking 

Death Due to Lung 

Cancer 

mentholation of cigarettes is an attribute that 

contributes to the health risks of smoking. 

United States cessation among 5,887 Plain cigarettes 1.0 (reference) 

(Lung Health smokers with mild- Menthol smokers 0.96 (0.70-1.32) 

Study) moderate airway 

obstruction. About 

20% (1,216) smoked 

menthol cigarettes at 

baseline. There were 

240 deaths due to lung 

cancer in 14 years of 

follow-up. 

All were current or 

former smokers. 

Adjusted for age, sex, cigarettes/day at 

baseline, FEV1 percentage of 

predicted, randomization group, race, 

and baseline years of education. 

Sidney et al. 

1995 

United States 

(Kaiser 

Permanente) 

Lung cancer 

Cohort study (11,761 

subjects; 93 lung 

cancers among 3,654 

menthol smokers and 

225 lung cancers 

among 8,107 

nonmenthol smokers 

followed for a mean of 

approximately 8 years) 

All were current 

smokers of >20 years. 

Men 

Nonmenthol smokers 

Menthol smokers 

1-9 yrs smoking menthol 

10-19 yrs smoking menthol 

>20 yrs smoking menthol 

Women 

Nonmenthol smokers 

Menthol smokers 

1-9 yrs smoking menthol 

10-19 yrs smoking menthol 

>20 yrs smoking menthol 

Adjusted Relative Risks (95% CI) 

1.0 (reference) 

1.45 (1.03-2.02)* 

1.10 (0.65-1.87) 

1.32 (0.84-2.08) 

1.59 (0.96-2.63) 

1.0 (reference) 

0.75 (0.51-1.11) 

0.72 (0.38-1.39) 

1.01 (0.61-1.69) 

0.70 (0.40-1.23) 

Adjusted for age, race, education, 

cigarettes/day, and duration of 

smoking. 

Mentholated cigarette use was associated with a 

statistically significant 45% increase in the 

incidence of lung cancer relative to 

nonmentholated cigarette use in men who were 

long-term smokers. 

This study suggests that there is an increased risk 

of lung cancer associated with mentholated 

cigarette use in male smokers but not in female 

smokers. We cannot explain why the association 

between mentholated cigarette use and lung 

cancer was present in men only. 

* denotes statistically significant increase in risk 

92
 

Chapter 3 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-9. Comparative Risk of Lung Cancer Associated with Menthol Cigarettes vs. that Associated 

with Nonmenthol Cigarettes (N=9) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Stellman et al. 

2003 

United States 

Lung cancer 

Case-control study 

(1,710 White male and 

1,321 White female 

cases, 254 Black male 

and 163 Black female 

cases; 8,151 hospital 

controls). Prevalence 

of menthol smoking 

was 13.5-23.7% for 

White subjects and 

40.8-51.8% for Black 

subjects. 

Subjects were non-, 

current, or former 

smokers. Data 

presented here are for 

current smokers. 

White Men 

Nonmenthol 

Menthol 

Black Men 

Nonmenthol 

Menthol 

White Women 

Nonmenthol 

Menthol 

Black Women 

Nonmenthol 

Menthol 

Adjusted Odds Ratios (95% CI) 

1.0 (reference) 

0.83 (0.63-1.09) 

1.0 (reference) 

1.34 (0.79-2.29) 

1.0 (reference) 

0.61 (0.44-1.06) 

1.0 (reference) 

0.79 (0.41-1.54) 

Adjusted for age, education, BMI, and 

pack-years. 

Smokers of menthol flavored cigarettes were at no 

greater risk for lung cancer than were smokers of 

unflavored brands. 

ORs among smokers of menthol cigarettes were 

practically the same as among smokers of 

nonmenthol cigarettes. 

While Black smokers in our study were more likely 

to choose menthol than nonmenthol brands; our 

data provide no evidence that menthol cigarettes 

per se produce greater lung cancer risk than do 

nonmenthol brands. 

* denotes statistically significant increase in risk 

93
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-10. Comparative Risk of Esophageal Cancer Associated with Menthol Cigarettes vs. that Associated 

with Nonmenthol Cigarettes (N=2) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Hebert and Kabat 

1988 (letter to the 

editor) 

United States 

Esophageal cancer 

Case-control study (216 

male and 96 female 

cases; 305 male and 157 

female hospital controls) 

Men 

Not specified 

>10 yrs smoking menthol 

Women 

Not specified 

>10 yrs smoking menthol 

Relative Risks (95% CI) 

1.0 (reference) 

0.70 (0.29-1.73) 

1.0 (reference) 

1.53 (0.61-3.86) 

Not clear if risk estimates are 

adjusted for confounders. 

We analyzed existing data from a case-control 

study of esophageal cancer and found no 

menthol effect. 

Hebert and Kabat 

1989 

United States 

Esophageal cancer 

Case-control study (209 

male and 94 female 

cases; 301 male and 152 

female hospital 

controls). There were 

45 ever-smokers of 

menthol among the 

cases and 66 among the 

controls. 

All subjects were current 

smokers. 

Men 

Nonmenthol only 

<10 yrs smoking menthol 

>10 yrs smoking menthol 

Women 

Nonmenthol only 

<10 yrs smoking menthol 

>10 yrs smoking menthol 

Adjusted Odds Ratios (95% CI) 

1.0 (reference) 

0.50 (0.23-1.07) 

1.03 (0.39-6.89) 

1.0 (reference) 

1.50 (0.54-4.17) 

2.30 (0.93-5.72) 

Adjusted for education, religion, 

alcohol consumption, race, 

cigarettes/day, and smoking 

duration. 

Our results do not support the hypothesized 

relationship between menthol cigarette 

smoking and esophageal cancer. 

Because of the limitations of this study we 

feel the issue of menthol cigarette smoking 

and esophageal cancer is not resolved. We 

recommend additional studies of ample size 

in appropriate populations or hospitals whose 

‘catchment’ areas include typical American 

Blacks. 

Chapter 3 - Appendix 

94
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-11. Comparative Risk of Oropharyngeal Cancer Associated with Menthol Cigarettes vs. that Associated 

with Nonmenthol Cigarettes (N=1) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Kabat and 

Hebert 1994 

United States 

Oropharyngeal cancer 

Case-control study (194 

male and 82 female 

cases; 845 male and 411 

female hospital 

controls). Only 5% of 

subjects had smoked 

menthol exclusively; 

ever-use of menthol was 

also low (26% of men, 

34% of women). 

All subjects were current 

smokers. 

Men 

Nonmenthol only 

1-14 yrs smoking menthol 

>15 yrs smoking menthol 

Women 

Nonmenthol only 

1-14 yrs smoking menthol 

>15 yrs smoking menthol 

By Subsite Among Men Who

Ever Smoked Menthol* 

Tongue 

Gum, floor of mouth, other 

Pharynx 

By Subsite Among Women

Who Ever Smoked Menthol* 

Tongue 

Gum, floor of mouth, other 

Pharynx 

*Reference group for subsite 

analyses is smokers of 

nonmenthol only. 

Adjusted Relative Risks (95% CI)

1.0 (reference) 

0.6 (0.3-1.1) 

0.9 (0.5-1.6) 

1.0 (reference) 

1.0 (0.7-2.1) 

0.7 (0.5-1.7) 

0.4 (0.1-1.0) 

0.6 (0.3-1.2) 

1.7 (0.8-3.4) 

1.3 (0.5-3.2) 

0.5 (0.2-1.3) 

1.2 (0.4-3.7) 

Adjusted for age, education, filter 

use, race, BMI, hospital, alcohol, 

and cigarettes/day. 

These results indicate that the use of 

mentholated cigarettes is unlikely to be an 

important independent factor in 

oropharyngeal cancer. 

In analyses by subsite, menthol use was 

positively associated only with cancer of 

the pharynx in males, although the 

magnitude of the association was small. 

Chapter 3 - Appendix 

95
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-12. Comparative Risk of Other Smoking-Related Cancers Associated with Menthol
 

Cigarettes vs. that Associated with Nonmenthol Cigarettes (N=1)
 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT 

AUTHORS’ 

CONCLUSIONS 

Friedman et al. 

1998 

United States 

(Kaiser 

Permanente) 

Smoking-related 

cancers other than 

lung 

Cohort study 

(11,760 subjects; 69 

cancers among 3,654 

menthol smokers and 

212 cancers among 

8,106 nonmenthol 

smokers followed for 

more than 10 years). 

All were current 

smokers of >20 years. 

Men Who Smoked Menthol* 

All cancers other than lung 

Upper aerodigestive 

Pancreas 

Renal adenocarcinoma 

Other urinary tract 

Women Who Smoked Menthol* 

All cancers other than lung 

Upper aerodigestive 

Pancreas 

Renal adenocarcinoma 

Other urinary tract 

Uterine cervix 

*Reference group for all comparisons is 

smokers of plain cigarettes. 

Rate Ratios (95% CI) 

0.76 (0.52-1.11) 

0.68 (0.36-1.28) 

0.60 (0.25-1.44) 

1.28 (0.39-4.15) 

0.83 (0.45-1.55) 

0.79 (0.53-1.18) 

0.70 (0.30-1.67) 

0.76 (0.32-1.81) 

0.73 (0.08-7.00) 

0.71 (0.30-1.68) 

1.06 (0.53-2.12) 

Adjusted for age. 

Risk was not increased among persons who 

currently smoked mentholated compared 

with plain cigarettes for all of the non-lung 

smoking-related cancers combined or for 

most sites studied. 

Results were similar when current smokers of 

mentholated and plain cigarettes were 

restricted, respectively, to persons who 

reported smoking mentholated cigarettes for 

at least 10 years and for less than six months. 

The association of mentholation with lung 

cancer in this study population may be merely 

a chance finding, particularly as it was absent 

in women and has not been replicated 

elsewhere. 

Most analyses did not present risks by race. 

However, the authors did discuss prostate 

cancer because of its higher incidence rate 

among African Americans. They found no 

statistically significant excess risk associated 

with mentholation in analyses not controlled 

for race (rate ratio=1.15, 95% CI:0.82-1.62), 

and in Cox proportional hazards regression 

controlling for age and race (rate ratio=1.12; 

95% CI:0.80-1.58). 

Chaper 3 - Appendix 

96
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-13. Comparative Risk of Other Cardiac/Lung Outcomes Associated with Menthol
 

Cigarettes vs. that Associated with Nonmenthol Cigarettes (N=2)
 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Murray et al. 2007 

United States 

(Lung Health 

Study) 

Coronary heart 

disease 

Cardiovascular 

disease 

Clinical trial of 

smoking cessation 

among 5,887 subjects 

(age 35-60) with mildmoderate airway 

obstruction. About 

20%(1,216) smoked 

menthol cigarettes at 

baseline. There were 

731 deaths due to any 

cause, 77 deaths due to 

CHD, and 163 deaths 

due to CVD in 14 

years of follow-up. 

All were current or 

former smokers. 

Menthol Smokers* 

Death Due To 

Coronary heart disease 

Cardiovascular disease 

Any cause 

Adjusted Hazard Ratios (95% CI) 

1.31 (0.77-2.22) 

1.03 (0.70-1.52) 

0.997 (0.83-1.20) 

Adjusted for age, sex, cigarettes/day at 

baseline, FEV1 percentage of predicted, 

randomization group, race, and baseline 

years of education. 

We found no evidence in our data that 

mentholation of cigarettes is an attribute that 

contributes to the health risks of smoking. Still, 

the hazard ratio associated with smoking menthol 

cigarettes and coronary heart disease (1.31) is of 

sufficient magnitude that one can imagine that it 

might reach statistical significance in a study of 

sufficient sample size. 

* denotes statistically significant increase in risk 

Chapter 3 - Appendix 

97
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-13. Comparative Risk of Other Cardiac/Lung Outcomes Associated with Menthol 

Cigarettes vs. that Associated with Nonmenthol Cigarettes (N=2) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE MEASURE OF EFFECT AUTHORS’ CONCLUSIONS 

Pletcher et al. 2006 

United States 

(CARDIA study) 

Atherosclerotic 

disease 

Lung function 

Cohort study (5,115 

subjects; 972 smoked 

menthol and 563 

smoked nonmenthol at 

baseline); 15-year 

follow-up. 

Coronary Calcification

Nonmenthol cigarettes 

(per pk-yr increase) 

Menthol cigarettes 

(per pk-yr increase) 

p-value comparing strength of 

association (nonmenthol vs. 

menthol) 

Lung Function 

Nonmenthol cigarettes 

(per pk-yr increase) 

Menthol cigarettes 

(per pk-yr increase) 

p-value comparing strength of 

association (nonmenthol vs. 

menthol) 

Adjusted Odds Ratios (per 10-packyear increase) (95% CI)

1.27 (1.01-1.60)* 

1.33 (1.06-1.68)* 

0.75 

Excess Decline in FEV1 (mL) (95%

CI) 

84 (32-137) 

80 (30-129) 

0.88 

Adjusted for age, sex, ethnicity, 

socioeconomic status (education, 

income), habits (alcohol consumption 

and exercise), cumulative exposure to 

cigarettes, and differential loss to followup. 

Menthol and nonmenthol cigarettes seem to be 

equally harmful per cigarette smoked in terms of 

atherosclerosis and pulmonary function decline. 

Mentholation of cigarettes does not seem to 

explain disparities in ischemic heart disease and 

obstructive pulmonary disease between African 

Americans and European Americans in the United 

States. 

* denotes statistically significant increase in risk 

Chapter 3 - Appendix 

98
Chapter 3 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Ahijevych and 

Parsley 1999 

95 female smokers 

49 menthol and 46 

nonmenthol smokers 

48 Black and 47 White 

CO measured 2 min prior 

to smoking and 2 min after 

Blood sample for nicotine 

and baseline cotinine 

obtained 1 min before 

smoking and for nicotine 1 

min after 

Cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Cotinine/cigarette ratio 

Menthol smokers 

Nonmenthol smokers 

239* 

189 

17.8* 

13.1 

*p<0.05 (unadjusted), 

menthol greater than 

nonmenthol 

No significant interaction 

effects of ethnicity and 

menthol preference on 

smoke constituent 

exposure 

Menthol smokers had higher cotinine levels 

(p=0.02) and higher cotinine/cigarette ratios 

(p=0.04) compared to nonmenthol smokers. 

Ahijevych and 

Wewers 1994 

142 female smokers 

130 menthol and 12 

nonmenthol smokers 

142 Black 

Self-reported average daily 

cigarette consumption 

Saliva sample for cotinine 

analysis obtained while 

completing questionnaire 

Cigarettes per day (CPD) 

Menthol smokers 

Nonmenthol smokers 

Cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Cotinine/cigarette (ng/ml/cigarette) 

Menthol smokers 

Nonmenthol smokers 

14.8 ± 9.7 

11.4 ± 5.7 

394 

369 

37.9 

33.6 

No significant difference 

(unadjusted) 

The average cotinine concentration for 

women smoking menthol cigarettes was not 

significantly different from the mean cotinine 

concentration for nonmenthol smokers. 

Menthol smokers in this study tended to have 

a nonsignificantly higher smoking rate than 

nonmenthol smokers. 

Fifty-eight percent of the total sample had 

cotinine/cigarette ratios >25 ng/ml/cigarette 

and were classified as underreporters. 

99
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Ahijevych et al. 

2002 

32 female smokers 

20 menthol and 12 

nonmenthol smokers 

16 African American and 16 

Caucasian 

Subjects smoked ad libitum 

on day 1. Plasma samples 

for cotinine assays were 

obtained every 8 h to 

establish a baseline. 

Subjects abstained from 

smoking day 2-7; samples 

were obtained for cotinine 

analysis every 8 h until 

discharge at 7 PM of day 7. 

Abstinence was confirmed 

via exhaled CO 

measurement. 

CPD 

Menthol smokers 

Nonmenthol smokers 

Baseline cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Cotinine/cigarette ratio 

Menthol smokers 

Nonmenthol smokers 

Cotinine half-life (hr) 

Menthol smokers 

Nonmenthol smokers 

19.8 ± 7.5 

21.6 ± 7.3 

342 ± 123* 

230 ± 123 

20.7 ± 12.8* 

12.4 ± 8.8 

23.1 ± 7.9 

18.1 ± 7.9 

p<0.05 (unadjusted), 

menthol greater than 

nonmenthol 

There was a significantly (p=0.019) greater 

baseline cotinine concentration among 

smokers of menthol compared with 

nonmenthol cigarettes, with a similar number 

of cigarettes smoked per day. The 

cotinine/cigarette ratio was significantly 

(p=0.05) higher in menthol smokers 

compared with nonmenthol smokers. 

Menthol smokers had a nonsignificantly 

longer cotinine half-life than nonmenthol 

smokers. 

Allen and 

Unger 2007 

432 smokers 

296 menthol smokers 

136 nonmenthol smokers 

199 men and 233 women 

432 African American 

Breath and saliva samples 

provided; timing 

unspecified 

Cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Carbon monoxide (CO) (ppm) 

Menthol smokers 

Nonmenthol smokers 

347.7 ± 182.73 

386.0 ± 192.51 

16.88 ± 8.06 

16.46 ± 8.32 

No significant differences 

(unadjusted) 

Menthol and nonmenthol smokers did not 

differ significantly on CO or salivary cotinine. 

Chapter 3 - Appendix 

100
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Benowitz et al. 14 smokers CPD Our data do not support the hypothesis that 

2004 Menthol smokers 28.3 mentholated cigarette smoking results in a 

12 men and 2 women 

7 African American and 7 

Nonmenthol smokers 

Nicotine intake (mg) 

22.1 greater absorption of tobacco smoke toxins. 

Our finding of impaired metabolism of 

nicotine while mentholated cigarette smoking 

White Menthol smokers 29.8 suggests that mentholated cigarette smoking 

Two-period crossover 

study. Subjects randomly 

Nonmenthol smokers 

Nicotine/cigarette (mg) 

30.6 enhances systemic nicotine exposure. 

assigned to smoking either Menthol smokers 1.49 

menthol or nonmenthol 

cigarettes for a one-week 

period. All subjects smoked 

nonmenthol cigarettes 

Nonmenthol smokers 

Unlabeled nicotine in plasma 

(ng/ml·h) 

1.53 

during 1st week as washout. Menthol smokers 404 

Blood sample for baseline 

nicotine analysis obtained at 

Nonmenthol smokers 

Blood carboxyhemoglobin (%·h) 

388 

time of eligibility evaluation Menthol smokers 109.8 

While hospitalized on days 

3 to 6 of each treatment 

period, subjects smoked 20 

Nonmenthol smokers 

Disposition Kinetics of Nicotine 

Total clearance (ml/min) 

116.1 

cigarettes per day, one every Menthol smokers 1289 

45 min, from 8 AM to 11 

PM. 

Nonmenthol smokers 

Renal clearance (ml/min) 

1431** 

On day 5 each subject Menthol smokers 87 

received a 30-min infusion 

of a 50:50 mixutre of 

nicotine-d2 and cotinine-d4. 

Nonmenthol smokers 

Nonrenal clearance (ml/min) 

82 

Blood samples were Menthol smokers 1202 

collected at 8 AM, noon, 

then 10, 20, 30, 45, 60 and 

90 min and 2, 3, 4, 8, 12, 16, 

Nonmenthol smokers 1339** 

Chapter 3 - Appendix 

101
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Benowitz et al. 20, 24, 44 and 68 h T1/2 (min; half-life) 

2004 postinfusion. Urine was Menthol smokers 156 

(continued) collected for analysis of 

nicotine and metabolites for 

the first 8 h after start of 

infusion and for 24 h on 

Nonmenthol smokers 

Vss (L; volume of distribution at 

steady state)

140 

each hospital day for Menthol smokers 223 

analysis of menthol 

concentration. Blood 

samples were obtained two 

days after discharge at 44 

Nonmenthol smokers 

F (ml/min; fractional conversion of

nicotine to cotinine) 

219 

and 68 h. Menthol smokers 0.66 

Nonmenthol smokers 

CLnic cot (ml/min; clearance) 

0.65 

Menthol smokers 850 

Nonmenthol smokers 

Disposition Kinetics of Cotinine 

Total clearance (ml/min) 

940 

Menthol smokers 47.1 

Nonmenthol smokers 

Renal clearance (ml/min) 

50.0 

Menthol smokers 10.3 

Nonmenthol smokers 

Nonrenal clearance (ml/min) 

11.3 

Menthol smokers 36.8 

Nonmenthol smokers 

T1/2 (min; half-life) 

38.7 

Menthol smokers 1039 

Nonmenthol smokers 1049 

Chapter 3 - Appendix 

102
 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Benowitz et al. 

2004 

(continued) 

Vss (L; volume of distribution at 

steady state) 

Menthol smokers 

Nonmenthol smokers 

Urinary Recovery 

Nicotine (%) 

Menthol smokers 

Nonmenthol smokers 

Nicotine glucuronide (%) 

Menthol smokers 

Nonmenthol smokers 

Cotinine (%) 

Menthol smokers 

Nonmenthol smokers 

Cotinine glucuronide (%) 

Menthol smokers 

Nonmenthol smokers 

3’-hydroxycotinine (%) 

Menthol smokers 

Nonmenthol smokers 

3’-hydroxycotinine glucuronide (%) 

Menthol smokers 

Nonmenthol smokers 

64 

65 

43.3 

32.9 

13.7 

14.8 

24.5 

29.0 

8.7 

9.8 

7.0 

11.1 

2.7 

4.1 

**p<0.05 (unadjusted), 

nonmenthol greater than 

menthol 

Chapter 3 - Appendix 

103
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Benowitz et al. 

2010 

127 smokers 

60 menthol and 67 

nonmenthol smokers 

62 African American and 65 

non-African American 

Blood samples were 

obtained for nicotine and 

cotinine. Urine samples 

were obtained for 

creatinine, nicotine and its 

five major metabolites, 

NNAL, and metabolites of 

several PAHs. The time of 

smoking the last cigarette 

prior to blood and urine 

sampling was recorded. 

CPD (mean over 3 days) 

Menthol smokers 

Nonmenthol smokers 

Plasma cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Urine nicotine equivalents (pmol/mg 

creat) 

Menthol smokers 

Nonmenthol smokers 

Urine menthol (μg/mg creat) 

Menthol smokers 

Nonmenthol smokers 

Urine NNAL (pmol/mg creat) 

Menthol smokers 

Nonmenthol smokers 

Urine total PAHs (pmol/mg creat) 

Menthol smokers 

Nonmenthol smokers 

18.8 

17.0 

202 

217 

47.2 

59.8** 

4.8* 

2.1 

0.9 

1.2 

81.6 

115.2** 

*p<0.05 (unadjusted), 

menthol greater than 

nonmenthol 

**p<0.05 (unadjusted), 

nonmenthol greater than 

menthol 

Urine menthol is measurable in the great 

majority of menthol cigarette smokers, and 

urine menthol is highly correlated with 

exposure to nicotine. Menthol is not 

independently associated with carcinogen 

exposure when nicotine intake is considered. 

Reviewer comment: Neither plasma cotinine 

nor urinary nicotine equivalents was higher in 

menthol smokers as compared to 

nonmenthol smokers (urinary nicotine 

equivalents were significantly higher in 

nonmenthol smokers as compared to 

menthol smokers). 

Chapter 3 - Appendix 

104
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Clark et al. 

1996 

161 smokers 

76 menthol and 85 

nonmenthol smokers 

74 men and 87 women 

65 Black and 96 White 

Subjects abstained from 

smoking for 1 h followed by 

blood sampling for cotinine 

analysis. Subjects then 

smoked 1 cigarette. CO 

measurements were 

obtained prior to smoking 

and within 120 s of smoking 

and within 120 s of 

completing the test 

cigarette. 

Butts of all cigarettes 

smoked for 1 week were 

collected. 

Serum cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Difference (menthol –nonmenthol) 

Expired-air CO (ppm) 

Menthol smokers 

Nonmenthol smokers 

478.2* 

349.1 

84.5*** 

40.3 

35.8 

*p<0.05 (unadjusted 

data), menthol greater 

than nonmenthol 

***p<0.05 (adjusted for 

race, CPD and mean 

amount of cigarette 

smoked), menthol greater 

than nonmenthol 

After adjusting for race, CPD, and mean 

amount of each cigarette smoked, menthol 

was associated with higher cotinine levels 

(p=0.03) and carbon monoxide 

concentrations (p=0.02). 

Chapter 3 - Appendix 

105
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Gan et al. 2008 1,520 smokers 

346 menthol and 1,174 

nonmenthol smokers 

840 men and 680 women 

189 Black and 1331 nonBlack 

Blood samples obtained 

during clinical examination 

in NHANES 1999-2002 

Cotinine (nmol/L) 

Menthol smokers 

Nonmenthol smokers 

1333.8 ± 40.1 

1230.3 ± 24.5 

No significant difference 

(adjusted for sex, CPD, 

age, race, BMI, poverty 

status and nicotine 

content per cigarette) 

We observed higher serum cotinine 

concentrations in those who used 

mentholated cigarettes compared with 

nonmentholated cigarettes (103.4 nmol/L; 

p=0.037). 

Reviewer comment: This difference was no 

longer significant in the multivariate analysis 

which includes adjustment for other factors 

(p=0.632). 

Heck 2009 112 smokers CPD (median) There were no significant differences between 

Menthol smokers 27 menthol and nonmenthol smokers in any 

54 menthol smokers and 58 

nonmenthol smokers 

Nonmenthol smokers 

Carboxyhemoglobin (%) 

27 biomarker concentrations (unadjusted and 

creatinine-adjusted); p-values ranged from 0.2 

to 0.8. 

50 men and 62 women Menthol smokers 5.9 

28 Black and 84 White 

Nonmenthol smokers 

Nicotine (μg/ml) 

6.5 The present blood (carboxyhemoglobin) and 

urine (total nicotine equivalents, total NNAL) 

biomarkers findings are not consistent with 

Subjects smoked specified Menthol smokers 1.5 speculation that smokers of mentholated 

brands of their preferred 

cigarette type ad libitum for 2 

weeks prior and during the 

Nonmenthol smokers 

Cotinine (ug/ml) 

1.7 cigarettes may exhibit an increased smoking 

intensity or smoke constituent exposures 

relative to those smoking nonmentholated 

1-week study interval. 24-h Menthol smokers 3.3 cigarettes of broadly similar design and FTC 

urine collections and a 

blood sample were obtained 

on the 1st day and 7th day of 

Nonmenthol smokers 

Total nicotine equivalents (μg/ml) 

4.3 smoke yield. 

the study period. Menthol smokers 15.5 

Nonmenthol smokers 17.7 

Chapter 3 - Appendix 

106
 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Heck 2009 Cigarette butts were Total nicotine equivalents (mg/24 h) 

(continued) collected during two 24-h Menthol smokers 21.1 

intervals preceding blood 

and urine collections. 

Nonmenthol smokers 

Nicotine-glucuronide (μg/ml) 

24.2 

Menthol smokers 0.3 

Nonmenthol smokers 

Cotinine-glucuronide (μg/ml) 

0.5 

Menthol smokers 1.9 

Nonmenthol smokers 

trans-3’-hydroxycotinine (μg/ml) 

2.7 

Menthol smokers 5.9 

Nonmenthol smokers 

trans-3’-hydroxycotinine-glucuronide 

(μg/ml) 

6.6 

Menthol smokers 1.3 

Nonmenthol smokers 

NNAL (pg/ml) 

1.6 

Menthol smokers 67.9 

Nonmenthol smokers 

NNAL-glucuronide (pg/ml) 

77.15 

Menthol smokers 164.6 

Nonmenthol smokers 

Total NNAL (pg/ml) 

212.4 

Menthol smokers 239.4 

Nonmenthol smokers 

Total NNAL (ng/24-h urine) 

303.6 

Menthol smokers 300.3 

Nonmenthol smokers 419.4 

Chapter 3 - Appendix 

107
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Heck 2009 

(continued) 

No significant differences 

(unadjusted) 

Ho et al. 2009 700 light smokers (≤10 

CPD) 

569 menthol smokers 

131 nonmenthol smokers 

233 men and 467 women 

700 African American 

All subjects were 

participants in a doubleblind, placebo-controlled 

smoking cessation study. 

Cigarettes per day were selfreported. 

Blood sample for nicotine 

and its metabolites was 

collected at study 

randomization. Expired 

CO levels were also 

measured. 

CPD 

Menthol smokers 

Nonmenthol smokers 

Expired CO (ppm) 

Menthol smokers 

Nonmenthol smokers 

Plasma cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Plasma 3’-hydroxycotinine 

(Correlation coefficient)

Menthol smokers 

Nonmenthol smokers 

7.07 

7.53 

13.49 

14.74 

242.93 

246.84 

0.45 

0.46 

No significant differences 

(unadjusted) 

Those who smoked mentholated cigarettes 

trended toward reporting fewer CPD 

compared with those who did not (p=0.05), 

although no difference was found for expired 

CO or plasma cotinine levels between 

mentholated and nonmentholated cigarette 

smokers. 

The correlation coefficients between CPD 

and expired CO with plasma nicotine and its 

metabolites were generally not altered when 

analyzed separately by mentholated cigarettes. 

Chapter 3 - Appendix 

108
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Jarvik et al. 

1994 

20 male smokers 

10 menthol and 10 

nonmenthol smokers 

10 Black and 10 White 

Study participants attended 

2 testing sessions of 1-2 h 

each separated by at least 1 

week. In one session they 

smoked an experimentersupplied commercial 

menthol cigarette and in the 

other a regular cigarette. 

Blood samples were 

obtained prior to smoking 

and at 2-5 min after 

completion of smoking for 

analysis of 

carboxyhemoglobin. Endexpired CO samples were 

obtained immediately prior 

to and approximately 1 min 

after smoking. 

Total particulate matter, inhaled (mg) 

Menthol smokers 

Nonmenthol smokers 

Total particulate matter, (% retained) 

Menthol smokers 

Nonmenthol smokers 

Carboxyhemoglobin boost (% change) 

Menthol smokers 

Nonmenthol smokers 

CO boost (change in ppm) 

Menthol smokers 

Nonmenthol smokers 

10.16 

9.31 

69.9 

72.0 

1.27 

0.98 

6.53 

5.79 

No significant differences 

(unadjusted) 

Compared to regular cigarettes, mentholated 

cigarettes produced a significantly greater 

boost in carbon monoxide measured as both 

blood carboxyhemoglobin and end-expired 

carbon monoxide. 

Reviewer comment: Although the authors 

conclude that there were significant 

differences between menthol and nonmenthol 

smokers, the results of the statistical analysis 

do not support this finding. 

Chapter 3 - Appendix 

109
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Muscat et al. 

2009 

525 smokers 

284 menthol smokers and 

241 nonmenthol smokers 

258 men and 267 women 

237 Black and 288 White 

Urine was collected at 9 

AM. Subjects were asked to 

abstain from smoking from 

midnight the previous night. 

Plasma cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Urinary cotinine (μg) 

Menthol smokers 

Nonmenthol smokers 

Thiocyanate (μm/L) 

Menthol smokers 

Nonmenthol smokers 

NNAL+NNAL-Gluc (pmol/mg 

creatinine) 

Menthol smokers 

Nonmenthol smokers 

NNAL-Gluc/NNAL 

Menthol smokers 

Nonmenthol smokers 

371 ± 252 

330 ± 249 

4246 ± 4143 

4193 ± 4532 

166 ± 48 

167 ± 50 

2.9 ± 2.1 

3.2 ± 2.2 

3.0 ± 1.6 

3.8 ± 2.5** 

**p<0.05 (adjusted for 

age, education, CPD, race 

and sex), nonmenthol 

greater than menthol 

There were no significant differences in the 

mean concentrations of all cigarette smoke 

metabolites between menthol and 

nonmenthol smokers in Blacks and Whites, 

after adjustment for sex and other factors. 

The ratio of NNAL-Gluc to NNAL, a 

possible indicator of lung cancer risk, was 

significantly lower in menthol versus 

nonmenthol smokers. 

These data indicate that menthol is not 

associated with a higher exposure to tobacco 

smoke carcinogens. Menthol may not be 

more hazardous than other cigarette 

formulations for most smokers, although it 

cannot be ruled out at this time that some 

menthol smokers are possibly at increased 

risk for lung cancer because of selective 

inhibition of UDP-glucuronosyltransferase 

enzymes. 

Chapter 3 - Appendix 

110
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Mustonen et al. 

2005 

307 smokers 

88 menthol and 219 

nonmenthol smokers 

149 men and 158 women 

51 Black and 256 White 

Subjects were all smokers 

recruited for a clinical 

smoking cessation trial 

Salivary cotinine samples 

and CO levels were 

obtained at first two precessation visits which were 

scheduled to allow at least 6 

waking hours for each 

participant to reach his or 

her typical level of cigarette 

consumption. 

CPD 

Menthol smokers 

Nonmenthol smokers 

Sex x race x cigarette type interaction 

Salivary cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Sex x cigarette type interaction 

Sex x race x cigarette type interaction 

Cotinine/CPD

Menthol smokers 

Nonmenthol smokers 

Sex x cigarette type interaction 

Sex x race x cigarette type interaction 

Not provided 

Not provided 

p=0.002 

476.1 ± 218.3 

441.9 ±197.3 

p=0.05 

p=0.05 

23.3 ± 13.6* 

19.4 ± 9.4 

p=0.01 

p<0.001 

*p=0.004 (unadjusted); 

menthol is greater than 

nonmenthol 

No differences in CPD were found between 

smokers of nonmenthol and menthol 

cigarettes (p=0.44). Cotinine levels were 

higher among menthol smokers than among 

nonmenthol smokers, but this difference did 

not reach statistical significance. The 

cotinine/CPD ratio was, however, higher 

among menthol smokers than nonmenthol 

smokers. 

We found a significant sex x race x menthol 

interaction on salivary cotinine level as well as 

cotinine/CPD ratio. 

CPD was self-reported. 

Chapter 3 - Appendix 

111
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Patterson et al. 

2003 

190 smokers 

55 menthol and 135 

nonmenthol smokers 

95 men and 95 women 

63% Caucasian 

25% African American 

12% Hispanic, Asian, other 

or mixed 

Subjects were all treatmentseeking smokers; data were 

collected at baseline 

assessment. 

Subjects were instructed to 

smoke 1 cigarette 

immediately prior to 

entering research center at 

which time CO levels were 

measured. Approximately 

40 min later, subjects 

smoked 1 cigarette. Blood 

samples for nicotine and 

cotinine analyses were 

obtained before and after 

(within 3 min) of “boost 

cigarette. 

Nicotine boost (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Baseline cotinine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Baseline nicotine (ng/ml) 

Menthol smokers 

Nonmenthol smokers 

Median (SD) 

11.2 ± 5.5 

10.8 ± 5.0 

316.5 ± 147.5 

276.5 ± 119.2 

20.9 ± 10.3 

19.3 ± 10 

No significant differences 

(unadjusted) 

Menthol/nonmenthol brand was not 

associated with nicotine boost or baseline 

nicotine. Baseline cotinine was significantly 

elevated among menthol smokers as 

compared to nonmenthol smokers (p<0.10). 

Reviewer comment: Although the authors 

conclude that there was a significant 

difference between menthol and nonmenthol 

smokers, the results of the statistical analysis 

do not support this finding. 

Chapter 3 - Appendix 

112
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Signorello et al. 

2009 

225 smokers 

139 menthol and 116 

nonmenthol smokers 

128 men and 127 women 

130 Black and 125 White 

Blood samples for cotinine 

analysis were obtained at 

time of enrollment. 

Subjects self-reported 

number of cigarettes 

smoked in previous 24 h at 

time of blood collection. 

Difference in cotinine (ng/ml) in 

menthol vs. nonmenthol 

Black men 

White men 

Black women 

White women 

-6.2 

-1.0 

-12.4 

-18.1 

No significant difference 

(adjusted) 

We observed no positive association between 

cotinine levels and menthol cigarette use. 

Strasser et al. 

2011 

109 smokers 

32 menthol and 77 

nonmenthol smokers 

64 men and 45 women 

105 Caucasian and 4 nonCaucasian 

Blood samples for nicotine 

metabolite analysis and 

urine samples for total 

NNAL were obtained. 

Time since last cigarette not 

provided. 

Nicotine metabolite ratio (ratio of 

cotinine and 3’-hydroxycotinine) 

Menthol smokers 

Nonmenthol smokers 

Not provided 

Not provided 

No significant difference 

(unadjusted) 

NMR was non-significantly higher among 

participants who smoked nonmenthol 

cigarettes (p=0.10). 

Chapter 3 - Appendix 

113
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Wang et al. 

2010 

3341 smokers 

1044 menthol and 2297 

nonmenthol smokers 

1419 men and 1922 women 

614 African American and 

2727 White 

24 h urine samples were 

collected for determination 

of nicotine and five major 

metabolites. Blood samples 

were collected for serum 

cotinine analysis and 

carboxyhemoglobin 

determination. 

Subjects collected all 

cigarettes butts during 24 h 

urine collection period. 

CPD 

Menthol smokers 

Nonmenthol smokers 

Nicotine equivalents (mg/24 h) 

Menthol smokers 

Nonmenthol smokers 

Nicotine equivalents per cigarette 

(mg/cig) 

Menthol smokers 

Nonmenthol smokers 

Carboxyhemoglobin (% sat) 

Menthol smokers 

Nonmenthol smokers 

Serum cotinine (ng/ml)

Menthol smokers 

Nonmenthol smokers 

15.0 ± 8.7 

16.8 ± 9.0** 

12.78 ± 7.80 

13.51 ± 7.94** 

0.96 ± 0.67* 

0.90 ± 0.67 

5.18 ± 2.27 

5.35 ± 2.28** 

188.94 ± 108.43 

183.44 ± 105.39 

*p<0.05 (unadjusted); 

menthol greater than 

nonmenthol 

**p<0.05 (unadjusted); 

nonmenthol greater than 

menthol 

Smoking mentholated cigarettes does not 

increase daily exposure to smoke constituents 

as measured by nicotine equivalents (NE) and 

carboxyhemoglobin (COHb). 

Analyses of variance revealed no statistically 

significant effects of mentholated cigarettes 

on NE/24 h, COHb, serum cotinine and 

NE/cigarette. 

Reviewer comment: The statistically 

significant difference found in the univariate 

analysis (higher nicotine equivalents in 

menthol vs. nonmenthol) disappeared after 

adjustment for other factors (age, sex, BMI, 

race, smoking machine derived tar delivery 

category, CPD, U.S. Census region, annual 

household income, education and two- and 

three-way interactions) 

Chapter 3 - Appendix 

114
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Williams et al. 

2007 

142 smokers 

79 menthol (47 

schizophrenic, 32 control) 

and 63 nonmenthol (42 

schizophrenic, 21 control) 

smokers 

89 schizophrenic smokers 

and 53 control smokers 

Menthol smokers included 

33 Blacks, 33 Whites, 8 

Hispanic/Latino, 4 Asians 

and 1 Other. 

Exhaled CO measurements 

and blood samples for 

nicotine, cotinine and trans3’-hydroxycotinine were 

obtained on the afternoon 

of a normal smoking day 

approximately 2 min after 

smoking their usual 

cigarettes. 

Serum nicotine (ng/ml)a 

Menthol smokers 

Nonmenthol smokers 

Nicotine/CPDb 

Menthol smokers 

Nonmenthol smokers 

Serum cotinine (ng/ml)a 

Menthol smokers 

Nonmenthol smokers 

Cotinine/CPDb 

Menthol smokers 

Nonmenthol smokers 

COa 

Menthol smokers 

Nonmenthol smokers 

3-HC/cotinine ratioa 

Menthol smokers 

Nonmenthol smokers 

Predictors of serum nicotine levelc 

Menthol smokers 

Nonmenthol smokers 

a Adjusted for group, CPD and race 

b Adjusted for group and race c Regression model included variables for 

FTC nicotine machine-measured delivery, 

age, education, marital status, age at onset 

of smoking, sex, race, CPD, employment 

status, time of blood draw, and number of 

past quit attempts. 

27.2 ± 10.9* 

22.4 ± 10.8 

1.3 ± 0.8 

1.2 ± 0.7 

294.3 ± 172.2* 

239.8 ± 121.2 

13.5 ± 9.8 

12.4 ± 8.5 

25.1 ± 10.9* 

20.6 ± 8.5 

0.41 ± 0.32 

0.43 ± 0.27 

Odds Ratio 

1.30* 

1.0 (Reference) 

*p<0.05; menthol greater 

than nonmenthol 

Serum nicotine levels, serum cotinine levels, 

and expired CO were higher in smokers of 

menthol compared with nonmenthol 

cigarettes, with no differences in 2­

hydroxycotinine/cotinine ratios between 

groups when controlling for race. Backward 

stepwise linear regression models showed 

that, in addition to having a diagnosis of 

schizophrenia, smoking menthol cigarettes 

was a significant predictor of nicotine and 

cotinine levels. 

Reviewer comment: The results of the linear 

regression analyses were presented for 

predictors of serum nicotine only; no data 

were provided on predictors of serum 

cotinine levels. 

Chapter 3 - Appendix 

115
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3-14. Comparison of Biomarkers of Tobacco Smoke Exposure (N=19) (Continued) 

CITATION 

STUDY 

POPULATION 

AND DESIGN 

FACTORS MEASURED MEASURE OF 

EFFECT 

AUTHORS’ 

CONCLUSIONS/COMMENTS 

Xia et al. 2010 1373 tobacco users 

1053 of 1373 tobacco users 

were cigarette smokers; % 

menthol smokers not 

reported 

844 men and 533 women 

349 non-Hispanic Black, 

703 non-Hispanic White, 

145 Mexican-American and 

180 Other 

Sample included all tobacco 

users from NHANES 2007­

2008 (N=9762) 

Urine samples for urinary 

total NNAL were collected 

from all NHANES 

participants 6 years of age 

or older. 

NNAL 

Menthol smokers 

Nonmenthol smokers 

Geometric Means (95% 

CI) 

285 (243-334) 

331 (304-360) 

No significant difference 

(adjusted for serum 

cotinine, urinary 

creatinine, CPD and FTC 

tar levels) 

Although NNAL concentrations among 

menthol smokers were lower than those 

among nonmenthol smokers, the difference 

did not achieve statistical significance 

(p=0.095). 

Chapter 3 - Appendix 

116
 

 

 

 

 

 

CHAPTER 4. 

EVIDENCE IS INADEQUATE TO CONCLUDE THAT MENTHOL IN CIGARETTES
 

ADVERSELY IMPACTS SMOKING INITIATION BEHAVIORS 

One element of FDA’s consideration is the question of whether menthol versus nonmenthol 

cigarette use may adversely impact smoking initiation behaviors. Speculative adverse effects include 

an increase in smoking initiation rate and/or an earlier onset of established smoking among menthol 

versus nonmenthol cigarette smokers. Smoking initiation has been defined as the transition from 

never smoking to becoming an experimenting smoker (i.e., smoking >1 cigarette but <100 cigarettes 

lifetime), experimenting smoking to becoming an established smoker (i.e., >100 cigarettes lifetime 

and smoking on some days), and/or from established smoking to becoming a daily smoker. This 

latter transition may be more appropriately examined as a measure of smoking dependence, as it 

provides the clearest distinction between smoking experimenters and true initiators of established 

smoking. 

An assessment of whether menthol versus nonmenthol cigarette use impacts smoking initiation rate 

should begin with an examination of the cigarette type used by experimenting smokers to initiate 

established smoking. Currently, no published studies report data on this issue or any other 

transition. In the absence of such published studies, data from nationally representative surveys and 

individual studies of specific populations have been used to infer a role for menthol versus 

nonmenthol cigarettes during smoking initiation. However, the available information from these 

sources is not currently adequate to draw any firm conclusions about the specific relationship 

between menthol smoking (as compared to nonmenthol smoking) and becoming an established 

smoker. 

Although nationally representative surveys do not currently collect respondent data on cigarette type 

used during smoking initiation, they do provide important information on smoking initiation 

behaviors. For example, available data allow researchers to estimate the proportion of respondents 

that began smoking within the last 12 months preceding the survey, and thus allow trend analyses of 

estimated year-to-year smoking initiation rates. These data can be further stratified based on 

demographic and smoking behavior characteristics, including race/ethnicity, sex, current age and 

current cigarette type preference. Existing trend analyses of year-to-year initiation rates suggest that 

the percentage of individuals initiating smoking, as represented by never smokers transitioning to 

established or daily smoking has not significantly changed over the last several years. This finding is 

consistent with national survey data indicating a steady decline in smoking prevalence during the 

past two decades. 

National surveys also collect data that allow researchers to estimate average ages of smoking 

initiation (i.e., age at first cigarette smoked, age at first regular smoking and/or age at first daily 

smoking); these data can be further stratified based on race/ethnicity, sex, current age and current 

cigarette type preference. Although such survey data may inform questions of whether cigarette 

type preference impacts onset of smoking experimentation and subsequent transition to established 

(or daily) smoking, a given observational association cannot be regarded as conclusive evidence for a 

Chapter 4 

117
 

 

 

 

 

 

cause-and-effect relationship in this or any other area of study. Nevertheless, earlier onset of 

smoking might be interpreted as evidence of an adverse population-level effect since total duration 

of smoking and early age of smoking initiation have been observed to be substantial predictors of 

chronic disease risk among smokers. 

Conversely, findings from a number of nationally representative surveys consistently indicate that 

current menthol cigarette smokers are more likely to report significantly older initiation ages (i.e., 

later onset of smoking) compared to nonmenthol smokers. Findings from epidemiology studies of 

smoking-associated chronic diseases among menthol versus nonmenthol smokers (discussed in 

Chapter 3 of this report) are consistent with the smoking initiation data discussed in this chapter. As 

expected with a similar to later (but not earlier) initiation age among smokers who report a 

preference for menthol cigarettes, the epidemiology studies report no increase in disease risk 

associated with the use of menthol versus nonmenthol cigarettes. 

Existing data from nationally representative surveys as well as studies based on populations that are 

not necessarily representative of the overall (smoking) population, do not provide data on cigarette 

type (menthol versus nonmenthol) used during smoking initiation. Trend analyses based on 

nationally representative smoking populations suggest that smoking initiation rates (including those 

among menthol cigarette smokers) have remained largely unchanged during the past several years, 

and that current smokers of menthol cigarettes are more likely to delay onset of smoking compared 

to nonmenthol smokers. Although these data are suggestive of no causal relationship between 

menthol cigarette use and adverse smoking initiation behaviors, they do not directly address the 

cigarette type used to initiate smoking. Thus, using the Surgeon General’s framework for assessing 

causality, it must be concluded that the “evidence is inadequate to infer the presence or 

absence of a causal relationship” between menthol cigarette use and adverse smoking initiation 

behaviors. 

This chapter reviews what is known about the complex process of smoking initiation, discusses the 

most appropriate way to assess smoking initiation, and reviews the available data on initiation 

behaviors. Although there are a limited number of methodologically sound studies that attempt to 

examine the impact of cigarette type on smoking initiation, the available evidence discussed below 

suggests that menthol versus nonmenthol cigarette use does not adversely impact smoking initiation 

behaviors. 

FACTORS ASSOCIATED WITH SMOKING INITIATION BEHAVIORS 

Most studies report that experimentation with cigarette smoking and transition to established 

smoking typically begins during adolescence. Research indicates that this process is associated with 

a complex interplay among cultural, sociodemographic, intrapersonal, environmental, genetic and 

behavioral factors. Some of the factors that influence or correlate with the uptake of smoking 

include age; ethnicity/race; family socioeconomic status and personal income; use or approval of 

tobacco use by peers or siblings; lack of skills to resist influences to use tobacco; smoking by parents 

or guardians; lack of parental involvement or support; psychological reactance to adult authority or 

parental control; accessibility, availability or price of tobacco products; a perception that tobacco use 

Chapter 4 

118
 

 

 

 

 

 

is the norm; low levels of academic achievement; low self-image or self-esteem; stress, depression or 

distress; and aggressive behavior such as fighting or carrying weapons (Batra et al. 2003; Campaign 

for Tobacco-Free Kids 2010a; Miller et al. 2006; USDHHS 1994, 2000). Adolescents who use 

tobacco are likewise at an increased risk for other potentially harmful behaviors (e.g., the use of 

alcohol/other drugs, high-risk sexual behavior). The sheer number of these factors documented to 

influence early smoking behaviors, each constrained by unique biases, interactions and imprecisions, 

suggests that the definitive study and conclusive identification of a role for menthol cigarette use as 

an independent factor for smoking initiation behavior(s) will be difficult. 

DIFFICULTIES IN ASSESSING SMOKING INITIATION BEHAVIORS 

There are inherent difficulties in studying smoking initiation behaviors. Most studies report that 

smoking experimentation and transition to established smoking typically begins at a time when 

young people cannot purchase cigarettes legally. Hence, young smokers often do not make choices 

about brand preference, or obtain cigarettes in the manner that adults do. Young smokers are 

undoubtedly strongly influenced by the types of cigarettes used by the smokers around them. To 

the degree that young smokers obtain cigarettes from others, they may know little about what type 

of cigarette they are smoking. As noted by researchers who have studied this issue, “It is not 

surprising that many youths could not recall any details regarding the brand, strength, or 

mentholation of their first cigarette, since the first cigarette is most commonly provided by others 

and this information is rarely written on the cigarette” (DiFranza et al. 2004). Moreover, brand or 

style of the cigarette with which young smokers initiate smoking may bear no predictable 

relationship to a future brand purchased legally. An additional complication is that, adolescents may 

not report their smoking activities accurately. Some may be unwilling to report that they engage in 

an activity that is illicit, as well as unhealthful, while others may view reporting smoking in a positive 

light as evidence of rebellion and a challenge to authority. 

Analyses are further complicated by the fact that there is no single definition of what constitutes 

“smoking initiation,” with researchers often employing different definitions that are dictated by 

available data sets. Secondary analyses of baseline data from studies designed to examine disease 

risk or smoking initiation are limited by the original study design. Even nationally representative 

surveys collect respondent data based on different definitions of smoking initiation, ranging from 

first cigarette (or puff) smoked to established (or even daily) smoking. Caution is warranted when 

interpreting (and comparing) findings from individual studies. An additional complexity is the 

knowledge that only about 25% of self-reported youth smokers actually transition to established or 

daily smoking (Deyton 2010). While it is encouraging that only 1 in 4 youths experimenting with 

cigarettes actually transition to established smoking (a more appropriate measure of smoking 

initiation), it is clear that study findings based on first cigarette (or puff) smoked or other early 

experimentation-phase smoking behaviors significantly overestimate the true initiation of established 

smoking. 

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Ideal Study for Assessing Role of Menthol Cigarette Use During Smoking Initiation 

The ideal study evaluating whether menthol versus nonmenthol cigarette use adversely impacts 

smoking initiation behaviors would enroll a large, nationally-representative cohort of young people; 

enrollment would likely include an over-sampling of African American and Hispanic youth. This 

cohort would be followed for a number of years to capture data through the age 20 or 21 years, 

when most long-term smokers have established their smoking behaviors. All participants would be 

re-interviewed (in person) at regular intervals, e.g., at least every 6 months, to minimize the impact 

of recall bias. Individuals would be asked about experimentation with different types of cigarettes, 

their smoking intensity (cigarettes per day), and would provide a urine sample for cotinine analysis to 

verify smoking status. In addition, detailed information would be collected at baseline (and, for 

certain variables, at each follow-up visit) on sociodemographic factors, smoking behavior (amount 

smoked, timing of first and last cigarette, whether smoking is done mainly socially), nicotine 

dependence, alcohol consumption, body mass index, and health/respiratory symptoms. Such a 

study would make it possible to monitor smoking initiation behaviors, to verify the stability of 

cigarette type smoked (menthol versus nonmenthol), and to assess the development of dependence. 

It would also enable researchers to confidently adjust for numerous variables that might confound 

the association between menthol cigarette use and initiation behaviors. 

None of the available studies meets all of the criteria described above, including the unpublished 

secondary analysis of Nonnemaker et al. (unpublished) that TPSAC heavily relied upon in the 

developments of its menthol model and its conclusions with respect to the effects of menthol on 

smoking initiation. The ideal study described above would, in fact, likely be difficult to conduct. 

BEST AVAILABLE SCIENCE WAS DETERMINED THROUGH A RIGOROUS 

PROCESS 

There are two potential sources of data on menthol cigarette use and smoking initiation behaviors: 

nationally representative surveys and individual studies of specific populations. Data from studies 

based on nationally representative surveys are generally more informative due to the fact that the 

sample populations have been weighted to achieve nationally representative estimates aligned with 

the U.S. population; hence, study findings are considered to be representative of the entire smoking 

population. This is not the case for individual studies based on specific populations; findings from 

these studies may only be considered representative of the entire smoking population if the authors 

demonstrated the external validity of the study through appropriate comparisons. 

As previously discussed, the available studies do not collect information on the cigarette type used 

by experimenting smokers to initiate established smoking. However, these studies collect data that 

allow researchers to estimate average ages of smoking initiation; and, these data can be further 

stratified based on race/ethnicity, sex, current age and current cigarette type preference. Such data 

are informative as to whether cigarette type preference impacts the onset of smoking initiation, with 

earlier onset of smoking likely to be suggestive of an adverse population-level effect. 

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Chapter 4 

 

 

 

 

 

 

A comprehensive search of the literature and methodologic evaluation of the identified studies on 

the association between menthol cigarette use and smoking initiation behaviors was performed by 

Covance at the request of Lorillard. The report of their analysis has been provided to TPSAC and a 

summary of the findings were presented to TPSAC on February 10, 2011. An updated report from 

Covance (as referenced in Chapter 1) includes an evaluation of additional recent studies. 

The Covance report describes in detail the rigorous and objective process used to identify and 

evaluate the available published literature on this topic. Briefly, a systematic search of the published 

literature was conducted to identify studies that addressed use of menthol cigarettes and smoking 

initiation behaviors. Covance then evaluated these articles for overall methodologic quality (using 

criteria developed by FDA for Healthcare Research and Quality (Ranney et al. 2006)), and for ability 

to support inferences related to menthol cigarette use. Study quality ratings for these two measures 

included poor, poor/fair, fair, fair/good, and good. The studies were categorized into three tiers as 

follows: 

•	 Tier 1 studies were those rated by Covance as fair or better with respect to both overall 

quality and ability to support inferences related to menthol cigarette use; 

•	 Tier 2 studies were those rated by Covance as fair or better with respect to overall quality, 

but lower than fair with respect to ability to support inferences related to menthol cigarette 

use; and 

•	 Tier 3 studies were those rated by Covance as lower than fair with respect to both categories. 

Six articles were identified that evaluated menthol cigarettes and smoking initiation behaviors. Of 

these, Covance’s ratings placed four studies in Tier 1, no studies in Tier 2, and two studies in Tier 3, 

as shown below. 

Table 4-1.	 Studies of Menthol Smoking and Initiation Behaviors (N=6) 

Quality Ratings by Covance 

Citation Overall Quality 

Rating 

Rating: Menthol 

Inferences 

Tier 1 

Appleyard et al. 2001 Good Fair 

Cubbin et al. 2010 Fair/Good Fair/Good 

Fernander et al. 2010 Fair/Good Fair 

Lawrence et al. 2010 Good Good 

Tier 2 No studies identified 

Tier 3 Ahijevych and Parsley 1999 Poor Poor 

Okuyemi et al. 2004 Poor Poor 

121
 

 

 

 

 

 

 

 

 

 

Tier 1 Studies on Menthol Smoking and Initiation Behaviors 

The Tier 1 studies are considered to be the “best available science” for assessing the effect of 

menthol versus nonmenthol cigarette use on smoking initiation behaviors. All four studies provide 

findings based on nationally representative populations, although one limited analyses to specific 

demographic groups (i.e., Asian American and Hawaiian/Pacific Islander youth). None of the 

nationally representative surveys asked respondents about the type of cigarette smoked during the 

initial smoking experience, the type of cigarette used when regular smoking began or the type first 

purchased (which may better reflect preference). The studies are summarized in Appendix Table 4-3 

and discussed below. 

Appleyard et al. (2001) conducted an analysis of data from the 2000 National Youth Tobacco 

Survey (NYTS) to better understand smoking behaviors among Asian American and 

Hawaiian/Pacific Islander youth. The analysis is not very useful in understanding what, if any, role 

menthol cigarette use plays during smoking initiation, as it does not compare initiation among youth 

who smoked menthol cigarettes with those who smoked nonmenthol cigarettes. A few findings of 

interest did relate to menthol cigarette use. For example, White and Hispanic youth were more 

likely to smoke menthol cigarettes in middle school than in high school; the opposite was true for 

Asian Americans, Hawaiian/Pacific Islanders and African Americans (specific percentages not 

provided). 

Cubbin et al. (2010) conducted a cross-sectional analysis of data from the 2005 National Health 

Interview Survey (NHIS) and Cancer Control Supplement. Adult daily smokers (aged ≥18 years; 

N=66,145) were asked how old they were when they started smoking cigarettes “fairly regularly.” 

Among menthol cigarette smokers, Whites became regular smokers earlier than their Black and 

Hispanic counterparts, i.e., age of initiation was about 2 years younger for White females and 1.5-3 

years younger for White males. Among nonmenthol smokers, Whites similarly initiated smoking 

earlier, but the differences were only significant in comparison with Hispanic males and females. 

There were no sex differences among any racial/ethnic group for either cigarette type (menthol or. 

nonmenthol); and, within each demographic group, there were no differences in age of initiation by 

cigarette type. The authors concluded that the results do not support the hypothesis that menthol 

smokers initiate smoking at an earlier age compared to nonmenthol smokers. Note that the survey 

did not collect information on whether respondents initiated with menthol or nonmenthol 

cigarettes; thus, it does not provide insight into whether early experiences with menthol cigarettes 

may be associated with subsequent regular smoking. 

Fernander et al. (2010) conducted a cross-sectional analysis of data from the 2003 and 2006/07 

Tobacco Use Supplement to the Current Population Survey (TUS-CPS). After adjustment for 

demographic and smoking variables, findings from multivariate logistic models suggested that the 

longer the delay of initiation (established smoking), the more likely that individual respondents 

reported smoking menthol cigarettes as an adult. The authors concluded that menthol smokers tend 

to start smoking at significantly older ages (i.e., later onset of smoking initiation) than smokers of 

nonmenthol cigarettes. As with the NHIS, this survey did not collect information on whether 

respondents started out smoking menthol or nonmenthol cigarettes; thus, it does not provide insight 

Chapter 4 

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into whether early experiences with menthol cigarettes may be associated with subsequent regular 

smoking. 

Lawrence et al. (2010) conducted a cross-sectional analysis of data from the 2003 and 2006/07 

TUS-CPS. After adjustment for sociodemographic and smoking variables in the multivariate logistic 

regression model, no significant associations between age at onset of regular smoking and menthol 

use among all current smokers were found. When the analysis was stratified by sex, older onset of 

established smoking (aged ≥18 years compared to aged 15-17 years) was significantly associated with 

current menthol versus nonmenthol cigarette use among female smokers; there were no significant 

differences among male smokers. As mentioned previously, this survey did not collect information 

on whether respondents started out smoking menthol or nonmenthol cigarettes; thus, it does not 

provide insight into whether early experiences with menthol cigarettes may be associated with 

subsequent regular smoking. 

The weight of evidence provided by these highest-quality studies does not support the contention 

that menthol in cigarettes is causally associated with earlier initiation of smoking among the general 

population or among ethnic subpopulations. In fact, menthol smokers are more likely to report later 

onset of smoking initiation when compared with nonmenthol smokers. 

Tier 3 Studies on Menthol Smoking and Initiation Behaviors 

Two Tier 3 studies (Ahijevych and Parsley 1999, Okuyemi et al. 2004) were rated poor in overall 

quality and in their ability to draw menthol inferences, and are not discussed in detail here. 

Studies Not Designed to Address Initiation Behaviors 

Covance assigned studies to behavior classification categories (initiation, cessation or dependence) 

according to the study’s primary outcomes. This resulted in some studies that are often discussed in 

the context of initiation to be assigned to other behavior categories. Because they have been 

discussed in TPSAC meetings, they are mentioned briefly here. 

DiFranza et al. (2004) was categorized by Covance as a Tier 1 dependence study and is presented 

in detail in Chapter 5B. In this study, authors conducted a “retrospective/prospective” longitudinal 

analysis of seventh graders followed for 30 months as part of the Development and Assessment of 

Nicotine Dependence in Youth Study. The subjects were interviewed three times per year for three 

years, with the goal of understanding whether the recalled reaction to a first cigarette was predictive 

of later nicotine dependence. This analysis focused on 237 subjects who reported that they had 

inhaled cigarette smoke; only about half of these could recall whether the first cigarette they had 

smoked was menthol or nonmenthol. The authors found that reactions to the initial smoking 

experience were unrelated to cigarette mentholation; reactions were likewise unrelated to sex, 

cigarette brand or strength of cigarette. 

Hersey et al. (2006) was categorized by Covance as a Tier 3 study addressing cessation and 

dependence. Given its low rating, the study is not discussed in detail in Chapters 5A or 5B. 

However, because the findings of this study have been mentioned in discussion of initiation in 

Chapter 4 

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TPSAC meetings, they are mentioned here briefly. In this study, the authors analyzed data from the 

2000 and 2002 NYTS, and reported that menthol cigarette smoking was more prevalent among 

students who had smoked <1 year (i.e., beginner smokers) than among students who had smoked 

>1 year (i.e., experienced smokers). The authors suggested that menthol cigarettes may be a “starter 

product” during youth uptake of smoking, but cautioned against interpreting findings as predictive 

of future smoking (i.e., “gateway” effect). Study findings were likely compromised by the significant 

loss of sample (i.e., due to nonresponse to the survey and indeterminate menthol status), 

inconsistency between survey items in the 2000 and 2002 NYTS, and the study’s cross-sectional 

design. A subsequent analysis by the same authors (Hersey et al. 2010, discussed below) did not 

substantiate the “starter product” assertions made in this earlier study. 

Additional studies provided data on smoking initiation behaviors among menthol versus 

nonmenthol cigarette smokers (Hyland et al. 2002, Hymowitz et al. 1995, Pletcher et al. 2006). 

Corresponding findings were based on baseline characteristics of specific populations and are not 

discussed here despite their findings of no differences in menthol versus nonmenthol in age at 

which smoking was started (Hyland et al. 2002; Hymowitz et al. 1995) or at which first cigarette was 

smoked (Pletcher et al. 2006). 

Recent Publications of Data from National Cross-Sectional Surveys 

There were three additional publications (included in the recent Nicotine and Tobacco Research 

December 2010 Supplement and March 2011 issue) that examined smoking initiation behaviors and 

menthol versus nonmenthol cigarette use based on data from nationally representative surveys 

(NYTS and NSDUH). Due to the timing of publication, these studies were not included in the 

Covance review; thus, they have not been placed into a specific quality tier. These studies are 

discussed briefly. 

Hersey et al. (2010) analyzed cross-sectional data from the 2006 NYTS, and provided findings 

from youth (i.e., past month smokers) that had a usual brand of cigarette and could identify that 

usual brand as either menthol or nonmenthol (N=3,281). Menthol cigarette use was found to be 

more common among more experienced smokers (i.e., those having smoked for >1 year) of middle 

school age than among beginner smokers (i.e., those having smoked <1 year), 54.7% vs. 42.2%, 

respectively. Among high school smokers, the proportions smoking menthol cigarettes as their 

usual brand were similar among more experienced and beginner smokers (43.1% vs. 42.8%, 

respectively). No statistical tests were performed on these data to determine whether the observed 

differences were significant. Nonetheless, these findings directly contradicted earlier findings from 

the same authors examining data from the 2000 and 2002 NYTS (Hersey et al. 2006, discussed 

previously), that were used to support the contention that menthol cigarettes might serve as a 

“starter product” during youth uptake of smoking. 

Rock et al. (2010) conducted an analysis of data from the 2004-2008 NSDUH, the objective being 

to examine menthol versus nonmenthol cigarette use patterns among racial and ethnic groups; 

similar analyses were performed on different age groups. These data do not address initiation 

directly as participants were not asked which type of cigarette they used when they began smoking; 

rather, analyses focused on trends of menthol versus nonmenthol cigarette type preference. 

Chapter 4 

124
 

 

Findings suggested that menthol cigarette preference (i.e., use among current smokers, and not 

smoking prevalence among the overall population) increased during the period of 2004-2008 among 

White adolescent smokers, but not among African American or Hispanic adolescent smokers. 

Increases were likewise reported for Hispanic and White young adult smokers. For all race/ethnic 

groups except African Americans, menthol cigarette smoking was more common among the 

youngest smokers (age 12-17 years) compared to smokers in the older age groups (age 18-25 years or 

age ≥26 years). Among African Americans, menthol cigarette smoking was more common among 

smokers in the older age groups. 

As discussed in Chapter 2, estimates of menthol cigarette preference from the NSDUH are based on 

an overly inclusive question that may misclassify smokers whose usual brand is nonmenthol but 

have smoked any menthol cigarette(s) in the past month. Estimates of menthol preference among 

current smokers from the NSDUH are typically higher than those from surveys that base estimates 

of menthol preference on usual cigarette (or brand) smoked. Additionally, current smokers in the 

NSDUH estimates were defined as having smoked all or part of a single cigarette in the last 30 days, 

a much more inclusive definition of smoking compared to that used by other surveys (i.e., having 

smoked ≥100 cigarettes lifetime and currently smoking on some days or every day). Hence, the 

potential exists that estimates provided by the NSDUH are somewhat exaggerated, particularly 

among younger, less experienced smokers. 

Yu (2011) reported an analysis of a national sampling of 305 American Indian/Alaska Native 

adolescent smokers in grades 6-12 who were participants in the 2006 National Youth Tobacco 

Survey. Just over half of the respondents reported ever having experimented with or initiating the 

cigarette smoking (54%). However, only 12% of these respondents reported experience with 

menthol cigarettes, suggesting that menthol added to cigarettes does not lead to an increase in 

experimentation or initiation of smoking among this American Indian/Alaska Native adolescent 

subpopulation compared to nonmenthol cigarettes. 

Unpublished Analyses Presented to TPSAC 

In July 2010 and January 2011, unpublished analyses that examined menthol versus nonmenthol 

cigarette use and smoking initiation behaviors were presented to TPSAC. Although these analyses 

have not undergone peer review, the authors reported conclusions are mentioned here briefly: 

•	 Curtin (unpublished) analyzed data from several large nationally representative surveys and 

reported that: 

o	 Among demographic groups reporting higher menthol versus nonmenthol smoking 

preference, female smokers indicated significantly older mean ages for initiating 

established smoking. Significant differences were suggested for age at first cigarette 

smoked (0.80 years; NSDUH), age at first regular smoking (1.18 years; NHANES) 

and age at first daily smoking (0.96 years; NSDUH). No significant differences were 

suggested for non-Hispanic Black, adolescent or young adult menthol versus 

nonmenthol smokers based on estimated mean initiation ages. 

Chapter 4 

125
 

 

 

o	 Regression models that controlled individually for sex or current age suggested an 

association between older smoking initiation age and menthol cigarette use, i.e., for 

age at first cigarette smoked (NHANES and NSDUH), age at first regular smoking 

(NHANES and NHIS) and age at first daily smoking (NSDUH). Significant 

differences persisted when controlling for the combinations of race/ethnicity and 

current age or sex and current age. 

o	 For first daily smoking, a significantly older (0.63 years; p<0.05) smoking initiation 

age among menthol smokers was indicated after controlling for the combination of 

current age, sex and race/ethnicity. 

•	 Nonnemaker et al. (unpublished) conducted a secondary analysis of a longitudinal cohort 

of middle/high school youth to examine the influence of early menthol and nonmenthol 

cigarette use (and switching) on the progression from experimentation to established/daily 

smoking over a 3-year interval. Results were not entirely consistent, but the authors 

suggested that an early stated preference for menthol cigarettes was associated with 

indicators of progression to established smoking and higher levels of nicotine dependence. 

This study has numerous limitations, including use of a sample population that was not 

representative of the overall youth population and sample sizes that were likely insufficient 

to draw valid conclusions. Notably in this regard, the numbers of African American daily, 

regular and established smokers ranged from 11-13 subjects up to Wave 3 of the survey, 

with 5-6 added in the Third Wave for each categorical definition of initiation. These 

extremely small sample numbers are, by any standard, inadequate to support estimations of 

initiation behaviors of the general national population of African American adolescents. 

In summary, an analysis of the studies described above (those not designed to directly address 

cigarette type used during smoking initiation, recently published studies that were not rated by 

Covance, and unpublished analyses presented to TPSAC) do not support the conclusion that 

menthol in cigarettes adversely effects smoking initiation or progression to regular smoking. 

TREND DATA FOR SMOKING INITIATION RATES 

The weakness in national survey data with regard to evaluating the effect of menthol cigarettes on 

smoking initiation is that they have historically not collected respondent data on cigarette type 

preference during initiation. Although cross-sectional analyses of national survey data are limited to 

assessments based on current cigarette type preference (e.g., usual brand smoked), comparisons 

across survey years are possible based on combined sample populations. This allows researchers to 

identify the proportion of respondents that began smoking within the 12 months preceding 

participating in each survey, and thereby examine year-to-year smoking rates based on 

sociodemographic and smoking behavior characteristics, including current cigarette type preference. 

Existing trend analyses of year-to-year initiation rates indicate that the percentage of never smokers 

transitioning to established or daily smokers has not significantly changed over the last several years. 

Data provided by the NSDUH indicate that adolescent smoking initiation rates, overall or stratified 

by sex, were not significantly different from 2002 to 2008 (Figure 4-1). Among youths aged 12-17 

Chapter 4 

126
years who had not smoked cigarettes prior to the past year, the smoking initiation incidence rate (i.e., 

transition to daily smoking) showed no significant difference between 2002 and 2008. Among males 

in this group, the decrease in past year initiation rate from 6.1% in 2002 to 5.7% in 2008 was not 

significant; nor was the decrease from 7.4% in 2002 to 6.7% in 2008 among females (SAMHSA 

2009). 

Figure 4-1. Annual smoking initiation* rate as percent of respondents 

(NSDUH, 2002-2008) 

3

6

9

12

15

Past Year Cigarette Initiation (%)

male female total

0

2002 2003 2004 2005 2006 2007 2008

*Smoking initiation (daily smoking) estimates based on percent of survey respondents that 

reported initiating smoking ≤12 months prior to survey participation (SAMHSA 2009). 

Analyses, conducted by the tobacco industry and presented to the TPSAC during the July 2010 

meeting, examined the transition from never smoking to established smoking (i.e., smoking on ≥10 

of the last 30 days) based on nationally representative data from the 1999-2008 NHANES. Year-toyear smoking initiation rates were estimated based on the proportion of respondents that began 

smoking ≤12 months prior to the survey; current menthol versus nonmenthol cigarette use was 

approximated based on usual cigarette (or brand) smoked, and analyses were conducted for the 

overall study population, as well as for demographic groups stratified by race/ethnicity, sex, current 

age and menthol status. 

While somewhat underpowered (N=267), these analyses suggest no significant differences over time 

for rates of smoking initiation (i.e., transitioning to established smoking) among all new smokers, or 

after stratifying (all new smokers) by current cigarette type preference (menthol versus nonmenthol) 

(see Table 4-2; full demographics data is provided in Appendix Table 4-4). While currently 

unpublished, these data are readily available for confirmatory re-analysis from the original data 

source (CDC 2009). 

Chapter 4 

127
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Table 4-2. Analysis of time trends for smoking initiation* (NHANES, 1999-2008) 

All New Smokers1 

New Smokers1 

Nonmenthol Menthol 

Estimate p-value Estimate p-value Estimate p-value 

Total Initiation rate2 0.40 0.01* 0.35 0.010* 0.05 0.38 

2 year change3 0.04 0.17 0.01 0.65 0.03 0.17 

Sex 

Male Initiation rate2 0.63 0.006* 0.55 0.012 0.08 0.30 

2 year change3 0.00 0.88 -0.02 0.60 0.01 0.56 

Female Initiation rate2 0.19 0.09 0.17 0.114 0.02 0.68 

2 year change3 0.07 0.05 0.03 0.24 0.04 0.08 

Race/Ethnicity 

Non-Hispanic 

White Initiation rate2 0.35 0.01* 0.33 0.03* 0.11 0.20 

2 year change3 0.05 0.09 0.02 0.46 0.00 0.80 

Non-Hispanic 

Black Initiation rate2 0.37 0.01* 0.07 0.13 0.18 0.09 

2 year change3 0.02 0.33 0.05 0.04* 0.04 0.18 

Other Initiation rate2 0.63 0.10 0.51 0.11 0.11 0.30 

2 year change3 0.00 0.99 -0.02 0.78 0.02 0.49 

Age Group 

(years) 

12 to 17 Initiation rate2 1.41 0.03* 1.13 0.03* 0.28 0.07 

2 year change3 -0.08 0.51 -0.05 0.62 -0.03 0.38 

18 to 24 Initiation rate2 0.84 0.10 0.64 0.15 0.21 0.54 

2 year change3 0.24 0.11 0.12 0.32 0.12 0.29 

25 to 29 Initiation rate2 0.60 0.10 0.30 0.27 0.30 0.31 

2 year change3 -0.03 0.68 -0.02 0.74 -0.01 0.93 

30 + Initiation rate2 0.31 0.05 0.30 0.01* 0.01 0.82 

2 year change3 0.00 0.91 -0.02 0.35 0.02 0.25 1 New smokers initiated smoking ≤12 months prior to survey participation, and reported using cigarettes ≥10 of the last 

30 days. 2 The average initiation rate is the y-intercept from the linear regression model. The p-value indicates whether the 

initiation rate is statistically significantly different from zero (* indicates p<0.05). 3 The NHANES is implemented over a two year interval. The two year change indicates change in smoking initiation 

over the two year interval compared to the average initiation rate for each stratum. The p-value indicates whether the 

difference from the average initiation rate is statistically significant (* indicates p<0.05). 

128
 

 

 

 

 

A borderline significant (p=0.0517) increase over time was suggested for the rate of smoking 

initiation among females overall, but there were no significant differences in smoking initiation rates 

among females or males currently smoking menthol compared to nonmenthol cigarettes. 

Likewise, there were no significant differences over time for smoking initiation rates among nonHispanic Whites or respondents of “other” race/ethnicity, overall or after stratifying by current 

menthol or nonmenthol cigarette use; there was a small but significant increase for non-Hispanic 

Blacks currently smoking nonmenthol cigarettes (p=0.04). 

Finally, there was a slight decline suggested over time for smoking initiation among respondents 

aged 12-17 and 25-29 years, overall and after stratifying by current menthol or nonmenthol cigarette 

use; however, there were no significant trends for smoking initiation rates by age at survey. 

MENTHOL MARKET SHARE COMPARED TO YOUTH SMOKING RATES 

Although an analysis of the preference for menthol cigarettes (expressed as menthol share-ofmarket) compared to youth smoking rates does not directly address the topic of initiation, it 

provides additional supportive evidence that youth smoking rates are not influenced by the 

availability of menthol. A state-by-state comparison of menthol share-of-market and youth smoking 

incidence in 2009 shows a poor correlation between the two (see Figure 4-2). 

Figure 4-2. Menthol Market Share Compared to Youth Smoking Rates (2009) 

 

30.0% 

25.0% 

20.0% 

15.0% 

10.0% 

5.0% 

0.0% 

0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 

KY Youth Smoking Rate – 

IN 

NH TN OK AR 

TX 

ND NE WV 

SD 

NM 

WY 

SC AL 

Average (19.5%) 

IA MO 

NV KS

MN 

CA 

AZ 

VT CO 

AK 

ME 

OR 

MT PA 

DE 

GAWI NJ 

MS 

MI 

CT 

NC

IL 

OH LA 

VA MA 

ID WA NY 

RI 

FL 

DC 

HI MD 

UT 

Menthol Market Share 

Youth Smoking Rate (%) 

– Average (28.9%) 

 

Menthol Market Share (%) 

 

Sources: For youth smoking rates, Campaign for Tobacco-Free Kids (2010b); for menthol market share, Management 

Science Associates, Inc. (confidential industry data). 

Chapter 4 

129
 

 

 

 

 

Notably, menthol market share is inversely related to youth smoking among all 50 states to a 

statistically significant degree. These data indicate that youth smoking rates are generally lower in 

states with higher menthol market share. There is no evidence that youth smoking rates in the U.S. 

would decline if menthol cigarettes were not available. 

The lack of correlation between menthol market share and youth smoking rates is also indicated on 

a global basis. In many countries, the share of menthol is very low and, in some, menthol cigarettes 

are effectively unavailable. Many of these countries continue to have adult and youth smoking rates 

that are higher than those in the U.S. (see Figure 4-3). There is no relationship between menthol 

share and youth usage or smoking incidence globally. Absence of menthol cigarettes in the 

marketplace has not resulted in lower youth smoking rates. 

Figure 4-3. Menthol Market Share Compared to Youth and Adult Smoking 

Rates - International 

Sources: For smoking prevalence, WHO (2009); for menthol market share from foreign countries, A.C. Nielsen 

(confidential industry data); for menthol market share in U.S., Management Science Associates, Inc. (confidential 

industry data). 

SWITCHING BETWEEN MENTHOL AND NONMENTHOL 

It has been suggested during the TPSAC meetings that there could be an adverse population-level 

effect as a result of switching patterns among menthol and nonmenthol cigarette smokers. Data 

were presented to suggest that among African Americans (aged ≤40 years) participating in the 

Kaiser Permanente Cohort Study (1979-1986), nonmenthol smokers were ~4-times more likely 

(i.e., 14.6% vs. 3.6%) to switch to menthol cigarettes than menthol smokers were to switch to 

Chapter 4 

130
 

 

 

 

 

 

nonmenthol cigarettes (Sidney et al. 1989). A second study analyzed data from a small population of 

smokers (N=178), and reported no difference in switching behavior based on menthol status 

(Pletcher et al. 2006). Neither study was based on a nationally representative population of smokers. 

More recent data on switching behaviors were provided as an unpublished analysis during the 

November 2010 TPSAC meeting. In contrast to findings from the earlier studies, current smokers 

(aged 16-24 years) participating in the National Youth Smoking Cessation Survey (2003-2005) 

provided data to suggest that 15.0% (95% CI:10.8-19.2) of menthol smokers at baseline had 

switched to nonmenthol cigarettes after two years of follow-up, while 6.9% (95% CI:4.9-8.9) of 

nonmenthol smokers had switched to menthol cigarettes (Giovino unpublished). The likelihood of 

switching cigarette types was notably higher for White menthol and nonmenthol smokers (20.4% 

and 5.6%, respectively) than for other racial groups. 

While the Giovino findings were presented as a nationally representative survey that included 1,045 

youth smokers, only 58 menthol and 55 nonmenthol cigarette smokers actually reported switching 

during the 24-month study, i.e., ~90% of participants did not switch cigarette type. Despite the 

small numbers of menthol and nonmenthol smokers included in the analysis, and despite the low 

rate of switching, study findings were suggested to “lend further credence on menthol as a starter 

product for young smokers.” These data have similarly been suggested to provide strong evidence 

that younger smokers are more likely to initiate smoking with mentholated products and progress to 

smoking nonmentholated varieties in a short period of time. Neither of these statements is 

supported by the available data. 

In summary, available published data on reported switching between menthol and nonmenthol 

cigarettes is mixed and inconclusive, and does not support a conclusion that such switching, 

generally or within subpopulations of smokers, has any meaningful effect on the individual or 

population risks associated with smoking. 

CONCLUSIONS 

This review of the methodologically sound literature on menthol cigarette use and smoking initiation 

behaviors demonstrates that smoking initiation rates (i.e., transitioning from never smoking to 

established or daily smoking) have not significantly changed during the last decade; and, that current 

menthol cigarette smokers are more likely to report later onset of smoking initiation than 

nonmenthol smokers. 

The weight of evidence provided by the highest-quality studies does not support the contention that 

menthol in cigarettes is causally associated with earlier initiation of smoking among the general 

population or among demographic groups. An analysis of available studies not designed to directly 

address cigarette type used during smoking initiation, along with several unpublished or very recently 

published studies, provides no evidence that menthol in cigarettes adversely effects smoking 

initiation or progression to regular smoking. 

Chapter 4 

131
An analysis of available published data on reported switching between menthol and nonmenthol 

cigarettes is mixed and inconclusive, and does not support a conclusion that such switching, 

generally or within subpopulations of smokers, has any meaningful effect on the individual or 

population risks that attend smoking. 

Although these data are suggestive of no causal relationship between menthol cigarette use and 

adverse smoking initiation behaviors, they do not directly address the cigarette type used to initiate 

smoking. Thus, using the Surgeon General’s framework for assessing causality, it must be 

concluded that the “evidence is inadequate to infer the presence or absence of a causal 

relationship” between menthol cigarette use and adverse smoking initiation behaviors. 

Chapter 4 

132
 

 

 

 

 

 

 

 

 

 

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white women cigarette smokers. Addict Behav. 24(1):115-120. 

Appleyard J, Messeri P, Haviland ML. 2001. Smoking among Asian American and 

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Batra V, Patkar AA, Berrettini WH, Weinstein SP, Leone, F.T. 2003. The genetic determinants of 

smoking. Chest 123:1730-1739. 

Campaign for Tobacco-Free Kids. 2010a. How Parents Can Protect Their Kids from Becoming 

Addicted Smokers. Washington: Campaign for Tobacco-Free Kids. Available at: 

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Curtin GM. [unpublished]. Epidemiological analysis of menthol cigarette use: demographics and 

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2004. Recollections and repercussions of the first inhaled cigarette. Addict Behav. 29(2):261-272. 

Fernander A, Rayens MK, Zhang M, Adkins S. 2010. Are age of initiation and purchasing patterns 

associated with menthol smoking? Addict. 105:39-45. 

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Giovino GA. [unpublished]. Patterns of and recent trends in the use of mentholated cigarettes in 

the United States. Available at: 

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Tobacco 

ProductsScientificAdvisoryCommittee/ucm238818.htm. 

Hersey JC, Nonnemaker JM, Homsi G. 2010. Menthol cigarettes contribute to the appeal and 

addiction potential of smoking for youth. Nicotine Tob Res. 12:S136-S146. 

Hersey JC, Ng SW, Nonnemaker JM, Mowery P, Thomas KY, Vilsaint MC, Allen JA, Haviland ML. 

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Hyland A, Garten S, Giovino GA, Cummings KM. 2002. Mentholated cigarettes and smoking 

cessation: findings from COMMIT. Community Intervention Trial for Smoking Cessation. Tob. 

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Hymowitz N, Corle D, Royce J, Hartwell T, Corbett K, Orlandi M, Piland N. 1995. Smokers' 

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Lawrence D, Rose A, Fagan P, Moolchan ET, Gibson JT, Backinger CL. 2010. National patterns 

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Nonnemaker J, Hersey J, Homsi G, Busey A. [unpublished]. Menthol cigarettes and youth smoking 

update. Paper presented to: TPSAC, 10-11 Jan 2011. 

Okuyemi KS, Ebersole-Robinson M, Nazir N, Ahluwalia JS. 2004. African-American menthol and 

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Pletcher MJ, Hulley BJ, Houston T, Kiefe CI, Benowitz N, Sidney S. 2006. Menthol cigarettes, 

smoking cessation, atherosclerosis, and pulmonary function: the Coronary Artery Risk Development 

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Rock VJ, Davis SP, Thorne SL, Asman KJ, Caraballo RS. 2010. Menthol cigarette use among racial 

and ethnic groups in the United States, 2004-2008. Nicotine Tob Res. 12:S117-S124. 

Sidney S, Tekawa I, Friedman GD. 1989. Mentholated cigarette use among multiphasic examinees, 

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Substance Abuse and Mental Health Services Administration (SAMHSA). 2009. Results from the 

2008 National Survey on Drug Use and Health: National Findings. Office of Applied Studies, 

NSDUH Series H-36, HHS Publication No. SMA 09-4434. Rockville, MD. Available at: 

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U.S. Department of Health and Human Services (USDHHS). 2000. Reducing Tobacco Use: A 

Report of the Surgeon General. Atlanta: U.S. Department of Health and Human Services, Centers 

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for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. Available 

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World Health Organization (WHO). 2009. WHO Report on the Global Tobacco Epidemic, 2009: 

Implementing smoke-free environments. Available at: 

http://www.who.int/tobacco/mpower/2009/gtcr_download/en/index.html. 

Yu M. 2011. Tobacco use among American Indian or Alaska Native middle and high-school 

students in the United States. Nicotine Tob Res. 13(3):173-181. 

Chapter 4 

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Chapter 4 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 4-3. Higher Quality Studies on Menthol Cigarette Smoking and Initiation Behaviors (N=4) 

CITATION OUTCOME 

STUDY TYPE MEASURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Appleyard et al. 

2001 

United States 

Initiation of smoking 

Prevalence of menthol 

cigarette use among youth 

by race 

Analysis of 2000 National 

Youth Tobacco Survey 

(NYTS) dataset comprising a 

nationally representative 

sample of 35,828 middle and 

high school students. 

This analysis focused on a 

nationally representative 

sample of Asian American 

youth (n=1,742) and a 

smaller sample of 

Hawaiian/Pacific Islander 

youth that is not nationally 

representative (n=487). 

Current smokers were 

defined as those reporting 

smoking a cigarette on at 

least one of the past 30 days. 

Participants were asked: 

“How old were you when 

you smoked a whole cigarette 

for the first time?” and “Is 

the brand of cigarettes that 

you usually smoked during 

the past 30 days 

mentholated?” 

Percentage of Youth Who

Usually Smoke Mentholated 

Cigarettes 

Asian American 

Hawaiian/Pacific-Islander 

African American 

Hispanic 

White 

Percentage 

Estimates (95% CI) 

58.4% (50.8-66.0) 

46.1% (33.4-58.8) 

73.6% (68.9-78.2) 

51.3% (47.2-55.3) 

32.2% (28.2-36.3) 

NYTS 2000 data 

indicate that during the 

last year of high school, 

one third of Asian 

American youth are 

smokers. Of these 

youth, 60% report that 

their usual brand of 

cigarettes is a menthol 

brand. 

White and Hispanic 

youth are more likely to 

smoke menthol 

cigarettes in middle 

school than in high 

school; the opposite is 

true for Asian 

Americans, 

Hawaiian/Pacifc 

Islanders, and African 

Americans (specific 

percentages not 

provided). 

The reported conclusions are 

supported by the study data. 

However, this study does not 

compare initiation among 

youth who smoke menthol 

cigarettes with those who 

smoke nonmenthols. It only 

presents data on percent of 

each race that initiated 

smoking (of any type) in 

grade, middle, and high 

school. 

Initiation was defined as age 

at which the subject first 

smoked a whole cigarette. 

This paper focuses on 

smoking among Asian 

American and 

Hawaiian/Pacific Islander 

youth. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

136
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 4-3. Higher Quality Studies on Menthol Cigarette Smoking and Initiation Behaviors (N=5) (Continued) 

CITATION OUTCOME 

STUDY TYPE MEASURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Cubbin et al. 

2010 

United States 

Age of initiation 

Cross-sectional analysis of 

data from the 2005 National 

Health Interview Survey 

Cancer Control Supplement. 

Analysis was based on 21,196 

Black, Hispanic, and White 

women and men aged 25-64 

years (current, former, and 

never-smokers who reported 

menthol status). 

Menthol use was defined as 

“usual cigarette brand was 

menthol.” 

Age of initiation question 

was not provided in report. 

Cessation data are included in 

Table 5-3; dependence data 

are included in Table 5-4. 

Menthol Smokers 

Black women 

Black men 

Hispanic women 

Hispanic men 

White women 

White men 

Nonmenthol Smokers 

Black women 

Black men 

Hispanic women 

Hispanic men 

White women 

White men 

Predicted Mean Age 

of Initiation by 

Cigarette Type (99% 

CI) 

19.8 (18.9, 20.8) 

18.6 (17.8, 19.5) 

19.9 (18.0, 21.9) 

20.5 (17.6, 23.5) 

17.7 (17.0, 18.5) 

17.2 (16.3, 18.1) 

19.2 (17.4, 20.9) 

17.5 (16.0, 19.1) 

19.9 (18.2, 21.6) 

18.6 (17.6, 19.7) 

17.5 (17.1, 17.8) 

17.1 (16.7, 17.5) 

Adjusted for age, 

income, and 

education. 

The results do not 

support the hypothesis 

that menthol smokers 

initiate earlier. 

Among menthol 

smokers, White women 

and men started 

smoking earlier than 

their Black and Hispanic 

counterparts. 

There were no sex 

differences for any 

racial/ethnic group for 

either cigarette type. 

Within each 

demographic group, 

there were no 

differences in age of 

initiation by type of 

cigarette. 

Conclusions are supported 

by study data. 

Large national populationbased survey with many 

menthol smokers. 

Cross-sectional nature of 

analysis does not permit 

causal conclusions. 

Authors do not have 

information on type of 

cigarette used at initiation 

(menthol vs. nonmenthol). 

Thus, “menthol smoker” 

refers to preference as an 

adult. 

Menthol use was selfreported. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

Chapter 4 - Appendix 

137
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 4-3. Higher Quality Studies on Menthol Cigarette Smoking and Initiation Behaviors (N=5) (Continued) 

CITATION OUTCOME 

STUDY TYPE MEASURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Fernander et al. 

2010 

United States 

Age of initiation 

Cross-sectional analysis of 

data from the 2003 and 

2006/07 Tobacco Use 

Supplement to the Current 

Population Survey. 

Analysis was based on 66,145 

current smokers (age 18 and 

older). 16,294 smoked 

menthol, 46,899 smoked 

nonmenthol, and 2,952 did 

not respond. 

Menthol use was assessed by: 

“Is your usual cigarette 

brand menthol or 

nonmenthol?” 

Age of initiation was assessed 

by: “How old were you 

when you first started 

smoking cigarettes fairly 

regularly?” (answer given as 

age in years) 

Smoking Preference

Nonmenthol 

Menthol 

Mean age of Initiation 

All Smokers 

<18 

>18 

Menthol Smokers 

<18 

>18 

Nonmenthol Smokers 

<18 

>18 

Adjusted Odds

Ratio of Delayed 

Initiation (95% CI) 

1.0 (reference) 

1.01 (1.00-1.01)* 

Adjusted for 

demographic and 

smoking variables. 

Percent (95% CI) 

55.3 (+0.5) 

44.7 (+0.5) 

53.2 (+0.9) 

46.8 (+0.9) 

56.2 (+0.6) 

43.8 (+0.6) 

Menthol smokers in the 

U.S. tend to start 

smoking later than 

smokers of other types 

of cigarettes. This 

finding is suggestive only 

and requires further 

study. 

Conclusions are supported 

by study data. 

Large national populationbased survey with many 

menthol smokers. 

Cross-sectional nature of 

analysis does not permit 

causal conclusions. 

Authors do not have 

information on type of 

cigarette used at initiation 

(menthol vs. nonmenthol). 

Thus, “menthol smoker” 

refers to preference as an 

adult. 

Menthol use was selfreported. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

Chapter 4 - Appendix 

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Table 4-3. Higher Quality Studies on Menthol Cigarette Smoking and Initiation Behaviors (N=5) (Continued) 

CITATION OUTCOME 

STUDY TYPE MEASURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Lawrence et al. 

2010 

United States 

Age at onset of regular

smoking 

Cross-sectional analysis of 

data from the 2003 and 

2006/07 Tobacco Use 

Supplement to the Current 

Population Survey. 

Analysis was based on 69,193 

current smokers (age 18 and 

older). 16,294 (25.8%) 

smoked menthol cigarettes 

and 46,899 (74.2%) smoked 

non-menthol cigarettes. 

Analyses were restricted to 

self-respondents who 

comprised 64.6% of the 2003 

sample and 75.1% of the 

2006/07 sample. 

Dependence data are 

included in Table 5-4. 

Age at Onset of Regular 

Smoking 

All Current Smokers 

≤14

15-17 

18+ 

Current Male Smokers 

≤14

15-17 

18+ 

Current Female Smokers 

≤14

15-17 

18+ 

Adjusted Odds

Ratio of Menthol 

Use (95% CI) 

0.99 (0.90-1.09) 

0.95 (0.89-1.02) 

1.0 (reference) 

1.10 (0.95-1.28) 

1.01 (0.91-1.12) 

1.00 (reference) 

0.89 (0.79-1.01) 

0.90 (0.82-0.99)** 

1.0 (reference) 

Adjusted for other 

sociodemographic and 

smoking behavior 

variables that were 

significant in the 

bivariate regression 

analysis. 

Race/ethnicity, sex and 

age are significant 

correlates of 

mentholated cigarette 

smoking among current 

smokers. 

The age of smoking 

onset was associated 

significantly with 

mentholated cigarette 

use among women but 

not among men or 

among the total sample. 

Large national populationbased survey with many 

menthol smokers. 

Cross-sectional nature of 

analysis does not permit 

causal conclusions. 

Authors do not have 

information on type of 

cigarette used at initiation 

(menthol vs. nonmenthol). 

Thus, “menthol smoker” 

refers to preference as an 

adult. 

Menthol use was selfreported. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

Chapter 4 - Appendix 

139
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 4-4. Distribution of Menthol versus Nonmenthol Current Cigarette Smokinga (NHANES, 1999-2008); 

Demographic Characteristics for New Smokers (Smoking for 1 year or less) 

Variable Survey Year Frequency 

Regular (nonmenthol) Menthol 

Weighted 

frequencyb Percent 95% CIc Frequency Weighted frequencyb Percent 95% CIc 

Total 

1999-2000 41 1,532,287 91.0 82.7, 99.3 9 151,989 9.0 0.7, 17.3 

2001-2002 47 1,470,946 65.5 51.2, 79.8 22 774,736 34.5 20.2, 48.8 

2003-2004 45 1,411,493 74.0 57.1, 90.8 17 496,282 26.0 9.2, 42.9 

2005-2006 38 1,106,681 73.9 55.3, 92.5 12 390,458 26.1 7.5, 44.7 

2007-2008 20 924,677 66.7 42.8, 90.5 16 462,253 33.3 9.5, 57.2 

Sex 

Males 

1999-2000 25 1,192,276 94.1 85.9, 100 3 74,565 5.9 0.0, 14.1 

2001-2002 32 907,469 69.9 52.1, 87.7 11 390,587 30.1 12.3, 47.9 

2003-2004 27 823,380 79.2 62.3, 96.2 8 215,595 20.8 3.8, 37.7 

2005-2006 21 616,418 75.4 40.4, 100 6 200,787 24.6 0.0, 59.6 

2007-2008 10 593,603 81.2 56.9, 100 7 137,361 18.8 0.0, 43.1 

Females 

1999-2000 16 340,011 81.5 50.4, 100 6 77,424 18.5 0.0, 49.6 

2001-2002 15 563,477 59.5 30.3, 88.6 11 384,149 40.5 11.4, 69.7 

2003-2004 18 588,113 67.7 38.7, 96.7 9 280,686 32.3 3.3, 61.3 

2005-2006 17 490,263 72.1 55.9, 88.3 6 189,670 27.9 11.7, 44.1 

2007-2008 10 331,075 50.5 29.8, 71.2 9 324,892 49.5 28.8, 70.2 

Race/ethnicity 

NonHispanic 

White 

1999-2000 15 1,205,419 100.0 100, 100 0.0 

2001-2002 18 924,462 68.7 58.0, 79.5 8 420,488 31.3 20.5, 42.0 

2003-2004 19 988,547 79.9 53.6, 100 5 248,017 20.1 0.0, 46.4 

2005-2006 16 741,267 75.0 35.4, 100 4 247,224 25.0 0.0, 64.6 

2007-2008 13 826,011 78.7 52.0, 100 5 223,070 21.3 0.0, 48.0 

NonHispanic 

Black 

1999-2000 9 58,625 35.5 11.6, 59.5 6 106,442 64.5 40.5, 88.4 

2001-2002 10 67,471 33.0 0.0, 97.8 5 137,178 67.0 2.2, 100 

2003-2004 12 110,581 51.4 24.1, 78.7 7 104,624 48.6 21.3, 75.9 

2005-2006 4 78,781 49.1 48.2, 49.9 4 81,808 50.9 50.1, 51.8 

2007-2008 0 0 0.0 0 5 124,568 100.0 0 

Chapter 4 - Appendix 

140
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 4-4. Distribution of Menthol versus Nonmenthol Current Cigarette Smokinga (NHANES, 1999-2008); 

Demographic Characteristics for New Smokers (Smoking for 1 year or less) (Continued) 

Variable Survey Year Frequency 

Regular (nonmenthol) Menthol 

Weighted 

frequencyb Percent 95% CIc Frequency Weighted 

frequencyb Percent 95% CIc 

Other 

1999-2000 17 268,244 85.5 42.7, 100 3 45,547 14.5 0.0, 57.3 

2001-2002 19 479,013 68.8 35.4, 100 9 217,071 31.2 0.0, 64.6 

2003-2004 14 312,365 68.5 40.1, 96.9 5 143,641 31.5 3.1, 59.9 

2005-2006 18 286,633 82.4 54.6, 100 4 61,426 17.6 0.0, 45.4 

2007-2008 7 98,667 46.3 16.6, 75.9 6 114,615 53.7 24.1, 83.4 

Current age (years) 

12 to 17 

1999-2000 13 253,684 85.3 50.5, 100 2 43,606 14.7 0.0, 49.5 

2001-2002 14 191,992 74.9 74.0, 75.9 3 64,189 25.1 24.1, 26.0 

2003-2004 16 292,765 85.8 74.1, 97.4 4 48,578 14.2 2.6, 25.9 

2005-2006 13 292,094 81.2 44.7, 100 3 67,594 18.8 0.0, 55.3 

2007-2008 3 168,902 95.6 0 1 7,730 4.4 0 

18 to 24 

1999-2000 12 496,587 90.5 51.1, 100 2 52,033 9.5 0.0, 48.9 

2001-2002 11 258,171 41.3 11.0, 71.6 13 367,137 58.7 28.4, 89.0 

2003-2004 12 469,666 59.0 35.0, 83.0 10 326,663 41.0 17.0, 65.0 

2005-2006 10 270,980 72.0 0.0, 100 2 105,198 28.0 0.0, 100 

2007-2008 8 417,678 62.5 9.8, 100 8 251,046 37.5 0.0, 90.2 

25 to 29 

1999-2000 0 0 

2001-2002 2 95,827 39.4 3 147,156 60.6 

2003-2004 1 65,699 48.2 0.0, 100 1 70,492 51.8 0.0, 100 

2005-2006 1 67,531 67.6 2 32,322 32.4 

2007-2008 1 24,863 24.8 1 75,392 75.2 

≥30 

1999-2000 16 782,017 93.3 82.2, 100 5 56,350 6.7 0.0, 17.8 

2001-2002 20 924,955 82.5 69.6, 95.4 3 196,254 17.5 4.6, 30.4 

2003-2004 16 583,363 92.0 73.3, 100 2 50,549 8.0 0.0, 26.7 

2005-2006 14 476,076 72.0 59.3, 84.7 5 185,344 28.0 15.3, 40.7 

2007-2008 8 313,235 71.0 25.7, 100 6 128,085 29.0 0.0, 74.3 a Current cigarette smoking defined as having smoked on 10 or more of the last 30 days 

b Frequency among survey respondents weighted to represent the population of the United States c 95% confidence interval around estimated percentages 

Chapter 4 - Appendix 

141
 

 

 

 

 

 

 

 

 

 

 

 

 

 

CHAPTER 5A. 

MENTHOL IN CIGARETTES HAS NO MEANINGFUL IMPACT
 

ON SMOKING CESSATION
 

Concern has been raised about whether it may be harder to quit smoking menthol cigarettes than 

nonmenthol cigarettes. Information on this issue comes from two major sources: nationally 

representative surveys and individual studies of specific populations. While these data sources 

provide some opportunities to examine adolescent smoking behaviors, virtually all of the existing 

data on smoking cessation come from studies of adults. 

When assessing this literature, it is imperative to base conclusions on those studies that are 

methodologically sound. Many of the published studies have serious flaws or do not make 

appropriate inferences based on their findings. Although a limited number of studies may suggest 

that menthol cigarette smokers have lower rates of cessation compared to nonmenthol smokers, 

critical evaluation of the findings often indicates that the stated conclusions are not truly supported 

by the data. FDA must base its regulatory policy only on those studies that present strong science. 

And, because smoking cessation attempts are plagued by relapses, it is also essential that FDA give 

greatest weight to those studies that examine long-term successful cessation (6 months or longer) 

rather than short-term (past 7 days) cessation (Pierce and Gilpin 2003). 

This chapter reviews what is known about the complex process of quitting smoking, discusses the 

most appropriate way to assess cessation, and reviews the available data, with emphasis placed on 

the most methodologically sound studies. Critical review of the best available studies indicates that 

individuals who smoke menthol cigarettes do not have significantly lower rates of quitting smoking 

compared to individuals who smoke nonmenthol cigarettes. Given the overall consistency of this 

lack of significant findings among the best studies, using the Surgeon General’s framework for 

assessing causality leads to the conclusion that the “evidence is suggestive of no causal 

relationship” between menthol cigarette use and reduced smoking cessation. Further, as discussed 

later in Chapter 5B, the methodologically sound studies that compare nicotine or smoking 

dependence between menthol and nonmenthol smokers do not suggest that menthol cigarette 

smokers are any more dependent on or addicted to cigarettes. With respect to this endpoint, the 

“evidence is suggestive of no causal relationship” between menthol cigarette use and nicotine 

or smoking dependence. The rationale and scientific basis for these conclusions are discussed in 

further detail below. 

FACTORS ASSOCIATED WITH SMOKING CESSATION 

Quitting smoking is a difficult process. Every year, many smokers try to quit but most do not 

succeed. There has been much interest in identifying factors associated with making a quit attempt 

and with successful long-term smoking cessation. Research indicates that changing smoking 

behavior usually involves a series of stages (pre-contemplation, contemplation, and preparation), 

with each stage influenced by different factors. Many studies have evaluated individual aspects of 

smokers’ characteristics to determine the predictors of successful smoking cessation, and have 

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identified a number of demographic, behavioral (including smoking behavior), psychological, and 

environmental factors that play a role. 

A recent analysis by investigators associated with the Centers for Disease Control and Prevention 

(Lee and Kahende 2007) evaluated data from a representative sample of the U.S. Population (2000 

National Health Interview Survey (NHIS)) to determine significant predictors of smoking cessation. 

The authors reported that successful quitters tended to have rules against smoking in their homes, 

were less likely to have switched to light cigarettes for health concerns, and were more likely to be 

aged ≥35 years, married or living with a partner, be non-Hispanic White, and have at least a college 

education. 

There are ethnic and social differences in smoking cessation among various subgroups of the 

population. Although many factors are recognized to play a role in smoking cessation, major 

reviews of the literature have not identified menthol cigarette use as a significant factor. In recent 

years, researchers have raised the question of whether smoking menthol cigarettes adversely impacts 

cessation behavior or success in quitting. 

DIFFICULTIES IN ASSESSING SMOKING CESSATION 

Assessing smoking cessation is not straightforward. Studies differ in terms of how cessation is 

defined, study design and methodology used, and population evaluated. Therefore, it is not 

surprising that some studies provide more useful information about the relationship between 

menthol cigarette smoking and cessation than others. 

It is especially important to clarify what is meant by smoking cessation. Many smokers who attempt 

to quit smoking manage only short-term abstinence; 75-80% of people who try to quit smoking will 

relapse within six months (NIDA 2009). Hence, the most valuable and definitive studies are those 

that define cessation as long-term abstention from smoking, which in practice can be defined as not 

smoking any cigarettes for six months or more. 

The ideal study of whether smoking menthol cigarettes reduces a smoker’s ability to quit would 

enroll a large cohort of subjects representative of smokers in the general smoking population (with 

over-sampling of African American smokers to ensure adequate numbers of menthol and 

nonmenthol smokers) and follow the cohort for a number of years. All participants would be recontacted in person at 1-year intervals and would answer questions about their smoking, whether 

they had quit, and would provide a urine sample (for cotinine analysis1

) to verify quitting. In 

addition, detailed information would be collected at baseline (and, for certain variables, at each 

annual visit) on sociodemographic factors, smoking behavior, nicotine dependence, alcohol 

consumption, body mass index, and health and respiratory symptoms. Such a study would make it 

possible to verify the stability of type of cigarette smoked (menthol versus nonmenthol), to assess 

long-term cessation, and to validate nonsmoking status at multiple points in time with urinary 

cotinine measurements. It would also enable researchers to adjust for numerous variables that might 

confound the association of menthol cigarette use and smoking cessation. 

1 Measurement of cotinine, a primary metabolite of nicotine that has a half-life of 16 to 18 hours and that can be 

detected in urine, saliva, or serum, provides a reliable means of determining smoking status and other tobacco product 

use or exposure over a period of 2 to 3 days (Montalto and Wells 2007). 

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None of the available studies meets all of these criteria. However, some of the studies are superior 

to others. Prospective studies that follow current smokers over time and document long-term 

cessation provide the most informative data. Second, cross-sectional studies of large, nationally 

representative populations with high participation rates that gather data on quit attempts and length 

of time without smoking are informative. Finally, studies of individuals in randomized trials of 

cessation medications or attending short-term smoking cessation clinics that employ multiple 

assistance strategies may have biased samples of subjects and, while they should be considered, 

cannot reflect quitting patterns in the general population (Freund et al. 1992). 

BEST AVAILABLE SCIENCE WAS DETERMINED THROUGH A RIGOROUS 

PROCESS 

As noted above, there are two potential sources of data on menthol smoking and cessation: 

nationally representative surveys and individual studies of specific populations. These sources of 

information are fairly consistent in showing that smokers of menthol cigarettes are no less likely to 

quit smoking than smokers of nonmenthol cigarettes. 

At the request of the Lorillard Tobacco Company, Covance conducted a comprehensive search of 

the literature on the association between menthol cigarette use and smoking cessation and evaluated 

the identified studies for methodologic quality. The report of Covance’s analysis has been provided 

to TPSAC and the findings were presented to TPSAC in summary fashion on February 10, 2011. 

An updated report from Covance (as referenced in Chapter 1) includes an evaluation of additional 

recent studies. 

The Covance report describes in detail the rigorous and objective process used to identify and 

evaluate the available published literature. Briefly, a systematic search of the published literature was 

conducted to identify studies that addressed use of menthol cigarettes and a variety of cessation 

behaviors. Covance then evaluated these articles for methodologic quality (using criteria developed 

by FDA for Healthcare Research and Quality (Ranney et al. 2006)), and for ability to support 

inferences related to menthol. Quality ratings for these two measures included: poor, poor/fair, 

fair, fair/good, and good. The studies were categorized into three tiers as follows: 

•	 Tier 1 studies were those rated by Covance as fair or better with respect to both overall 

quality and ability to support inferences related to menthol cigarette use; 

•	 Tier 2 studies were those rated by Covance as fair or better with respect to overall quality, 

but lower than fair with respect to ability to support inferences related to menthol cigarette 

use; and 

•	 Tier 3 studies were those rated by Covance as lower than fair with respect to both categories. 

Twenty-five articles were identified that evaluated the relationship between menthol cigarette use 

and smoking cessation. Of these, Covance’s ratings placed 15 studies in Tier 1, four studies in 

Tier 2, and six studies study in Tier 3, as shown below. 

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Chapter 5 

 

 

 

 

 

Table 5-1. Studies of Menthol Smoking and Cessation Behaviors (N=25) 

Quality Ratings by Covance 

Citation Overall Quality Rating Rating: Menthol 

Inferences 

Tier 1 

Alexander et al. 2010 Fair/Good Fair/Good 

Berg et al. 2010 Fair Fair 

Cubbin et al. 2010 Fair/Good Fair/Good 

Fagan et al. 2010 Fair/Good Fair 

Foulds et al. 2006 Fair Fair 

Gandhi et al. 2009 Good Fair 

Gundersen et al. 2009 Good Fair/Good 

Hyland et al. 2002 Fair Fair 

Murray et al. 2007 Fair/Good Fair/Good 

Muscat et al. 2002 Fair Fair 

Okuyemi et al. 2003 Fair Fair 

Okuyemi et al. 2007 Good Fair 

Pletcher et al. 2006 Good Good 

Stahre et al. 2010 Fair Fair 

Trinidad et al. 2010 Good Fair/Good 

Tier 2 

Bover et al. 2008 Fair Poor 

Cropsey et al. 2009 Good Poor 

Fu et al. 2008 Fair Poor 

Hymowitz et al. 1995 Fair Poor 

Tier 3 

Ahijevych and Parsley 1999 Poor Poor 

Fagan et al. 2007 Poor/Fair Poor 

Harris et al. 2004 Poor Poor 

Hersey et al. 2006 Poor/Fair Poor/Fair 

Li et al. 2005 Poor Poor 

Okuyemi et al. 2004 Poor Poor 

Tier 1 Studies on Menthol Cigarette Smoking and Cessation Behaviors 

The 15 Tier 1 studies are considered to be the “best available science” for assessing the effect of 

menthol cigarette use and smoking cessation. These studies are summarized in Appendix Table 5-3 

and are assessed below in a hierarchical fashion, as follows: 

•	 Prospective or cross-sectional studies that assess long-term (at least 6 months) cessation: 

Hyland et al. 2002, Murray et al. 2007, Muscat et al. 2002, Pletcher et al. 2006. 

•	 Cross-sectional studies of nationally representative populations with high participation 

rates that examined quit attempts and time since quitting: Alexander et al. 2010, Cubbin 

et al. 2010, Fagan et al. 2010, Gundersen et al. 2009, Stahre et al. 2010, Trinidad et al. 

2010. 

•	 Studies from smoking cessation clinics that examined only short-term (7-day) cessation: 

Berg et al. 2010, Foulds et al. 2006, Gandhi et al. 2009, Okuyemi et al. 2003, Okuyemi et 

al. 2007. 

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There are important differences between those studies in the first two categories and those in the 

third. Studies in the first two categories tend to be larger, have subjects that are more representative 

of the general smoking population, and evaluate spontaneous quitting (which is how the majority of 

people quit). Those studies in the third category tend to be smaller, enroll subjects that are not 

representative of the general smoking population (e.g., two are composed of only African American 

light smokers), and consist solely of individuals who sought smoking cessation assistance. Smokers 

who seek assistance from cessation clinics consider themselves to be more highly dependent than 

smokers who are representative of the general population (Etter et al. 2009). Based on the findings 

from the first two categories of studies combined, smoking menthol cigarettes does not adversely 

impact the ability to achieve long-term cessation compared to smoking nonmenthol cigarettes. 

Prospective and Cross-Sectional Studies that Examined Long-Term Cessation 

Four studies (three prospective and one cross-sectional) compared long-term cessation (6 months or 

more) among menthol and nonmenthol smokers. Three of these found no significant difference in 

long-term quitting among menthol compared to nonmenthol smokers (Hyland et al. 2002, Murray et 

al. 2007, Muscat et al. 2002). The fourth study (Pletcher et al. 2006) found no significant differences 

in 4 of 5 cessation measures, but there was a significant increase in the remaining measure, i.e, 

documented relapse, among menthol cigarette smokers. These studies are described briefly below: 

Hyland et al. (2002) examined the association between smoking menthol cigarettes and 

quitting in the COMMIT trial of smoking cessation. The study was large, involving a 

random sample of more than 13,000 smokers (aged 25-64 years) from a representative 

sample of households in ten U.S. communities. Approximately 24% of current smokers 

smoked menthol cigarettes at baseline in 1988. Multivariate regression was used to assess 

the association between baseline menthol cigarette use and cessation in 1993 (defined as not 

having smoked any cigarettes in the past 6 months). Nearly one-quarter of baseline smokers 

quit smoking between 1988 and 1993; the adjusted relative risk of quitting was no different 

for menthol compared to nonmenthol smokers (RR=1.00; 95% CI:0.90-1.11). The authors 

concluded that “Use of mentholated cigarettes was not associated with quitting.” 

Furthermore, none of the race/ethnicity-specific analyses revealed any significant 

associations with menthol cigarette use. 

Murray et al. (2007) describe an analysis of data from the Lung Health Study, a clinical trial 

of smoking cessation that included 5,887 current smokers at baseline with mild to moderate 

airway obstruction. About 20% had smoked menthol cigarettes at baseline. Sustained 

quitting was assessed at five annual visits, and required biochemical confirmation as well as 

no recollection (at any annual visits) of any months in which ≥1 cigarette per day was 

smoked. After 5 years of follow-up, there were no significant differences in the proportion 

of quitters among menthol smokers compared to nonmenthol smokers for either men or 

women. Effects by race were not addressed. The authors concluded, “We found no 

difference in success at smoking cessation with or without menthol.” 

Muscat et al. (2002) performed a cross-sectional analysis of smoking habits among 19,545 

subjects in a case-control study of smoking and lung cancer. The investigators examined 

whether menthol cigarette use was associated with heavy smoking or quitting, and whether 

menthol cigarette use explained racial differences in these smoking behaviors. All subjects 

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were current or former smokers; of these, 3,005 smoked menthol cigarettes. Quitting was 

defined as not smoking ≥1 cigarette each day in the past year. The adjusted prevalence odds 

ratio of continued smoking versus quitting associated with menthol cigarette use was 1.1 

(95% CI:1.0-1.2) for both Blacks and Whites. The authors concluded that “The risk of 

quitting was not associated with cigarette menthol flavor.” Furthermore, menthol cigarette 

use was not associated with continued smoking among either Blacks or Whites. 

Pletcher et al. (2006) analyzed data on subjects in the CARDIA cohort study who were 

smokers at baseline, and assessed cessation after 15 years of follow-up. There were no 

significant associations between menthol smoking and 4 of 5 measures of cessation 

examined, including not currently smoking, recent quit attempts, cessation if recent quit 

attempt and sustained cessation. The most stringent of these measures was sustained 

cessation, which was defined as no current smoking in the past 2 CARDIA exams (2 to 5 

years apart) (OR=0.70; 95% CI:0.48-1.03). The only significant association was with an 

outcome referred to as documented relapse, i.e., smoking at one follow-up visit after selfreported quitting at a prior visit (OR=1.89, 95% CI:1.17-3.05). Based on this single finding, 

the authors concluded that “ . . . menthol cigarettes may be harder to quit smoking.” The 

limited number of European American menthol smokers and African American nonmenthol 

smokers in this cohort made it difficult to differentiate the independent effects of menthol 

cigarette use from the confounding influence of ethnicity. 

Cross-Sectional Studies of Nationally Representative Populations 

Some of the nationally representative surveys described in Chapter 2 (the Tobacco Use Supplement 

to the Current Population Survey and the National Health Interview Survey) provide data on 

menthol cigarette use and smoking cessation. Findings from these surveys are more generalizable to 

the overall smoking population than those from tobacco cessation clinics, and are thus informative 

with respect to potential population-level effects. It is important to recognize that cessation is 

typically assessed in these surveys as a “quit attempt” (which could be defined as not smoking for 

even one day in the past 12 months), which is much less rigorous than the long-term (at least six 

months) smoking cessation definition in the studies evaluated above. Six analyses of menthol 

cigarette smoking and quit attempts based on these nationally representative surveys are summarized 

below. 

Tobacco Use Supplement to the Current Population Survey (TUS-CPS) 

Three analyses were based on the TUS-CPS; two found no evidence that quitting behaviors differ 

significantly between menthol and nonmenthol smokers. 

Alexander et al. (2010) assessed life-time attempts to quit (defined as ever stopped smoking for ≥1 

day) among 30,176 current smokers in the 2006/07 TUS-CPS. After controlling for occupational 

status and work-place cessation policies, menthol smokers did not differ significantly from 

nonmenthol smokers in life-time attempts to quit smoking (OR 0.98; CI:0.83-1.15). 

Fagan et al. (2010) assessed slightly different cessation measures (i.e., was there a quit attempt of 

≥1 day in past 12 months; abstinence >2 weeks vs. ≤2 weeks; and intent to quit in the next 30 days) 

among 46,273 adults who were current daily smokers in the 2003 and 2006/07 TUS-CPS. 

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Multivariate models did not show significant associations between usual cigarette type (menthol 

versus nonmenthol) and any of the three cessation outcomes evaluated. The authors concluded that 

their data do not support the hypothesis that menthol smokers experience greater difficulty quitting. 

Trinidad et al. (2010) conducted a third analysis of data from the TUS-CPS, examining menthol 

cigarette use and smoking cessation among adults (aged 20-65 years) of different racial/ethnic 

groups (African American, Asian American/Pacific Islander, Hispanic/Latino, Native American, 

non-Hispanic White) in the 2003 and 2006/07 surveys. Researchers examined pre-quitting 

behaviors among current smokers and successful cessation (being quit for ≥6 months) among 

former smokers. Findings from adjusted logistic regression models indicated that African 

Americans and Hispanic/Latinos (but not other races) who smoked menthol cigarettes were 

significantly more likely to be seriously considering quitting in the next 6 months and to have a 

positive estimation of quitting successfully compared to those who smoked nonmenthol cigarettes. 

With respect to cessation, across race/ethnic groups, former regular smokers of menthol cigarettes 

were less likely to have experienced long-term quitting success. 

National Health Interview Survey (NHIS) 

Three analyses based on the 2005 NHIS compared long-term cessation among menthol and 

nonmenthol smokers; one of these found no evidence that menthol smokers have a harder time 

quitting than nonmenthol smokers. 

Cubbin et al. (2010) analyzed 21,196 adults who reported their menthol status by race (Black, 

White, Hispanic) and sex; they found no significant differences by cigarette type in percent making a 

quit attempt in the past year. The only significant difference was in time since quitting in one racial 

subgroup; White women who smoked menthol cigarettes reported longer cessation than those who 

smoked nonmenthol cigarettes (15 vs. 12.5 years; p<0.01). 

The two other analyses based on the 2005 NHIS reported some findings that suggested there could 

be poorer cessation outcomes among non-White menthol smokers. 

Stahre et al. (2010) examined the population quit ratio (i.e., total number of former smokers 

divided by total life-time smokers), and use of quit aids among 12,004 current or former adult 

smokers. Curiously, the sample population was not weighted to provide nationally representative 

estimates, likely limiting the generalizability of study findings to the overall population of smokers. 

There were no significant differences in quit ratios for menthol versus nonmenthol smokers among 

Whites, Asian Americans or Hispanics, but there was for African Americans. Regression analysis 

showed a significant interaction between menthol status and African American race, such that 

African American menthol smokers were significantly less likely than White nonmenthol smokers to 

have quit smoking (AOR 0.72; CI:0.53-0.97). 

Gundersen et al. (2009) analyzed 7,815 current and former smokers and found that the association 

between menthol smoking and cessation was different for Whites compared to non-Whites (Blacks 

and Hispanics combined). Non-White menthol cigarette smokers were significantly less likely to 

have stopped smoking compared to non-White nonmenthol smokers (OR=0.55; 95% CI:0.43-0.71), 

whereas White menthol smokers were significantly more likely to have quit compared to White 

nonmenthol smokers (OR=1.17; 95% CI:1.00-1.36). Study findings assumed that a causal 

connection between menthol smoking and an ability to quit operated in an opposite direction for 

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Whites and non-Whites, an assumption that is not supported by a plausible mechanism. When races 

were examined individually, there was no difference in cessation between Black menthol and 

nonmenthol smokers, and Hispanic menthol smokers were significantly less likely to have quit than 

Hispanic nonmenthol smokers. The findings from these two analyses suggest that variables other 

than menthol (e.g., socioeconomic status, metabolic issues, uncontrolled confounding) may account 

for the race-associated differences found in different analyses of the same survey data. 

Studies from Smoking Cessation Clinics with Short-Term Cessation Measures 

Five studies conducted in smoking cessation and tobacco treatment clinics provide relevant data on 

menthol and nonmenthol smokers. The clinic-based studies were all designed to assess the efficacy 

of various pharmacological and other therapies in promoting cessation, but not to evaluate menthol 

in a controlled fashion as an independent variable. In addition, these studies have important 

differences from those using more representative sample populations. The following studies 

involved specific groups of subjects who sought help in quitting smoking and thus are not 

representative of the general population; they followed the subjects for shorter durations (4 weeks to 

26 weeks); and they defined cessation much less stringently (i.e., only 7 days of abstinence). These 

studies generally found no difference in rates of cessation for menthol and nonmenthol smokers, 

although one study (Gandhi et al. 2009) showed that African Americans and Latinos who smoked 

menthol cigarettes have reduced success in quitting compared with nonmenthol smokers in the 

same racial groups. 

Berg et al. (2010) investigated factors predicting smoking reduction among Black light smokers 

(<10 cigarettes/day) enrolled in a 26-week cessation trial. Quitters were defined based on selfreported cessation verified by salivary cotinine concentrations of ≤20 ng/mL (which indicates only 

that there was no tobacco use or nicotine replacement therapy in the past 2-3 days). The authors did 

not draw specific conclusions about the relationship between menthol smoking and cessation, even 

though 81% of the subjects smoked menthol cigarettes. However, examination of the data shows 

that smoking menthol cigarettes did not significantly affect either reduction of smoking or cessation 

in this study group. 

Foulds et al. (2006) evaluated a cohort of the first 1,021 patients attending a free tobacco treatment 

clinic who made a quit attempt (41% of whom smoked menthol cigarettes).

2

 Logistic regression was 

used to identify factors associated with abstinence at 4 weeks and 6 months of follow-up. Cessation 

was defined as not having used any tobacco in the past 7 days. Although the authors concluded 

that, “Those smoking nonmenthol cigarettes at assessment showed a trend toward being more likely 

to be abstinent” at 4 weeks (AOR=1.359; 95% CI:0.996-1.856, p=0.053), this finding was not 

significant. Cigarette type was not associated with 26 week abstinence. This study shows why it is 

important to follow subjects for more than just a few weeks, and why it is important to look beyond 

the stated conclusions to the actual data. Results were not presented by race but 66% of the subjects 

were White. It should be noted that one-third of subjects included in this study were lost to followup. 

2 Foulds et al. (2006), Gandhi et al. (2009) and Bover et al. (2008) all reported on consecutive patients from the same 

smoking cessation clinic. Given that the enrollment period overlapped, the study samples likely contained some subset 

of identical patients. Thus, these three studies should not be considered as entirely independent analyses. 

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Gandhi et al. (2009) evaluated quit rates among 1,688 consecutive patients (White, African 

American and Latino smokers) at a tobacco treatment clinic.

2

 Cessation, which was defined as 7-day 

point prevalence, was assessed at 4 weeks and 6 months. The authors concluded that, despite 

smoking fewer cigarettes per day, African American and Latino menthol smokers had reduced 

success in quitting compared to nonmenthol smokers of the same racial groups. For African 

Americans, the odds ratio for abstinence at 6 months associated with menthol smoking (compared 

to nonmenthol smoking) was 0.48 (95% CI:0.25-0.90); for Latinos, it was 0.64 (95% CI:0.20-1.80). 

However, among Whites, who made up the majority (64%) of the study group, menthol smokers 

were no less likely to quit than nonmenthol smokers (OR=1.0; 95% CI:0.80-1.40). It should be 

noted that, at six months, 42% of subjects had been lost to follow-up. 

Okuyemi et al. (2003) reported that African American menthol smokers had lower cessation rates 

after 6 weeks of treatment with bupropion. The randomized clinical trial involved 600 African 

Americans, 471 of whom were menthol smokers. Cessation was defined as 7 days of abstinence. 

While there was a significant difference between menthol and nonmenthol smokers in terms of 

percent abstinent at 6 weeks (p=0.006), that difference had disappeared by the terminal 6-month 

evaluation (p=0.21). Thus, if the reported effect of menthol on buproprion efficacy among African 

American smokers is real, it appears to be only transient in nature. Furthermore, abstinence rates 

did not differ by menthol status among those who received placebo, suggesting that menthol added 

to cigarettes does not influence spontaneous cessation (not aided by pharmaceuticals). 

Okuyemi et al. (2007) reported that among African American light smokers (<10 cigarettes/day), 

use of menthol cigarettes is associated with lower cessation rates. Researchers performed a 

secondary analysis of data from a randomized clinical trial involving 755 African Americans, 82% of 

whom were menthol smokers. Cessation was defined as 7 days of abstinence. At 26 weeks, 11.2% 

of menthol smokers versus 18.8% of nonmenthol smokers had achieved abstinence (p=0.015). 

However, these percentages are not adjusted, even though there were significant differences 

between menthol and nonmenthol smokers in potentially confounding factors, including age and 

duration of smoking in years. Other analyses that considered relevant confounders did not show a 

significant difference in cessation success for menthol compared with nonmenthol cigarette 

smokers. For example, adjusted logistic regression models stratified by age group (aged <50 and 

≥50 years) did not indicate that menthol versus nonmenthol status was significantly associated with 

abstinence. 

Tier 2 Studies on Menthol Smoking and Cessation Behaviors 

Four Tier 2 studies address this topic but have major weaknesses that preclude drawing sound 

conclusions. The studies are mentioned here briefly because they have been discussed at the 

TPSAC meetings. 

•	 Bover et al. (2008) found that menthol smoking was not a significant predictor of 

abstinence at 26 weeks among a group of smokers who sought treatment at a tobacco 

dependence clinic.

2

 The study suffered from a high attrition rate (~40%), and was not 

designed to evaluate menthol smoking and cessation directly. 

•	 Cropsey et al. (2009) found that smoking menthol cigarettes was not associated with 

different quit rates among Black and White female prisoners. The study had a high 

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attrition rate, and the results of this study cannot be generalized to a non-prison 

population. 

•	 Fu et al. (2008) found pharmacotherapy was more likely to be effective among menthol 

than nonmenthol cigarette smokers, with no difference in cessation success associated 

with cigarette type among patients randomized to usual care. 

•	 Hymowitz et al. (1995) analyzed data from the COMMIT trial by race/ethnicity, but 

did not attempt to link menthol smoking status with cessation outcomes. 

Six Tier 3 studies (Ahijevych and Parsley 1999, Fagan et al. 2007, Harris et al. 2004, Hersey et 

al. 2006, Li et al. 2005, Okuyemi et al. 2004) were all rated poor overall and in their ability to draw 

menthol inferences, and are not discussed in detail here. 

Unpublished Analyses Presented to TPSAC 

In July 2010 and January 2011, a number of unpublished analyses that addressed menthol cigarette 

use and smoking cessation were presented to TPSAC. Although these analyses have not undergone 

peer review, the authors’ reported conclusions are mentioned here briefly: 

•	 Curtin (unpublished) analyzed data from several large surveys and reported that: 

o	 According to the 2005/06 and 2007/08 NHANES, adolescent (aged 12-17 years) 

menthol cigarette smokers overall were no less likely to have reported past-year cessation 

attempts than nonmenthol smokers (49.2% vs. 53.3%, respectively; p=0.72). Similarly, 

there were no significant differences in the likelihood of attempting to quit smoking for 

menthol compared to nonmenthol cigarette smokers when stratified by race/ethnicity or 

sex. 

o	 According to the 2005 NHIS, adult menthol cigarette smokers overall were significantly 

more likely to have reported any quit attempt during the past 12 months compared to 

nonmenthol smokers (48.6% vs. 41.0%, respectively; p<0.001). Stratifying by 

race/ethnicity, sex, or current age indicated that non-Hispanic Black female, and younger 

(aged 18-24 years) menthol smokers were significantly more likely to have reported any 

past-year quit attempt compared to nonmenthol smokers (49.1% vs. 43.6%, p=0.02; 

53.4% vs. 38.6%, p<0.0001; and 57.9% vs. 46.4%, p=0.01). In regression models that 

controlled for the combination of race/ethnicity, sex and current age, the higher odds of 

reporting any past-year quit attempt associated with menthol compared to nonmenthol 

cigarette smoking was significant (OR 1.23; 95% CI:1.06-1.44; p=0.007). 

o	 According to the 2007 NYTS, adolescent (aged 9-21 years) menthol cigarette smokers 

overall were no less likely to have reported past-year cessation attempts than 

nonmenthol smokers (59.6% vs. 56.1%, respectively; p=0.27). Similarly, there were no 

significant differences in the likelihood of attempting to quit smoking for menthol 

compared to nonmenthol cigarette smokers when stratified by race/ethnicity or sex. 

•	 Delnevo et al. (unpublished) attempted to replicate Gundersen et al. (2009) by examining 

menthol smoking and cessation in the 2003 and 2006/07 TUS-CPS. It was reported that 

menthol smokers were significantly less likely to have quit smoking than nonmenthol 

smokers, and that the effect was more pronounced among Blacks and Puerto Ricans. 

•	 Hyland and Kasza (unpublished) evaluated data from the International Tobacco Control 

Four Country Survey and found that making a quit attempt, successful cessation and 

successful cessation among those making a quit attempt were generally similar among 

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menthol and nonmenthol smokers, although there were exceptions for some 

racial/ethnic/sex subgroups (Hispanic menthol smokers may be more dependent than 

Hispanic nonmenthol smokers). 

•	 Hyland and Rivard (unpublished) evaluated data from the COMMIT trial of smoking 

cessation and reported that menthol smokers were as likely as nonmenthol smokers to try to 

quit smoking and to be successful in quitting. 

•	 King et al. (unpublished) evaluated data from a clinical trial of naltrexone/nicotine 

patch/counseling in smoking cessation and found that menthol status, race, and medication 

interacted to affect outcomes. Among Whites, menthol smoking had no effect on quit rates; 

however, among African Americans, menthol users had lower quit rates than nonmenthol 

users when given standard treatment of patch and counseling, which was reversed with the 

addition of naltrexone. 

•	 Reitzel (a) (unpublished) analyzed data from the Project CARE longitudinal cohort study 

and found that menthol cigarette use was not significantly related to continuous abstinence 

from smoking through week 26 of follow-up. 

•	 Reitzel (b) (unpublished) analyzed data from the BREAK FREE clinical trial of smoking 

cessation and found that menthol cigarette smokers had higher rates of continuous smoking 

abstinence than nonmenthol smokers at follow-up, but that these differences were not 

significant. 

•	 Reitzel (c) (unpublished) analyzed data from the MOM clinical trial of smoking relapse 

prevention among post-partum women and found that menthol cigarette smokers had lower 

rates of continuous abstinence from smoking than nonmenthol smokers at follow-up but 

that these differences were not significant. White menthol smokers were less likely to 

maintain continuous smoking abstinence than White nonmenthol smokers, but the number 

of subjects in these analyses was small. 

•	 Unger et al. (unpublished) analyzed intention to quit smoking in a community-based 

survey of African American smokers and found no significant differences between menthol, 

nonmenthol and combined-type smokers. Certain subgroups of African American menthol 

smokers (light smokers and those with a high school education) may be less likely to express 

intentions to quit than nonmenthol smokers in these subgroups. 

MENTHOL CIGARETTES AND CESSATION BY RACE 

As noted above, 7 of the 15 Tier 1 studies presented cessation results by race. Three studies found 

that menthol smoking was not significantly associated with lower cessation rates among any of the 

races examined. Hyland et al. (2002) and Cubbin et al. (2010) examined Whites, Blacks and 

Hispanics, while Muscat et al. (2002) examined Blacks and Whites. 

Three studies reported different effects of menthol by race. Gandhi et al. (2009) found that, despite 

smoking fewer cigarettes per day, African American and Latino menthol smokers had reduced 

success in quitting compared to nonmenthol smokers of the same race. This was not true for White 

menthol smokers. Gundersen et al. (2009) and Stahre et al. (2010) both examined the data from the 

NHIS, and found some evidence that non-White menthol smokers had poorer cessation outcomes 

than nonmenthol smokers (contradicting the findings of Cubbin et al. 2010, cited above). 

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The seventh study (Trinidad et al. 2010) examined non-Hispanic Whites, African Americans, 

Hispanics, Asian American/Pacific Islanders and Native American/Alaska natives. Findings 

suggested that across all of these racial/ethnic groups, individuals who used to regularly smoke 

mentholated cigarettes were less likely to have experienced long-term quitting success. 

The remaining eight studies included only African American subjects (Berg et al. 2010, Okuyemi et 

al. 2003, Okeuyemi et al. 2007) or did not present results by race (Alexander et al. 2010, Fagan et al. 

2010, Foulds et al. 2006, Murray et al. 2007, Pletcher et al. 2006). 

MENTHOL CIGARETTES AND CESSATION AMONG YOUNG PEOPLE 

The published literature does not directly address smoking cessation among young people. 

However, some relevant information can be gleaned from the unpublished analyses of the nationally 

representative surveys by Curtin (unpublished) mentioned above. In the NHANES, adolescent 

(aged 12-17 years) menthol cigarette smokers overall were no less likely to have reported past-year 

cessation attempts than nonmenthol smokers (49.2% vs. 53.3%, respectively; p=0.72). In the 2005 

NHIS, younger (aged 18-24 years) menthol cigarette smokers were significantly more likely to have 

reported any past-year quit attempt compared to nonmenthol smokers (57.9% vs. 46.4%, p=0.01). 

Finally, in the 2007 NYTS, adolescent (aged 9-21 years) menthol cigarette smokers overall were no 

less likely to have reported past-year cessation attempts than nonmenthol smokers (59.6% vs. 

56.1%, respectively; p=0.27). 

CONCLUSION 

This review of the methodologically sound (Tier 1) literature on menthol cigarette smoking and 

cessation demonstrates that the most relevant studies, i.e., those that address successful long-term 

quitting, do not indicate that smokers of menthol cigarettes are significantly less likely to quit than 

are smokers of nonmenthol cigarettes. There is a sufficient number of high-quality studies that 

consistently find that menthol cigarette use has no meaningful impact on smoking cessation. Three 

of the cross-sectional studies, two of which only examined quit attempts on a single day (Gundersen 

et al. 2009, Stahre et al. 2010, Trinidad et al. 2010) and one of the three analyses of basically the 

same smoking cessation clinic population (Gandhi et al. 2009) reported some findings that suggested 

that among non-Whites, menthol smokers were less likely to be former smokers than nonmenthol 

smokers. However, if menthol is a factor that affects the ability to quit smoking, one would expect 

to see consistency among White and non-White subjects. This race-associated inconsistency 

suggests that some other factor affects the ability to quit, rather than menthol itself. 

Thus, according to the Surgeon General’s framework for assessing causality, the “evidence is 

suggestive of no causal relationship” between menthol cigarette use and success in smoking 

cessation. This is based on a consideration and synthesis of findings from a number of large, 

methodologically sound investigations of prospective cohorts and cross-sectional analyses of 

nationally representative population samples. The findings from these studies are more consistent 

and relevant than are the findings derived from, for example, smoking cessation clinic studies 

designed to evaluate various quit-smoking therapies. 

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CHAPTER 5B.
 

MENTHOL IN CIGARETTES HAS NO MEANINGFUL IMPACT
 

ON NICOTINE DEPENDENCE
 

An important element of cessation is the degree of a smoker’s dependence on nicotine. The more 

heavily dependent on nicotine an individual is, the harder it may be for that individual to quit. 

Dependence has been assessed by a variety of measures. While the best measures for assessing 

dependence have been debated, use of multiple measures or a composite measure is generally 

considered to be preferable to any single measure. For example, the Fagerström Test of Nicotine 

Dependence (FTND) is a reliable, validated and widely accepted composite measure of nicotine 

dependence (Heatherton et al. 1991). The FTND instrument provides an overall score based on 6 

items: 

•	 How soon after you wake up do you smoke your first cigarette? 

•	 Do you find it difficult to refrain from smoking in places where it is forbidden (e.g., in 

church, at the library, in the cinema, etc.)? 

•	 Which cigarette would you hate most to give up? 

•	 How many cigarettes per day do you smoke? 

•	 Do you smoke more frequently during the first hours after awakening than during the rest of 

the day? 

•	 Do you smoke if you are so ill that you are in bed most of the day? 

The FTND has been correlated with biochemical measures of smoking intensity, including 

concentrations of exhaled air carbon monoxide, salivary cotinine and salivary nicotine. Also useful 

is the 10-item Hooked on Nicotine Checklist (HONC), a reliable and valid measure of loss of 

autonomy over nicotine that has been used for screening adolescents for nicotine dependence 

(DiFranza et al. 2002). 

The methodologically sound studies that compare nicotine dependence between menthol and 

nonmenthol cigarette smokers do not suggest that menthol smokers are any more addicted to 

smoking. Using the Surgeon General’s framework for assessing causality leads to the conclusion 

that the “evidence is suggestive of no causal relationship” between menthol cigarette use and 

nicotine dependence. 

BEST AVAILABLE SCIENCE WAS DETERMINED THROUGH A RIGOROUS 

PROCESS 

Relevant studies on menthol cigarette use and nicotine dependence were identified by Covance 

through the process described in Chapters 4 and 5A. Briefly, a systematic search of the published 

literature was conducted and Covance evaluated the relevant articles for methodologic quality (using 

criteria developed by FDA for Healthcare Research and Quality) and for ability to support 

inferences related to menthol. Rating choices for these two measures of study quality included: 

poor, poor/fair, fair, fair/good, and good. The studies were categorized into three tiers as follows: 

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•	 Tier 1 studies were those rated by Covance as fair or better with respect to both overall 

quality and ability to support inferences related to menthol cigarette use; 

•	 Tier 2 studies were those rated by Covance as fair or better with respect to overall quality, 

but lower than fair with respect to ability to support inferences related to menthol cigarette 

use; and 

•	 Tier 3 studies were those rated by Covance as lower than fair with respect to both categories. 

Twenty-two articles were identified that evaluated the relationship between menthol cigarette use 

and nicotine dependence. Of these, Covance’s ratings placed 10 studies in Tier 1, five studies in Tier 

2, and seven studies study in Tier 3, as shown below. 

Table 5-2.	 Studies of Menthol Smoking and Nicotine Dependence (N=22) 

Quality Ratings by Covance 

Citation1 Overall Quality Rating Rating: Menthol 

Inferences 

Tier 1 

Ahijevych and Ford 2010 Fair/Good Fair 

Cubbin et al. 2010 Fair/Good Fair/Good 

DiFranza et al. 2004 Fair Fair 

Fagan et al. 2010 Fair/Good Fair 

Hyland et al. 2002 Fair Fair 

Lawrence et al. 2010 Good Good 

Mendiondo et al. 2010 Fair/Good Fair 

Moolchan et al. 2006 Good Good 

Muhammad-Kah et al. 2010 Fair/Good Fair/Good 

Muscat et al. 2002 Fair Fair 

Tier 2 

Ahijevych and Wewers 1993 Fair Poor 

Ahijevych et al. 2002 Fair Poor 

Bover et al. 2008 Fair Poor 

Hymowitz et al. 1995 Fair Poor 

Muscat et al. 2009 Fair Poor 

Tier 3 

Ahijevych and Parsley 1999 Poor Poor 

Collins and Moolchan 2006 Poor Poor 

Hersey et al. 2006 Poor/Fair Poor/Fair 

Li et al. 2005 Poor Poor 

Muilenburg and Legge 2008 Poor Poor 

Okuyemi et al. 2004 Poor Poor 

Wackowski and Delnevo 2007 Poor/Fair Poor 1 A number of additional studies provide data on measures of dependence (e.g., CPD, TTFC); however, as these data 

were provided as measures at baseline and dependence was not considered to be a primary outcome, they are not 

included here. These studies include Stahre et al. 2010, Fu et al. 2008, Gandhi et al. 2009, Murray et al. 2007 and 

Mustonen et al. 2005. 

Tier 1 Studies on Menthol Smoking and Nicotine Dependence 

The 10 Tier 1 studies are considered to be the “best available science” for assessing the effect of 

menthol cigarette use on nicotine dependence. These studies are described below and summarized 

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in Appendix Table 5-4. Studies encompass a variety of designs, including the large, well-conducted 

Total Exposure Study, a prospective study of the COMMIT trial, 5 cross-sectional analyses of 

nationally representative surveys (NHIS and TUS-CPS), and analyses of data from smoking 

cessation clinics. These 10 studies assessed subjects using the best measures of dependence (TTFC, 

CPD, FTND and/or HONC), and consistently indicated that menthol cigarette smokers are not 

significantly more dependent on nicotine than nonmenthol smokers. 

Ahijevych and Ford (2010) analyzed data on nicotine dependence from daily and non-daily young 

adult smokers (aged 18-24 years) in the 2006/07 TUS-CPS. Among daily smokers (N=2,241), there 

were no significant associations between menthol brand preference and either TTFC or CPD. 

Among non-daily smokers (N=688), menthol brand preference was not associated with cigarettes 

smoked per day but was associated with shorter time to first cigarette. Although the findings were 

mixed for the dependence outcomes examined, the authors concluded that, “Young adult non-daily 

smokers who preferred menthol cigarettes were significantly more dependent than those who 

preferred nonmenthol cigarettes, as shown by the shorter TTFC.” 

Cubbin et al. (2010) conducted a cross-sectional analysis of 21,196 adults from the 2005 NHIS and 

Cancer Control Supplement who reported their menthol status by race and sex. Menthol and 

nonmenthol smokers were compared on predicted mean CPD after adjustment for age, income and 

education. The authors found no significant differences for any group (stratified by race and sex) in 

the number of cigarettes smoked per day by cigarette type (menthol versus nonmenthol). The 

authors concluded that: “The results do not suggest that menthol smokers smoke more than 

nonmenthol smokers.” 

DiFranza et al. (2004) conducted a “retrospective/prospective” longitudinal analysis of seventh 

graders followed for 30 months as part of the Development and Assessment of Nicotine 

Dependence in Youth Study. The subjects were interviewed three times per year for three years, 

with the goal of understanding whether the recalled reaction to a first cigarette was predictive of 

later nicotine dependence. This analysis focused on 237 subjects who reported that they had inhaled 

cigarette smoke; only about half of them could recall whether the first cigarette they had smoked 

was menthol or nonmenthol. The authors found that reactions to the initial smoking experience 

were unrelated to cigarette mentholation; reactions were likewise unrelated to sex, cigarette brand or 

strength of cigarette. Only 59 subjects had smoked enough to establish a favorite brand; 42% 

indicated Newport as a favorite brand. The strength of the addiction, as measured by the HONC, 

did not differ according to the favorite brand, brand strength or menthol content. The mean 

HONC score was 6.0 for subjects whose favorite brand was menthol and 6.0 for subjects whose 

favorite brand was nonmenthol. 

This study has a number of important strengths, including its prospective nature, the fact that 

subjects were not expected to recall experiences from a long time ago, the use of an unselected 

population, and the inclusion of a validated measure of dependence. The study also had a number 

of limitations, including a small sample size, the fact that it focused on a variety of subjective 

symptoms, the fact that half of the subjects could not recall whether the first cigarette they smoked 

was menthol or nonmenthol, and the small number of African American (i.e., 4% of subjects). 

Fagan et al. (2010) analyzed 46,273 current adult daily smokers in the 2003 and 2006/07 TUS-CPS 

to determine whether there was association between menthol cigarette smoking and increased CPD 

or decreased TTFC after waking. Study data indicated that menthol smokers reported smoking 

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significantly fewer CPD than nonmenthol smokers (13.05 vs. 15.01, p<0.001). Comparisons of 

TTFC were made between menthol and nonmenthol smokers stratified by cigarettes smoked per 

day (≤5, 6-10, 11-19, ≥20). In general, there were no significant differences between menthol and 

nonmenthol smokers, regardless of whether TTFC was defined as ≤5 minutes or ≤30 minutes after 

waking. A single significant difference suggested that menthol smokers who smoked 6-10 CPD 

were more likely than nonmenthol smokers of 6-10 CPD to have their first cigarette within 5 

minutes after waking (OR 1.22; 95% CI:1.05-1.43). The authors focused on this one marginally 

significant finding to conclude that menthol smokers who reported consuming 6-10 CPD show 

greater signs of nicotine dependence than comparable nonmenthol smokers. However, it is 

inappropriate to focus on this single finding when the overall pattern of results suggests no 

difference in TTFC between menthol and nonmenthol smokers. The authors acknowledge that the 

effect was not dose-dependent, as the odds ratios for TTFC after waking did not increase as 

smoking intensity increased for menthol smokers. 

Hyland et al. (2002) examined the association between smoking menthol cigarettes and measures 

of nicotine dependence in the COMMIT trial of smoking cessation. The study involved a random 

sample of more than 13,000 smokers (aged 25-64 years) from a representative sample of households 

in ten U.S. communities. Data were collected first in 1988 and then 5 years later in 1993. 

Multivariate regression was used to assess the association between menthol cigarette use in 1988 and 

TTFC as reported in 1988. Overall, menthol smokers reported a significantly longer TTFC than 

nonmenthol smokers; this difference was no longer significant when the analyses were stratified by 

race. Linear regression was used to assess the association between menthol use in 1988 and 

estimated change in cigarettes smoked per day in 1993. There were no significant associations 

between menthol use and change in number of cigarettes smoked per day in either overall or racespecific analyses. The authors concluded that menthol smokers do not exhibit greater signs of 

nicotine dependence than do nonmenthol smokers. 

Lawrence et al. (2010) conducted a cross-sectional analysis of 63,193 current adult smokers in the 

2003 and 2006/07 TUS-CPS, 25.8% of whom smoked menthol cigarettes. This analysis was 

restricted to self-respondents who comprised 64.6% of the 2003 sample and 75.1% of the 2006/07 

sample. Multivariate regression was used to evaluate the association between menthol use and 

CPD/ TTFC (≤30 minutes vs. >30 minutes). Among all current smokers, heavy smokers (≥20 

cigarettes per day) were significantly less likely to be menthol smokers than were light smokers (≤5

cigarettes per day). This association was no longer significant when the analyses were stratified by 

sex. Also, whether subjects smoked their first cigarette within 30 minutes of waking was not a 

significant predictor of menthol smoking; this was true for all smokers, as well as male and female 

smokers when assessed separately. The authors did not draw any conclusions about menthol and 

dependence specifically, although they did note that prevalence of menthol use is significantly higher 

among individuals who smoke on some days than among individuals who smoke every day. 

Mendiondo et al. (2010) analyzed cross-sectional data from 12,004 current or former adult 

smokers in the 2005 NHIS and Cancer Control Supplement. Multivariate regression was used to 

assess the association between menthol use and CPD in two separate analyses of current and former 

smokers. Current menthol smokers smoked significantly fewer CPD after controlling for sex, age 

and race compared to current nonmenthol smokers. There was no difference among former 

smokers. 

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Moolchan et al. (2006) conducted a clinical evaluation of 91 adolescent smokers who were 

recruited for a smoking cessation study. These authors examined nicotine metabolism (cotinine to 

trans-3’-hydroxycotinine ratio) in an effort to explain the lower smoking rates among African 

Americans compared to Caucasians. African Americans had similar FTND scores compared to 

Caucasians (FTND scores were not provided for menthol smokers only, although 86% of the 

subjects smoked menthol cigarettes), yet smoked significantly fewer CPD and had significantly lower 

nicotine metabolite ratios than Caucasians. Although the focus of the study was on racial 

differences in nicotine metabolism, the authors did note that the results were essentially unchanged 

when looking only at the subgroup who smoked menthol cigarettes. This suggested that the 

observed difference was due to factors other than menthol. 

Muhammad-Kah et al. (2010) evaluated nicotine dependence in the Total Exposure Study, a large 

cross-sectional study of adult smokers. The analysis focused on 1,044 menthol and 2,297 

nonmenthol smokers. Dependence was assessed by overall FTND score, as well as the scores on 

the six individual items that make up the FTND. The authors found that, when odds ratios were 

adjusted by race, sex, age, tar yield, income and education, menthol status had no statistically 

significant effect on any single item of the FTND or on the overall scores (OR=1.05; 95% CI:0.91­

1.22) compared with nonmenthol smoking. In addition, menthol smokers did not have increased 

odds of smoking within the first 30 minutes after waking compared to nonmenthol smokers. The 

authors concluded that, “Our results add to the existing evidence that menthol does not increase 

nicotine dependence.” 

Muscat et al. (2002) performed a cross-sectional analysis of smoking habits among 19,545 subjects 

in a case-control study of smoking and lung cancer (see Chapter 3A). The investigators examined 

whether menthol cigarette use was associated with heavy smoking (defined as ≥21 CPD) and 

whether menthol cigarette use explained racial differences in these smoking behaviors. All subjects 

were current or former smokers; of these, 3,005 (15.4%) smoked menthol cigarettes. After 

adjustment for age, education, case-control status, sex and years of smoking, there were no 

significant differences in cigarette type (menthol versus nonmenthol) among White current or 

former heavy smokers. Among Black current and former smokers, heavy smokers were significantly 

less likely to be menthol smokers than nonmenthol smokers. According to the authors, the findings 

suggest that menthol does not increase the addictive properties of nicotine. 

In summary, the available studies of highest methodological quality discussed above provide strong 

evidence that menthol in cigarettes does not contribute to higher nicotine dependence. 

Tier 2 and 3 Studies of Menthol Smoking and Nicotine Dependence 

Five Tier 2 studies address this topic but have weaknesses that preclude drawing sound conclusions. 

None of these studies examined CPD, TTFC or composite measures of nicotine dependence.3 They 

are mentioned here briefly because they have been discussed at the TPSAC meetings. 

•	 Ahijevych and Wewers (1993) tested a model of nicotine dependence in a convenience 

sample of 187 African American women who largely smoked menthol cigarettes; 

however, menthol status was not included as a variable in the model. 

3 One study (Muscat et al. 2009) did include these measures, but numerical inconsistencies in the paper make it difficult 

to interpret. 

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•	 Ahijevych et al. (2002) examined various factors, including menthol cigarette 

preference, on plasma cotinine half-life in African American and Caucasian women 

during 6 days of smoking abstinence. African American smoking of menthol cigarettes 

was a significant predictor of cotinine half-life in comparison to Caucasian nonmenthol 

cigarette smoking. 

•	 Bover et al. (2008) found that menthol cigarette smoking was among many factors 

significantly associated with waking at night to smoke (a measure of nicotine 

dependence) among a group of smokers who sought treatment at a tobacco dependence 

clinic. The study suffered from a high attrition rate (approximately 40%), and the study 

was designed to assess efficacy of treatment rather than to evaluate menthol smoking 

and dependence. 

•	 Hymowitz et al. (1995) analyzed data from the COMMIT trial by race/ethnicity but did 

not attempt to link menthol smoking status with dependence outcomes. 

•	 Muscat et al. (2009) conducted a cross-sectional study of 525 Black and White 

volunteers, and reported that after adjustment for confounders menthol smoking was 

not significantly associated with several measures of dependence (high score on the 

FTND, time to first cigarette of ≤30 minutes, daily cigarette amount, or heavy smoking). 

Numerical inconsistencies in this paper make it difficult to interpret. 

Seven Tier 3 studies (Ahijevych and Parsley 1999, Collins and Moolchan 2006, Hersey et al. 

2006, Li et al. 2005, Muilenburg and Legge 2008, Okuyemi et al. 2004, Wackowski and 

Delnevo 2007) were all rated lower than fair overall and poor in their ability to draw menthol 

inferences, and are not discussed in detail here. 

Unpublished Analyses Presented to TPSAC 

In July 2010 and January 2011, a number of unpublished analyses that addressed menthol cigarette 

use and smoking cessation were presented to TPSAC. Although these analyses have not undergone 

peer review, the authors reported conclusions are mentioned here briefly: 

•	 Curtin (unpublished) analyzed data from several large nationally representative surveys and 

reported that: 

o	 Based on data from the NHIS, female and young adult menthol smokers reported 

smoking significantly fewer CPD (12.60 vs. 14.34 CPD for females; 10.47 vs. 12.51 CPD 

for young adults) compared to nonmenthol smokers. 

o	 Based on data from the NSDUH, female menthol smokers were significantly more likely 

(p=0.0002) to be represented in lower versus higher cigarette use categories (70%, 22.6% 

and 7.3% reported smoking ≤10, 11-20 and >20 CPD, respectively) compared to 

nonmenthol smokers (59.7%, 30.4% and 9.9%, respectively). Menthol smokers aged 18­

23 years were significantly more likely (p=0.01) to be represented in lower versus higher 

cigarette use categories (81.2%, 16.0% and 2.8% reported smoking ≤10, 11-20 and >20 

CPD, respectively) compared to nonmenthol smokers (75.2%, 20.7% and 4.1%, 

respectively). 

o	 No significant differences for CPD were indicated for non-Hispanic Black or adolescent 

menthol versus nonmenthol smokers participating in the NHANES, NHIS or NSDUH. 

o	 Findings from the NYTS were markedly different from those provided by the larger 

NHANES, NHIS and NSDUH; as discussed in Chapter 2, analyses of NYTS data 

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identified demographic characteristics associated with menthol cigarette preference that 

were different from those provided by other nationally representative surveys. Specific 

to dependence outcomes, menthol smokers aged 9-21 years were significantly more 

likely (p<0.0001) to be represented in higher versus lower cigarette use categories 

compared to nonmenthol smokers; similar findings were suggested for both sexes, as 

well as non-Hispanic Whites. 

o	 Based on regression models that adjusted individually for demographic variables, 

significantly fewer CPD generally persisted for menthol versus nonmenthol smokers 

when controlling for current age, sex or race/ethnicity. This was the case regardless of 

whether CPD was provided as continuous (NHANES and NHIS) or categorized 

(NSDUH) data. 

o	 Significantly lower estimates for CPD among menthol smokers from the NHANES and 

NSDUH only persisted when controlling for the combination of current age and sex. 

Significantly lower CPD for menthol smokers from the larger NHIS generally persisted 

when controlling for all combinations of demographic variables. 

•	 Hersey et al. (unpublished) evaluated data on 5,511 youth surveyed by Legacy for Health, 

of whom 216 reported past-month menthol smoking and 366 reported past-month 

nonmenthol smoking. Findings from regression models indicated that menthol versus 

nonmenthol smoking was not a significant predictor of nicotine dependence; and, there was 

no significant interaction between menthol versus nonmenthol smoking and mean CPD. 

Some evidence was provided to suggest that menthol smoking may be associated with higher 

levels of nicotine dependence among smokers smoking less than one year. 

•	 Hyland and Kasza (unpublished) evaluated data from the International Tobacco Control 

Four Country Survey and found that indicators of dependence (TTFC and CPD) were 

generally similar among menthol and nonmenthol smokers, although there were exceptions 

for some racial/ethnic/sex subgroups (Hispanic menthol smokers may be more dependent 

than Hispanic nonmenthol smokers). 

•	 Hyland and Rivard (unpublished) evaluated data from the COMMIT trial of smoking 

cessation and found that switching between menthol and nonmenthol cigarettes was 

uncommon, regardless of race. Furthermore, menthol smokers were as likely as nonmenthol 

smokers to increase the time to their first cigarette and decrease the number of cigarettes 

smoked per day. 

•	 Muscat (unpublished) examined data from a community-based study of Black and White 

smokers and reported that smoking menthol cigarettes did not affect the significant 

association between TTFC and blood cotinine levels. Similar or slightly higher cotinine 

values were found for menthol smokers compared to nonmenthol smokers for each TTFC 

category, but the results were not significant. 

•	 Nonnemaker et al. (unpublished) conducted a secondary analysis of a longitudinal cohort 

of middle/high school youth to examine the influence of early menthol and nonmenthol 

cigarette use (and switching) on the progression from experimentation to established/daily 

smoking over a 3-year interval. Results were not entirely consistent, but the authors 

suggested that an early stated preference for menthol cigarettes was associated with higher 

levels of nicotine dependence (β=1.04; 95% CI:0.26-1.82). This study has numerous 

limitations, including use of a sample population that was not representative of the overall 

youth population. 

•	 Reitzel (a) (unpublished) analyzed data from the Project CARE longitudinal cohort study 

and found that menthol cigarette use was not significantly related to tobacco dependence (as 

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assessed by the WISDM-68 multi-dimensional measure of dependence, CPD or TTFC) 

through week 26 of follow-up. Post-hoc analyses showed a single significant finding; among 

Latinos, menthol smokers scored higher than nonmenthol smokers on the WISDM-68 

Behavioral Choice/Melioration subscale, suggesting greater dependence. 

•	 Reitzel (b) (unpublished) analyzed data from the BREAK FREE clinical trial of smoking 

cessation and found that menthol cigarette smoking was unrelated to the majority of 

dependence indicators, including 12 of 13 WISDM-68 subscales, the WISDM-68 total score, 

CPD and TTFC. However, menthol cigarette use was significantly associated with the 

Taste/Sensory Processes subscale of the WISDM-68 in adjusted analyses. 

•	 Reitzel (c) (unpublished) analyzed data from the MOM clinical trial of smoking relapse 

prevention among post-partum women and found that although menthol cigarette use was 

significantly associated with some, but not all, indicators of tobacco dependence in 

unadjusted analyses, these associations were not maintained in adjusted analyses. Post-hoc 

analyses revealed that Black menthol users smoked significantly more pre-quit cigarettes per 

day than did Black nonmenthol users. 

•	 Unger et al. (unpublished) analyzed nicotine dependence (as assessed by TTFC ≤30 

minutes) in a community-based survey of African American smokers and found no 

significant differences among menthol, nonmenthol, and combined smokers. 

In addition, Thorne et al. (2010) presented findings from the 2001-2006 NHANES on menthol 

cigarette use and dependence at the 2010 American Public Health Association meeting (on behalf of 

FDA). The data indicated that menthol cigarette smokers report significantly fewer CPD and 

shorter durations of smoking compared to nonmenthol smokers. There were no significant 

differences in TTFC or nicotine dependence scores (Heaviness of Smoking Index), leading to the 

conclusion of no difference in dependence levels between menthol and nonmenthol smokers. 

MENTHOL CIGARETTES AND DEPENDENCE AMONG ADOLESCENTS 

Several studies provide some insight into menthol cigarette use and indicators of dependence among 

adolescent smokers. Two published studies found to be high quality (i.e., Tier 1) during the 

Covance literature review failed to find evidence of a difference between adolescent menthol and 

nonmenthol cigarette smokers. 

•	 DiFranza et al. (2004) found no difference in strength of addiction between menthol and 

nonmenthol adolescent smokers who had “ever inhaled on a cigarette,” as measured by the 

Hooked on Nicotine Checklist. 

•	 Moolchan et al. (2006) found no difference in FTND score between African American 

(86% of whom smoked menthols) and Caucasian smokers (adolescents aged 13 to 17 years). 

Four other studies (Collins and Moolchan 2006, Hersey et al. 2006, Muilenburg and Legge 

2008, Wackowski and Delnevo 2007) provided mixed results, but were judged by Covance to be 

poor both with respect to overall quality as well as ability to support menthol inferences related to 

dependence (i.e., Tier 3). 

•	 Collins and Moolchan (2006) analyzed interview data for 572 adolescent smokers enrolled 

in an urban Baltimore smoking cessation treatment study, comprising 46.9% African 

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Americans and having an overall 92.8% population preference for menthol cigarettes. The 

study found that similar percentages of menthol and nonmenthol smokers report smoking 

their first cigarette 6-30, 31-60 or >60 minutes after waking; a single difference was 

suggested for menthol smokers reporting a TTFC less than 5 minutes after waking. The 

data likewise indicated no differences for CPD or FTND score based on menthol status. 

•	 Hersey et al. (2006) analyzed data from the 2000-2002 NYTS and reported that menthol 

smokers had a 45% higher odds of being above the median on nicotine dependence; these 

data were inconsistent with data from the same population indicating that menthol smokers 

were significantly less likely to report smoking on ≥20 of the last 30 days or to smoke ≥6 

cigarettes per day. 

•	 Muilenburg and Legge (2008) examined data from a 2006 survey of six secondary schools 

in a large southeastern metropolitan area. The sample population was not representative of 

the overall adolescent smoking population, which was further underscored by the unique 

finding that menthol smokers, independent of race, “exhibit high risk levels” for “Days 

smoked in month,” “Cigs. smoked in month,” and “last time Smoked,” contrary to virtually 

all other studies of menthol smokers. 

•	 Wackowski and Delnevo (2007) analyzed data from the 2004 NYTS, reporting that 

menthol smoking was associated with an increased adjusted odds ratio of needing a cigarette 

within 1 hour (AOR=2.6; 95% CI:1.6-4.3) and experiencing cravings (AOR=1.2; 95% 

CI:1.1-2.2); no significant differences were reported for feeling irritable or an inability to 

quit, and no overall dependency score was reported. The study also reported considerably 

more variability in adolescents’ reporting of usual, regular or exclusive smoking of menthol 

cigarettes than is typically reported by adult smokers. Also, the authors cautioned that 

“...[t]he NYTS was not designed to test hypotheses related to menthol use and 

dependence.” 

Additional information on dependence among adolescents is presented in three unpublished 

analyses provided during the TPSAC meetings; all three were discussed above. 

•	 Curtin (unpublished) analyzed data from several large nationally representative surveys 

and found no significant differences in CPD between adolescent menthol versus 

nonmenthol smokers in the NHANES or NSDUH. In contrast, adolescent menthol 

smokers from the NYTS were suggested to be significantly more likely to be represented in 

higher versus lower cigarette use categories compared to nonmenthol smokers. This survey 

differs from the other surveys with regard to both target population and data collection 

methodology; the implications of these differences have been previously discussed (refer to 

Chapter 2). 

•	 Hersey et al. (unpublished) evaluated data on 5,511 youth surveyed by Legacy for Health. 

Findings indicated that menthol versus nonmenthol smoking was not a significant predictor 

of nicotine dependence. Some evidence was provided to suggest that menthol smoking may 

be associated with higher levels of nicotine dependence among smokers smoking less than 

one year. 

•	 Nonnemaker et al. (unpublished) analyzed a longitudinal cohort of middle/high school 

youth to examine the influence of early menthol and nonmenthol cigarette use (and 

switching) on the progression from experimentation to established/daily smoking over a 3­

year interval. Results were not entirely consistent, but the authors suggested that an early 

stated preference for menthol cigarettes was associated with higher levels of nicotine 

Chapter 5 

162
 

 

 

 

dependence. Among other limitations, this study used a sample population that was not 

representative of the overall youth population. 

An additional publication examined smoking dependence among adolescents and menthol (versus 

nonmenthol) cigarette use based on data from the NYTS. Due to the timing of publication, this 

study was not included in the Covance review; thus, it was not placed into a specific quality tier. It is 

discussed here briefly. 

•	 Hersey et al. (2010) analyzed cross-sectional data from the 2006 NYTS, and provided 

findings from past-month smokers to suggest that smoking menthol cigarettes was 

significantly associated with reduced time to “needing” a cigarette. Among established 

smokers, but not all smokers with a usual brand, smoking a menthol brand was significantly 

associated with feeling restless and irritable without smoking and with experiencing cravings 

after going without smoking for a few hours. 

Collectively, the available studies on adolescent smokers are not conclusive with respect to any 

impact of menthol versus nonmenthol smoking on adolescent dependence. A combination of 

mixed findings in some studies (several showing no menthol effect) and overall lack of quality in 

study design precludes drawing definitive conclusions that menthol smoking has an effect on 

increased measures of adolescent dependence compared to nonmenthol smoking. Further, as 

discussed in Chapter 2, approximately only one-quarter of young smokers go on to become regular 

smokers, indicating that three-quarters of youth smokers quit smoking during the experimentation 

phase, which dramatically limits the inferences that can be drawn with respect to adolescent smoking 

dependence. 

CONCLUSIONS 

This review of literature on menthol cigarette smoking and measures of nicotine dependence 

demonstrates that the most methodologically sound studies do not find that menthol smokers are 

any more dependent on nicotine than are nonmenthol smokers. The 10 Tier 1 studies examined 

several measures of nicotine dependence, including multi-factor FTND and HONC, as well as single 

measures of CPD and TTFC. 

•	 Three studies evaluated FTND, which is a more comprehensive measure of nicotine 

dependence; none of these three studies (including the very large Total Exposure Study) 

found a difference between menthol and nonmenthol smokers. 

•	 A single study evaluating dependence among adolescents using the HONC found that the 

strength of the addiction did not differ according to the favorite brand of cigarette, brand 

strength or menthol content. 

•	 Eight studies evaluated CPD; menthol cigarette smokers either smoked significantly fewer 

CPD than nonmenthol smokers (N=4 studies), or there were no differences (N=4 studies). 

•	 Five studies evaluated TTFC; three found no differences between menthol and nonmenthol 

smokers. The other two studies do not provide compelling evidence of a significant 

difference. Ahijevych and Ford (2010) focused on their finding that non-daily menthol 

smokers had a significantly shorter TTFC than nonmenthol smokers. However, the fact that 

this was not true for daily smokers, nor was there a significant difference in CPD among 

Chapter 5 

163
 

 

 

either daily menthol and nonmenthol smokers or non-daily menthol and nonmenthol 

smokers argues against greater dependence among menthol smokers. Fagan et al. (2010) 

found a significant difference between menthol and nonmenthol smokers in only one of 

eight subgroups examined, i.e., smokers of 6-10 CPD only when TTFC was defined as ≤5

minutes after waking. 

Even those studies assessed to be of lower quality (Tier 2) generally show that menthol smokers are 

either less dependent or are no different in their dependence measures than nonmenthol smokers. 

In the few studies in which differences were reported in measures of dependence between menthol 

and nonmenthol smokers, those differences were small for both adolescents and adult smokers. 

Given the number of high-quality studies and their consistent findings with respect to adult 

dependence, and the lack of any conclusive evidence with respect to adolescents, using the Surgeon 

General’s framework for assessing causality, it is reasonable to conclude that the “evidence is 

suggestive of no causal relationship” between smoking menthol cigarettes and significantly 

increased levels of nicotine dependence. 

Chapter 5 

164
 

 

 

 

 

 

 

 

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Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Alexander et al. 

2010 

United States 

Cessation 

Cross-sectional 

analysis of data from 

the 2006/07 Tobacco 

Use Supplement to 

the Current 

Population Survey. 

Analysis was based on 

30,176 current 

smokers (age 18 and 

older). 

Cessation was 

assessed by: ever 

stopped smoking for 1 

day or longer because 

you were trying to 

quit; number of quit 

attempts in past 12 

months; and longest 

length of time you 

quit smoking. 

Tobacco Preference 

Nonmenthol smoker 

Menthol smokers 

Tobacco Preference 

Nonmenthol smoker 

Menthol smokers 

Tobacco Preference 

Nonmenthol smoker 

Menthol smokers 

Odds Ratio (95% CI) for Ever

Stopped Smoking for 1 Day or 

Longer 

1.0 (reference) 

0.98 (0.83-1.15) 

Adjusted for age, race, sex, 

education and income. 

Mean No. Times Stopped 

Smoking in Past Month (%) 

3.8 (3.6-3.9) 

4.0 (3.6-4.4) 

Longest Length of Time 

Stopped Smoking (%) 

1.0 (1.7-2.3) 

2.2 (1.9-2.5) 

After controlling for 

occupational status and 

work-place smoking 

policies, smokers of 

menthol cigarettes in the 

United States appear to 

have similar selfreported life-time rates 

of attempts to stop 

smoking as nonmenthol 

smokers. 

In this exploratory study, 

menthol versus 

nonmenthol as a factor 

in quitting was not 

significant. 

Conclusions are supported by 

study data. 

Large nationally representative 

survey with many menthol 

smokers. 

Cross-sectional nature of 

analysis does not permit causal 

conclusions. 

Goal of this study was to 

examine the role of occupation 

status on the quitting behaviors 

of menthol versus nonmenthol 

smokers. 

Menthol use and quitting 

behaviors were self-reported. 

“Quitting” was not defined 

very strictly (i.e., ever stopped 

smoking for 1 day or longer). 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

170
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Berg et al. 2010 

United States 

Cessation 

Randomized clinical 

trial of smoking 

cessation among 539 

Black light smokers 

(<10 CPD). About 

81% smoked menthol 

cigarettes at baseline. 

95 subjects quit by the 

end of the trial. 

Cessation was 

assessed at 26 weeks. 

There were 3 

categories of smoking 

status. Reducers were 

those who reduced 

their smoking by 

>50% from baseline 

but did not quit. 

Nonreducers did not 

reduce their smoking 

by >50%. Quitters 

reported abstinence 

that was verified by 

salivary cotinine <20 

ng/ml. 

% Smoking Menthol at 

Baseline 

Whole group: 80.6 

% Smoking Menthol at 26

Weeks 

No reduction: 83.9 

Reduction: 80.8 

Cessation: 72.6 

p=0.07 

Conclusions do not 

directly address menthol. 

Authors mention that, 

although using menthol 

cigarettes did not 

significantly contribute 

to the multivariate 

model, more 

nonreducers used 

menthol cigarettes than 

did reducers, as indicated 

by the bivariate analyses. 

Study was not designed to 

examine the relationship 

between menthol smoking and 

cessation. 

Despite the authors’ comment, 

smoking menthol cigarettes was 

not a statistically significant 

predictor of reduction or 

cessation. 

Clinical trial. 

Cessation was assessed at 26 

weeks; defined as salivary 

cotinine <20 ng/ml. 

All subjects were Black light 

smokers, which limits 

generalizability of the findings. 

Chapter 5 - Appendix 

171
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Cubbin et al. 

2010 

United States 

Cessation 

Cross-sectional 

analysis of data from 

the 2005 National 

Health Interview 

Survey and Cancer 

Control Supplement. 

Analysis was based on 

21,196 Black, 

Hispanic, and White 

women and men aged 

25-64 years (current, 

former, and neversmokers who reported 

menthol status). 

Menthol use was 

defined as “usual 

cigarette brand was 

menthol.” 

Cessation was 

assessed by 

proportion with a quit 

attempt in the past 

year among every-day 

smokers, and time 

since quitting among 

former smokers. 

Initiation data are 

included in Table 4-3; 

dependence data are 

included in Table 5-4. 

Menthol Smokers 

Black women 

Black men 

Hispanic women 

Hispanic men 

White women 

White men 

Nonmenthol Smokers 

Black women 

Black men 

Hispanic women 

Hispanic men 

White women 

White men 

% Who Attempted to Quit in 

Past Year by Cigarette Type 

(99% CI) 

49.9 (40.0, 59.9) 

48.6 (37.1, 60.1) 

46.7 (27.8, 65.7) 

57.9 (38.0, 77.8) 

43.2 (35.8, 50.7) 

40.7 (31.2, 50.2) 

39.7 (24.3, 55.2) 

37.6 (21.6, 53.6) 

42.5 (30.7, 54.3) 

38.4 (28.3, 48.5) 

39.8 (35.7, 43.9) 

36.8 (32.6, 41.0) 

Adjusted for age, income, and 

education. 

The results do not 

support the hypothesis 

that menthol smokers 

have a harder time 

quitting (making a quit 

attempt and length of 

time since quitting) than 

nonmenthol smokers. 

There were no 

statistically significant 

differences by 

race/ethnicity, sex or 

cigarette type in quit 

attempts. 

White women who 

smoked menthol 

cigarettes reported 

longer cessation 

compared with those 

who smoked 

nonmenthol cigarettes. 

Conclusions are supported by 

study data. 

Large national populationbased survey with many 

menthol smokers. 

Cross-sectional nature of 

analysis does not permit causal 

conclusions. 

Menthol use was self-reported. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

172
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Fagan et al. Cessation Quit Attempt in Past 12 These data do not Conclusions are supported by 

2010 Months vs. None Odds Ratios (95% CI) support the hypothesis study data. 

Cross-sectional Nonmenthol <5CPD 1.0 (reference) that menthol smokers 

United States analysis of data from 

the 2003 and 2006/07 

Menthol <5CPD 1.10 (0.91-1.34) experience greater 

quitting difficulty. 

Large nationally representative 

survey with many menthol 

Tobacco Use Nonmenthol 6-10 CPD 1.0 (reference) smokers. 

Supplement to the 

Current Population 

Menthol 6-10 CPD 0.92 (0.83-1.02) The multivariate models 

did not show significant Cross-sectional nature of 

Survey. Nonmenthol 11-19 CPD 1.0 (reference) associations between analysis does not permit causal 

Analysis was based on 

Menthol 11-19 CPD 0.99 (0.85-1.16) usual cigarette brand and 

quit attempts in past 12 

conclusions. 

46,273 current daily Nonmenthol 20+CPD 1.0 (reference) months or duration of Menthol use and quitting 

smokers (age 18 and 

older). 

Cessation was 

assessed by: number 

Menthol 20+ CPD 

Abstinent >2 Weeks vs. 

<2 Weeks 

0.97 0.88-1.07) smoking abstinence >2 

weeks in the past 12 

months. 

behaviors were self-reported. 

A “quit attempt” was not 

defined very strictly (i.e., ever 

stopped smoking for 1 day or 

of quit attempts (ever Nonmenthol <5CPD 1.0 (reference) longer). 

stopped smoking for 1 

day or longer) in past 

Menthol <5CPD 1.03 (0.78-1.36) 

12 months; and length Nonmenthol 6-10 CPD 1.0 (reference) 

of smoking abstinence 

in past 12 months. 

Menthol 6-10 CPD 0.97 (0.82-1.14) 

Nonmenthol 11-19 CPD 1.0 (reference) 

Dependence data are 

included in Table 5-4. 

Menthol 11-19 CPD 1.05 (0.82-1.36) 

Nonmenthol 20+CPD 1.0 (reference) 

Menthol 20+ CPD 0.93 (0.79-1.12) 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

173
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Foulds et al. 

2006 

Cessation 

Convenience sample 

of first 1,021 patients 

at a free tobacco 

treatment clinic who 

made a quit attempt. 

41% smoked menthol 

cigarettes. 320 

reported abstinence at 

6 months. 66% of 

subjects were White. 

Abstinence (selfreported 7-day point 

prevalence) was 

assessed at 4 weeks 

and 6 months. 

Cessation was defined 

as not smoking in past 

7 days. Biochemical 

confirmation of 

smoking abstinence 

was confirmed by CO 

level <10 ppm at inperson follow-ups. 

Current Brand 

Menthol? 

Yes 

No 

Adjusted Odds Ratio (95%

CI) for Abstinence at 4 Weeks 

1.00 (reference) 

1.359 (0.996-1.856) 

p=0.053 

Adjusted for age, education, 

employment status, time-tofirst-cigarette, baseline stage of 

change, and number of face-toface contacts with clinic 

ORs were not presented for 

abstinence at 26 weeks, as 

menthol versus nonmenthol was 

not a significant predictor of 

abstinence at 26 weeks. 

Menthol smokers were 

less likely to achieve 

abstinence in univariate 

analyses and this item 

remained in the model 

predicting 4-week 

outcome. 

Menthol preference is 

one of many predictors 

of abstinence. 

Conclusions are not fully 

supported by study data. While 

“menthol cigarettes remained 

in the model” at 4 weeks, it was 

only of borderline significance 

(p=0.053). 

The authors did not directly 

address the association between 

menthol smoking and 

abstinence at 26 weeks. It is 

reasonable to conclude that 

there was no significant 

relationship, since menthol was 

not included as a variable in the 

model at 26 weeks. 

Cessation was assessed at 4 

weeks and 6 months. Defined 

as 7 days of abstinence; selfreported abstinence was 

biochemically verified at inperson follow-ups. 

This is a convenience sample of 

volunteers seeking treatment at 

a clinic; generalizability is 

limited. Results not presented 

by race. 

One-third of subjects were lost 

to follow-up at 26 weeks. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

174
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Gandhi et al. 

2009 

United States 

Cessation 

Retrospective analysis 

of 1,688 patients 

attending a specialist 

smoking cessation 

service. Overall, 

46.1% smoked 

menthol cigarettes 

(81% of African 

Americans, 66% of 

Latinos, 32% of 

Whites). 

Cessation (assessed at 

4 weeks and 6 months 

was defined as 7-day 

point prevalence of 

abstinence. 

Abstinence was selfreported and 

biochemically verified 

(exhaled CO). 

Race 

White 

Nonmenthol 

Menthol 

African American 

Nonmenthol 

Menthol 

Hispanic/Latino 

Nonmenthol 

Menthol 

Race 

White 

Nonmenthol 

Menthol 

African American 

Nonmenthol 

Menthol 

Hispanic/Latino 

Nonmenthol 

Menthol 

Adjusted Odds Ratios (95% 

CI) for Abstinence at 4 Weeks 

1.0 (reference) 

0.96 (0.72-1.20) 

1.0 (reference) 

0.32 (0.16-0.62)** 

1.0 (reference) 

0.43 (0.10-0.90)** 

Adjusted Odds Ratios (95% 

CI) for Abstinence at 6 

Months 

1.0 (reference) 

1.0 (0.80-1.40) 

1.0 (reference) 

0.48 (0.25-0.90)** 

1.0 (reference) 

0.64 (0.20-1.80) 

Adjusted for age, education, sex, 

employment status, type of 

insurance, CPD, age smoked for 

first time, awaken at night to 

smoke, TTFC, previous quit 

attempts, presence of smokingrelated disease. 

Despite smoking fewer 

cigarettes per day, 

African American and 

Latino menthol smokers 

experience reduced 

success in quitting as 

compared with 

nonmenthol smokers 

within the same 

ethnic/racial groups. 

Conclusions are supported by 

study data. 

However, note that White 

subjects made up the majority 

(64%) of the study group; 

White menthol smokers were 

no less likely to quit than White 

nonmenthol smokers. 

Cessation was assessed at 4 

weeks and 6 months; defined as 

not smoking for 7 days. 

Abstinence was self-reported 

and verified biochemically. 

Menthol use was self-reported. 

Loss to follow-up by 6 months 

was high (42%). 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

175
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Gundersen et 

al. 2009 

United States 

Cessation 

Cross-sectional 

analysis of data from 

the 2005 National 

Health Interview 

Survey. Subjects were 

7,815 Black, White, 

and Hispanic current 

and former smokers 

who had made a quit 

attempt. 26.5% 

smoked menthol 

cigarettes. 

Former smokers were 

those who had 

smoked at some point 

but were now 

smoking “not at all.” 

Current smokers now 

smoked every day or 

some days. 

Race 

White 

Nonmenthol 

Menthol 

Hispanic 

Nonmenthol 

Menthol 

Black 

Nonmenthol 

Menthol 

Non-White (Black + 

Hispanic) 

Nonmenthol 

Menthol 

Adjusted Odds Ratios for

Cessation (95% CI) 

1.0 (reference) 

1.17 (1.00-1.36)* 

1.0 (reference) 

0.61 (0.39-0.97)** 

1.0 (reference) 

0.78 (0.56-1.09) 

1.0 (reference) 

0.55 (0.43-0.71)** 

Adjusted for age, education, sex, 

cigarettes per day, census region, 

and perceived risk of cancer. 

Our findings provide 

some support for the 

hypothesis that menthol 

smoking can lead to 

poorer cessation 

outcomes, but only for 

non-White smokers. 

Non-White menthol 

smokers were less likely 

to have quit compared to 

non-White nonmenthol 

smokers, but White 

menthol smokers were 

more likely to have quit 

compared to White 

nonmenthol smokers. 

Study does not permit 

definitive conclusions. It is 

true that cessation results 

differed by race. Non-White 

menthol smokers were less 

likely to be former smokers 

whereas White menthol 

smokers were more likely to be 

former smokers. However, 

when the analysis was restricted 

to Blacks, there was no 

difference in cessation between 

menthol and nonmenthol 

smokers. This suggests that 

variables other than menthol 

may be relevant. 

Study is large and subjects are 

nationally representative. 

Cross-sectional nature of 

analysis does not permit causal 

conclusions. 

Cessation was defined as now 

smoking “not at all” 

(apparently no duration 

requirement). 

Smoking status and menthol 

use was self-reported. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

176
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Hyland et al. 

2002 

Cessation 

Prospective study. 

Subjects were 13,286 

baseline smokers (age 

25-64) in the 

COMMIT trial of 

smoking cessation. 

24% smoked 

menthols in 1988. 

Smoking was 

reassessed after 5 

years. 

Cessation was defined 

as not having smoked 

any cigarettes in the 

past 6 months. 

Dependence data are 

included in Table 5-4. 

Race 

Overall 

White, non-Hispanic 

Black, non-Hispanic 

Hispanic 

(Reference group not 

defined but appears to be 

smokers of nonmenthol 

cigarettes.) 

Relative Risks for Menthol 

Use in 1988 on Quitting in 

1993 (95% CI) 

1.0 (0.90-1.11) 

0.94 (0.83-1.05) 

1.04 (0.73-1.47) 

1.22 (0.80-1.87) 

Adjusted for sex, age, 

race/ethnicity, education, 

cigarettes smoked per day, time 

to first cigarette in the morning, 

history of past serious quit 

attempts, age started smoking, 

desire to stop smoking, 

frequency of alcohol 

consumption, use of noncigarette tobacco product, 

pricing tier of cigarette smoked, 

and the presence of another 

smoker in the household. 

Use of mentholated 

cigarettes was not 

associated with quitting. 

None of the 

race/ethnicity-specific 

analyses revealed any 

significant associations. 

Menthol users who had 

greater levels of 

dependence had lower 

quit rates than menthol 

users who had lower 

levels of dependence. 

Conclusions are supported by 

study data. 

Large prospective study. 

Cessation was assessed at 5 

years; defined as 6 months of 

abstinence. 

Subjects were a random sample 

from a representative sample of 

households in 10 U.S. 

communities. 

Menthol use and smoking 

status were assessed by selfreport. 

Menthol status only collected at 

baseline in 1988. 

High rate of attrition (34%) 

over time. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

177
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Murray et al. Cessation Cessation at 5 Years: Menthol We found no difference Conclusions are supported by 

2007 

Clinical trial of Men 

vs. Plain Smoker at Baseline 

(%) 

in success at smoking 

cessation with or 

study data. 

United States smoking cessation. Sustained quitter 16.6 vs. 17.2 without menthol. Large clinical trial. 

(Lung Health There were 5,887 Intermittent smoker 26.0 vs. 26.9 

Study) subjects (age 35-60), 

all current or former 

smokers with mild to 

moderate airway 

obstruction. About 

20% (1,216) smoked 

menthol cigarettes at 

baseline. 

Cessation was 

assessed at 5 years. 

Sustained quitters 

were biochemically 

confirmed at 5 annual 

visits and did not 

recall at any annual 

visit any months 

where smoked >1 

CPD. Intermittent 

smokers were 

biochemically 

confirmed as quitters 

at some but not all 

annual visits. 

Continuing smokers 

reported smoking at 

all annual visits. 

Continuing smoker 

Chi square, p-value 

Women 

Sustained quitter 

Intermittent smoker 

Continuing smoker 

Chi square, p-value 

57.3 vs. 55.9 

0.80 

13.8 vs. 15.4 

30.4 vs. 28.7 

55.9 vs. 55.9 

0.57 

Percentages are unadjusted. 

We conclude that our 

data contain no evidence 

that mentholation of 

cigarettes increases the 

hazards of smoking. 

Cessation was assessed at 5 

years of follow-up; sustained 

quitters were biochemically 

confirmed as quitters at the 5 

annual visits and did not recall 

at any annual visit any month 

with mean smoking >1 

cigarette per day. 

Results were not presented by 

race. 

Subjects had some degree of 

impaired lung function at 

baseline. 

Menthol use was self-reported. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

178
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Muscat et al. 

2002 

Cessation 

Cross-sectional 

analysis of data from 

case-control study on 

smoking and lung 

cancer. There were 

19,545 subjects, 3,005 

of whom smoked 

menthol cigarettes. 

All were current or 

former smokers. 

Ever-smokers smoked 

>1 CPD in one year. 

Former smoker were 

ever-smokers who did 

not smoke at least 1 

CPD in the past year. 

Dependence data are 

included in Table 5-4. 

Whites 

Current versus former 

nonmenthol smokers 

Current versus former 

menthol smokers 

Blacks 

Current versus former 

nonmenthol smokers 

Current versus former 

menthol smokers 

Adjusted Prevalence Odds

Ratios of Continued Smoking 

vs. Quitting (95% CI) 

1.0 (reference) 

1.1 (1.0-1.3) 

1.0 (reference) 

1.1 (0.8-1.4) 

Adjusted for age, sex, education, 

case-control status, years of 

smoking, and cigarettes per day. 

The risk of quitting was 

not associated with 

cigarette menthol flavor. 

Cigarette mentholation 

was not associated with 

continued smoking in 

Blacks and in Whites. 

Blacks were less likely 

than Whites to have quit 

smoking regardless of 

the brand of cigarettes. 

The reason for the lower 

quit rate in Blacks is 

poorly understood but 

could be due to lack of 

perceived benefits, 

medical advice, and 

social support. 

Conclusions are supported by 

study data. 

Cross-sectional analysis; 

consequently, does not permit 

causal conclusions. 

Cessation was defined as not 

smoking at least 1 CPD in the 

year prior to study interview. 

Menthol use was self-reported. 

Most subjects who smoked 

menthol during their lifetime 

also smoked nonmenthol 

cigarettes. Subjects were 

classified as menthol smokers if 

LAST brand smoked was 

menthol. 

Population was older and male; 

some were lung cancer patients. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

179
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Okuyemi et al. Cessation Tobacco Preference Abstinence at 6 Weeks African American Conclusions are misleading. 

2003 Nonmenthol smokers 41.5% menthol smokers had While there was a significant 

Randomized clinical Menthol smokers 28.3% lower smoking cessation difference between menthol 

United States trial of sustainedrelease bupropion for p=0.006* rates after 6 weeks of 

treatment with 

and nonmenthol smokers at 6 

weeks, that difference had 

smoking cessation. Tobacco Preference Abstinence at 6 Months bupropion-SR, thereby disappeared by 6 months. 

Subjects were 600 Nonmenthol smokers 27.0% putting menthol smokers 

African American Menthol smokers 21.4% at greater risk from the The difference was only seen 

smokers, 471 of 

whom smoked 

menthol cigarettes. 

Cessation (7-day point 

prevalence) was 

assessed at 6 weeks 

and 6 months. 

Self-reported 

abstinence was 

confirmed by expired 

CO assessment. 

Dependence data are 

included in Table 5A-1. 

p=0.21 health effects of 

smoking. 

The lower cessation rates 

among menthol cigarette 

smokers were found 

only in those younger 

than 50 years. 

among subjects treated with 

bupropion at 6 weeks, not 

among subjects who received 

placebo at 6 weeks. 

Clinical trial. 

Cessation was assessed at 6 

weeks and 6 months. Defined 

as 7 days of abstinence; selfreported abstinence was 

biochemically verified. 

All subjects were African 

American, thus limiting ability 

to generalize. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

180
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Okuyemi et al. 

2007 

United States 

Cessation 

Randomized clinical 

trial of nicotine gum 

and counseling for 

smoking cessation. 

Subjects were 755 

African American 

light smokers (<10 

CPD). 81.7% smoked 

menthol cigarettes. 

Cessation (7-day point 

prevalence) was 

assessed at 8 weeks 

and 26 weeks. 

Self-reported 

abstinence was 

confirmed by urinary 

cotinine. 

Tobacco Preference 

Menthol smokers 

Nonmenthol smokers 

By Age 

<Age 50 

Menthol smokers 

Nonmenthol smokers 

>Age 50

Menthol smokers 

Nonmenthol smokers 

7-Day Verified Abstinence at 

26 Weeks 

11.2% 

18.8% 

p=0.015* 

Percentages are unadjusted. 

Adjusted Odds Ratio (95%

CI) 

1.0 (reference) 

2.077 (0.944-4.569) 

1.0 (reference) 

1.676 (0.760-3.698) 

Adjusted for drug and 

counseling treatment 

assignments, as well as 

confidence to quit smoking 

(note that the ORs are not 

adjusted for duration of smoking 

in years, even though 

nonmenthol smokers had 

smoked significantly longer than 

menthol smokers at baseline). 

Among African 

American light smokers, 

use of menthol cigarettes 

is associated with lower 

cessation rates. 

Conclusions are not supported 

by study data. 

Percentages presented here are 

not adjusted, even though there 

were significant differences 

between menthol and 

nonmenthol smokers (age, 

duration of smoking in years, 

confidence in quitting). 

Analyses based on actual 

randomization showed no 

differences between menthol 

and nonmenthol smokers. 

Logistic regression by age 

group (<50 vs. >50) that 

considered some potential 

confounders did not find that 

menthol/nonmenthol status to 

be significantly associated with 

abstinence. 

Clinical trial. Cessation was 

assessed at 6 weeks; defined as 

7-day point prevalence. 

Self-reported abstinence was 

biochemically verified. 

All subjects were African 

American light smokers, thus 

limiting ability to generalize. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

181
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Pletcher et al. 

2006 

United States 

(CARDIA 

study) 

Cessation 

Cohort study. There 

were 5,115 subjects; 

972 smoked menthol 

and 563 smoked 

nonmenthol at 

baseline. 15 years of 

follow-up. 

Cessation was 

measured at 2, 5, 7, 

10, and 15 years of 

follow-up. 

Cessation assessed by 

5 measures: not 

currently smoking; 

recent quit attempts; 

cessation if recent quit 

attempt; sustained 

cessation (no current 

smoking in past 2 

CARDIA exams); and 

documented relapse 

(those who reported 

no smoking at one 

exam and then current 

smoking at their final 

exam). 

Measure of Cessation 

Not currently smoking 

Recent quit attempt 

Cessation if recent quit 

attempt 

Sustained cessation 

Documented relapse 

Adjusted Odds Ratios (95% 

CI) for Menthol vs. 

Nonmenthol 

0.90 (0.68-1.19) 

0.77 (0.57-1.06) 

0.98 (0.69-1.39) 

0.70 (0.48-1.03) 

1.89 (1.17-3.05)* 

Adjusted for age, sex, ethnicity, 

social factors (education, marital 

status, employment, health 

insurance status) and cigarettes 

per day at baseline. 

Menthol cigarettes may 

be harder to quit 

smoking. 

Conclusions are not fully 

supported by study data. 

There were no significant 

associations between menthol 

smoking and 4 of 5 measures 

of cessation (including the most 

stringently defined outcome of 

sustained cessation. The only 

measure that was significantly 

associated was “documented 

relapse.” 

Large prospective study with 

long-term follow-up. 

Cessation was assessed at 2-15 

years; sustained cessation was 

defined as no smoking in the 

past 2 CARDIA exams. 

Cessation was self-reported, 

but was assessed at multiple 

visits. 

The limited number of 

European American menthol 

smokers (189) and African 

American nonmenthol smokers 

(95) made ethnicity-specific 

analyses somewhat imprecise. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

182
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Stahre et al. 

2010 

United States 

Cessation 

Cross-sectional 

analysis of data from 

the 2005 National 

Health Interview 

Survey Cancer 

Control Supplement. 

Analysis was based on 

12,004 current or 

former smokers age 

18 or older for whom 

menthol cigarette 

status was known. 

Menthol use was 

defined as “usual 

cigarette brand was 

menthol.” 

Cessation was 

assessed by the 

population quit ratio 

and the utilization of 

evidence-based 

smoking cessation 

aids. 

Predictors of 

Population Quit Ratio 

Interaction of 

Menthol/Race 

Nonmenthol x White 

Menthol x African 

American 

Menthol x American 

Indian/Alaskan native 

Menthol x Asian 

Predictors of Utilization 

of Any Quit Aid 

Current Smokers 

Nonmenthol smoker 

Menthol smoker 

Former Smokers 

Nonmenthol smoker 

Menthol smoker 

Adjusted Odds Ratio (95%

CI) 

1.00 (reference) 

0.72 (0.53-0.97)* 

2.00 (0.56-7.23) 

0.74 (0.37-1.48) 

Adjusted for age group, sex, 

region, marital status, and 

average number of cigarettes per 

day. 

1.00 (reference) 

1.05 (0.80-1.36) 

1.00 (reference) 

1.29 (0.74-2.26) 

Menthol cigarette 

smoking is associated 

negatively with 

successful smoking 

cessation among African 

Americans. 

African American 

menthol smokers were 

significantly less likely 

than White nonmenthol 

smokers to have quit 

smoking. 

Menthol smoking status 

was not associated with 

differences in utilization 

of quit aids. 

Conclusions are supported by 

study data. 

Large nationally representative 

survey with many menthol 

smokers. 

Cross-sectional nature of 

analysis does not permit causal 

conclusions. 

Menthol use and use of quit 

aids were self-reported. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

183
 

 

Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-3. Higher Quality Studies on Menthol Smoking and Cessation Behaviors (N=15) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Trinidad et al. Cessation Adjusted ORs (95% CI) of Across race/ethnic Conclusions are supported by 

2010 

Cross-sectional 

Former Smokers 

Non-Hispanic Whites 

Cessation >6 Mos groups, those who used 

to regularly smoke 

study data. 

United States analysis of data from Nonmenthol 1.0 (reference) mentholated cigarettes Large nationally representative 

the 2003 and 2006/07 

Tobacco Use 

Supplement to the 

Menthol 

African American 

0.28 (0.25-0.33)** were less likely to have 

experienced long-term 

quitting success. 

survey with many menthol 

smokers. 

Current Population Nonmenthol 1.0 (reference) Cross-sectional nature of 

Survey. 

Analysis was based on 

Menthol 

Hispanics

0.23 (0.17-0.31)** African Americans and 

Hispanics/Latinos (but 

not other races) who 

analysis does not permit causal 

conclusions. 

current and former Nonmenthol 1.0 (reference) smoked menthols were Menthol use and quitting 

smokers (age 20-65). 

Successful cessation 

was assessed at being 

Menthol 

Asian American/

Pacific Islander 

0.48 (0.34-0.69)** significantly more likely 

to be seriously 

considering quitting in 

the next 6 months and 

behaviors were self-reported. 

Quitting was defined more 

rigorously in this analysis (quit 

quit for >6 months. Nonmenthol 1.0 (reference) were significantly more for >6 months) than in other 

Pre-quitting behaviors 

(intention of quitting 

in the next 6 months 

and positive 

Menthol 

Native American/ 

Alaska Native 

0.22 (0.11-0.45)** likely to have a positive 

estimation of quitting 

successfully in the next 6 

months compared to 

analyses of this survey. 

The large number of statistical 

comparisons increases the 

estimation of quitting Nonmenthol 1.0 (reference)** those who smoked likelihood that some findings 

success in the next 6 

months) were also 

examined. 

Menthol 0.49 (0.14-1.71) nonmenthols. may be due to chance. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

184
 

 

Chapter 5. - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Ahijevych and Dependence Association of Menthol Binary Logit Model Young adult non-daily Conclusions are not fully 

Ford 2010 

Cross-sectional 

Brand Preference with 

TTFC (<30 min) 

Coefficient (SE) smokers who preferred 

menthol cigarettes were 

supported by study data. If 

non-daily smokers were truly 

United States analysis of data from 

the 2006/07 Tobacco 

Use Supplement to 

the Current 

Population Survey. 

Analysis was based on 

2,241 daily and 688 

non-daily young adult 

smokers (age 18-24). 

Dependence was 

assessed by: cigarettes 

per day and time to 

first cigarette after 

waking (≤30 min after 

waking vs. >30 min).. 

Among daily smokers 

Among non-daily smokers 

Association of Menthol 

Brand Preference with 

Average CPD

Among daily smokers 

Among non-daily smokers 

0.151 (0.088) 

0.709 (0.317)* (p<0.05) 

Poisson Model 

Coefficient (SE) 

0.022 (0.031) 

-0.018 (0.110) 

significantly more 

dependent than those who 

preferred nonmenthol 

cigarettes, as shown by the 

shorter TTFC. 

Among daily smokers, 

there was no association 

between menthol brand 

preference and smoking 

within 30 minutes of 

waking. However, among 

non-daily smokers, 

menthol users were more 

likely to smoke with 30 

minutes of waking 

compared to those who 

smoked nonmenthol 

cigarettes. 

Menthol brand preference 

was not significantly 

associated with cigarettes 

per day. 

more nicotine dependent, 

this should have been 

reflected in a higher CPD. 

Large nationally 

representative survey with 

many menthol smokers. 

Cross-sectional nature of 

analysis does not permit 

causal conclusions. 

Menthol use and dependence 

behaviors were self-reported. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

185
Chapter 5 - Appendix 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Cubbin et al. 

2010 

United States 

Dependence 

Cross-sectional 

analysis of data from 

the 2005 National 

Health Interview 

Survey and Cancer 

Control Supplement. 

Analysis was based on 

3,902 Black, Hispanic, 

and White women and 

men aged 25-64 years 

who were current 

everyday smokers. 

Menthol use was 

defined as “usual 

cigarette brand was 

menthol.” 

Dependence was 

assessed by predicted 

mean number of 

cigarettes smoked per 

day. 

Initiation data are 

included in Table 4-3; 

cessation data are 

included in Table 5-3. 

Menthol Smokers 

Black women 

Black men 

Hispanic women 

Hispanic men 

White women 

White men 

Nonmenthol Smokers 

Black women 

Black men 

Hispanic women 

Hispanic men 

White women 

White men 

Predicted Mean Number 

of Cigarettes Smoked 

per Day by Cigarette 

Type (99% CI) 

11.5 (10.0, 13.0) 

13.9 (12.1, 15.8) 

8.8 (6.7, 11.0) 

12.9 (9.6, 16.2) 

16.2 (14.9, 17.5) 

18.9 (17.3, 20.6) 

11.7 (9.4, 13.9) 

13.0 (10.3, 15.7) 

10.0 (8.5, 11.4) 

12.5 (10.6, 14.5) 

16.9 (16.2, 17.6) 

20.7 (19.8, 21.6) 

Adjusted for age, income 

and education. 

The results do not support 

the hypothesis that 

menthol smokers smoke 

more than nonmenthol 

smokers. 

There were no significant 

differences for any group 

in the number of cigarettes 

smoked per day by 

cigarette type (menthol 

versus nonmenthol). 

Conclusions are supported by 

study data. 

Large national populationbased survey with many 

menthol smokers. 

Cross-sectional nature of 

analysis does not permit 

causal conclusions. 

Menthol use was selfreported. 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

186
Chapter 5 - Appendix 

* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

DiFranza et al. 

2004 

United States 

Dependence 

Retrospective/prospe 

ctive longitudinal 

analysis of a cohort of 

7th graders followed 

for 30 months (part of 

the Development and 

Assessment of 

Nicotine Dependence 

in Youth study). 

Detailed information 

was collected (3 times 

annually for 3 years), 

including first puff, 

first inhalation, first 

monthly and daily use, 

and first occurrence of 

10 indicators of lost 

autonomy over use of 

nicotine (using the 

Hooked on Nicotine 

Checklist). 

Subjects were 

considered to be 

tobacco users if they 

had ever used any 

form of tobacco. This 

analysis focused on 

237 subjects who had 

inhaled a cigarette. 

Strength of Addiction 

Favorite brand is 

nonmenthol 

Favorite brand is menthol 

Of the 237 subjects who 

reported they had inhaled a 

cigarette, only 51% could 

recall whether it was 

mentholated. Menthol 

cigarettes accounted for 42% 

of the first inhaled cigarettes. 

59 subjects had smoked 

enough to establish a favorite 

brand; for 42%, it was 

Newport. 

Mean Score on Hooked 

on Nicotine Checklist 

6.0 (s.d.=3.3) 

6.0 (s.d.=3.4) 

t=0.22 

The strength of the 

addiction, as measured by 

the Hooked on Nicotine 

Checklist, did not differ 

according to the favorite 

brand, brand strength or 

menthol content. 

It is not surprising that 

many youths could not 

recall any details regarding 

the brand, strength, or 

mentholation of their first 

cigarette, since the first 

cigarette is most commonly 

provided by others and this 

information is rarely 

written on the cigarette. 

Conclusions are supported by 

study data. 

Dependence was assessed by 

the 10-item Hooked on 

Nicotine Checklist, a reliable 

and valid measure of loss of 

autonomy over nicotine that 

has been used for screening 

adolescents for nicotine 

dependence. 

Strengths include: 

prospective nature of study; 

short recall time for subjects; 

use of unselected population; 

inclusion of a measure of 

dependence. 

Limitations include: small 

sample size; subjective nature 

of symptoms; small number 

of African Americans (only 

4% of subjects. 

187
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Fagan et al. 

2010 

United States 

Dependence 

Cross-sectional 

analysis of data from 

the 2003 and 2006/07 

Tobacco Use 

Supplement to the 

Current Population 

Survey. 

Analysis was based on 

46,273 current daily 

smokers (age 18 and 

older). 

Dependence was 

assessed by: cigarettes 

per day and time to 

first cigarette after 

waking. Responses 

were grouped into 

TTFC ≤30 min after 

waking vs. >30 min; 

TTFC ≤5 min after 

waking vs. >5 min. 

Cessation data are 

included in Table 5-3. 

CPD 

Nonmenthol 

Menthol 

No usual type 

TTFC (≥30 min vs. <30 

min)

Nonmenthol ≤5CPD 

Menthol <5CPD 

Nonmenthol 6-10 CPD 

Menthol 6-10 CPD 

Nonmenthol 11-19 CPD 

Menthol 11-19 CPD 

Nonmenthol 20+CPD 

Menthol 20+ CPD 

TTFC (≥5 min vs. <5 min)

Nonmenthol ≤5CPD 

Menthol <5CPD 

Nonmenthol 6-10 CPD 

Menthol 6-10 CPD 

Nonmenthol 11-19 CPD 

Menthol 11-19 CPD 

Geometric Mean (95% 

CI) 

15.01 (14.88-15.14) 

13.05 (12.86-13.23) 

12.53 (11.81-13.31) 

p<0.001 for nonmenthol 

versus menthol and 

nonmenthol versus no 

usual type 

Adjusted Odds Ratio 

(95% CI)

1.0 (reference) 

1.20 (0.96-1.50) 

1.0 (reference) 

1.09 (0.97-1.22) 

1.0 (reference) 

0.98 (0.84-1.14) 

1.0 (reference) 

1.05 (0.95-1.16) 

1.0 (reference) 

0.94 (0.60-1.47) 

1.0 (reference) 

1.22 (1.05-1.43)* 

1.0 (reference) 

1.18 (0.97-1.45) 

Findings from this national 

survey of daily smokers 

demonstrate that menthol 

smokers in the United 

States who report 

consuming 6-10 cigarettes 

per day show greater signs 

of nicotine dependence 

than comparable 

nonmenthol smokers. 

The ORs for TTFC after 

waking did not increase as 

smoking intensity increased 

for menthol smokers; the 

relationship was non-linear. 

Conclusions are supported by 

study data. 

However, the authors 

focused on the single 

statistically significant finding 

among a number of 

nonsignificant findings. It is 

inappropriate to focus on this 

single finding (shorter TTFC 

among menthol smokers of 

6-10 cigarettes when TTFC is 

defined as <5 minutes, but 

not <30 minutes) and ignore 

the overall pattern of results: 

that TTFC is generally similar 

among menthol and 

nonmenthol smokers. 

Large nationally 

representative survey with 

many menthol smokers. 

Cross-sectional nature of 

analysis does not permit 

causal conclusions. 

Menthol use and dependence 

behaviors were self-reported. 

Chapter 5 - Appendix 

188
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Fagan et al. 

2010 

(continued) 

United States 

Nonmenthol 20+CPD 

Menthol 20+ CPD 

1.0 (reference) 

1.03 (0.95-1.13) 

Adjusted for 

sociodemographic and 

smoking behavior 

characteristics. 

Chapter 5 - Appendix 

189
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Hyland et al. 

2002 

United States 

Dependence 

Prospective study. 

Subjects were 13,286 

baseline smokers (age 

25-64) in the 

COMMIT trial of 

smoking cessation. 

24% smoked 

menthols in 1988. 

Smoking was 

reassessed after 5 

years. 

There were 2 

measures of nicotine 

dependence: time to 

first cigarette (TTFC) 

in the morning in 

1988, and amount 

smoked among 

continuing smokers in 

1993 (weighted 

average of number of 

cigarettes smoked per 

weekday and weekend 

day). 

Cessation data are 

included in Table 5-3. 

Race 

Overall 

White, non-Hispanic 

Black, non-Hispanic 

Hispanic 

Race 

Overall 

White, non-Hispanic 

Black, non-Hispanic 

Hispanic 

(Reference group not defined 

but appears to be smokers of 

nonmenthol cigarettes.) 

Odds Ratios for Menthol 

Use in 1988 on TTFC in 

1988 (95% CI) 

0.90 (0.81-0.99)* 

0.91 (0.81-1.02) 

0.89 (0.69-1.28) 

0.86 (0.50-1.45) 

Estimated Change in 

CPD in 1993 Associated 

with Menthol use in 1988 

0.11 (-0.38-0.60) 

0.00 (-0.56-0.56) 

0.47(-1.4-2.3) 

1.16 (-1.3-3.6) 

Adjusted for sex, age, 

race/ethnicity, education, 

cigarettes smoked per day, 

time to first cigarette in the 

morning, history of past 

serious quit attempts, age 

started smoking, desire to 

stop smoking, frequency of 

alcohol consumption, use 

of non-cigarette tobacco 

product, pricing tier of 

cigarette smoked, and the 

presence of another 

smoker in the household. 

Mentholated cigarette 

smokers do not exhibit 

greater signs of nicotine 

dependence as measured 

by the likelihood of future 

cessation, TTFC in the 

morning, or number of 

cigarettes smoked per day. 

Overall, menthol smokers 

were slightly less likely to 

report smoking within 10 

minutes after waking. 

Race/ethnicity-specific 

analyses show similar effect 

sizes. 

No associations were 

observed between menthol 

use in 1988 and amount 

smoked among continuing 

smokers in 1993. 

Conclusions are supported 

by study data. 

Large prospective study. 

In addition to cessation at 5 

years, there were two 

measures of dependence 

(TTFC in 1988 and estimated 

change in CPD among 

continuing smokers in 1993). 

Subjects were a random 

sample from a representative 

sample of households in 10 

U.S. communities. 

Menthol use and smoking 

status were assessed by selfreport. 

Menthol status only collected 

at baseline in 1988. 

High rate of attrition (34%) 

over time. 

Chapter 5 - Appendix 

190
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Lawrence et al. 

2010 

United States 

Dependence 

Cross-sectional 

analysis of data from 

the 2003 and 2006/07 

Tobacco Use 

Supplement to the 

Current Population 

Survey. 

Analysis was based on 

69,193 current 

smokers (age 18 and 

older). 16,294 

(25.8%) smoked 

menthol cigarettes and 

46,899 (74.2%) 

smoked non-menthol 

cigarettes. 

Analyses were 

restricted to selfrespondents who 

comprised 64.6% of 

the 2003 sample and 

75.1% of the 2006/07 

sample. 

Dependence was 

assessed by cigarettes 

per day and TTFC 

(<30 minutes vs. >30 

minutes). 

Initiation data are 

included in Table 4-3. 

Cigarettes Per Day 

All Current Smokers 

≤5 

6-10 

11-19 

20+ 

Current Male Smokers 

≤5 

6-10 

11-19 

20+ 

Current Female Smokers 

≤5 

6-10 

11-19 

20+ 

Cigarettes Within 1st 30 

min of Waking 

All Current Smokers 

No 

Yes 

Current Male Smokers 

No 

Yes 

Current Female Smokers 

No 

Yes 

Adjusted Odds Ratio of

Menthol Use (95% CI) 

1.0 (reference) 

1.03 (0.91-1.16) 

0.96 (0.84-1.11) 

0.84 (0.74-0.96)** 

1.0 (reference) 

1.09 (0.90-1.31) 

1.00 (0.81-1.25) 

0.85 (0.69-1.03) 

1.0 (reference) 

0.98 (0.84-1.15) 

0.93 (0.77-1.12) 

0.84 (0.71-1.00) 

1.0 (reference) 

1.05 (0.96-1.14) 

1.0 (reference) 

1.05 (0.92-1.19) 

1.0 (reference) 

1.04 (0.95-1.15) 

Adjusted for 

sociodemographic and 

smoking behavior variables. 

Prevalence of menthol use 

is significantly higher 

among individuals who 

smoke on some days than 

among individuals who 

smoke every day. 

Time to first cigarette was 

not found to be a 

significant predictor of 

menthol cigarette smoking. 

Large national populationbased survey with many 

menthol smokers. 

Cross-sectional nature of 

analysis does not permit 

causal conclusions. 

Menthol use was selfreported. 

Where sufficient numbers 

permitted race-specific 

analyses, there were no 

differences between menthol 

and nonmenthol users in 

cigarettes per day (Whites, 

Blacks) or TTFC (Whites, 

Hispanics). 

Chapter 5 - Appendix 

191
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Mendiondo et 

al. 2010 

United States 

Dependence 

Cross-sectional 

analysis of data from 

the 2005 National 

Health Interview 

Survey and Cancer 

Control Supplement. 

Analysis was based on 

12,004 women and 

men aged 25-64 years 

who were current 

everyday or former 

smokers. 

Menthol use was 

defined as “usual type 

of cigarette smoked.” 

Dependence was 

assessed by predicted 

mean number of 

cigarettes smoked per 

day. 

Current Smokers 

Nonmenthol 

Menthol 

Former Smokers 

Nonmenthol 

Menthol 

Adjusted Odds Ratios

(95% CI) for Number 

Cigarettes Per Day 

1.0 (reference) 

0.99 (0.98-1.00)** 

1.0 (reference) 

1.00 (1.00-1.00) 

Adjusted for age, race and 

sex. 

Menthol smokers reported 

smoking fewer cigarettes 

per day than their 

nonmenthol counterparts. 

Further studies may need 

to tease out the healthrelated significance of 

smoking fewer menthol 

cigarettes per day but 

having similar health 

outcomes to those who 

smoke more nonmenthol 

cigarettes per day. 

Conclusions are supported 

by study data. 

Large national populationbased survey with many 

menthol smokers. 

Cross-sectional nature of 

analysis does not permit 

causal conclusions. 

Menthol use was selfreported. 

Chapter 5 - Appendix 

192
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Moolchan et al. 

2006 

United States 

Dependence 

Clinical evaluation of 

91 adolescent smokers 

(age 13-17) who were 

recruited for a 

smoking cessation 

study. They had to 

smoke >10 CPD, 

score >5 on the 

FTND, and be 

motivated to quit. 

86% (n=79) of them 

smoked menthols. 

To investigate the 

potential mechanism 

of lower smoking 

rates among African 

Americans (compared 

to Caucasians), two 

nicotine metabolite 

ratios were measured 

as markers of the 

metabolic disposition 

of nicotine (3HC to 

COT, and COT to 

CPD). 

Entire Group

CPD (Mean) 

Caucasians 

African Americans 

FTND Score (Mean) 

Caucasians 

African Americans 

3HC/COT Ratio (Mean) 

Caucasians 

African Americans 

COT/CPD Ratio (Mean) 

Caucasians 

African Americans 

Menthol Smokers 

Cigarettes/Day (Mean) 

Caucasians 

African Americans 

3HC/COT Ratio (Mean) 

Caucasians 

African Americans 

COT/CPD Ratio (Mean) 

Caucasians 

African Americans 

19.6 

15.1 

p=0.013* 

7.1 

6.7 

NS 

0.35 

0.26 

p=0.026* 

8.5 

12.1 

p=0.033* 

20.3 

15.1 

p=0.007* 

0.35 

0.27 

p=0.041* 

8.2 

12.1 

p=0.028* 

Among the entire group, 

African American 

adolescents smoked 

significantly fewer 

cigarettes per day and had 

significantly lower nicotine 

metabolite ratios than 

Caucasian adolescents. 

Results were essentially 

unchanged when looking at 

the subgroup who smoked 

menthols, suggesting that 

the observed differences 

are due to factors other 

than menthol smoking. 

Conclusions are supported 

by study data. 

Clinical evaluation of subjects 

in a smoking cessation study. 

Note that this study focused 

on racial differences in 

nicotine metabolism. There 

are limited data related to 

menthol/nonmenthol 

smoking. 

All subjects were adolescents 

who sought cessation 

treatment, thus limiting the 

generalizability of the results. 

Dependence was assessed by 

the FTND. FTND scores 

were not provided for the 

subgroup of menthol 

smokers, although most of 

the subjects (86%) were 

menthol smokers. 

Chapter 5 - Appendix 

193
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

MuhammadKah et al. 2010 

United States 

Dependence 

Stratified, crosssectional, 

observational, multicenter ambulatory 

study (the Total 

Exposure Study). 

Subjects were adult 

men and women in 

generally good health 

who had smoked at 

least one cigarette per 

day for at least the 

past 12 months. 

This analysis focused 

on 1,044 menthol and 

2.297 nonmenthol 

smokers. 

Dependence was 

assessed by the 

Fagerström Test of 

Nicotine Dependence 

(FTND), as well as its 

6 individual elements. 

Overall FTND Score 

Nonmenthol smokers 

Menthol smokers 

TTFC (>30 min vs. <30 

min) 

Nonmenthol smokers 

Menthol smokers 

Adjusted Odds Ratios

(95% CI) 

1.0 (reference) 

1.05 (0.91-1.22) 

Menthol smokers did not 

have higher FTND scores 

than nonmenthol smokers. 

1.0 (reference) 

0.88 (0.72-1.05) 

Menthol smokers did not 

have increased odds of 

smoking within the 1st 30 

minutes after waking 

compared to nonmenthol 

smokers. 

Odds ratios adjusted for 

race, sex, age, income, 

education, and tar yield 

category. 

Our results add to the 

existing evidence that 

menthol does not increase 

nicotine dependence. 

Adult menthol smokers 

had no increased odds of 

having higher FTND 

scores as compared to 

nonmenthol smokers. 

When adjusted by race, 

sex, age, tar yield category, 

income and education, 

menthol status had no 

statistically significant 

effect on any single item of 

FTND or on the overall 

scores. 

Conclusions are supported 

by study data. 

Large cross-sectional analysis. 

Cross-sectional nature of 

study does not permit causal 

conclusions. 

Dependence was assessed by 

the FTND, as well as its 

individual elements. 

Menthol use was selfreported. 

Chapter 5 - Appendix 

194
* denotes statistically significant increase in risk 

** denotes statistically significant decrease in risk 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5-4. Higher Quality Studies on Menthol Smoking and Indicators of Dependence (N=10) (Continued) 

CITATION OUTCOME 

STUDY TYPE EXPOSURE RESULTS AUTHORS’ CONCLUSIONS 

STRENGTHS AND 

WEAKNESSES 

Muscat et al. 

2002 

United States 

Dependence 

Cross-sectional 

analysis of data from 

case-control study on 

smoking and lung 

cancer. There were 

19,545 subjects, 3,005 

of whom smoked 

menthol cigarettes. 

All were current or 

former smokers. 

Dependence was 

assessed as the 

prevalence of heavy 

smoking (>21 CPD). 

Cessation data are 

included in Table 5-3. 

Whites 

Current Smokers 

Nonmenthol 

Menthol 

Former Smokers 

Nonmenthol 

Menthol 

Blacks 

Current Smokers 

Nonmenthol 

Menthol 

Former Smokers 

Nonmenthol 

Menthol 

Adjusted Prevalence 

Odds Ratios of Heavy 

Smoking (>21 CPD) 

(95% CI) 

1.0 (reference) 

0.9 (0.8-1.0) 

1.0 (reference) 

0.9 (0.8-1.0) 

1.0 (reference) 

0.7 (0.5-0.9)** 

1.0 (reference) 

0.6 (0.4-0.9)** 

Adjusted for age, 

education, case-control 

status, sex, and years of 

smoking. 

Menthol was inversely 

associated with smoking 

more than one pack per 

day. 

Both Black and White 

smokers of mentholated 

cigarettes smoked fewer 

cigarettes per day than 

smokers of other 

cigarettes. 

The findings suggest that 

menthol does not increase 

the addictive properties of 

tobacco nicotine. 

Conclusions are supported 

by study data. 

Cross-sectional analysis; 

consequently, does not 

permit causal conclusions. 

Nicotine dependence was 

assessed as the prevalence of 

heavy smoking (>21 CPD). 

Menthol use was selfreported. 

Most subjects who smoked 

menthol during their lifetime 

also smoked nonmenthol 

cigarettes. Subjects were 

classified as menthol smokers 

if LAST brand smoked was 

menthol. 

Population was older and 

male; some were lung cancer 

patients. 

Chapter 5 - Appendix 

195
 

 

 

 

 

 

 

 

 

 

 

 

 

 

CHAPTER 6. 

SEVERAL HYPOTHESES POSED BY TPSAC ARE SPECULATIVE
 

A review of meeting transcripts and presentations given at TPSAC meetings makes it apparent that 

some committee members are concerned about a number of issues not addressed in the previous 

chapters. Although these issues are discussed often, little information has been presented to date to 

support the validity of these claims. TPSAC should be reminded that with no increase in disease 

risk, as demonstrated by numerous high-quality epidemiology studies, and no convincing evidence 

that use of menthol cigarettes affects biomarkers of exposure or potential harm, smoking 

topography, or smoking behavior, the issues described below are primarily of academic interest. 

This chapter briefly reviews some of the hypotheses that have been discussed at TPSAC meetings 

and points out the speculative nature of each one. 

HYPOTHESIS: SMOKERS PERCEIVE MENTHOL CIGARETTES AS BEING LESS 

HARMFUL 

Published scientific research does not indicate that contemporary smokers have a perception that 

menthol cigarettes are less hazardous than nonmenthol cigarettes. This research shows that smokers 

generally perceive menthol cigarettes as equally, if not more, hazardous than nonmenthol cigarettes. 

In a study published in 2004, Bansal et al. asked survey respondents to indicate their level of 

agreement with a number of statements regarding the perception of risk associated with menthol 

cigarettes including “menthol cigarettes are safer than regular cigarettes.” The results showed a 

greater awareness that menthol cigarettes were as dangerous to health as nonmenthol cigarettes 

(Bansal et al. 2004). 

A recent publication also found that smokers do not perceive menthol cigarettes to be less 

hazardous than nonmenthol cigarettes. Wackowski et al. (2010) published a study analyzing data 

from the 2005 New Jersey Adult Tobacco Survey, which asked participants to compare how risky 

menthol cigarettes were versus nonmenthol cigarettes. Wackowski et al. found few menthol 

smokers (2.4%) and few people overall (4.0%) perceive menthol cigarettes to be less risky than 

nonmenthol cigarettes. To the contrary, a considerable proportion of menthol smokers (30.2%) and 

all respondents (25.9%) believed menthol cigarettes to be more risky than nonmenthol cigarettes. 

Recent government data also demonstrate that menthol cigarette smokers perceive a greater risk of 

harm from smoking than nonmenthol cigarette smokers. From 2000 to 2008, as part of the 

NSDUH, consumers were asked, “How much do people risk harming themselves physically and in 

other ways when they smoke one or more packs of cigarettes per day? Answer options were: No 

Risk; Slight Risk; Moderate Risk; or Great Risk." (NSDUH 2000-2008). 

Responses to this question showed that menthol smokers perceive an equal or slightly greater health 

risk from smoking than nonmenthol smokers. Moreover, the perception that smoking presents a 

great risk of harm increased for both menthol smokers and nonmenthol smokers from 2000 to 2008 

(see Figure 6-1). The same perception is true among adolescent smokers (see Figure 6-2). 

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Figure 6-1. Percentage of Menthol vs . Nonmenthol Smokers Who Believe Smoking 

Presents a Great Risk of Harm (NSDUH) 

Figure 6-2. Percentage of Menthol vs. Nonmenthol Smokers (Age 12-17) Who Believe 

Smoking Presents a Great Risk of Harm (NSDUH) 

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NSDUH data also show that Hispanic and African American menthol smokers perceive a greater 

risk of harm from smoking than White menthol smokers. Moreover, the perception that smoking 

presents a great risk of harm increased for Hispanic, African American and White menthol smokers 

from 2000 to 2008 (see Figure 6-3). 

Figure 6-3. Percentage of Menthol Smokers by Race/Ethnicity Who Believe 

Smoking Presents a Great Risk of Harm (NSDUH) 

Other published survey data on this issue going back 25 years are consistent with NSDUH. The 

1986 Adult Use of Tobacco Survey reported that menthol smokers' beliefs about the health effects 

of smoking differed little from the beliefs of nonmenthol smokers (AUTS 1989). Data from the 

1987 National Health Interview Study (NHIS) also indicated few differences between menthol and 

nonmenthol smokers' risk beliefs; further, the NHIS showed that menthol smokers were more likely 

than nonmenthol smokers to agree that smoking causes various ailments (NHIS 1987). 

HYPOTHESIS: MENTHOL INCREASES HARM THROUGH CHEMOSENSORY 

EFFECTS 

Some authors have speculated that menthol increases the harm of smoking through its 

chemosensory effects. They have suggested that menthol goes beyond its role as just a flavoring by 

masking irritation and pain sensations associated with smoking, enabling easier smoking initiation 

and increased exposure due to changes in respiratory patterns (e.g., Kreslake et al. 2008, Wayne and 

Connolly 2004). It is important to note, however, that support for menthol’s purported 

desensitization and anesthetic properties is very limited and information on this topic has been 

largely obtained from laboratory and clinical protocols using methods of administration and doses 

unlike those in actual smoking. Experience with cigarette product development indicates no special 

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role of menthol in this regard, particularly with respect to the chemosensory properties (primarily 

irritation) of nicotine in smoke. 

The aroma, flavor, and cooling thermal properties of menthol have made it popular in personal and 

health care products, particularly in topical and oral care formulations. In the majority of instances 

(most of which precede any modern mechanistic research or the structural characterization of the 

receptor for thermal coldness), use of menthol rests simply on its simple sensory properties explored 

empirically. Understanding the role of menthol in cigarettes has very much an empirical basis, just 

as understanding its’ role in personal care and over-the-counter products. Admittedly, marketing 

once implied that a menthol cigarette could soothe the irritated throat, but whether it did or not was 

never explored with scientific rigor. The tobacco industry has relied principally on traditional taste 

and sensory evaluation, using panels of internal expert smokers and consumer panels to develop its 

products. The characteristic taste and sensory notes imparted by menthol in some tobacco products 

marketed as having a mentholated character is simply preferred by a minority of smokers and is not 

preferred or even regarded as quite distasteful by the majority of smokers. Ultimately, menthol is a 

characterizing flavor used in cigarettes to meet the taste preferences of some smokers; it is 

recognized that reactions to menthol vary considerably, and range from aversion to liking among 

individual smokers. 

Menthol can impart not only cooling, but also a minty aroma and flavor to products (Eccles and 

Jones 1994, Werley et al. 2007) and can even impart bitterness, depending on the location of 

application on the tongue (Green and Schullery 2003). These actions derive from a pattern of 

activity of smell, taste, and chemesthetic receptors. Contemporary research in the chemosensory 

and food technology fields has provided a considerable insight into the mechanistic basis of 

receptor-mediated chemesthetic stimuli that are subjectively perceived very differently by different 

individuals. Those perceptions span the entire spectrum of preferences from enjoyment to powerful 

aversion. These sensory notes include the cooling properties of menthol and other natural and 

synthetic compounds; the hot, peppery properties of red and black pepper principles; and the 

tingling sensations imparted by beverage carbonation. Menthol and similar sensory stimuli mediate 

their effects through mixed agonism, antagonism, sensitization, and desensitization across neural 

fibers, as is the normal rule for any flavor or sensory component of a complex product mixture. 

In recent years, the characterization of the TRP (transient receptor potential) super-family of 

receptors illustrates how one set of receptors can actually respond to more than one type of 

stimulation. TRPM8 receptors react in sensations of cooling, TRPV1 receptors respond to warmth 

and the burning from capsicum compounds, TRPA1 receptors react to a broad range of noxious 

compounds, such as those in wasabi and mustard, as well as compounds such as carbonyls that are 

present as normal constituents of tobacco smoke. Different parts of TRPA1 channels respond to 

different irritants and, it seems, to some cooling compounds, giving it an enormous breadth of 

“tuning.” The responses may also change with level of stimulation (Dessirier et al. 2001, Eccles and 

Jones 1983, McKemy 2005, Patel et al. 2007). For example, application of menthol at low 

concentrations to skin or mucosal surfaces produces a cooling sensation, whereas at higher exposure 

levels it can produce sensation of burning, irritation, or pain. The effect of just one among many 

level-dependent chemosensory stimuli found in cigarette smoke, demonstrated in isolation or in 

simple interaction experiments, is in all likelihood an inadequate basis to represent phenomena that 

may occur from inhalation exposure to the exceedingly complex smoke aerosol. Some of the major 

sensory components of the cigarette smoking experience, such as “throat grab” or “chest impact,” 

as well as the taste of cigarette smoke itself, are subjectively perceived as desirable or powerfully 

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aversive by smokers and nonsmokers, or among different smokers. The intensity of the taste or 

sensory contributions of menthol are similarly perceived very differently by different smokers, so 

simplistic general conclusions drawn from experimental dosing with pure menthol are entirely 

inadequate to account for the very different subjective taste perceptions that different smokers 

report for menthol and nonmenthol cigarettes. 

It has been suggested by some authors that menthol desensitizes the airway to irritation from the 

components of smoke, including nicotine, and thereby makes it easier or more desirable to smoke 

more (e.g., Dessirier et al. 2001). Experimental and clinical studies have shown both increased and 

decreased sensitivity due to the presence of menthol (e.g., Dessirier et al. 2001, Foster et al. 1993, 

Green and McAuliffe 2000, Hans 2006, Lee et al. 2007, Reeh and Kichko 2006, Renner et al. 2008, 

Talavera et al. 2009, Xiao et al. 2008, Zanotto et al. 2008). Most of these studies have involved use 

of in vitro experimental systems to examine mechanistic aspects of the interaction of menthol with 

peripheral receptors and individual compounds (e.g., nicotine) or topical application of compounds. 

Whereas such studies may have contributed some understanding of the action of menthol, they do 

not provide a sound scientific basis for the hypothesis that menthol may alter perception in the 

complex matrix of cigarette smoke, beyond the familiar characterizing flavor that it imparts. The 

degree of promiscuity for ligands by the TRP family of receptors, the ranges and degree of overlap 

in their sensory signals, and the complex mixture that is cigarette smoke have rendered a 

determination of any net effect of mentholated cigarette smoke elusive. Further confounding the 

pharmacology is research indicating that nicotine itself has nicotinic acetylcholine receptorindependent irritant properties mediated through TRPA1 (Talavera et al. 2009) in addition to local 

nicotinic receptor-mediated irritation in the respiratory tract (Lee et al. 2007). A further example is 

provided by the Philip Morris USA-funded clinical study of Renner et al. (2008) that found menthol 

had no effect on the perception of stinging and burning from nicotine pulses administered as a 

vapor to the nasal mucosa in adult smokers. Although this study did not evaluate the effects of 

menthol in cigarette smoke, it did evaluate exposures in routes and target receptors more directly 

relevant to the actual smoking experience than in vitro or ex vivo experimental systems. 

Some have asserted that menthol may, through local anesthetic effects, attenuate irritation produced 

by inhaled cigarette smoke (e.g., Ahijevych and Garrett 2004, Patel et al. 2007, Wayne and Connolly 

2004); this claim is poorly supported by mechanistic data. Galeotti et al. (2001) is often cited in 

support of such a local anesthetic effect. That report showed that menthol reduced muscle 

contractions under experimental conditions in the rat (in vitro phrenic nerve hemidiaphragm 

preparation) and the rabbit (in vivo), but did not block the action potentials of sensory nerves, a key 

feature of local anesthetics. Other researchers have also provided mechanistic evidence that 

menthol fails to block action potentials (e.g., Haeseler et al. 2002, Hans 2006, Swandulla et al. 1987). 

It has been suggested that menthol in topical preparations at high concentrations may relieve pain 

via production of a warming sensation similar to that of heat therapy (Harris 2006). Nevertheless, 

menthol does not exhibit features characteristic of local anesthetic action in that it does not appear 

to block current-induced neuronal action potentials nor have any effect on neuronal sodium 

channels. 

Menthol also has proalgesic properties (Sherkheli et al. 2008). The relative strength of menthol as an 

analgesic is weak compared to other over-the-counter (OTC) sore throat medications, including 

Cepacol (benzocaine) and Sucrets (dyclonine), as evidenced by their use of other main active 

ingredients in place of or in conjunction with menthol. The amount of menthol used is ~4-7 times 

higher in Cepacol lozenges than the 0.5 mg estimate of smoke menthol, and menthol is not a 

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primary therapeutic compound for the treatment of cough of any origin (Irwin et al. 2006). Menthol 

is similarly not useful as a clinical anesthetic for oral or dental procedures (i.e., laryngoscopy, 

endotracheal intubation, endoscopy, cavity preparation, or endodontics). The lack of clinical use as 

an anesthetic or antitussive, even for these relatively minor procedures runs counter to the claims 

that menthol is an effective topical anesthetic in the oral and upper respiratory regions. Markedly 

more efficacious drugs (Cetacaine®, injectable lidocaine, injectable bupivicaine, etc.) are readily 

available and are widely used to achieve clinically significant local anesthesia. 

Further, it has been speculated that menthol causes smokers to inhale more deeply. This claim 

appears to be based on reports that menthol increases the perception of nasal airflow and decreases 

respiratory rates (Wayne and Connolly 2004). While it has been reported that menthol increases the 

perception of nasal airflow, this perception is not accompanied by any actual physical changes in the 

airway (e.g., Eccles and Jones 1983, Eccles et al. 1989, Eccles et al. 1990, Houghton and Beardsmore 

1998). Enhanced stimulation of cold receptors is likely to account for this sensation of increased 

nasal airflow and respiratory ease (Nishino et al. 1997). Some reports have suggested that menthol 

can decrease respiratory rates in experimental animals (e.g., Orani et al. 1991, Sant’Ambrogio et al. 

1992) and humans (Sloan et al. 1993). However, these studies have limited relevance to real-world 

smoking exposures to menthol in that they involve measurements in anesthetized animals exposed 

to menthol by inhalation and of voluntary breath-holding in humans who ingested menthol 

lozenges. Doubts about the ability of menthol to affect breathing patterns in smokers significantly 

and uniformly are especially appropriate in light of the mixed and inconsistent findings regarding the 

effects of menthol in clinical smoking topography studies. 

Any case for added harm due to menthol based on existing scientific data surrounding these 

hypotheses is not convincing. The arguments discussed before TPSAC appear to be constructed 

largely by citing behavioral principles and effects out of context, and fall far short of providing a 

sound scientific basis of evidence for any real, incrementally adverse public health outcome. Basing 

any conclusion or recommendation on evidence of this type directly contradicts the mandate issued 

by the Director of the Center for Tobacco Products, Dr. Lawrence Deyton, at the first TPSAC 

meeting during which he stated that the success of TPSAC was dependent on being “guided by the 

best science” and that “the advice you give us [must be] based on the science and the science alone” 

(TPSAC 2010a p.39). Claims regarding the role of menthol in encouraging smoking initiation and 

maintenance, discouraging quitting by making satisfying low-yield cigarettes, or increasing the 

addictiveness of smoking are not supported by clear evidence (as discussed in detail in previous 

sections of this report). Furthermore, there is a lack of sound data connecting available knowledge 

of the physiologic, pharmacologic, and neurochemical mechanisms of menthol’s sensory impact to 

specific smoking-related behaviors. These behaviors are more informatively measured by other, 

more direct methods by extrapolation from laboratory research on menthol in isolation in 

experimental systems to complex human behaviors. 

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HYPOTHESIS: MENTHOL “MAKES THE POISON GO DOWN EASIER” 

At many TPSAC meetings, committee members and attendees have repeatedly made the assertion 

that menthol makes the “poison go down easier.” While exactly what this means has never been 

stated, it may be another way of saying that menthol cigarettes make it easier to start smoking, inhale 

more deeply, or make it harder to quit. The literature discussed in the previous chapters (3-5) does 

not provide evidence in support of this hypothesis. FDA and TPSAC have received written and 

verbal information that menthol added to cigarettes does not in fact reduce the harshness or 

irritation of cigarette smoke. Product developers in the tobacco industry have long appreciated that 

increases in smokers’ perceptions of smoke harshness by product design features such as filter tip 

ventilation or excessive dryness of the cigarette tobacco filler are not ameliorated by added menthol. 

Neither the available body of scientific evidence on smoking topography nor comparisons of 

biomarkers of smoke exposure in menthol and nonmenthol cigarette smokers have not 

substantiated the facilitation of deeper smoke inhalation. Most importantly, the epidemiology 

studies, which incorporate the combined influences of all aspects of smoking behavior, consistently 

fail to show that menthol smoking is associated with any significant increase in disease risk 

compared to nonmenthol smoking. 

Smokers’ stated reasons for choosing a particular cigarette brand are numerous and complex, and 

vary considerably from smoker to smoker. Menthol content is only one factor related to consumer 

acceptability. Smokers accept or reject cigarettes based on a variety of product attributes and 

sensory characteristics, including strength of taste, strength of menthol flavor, smoothness of taste, 

harshness of taste, refreshment of taste, tobacco taste, and balance of menthol taste and tobacco 

taste. Other factors such as price and the cigarette brand favored by an individual’s family or social 

group also may be important determinants in making choices regarding preferred cigarette brands. 

Consumer research consistently shows that smokers who prefer menthol over nonmenthol 

cigarettes do so primarily because of taste. Some of the industry’s studies of the physiologic, 

pharmacologic, and neurochemical mechanisms of sensory impact have been carried out to better 

understand how different cigarette ingredients may affect chemosensory responses and to 

understand consumers’ reactions to different products. The findings of these types of mechanistic 

studies are not typically used to design and develop cigarette products, but rather to understand how 

flavors or other design components might be adjusted to compensate for reported taste and sensory 

deficits. Taste preferences and even how menthol taste characteristics are described are not 

consistent among individuals, but some menthol cigarette smokers are able to detect slight 

differences in menthol levels and can taste the differences among different cigarette brands. These 

perceptions are not unlike those for tobacco taste itself among smokers who prefer nonmenthol 

brands. Individuals have their own perceptions and preferences of the menthol taste characteristics, 

and the majority of U.S. smokers prefer no menthol taste at all. 

Speculative explanations of how menthol may mask nicotine or other components of cigarette 

smoke based on existing mechanistic data do not appear to be as likely or important reasons for 

brand selection as are simple subjective taste preferences. In fact, some menthol smokers appear to 

prefer the taste impact associated with cigarettes having a lower nicotine yield balanced with the 

menthol flavoring characteristic. It is worthwhile to note, of course, that nonmenthol smokers also 

make choices regarding their preferred brand based on taste and reject the menthol flavor 

characteristic in favor of preferred choices among tobacco flavor characteristics. This spectrum of 

tobacco taste characteristics includes such elements as burley tobacco character, bright tobacco 

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character, oriental/Turkish notes, and a variety of other terms of the cigarette developer’s art that 

are typically interpreted by the smoker as a simple taste preference for one cigarette over another. 

DiFranza et al. (2004) conducted a “retrospective/prospective” longitudinal analysis of a cohort of 

seventh graders who were followed for 30 months (part of the Development and Assessment of 

Nicotine Dependence in Youth Study) to assess subjects’ reactions to their first cigarettes and 

whether these reactions were predictive of later nicotine dependence. The analysis focused on 237 

subjects who reported that they had inhaled a cigarette; only about half of them could recall whether 

the first cigarette they had smoked was mentholated or not. The authors found that reactions to the 

initial smoking experience (irritation; nausea; dizziness; relaxation; felt good, or good and bad; desire 

to smoke again, yes or maybe) were unrelated to mentholation. They were also unrelated to sex, 

cigarette brand, or strength of cigarette. In addition, for the 59 subjects who smoked enough to 

have established a favorite brand, the strength of the addiction, as measured by the Hooked on 

Nicotine Checklist, did not differ according to the favorite brand, brand strength, or menthol 

content. Although this study has some limitations (small sample size, subjectivity of symptoms, few 

subjects who could recall mentholation of first cigarette, few African American subjects), it argues 

against the assertion that menthol in cigarettes alters the smoking experience to make it more 

pleasurable and easier to continue than nonmenthol cigarettes, i.e., menthol does NOT “make the 

poison go down easier.” 

HYPOTHESIS: MENTHOL INCREASES POTENTIAL FOR ABUSE 

The concept of abuse liability has been raised by some members of TPSAC. The FDA defines 

products with abuse potential (a term interchangeable with abuse liability) as “a drug that is used in 

nonmedical situations, repeatedly or even sporadically, for the positive psychoactive effects it 

produces. These drugs are characterized by their central nervous system (CNS) activity” (FDA 

2010b). The applicability of this concept to menthol cigarettes is unclear, as the central nervous 

system effects of menthol cigarettes have not been documented (Ahijevych and Garrett 2004). 

Furthermore, drugs with abuse potential often (but not always) produce dependence and may lead to 

addiction (FDA 2010b). As discussed in Chapter 5, a review of the methodologically sound 

literature on menthol smoking and cessation demonstrates that the most relevant studies – those 

that address successful long-term quitting – do not indicate that smokers of mentholated cigarettes 

are less likely to quit than are smokers of nonmentholated cigarettes. Additionally, the studies that 

address other measures of nicotine dependence do not find that menthol smokers are any more 

dependent on nicotine than nonmenthol smokers. 

HYPOTHESIS: MENTHOL SMOKERS WHO SMOKE 6-10 CIGARETTES/DAY ARE 

UNIQUELY AFFECTED 

Based on the findings of a recent study (Fagan et al. 2010), TPSAC members speculated that 

menthol smokers who smoke fewer than 10 cigarettes per day are more dependent than those who 

smoke more than 10 cigarettes per day. Fagan et al. conducted an analysis of the pooled datasets of 

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the 2003 and 2006/07 TUS-CPS. The data showed that after adjustment for multiple factors,

1 

subjects who smoked their first cigarette within 5 minutes of waking were more likely to be menthol 

smokers of 6-10 cigarettes per day than nonmenthol smokers of 6-10 cigarettes per day (OR=1.22, 

95% CI: 1.05-1.43). When the same analysis was conducted on smokers of <5, 11-19 and ≥20 

cigarettes per day, there were no significant differences between menthol and nonmenthol smokers. 

No significant differences were found in any other measures of dependence, including whether 

subjects smoked their first cigarette within 30 minutes of waking, had a quit attempt lasting 1 day or 

longer within the past 12 months, and length of smoking abstinence. As discussed in Chapter 5B, 

the authors focused on this one significant finding to conclude that menthol smokers who reported 

consuming 6-10 CPD show greater signs of nicotine dependence than comparable nonmenthol 

smokers. However, it is inappropriate to focus on this single finding when the overall pattern of 

results suggests no difference in TTFC between menthol and nonmenthol smokers. The authors 

acknowledge that the effect was not dose-dependent, as odds ratios for TTFC after waking did not 

increase as smoking intensity increased for menthol smokers. 

Given that Fagan et al. (2010) is the only study that looks specifically at menthol smokers of 6-10 

cigarettes per day, at the request of TPSAC, Altria conducted an analysis of the Total Exposure 

Study (TES) dataset that included only those subjects who smoked ≤10 cigarettes per day and 

compared menthol to nonmenthol smokers on biomarkers of exposure (nicotine equivalents, 

carboxyhemoglobin, serum cotinine, total NNAL), FTND scores and TTFC. There were no 

significant differences in exposure and dependence measures among menthol smokers as compared 

to nonmenthol smokers of ≤10 cigarettes per day. These results were consistent with the previous 

findings from the TES, observed among all adult smokers. Additionally, this analysis adds to the 

substantial body of evidence that indicates no effect of menthol on exposure or dependence 

measures. 

HYPOTHESIS: VARIATIONS IN MENTHOL LEVEL DRIVE BRAND POPULARITY 

TPSAC has discussed a single published paper that has asserted that the tobacco industry has 

manipulated levels of menthol downward to increase the appeal of menthol cigarettes to adolescents 

(Kreslake et al. 2008). The Industry has previously submitted detailed product data to the FDA that 

refutes this assertion. The industry led a discussion with TPSAC on this subject during the July 15­

16, 2010 TPSAC meeting (TPSAC 2010b p.17) with the example of the leading menthol brand, 

Newport, discussed in some detail. It should not be surprising that some competitors of the 

manufacturer of Newport may have speculated internally with regard to the reasons for Newport’s 

increasing success in the marketplace in prior decades, as such analysis and hypothesis is a normal 

component of free market competition. Some of these analyses included hypotheses relating to the 

moderately lower levels of menthol in Newport compared to those found in some competitive 

brands. The fact is that menthol levels in existing products have generally remained stable over time 

and any significant changes can be explained by changes in regulations or other business reasons, 

such as blend consolidations or target level adjustments due to revised (improved) analytical 

methodology for determining menthol. As a compelling example of this fact, the amount of 

1 Odds ratios were adjusted for sex, age, race/ethnicity, marital status, educational attainment, annual family income, 

employment/occupational status, region, metropolitan status, survey year, age of onset, total years smoked daily and 

smoking status 12 months ago. 

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menthol in the most popular menthol brand, Newport Kings Box, did not change substantially from 

1972 through 2009.2 As Figure 6-4 demonstrates, the pack menthol levels have not changed beyond 

normal production variation parameters for years prior to the design changes employed as a result of 

compliance with new fire safe cigarette standards. Pursuant to Section 904 of the Act, the Industry 

has reported to the FDA the amounts of menthol applied to each brand and sub-brand of its 

cigarettes. 

Figure 6-4. Newport Full Flavor 80mm Menthol Level (1993-2010) 

Introduction of Fire Standards Compliant (FSC) Cigarette Regulations 

Beginning with New York in 2004, all states and the District of Columbia require or will require 

each cigarette manufacturer to certify that its cigarettes comply with the testing and performance 

standards of American Society for Testing and Materials Standard E21S7-04b. The paper 

technologies typically used by the industry to achieve low ignition propensity (LIP) compliance 

typically slowed the burn rate of the cigarette, increased the number of puffs, and increased tar and 

nicotine deliveries. To maintain consumer acceptance and smoke deliveries consistent with pre-LIP 

cigarettes, companies employed cigarette design changes, including adjusting the levels of some 

additives and adjusting cigarette filter efficiency and ventilation. In some cases, these design changes 

required an increase in the amount of menthol applied to the cigarettes due to, among other things, 

increased filtration or increased filter ventilation (also called air dilution). Because menthol is filtered 

at roughly the same rate as tar and nicotine, increased filter efficiency or ventilation causes the 

menthol delivered in the smoke to be reduced. To ensure that products were delivering the same 

menthol taste preferred by the consumers of those brands, the amount of menthol in the cigarette 

was increased to the level necessary to approximate the menthol delivery in the smoke of those 

brands prior to the design changes. In other cases, the amount of menthol applied to the cigarette 

was not changed, but the level of filter ventilation was increased to maintain consistent smoke 

2 See Lorillard’s submission and presentation on “Characterization of Menthol” to TPSAC on July 15-16, 2010, for a 

detailed discussion of the levels of menthol in Lorillard cigarettes. 

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delivery (i.e., ‘tar’) according to pre-regulation design criteria. In these cases, the actual smoke 

delivery of menthol decreased as the result of compliance with FSC regulations. 

In addition, the TPSAC discussions at the March 30-31, 2010 meeting referred to the belief that 

cigarette brands reportedly preferred by younger smokers have lower levels of menthol than do 

brands reportedly preferred by older smokers, and that cigarette manufacturers had lowered menthol 

levels as a general strategy to attract youthful smokers in recent years. This notion has arisen largely 

from a single paper published in 2008 by Kreslake et al. The methodology employed in this study 

(a two point trend analysis based on incompatible analyses performed years apart by different 

methods in different laboratories) is not scientifically sound, as it does not provide a statistically 

representative characterization of the menthol levels for products having annual production volumes 

of billions of units. The data discussed above and the detailed documents supplied to FDA by the 

industry for a case study of the current most popular menthol brand unequivocally refute the 

assertion that menthol levels in products have been lowered to attract youth. 

HYPOTHESIS: MANUFACTURERS MARKET MENTHOL CIGARETTES 

DIFFERENTLY THAN NONMENTHOL CIGARETTES 

Cigarette marketing practices is a difficult topic to discuss from a single industry perspective. There 

are many cigarette manufacturers with each company independently deciding how to market its 

products. 

At the July 15, 2010 TPSAC meeting, the three largest cigarette manufacturers (Altria on behalf of 

Philip Morris USA, R.J. Reynolds Tobacco, and Lorillard Tobacco Company) provided TPSAC with 

written submissions and presentations about their particular marketing practices for their menthol 

cigarette brands. Each company independently emphasized that the marketing of menthol cigarettes 

involves the same activities used for the marketing of nonmenthol cigarettes. 

At that meeting, the submissions and presentations of the three largest cigarette manufacturers 

noted the following common practices for the marketing of menthol cigarette brands: 

•	 The same practices are used to market both menthol and nonmenthol cigarettes. 

•	 All marketing efforts are directed to adult smokers with the intent of maintaining brand 

loyalty or attracting smokers of competitive brands. Cigarettes are not marketed to nonsmokers. 

•	 No marketing activities are directed to youth. Smoking is an adult choice. Underage 

persons should not smoke. 

•	 The commonly used marketing activities included: 

o	 Retail merchandising and point-of-sale advertising, 

o	 Direct mail, electronic mail, and branded websites directed to age-verified adults, 

and 

o	 Retail price promotions, which account for the vast majority of all marketing 

expenditures (TPSAC 2010b p.295). 

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For decades, cigarette brand marketing has been subject to ever-increasing and substantial 

prohibitions, restrictions and requirements imposed by Congress, federal agencies, and state and 

local authorities. Over the last ten to fifteen years, there have been additional dramatic and 

substantial changes in how the tobacco industry markets cigarettes. Today, no other legal consumer 

product is subject to more restrictive marketing requirements than cigarettes. All cigarette brand 

marketing, both menthol and nonmenthol cigarettes, must comply with the extensive restrictions set 

forth in the Tobacco Settlement Agreements (TSAs)3 and the Act. 

The TSAs include a number of restrictions on the marketing of all cigarette brands. First and 

foremost, the TSAs prohibited the direct or indirect targeting of youth through advertising, 

promotion or marketing or any action the primary purpose of which is to initiate, maintain or 

increase the incidence of youth smoking. The TSAs also included, among other things, prohibitions 

on (1) the use of cartoons in advertising, promotion or packaging of cigarettes, (2) most outdoor 

advertising, including billboards, transit and stadium/arena advertising, (3) placement of tobacco 

products in movies or television shows, (4) brand name sponsored concerts, and (5) distribution of 

merchandise with cigarette brand names and logos. 

In addition to the TSA restrictions, the Act contains additional prohibitions on (1) self-service 

displays except in adult-only facilities, (2) free cigarette sampling, (3) providing gifts (other than 

cigarettes) in consideration of the purchase of tobacco products, (4) brand name sponsorships, and 

(5) co-marketing of tobacco products with other FDA-regulated products. 

The Act also limits nearly all cigarette advertising and labeling to black text on white background4 

and requires larger warnings5, including graphic warnings for all cigarette packaging and advertising. 

FDA has also announced that it is considering additional restrictions on outdoor advertising (FDA 

2010a). 

The TSAs of the late 1990s and the Act’s passage in 2009 fundamentally changed the way cigarettes 

are marketed and sold in the United States. It serves no meaningful regulatory purpose for FDA or 

other forward-looking regulatory bodies to continue to revisit industry marketing practices or 

industry documents from decades ago, as those practices are no longer relevant in a post-TSA and 

post-Act environment. Further, most of marketing restrictions in the Act took effect in June 2010. 

The effectiveness of these restrictions should be measured before determining if other actions are 

required. 

3 In 1998, the Major Manufacturers, including Lorillard, RJRT and Philip Morris U.S.A. and other Original Participating 

Manufacturers, signed an agreement with the Attorneys General of 46 states, five U.S. territories and the District of 

Columbia (Master Settlement Agreement or MSA). The MSA, along with similar agreements entered into with the 

States of Florida, Mississippi, Texas and Minnesota, are referred to as the Tobacco Settlement Agreements (TSAs). 

4 FDA announced it would be exercising enforcement discretion and not commence enforcement of this requirement 

while the injunction against enforcement issued in Commonwealth Brands, Inc. v. United States, No. 1:09-CV-117-M 

(W.D. Ky. Jan. 4, 2010) is pending appeal. 5 New warning requirements for cigarettes under the Act have not yet taken effect. According to the Act, new warning 

requirements must take effect by September 22, 2012. 

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No Health Claims in Menthol Advertising 

Similarly, it serves no purpose to assert that menthol ads contain health claims based on ads that 

have not been published for several decades. The Cigarette Advertising Guides, promulgated by the 

Federal Trade Commission (FTC) in 1955, prohibited both explicit and implicit health claims in 

cigarette ads (FTC 1955). Furthermore, all health-related claims in advertising are prohibited by 

both the TSAs and the Act. 

Terms such as “cool,” “smooth,” “fresh,” “refreshing,” and “mild,” as well as images of water, 

springtime and other refreshing imagery are deemed by some to be used in menthol cigarette 

advertising in an effort to implicitly communicate that menthol cigarettes are less hazardous than 

nonmenthol cigarettes. First, as shown earlier in this chapter, menthol smokers do not perceive 

smoking as less risky. Second, cigarettes are marketed as having “cool” and “fresh” tastes and 

sensations consistent with what adult smokers seek in menthol brands and consistent with the flavor 

characteristics of the particular brand. Interestingly, some of these terms, particularly “smooth,” 

“fresh,” “refreshing,” and “mild” have been or are also used in advertising for nonmenthol 

cigarettes. But more importantly, such terms are only intended to communicate taste, flavor and 

satisfaction. In fact, these terms are the same terms that smokers, themselves, use to describe 

preferred cigarette taste characteristics. 

Menthol Cigarettes Are More Expensive Than Nonmenthol Cigarettes 

For at least the last ten years, the great majority of Industry marketing expenditures have gone 

toward retail price promotions. The reason for this is straightforward: the cost of cigarettes has 

risen dramatically. Much of the increased cost is due to substantially higher local, state and federal 

cigarette taxes. For example, due to changes in the federal excise tax in 2009 and the most recent 

New York state excise tax increase in 2010, New York City smokers pay more than $7 per pack in 

federal, state, and local excise and sales taxes. Retail price promotions are only legally available to 

adult purchasers of cigarettes. 

At the July TPSAC meeting, the three largest manufacturers discussed pricing of menthol cigarettes 

compared to nonmenthol cigarettes as part of their marketing presentations. The prices for menthol 

cigarettes, after all promotional discount, were slightly higher than nonmenthol cigarettes (TPSAC 

2010b p.295). At the November 18, 2010 TPSAC meeting, RTI International (RTI) presented 

background information for TPSAC about pricing and promotion of menthol cigarettes and 

confirmed that the prices of menthol cigarettes were slightly higher than nonmenthol cigarettes (RTI 

2010). RTI also noted that promoted cigarettes accounted for a greater percentage of sales for 

menthol cigarettes than for nonmenthol cigarettes (RTI 2010). However, a comparison of the 

values of the promotions was not provided. Most importantly, prices at retail reflect prices after 

promotions (TPSAC 2010b p.295). The fact that menthol cigarettes may be promoted more than 

nonmenthol cigarettes does not change the simple fact that consumers pay higher prices for 

menthol cigarettes. 

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CHAPTER 7. 

A BAN ON MENTHOL CIGARETTES
 

WILL RESULT IN SIGNIFICANT COUNTERVAILING EFFECTS
 

The previous chapters demonstrated that smoking menthol cigarettes do not disproportionately 

impact the public health compared to smoking nonmenthol cigarettes. However, in order to fully 

assess countervailing effects as required by the Act, this chapter considers the consequences if a ban 

on the sale of menthol cigarettes were imposed. 

BANNING MENTHOL CIGARETTES WOULD INCREASE BLACK MARKET 

CIGARETTE SALES AND PRODUCE A RANGE OF PUBLIC HEALTH PROBLEMS 

Section 907(b)(2) of the Act requires FDA and TPSAC to: 

“...consider all other information submitted in connection with a proposed [tobacco 

product] standard, including information concerning the countervailing effects of the 

tobacco product standard on the health of adolescent tobacco users, adult tobacco users, or 

nontobacco users, such as the creation of a significant demand for contraband or other 

tobacco products that do not meet the requirements of this chapter and the significance of 

such demand.” 

If the United States government were to ban menthol cigarettes, nearly 30 percent of all cigarettes 

consumed in the United States would be outlawed. History has shown that when consumer 

preferences are blocked by government policy, black markets will emerge and criminal enterprises 

will flourish. 

Under a menthol ban, contraband menthol cigarettes would inevitably be sold through an expansion 

of the sophisticated black market that currently exists. There would be no way to monitor the 

quality and safety of the cigarettes or their ingredients – or whether they are sold to underage 

individuals. Furthermore, there is no evidence that overall smoking rates would decline significantly. 

This chapter demonstrates the unintended and negative impacts on public health that would result 

from efforts to ban menthol cigarettes. Congress’ purpose of granting FDA with authority to 

regulate tobacco was to create order and supervision of the industry – not create chaos the likes of 

which have not been seen since Prohibition1 (Altria Client Services 2010). In addition to the 

scientific information presented elsewhere, FDA must carefully consider the countervailing effects 

of a menthol ban as demonstrated here. 

1 A report submitted by Altria Client Services Inc. on behalf of Philip Morris USA, Inc. for the January 10, 2011 TPSAC 

meeting (“Countervailing Effects of a Ban on Menthol Cigarettes”), notes that, from 1920 to 1933, the sale, 

manufacture and transportation of alcohol were banned during Prohibition in the United States. During this time the 

federal government devoted nearly half its law enforcement resources to enforcing Prohibition, as millions of otherwise 

honest citizens routinely flouted the law. Research showed that per capita consumption of alcohol actually increased 

during Prohibition. 

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A Large-Scale Illegal Market in Cigarettes Has Been Well Documented 

One fact is without dispute: a significant and troubling illicit market in counterfeit and contraband 

cigarettes currently exists in the United States. 

With the infrastructure of the black market already in place, some federal agencies expect the sale of 

contraband cigarettes to expand even without the added stimulus of a ban of menthol cigarettes. A 

U.S. Department of Treasury report (2010) to Congress said: “The scope of this problem will 

certainly multiply, based upon the tax increases imposed under CHIPRA [the Children’s Health 

Insurance Program Reauthorization Act of 2009] and similar tax increases at the state level in recent 

years.” It added: “Tax evasion schemes function in a variety of ways and continuously evolve in 

efforts to outpace enforcement and operate beyond its reach.” 

Experts at the Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF) describe, in a report for 

the Department of Justice Inspector General (USDOJ 2009), the diversion of tobacco as a global 

problem and say that illegal cigarettes are the No. 1 black market commodity in the world. ATF 

officials told the Department of Justice Inspector General that individuals and organized crime 

groups have been involved for decades. These groups are now running larger scale diversion 

schemes that are more complicated with the enterprises having all the characteristics of a structured 

business model that mirrors legitimate tobacco manufacturers – a source, a warehousing system, a 

shipping network and finally a retail outlet. ATF’s diversion program “has not kept pace with the 

level of diversion activity and increasingly complex diversion schemes,” the report concluded. 

And recently, a submission by the United States to the World Trade Organization (2010), dated 

November 16, 2010, acknowledges that millions of adults regularly smoke menthol cigarettes and 

expressed its concern that banning “any type of cigarette favored by a large portion of U.S. 

smokers” could significantly expand the existing black market and result in harmful consequences. 

The U.S. government submission, made in connection with a dispute resolution with Indonesia 

regarding certain flavored cigarettes, including clove cigarettes, added: 

“Banning all cigarettes – or any type of cigarette favored by a large portion of U.S. smokers 

– could significantly increase the existing black market for cigarettes and all the attendant 

contraband trafficking and other illegal activity. There is already a sizeable black market for 

cigarettes in the United States. The Treasury Department’s Alcohol and Tobacco Tax and 

Trade Bureau (“TTB”) estimates that around $2 billion dollars in federal excise tax revenue 

is lost each year due to this black market.” [Emphasis added.] 

In March 2011, the U.S. Government Accountability Office (GAO) also observed the pervasiveness 

of the current black market in cigarettes in a report on the illicit trade of tobacco in the United 

States (GAO 2011). GAO noted the range of schemes used to import both genuine and counterfeit 

product for distribution on the black market and stated that federal and state law enforcement 

officials acknowledge that “the patterns of smuggling and diversion are not static, but change in 

response to many factors, including changes in tobacco taxes, tobacco regulation and law 

enforcement activity.” Further, GAO said that the “illicit trade in tobacco products, according to 

U.S. law enforcement agencies, is also a source of financing for both domestic and international 

criminal activities.” 

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In combination, these reports by U.S. agencies – from government experts who are closest to the 

problem of contraband markets – provide compelling evidence of the extent, dangers and potential 

growth opportunities of contraband markets that currently exist. 

Another perspective of the pervasiveness of contraband markets is provided by Canada. Today, one 

out of every two packs of cigarettes sold in some areas of Canada is illegal (Bryans D 2011). A 

special Canadian task force advising Canada’s Minister of Public Safety on the sale of contraband 

tobacco concluded: 

“Persons involved in contraband tobacco, including the end users, are undermining global 

and domestic health objectives, contributing to the proliferation of organized crime, inviting 

criminals into their communities, undermining the local legitimate economy, and evading 

taxes that support Canada’s programs” (Task Force 2009). 

The task force cited a study (GfK 2008) for cigarette manufacturers that found about 30 percent of 

tobacco purchased in Canada is bought illegally, and that illegal cigarettes were in one out of five 

smokers’ homes. The study also found that the problem is at its worst in Quebec and Ontario, 

where rates hover around 40 percent and 50 percent respectively. An estimated 13 billion illegal 

cigarettes were bought in 2008, up from 10 billion a year earlier. Regular analyses of cigarette butts 

collected at various locations found that a quarter to a third of the cigarettes smoked at various high 

schools were contraband. 

Estimating the Size of an Expanded Black Market if Menthol is Banned 

TPSAC received a variety of submissions and presentations cautioning that any ban or other similar 

restriction on the sale of menthol cigarettes would lead to an explosion of the black market and the 

unregulated manufacture and distribution of contraband products lacking the product standards of 

U.S. manufacturers. They included among others: 

• Altria Client Services Inc. (2010) 

• Ontario Convenience Store Association (Bryans 2011) 

• Center for Regulatory Effectiveness (Levinson 2011) 

• Compass Lexecon (2010) 

• Law Enforcement Alliance of America (2010) 

• Maryland Association of Tobacco and Candy Distributors (2010) 

• National Association of Attorneys General (2011) 

• National Association of Convenience Stores (2010) 

• National Organization of Black Law Enforcement Executives (2010) 

• National Troopers Coalition (2010) 

• National Black Chamber of Commerce (2011) 

• American Wholesale Marketers Association (2011) 

Using various methodologies and assumptions, three studies attempted to estimate the impact of a 

menthol ban on the U.S. contraband market. Each study used a different approach to provide a 

range of estimates on the size of an expected illegal tobacco market. It is difficult to estimate the 

size of the current illegal tobacco market with absolute certainty. Such studies are constrained 

Chapter 7 

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because black market participants – buyers and sellers alike – do not report information as they do 

for legal cigarette sales. 

All three studies uniformly agreed that banning menthol cigarettes would lead to the manufacture, 

sale and purchase of menthol contraband cigarettes and the creation of a significantly expanded 

black market. The studies: 

Compass Lexecon (2010). In a study commissioned by Lorillard, economists concluded that a ban 

on the sale of menthol cigarettes would not lead to a significant reduction in aggregate smoking. 

“Following a ban,” it said, “menthol smokers are likely to turn to the black market and to nonmenthol cigarettes, thereby substantially mitigating the decline in cigarette smoking.” 

The study found that a 10 percent increase in the effective price of illegal menthol cigarettes would 

lead to an initial decline in overall smoking of only about one percent and black market sales would 

be about 87 percent of current menthol sales. Prices 25 percent higher would lead to menthol sales 

of about 72 percent of the current size of the current sales, and total smoking would initially fall by 

about two percent. 

It is important to note that the “effective price” cited in the study is not just the money paid. It is an 

economic price, which includes not only the money paid but also the effort required and the 

reluctance consumers must overcome to purchase on the black market. Said another way, if prices 

for illegal menthol cigarettes stay the same as the prices before a ban, effective prices would increase 

because consumers would have to expend additional time and effort to overcome the illegality and 

potential inconvenience to acquire contraband cigarettes. 

It is also worth noting here, however, that bootleggers have substantial incentives to reduce pre-ban 

monetary prices, which would result in consumers actually spending less money to purchase 

menthol cigarettes. This incentive is provided by the amount of taxes that are not collected in black 

market transactions. A large amount of the sales price, if purchased legally, is related to taxes 

(e.g., total taxes in New York City are more than $7 per pack and more than $5 per pack in 

Chicago). Bootleggers could reduce the monetary sales price and yet still enjoy very high profits, 

providing lucrative incentives for both dealers and consumers to engage in the black market sale of 

menthol cigarettes. 

Altria Client Services Inc. (2010). Altria Client Services Inc., on behalf of Philip Morris USA Inc., 

noted that criminal organizations already distribute large volumes of illicit cigarettes and make 

significant profits in the United States. The report added: “A ban on menthol would be an 

irresistible opportunity to dramatically expand those criminal operations, the volumes of illicit 

cigarettes they distribute, and their profits.” 

Altria’s study assessed the impact of varying levels of contraband sales. If only 20 percent of the 

current taxed menthol volume migrated to the illicit market, it said, it would double the size of the 

existing illicit cigarette market and represent 10 percent of cigarettes sold in the United States – 

about 33 billion sticks and $8 billion in untaxed annual sales – roughly equivalent to the revenues of 

Campbell’s Soup© or eBay©. The report provided the potential impacts of menthol smoker 

migration to illicit cigarette markets, see Table 7-1 below. 

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Chapter 7 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 7-1. Potential impacts of menthol cigarette volume moving to the U.S. 

illicit cigarette market 

Migration of additional menthol 

cigarette volume to illicit market 0% 10% 20% 30% 40% 100% 

Resulting illicit market (billions of 

sticks) 

16 25 33 42 50 102 

Share of U.S. cigarette market 5% 8% 10% 13% 16% 32% 

Approximate illicit sales ($ billion) 4 6 8 10 12 25 

Of which approximate tax losses 

($ billion) 

2 3 4 5 6 12 

Source data: Total U.S. total volume of 317.7 billion sticks, $77 billion in retail sales,
 

27% menthol share, and $37.5 billion in total tax revenue.
 

Table reproduced from Altria Report, Table 1.2
 

Center for Regulatory Effectiveness (Levinson 2011). From a practical perspective, the Center 

for Regulatory Effectiveness (CRE) said, “there is no reason to assume that a menthol ban would 

have much long-term impact on U.S. consumption of menthol-flavored cigarettes. The evidence 

clearly demonstrates that there is essentially limitless cigarette manufacturing capacity overseas and 

domestically.” 

Given the uncertainties of contraband markets, CRE said it is possible to “reasonably conclude” that 

a menthol ban could lead to an increase in consumption of menthol flavored cigarettes. That is 

because street-level prices (without taxes) are lower, leading to higher consumption; street-level 

vendors act as an “advertising mechanism,” and a contraband market “increases youth access to 

tobacco.” Assessing various scenarios, CRE conservatively estimated that if a menthol ban were 

imposed, the contraband market that exists today would increase by about 45 percent. 

Based on these studies and other available data, it would be speculative and premature to conclude 

that banning menthol cigarettes will reduce overall smoking prevalence. This factor alone – the 

continued availability of menthol cigarettes through contraband channels – will undermine any 

anticipated public health benefit of removing menthol cigarettes from the legitimate marketplace. 

Countervailing Effects on the Public Health from an Expanded Black Market 

In determining the regulation of tobacco products, Congress applied a standard based on the net 

effect on public health. The creation of a significant black market for menthol cigarettes – in 

addition to enabling the circumvention of the policy decision to prevent individuals from obtaining 

menthol cigarettes – would have adverse public health consequences. The countervailing effects on 

public health would be manifested in several ways: 

Negative impact on public health with unregulated contraband cigarettes 

Two purposes of the Act were to provide FDA with the authority: 

•	 “to set national standards controlling the manufacture of tobacco products and the identity, 

public disclosure, and amount of ingredients used in such products.” 

217
 

 

 

 

 

•	 “to regulate the levels of tar, nicotine, and other harmful components of tobacco
 

products...”
 

Any policies that result in an increased supply of cigarettes not manufactured according to legal 

requirements demands analysis because such policies would be contrary to the purposes and intents 

of the Act. Illegal cigarettes evade quality control standards of cigarettes regulated by FDA under 

the Act, and likely contain more harmful constituents. Because illicit manufacturers cannot be 

effectively regulated, Americans will be deprived of the significant benefits of the Act. 

Counterfeit cigarettes pose serious health risks over and above the normal health risks posed by 

smoking. As noted in the U.S. submission to the World Trade Organization, black market cigarettes 

“may be even less safe than those that are currently being sold in the U.S. market” (First Submission 

2010). The ATF states in a fact sheet (2010) that: 

“The trade of counterfeit tobacco products is also a rapidly growing global problem. 

Smokers who are tricked into buying fake cigarettes don’t get the product they’re expecting. 

While all cigarettes are dangerous and cause disease, it has been reported that counterfeit 

cigarettes had 75 percent more tar, 28 percent more nicotine and about 63 percent more 

carbon monoxide than genuine cigarettes. Furthermore, many are even contaminated with 

sand and other packaging materials such as bits of plastic.” 

“...Since these are illegally manufactured and imported cigarettes, consumers do not know 

what ingredients are used to manufacturer these cigarettes. Counterfeit cigarettes pose a 

significant health risk to consumers because of this reason.” [Emphasis added] 

Moreover, researchers from the National Center for Environmental Health at the Centers for 

Disease Control and Prevention have found that levels of cadmium, thallium and lead in mainstream 

smoke “were far greater for counterfeit than the authentic brands, in some cases by an order of 

magnitude” (Pappas et al. 2007). 

The CRE monograph lists published literature and research findings, reported by governments in 

some instances, that have detailed levels of metals and miscellaneous contaminants found in illegally 

manufactured cigarettes (Levinson 2011). It cites studies that illustrate the heightened levels of 

substances like cadmium, thallium and lead in counterfeit cigarettes. For example, the CRE 

monograph references research conducted by the New York State Department of Health that found 

levels of many metals “were significantly higher in counterfeit cigarette samples than in genuinebrand cigarette samples.” See Figure 7-1. 

Chapter 7 

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 Metal Concentrations in Counterfeit Cigarettes as a Percentage of 

their Concentration In Legal Product (μg per cigarette) 

Figure 7-1. Many Toxic Metals are in Higher Concentrations in Counterfeit Cigarettes 

(NY) 

Figure reproduced from CRE monograph, Figure 5 (Levinson 2011); original source: Swami et al. 2009, 

Table 8B 

Another study included in CRE’s report, conducted in Australia in 2007, addressed the health 

impact of illicit tobacco (Aitken et al. 2009). The study compared the health of past and current 

smokers of illicit tobacco with that of smokers of licit tobacco. It found that current users of illicit 

tobacco had significantly greater odds of beginning smoking at a younger age than the legal age. The 

results also implied a relationship between illicit tobacco smoking and decreased physical health. 

The report said, “The public health message that emerges from our data is that people who smoke 

or have smoked illicit tobacco report significantly worse health than smokers of licit tobacco.” 

In addition, there is little evidence before TPSAC that banning menthol would significantly reduce 

overall smoking. Not only will greater numbers of smokers buy illicit menthol cigarettes, but other 

smokers undoubtedly will make their own through self-mentholation, buy cigarettes illegally over the 

Internet or through the mail, or roll their own cigarettes. At the January TPSAC meeting, a National 

Association of Attorneys General presentation showed that loose menthol tobacco (roll-your-own 

and pipe tobacco) are already available in the market as are menthol little cigars, which often look 

and smoke similar to cigarettes. 

Illicit tobacco markets undermine efforts to prevent underage smoking 

As illicit tobacco markets grow, the effectiveness of policies to prevent underage smoking 

diminishes. A robust black market with lower prices leads to sales unprotected by regulation and 

standard age checks by retailers. These new sales avenues create greater availability of cigarettes for 

adolescents and can increase adolescent smoking (Levinson 2011, Compass Lexecon 2010). If this 

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occurs, it would hinder the progress the United States has made toward reducing access to cigarettes 

for minors. 

Underage individuals gain greater access to cigarettes in black markets because smugglers, “white 

van” salesmen and street corner vendors do not worry about age verification. Canadian studies of 

cigarette butts collected at high schools confirm this conclusion. They show that an increasing 

number of teens are acquiring contraband tobacco as that country’s black market expands. A 2007 

study showed that roughly 35 percent of cigarette butts collected near Quebec high schools were 

contraband (CCSA 2009). TPSAC was presented with evidence from Canada that the burgeoning 

black market there had the effect of increasing youth access to cigarettes: 

“Provinces that suffered the greatest increase in black market sales – specifically Ontario and 

Quebec – saw teen smoking increase relative to the rest of Canada. Between 1991 and 1994 

– the period during which black market sales peaked, as discussed above – smoking 

prevalence among 15- to 19-year-olds rose by 35 percent in Ontario and by 14 percent in 

Quebec. By contrast, in the rest of Canada, smoking prevalence among 15- and 19-year-olds 

rose by only 10 percent between 1991 and 1994. This result suggests that substantial growth 

in black market sales can affect youth smoking.” (Compass Lexecon). 

For underage smokers, a contraband market not only serves as a major tobacco source but also 

provides them cigarettes that contain ingredients and constituents potentially even more dangerous 

than lawful cigarettes. 

Expansion of criminal enterprises, requiring increased spending by law enforcement 

As the Department of Treasury notes, enforcement measures aimed today at black market tobacco 

operations are “insufficient to countervail the lure of high profit potential” (Dept. of Treasury 2010). 

This same report to Congress says that “illicit trade has been linked to organized crime and violent 

crime, and poses a serious risk to our national security.” The ATF also recently noted, “Organized 

criminal groups, including those with ties to terrorist organizations, have increasingly engaged in the 

illegal trafficking of tobacco products, particularly counterfeit and lawfully manufactured cigarettes 

(2010). 

The associated increases in crime, given a larger black market, will undoubtedly require more 

government spending on law enforcement, courts and prisons if government chooses to combat the 

problem. 

To our knowledge there is no estimate for added expenditures necessary to ensure effective 

enforcement of today’s contraband problem, much less the additional costs to enforce a significantly 

expanded contraband market if menthol cigarettes are banned. Nonetheless, effective enforcement 

would almost certainly include several initiatives, such as: 

•	 Increased coordination with domestic and international law enforcement partners to identify 

and target criminal organizations 

•	 Development and support of innovative law enforcement models to target and disrupt 

smuggling and distribution networks 

•	 Coordination with judicial officials to ensure appropriate application of federal mandates 

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• Mechanisms to deter organized crime’s involvement in the trade of illicit tobacco 

• Intelligence assessments on contraband tobacco 

• Adding more law enforcement personnel 

Initiatives like these would be expensive and would be difficult to fund in an era of limited federal 

and state resources. Properly funding enforcement efforts might require diverting resources from 

fighting other crime issues, a step that federal agencies have not been willing to take so far. For 

example, the 2009 Inspector General Report (USDOJ 2009) commented: 

“ATF has placed a lower priority on its alcohol and tobacco diversion mission area 

compared with its other mission areas involving firearms, arson, and explosives. 

Proportionately, ATF commits few resources to its diversion mission....” 

“We recognize that the number of investigations does not always reflect the amount of work 

conducted because diversion cases can be large, include numerous targets, and can take a 

long time to develop. However, we found other indications of ATF’s lack of emphasis on 

its diversion mission, including minimal resources and staffing levels for the diversion 

mission, and field structures that do not include diversion groups. Consequently, ATF’s 

diversion program has neither adequate resources nor an adequate structure for addressing 

the significant tax revenue losses to state and federal governments caused by tobacco 

diversion and its potential links to other criminal activities.” 

Impact on urban communities 

In testimony and statements to TPSAC, representatives of groups who regularly work in urban 

communities voiced concern about the practical impact of a menthol ban on urban communities. 

The National Organization of Black Law Enforcement Executives (NOBLE), for example, 

expressed concern about the ramifications of a contraband market in which counterfeit and 

smuggled cigarettes are sold on the streets and neighborhoods (NOBLE 2010). In their statement 

NOBLE noted, “If unregulated sales to minors spike through street sales in African American 

communities, it would create a problem for law enforcement – potentially even leading to wrongful 

and selective prosecutions, and to what end?” 

Mark Little, former chair of The National Black Chamber of Commerce and director of Maryland 

Chamber of Commerce, testified that a ban would cause the current illicit market to expand (Little 

2010): 

“It is not a stretch to believe that it would be controlled by organized crime, or that street 

sales would increase in black communities, or that unregulated sales to minors would 

increase. Is this how the FDA wants our police, prosecutors and judges spending their time 

– by policing unregulated sales to minors of cigarettes, and an upsurge in contraband sales, 

all due to a decision that lacks scientific credibility? When it comes to menthol, it is this 

committee’s job to present a credible decision to Americans in general, and specifically to 

black Americans.” 

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Similar sentiments were expressed at a TPSAC meeting by a representative of the Congress of Racial 

Equality (CORE). 

“Your study is highly significant and symbolic for the African-American community for the 

simple reason that menthol cigarettes are indeed popular with blacks. It’s no secret that 

menthol cigarettes provide a taste and flavor that is preferred by many African-Americans, 

some even call it in my community the black man’s cigarette.” 

“...there are significant indications that a ban on menthol would boomerang and create a 

bad situation in our community. It is CORE’s hope that the advisory panel will fulfill its 

requirement of considering the unintended consequences of a ban on menthol cigarettes. 

Any recommendation must be grounded in a real world understanding of the devastating 

impact that illegal counterfeiting, smuggling, distribution and consumption of cigarettes has 

on our lives and on our streets.” 

“If smokers were a captive population and tobacco products a captive industry, you might 

be able to make a case that banning menthol could work. But because there would be a 

strong demand fed by many alternative sources of cigarettes, banning menthol would be a 

self-defeating and indeed a very harmful step for my community. It would drive more 

smokers to unlicensed, unregulated, side of the street, and more troubling, it would give 

underage access to kids making it easy for them to smoke unregulated cigarettes. And we 

have to ask ourselves, is that really what we want to do.” 

“If menthol is banned, history shows that a large underground market would be created and 

many questions should follow. They involve questions of how effective contraband tobacco 

enforcement has been to date and the cost of additional law enforcement.” (CORE 2011) 

Foregone government revenue 

A substantially expanded black market means that federal, state and local governments would 

experience significant reductions in cigarette excise tax collections. According to the Altria report 

(2010), previously mentioned, the sale of cigarettes generated approximately $37.7 billion in federal, 

state and local government revenues in fiscal year 2009. Menthol cigarettes accounted for 

approximately 27 percent of the U.S. taxed cigarette base that year. As a result, if all menthol 

cigarettes were removed from the taxed cigarette market, up to $10.2 billion in government 

revenues, including Tobacco Settlement Agreement (TSA) monies, would be lost. See Table 7-2. A 

significant part of these taxes and TSA funds are earmarked for specific purposes, including 

education and children’s health care programs. 

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Table 7-2.	 Estimated fiscal 2009 cigarette revenue by category, based on the 

assumption that menthol cigarettes made up 27% of the U.S. taxed 

cigarette market that year ($ billion) 

Revenues Total1 Menthol2 

Federal excise tax 8.5 2.3 

State excise tax 15.8 4.3 

State sales tax 4.1 1.1 

Local excise tax 0.5 0.1 

[T]SA 8.8 2.4 

Total $37.7 billion $10.2 billion 1 Orzechowski and Walker (2009), The Tax Burden on Tobacco (44). Prepared with the financial support of 

Altria Client Services, the Lorillard Tobacco Company, and Reynolds American. 

2 Menthol revenue calculations are estimated based upon a 27% market share assumption; state figures do 

not represent a weighted-average calculation. 

Table reproduced from Altria Report, Table 4.1 

Because the illegal movement of tobacco is an international problem that crosses porous borders, 

lost government revenue is likewise an international problem (Lencucha and Callard 2011). A study 

of 12 diverse countries (excluding the United States) found that the lost excise tax revenue between 

2003 and 2008 for the most-sold brand ranged from more than $23 million a year in Ecuador to 

almost $5 billion a year in the UK. Along with the lost revenue, it added: “Illicit trade compromises 

health outcomes to the extent that it undermines price strategies, labeling requirements or other 

policies aimed at reducing the demand for tobacco products... For the countries we studied, lost 

revenue due to the illicit trade of cigarettes is higher than government investments in tobacco 

control.” 

Loss of jobs dependent in whole or part on the legal sale of menthol cigarettes 

Many thousands of working Americans rely upon menthol sales beyond the factory workers who 

manufacture them. According to the Altria study, nearly 500,000 American jobs depend in whole or 

part on the legal sale of menthol cigarettes (2010). 

Job losses would vary along the stage of the tobacco value chain, but are likely to have a 

disproportionate impact on small, independent convenience store owners, tobacco growers and 

independent distributors to convenience stores. See Table 7-3 below. The sad truth is that a ban of 

menthol cigarettes would cost jobs in the United States, only to replace them with jobs overseas at 

contraband manufacturers. 

223
Chapter 7 

 

 

 

 

 

Table 7-3. Summary of employment across the tobacco value chain 

Growers Processors & 

Manufacturers 

Distributors & 

Transportation 

Selling 

Organizations 

Primary activities Farm, harvest, 

cure, grade and 

wholesale 

tobacco leaf 

Procure, process, 

pack and supply 

tobacco for the 

manufacture of 

cigarettes 

Warehousing and 

transport of 

cigarettes to retail 

outlets 

Retail outlets 

such as 

convenience 

stores that sell 

cigarettes to 

adults 

Estimated total 

employment 

62,000 19,000 40,000 Convenience 

only: 1-1.5 

million. 

Other outlets: 4-5 

million 

Jobs at risk if all 

menthol cigarette 

volume were 

eliminated 

25,000 3,500 3,000 475,000 

Table reproduced from Altria Report, Table 5.1 

Building the Knowledge Base 

After passage of the Act, the Center for Tobacco Products at FDA noted the importance of building 

a “knowledge base required for meaningful regulation of tobacco products...” (Deyton et al. 2010). 

However, TPSAC has not developed the knowledge base sufficient to assess the countervailing 

health impacts of a ban, including the effects of contraband. In fact, TPSAC received only one onehour background briefing on the topic. Industry and other interested groups provided substantial 

information regarding the unintended consequences of a menthol ban, but that was limited to 

written public submissions and oral comments during the public session of meetings in which 

speakers were provided 5-10 minutes to speak. 

Congress explicitly asked TPSAC to address the issue of contraband. From the day TPSAC 

convened its first meeting on March 30, 2010, it had the opportunity and the responsibility to help 

build a knowledge base in the countervailing impact of menthol regulation, including the adverse 

public health impact of creating an expanded contraband market. 

Such steps should have included engaging various components of the federal government that deal 

with tobacco diversion on a daily basis, such as the Bureau of Alcohol, Tobacco, Firearms and 

Explosives, and the Alcohol and Tobacco Tax and Trade Bureau (TTB); commissioning studies and 

white papers; seeking advice from law enforcement agencies and experts who deal with these issues 

on a daily basis; commissioning studies on the adverse health impact of ingredients in contraband 

cigarettes from expert scientists and researchers at the U.S. Centers from Disease Control and 

Prevention; consulting with other federal and state experts; seeking testimony from international 

experts about the capacity to produce illicit cigarettes in China, Eastern Europe and elsewhere; and 

assessing the experience of other countries in determining the impact of unregulated contraband 

sales on youth smoking rates. 

224
 

 

 

 

 

 

 

 

 

 

 

TPSAC, however, eschewed all of these avenues. It is too late now to remedy the unmistakable 

omissions in TPSAC’s public record. It is hoped that TPSAC’s final report – underway at this 

writing – acknowledges these deficiencies and its incomplete effort to study the “countervailing 

effects” as Congress mandated. FDA, nonetheless, must rigorously assess the countervailing effects 

of any potential regulation of menthol cigarettes. 

A rigorous assessment must include: 

1.	 Economic studies assessing the likely size and impact of an expanded contraband market if 

menthol cigarettes are restricted or banned: Assess the size of today’s contraband market in the 

United States and provide a range of estimates on the size of an expanded contraband market if 

menthol cigarettes are restricted or banned. 

2.	 Public health assessments of contaminants in illicit cigarettes and their impact on public health: 

Assess the ingredients and constituents found in samples of counterfeit cigarettes now sold in 

the United States, such as toxic metals like lead, along with the tar, nicotine and carbon 

monoxide levels; assess the increased health risks posed by the prevalence of contraband 

cigarettes in other countries that might be diverted to the United States. 

3.	 Research regarding the adverse health consequences caused by undermining youth anti-smoking 

efforts: Assess how the expected increased illicit cigarette trade jeopardizes progress on 

reducing underage initiation and thus runs contrary to the Act’s goals of further helping prevent 

underage access. 

4.	 Research regarding the impact of increased black market cigarette activity on criminal activity, 

and the added cost burdens to law enforcement: Evaluate the entirety of the tobacco products 

diversion problem -- whether additional controls are needed, the likelihood of associated 

criminal activity, and an assessment of efforts and resources needed, including their costs, to 

enforce any regulation or ban of menthol cigarettes. 

These topics demand conscientious study because of the possibilities of unintended consequences of 

any action to restrict or ban menthol cigarettes. Economic and political history shows that any 

regulatory intervention in complex social and economic systems can create unintended 

consequences. When regulatory actions impose a new set of circumstances upon consumers, 

governments cannot always predict how the market – people – will react (Scanlon 2011). Often the 

unintended consequences are more harmful than the problem they intended to solve. 

Two recent examples of unintended consequences in other arenas are instructive. One involves 

online gambling. Even though online gambling was effectively made illegal in 2006, several sources 

forecast that the industry has actually expanded in size since then. Another example is the result of 

laws enacting electronic systems to track the sales of cold medicine used to make methamphetamine. 

After reviewing Drug Enforcement Agency data from 2000 to 2009, the Associated Press reported 

that the “lure of such easy money has drawn thousands of new people into the methamphetamine 

underworld over the last few years.” Further, the Associated Press noted the tracking system “failed 

to curb the drug trade and instead created a highly lucrative market for profiteers...” (USA Today 

2011) 

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CONCLUSION 

A comprehensive public health assessment and recommendation on the impact of the use of 

menthol cigarettes must include a thorough inquiry into the illegal tobacco problem in the United 

States. It is a fundamental and indispensable piece of the public health puzzle and is required to be 

considered under the Act. 

As this chapter shows, today’s illegal tobacco market already poses daunting challenges for 

government, retailers, and the public health community in the United States. Banning menthol 

cigarettes would fuel a larger illegal cigarette market and result in negative impacts on public health. 

The negative impacts on public health would be: 

•	 Thousands upon thousands of Americans, both young and old, will be exposed to more 

harmful ingredients and constituents and thus deprived of the significant benefits of the Act. 

A ban would lead to the increased availability of illegal cigarettes that do not comply with 

regulations that apply to the rest of the tobacco industry, such as ingredient and constituent 

reporting and disclosures. 

•	 The expanded sales of contraband cigarettes will increase youth access to tobacco. For 

decades, successive governments have worked to keep cigarettes out of the hands of youth. 

Sellers of illicit cigarettes, however, flout the law. They do not care about age verification, 

undermining tobacco control programs. 

•	 Criminal networks that traffic in illegal cigarettes will expand. Tobacco trafficking and 

organized crime often go hand in hand. As official U.S. government reports cite, these 

criminal networks today also traffic in drugs, firearms and alcohol. Lured by additional and 

large profits from selling illicit menthol cigarettes, criminal organizations will expand their 

operations, distribution, and sales. The increased profits will fund other criminal activities, 

such as drug and gun trafficking. 

•	 The increased crime that results from more smuggling will require greater government 

spending on law enforcement, courts and corrections. At a time when federal and state 

governments are entering an era of budget deficits, a menthol ban would place a significant 

“unfunded mandate” on governments. Governments will be forced to devote more 

resources, including financial resources, to law enforcement efforts to combat the black 

market and other illegal activities. 

•	 At the same time, an increase in contraband tobacco sales – and a resulting decrease in licit, 

regulated sales – will mean lost revenues for federal and state governments. Menthol 

cigarettes generated more than $10 billion in federal, state and local government revenues in 

2009. 

•	 Thousands of jobs will be at risk. Up to 500,000 jobs depend wholly or in part on menthol 

cigarette sales. With a shift of sales from legal to illegal markets, banning menthol cigarettes 

will affect thousands of jobs. 

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By passing the Family Smoking Prevention and Tobacco Control Act, Congress specifically granted 

FDA the authority to regulate tobacco products in order to regulate the manufacture and sale of 

cigarettes. However, if FDA were to impose a ban on the sale of menthol cigarettes, it would result 

in severe unintended consequences including exacerbating an already troubling illicit tobacco trade, 

creating an unregulated contraband market and undermining the precise public health safeguards 

that Congress intended. 

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worse health than other smokers. Nicotine Tob Res. 11(8) 996-1001. 

Altria Client Services. 2010. Countervailing effects of a ban on menthol cigarettes. Presented at: 

TPSAC, 10 Feb 2011. Public submission for January 25, 2010 TPSAC meeting. Cohen C, recipient. 

30 Dec 2010. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM246043.pdf. 

American Wholesale Marketers Association. 2011. Testimony by: Scott Ramminger (President and 

CEO) to TPSAC, 17 March. 

Bryans D (President of Ontario Convenience Store Association). 2011. Testimony to TPSAC, 10 

Jan. Public submission for February 10, 2011 TPSAC meeting. Cohen C, recipient. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM243630.pdf. 

Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF). 2010. Fact Sheet, ATF Tobacco 

Diversion. Available at: http://www.atf.gov/publications/factsheets/factsheet-tobaccodiversion.html. 

Canadian Convenience Stores Association (CCSA). 2009. Time for Action. Available at: 

http://www.productdisplayban.com/NR/rdonlyres/FF8F67CA-AA88-4F81-8883-

3F51370201FF/0/CCSA_Contraband.pdf. 

Compass Lexecon. 2010. Estimating consequences of a ban on the legal sale of menthol cigarettes. 

Presented at: TPSAC, 18 Nov and 10 Jan 2011. Public submission for January 10, 2011 TPSAC 

meeting with resubmission for corrections for February 10, 2011 TPSAC meeting. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM243622.pdf. 

Congress of Racial Equality (CORE). 2011. Testimony to TPSAC, 2 Mar. 

Deyton L, Sharfstein J, Hamburg M. 2010. Tobacco Product Regulation – A Public Health 

Approach. New England J Med. 362:1753-1756. 

Family Smoking Prevention and Tobacco Control Act. 2009. Pub. L. No. 111-31. 22 June. 

GfK Research Dynamics. 2008. Illegal Tobacco Sales: A Crisis for Canadians. Canadian Tobacco 

Manufacturer’s Council. Available at: http://www.stopcontrabandtobacco.ca/pdf/2008gFk.pdf. 

U.S. Government Accountability Office (GAO). 2011. Illicit Tobacco: Various Schemes Are Used 

to Evade Taxes and Fees. Available at: http://www.gao.gov/products/GAO-11-313. 

Law Enforcement Alliance of America. 2010. Public submission for September 27, 2010 TPSAC 

meeting. Clark C, recipient. 16 Sep. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM232837.pdf. 

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Lencucha R, Callard C. 2011. Lost revenue estimates from the illicit trade of cigarettes: a 12-

country analysis. Tob Control. [Epub ahead of print]. 

Levinson B. 2011. An Inquiry into the Nature, Causes and Impacts of Contraband Cigarettes. 

Center for Regulatory Effectiveness Monograph. Public submission for February 10, 2011 TPSAC 

meeting. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM243625.pdf. 

Little, Mike (former chair of National Black Chamber of Commerce and director of Maryland 

Chamber of Commerce). 2010. Testimony to TPSAC, 18 Nov. 

Maryland Association of Tobacco Candy Distributors. 2010. Public submission for November 18, 

2010 TPSAC meeting. Cohen C, recipient. 9 Nov. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM238840.pdf. 

National Association of Attorneys General. 2011. Potential Market Reaction to a Ban on Menthol 

Cigarettes. Presented at: TPSAC, 10 Jan. 

National Association of Convenience Stores. 2010. Presented at: TPSAC, 18 Nov 2011. Public 

submission for July 15, 2010 TPSAC meeting with resubmission for September 27, 2010 TPSAC 

Menthol Subcommittee meeting. Stark C, recipient. 16 Sep. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM232841.pdf. 

National Black Chamber of Commerce (NBCC). 2011. Testimony by: Harry C. Alford (President 

and CEO) to TPSAC, 17 March. 

National Organization of Black Law Enforcement Executives (NOBLE). 2010. Public submission 

to September 27, 2010 TPSAC meeting. Clark C, recipient. 16 Sep. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM232843.pdf. 

National Troopers Coalition (NTC). 2010. Public submission to September 27, 2010 TPSAC 

meeting. Stark C, recipient. 27 Sep. Available at: 

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/TobaccoProd 

uctsScientificAdvisoryCommittee/UCM232845.pdf. 

Orzechowski W, Walker RC. 2009. The tax burden on tobacco. Arlington, VA: vol. 44. 

Pappas RS, Polzin GM, Watson CH, Ashley DL. 2007. Cadmium, lead and thallium in smoke 

particulate from counterfeit cigarettes compared to authentic US brands. Food Chem Toxicol. 45(2) 

202-209. 

Salter J. Data: Cold-medicine tracking opened up meth black market. USA Today. 11 Jan. 

Scanlon, T. Letter to: TPSAC. 10 Jan 2011. 

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Swami K, Judd CJ Orsnini J. 2009. Trace metals analysis of legal and counterfeit cigarette tobacco 

samples using inductively coupled plasma mass spectrometry and cold vapor atomic absorption 

spectrometry. Spectrosc Lett. 42(8):479-490. 

Task Force on Illicit Tobacco Products. 2009. Report On The Status Of The Contraband Tobacco 

Situation In Canada. Presented to: the Minister of Public Safety Canada; Jul. 

U.S. Department of Justice, Office of the Inspector General. 2009. The Bureau of Alcohol, 

Tobacco, Firearms and Explosives’ Efforts to Prevent the Diversion of Tobacco. Available at: 

http://www.justice.gov/oig/reports/ATF/e0905.pdf. 

U.S. Department of the Treasury. 2010. Department of Treasury Report to Congress on Federal 

Tobacco Receipts List Due to Illicit Trade and Recommendations for Increased Enforcement. 5. 

U.S. First Written Submission. 2010. United States – Measures Affecting the Production and Sale 

of Clove Cigarettes (DS406). 16 Nov. Available at: 

http://www.worldtradelaw.net/wtodisputesubmissions/us/DS406_USFirstWrittenSubmission.pdf. 

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CHAPTER 8. 

CONCLUSIONS
 

TPSAC has been charged with issuing a report and recommendation to FDA on the impact of 

menthol in cigarettes on public health, including such use among children, African Americans, 

Hispanics, and other racial and ethnic minorities. This Industry Menthol Report is respectfully 

submitted to aid FDA in making a science-based regulatory decision regarding whether menthol 

cigarettes affect public health disproportionately compared to nonmenthol cigarettes. 

The Industry’s review was conducted with an emphasis on sound science. The relevant literature 

was identified through a comprehensive literature search and literature on each topic was evaluated 

in a rigorous manner. Conclusions related to each relevant topic were based on the most 

methodologically sound studies and those that were best able to support inferences related to 

menthol. Weight-of-the-evidence conclusions about causal inferences were developed according to 

the framework developed by the Surgeon General’s Reports. This framework has been applied for 

decades to understand relationships between smoking and health. Importantly, for most of the 

endpoints of interest, there are sufficient data available to draw conclusions with confidence. The 

conclusions of the Industry Menthol Report are provided, topic by topic, with justification, below. 

MAJOR CONCLUSIONS OF THE REPORT 

The conclusions of the Industry Menthol Report comply with FDA’s mandate to “follow the 

science.” 

Using the Surgeon General’s framework for assessing causality, a synthesis of the reliable data on the 

use of menthol in cigarettes, including data relating to its impact on disease and smoking behavior, 

leads to the conclusion that the “evidence is suggestive of no causal relationship” between 

menthol cigarettes and any disproportionate impact on the public health as a whole or for any 

demographic group when compared to nonmenthol cigarettes. As a result, there is no scientific 

basis to support the regulation of menthol cigarettes any differently than nonmenthol cigarettes. 

Demographics of Menthol Cigarette Preference and Current Trends in Smoking Prevalence 

Smoking prevalence refers to estimates of cigarette use among the overall population, whereas 

smoking preference refers to the percentage of smokers who smoke a particular type of cigarette 

(e.g., menthol versus nonmenthol). An increase in smoking prevalence in the population could 

represent an adverse population-level effect, while higher preference for a particular cigarette type 

that does not provide any increased risk for disease or adversely impact smoking behavior among a 

declining smoking population would not. Cigarette smoking in the overall population (prevalence) 

has steadily declined during the last two decades, irrespective of race/ethnicity, sex and age category. 

Menthol cigarettes are used by only a quarter of the smoking population (preference). The majority 

of all menthol smokers are White. The vast majority of African American smokers prefer menthol 

cigarettes, and it is reported that female smokers prefer menthol more than male smokers. Some 

studies appear to suggest that menthol cigarette preference is also higher among younger as 

Chapter 8 

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compared to older smokers. During the last two decades, declines in smoking prevalence have 

generally been more pronounced for minorities (including African Americans), females and 

adolescents, despite their preference for menthol. Also, prevalence of African American adolescent 

smoking is far below that of White adolescent smoking. 

Menthol in Cigarettes Does Not Change the Inherent Health Risks of Cigarette Smoking 

The available epidemiologic studies clearly demonstrate that smokers of menthol cigarettes are at no 

greater risk of developing chronic smoking-related diseases than are nonmenthol smokers. The 

number of studies and their consistency make it possible to draw this conclusion with confidence. 

While all epidemiology studies have limitations, the available studies are well-designed and wellanalyzed. The diseases studied include lung cancer (the most common smoking-related cancer), 

cancers of the upper aerodigestive tract (esophagus, larynx, oropharynx), and other cardiac and lung 

outcomes. The studies provide data on risks specific to both sexes and to both Whites and African 

Americans, and do not find that there is any subpopulation of menthol smokers who incur increased 

risks compared to nonmenthol smokers. Thus, it can be concluded that, according to the Surgeon 

General’s framework for assessing causality, the “evidence is suggestive of no causal 

relationship” between the use of menthol cigarettes and increased smoking-related disease risk 

above that caused by use of nonmenthol cigarettes. 

Menthol in Cigarettes Has No Meaningful Effect on Smoking Biomarkers 

The vast majority of studies of biomarkers of exposure to smoke constituents and biomarkers of 

potential harm have found no meaningful differences between menthol and nonmenthol smokers. 

The body of available scientific evidence from biomarker studies leads to the conclusion that the 

“evidence is suggestive of no causal relationship” between the use of menthol cigarettes and 

increases in biomarkers of exposure and potential harm over and above those caused by the 

smoking of nonmenthol cigarettes. 

Evidence on Menthol and Smoking Topography is Inadequate to Support a Conclusion that 

Menthol Cigarettes are Smoked More Intensely 

The available studies on menthol cigarettes and smoking topography differ in the ways that they 

attempt to measure smoking variables such as puffing, depth, volume and frequency; and many have 

weaknesses (e.g., small numbers of subjects, use of cigarettes differing in yield and menthol content, 

etc.). This makes it difficult to compare the studies and to reach definitive overall conclusions 

regarding these aspects of smoking topography. Although the findings are somewhat inconsistent, 

the majority of studies find no significant differences between menthol and nonmenthol smokers in 

smoking topography variables. These data provide no support for the presence of a clear and 

consistent association between menthol smoking and an adverse impact on smoking topography and 

provide no convincing support for the suggestion that menthol increases the exposure to smoke 

constituents through effects on smoking behavior. However, given the inconsistencies that exist, 

the “evidence is inadequate to infer the presence or absence of a causal relationship” 

between use of menthol cigarettes and adverse impacts on smoking topography. When placed in the 

context of the epidemiology and biomarker evidence referenced above, there is no reason to 

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conclude that smoking topography differences, if any, lead to any increased health risks over those 

of nonmenthol cigarettes. 

Menthol in Cigarettes Does Not Adversely Impact the Toxicologic Properties of 

Mainstream Smoke 

Toxicology studies show that menthol has no notable effects at exposures spanning the ranges 

typical for its flavor application in cigarettes. Additionally, the weight of the evidence on the 

toxicologic properties of the mainstream smoke from menthol cigarettes compared with 

nonmenthol cigarettes provides no indications of increased toxicity, consistent with a broader 

conclusion that menthol has no causal relationship to adverse impacts on public health. This leads 

to the conclusion that the “evidence is suggestive of no causal relationship” between menthol 

added to cigarettes and increases in the toxicity of cigarette smoke. 

Menthol in Cigarettes Does Not Meaningfully Alter the Chemical Composition of 

Mainstream Smoke 

The weight of the evidence clearly shows that the chemical compositions of the mainstream smoke 

from menthol and nonmenthol cigarettes are very similar, apart from the presence of menthol itself. 

Thus, the “evidence is suggestive of no causal relationship” between the use of menthol in 

cigarettes and potentially harmful changes in mainstream smoke chemistry. 

Evidence is Inadequate to Conclude that Menthol in Cigarettes Influences Smoking 

Initiation 

Smoking initiation rates have not changed significantly over the past decade. In addition, menthol 

smokers report later onset of initiation as compared to nonmenthol smokers. While some studies 

report that younger smokers have a higher preference for menthol cigarettes than older smokers, 

there are no studies that directly examine cigarette type (menthol versus nonmenthol) at the time of 

initiation. Although these data are suggestive of no causal relationship between menthol cigarette 

use and adverse smoking initiation behaviors, they do not directly address the cigarette type used to 

initiate smoking. Thus, using the Surgeon General’s framework for assessing causality, it must be 

concluded that the “evidence is inadequate to infer the presence or absence of a causal 

relationship” between menthol cigarette use and adverse smoking initiation behaviors, including 

higher or earlier smoking initiation by the general population or by subpopulations. 

Menthol in Cigarettes Has No Meaningful Impact on Smoking Cessation 

Review of the methodologically sound literature on menthol smoking and cessation demonstrates 

that the most relevant studies – those that address successful long-term quitting – do not indicate 

that smokers of menthol cigarettes are less likely to quit than smokers of nonmenthol cigarettes. 

There are a sufficient number of high-quality studies that consistently find that menthol has no 

meaningful impact on smoking cessation. A few studies (three cross-sectional studies and one of a 

smoking cessation clinic) reported some lower cessation rates among non-White menthol smokers 

only. However, if menthol is a factor that affects the ability to quit smoking, one would expect to 

see consistency among White and non-White subjects. This race-associated inconsistency suggests 

that some other factor, possibly related to socioeconomic status or genetics, affects the ability to 

quit, rather than menthol itself. Given the number of high-quality studies that consistently find that 

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menthol cigarette use has no meaningful impact on smoking cessation, using the Surgeon General’s 

framework for assessing causality leads to the conclusion that the “evidence is suggestive of no 

causal relationship.” 

Menthol in Cigarettes Has No Meaningful Impact on Nicotine Dependence 

Review of the methodologically sound literature on menthol smoking and measures of nicotine 

dependence demonstrates that menthol smokers are not any more dependent on nicotine than 

nonmenthol smokers, as assessed by a variety of measures including cigarettes per day (CPD), time 

to first cigarette (TTFC), and Fagerström Test for Nicotine Dependence (FTND). There are a 

sufficient number of studies, and they are consistent in their results. Menthol smokers do not 

smoke significantly more CPD than nonmenthol smokers; in fact, half of the studies reported that 

menthol cigarette smokers report significantly fewer CPD than nonmenthol smokers. Similarly, 

menthol and nonmenthol smokers do not differ significantly on composite measures of dependence. 

With respect to the studies that evaluated TTFC, half found no difference between menthol and 

nonmenthol smokers and about half found that menthol smokers had significantly shorter TTFC 

than nonmenthol smokers, but this was true only among limited subgroups of subjects. Given both 

the number of high-quality studies and their overall consistent findings, it is reasonable to conclude 

that the “evidence is suggestive of no causal relationship” between smoking menthol cigarettes 

and significantly increased levels of nicotine dependence. 

Numerous Hypotheses Put Forth by TPSAC are Speculative and Cannot Serve as the Basis 

for Regulatory Policy 

From review of meeting transcripts and presentations given at TPSAC meetings, it is apparent that 

committee members are concerned about a number of unfounded hypotheses. For example, 

TPSAC has addressed whether menthol cigarettes are perceived by menthol smokers as less harmful 

than nonmenthol cigarettes. The data show that this is not true. This and other speculative 

hypotheses are addressed in Chapter 6. 

A Ban on Menthol Cigarettes Will Result in Significant Countervailing Effects 

If a ban were imposed on menthol cigarettes, despite the scientific evidence that does not support 

regulating menthol cigarettes differently than nonmenthol cigarettes, the evidence unequivocally 

shows that the result would be a dramatically larger illegal cigarette market than currently exists. As 

a result, there also would be severe negative impacts on public health, including exposure of 

smokers to more harmful contraband cigarettes, increased access of youth to tobacco, increased 

criminal activity particularly in urban communities, reduced government revenues and loss of jobs. 

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