Reference	Addendum:	
 

Preliminary	Scientific	Evaluation	of	the	Possible	

Public	Health	Effects	of	Menthol	versus	

Nonmenthol	Cigarettes	
 

Food and Drug Administration
         

                         

               

             

   

       

           

           

       

   

       

   

                   

                   

               

       

               

   

   

           

     

       

Contents

Smoke chemistry and nonclinical toxicology ................................................................................................ 3
 

Smoke chemistry....................................................................................................................................... 3
 

Menthol as a singular compound – toxicology, pharmacology and therapeutic applications.................4
 

Antiproliferative effects of menthol as a singular compound.................................................................. 4
 

In vitro toxicity of menthol tobacco exposure.......................................................................................... 4
 

Conclusion................................................................................................................................................. 5
 

Physiology ..................................................................................................................................................... 5
 

Sensory effects.......................................................................................................................................... 5
 

Mechanisms of menthol action ................................................................................................................ 6
 

Effect of menthol on smoking topography ............................................................................................... 8
 

Conclusion................................................................................................................................................. 8
 

Biomarkers.................................................................................................................................................... 8
 

Biomarkers of exposure to Carbon Monoxide (CO).................................................................................. 8
 

Biomarkers of exposure to nicotine.......................................................................................................... 9
 

Menthol and Nonmentholsmokers........................................................................................................ 11
 

Biomarkers of exposure to TSNAs........................................................................................................... 11
 

Conclusion............................................................................................................................................... 12
 

Patterns of Use............................................................................................................................................ 12
 

Tobacco use supplement to the current population survey (CPS‐TUS).................................................. 12
 

National Survey on Drug Use and Health (NSDUH) ................................................................................ 12
 

National Health and Nutrition Examination Survey (NHANES)............................................................... 12
 

National Youth Cessation Survey............................................................................................................ 13
 

Conclusion............................................................................................................................................... 13
 

Marketing and Consumer Perception of Risk ............................................................................................. 13
 

Marketing................................................................................................................................................ 13
 

Marketing strategies........................................................................................................................... 13
 

Consumer Perceptions............................................................................................................................ 14
 

Conclusion............................................................................................................................................... 14
 

Initiation and Progression to Regular Use .................................................................................................. 14
 

First smoking experience ........................................................................................................................ 14
 

Progression to regular smoking .............................................................................................................. 15
 

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Conclusion............................................................................................................................................... 15
 

Dependence ................................................................................................................................................ 16
 

Time to first cigarette (ttfc)..................................................................................................................... 16
 

Cigarettes per day (cpd).......................................................................................................................... 16
 

Scales of nicotine dependence ............................................................................................................... 17
 

Industry documentsresearch ................................................................................................................. 17
 

Conclusion............................................................................................................................................... 17
 

Cessation..................................................................................................................................................... 17
 

Cohortstudies......................................................................................................................................... 17
 

Cross‐sectionalstudies............................................................................................................................ 18
 

Industry documentsresearch ................................................................................................................. 19
 

Conclusion............................................................................................................................................... 19
 

Disease Risk................................................................................................................................................. 19
 

Lung cancer............................................................................................................................................. 19
 

Multiple cancers...................................................................................................................................... 19
 

Multiple non‐cancer diseases................................................................................................................. 19
 

Conclusion............................................................................................................................................... 20
 

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Reference Addendum to the “Preliminary

Scientific	Evaluation of the	Possible

Public Health Effects of Menthol versus

Nonmenthol Cigarettes”

The “Preliminary Scientific Evaluation of the Possible Public Health Effects of Menthol versus

Nonmenthol Cigarettes” was submitted for Peer Review in August 2011. Since that time, several peer‐

reviewed articles have been published that relate to this topic. This reference addendum provides a

summary of updated research relevant to the full scientific review.

On March 27, 2013, a systematic literature search was conducted in the PubMed database using the

search term “menthol” and including articles published between July 1, 2011 and March 27, 2013. As

with the full scientific review, only original peer‐reviewed publications were used. Basic information on

menthol has been included here only as background; as with the full scientific review, this addendum is

not intended to be a comprehensive review of menthol itself but rather menthol as related to its use in

menthol cigarettes. General methodology caveats (e.g., self‐report) and descriptions(e.g., TRPM8

channels, large nationalsurveys) were discussed in the full scientific review, and will not be duplicated

here.

NOTE: The 2012 SGR, “Preventing Tobacco Use Among Youth and Young Adults”, did not contain any

information on the public health effects of menthol versus nonmenthol cigarettesthat was not included

in the original report.

Smoke chemistry and nonclinicaltoxicology

Seven additional articles regarding the association between menthol in cigarettes and smoke chemistry

and nonclinical toxicity were reviewed.

Smoke chemistry

One study compared the Federal Trade Commission (FTC)‐measured nicotine levels of menthol and

nonmenthol cigarette brands smoked by smokers who participated in the 2001‐2006 National Health and

Nutrition Examination Survey (NHANES), a nationally representative household survey. Participants

either provided a cigarette pack or information on their usual brand, and Universal Product Code

information was used to verify menthol versus nonmenthol classification. The researchersfound that

the brands of menthol cigarettessmoked by African Americans had a higher average FTC nicotine level

than the menthol cigarettessmoked by White smokers(Caraballo et al., 2011).

In anotherstudy, cigarettes with four different menthol levels were created and smoked through a

linear‐portsmoking machine. The collected total particulate matter (TPM) was analyzed for menthol,

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nicotine, tobacco‐specific nitrosamines(TSNAs), polynuclear aromatic hydrocarbons, cotinine, and

quinolone, and whole smoke was collected for measurement of volatile organic compounds. Although

differencesin the amount of menthol present in the TPM existed, there were no differencesin any of

the other target constituents. Thus, while menthol in TPM increased in a linear fashion, the other

measured constituentsremained unchanged (Gordon et al., 2011).

Using the Health Canada method of machine smoking, Bodnar and colleagues (2012) compared levels of

19 constituentsin 61 brand styles of fire‐standard compliant cigarettes. The researchersfound few

differencesin the measured levels of constituents between menthol and nonmenthol cigarettes. In

some cases, for some styles, there were greater levels of a constituent (e.g., 2‐aminonaphathalene,

catechol) in menthol cigarettes, while levels of other constituents(e.g., benzo[a]pyrene, catechol,

crotonaldehyde) were greater for nonmenthol cigarettes. There was no consistent direction of

difference and, in the case of catechol, the difference occurred in the opposite direction when “full

flavor” and “lights” were compared (Bodnar, Morgan, Murphy, & Ogden, 2012).

Brinkman and colleagues (2012) examined participant‐specificmainstream smoke for 4‐

(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), nicotine, ultrafine and fine particulate matter by

simulated use (used topography measurements) using a programmable linear smoking machine.

Overall, the researchersfound no differencesin fine particulate matter between menthol and

nonmenthol test cigarettes. However, a significantly larger mass of ultrafine particulate was collected

from the menthol cigarettes(p<0.05) (Brinkman et al., 2012).

Menthol as a singular compound – toxicology, pharmacology and therapeutic

applications

Anotherstudy found that, when added to mucoadhesive patches, menthol increased permeability of the

oral mucosa, as measured with a porcine buccal tissue preparation. This allowed greater absorption of

fenretinide, a chemopreventive compound (Wu et al., 2012).

Antiproliferative effects of menthol as a singular compound

Valero and colleagues(2012) examined the effects of menthol on cell survival and cell proliferation of

normal and cancerous human prostate cell lines. The prostate‐derived cell lines were cultured,

expression of TRMP8 receptors was confirmed, and proliferation was estimated using the methyl

tetralam (MTT) assay (which assesses metabolic activity). Menthol increased metabolic activity but

there was no consistent change in growth after stimulation of TRPM8 channels with menthol (Valero,

Mello de, Stuhmer, Viana, & Pardo, 2012).

In vitro toxicity of menthol tobacco exposure

Fowler and colleagues(2012) treated six cell types (rodent cell lines V79, CHL and CHO, p‐53 competent

human peripheral blood lymphocytes, TK6 human lymphoblastoid cells, and the human liver cell line

HepG2) with racemic menthol. Treatment with menthol was cytotoxic. However, the authorssuggest

that this is a “false positive” since there was no genotoxic effect as measured by micronucleusinduction.

The authors note that testing was limited by cytotoxicity, and even though required levels of cytotoxicity

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were induced, micronucleusinduction was not (Fowler et al., 2012). Thus, the dose‐response curve may

have been too narrow to detect micronucleusinduction.

Conclusion

The addition of these articles did not change the finding of the full scientific review, namely that the

weight of evidence supportsthe conclusion that, from a nonclinical toxicity standpoint, menthol in

cigarettesis not associated with either increased or decreased smoke toxicity.

Physiology

Seventeen additional articles regarding the association between menthol in cigarettes and

physiological response to tobacco smoke were reviewed.

Sensory effects

The effect of menthol on cough threshold was evaluated in 13 subjects (12 nonsmokers) during single‐

inhalation capsaicin challenges. Inhalation of menthol vapor prior to measuring cough thresholds

resulted in reduced sensitivity to cough in some subjects. That is, for some, but not all, of the subjects,

the amount of capsaicin needed to trigger a cough response was increased following menthol vapor

exposure. The authors concluded that adding menthol to cigarettes may increase the tolerability of

tobacco smoke by reducing the sensitivity of an airway defense mechanism (coughing) (Wise, Breslin, &

Dalton, 2012).

A study of 14 patients with chronic cough and airway sensitivity to environmental irritants and 15

control subjects evaluated the effect of inhaling nebulized menthol on cough threshold provoked with

capsaicin inhalation. Inhaled menthol reduced cough sensitivity to the inhaled capsaicin and influenced

inspiratory flows in the patients, an effect that did not occur in the control group (p<0‐05).

Furthermore, in people with chronic cough (without asthma, chronic obstructive pulmonary disease or

infection), pre‐inhalation of menthol reduced the threshold to capsaicin‐stimulated cough (p<0.05). The

authorsstate that “the use of menthol in different cigarette brands could be questioned since it could

conceal the natural irritation following smoking” (Millqvist, Ternesten‐Hasseus,& Bende, 2013).

The somatosensory effects of topically‐applied capsaicin and menthol were assessed in a cross‐over

study with 15 subjects. When menthol was topically applied to the gingiva, nine subjectsreported mild

levels of pain. Pain ratings were lower than those reported following application of capsaicin, and were

also more short‐lived. Menthol elicited hypersensitivity to both cold and warm stimuli (Lu, Baad‐

Hansen, List, Zhang, & Svensson, 2013).

A laboratory study involving 22 adults (age 21‐46 years) investigated the effect of menthol on stimulated

nasal irritation. In this study, participantssimultaneously sniffed clean air into one nostril while sniffing

a chemical vapor into the other. Acetic acid and allyl isothiocyanate produced nasal irritation, and

menthol pretreatment had different effects. Menthol exposure prior to stimulation with acetic acid

resulted in decreased sensitivity to irritation but prompted increased sensitivity to allyl isothiocyanate

(p<0.005). Thus, menthol can modify irritating stimuli differently (Wise, Preti, Eades, & Wysocki, 2011).

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In anotherstudy, researchers applied the irritant capsaicin to the nasal mucosa in order to assess

threshold to cough and urge to cough. When menthol alone was applied, subjects reported a refreshing

feeling and cooling sensation. Menthol administration decreased cough sensitivity produced by capsaicin

(p<0.05),such that higher levels of capsaicin were needed to produce coughing, and fewer coughs were

produced (p<0.01). Urge to cough also increased with higher capsaicin concentrations(p<0.01),

indicating that subjects were less sensitive to capsaicin. Subjects reported that menthol reduced the

intensity of capsaicin irritation of the nasal mucosa, thus increasing capsaicin tolerability (Buday et al.,

2012).

A randomized cross‐overstudy by Pereira and colleagues (2013) investigated the effect of inhaled

menthol on upper airway resistance during quiet breathing. The upper airway resistance of ten

participants was examined following exposure to menthol and was compared to regular room air. Nine

out of 10 participantsreported that that they could breathe more easily on the menthol test day;

however, upper airway resistance was not significantly affected (Pereira, Sim, Driver, Parker, &

Fitzpatrick, 2013). The discordance between sensation and physiological response has been noted in the

full scientific review.

Twenty subjects participated in a lateralization test of menthol, eucalyptol, mustard oil, a mixture of

menthol and eucalyptol, and a mixture of menthol and mustard oil. After exposure, participants

identified which nostril was presented with the target odorant. They also rated the intensity and

pleasantness of each odorant, and attached three descriptors. All odorants activated the trigeminal

system and were easily accurately lateralized (p<0.001). Menthol was described as cool, fresh and

tickling. Agonists of different trigeminal receptors had clearly dissociated lateralization scores. Thus,

activation of the trigeminal nerve by TRPM8 agonists (menthol, eucaluptol) elicited a different response

than the TRPM1 agonist mustard oil (Frasnelli, Albrecht, Bryant, & Lundstrom, 2011).

Ashley et al. (2012) conducted a study in Japan and Poland to investigate mouth level exposure (MLE) to

nicotine using filter analysis. In this cross‐overstudy, 800 subjects (regular nonmentholsmokers,

occasional and regular mentholsmokers)smoked each of five types of test cigarettes(nonmenthol and

four levels of natural or synthetic menthol, matched for their usual tar level) and completed

questionnaires assessing the sensory characteristics of the test cigarettes. Both Japanese and Polish

smokers who occasionally smoked menthol cigarettesreported increased perceived irritation as

compared to those who regularly smoked menthol cigarettes (p<0.05). In all Japanese smokers, the

level of menthol loading affected the perceived strength of menthol taste and intensity of cooling

(p<0.05); this effect was less notable among the Polish smokers. Both Japanese and Polish smokers

reported differencesin how synthetic and natural menthol cigarettes were perceived (Ashley, Dixon,

Sisodiya, & Prasad, 2012). Taken together, these data suggest that use of synthetic or natural menthol

may impact the sensory characteristics of the cigarette. Since the cigarette styles were matched for the

country, product differences may have contributed to country‐related differences.

Mechanisms of menthol action

Using isolated dorsal root ganglion neuronsfrom rats, the effects of heat, anthralic acid (ACA) and 2‐

aminoethyl diphenylborinate (2‐APB), both putative TRPM8 channel blockers, on stimulation of TRPM8

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currents by noxious cold or menthol. Menthol consistently produced TRPM8 currents, confirming its

activity at that receptor. Heat inhibited TRPM8 channel currents. Unlike the currents produced by

noxious cold, currents produced by menthol were blocked by neither ACA nor 2‐APB (Naziroglu & Ozgul,

2012). According to the authors, this study confirms that menthol activates TRPM8 channels; however,

it is unclear whether one or both of the putative TRPM8 blockers are acting at the TRPM8 site, given

conflicting reports of their blocking actions.

TRPM8 channelsensitivity to menthol was investigated using tetrameric TRPM8 constructs. Using

electrophysiological and intracellular Ca2+ as measurementsfor current activity in HEK293 cells

transfected with TRPM8 channels, researchers assessed the stoichiometry of menthol ligand attachment.

Up to four menthol molecules can independently bind to a single TRPM8 channel, with each bound

molecule producing a similar energetic stabilization of the open channel, resulting in a step‐ wise

stabilization of the open state (Janssens & Voets, 2011). This provides more specific information about

how menthol interacts with the TRPM8 channel.

An in vitro model of CYP2A6 and CYP2A13 activity (part of the metabolism pathway of nicotine and NNK)

was used to assess relative inhibition produced by several compounds, including menthol. When

activity was stimulated with coumarin, menthol was less potent as an inhibitor than the other tested

compounds. There was no evidence that menthol inactivated CYP2A6 or CYP2A13. The authors

concluded that menthol may not influence nicotine and NNK metabolism in smokers(Kramlinger, von

Weymarn, & Murphy, 2012).

Cheang and colleagues(2013) investigated the effect of treatment with menthol on rat aortae and

mesenteric and coronary arteries. Menthol induced relation (e.g., dilation) in the three types of arteries

in a concentration‐dependent manner. Using a smooth muscle cell line, the researchers determined

that this effect was mediated by inhibition of calcium influx (Cheang et al., 2013). This demonstrates

menthol activity at a receptor other than the TRPM8 receptor.

A study by Willis and colleagues(2011) used a mouse model to study the sensory irritation response

elicited by acrolein, acetic acid and cyclohexane vapors (smoke irritants). The irritation produced by

these chemicals was reversed by menthol, even at concentrationslower than in menthol cigarette

smoke (p<0.005). The TRPM8 receptor mediated this effect; other TRPM8 agonists also abolished the

irritant effect, and menthol’s effects were reversed by a TRPM8 antagonist. Menthol also acted via the

capsaicin receptor. The authors concluded that menthol may facilitate smoke inhalation (Willis, Liu, Ha,

Jordt, & Morris, 2011).

Hans and colleagues (2012) investigated how nicotinic receptors are modulated by menthol. Menthol

reversibly bound to both native and recombinant nicotinic receptorsin a concentration‐dependent

manner (p<0.005). Single channel and whole‐cell recordingsfrom nicotinic receptors expressed in HEK

tsA201 cells established that menthol acts as a negative allosteric modulator (Hans, Wilhelm, &

Swandulla, 2012). This finding suggests that menthol directly interacts with nicotinic receptors.

Using PET scans, Brody and colleagues(2012) compared the relative densities of α2β4 nicotinic

acetylcholine receptors(AChRs) of menthol (n=22) and nonmenthol (n=41)smokers. Mentholsmokers

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exhibited greater densities in the brainstem, cerebellum and corpus callosum (p<0.05), but not the

thalamus or prefrontal cortex. According to the author, this may be a result of greater exposure, and

may help explain why mentholsmokers have a more difficult time quitting compared to nonmenthol

smokers(Brody et al., 2012).

Effect of menthol on smoking topography

In a cross‐overstudy by Brinkman and colleagues(2012), nine participantssmoked either menthol or

nonmenthol cigarettesfor one week. During a single laboratory session,smoking topography

measurements were taken. When smoking the menthol test cigarettes, participants had greater volume

of inhaled smoke, took longer puffs and took more time while smoking (p<0.05). This suggests that,

when smoking menthol cigarettes, there was greater exposure to smoke. There were no inter‐puff

interval differences or differencesin inspiration time (Brinkman et al., 2012).

In a laboratory study, Strasser and colleagues(2013) randomized 32 adult smokersto an experimental

group (menthol Camel Crush for 15 days followed by nonmenthol Camel Crush for 15 days) or a control

group (usual brand for 30 days). Every five days, laboratory assessments of smoking topography (total

puff volume of each of two cigarettes) were taken. Compared to baseline, the experimental group

evidenced a slight increase in total puff volume when smoking menthol Camel Crush cigarettes,

compared to a larger increase under the nonmenthol Camel Crush condition (p=0.02) (Strasser et al.,

2013). That is, although both conditions produced increased puff volumes, there was a smaller increase

under the menthol Camel Crush condition. It is unclear whether these differences are the result of the

brand or the presence/absence of menthol versus nonmenthol. It is unknown if there was an influence

of time since usual brand on smoking behaviorsince there was no randomization to avoid order effects;

menthol Camel Crush always preceded nonmenthol Camel Crush, and increased exposure to Camel

Crush generally and/or greater time away from usual brand may impact behavior.

Conclusion

The addition of these articles did not change the conclusion presented in the full scientific review: the

weight of evidence supports the conclusion that menthol in cigarettes is likely associated with

altered physiological responses to tobacco smoke.

Biomarkers

Eleven additional articles evaluating the association between menthol in cigarettes and biomarkers of

exposure were reviewed.

Biomarkers of exposure to carbon monoxide (CO)

In the Strasser et al. study described above, laboratory assessments of biomarkers of exposure (including

breath carbon monoxide [CO] before and after smoking each of two cigarettes) were taken every five

days. CO measurements decreased from baseline in Camel Crush smokers(p=0.033), with no

differences between the Camel Crush conditions (Strasser et al., 2013). It is unknown if there was an

influence of time since usual brand on smoking behaviorsince there was no randomization to avoid

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order effects; menthol Camel Crush always preceded nonmenthol Camel Crush, and increased exposure

to Camel Crush generally and/or greater time away from usual brand may impact behavior.

Using data and biospecimensfrom the Total Exposure Study, a large cross‐sectionalstudy of smokers at

least 21 years, levels of carboxyhemoglobin of 1044 menthol and 2297 nonmentholsmokers were

compared. There was no difference (Sarkar, Wang, & Liang, 2012). It is unclear what, if any, adjustments

were made for this analysis.

Biomarkers of exposure to nicotine

A nonclinical study by Abobo and colleagues (2012) examined the effect of menthol on the

pharmacokinetics of nicotine. Rats were exposed to mainstream smoke under either a single‐cigarette

smoke inhalation procedure (1 puff/minute for 10 minutes) or a multiple‐cigarette smoke inhalation

procedure (equivalent to 17 cigarettes via 10 puffs every 12 hours). Following both the single‐ and

multiple‐cigarette smoke inhalation procedures, menthol cigarette smoke resulted in lower maximum

plasma levels of nicotine and cotinine (p<0.05). Following the multiple‐cigarette smoke inhalation

procedure, menthol appeared to influence nicotine metabolism as indicated by a shorter relative half‐

life. The authorssuggest that the reduced maximum levels of nicotine associated with mentholsmoke

may be impacted by differencesin aversiveness(i.e., the rats inhale less mentholsmoke as compared to

nonmentholsmoke), and/or an altered nicotine half‐life (Abobo, Ma, & Liang, 2012).

In a cross‐overstudy, Brinkman and colleagues (2012) found no differencesin urine levels of cotinine in

subjects who smoked either menthol or nonmenthol test cigarettesfor a week each ; When MLE to

nicotine was estimated by quantifying solanesol levels in cigarette butts, menthol cigarettes had higher

levels than nonmenthol cigarettes (p<0.05) (Brinkman et al., 2012).

In the study by Ashley et al. (2012) described above, Japanese smokersin the higher tar group (4 mg tar

yield) exhibited no effects of menthol loading or type of menthol on nicotine MLE. In the lower tar group

(1 mg tar yield), the occasional mentholsmokers had higher nicotine MLE when smoking the high loading

natural menthol cigarette as compared to the nonmenthol cigarette. Among Polish smokers,smokersin

the lower tar group with the low synthetic menthol cigarettes had higher MLE to nicotine as compared to

the high synthetic nicotine product (Ashley et al., 2012). Taken together, these data

suggest that use of synthetic or natural menthol may impact MLE to nicotine. As noted earlier, since the

cigarette styles were matched for the country, product differences may have contributed to country‐

related differences.

MLE was also assessed by Nelson and colleagues(2011). In this study, 1330 subjects who smoked their

usual brand‐style of cigarettes collected their butts for two days. A subset of this group repeated the

test cycle as a check of replicability. Saliva samples were collected after two days when the subjects

returned their butts. Six of the 26 brands included in this study were menthol brands. There were no

differencesin MLE per cigarette for menthol brands as compared to nonmenthol brands (Nelson, Chen,

Dixon, & Steichen, 2011). There were three times as many test‐cycles with nonmenthol cigarettes as

menthol cigarettes;such a skewed sample may have implicationsregarding confidence in the statistical

analyses. There was no information on the possible inclusion of menthol as an additive to the

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nonmenthol brands; even low levels of menthol may impact smoking behavior and, therefore, MLE of

nicotine.

In the study described above, Strasser and colleagues (2013) conducted laboratory assessments of

biomarkers of exposure (including nicotine and cotinine on days five, 20 and 35) every five days. The

researchersfound no effect of menthol/nonmenthol on nicotine or cotinine levels (Strasser et al., 2013).

It is unknown if there was an influence of time since usual brand on smoking behaviorsince there was

no randomization to avoid order effects; menthol Camel Crush always preceded nonmenthol Camel

Crush, and increased exposure to Camel Crush generally and/or greater time away from usual brand

may impact behavior.

In a study of adult smokers, Benowitz and colleagues (2011) compared the plasma nicotine levels of 60

mentholsmokersto those of 67 nonmentholsmokers. Plasma nicotine levels and urine nicotine

equivalents were significantly higher in regular compared to menthol cigarette smokers(p<0.05)

(Benowitz, Dains, Dempsey, Wilson, & Jacob, 2011). Over 70% of African American smokers smoked

menthol cigarettes, compared to 25% of White smokers; thus, race/ethnicity may be a factor mediating

these results.

Using 1999‐2004 NHANES data, Jones and colleagues(2012) investigated possible associations between

current menthol versus nonmenthol cigarette smokers and peripheral artery disease. As part of this

study, serum cotinine levels were compared. Menthol cigarette smokers(n=310) were observed to have

higher serum cotinine compared to nonmenthol cigarette smokers(n=734). As noted by the authors, a

cautiousinterpretation is warranted since this was a descriptive finding and the data were not adjusted

for smoking patterns,sociodemographic characteristics,smoking history (e.g., pack years), or other

factors (Jones, Apelberg, Samet, & Navas‐Acien, 2012).

A large cross‐sectionalstudy of 221 menthol and 274 nonmentholsmokers examined the association

between menthol and nicotine update as measured by plasma cotinine levels. Although several

covariates were associated with cotinine levels (e.g., time to first cigarette, race, age, BMI, cigarettes per

day [cpd]), smoking menthol cigarettes was not (p=0.66) (Muscat, Liu, Stellman, & Richie, Jr., 2012).

Using data and biospecimensfrom the previously described Total Exposure Study, total urinary cotinine,

glucuronide metabolite ratios for nicotine (nicotine‐N‐glucuronide/free nicotine) and cotinine (cotinine‐

N‐glucuronide/free cotinine, trans 3’‐hydroxy cotinine‐O‐glucuronide/free trans 3’‐hydroxy cotinine)

were calculated for 1044 menthol and 2297 nonmentholsmokers. There was no difference in total

levels of serum cotinine. Although there was no overall difference reported, menthol was a significant

factor (p=0.0145) for the cotinine metabolite ratios; they were higher among mentholsmokers as

compared to nonmentholsmokers. There was also a menthol x age effect on trans 3’‐hydroxy cotinine‐

O‐glucuronide ratios, however this effect was not described (Sarkar et al., 2012). Although other factors

were found to be significant (e.g., race, age, cpd), it is unclear what, if any, adjustments were made for

these analyses.

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Menthol and nonmenthol smokers

An analysis of data from 1918 menthol and nonmenthol smokers who participated in the 2001‐2006

NHANES compared serum cotinine levels of non‐Hispanic adult smokers(age ≥20 years) who reported

smoking a menthol brand of cigarettes (n=677) with those who reported smoking a nonmenthol brand

(n=1241). After adjusting for cpd, there were no differences between the serum cotinine levels of

mentholsmokers as compared to nonmentholsmokers(Caraballo et al., 2011). Sample sizes were

sufficiently large that the uneven subpopulations are not a concern (Caraballo et al., 2011).

Rostron (2012) used data from the 2007‐2010 NHANES to analyze data on total urinary cotinine

concentrations of 1452 everyday smokers and compare levels found between everyday menthol and

nonmentholsmokers. There were no differencesin cotinine levels of menthol and nonmenthol

smokers, despite menthol smokers generally smoking fewer cpd. The author noted that nicotine

exposure as measured by cotinine generally increased with cpd across race/ethnicity groups for U.S.

smokers, but he did not compare mentholsubpopulations(e.g., African American menthol smokers

compared to White mentholsmokers) and nonmentholsubpopulations(African American nonmenthol

smokers compared to White nonmentholsmokers). Less than 30% of those surveyed smoked menthol

cigarettes,suggesting that sample size may be a limitation (Rostron,B, 2012b).

Biomarkers of exposure to TSNAs

Jones et al. (2013) used data from 1999‐2010 NHANES to compare urine 4‐(methylnitrosamino) ‐1‐(3‐

pyridyl)‐1‐butanol (NNAL) levels in menthol smokers versus nonmenthol smokers. After adjusting for

demographic factors, serum cotinine levels were similar for menthol and nonmenthol smokers (Jones,

Apelberg, Tellez‐Plaza, Samet, & Navas‐Acien, 2013).

In a study of adult smokers, Benowitz and colleagues (2011) compared the urine NNAL levels of 60

mentholsmokersto those of 67 nonmentholsmokers and found no differencesin urine NNAL levels

(Benowitz et al., 2011).

A cross‐overstudy involving participants who smoked menthol and nonmenthol test cigarettesfor a

week each found no significant differencesin urinary levels of NNAL or the carcinogen metabolite 1‐

hydroxypyrene. When MLE to NNK was estimated by quantifying solanesol levels in cigarette butts,

menthol cigarettes were associated with higher estimated MLE NNK levels than nonmenthol cigarettes

(Brinkman et al., 2012).

An analysis of 2007‐2010 NHANES data on 1447 everyday smokers compared the total urinary NNAL

concentrations(adjusted for urinary creatinine levels) of menthol and nonmentholsmokers. Overall,

menthol use was associated with lower NNAL concentrations(p<0.05), an effect that was primarily

driven by White smokers. However, mentholsmokers overall, and White mentholsmokersspecifically,

also smoked fewer cpd and cpd was not included as a control variable. The author notes that NNAL

generally increased with cpd across race/ethnicity groups for U.S. smokers. Less than 30% of those

surveyed smoked menthol cigarettes,suggesting that sample size may be a limitation. Since the same

analysis found that lower cpd did not result in differencesin cotinine levels, the pharmacokinetic profiles

of these constituents may differ (Rostron,B, 2012b).

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.

Using data and biospecimensfrom the previously described Total Exposure Study, total serum NNAL,

and glucuronide metabolite ratios for NNAL (NNAL‐O‐ and N‐glucuronide/freeNNAL) were calculated for

1044 menthol and 2297 nonmentholsmokers. There was no difference in total levels of NNAL or the

glucuronide metabolite ratio (Sarkar et al., 2012).

Conclusion

The addition of these articles did not change the finding of the full scientific review that the weight of

evidence supports the conclusion that menthol in cigarettes is likely not associated with increased or

decreased levels of biomarkers of exposure.

Patterns of Use

Five additional articles related to the association between menthol in cigarettes and smoking patterns

were reviewed.

Tobacco use supplement to the current population survey (CPS‐TUS)

In a cross‐sectionalstudy, Delnevo and colleagues (2011) analyzed data from 2003 and 2006/7 Tobacco

Use Supplement to the Current Population Survey (TUS‐CPS) and compared the smoking cessation

prevalence of menthol and nonmentholsmokers. Five differentsample restrictions(using other tobacco

products, ever making a quit attempt, etc.) were used, so the sample size ranged from 71,193 to 24,465

participants. Overall, mentholsmokers were more likely to be female and aged 18‐24 years (Delnevo,

Gundersen, Hrywna, Echeverria, & Steinberg, 2011).

National Survey on Drug Use and Health (NSDUH)

Hickman and colleagues (2012) analyzed data from 24,157 people who participated in the 2008 and

2009 National Survey on Drug Use and Health (NSDUH). Data were categorized for menthol or

nonmenthol use, and for level of psychological distress(none/mild, moderate,severe). The overall

prevalence of menthol cigarette use was 33.3%. Menthol use was more prevalent among young adults,

African Americans, Native Hawaiians/Pacific Islanders, those with severe psychological distress, lower

education level, lower income level, and those who were unmarried and uninsured. The authors suggest

that menthol’s anesthetic and bronchodialation effects may influence metabolism of psychotropic

medications. This study agrees with previously discussed prevalence data (Hickman, III, Delucchi, &

Prochaska, 2012).

National Health and Nutrition Examination Survey (NHANES)

Data from 1943 smokers who participated in the 2001‐2006 National Health and Nutrition Examination

Survey (NHANES) were analyzed. Serum cotinine levels of non‐Hispanic adult smokers(≥20 years) who

reported smoking a menthol brand of cigarettes (n=677) were compared with those who reported

smoking a nonmenthol brand (n=1218). Less than 20% of White smokerssmoked menthol cigarettes,

compared to more than 70% of African American smokers(Caraballo et al., 2011).

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Another analysis using 1999‐2010 NHANES data estimated that 74.3% of smokerssmoked nonmenthol

cigarettes compared with 25.7% who smoked menthol cigarettes. This finding is similar to that of

Caraballo et al. (2011), but may be more representative of current use patterns since this analysis is

based upon more recent datasets(Jones et al., 2013).

National Youth Cessation Survey

The National Youth Smoking Cessation Survey (NYSCS) data were collected in 2003 from 2582 16‐24 year

olds who had ever smoked 20 lifetime cigarettes and had smoked within the past 30 days. From

baseline to the two‐year follow‐up, more baseline mentholsmokersswitched to nonmenthol cigarettes

than vice versa (Villanti et al., 2012).

Conclusion

The addition of these articles did not change finding in the full scientific review, namely that the weight

of evidence supports the conclusion that menthol in cigarettes is associated with particular patterns of

smoking.

Marketing and Consumer Perception of Risk

Five additional articles related to menthol cigarette marketing and consumer perception of risk were

reviewed.

Marketing

Marketing strategies

Researchers performed a cross‐sectional analysis of tobacco retail advertising in a California community

with a greater proportion of African Americansthan in California as a whole, and a “menthol share of

voice” (the proportion of all cigarette advertisementsin a store that featured menthol brands) was

calculated. On average, the menthol share of voice was higher in this community (36.9%) than the state

average (25.7%) (Dauphinee, Doxey, Schleicher, Fortmann, & Henriksen, 2013).

Henriksen and colleagues (2012) examined 407 stores within walking distance of 91 California high

schools and counted advertisementsfor menthol and nonmenthol cigarettes, and for promotions and

prices for Newport (leading menthol brand) and Marlboro (leading nonmenthol brand). The proportion

of advertisementsfor menthol cigarettesincreased with the proportion of African‐American students.

For each 10 percentage‐pointincrease in the proportion of African American students, there was an

increase of 5.9 percent in mentholshare of voice, and stores were 1.5 times more likely to advertise a

Newport promotion. The mentholshare of voice increased by 11.6 percentage points with each 10

percentage‐pointincrease in the proportion of neighborhood residents aged 10–17 years. Although this

is not a nationalstudy, it supports the notion that at least some menthol brands target some African

American neighborhoods, as well as those with younger demographics(Henriksen, Schleicher,

Dauphinee, & Fortmann, 2012).

Tobacco advertising prevalence and placement at the point of sale by neighborhood and store

characteristicsin the ethnically and economically diverse St. Paul, MN area was assessed using data from

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a cross‐sectional assessment of the advertising environment in 654 licensed tobacco vendors(conducted

in 2007) and demographic data taken from the Year 2000 US census. Sixty percent of the establishments

had an average of six menthol cigarette advertisements. About 10% of those had health words such as

“low tar”, “light”, “natural or “additive free” in their advertisements, and 47.5% had advertisements of

price deals. For total number of menthol ads, the proportion African American,

Asian, below 150% of the poverty line, on public assistance, and under the age of 18 years were

associated with more advertisements,the proportion White was associated with fewer advertisements

(p<0.05). Gas/convenience stores had more menthol advertisementsthan all other types of stores

except for tobacco shops and liquor stores (Widome, Brock, Noble, & Forster, 2012).

Consumer perceptions

A study of brand recognition among 2589 6th through 9th graders (ages 11‐15) in California found that the

top three recognized brands were Camel (52%), Marlboro (36%) and Newport (32%). However, there

was disproportionate recognition of Newport by African American students, with over double the brand

recognition levels for those students. This held true after adjustment for smoking by parents and peers.

This analysis was based on a cross‐sectionalsample from the longitudinal Survey of Teen Opinions about

Retail Environments(STORE) (Dauphinee et al., 2013).

In anotherstudy, adult smokers(n=923) who participated in the New Zealand International Tobacco

Control (ITC) projectsurvey were classified as either menthol or nonmenthol users and queried on their

beliefs about the harmfulness of menthol cigarettes. Current menthol users and smokersfrom the

Pacific region of New Zealand believed that menthols were less harmful than nonmenthol cigarettes.

Although these results reflect New Zealand’s cultural and advertising histories, these results are

applicable to the U.S. in that both countries have a documented history of advertising that links

healthfulness and menthol cigarettes (Wilson, Weerasekera, Peace, & Edwards, 2011).

Conclusion

The addition of these articles did not change the finding of the full scientific review that 1) the weight of

evidence supportsthe conclusion that the marketing of menthol cigarettesis likely associated with

brand preference and use among adolescents and the African American community and 2) the weight of

evidence is not sufficient to support a conclusion that consumer perceptions are associated with the use

of menthol cigarettes

Initiation and Progression to Regular Use

Four additional articles regarding the association between menthol and smoking initiation and

progression to regular use were reviewed.

First smoking experience

The study by Dauphinee et al. (2013) described above evaluated the relationship between brand

recognition and smoking initiation. A greater proportion of students who recognized Newport (a

menthol brand) brand at baseline initiated smoking; they were 49% more likely to initiate. Brand

recognition of Camel (menthol) or Marlboro (nonmenthol) did not predict initiation. Recognition of

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Newport explained some of the variance attributed to the finding that African American students were

more likely to initiate smoking (22%) compared to other students (15%), as recognition of Newport

predicted smoking initiation regardless of race. Although the original survey (STORE) was longitudinal, it

has only been administered three times, and some students only participated in two of the three waves.

There was disproportionate loss‐to‐follow‐up among boys, Hispanic students, younger students, and

studentsin lower grade levels. It is also unknown how smoking behavior was evaluated (e.g.,

experience versus regular smoking). Despite these limitations, this study providessupport that there

may be additional factors in the relationship of exposure to advertising on smoking initiation. Although

Newport was third in brand recognition, it was the only brand recognition that was associated with

future smoking behavior (Dauphinee et al., 2013).

A cross‐sectionalstudy of 928 treatment‐seekingwomen in the Boston area was performed by

Rosenbloom and colleagues(2012). Menthol (n=123) and nonmenthol (n=121)smoking women recalled

the age at which they started smoking. There was no difference; both groups started smoking at around

16 years of age. Since the participants were asked generally about the age they started smoking, it is

unclear whether they were reporting the age when they had their first cigarette or when they became

regular smokers(Rosenbloom, Rees, Reid, Wong, & Kinnunen, 2012).

Faseru and colleagues(2013) compared the baseline characteristics of 540 African American light (≤10

cpd) smokers participating in a clinical smoking cessation study. There was no difference between

menthol and nonmentholsmokersin the age of first cigarette smoked. Given the specific population

included as participants(African American light smokers), generalizability is limited. In addition,

drastically uneven numbers of menthol (452) and nonmenthol (88) smokers might have skewed the

results (Faseru et al., 2013).

Progression to regular smoking

The Faseru study cited above also found no difference in the age at which menthol and nonmenthol

smokersstarted smoking regularly (Faseru et al., 2013).

Using data from the longitudinal American Legacy Longitudinal Tobacco Use Reduction Study (ALLTURS),

a three‐wave longitudinal school‐based survey of middle‐ and high school students, Nonnemaker and

colleagues(2012) calculated the odds of escalating from non‐established to established smoking.

Menthol was associated with a higher likelihood of progressing to established smoking (odds ratio [OR]

= 1.8, confidence interval [CI]: 1.02‐3.16). Of the 638 participants, it is unclear how many were menthol

versus nonmentholsmokers(Nonnemaker et al., 2013).

Conclusion

The addition of these articles does not alter the finding of the full scientific review, namely that the

weight of evidence supportsthe conclusion that menthol in cigarettesis likely associated with increased

initiation and progression to regular smoking of cigarettes.

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Dependence

Nine additional articles related to the association between menthol cigarette use and tobacco

dependence were reviewed.

Time to first cigarette (ttfc)

The study by Rosenbloom and colleagues(2012) described above found a significant effect of menthol on

ttfc. Mentholsmokers were more likely to smoke within the first five minutes of waking (49%) as

compared to nonmentholsmokers(36%) (p<0.01). The authors concluded that mentholsmokersshowed

evidence of greater tobacco dependence compared to nonmentholsmokers(Rosenbloom et al.,

2012).

A survey of Minnesota Quitline users who registered for services and had a phone or mail survey follow‐

up 7 months post‐registration was analyzed for self‐reported cessation success of menthol (n=1172)

versus nonmenthol (n=5085) participants. Baseline demographic data found a difference in ttfc, with a

greater percentage of mentholsmokers reporting smoking within the first 5 minutes of waking, and

lower percentage reporting smoking their first cigarette more than 5 minutes after waking (p<0.05)

(D'Silva, Boyle, Lien, Rode, & Okuyemi, 2012).

A large cross‐sectionalstudy of 221 menthol and 274 nonmentholsmokers examined the association

between menthol and ttfc. There was a relationship between menthol and shorter ttfc (p<0.02), which

was driven by African American smokers. This suggeststhat while menthol smokers may be more

dependent, this effect is driven by African American mentholsmokers. That is, the differences between

a single subpopulation’s menthol and nonmentholsmokers was strong enough to drive overall

population differences, however it is unclear what is driving this difference between African American

menthol and nonmentholsmokers(Muscat et al., 2012).

Cigarettes per day (cpd)

During a cross‐overstudy by Brinkman and colleagues(2012), nine subjects were given either menthol

or nonmenthol cigarettesto smoke for a week each. On average, participantssmoked fewer menthol

cpd. However, of the nine participants, only one reported a study method brand as their usual brand.

Therefore, it is difficult to generalize this finding to national menthol versus nonmentholsmoking

populations(Brinkman et al., 2012).

The cross‐sectionalstudy by Rosenbloom and colleagues(2012) evaluated menthol preference on cpd.

Although race effects were found, there was no effect of menthol preference on cpd (menthol = 16.8

cpd; nonmenthol =18.8 cpd) (Rosenbloom et al., 2012).

The demographics of menthol and nonmentholsmokers participating in a PET scan study allowed

comparison of self‐reported cpd by group. There were no differences between the menthol (n=22) and

nonmenthol (n=41) groups, with mentholsmokerssmoking 19.9 ±5.8 cpd and nonmentholsmokers

smoking 18.4 ±3.7 cpd (Brody et al., 2012).

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Scales of nicotine dependence

The study by Brody et al. (2012) cited above allowed comparison of Fagerstrom Test of Nicotine

Dependence (FTND)score by group. The researchersfound no differences between the menthol (n=22)

and nonmenthol (n=41) groups (Brody et al., 2012).

Faseru and colleagues(2013), in the study described earlier, found no difference in the FTND scores

between menthol and nonmentholsmokers(Faseru et al., 2013).

Using data from ALLTURS study described earlier, Nonnemaker and colleagues (2012) calculated a scale

of nicotine dependence based on five questionsthat focus on ttfc on weekdays, ttfc on weekends, and

craving. Participants who initiated with menthol cigarettes had higher nicotine dependence scores (β‐

1.25, CI: 0.1‐2.4) (Nonnemaker et al., 2013).

The association between menthol use status and Heaviness of Smoking Index (HSI) was examined as

part of the baseline characteristics of 183 (83 menthol, 100 nonmenthol)smokersfrom a longitudinal

study examining risk perceptions over time among community smokers attempting to quit. The HSI of

mentholsmokers was no different from that of nonmentholsmokers(p=0.579) (Reitzel et al., 2013).

Industry documents research

Yerger (2011) reviewed publicly available tobacco industry documents on the topic of menthol and

nicotine dependence. The documents mainly focused on menthol’s sensory and physiological effects

and how these effects may interact with nicotine. According to these documents, the cooling and

anesthetic effects of menthol may alleviate nicotine’sirritating effects. Menthol may also act

synergistically with nicotine, may stimulate the trigeminal nerve, and may make low tar, low nicotine

tobacco products more acceptable. According to the documents, menthol level (but not nicotine level)

affects level of “impact” felt by the user (Yerger, 2011).

Conclusion

The addition of these articles does not change the conclusion of the full scientific review, namely that

the weight of evidence supportsthe conclusion that menthol in cigarettesis likely associated with

increased dependence.

Cessation

Seven additionalstudies addressing the link between menthol and smoking cessation were reviewed.

Cohort studies

The association between menthol use status and biochemically‐verified short term abstinence was

examined by Reitzel and colleagues(2013) in the study described above. Smoking status was assessed

via self‐report and exhaled CO at weeks 1, 2 and 3 post‐quit. There was no effect of menthol status on

continuousshort‐term abstinence (p=0.44); however, this was moderated by race. After adjusting for

demographic factors, menthol use was significantly associated with short‐term continuous abstinence

among White smokers(p=0.05), but not African American smokers. White mentholsmokers were five

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times less likely to maintain abstinent as compared to White nonmentholsmokers(OR = 0.21m CI 0.05‐

0.98) (Reitzel et al., 2013).

Cross‐sectional studies

Data collected as part of a randomized clinical trial were analyzed for race/ethnicity effects on post‐

partum maintenance of smoking abstinence. Participantssmoked prior to pregnancy (n=123 menthol;

n=121 nonmenthol) and stopped either during their pregnancy or within two months of becoming

pregnant. The outcome measure was continuous abstinence since delivery date, and was assessed at

eight and 26 weeks postpartum. Although responses were self‐reported, there was cotinine verification

of smoking abstinence. White menthol users, but not mentholsmokers of other race/ethnic subgroups,

were less likely to maintain continuous abstinence rates. Analyses were adjusted for a variety of factors,

including cpd and ttfc. As discussed in the full scientific review, since level of dependence may be an

intermediate factor impacting cessation success, thus, these analyses may have been overadjusted

(Reitzel et al., 2011).

The smoking cessation prevalence of menthol and nonmentholsmokers was compared by Delnevo and

colleagues (2011). This cross‐sectionalstudy analyzed data from 2003 and 2006/7 TUS‐CPS. Adjusted

odds of cessation were calculated using multiple logistic regressions. Overall, mentholsmokers were less

likely to be former smokersthan were nonmentholsmokers(AOR 0.91, 95% CI 0.87, 0.96), an effect that

was relatively small but consistent (Delnevo et al., 2011).

An analysis of data from a survey of Minnesota Quitline users, described above, found no significant

difference in quit status reported during the follow‐up; menthol was not a significant predictor of 30‐day

abstinence (D'Silva et al., 2012).

Data from the 2003 and 2006/7 TUS‐CPS were used to examine quit rates among menthol and

nonmentholsmokers. Although mentholsmokers were more likely to have made a quit attempt, they

were either 4% (2003) or 12% (2006/7) less likely to have quit successfully in the past year. The final

sample sizes are unclear,since the study authors did not indicate the number of subjects who met the

inclusion requirements(Levy et al., 2011).

A randomized double‐blind, placebo‐controlled smoking cessation study investigated the efficacy of

bupropion in promoting cessation in adult African American light (≤10 cpd) treatment‐seeking smokers

(n=540). Cotinine‐verified seven‐day point prevalence abstinence at week 7 (end of drug treatment)

and week 26 were compared. Compared to continuing smokers, those who were abstinent were more

likely to smoke nonmenthol cigarettes at week 7 (p=0.001) and week 26 (p=0.005). However, being a

menthol or nonmentholsmoker did not alter the efficacy of bupropion, which was higher than placebo

at week 7 (24% versus 13%), but not at week 26 (13% versus 10%). Thus, although smoking menthol

cigarettes was negatively associated with successful abstinence, it did not affect response to

pharmacotherapy (Faseru et al., 2013).

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Industry documents research

In a study of publicly available tobacco industry documents, Anderson (2011) reviewed documents on

the topic of menthol and smoking cessation behavior. The documents mainly focused on the cooling

and anesthetic effects of menthol. According to the documents, these effects may mask the short‐term

negative physiological effects of smoking such as throat pain, burning, cough. Documents also suggest

that these sensory effects may also allow some smokers who were dissatisfied with the smoking

experience to continue to smoke, and discourage them from quitting (Anderson, 2011).

Conclusion

The addition of these articles did not change the conclusion of the full scientific review, namely that the

weight of evidence supportsthe conclusion that menthol in cigarettesis likely associated with reduced

successin smoking cessation, especially among African American mentholsmokers.

Disease Risk

Four additional articles related to menthol and disease risk were reviewed.

Lung cancer

Using data from the 1987 National Health Interview Survey Cancer Control Supplement (with links to the

National Death Index), Rostron (2012) estimated lung cancer mortality hazards for menthol and

nonmentholsmokers. Menthol cigarette use had a lower hazard ratio (HR) for lung cancer mortality (HR

= 0.59, CI 0.37‐0.95) among 50+ year olds as compared use of nonmenthol cigarettes, but there was no

similar association with other causes of mortality. The author concluded that it is unknown how

differencesin smoking behavior and/or cigarette design may have impacted these findings. (Rostron,B,

2012a). These findings were commented on by Villanti et al. (Villanti, Giovino, Burns, & Abrams, 2013)

with a rebuttal by Rostron (Rostron, 2013).

Multiple cancers

Kabat and colleagues (2012) used data on age‐adjusted incidence rates of lung, esophageal,

oropharyngeal, and laryngeal cancersfrom the Surveillance, Epidemiology, and End Results (SEER)

program. Although not directly comparing menthol and nonmentholsmokers, Kabat and colleagues

inferred that menthol did not alter multiple types of cancer risk since the marketshare of menthol

cigarettes has remained stable over the past two decades, whereas cancer incidences have changed

over the past 35 years, and these changes differ greatly depending on race and sex. The authors

conclude that if menthol cigarettes had a “discernible effect” on the risk of smoking‐related cancers, the

incidence of these cancers in African Americans, especially African American females, would be higher,

since this group smokes menthol cigarettes at a higher prevalence than White smokers(Kabat,

Shivappa, & Hebert, 2012).

Multiple non‐cancer diseases

Using data from the 1999‐2004 NHANES, Jones and colleagues(2012) investigated possible associations

between current menthol versus nonmenthol cigarette smokers and peripheral artery disease. An

ankle‐brachial blood pressure index (ABI) calculation was made for 734 nonmentholsmoking adults and

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310 menthol smoking adults who were at least 40 years old. This calculation is a highly specific marker

for subclinical peripheral artery disease. After adjusting for risk factors, demographics, pack‐years of

smoking and serum cotinine, there was no significant difference in the association between smoking and

peripheral artery disease for currentsmokers of menthol and nonmenthol cigarettes. Although there

were half as many mentholsmokers as nonmentholsmokers, it is unlikely that small sample size

contributed to the negative results since even a directional trend did not exist (p=0.59) (Jones et al.,

2012).

Data from the 2001‐2008 NHANES was used to examine possible relationships between menthol

smoking and the odds of stroke, hypertension, myocardial infarction, congestive heart failure, and

COPD. The data were adjusted for demographic factors, and smoking quantity and duration. There

were increased odds of stroke in mentholsmokers(OR= 2.25, CI: 1.33‐3.78), particularly women and

non‐African Americans, as compared to the nonmentholsmoking counterparts. This increase was

slightly reduced, but still significant, when data were adjusted for being diagnosed by a health

professional,self‐reported hypertension, diabetes mellitus and dyslipidemia (OR=2.19, CI: 1.05‐4.58).

There were no significant differencesin the odds of any of the other diseases and smoking either

menthol or nonmenthol cigarettes. The author suggeststhat the menthol cigarette‐stroke association

may be underestimated since former smokers were not included in the analysis (Vozoris, 2012).

Conclusion

The addition of these articles did not change the conclusion of the full scientific review: the weight of

evidence supportsthe conclusion that menthol in cigarettesis not associated with an increase in disease

risk to the user.

Overall Conclusion

None of the additionally reviewed peer‐reviewed articles altered the findings of the full science report.

20
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Abobo CV, Ma J, Liang D. 

Effect of menthol on nicotine pharmacokinetics in rats after cigarette smoke inhalation. 

2012 NIH Grants and the state 

tobacco settlement funds (Texas) 

Nonclinical Rats N=8/group Consistent with th

single-cigarette excigarette exposurereductions in the mplasma concentratSimilar to that obssmoke inhalation, the mean maximucotinine The mean eliminanonmentholated asmoke exposures (49.4 vs. 37.3 minWe found that singcigarette significanplasma level and tnicotine but not the 

Anderson SJ. 

Menthol cigarettes and smoking cessation behaviour: a review of tobacco industry documents. 

2011 Contract from DHHS 

HHSN261201000035I 

Documents N/A 509 

documents qualitatively analyzed, 46 documents included 

Menthol’s cooling the short-term negsmoking such as tThis provides supeas psychological aabout the health dotherwise motivate 

Ashley M, Dixon M, Sisodiya A, Prasad K. 

Lack of effect of menthol level and type on smokers' estimated mouth level exposures to tar and nicotine and perceived sensorycharacteristics of 

2012 British American Tobacco 

(BAT) 

Human subjects 

Smokers (age 21-65) who smoked at least 10 cpd 

N=800 menthol and nonmenthol smokers (this was a “target”; number of actual completers 

There were no effeon mean nicotine smoker groups, busmoker groups the obtained higher msmoking the high lproduct (J1N 11.6non-menthol cigar

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

cigarette smoke. wasn’t given) The only significan

mean nicotine MLyield group where loading product (Pnicotine MLE than product (P1S 6.1 aproduct (P1N 6.3). . . for the two occgroups, the additiowas associated wiincrease in perceivThe effects of menof the strength of meffect were less clthe Japanese smogroups there were intensities of mentwith increasing methe results from thdifferences were n

Benowitz NL, Dains KM, Dempsey D, Wilson M, Jacob P. 

Racial differences in the relationship between number of cigarettes smoked and nicotine and carcinogen exposure. 

2011 NIH Grants Human 

laboratory study 

Healthy adult (age 18­65) smokers who smoked an average of ≥10 cpd for the past year or longer 

N=127 Plasma nicotine le

in regular comparesmokers. 

Bodnar JA, Morgan WT, Murphy PA, Ogden MW. 

Mainstream smoke chemistry analysis of samples from the 2009 US cigarette 

2012 R.J. Reynolds Tobacco 

Co. 

Nonclinical N/A N/A Menthol cigarette 

observed to be witmenthol cigarettes 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Abobo CV, Ma J, Liang D. 

Effect of menthol on nicotine pharmacokinetics in rats after cigarette smoke inhalation. 

2012 NIH Grants and the state 

tobacco settlement funds (Texas) 

Nonclinical Rats N=8/group Consistent with th

single-cigarette excigarette exposurereductions in the mplasma concentratSimilar to that obssmoke inhalation, the mean maximucotinine The mean eliminanonmentholated asmoke exposures (49.4 vs. 37.3 minWe found that singcigarette significanplasma level and tnicotine but not the 

Anderson SJ. 

Menthol cigarettes and smoking cessation behaviour: a review of tobacco industry documents. 

2011 Contract from DHHS 

HHSN261201000035I 

Documents N/A 509 

documents qualitatively analyzed, 46 documents included 

Menthol’s cooling the short-term negsmoking such as tThis provides supeas psychological aabout the health dotherwise motivate 

Ashley M, Dixon M, Sisodiya A, Prasad K. 

Lack of effect of menthol level and type on smokers' estimated mouth level exposures to tar and nicotine and perceived sensorycharacteristics of 

2012 British American Tobacco 

(BAT) 

Human subjects 

Smokers (age 21-65) who smoked at least 10 cpd 

N=800 menthol and nonmenthol smokers (this was a “target”; number of actual completers 

There were no effeon mean nicotine smoker groups, busmoker groups the obtained higher msmoking the high lproduct (J1N 11.6non-menthol cigar

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

market. 

Brinkman MC, Chuang JC, Gordon SM, Kim H, Kroeger RR, Polzin GM, Richter PA. 

Exposure to and deposition of fine and ultrafine particles in smokers of menthol and nonmenthol cigarettes. 

2012 Contract from the Centers 

for Disease Control and Prevention (CDC) 

Nonclinical and Laboratory 

Smokers (age 18-30) who smoked at least 1 pack/day for at least 6 months 

N=9 ... there were no s

measured in daily and participant spparticipants smokeThere were no sigof urinary cotinine nonmenthol cigareUrinary 1-HOP levdifferent between The menthol test chigher number (11ultrafine particles tcigarette. Participants smokcigarettes/day... atest cigarettes. ...participants took required a longer pmenthol cigarette, volume of smoke i(73 ml/cigarette) a

Brody AL, 2012 Tobacco-Related Disease Clinical study Healthy adult smokers N=22 Menthol and non-m

Mukhin AG, La Research Program, NIH (10-40 cpd) menthol not differ on any dCharite J, Ta K, Up-regulation of grant, Veterans Affairs smokers, measure, other thaFarahi J, Sugar nicotinic Type I Merit Review N=41 CA, Mamoun acetylcholine Award, endowment from nonmenthol Follow-up tests revMS, Vellios E, receptors in the Richard Metzner Chair smokers differences for the Archie M, menthol cigarette in Clinical corpus callosum... Kozman M, smokers. Neuropharmacology 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Phuong J, Arlorio F, Mandelkern MA. Buday T, Brozmanova M, Biringerova Z, Gavliakova S, Poliacek I, Calkovsky V, Shetthalli MV, Plevkova J. 

Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels. 

2012 VEGA no 1/0031/11 and 

Centre of Experimental and Clinical Respirology II (CEKR) co-financed from EU sources 

Human laboratory study 

Healthy non-smoking adults (average age 23) 

N=18 Both menthol isom

significantly moduthreshold, and totathe reduction of aicapsaicin challeng

Caraballo RS, Holiday DB, Stellman SD, Mowery PD, Giovino GA, Muscat JE, Eriksen MP, Bernert JT, Richter PA, Kozlowski LT. 

Comparison of serum cotinine concentration within and across smokers of menthol and nonmenthol cigarette brands among nonHispanic black and non-Hispanic white U.S. adult smokers, 2001­2006. 

2011 No funding source(s). 

Authors affiliated with the Centers for Disease Control and Prevention, RTI International, Georgia State University, Columbia University, State University of New York at Buffalo, Penn State College of Medicine 

Cohort survey (NHANES 2001-2006) 

Smokers (age ≥20) who 

had smoked on the day of or the day prior to the NHANES visit 

N=1943 Smoking a mentho

smoking a nonmeassociated (P< 0.0concentration in e...only a minority (smokers smoked mthe majority (73.9%menthol brand. Menthol cigarettes (1.24 mg) were on nicotine levels to tmg) smoked by wh

Cheang WS, Lam MY, Wong WT, Tian XY, Lau CW, Zhu Z, Yao X, Huang Y. 

Menthol relaxes rat aortae, mesenteric and coronary arteries by inhibiting calcium influx 

2013 National Basic Research 

Program of China, a research grant from Research Grants Council of Hong Kong, and CUHK Focused Investment Scheme B. 

Nonclinical Rat tissue, cell culture N/A The present study 

relaxes rat arteries probably vianifedipvascular smooth mindependent of the 

Dauphinee AL, Racial differences 2013 NIH grant Longitudinal 6th-9th grade students N=2589 On average, the p

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Doxey JR, in cigarette brand study with (age 11-15) in Vallejo, featured a mentho

Schleicher NC, recognition and some cross- California voice) was 36.9% Fortmann SP, impact on youth sectional than the average fHenriksen L. smoking. analyses 26.1)... 

...provide the branfor Marlboro, and The odds of smokfor students who rat baseline. 

Delnevo CD, Gundersen DA, Hrywna M, Echeverria SE, Steinberg MB. 

Smokingcessation prevalence among U.S. smokers of menthol versus non-menthol cigarettes. 

Cross-sectional TUS-CPS 

Black, White and Hispanic current smokers and those who have quit in the past 5 years 

N=71,193 to 24,465 (depending on sample restrictions) 

...there was a smabetween menthol cwhereby smokers signifıcantly less li

smokers of non-m

D'Silva J, Boyle RG, Lien R, Rode P, Okuyemi KS. 

Cessation outcomes among treatment-seeking menthol and nonmenthol smokers. 

2012 No funding source(s). 

Authors were affiliated with ClearWay Minnesota; University of Minnesota; Professional Data Analysts; Minnesota Department of Health 

Cross-sectional survey with single follow-up 

Cigarette smokers who called the Minnesota Quitline and registered for services 

N=1172 menthol smokers, N=5085 nonmenthol smokers 

...the odds of quittnot signifıcantly dismokers (OR 1.29controlling for the 

Faseru B, Choi WS, Krebill R, Mayo MS, Nollen NL, Okuyemi KS, Ahluwalia JS, Cox LS. 

Factors associated with smoking menthol cigarettes among treatment-seeking African American light smokers. 

2011 NIH Grant Clinical trial Treatment-seeking 

African-American light (≤10 cpd) smokers 

N=452 menthol, N=88 nonmenthol 

Table 1 Baseline cand non-menthol s

Faseru B, Nollen NL, Mayo MS, Krebill R, Choi 

Predictors of cessation in African American light smokers 

2013 NIH Grants; NRSA grant, 

American Cancer Society Institutional Research Grant 

Clinical trial Treatment-seeking 

African-American light (≤10 cpd) smokers 

N=540 Our current study 

effect of menthol oAmerican light smwere less likely to 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

WS, Benowitz NL, Tyndale RF, Okuyemi KS, Ahluwalia JS, Sanderson Cox L. 

enrolled in a bupropion clinical trial. 

non-menthol cigar

Fowler P, Smith K, Young J, Jeffrey L, Kirkland D, Pfuhler S, Carmichael P. 

Reduction of misleading ("false") positive results in mammalian cell genotoxicity assays. I. Choice of cell type. 

2012 European Cosmetic 

Industry Association, UK National Centre for the 3Rs (NC3Rs) 

Nonclinical 6 in vitro cell lines N/A It was cytotoxic, in

in RI at the top cowere no increases In other cases (e.glimited by cytotoxilevels of cytotoxici

Frasnelli J, Albrecht J, Bryant B, Lundström JN.Frasnelli J, Albrecht J, Bryant B, Lundström JN. 

Perception of specific trigeminal chemosensory agonists. 

2011 Postdoctoral fellowship 

from the Canadian Institutes of Health Research 

Human laboratory study 

Healthy adults with no reductions in sense of smell 

N=20 All stimuli clearly a

as demonstrated blateralizing them. The scores for methe highest correlaEucalyptol and mepredominantly coorespectively), fresh p and 0.7 p, respe

Gordon SM, Brinkman MC, Meng RQ, Anderson GM, Chuang JC, Kroeger RR, Reyes IL, Clark PI. 

Effect of cigarette menthol content on mainstream smoke emissions. 

2011 Battelle internal research 

and development funds 

Nonclinical N/A N/A Menthol in the TPM 

cigarettes at each investigated showapplied menthol coof nicotine, target quinolone in the ciunchanged. SimilaVOCs in mainstreacigarettes that werpuff-by-puff basis unaffected by the 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

the cigarettes. 

Hans M, Wilhelm M, Swandulla D. 

Menthol suppresses nicotinic acetylcholine receptor functioning in sensory neurons via allosteric modulation. 

2012 Altria Client Services, Inc. Nonclinical Nicotinic acetylcholine 

receptors (native and recombinant) 

N/A ...we show that nA

neurons are reversan IC50 of 111 lMfrom human a4b2 revealed that mensingle channel amopen time and a pWe conclude that menthol-mediated an allosteric modumenthol. 

Henriksen L, Schleicher NC, Dauphinee AL, Fortmann SP. 

Targeted advertising, promotion, and price for menthol cigarettes in California high school neighborhoods. 

2012 California’s TobaccoRelated Disease Research 

Program grant 

Cross-sectional study 

Stores within walking distance of California high schools 

N=407 For each 10 perce

proportion of Black menthol advertisinpoints... The menthol share percentage points increase in the proresidents ages 10–For each 10 perceproportion of Black advertising a Newgreater 

Hickman NJ 3rd, Delucchi KL, Prochaska JJ. 

Menthol use among smokers with psychological distress: findings from the 2008 and 2009 National Survey on Drug Use and Health. 

2012 NIH grants Nationally 

representative cohort study (NSDUH) 

Current smokers (age ≥18) who answered the item on menthol use 

N=24157 The prevalence of 

this national samp33.3%. The prevalence of among individuals distress, women, yAmericans, Native persons with feweincome, the unma

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Janssens A, Voets T. 

Ligand stoichiometry of the cold- and menthol-activated channel TRPM8. 

2011 Grants from the Belgian 

Federal Government, the Research FoundationFlanders, and the Research Council of the KU Leuven 

Nonclinical TRPM8 ion channels 

expressed in HEK293 cells 

N/A This indicates that 

bind up to four mestepwise stabilizat

Jones MR, Apelberg BJ, Samet JM, Navas-Acien A. 

Smoking, menthol cigarettes, and peripheral artery disease in U.S. adults. 

2012 NIH Grants Nationally 

representative survey from 1999-2004 (NHANES) 

Adults (age ≥ 40) N=5973 Serum cotinine an

concentrations wementhol cigarettes nonmenthol cigareWe observed no sassociation betweartery disease for nonmenthol and mheterogeneity = 0.

Jones MR, Apelberg BJ, Tellez-Plaza M, Samet JM, Navas-Acien A. 

Menthol cigarettes, race/ethnicity, and biomarkers of tobacco use in U.S. adults: the 1999-2010 National Health and Nutrition Examination Survey (NHANES). 

2012 NIH grants Cohort 

nationally representative survey from 1999-2010 (NHANES) 

Adult current smokers 

(including White, African American and Mexican American smokers) 

N=4603 In a representative 

smokers, current massociated with incadmium, an estatoxic metal, but noA total of 3,210 (74nonmenthol cigare(25.7%) participancigarettes... After further adjuscorresponding ratiand no longer statcotinine (1.03; 95% 

Kabat GC, Shivappa N,HÃ©bert JR. 

Mentholated cigarettes and smoking-related cancers revisited: an ecologic 

2012 NIH Grants Multiple years 

of SEER data 

Case and controls: lung. esophageal, oropharyngeal, laryngeal cancer 

Not given/Not appropriate 

Given the large difmentholated cigarmenthol had a dissmoking-related casee one or both of 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

examination. higher incidence ra

sexes compared to differences in the tBlacks and Whites 

Kramlinger VM, von Weymarn LB, Murphy SE. 

Inhibition and inactivation of cytochrome P450 2A6 and cytochrome P450 2A13 bymenthofuran, Î2- nicotyrine and menthol. 

2012 NIH Grants Nonclinical In vitro N/A Inhibition of CYP2

less potent (Ki of 1There was no indicCYP2A6 or CYP2A

Levy DT, Blackman K, Tauras J, Chaloupka FJ, Villanti AC, Niaura RS, Vallone DM, Abrams DB. 

Quit attempts and quit rates among menthol and nonmenthol smokers in the United States. 

2011 Legacy Nationally 

representative cross-sectional TUC-CPS from 2003 and 2006/7 

Adult smokers who had 

smoked at least 100 cigarettes and are either current or former smokers 

Unknown Table 1 presents t

and former smokeyears by cigarette 2007, about 70% ssmoked menthol, Although they had attempt, menthol snonmenthol smokquit successfully in 12%less likely in 2

Lu S, BaadHansen L, List T, Zhang Z, Svensson P. 

Somatosensory profiling of intraoral capsaicin and menthol in healthy subjects 

2013 NIH research grant Human 

laboratory study 

Healthy adults (mean age 31.5±7.5) 

N=15 More than half (9/

mild levels of pain Our study showed menthol on the ginhyperesthesia... 

Millqvist E, TernestenHasséus E, Bende M. 

Inhalation of menthol reduces capsaicin cough sensitivity and influences inspiratory flows in 

2013 Grants from the Regional 

Health Care Authority of West Sweden, the Swedish Asthma and Allergy Association and the Swedish Heart and 

Human laboratory study 

Patients: non-smokers with histories of cough and other airway symptoms induced by environmental irritants ( average age 51). 

N=14 (patients) N=15 (controls) 

We conclude that that is not caused infections, pre-inhcough sensitivity tinfluences inspirat

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

chronic cough. Lung Foundation 

Controls: healthy nonsmokers (average age 52). 

Muscat JE, Liu HP, Stellman SD, Richie JP Jr. 

Menthol smoking in relation to time to first cigarette and cotinine: results from a community-based study. 

2012 NIH Grants; contracts from 

DHHS; Pennsylvania Department of Health 

Human laboratory study 

Daily smokers (≥5 cpd 

for one or more years) 

N=495 . Overall there was 

smoking and a shoanalyzed by race, black subjects (P < The time to first cimenthol (P = 0.66with cotinine levels

Naziroğlu M, Ozgül C. 

Effects of antagonists and heat on TRPM8 channel currents in dorsal root ganglion neuron activated by nociceptive cold stress and menthol. 

2012 No funding source(s). 

Authors affiliated with University of Suleyman Demirel, Turkey 

Nonclinical Rat dorsal root ganglia N/A In the current stud

activated by menth

Nelson PR, Chen P, Dixon M, Steichen T. 

A survey of mouth level exposure to cigarette smoke in the United States. 

2011 No funding source(s). 

Authors affiliated with R.J. Reynolds Tobacco Company 

Human study Healthy smokers (≥7 

cpd) who smoked one of the selected brand styles as their usual brand style 

N= 1330 The regression lin

fell slightly below tcigarettes suggestlower MLEs per cistyles. However, dintercepts of the restatistically signific

Nonnemaker J, Hersey J, Homsi G, Busey A, Allen J, Vallone D. 

Initiation with menthol cigarettes and youth smoking uptake. 

2012 DHHS contract Cross-sectional 

survey 

Middle and high school students from 83 schools in seven communities and five states 

N=638 (progression analysis) or N=399 (dependence analysis) 

The models reveasignificant associainitiation [odds ratiinterval (CI): 1.02–established smokiAs shown, initiatio

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

positively and signdependence (b = 1

Pereira EJ, Sim L, Driver H, Parker C, Fitzpatrick M. 

The effect of inhaled menthol on upper airway resistance in humans: A randomized controlled crossover study. 

2013 Research grants from the 

Ontario Thoracic Society, William M. Spear Foundation, Queen’s University and Clinical Teachers Association at Queen’s University 

Human laboratory study 

Healthy adults (age 21±0.5 years) 

N=10 ...90% of participa

breathe easier on The present study receptor stimulatioinhaled menthol dairway respiration] subjects. 

Reitzel LR, Li Y, Stewart DW, Cao Y, Wetter DW, Waters AJ, Vidrine JI. 

Race moderates the effect of menthol cigarette use on short-term smoking abstinence. 

2013 NIH Grant; CDC grant, 

The University of Texas MD Anderson Cancer Center 

Cohort study Current smokers (age 

18-65), smoking ≥5 cpd for at least a year, willingness to quit 

N=183 The main effects o

continuous short-tnot significant... Menthol use was sshort-term continuamong White partWhite menthol uselikely to maintain cthan White nonme95% CI = 0.05–0.9

Reitzel LR, 2011 NIH Grants Clinical trial Women who smoked N= 123 White menthol use

Nguyen N, Cao Race/ethnicity prior to pregnancy and menthol continuous abstineY, Vidrine JI, moderates the quit either during smokers, users. Daza P, Mullen effect of pregnancy or within 2 121 PD, Velasquez prepartum months of becoming nonmenthol MM, Li Y, menthol cigarette pregnant smokers Cinciripini PM, use on postpartum Cofta-Woerpel smoking L, Wetter DW. abstinence. Rosenbloom J, A cross-sectional 2012 NIH Grant, the Harvard Cross-sectional Women smokers N=198 A greater proportio

Rees VW, Reid study on tobacco School Office for study African their first cigarette K, Wong J, use and Enrichment Programs and American, (p < 0.01)... Kinnunen T. dependence the Harvard School of N=730 White 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

among women: Does menthol matter? 

Dental Medicine The ANOVAs cond

menthol preferencper day, age of sm

Rostron B. 

NNAL exposure by race and menthol cigarette use among US smokers. 

2012 (epub) 

No funding source(s). 

Author affiliated with FDA 

Nationally representative survey (NHANES) 

NHANES smoker participants from 2007­2010 (age ≥20) 

N=1614 Menthol cigarette 

NNAL concentratioThis difference waNNAL concentratiocompared with noWhite smokers. Nicotine and carciby NNAL and cotinCPD across race/esmokers. 

Rostron B. 

Lung cancer mortality risk for U.S. menthol cigarette smokers. 

2012 No funding source(s). 

Author affiliated with FDA 

Nationally representative survey (NHISCCS) 

Adult participants (age 

≥ 18) who were smokers identified with either menthol or nonmenthol preference (pack verified) 

N=4832 The HR for lung ca

smokers at ages 5(95% CI = 0.37 – 0

Sarkar M, Wang J, Liang Q 

Metabolism of nicotine and 4­(methylnitrosamin o)-1-(3-pyridyl)-lbutanone (NNK) in menthol and non-menthol cigarette smokers 

2013 No funding source(s). 

Authors affiliated with Altria Client Services 

Multi-center, cross-sectional study (TES) 

Adult participants (age 

≥21) who reported smoking ≥1cpd for at least the past 12 months 

N=1044 menthol; 2297 nonmenthol 

Race, machine-smage interaction terfactors for the 3OHThe biomarkers of carboxyhemoglobnot statistically sig

Strasser AA, Ashare RL, Kaufman M, Tang KZ, Mesaros AC, Blair IA. 

The effect of menthol on cigarette smoking behaviors, biomarkers and subjective responses. 

2013 NIH Grants Human 

laboratory study 

Adult smokers (age 21­

65); smoke ≥10 cpd, smoke menthol cigarettes at least 80% of the time 

N=32 ...the experimenta

increase in total pbrand) to period 2 period 2 (menthol) 0.06) and a signifi1 and 3 (P = 0.02)There was a signif

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

from period 1 (basmean difference=1but there was no dand 3 (non-menthoexperimental grouCotinine values hanicotine values; theffects or interactio

Topp R, Winchester L, Mink AM, Kaufman JS, Jacks DE. 

Comparison of the effects of ice and 3.5% menthol gel on blood flow and muscle strength of the lower arm. 

2011 No funding(s) sources. 

Authors affiliated with the University of Louisville 

Human laboratory study 

Healthy adults (mean age 24.4) 

N=17 ...at 5 minutes afte

gel blood flow signartery by 42%. 

Topp R, Winchester LJ, Schilero J, Jacks D. 

Effect of topical menthol on ipsilateral and contralateral superficial blood flow following a bout of maximum voluntary muscle contraction. 

2011 University of Louisville 

Foundation, Hygienic Research Fund 

Human laboratory study 

Healthy adults (average age 24.19±2.97) 

N=16 ...the application o

gel or 10% menthoblood flow... 

The application of menthol wipe reduon the side receivi

Valero ML, Mello de Queiroz F, Stühmer W, Viana F, Pardo LA. 

TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells. 

2012 Financed by the MaxPlanck Society and grants 

SAF2010-14990 and PROMETEO2010-046, and a predoctoral fellowship from the Spanish government. 

Nonclinical Three human prostate 

cell lines (normal and cancerous) 

N/A We observed no c

growth after stimumenthol... 

Villanti AC, 

Giovino GA, Barker DC, 

Menthol brand switching among adolescents and 

2012 Schroeder Institute for 

Tobacco Research and Policy Studies at Legacy 

Longitudinal random-digit telephone 

Smokers (age 16-24) who had ever smoked 20 lifetime cigarettes 

N=1045 After 2 years, prop

menthol smokers cigarettes (15.0%; 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Mowery PD, Sevilimedu V, Abrams DB. 

young adults in the National Youth Smoking Cessation Survey. 

survey and had smoked within 

the past 30 days 

than baseline non

to menthol brands 

Vozoris NT. 

Mentholated cigarettes and cardiovascular and pulmonary diseases: a population-based study. 

2012 No funding source(s). 

Author affiliated with Kingston General Hospital; Queen’s University 

National representative survey (2001­2008 NHANES) 

Current smokers (age ≥20) with ascertained menthol smoker status 

N=5028 After also controlli

diagnosed, self-rediabetes mellitus, stroke remained sall (OR, 2.19; 95% 3.54; 95% CI, 1.60American (OR, 3.0mentholated cigarnonmentholated c

Widome R, Brock B, Noble P, Forster JL. 

The relationship of neighborhood demographic characteristics to point-of-sale tobacco advertising and marketing. 

2013 Grant from the Robert 

Wood Johnson Foundation; Minnesota Department o fHealth 

Cross-sectional study with US Census 

Licensed tobacco vendors in St. Paul, MN 

N=654 stores 

...higher minority pareas were more lof ads for menthol Stores in block groproportions of AfriBlacks, Asians, peunder the age of 1have more mentho

Willis DN, Liu B, Ha MA, Jordt SE, Morris JB. 

Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. 

2011 NIH Grants and the 

American Asthma Foundation 

Nonclinical mice N/A ...counterirritant e

model are appareequal to those presmoke. 

Wilson N, Weerasekera D, Peace J, Edwards R. 

Smokers have varying misperceptions about the harmfulness of menthol cigarettes: 

2011 Health Research Council 

of New Zealand 

Cross-sectional analysis of ITC (International Tobacco Control Policy Evaluation Survey) data 

Adult smokers from the 

2008/2009 wave who participated in this telephone survey 

N=923 ...some groups of 

users and Pacific ssmoking menthol cthan regular cigare

* Note: these statements are taken directly from articles and may not include all rele
   

                                 

             

                           

             

                                   

                         

                   

                                 

                         

                               

                               

                         

       

                                       

                           

     

                                         

               

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Anderson, S. J. (2011). Menthol cigarettes and smoking cessation behaviour: a review of tobacco

industry documents. Tobacco control, 20 Suppl 2, ii49‐ii56. 20/Suppl_2/ii49;10.1136/tc.2010.041947

Ashley, M., Dixon, M., Sisodiya, A., & Prasad, K. (2012). Lack of effect of menthol level and type

on smokers' estimated mouth level exposures to tar and nicotine and perceived sensory characteristics

of cigarette smoke. Regulatory toxicology and pharmacology : RTP, 63, 381‐390. S0273‐2300(12)00089‐

X;10.1016/j.yrtph.2012.04.010

Benowitz, N. L., Dains, K. M., Dempsey, D., Wilson, M., & Jacob, P. (2011). Racial differencesin

the relationship between number of cigarettessmoked and nicotine and carcinogen exposure. Nicotine

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Bodnar, J. A., Morgan, W. T., Murphy, P. A., & Ogden, M. W. (2012). Mainstream smoke

chemistry analysis of samplesfrom the 2009 US cigarette market. Regulatory toxicology and

pharmacology : RTP, 64, 35‐42. S0273‐2300(12)00093‐1;10.1016/j.yrtph.2012.05.011

Brinkman, M. C., Chuang, J. C., Gordon, S. M., Kim, H., Kroeger, R. R., Polzin, G. M. et al. (2012).

Exposure to and deposition of fine and ultrafine particlesin smokers of menthol and nonmenthol

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Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

national survey data. 

Wise PM, Breslin PA, Dalton P. 

Sweet taste and menthol increase cough reflex thresholds. 

2012 NIH Grants and Kraft 

Foods 

Human laboratory study 

Healthy adults (age 23­

36); 12 nonsmokers, 1 light smoker 

N=13 Inhalation of head

decreased cough concentration of cacough, relative to a solvent blank. 

Wise PM, Preti G, Eades J, Wysocki CJ. 

The effect of menthol vapor on nasal sensitivity to chemical irritation. 

2011 Institutional funds from the 

Monell Chemical Senses Center 

Human laboratory study 

Healthy adults (age 21­

46 

N=22 Pretreatment with 

sensitivity to nasa(participants requilateralize) but increisothiocyanate (lowrequired). 

Wu X, Desai KG, Mallery SR, Holpuch AS, Phelps MP, Schwendeman SP. 

Mucoadhesive fenretinide patches for sitespecific chemoprevention of oral cancer: enhancement of oral mucosal permeation of fenretinide by coincorporation of propylene glycol and menthol. 

2012 Fanconi Anemia Research 

Fund and NIH grants 

Nonclinical (porcine buccal preparation) 

N/A N/A vitro and in vivo re

was not significantcoincorporation of indicating that masand not the patch, the permeation rat

Yerger VB. 

Menthol's potential effects on nicotine dependence: a tobacco industry perspective. 

2011 DHHS Contract Documents 

research 

N/A N=309 

documents 

The tobacco indusoverrides the harsalleviates nicotinesynergistically intethe trigeminal nervfor a tobacco prodnicotine tobacco psmokers than nonproducts. 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

market. 

Brinkman MC, Chuang JC, Gordon SM, Kim H, Kroeger RR, Polzin GM, Richter PA. 

Exposure to and deposition of fine and ultrafine particles in smokers of menthol and nonmenthol cigarettes. 

2012 Contract from the Centers 

for Disease Control and Prevention (CDC) 

Nonclinical and Laboratory 

Smokers (age 18-30) who smoked at least 1 pack/day for at least 6 months 

N=9 ... there were no s

measured in daily and participant spparticipants smokeThere were no sigof urinary cotinine nonmenthol cigareUrinary 1-HOP levdifferent between The menthol test chigher number (11ultrafine particles tcigarette. Participants smokcigarettes/day... atest cigarettes. ...participants took required a longer pmenthol cigarette, volume of smoke i(73 ml/cigarette) a

Brody AL, 2012 Tobacco-Related Disease Clinical study Healthy adult smokers N=22 Menthol and non-m

Mukhin AG, La Research Program, NIH (10-40 cpd) menthol not differ on any dCharite J, Ta K, Up-regulation of grant, Veterans Affairs smokers, measure, other thaFarahi J, Sugar nicotinic Type I Merit Review N=41 CA, Mamoun acetylcholine Award, endowment from nonmenthol Follow-up tests revMS, Vellios E, receptors in the Richard Metzner Chair smokers differences for the Archie M, menthol cigarette in Clinical corpus callosum... Kozman M, smokers. Neuropharmacology 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Phuong J, Arlorio F, Mandelkern MA. Buday T, Brozmanova M, Biringerova Z, Gavliakova S, Poliacek I, Calkovsky V, Shetthalli MV, Plevkova J. 

Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels. 

2012 VEGA no 1/0031/11 and 

Centre of Experimental and Clinical Respirology II (CEKR) co-financed from EU sources 

Human laboratory study 

Healthy non-smoking adults (average age 23) 

N=18 Both menthol isom

significantly moduthreshold, and totathe reduction of aicapsaicin challeng

Caraballo RS, Holiday DB, Stellman SD, Mowery PD, Giovino GA, Muscat JE, Eriksen MP, Bernert JT, Richter PA, Kozlowski LT. 

Comparison of serum cotinine concentration within and across smokers of menthol and nonmenthol cigarette brands among nonHispanic black and non-Hispanic white U.S. adult smokers, 2001­2006. 

2011 No funding source(s). 

Authors affiliated with the Centers for Disease Control and Prevention, RTI International, Georgia State University, Columbia University, State University of New York at Buffalo, Penn State College of Medicine 

Cohort survey (NHANES 2001-2006) 

Smokers (age ≥20) who 

had smoked on the day of or the day prior to the NHANES visit 

N=1943 Smoking a mentho

smoking a nonmeassociated (P< 0.0concentration in e...only a minority (smokers smoked mthe majority (73.9%menthol brand. Menthol cigarettes (1.24 mg) were on nicotine levels to tmg) smoked by wh

Cheang WS, Lam MY, Wong WT, Tian XY, Lau CW, Zhu Z, Yao X, Huang Y. 

Menthol relaxes rat aortae, mesenteric and coronary arteries by inhibiting calcium influx 

2013 National Basic Research 

Program of China, a research grant from Research Grants Council of Hong Kong, and CUHK Focused Investment Scheme B. 

Nonclinical Rat tissue, cell culture N/A The present study 

relaxes rat arteries probably vianifedipvascular smooth mindependent of the 

Dauphinee AL, Racial differences 2013 NIH grant Longitudinal 6th-9th grade students N=2589 On average, the p

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Doxey JR, in cigarette brand study with (age 11-15) in Vallejo, featured a mentho

Schleicher NC, recognition and some cross- California voice) was 36.9% Fortmann SP, impact on youth sectional than the average fHenriksen L. smoking. analyses 26.1)... 

...provide the branfor Marlboro, and The odds of smokfor students who rat baseline. 

Delnevo CD, Gundersen DA, Hrywna M, Echeverria SE, Steinberg MB. 

Smokingcessation prevalence among U.S. smokers of menthol versus non-menthol cigarettes. 

Cross-sectional TUS-CPS 

Black, White and Hispanic current smokers and those who have quit in the past 5 years 

N=71,193 to 24,465 (depending on sample restrictions) 

...there was a smabetween menthol cwhereby smokers signifıcantly less li

smokers of non-m

D'Silva J, Boyle RG, Lien R, Rode P, Okuyemi KS. 

Cessation outcomes among treatment-seeking menthol and nonmenthol smokers. 

2012 No funding source(s). 

Authors were affiliated with ClearWay Minnesota; University of Minnesota; Professional Data Analysts; Minnesota Department of Health 

Cross-sectional survey with single follow-up 

Cigarette smokers who called the Minnesota Quitline and registered for services 

N=1172 menthol smokers, N=5085 nonmenthol smokers 

...the odds of quittnot signifıcantly dismokers (OR 1.29controlling for the 

Faseru B, Choi WS, Krebill R, Mayo MS, Nollen NL, Okuyemi KS, Ahluwalia JS, Cox LS. 

Factors associated with smoking menthol cigarettes among treatment-seeking African American light smokers. 

2011 NIH Grant Clinical trial Treatment-seeking 

African-American light (≤10 cpd) smokers 

N=452 menthol, N=88 nonmenthol 

Table 1 Baseline cand non-menthol s

Faseru B, Nollen NL, Mayo MS, Krebill R, Choi 

Predictors of cessation in African American light smokers 

2013 NIH Grants; NRSA grant, 

American Cancer Society Institutional Research Grant 

Clinical trial Treatment-seeking 

African-American light (≤10 cpd) smokers 

N=540 Our current study 

effect of menthol oAmerican light smwere less likely to 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

WS, Benowitz NL, Tyndale RF, Okuyemi KS, Ahluwalia JS, Sanderson Cox L. 

enrolled in a bupropion clinical trial. 

non-menthol cigar

Fowler P, Smith K, Young J, Jeffrey L, Kirkland D, Pfuhler S, Carmichael P. 

Reduction of misleading ("false") positive results in mammalian cell genotoxicity assays. I. Choice of cell type. 

2012 European Cosmetic 

Industry Association, UK National Centre for the 3Rs (NC3Rs) 

Nonclinical 6 in vitro cell lines N/A It was cytotoxic, in

in RI at the top cowere no increases In other cases (e.glimited by cytotoxilevels of cytotoxici

Frasnelli J, Albrecht J, Bryant B, Lundström JN.Frasnelli J, Albrecht J, Bryant B, Lundström JN. 

Perception of specific trigeminal chemosensory agonists. 

2011 Postdoctoral fellowship 

from the Canadian Institutes of Health Research 

Human laboratory study 

Healthy adults with no reductions in sense of smell 

N=20 All stimuli clearly a

as demonstrated blateralizing them. The scores for methe highest correlaEucalyptol and mepredominantly coorespectively), fresh p and 0.7 p, respe

Gordon SM, Brinkman MC, Meng RQ, Anderson GM, Chuang JC, Kroeger RR, Reyes IL, Clark PI. 

Effect of cigarette menthol content on mainstream smoke emissions. 

2011 Battelle internal research 

and development funds 

Nonclinical N/A N/A Menthol in the TPM 

cigarettes at each investigated showapplied menthol coof nicotine, target quinolone in the ciunchanged. SimilaVOCs in mainstreacigarettes that werpuff-by-puff basis unaffected by the 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

the cigarettes. 

Hans M, Wilhelm M, Swandulla D. 

Menthol suppresses nicotinic acetylcholine receptor functioning in sensory neurons via allosteric modulation. 

2012 Altria Client Services, Inc. Nonclinical Nicotinic acetylcholine 

receptors (native and recombinant) 

N/A ...we show that nA

neurons are reversan IC50 of 111 lMfrom human a4b2 revealed that mensingle channel amopen time and a pWe conclude that menthol-mediated an allosteric modumenthol. 

Henriksen L, Schleicher NC, Dauphinee AL, Fortmann SP. 

Targeted advertising, promotion, and price for menthol cigarettes in California high school neighborhoods. 

2012 California’s TobaccoRelated Disease Research 

Program grant 

Cross-sectional study 

Stores within walking distance of California high schools 

N=407 For each 10 perce

proportion of Black menthol advertisinpoints... The menthol share percentage points increase in the proresidents ages 10–For each 10 perceproportion of Black advertising a Newgreater 

Hickman NJ 3rd, Delucchi KL, Prochaska JJ. 

Menthol use among smokers with psychological distress: findings from the 2008 and 2009 National Survey on Drug Use and Health. 

2012 NIH grants Nationally 

representative cohort study (NSDUH) 

Current smokers (age ≥18) who answered the item on menthol use 

N=24157 The prevalence of 

this national samp33.3%. The prevalence of among individuals distress, women, yAmericans, Native persons with feweincome, the unma

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Janssens A, Voets T. 

Ligand stoichiometry of the cold- and menthol-activated channel TRPM8. 

2011 Grants from the Belgian 

Federal Government, the Research FoundationFlanders, and the Research Council of the KU Leuven 

Nonclinical TRPM8 ion channels 

expressed in HEK293 cells 

N/A This indicates that 

bind up to four mestepwise stabilizat

Jones MR, Apelberg BJ, Samet JM, Navas-Acien A. 

Smoking, menthol cigarettes, and peripheral artery disease in U.S. adults. 

2012 NIH Grants Nationally 

representative survey from 1999-2004 (NHANES) 

Adults (age ≥ 40) N=5973 Serum cotinine an

concentrations wementhol cigarettes nonmenthol cigareWe observed no sassociation betweartery disease for nonmenthol and mheterogeneity = 0.

Jones MR, Apelberg BJ, Tellez-Plaza M, Samet JM, Navas-Acien A. 

Menthol cigarettes, race/ethnicity, and biomarkers of tobacco use in U.S. adults: the 1999-2010 National Health and Nutrition Examination Survey (NHANES). 

2012 NIH grants Cohort 

nationally representative survey from 1999-2010 (NHANES) 

Adult current smokers 

(including White, African American and Mexican American smokers) 

N=4603 In a representative 

smokers, current massociated with incadmium, an estatoxic metal, but noA total of 3,210 (74nonmenthol cigare(25.7%) participancigarettes... After further adjuscorresponding ratiand no longer statcotinine (1.03; 95% 

Kabat GC, Shivappa N,HÃ©bert JR. 

Mentholated cigarettes and smoking-related cancers revisited: an ecologic 

2012 NIH Grants Multiple years 

of SEER data 

Case and controls: lung. esophageal, oropharyngeal, laryngeal cancer 

Not given/Not appropriate 

Given the large difmentholated cigarmenthol had a dissmoking-related casee one or both of 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

examination. higher incidence ra

sexes compared to differences in the tBlacks and Whites 

Kramlinger VM, von Weymarn LB, Murphy SE. 

Inhibition and inactivation of cytochrome P450 2A6 and cytochrome P450 2A13 bymenthofuran, Î2- nicotyrine and menthol. 

2012 NIH Grants Nonclinical In vitro N/A Inhibition of CYP2

less potent (Ki of 1There was no indicCYP2A6 or CYP2A

Levy DT, Blackman K, Tauras J, Chaloupka FJ, Villanti AC, Niaura RS, Vallone DM, Abrams DB. 

Quit attempts and quit rates among menthol and nonmenthol smokers in the United States. 

2011 Legacy Nationally 

representative cross-sectional TUC-CPS from 2003 and 2006/7 

Adult smokers who had 

smoked at least 100 cigarettes and are either current or former smokers 

Unknown Table 1 presents t

and former smokeyears by cigarette 2007, about 70% ssmoked menthol, Although they had attempt, menthol snonmenthol smokquit successfully in 12%less likely in 2

Lu S, BaadHansen L, List T, Zhang Z, Svensson P. 

Somatosensory profiling of intraoral capsaicin and menthol in healthy subjects 

2013 NIH research grant Human 

laboratory study 

Healthy adults (mean age 31.5±7.5) 

N=15 More than half (9/

mild levels of pain Our study showed menthol on the ginhyperesthesia... 

Millqvist E, TernestenHasséus E, Bende M. 

Inhalation of menthol reduces capsaicin cough sensitivity and influences inspiratory flows in 

2013 Grants from the Regional 

Health Care Authority of West Sweden, the Swedish Asthma and Allergy Association and the Swedish Heart and 

Human laboratory study 

Patients: non-smokers with histories of cough and other airway symptoms induced by environmental irritants ( average age 51). 

N=14 (patients) N=15 (controls) 

We conclude that that is not caused infections, pre-inhcough sensitivity tinfluences inspirat

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

chronic cough. Lung Foundation 

Controls: healthy nonsmokers (average age 52). 

Muscat JE, Liu HP, Stellman SD, Richie JP Jr. 

Menthol smoking in relation to time to first cigarette and cotinine: results from a community-based study. 

2012 NIH Grants; contracts from 

DHHS; Pennsylvania Department of Health 

Human laboratory study 

Daily smokers (≥5 cpd 

for one or more years) 

N=495 . Overall there was 

smoking and a shoanalyzed by race, black subjects (P < The time to first cimenthol (P = 0.66with cotinine levels

Naziroğlu M, Ozgül C. 

Effects of antagonists and heat on TRPM8 channel currents in dorsal root ganglion neuron activated by nociceptive cold stress and menthol. 

2012 No funding source(s). 

Authors affiliated with University of Suleyman Demirel, Turkey 

Nonclinical Rat dorsal root ganglia N/A In the current stud

activated by menth

Nelson PR, Chen P, Dixon M, Steichen T. 

A survey of mouth level exposure to cigarette smoke in the United States. 

2011 No funding source(s). 

Authors affiliated with R.J. Reynolds Tobacco Company 

Human study Healthy smokers (≥7 

cpd) who smoked one of the selected brand styles as their usual brand style 

N= 1330 The regression lin

fell slightly below tcigarettes suggestlower MLEs per cistyles. However, dintercepts of the restatistically signific

Nonnemaker J, Hersey J, Homsi G, Busey A, Allen J, Vallone D. 

Initiation with menthol cigarettes and youth smoking uptake. 

2012 DHHS contract Cross-sectional 

survey 

Middle and high school students from 83 schools in seven communities and five states 

N=638 (progression analysis) or N=399 (dependence analysis) 

The models reveasignificant associainitiation [odds ratiinterval (CI): 1.02–established smokiAs shown, initiatio

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

positively and signdependence (b = 1

Pereira EJ, Sim L, Driver H, Parker C, Fitzpatrick M. 

The effect of inhaled menthol on upper airway resistance in humans: A randomized controlled crossover study. 

2013 Research grants from the 

Ontario Thoracic Society, William M. Spear Foundation, Queen’s University and Clinical Teachers Association at Queen’s University 

Human laboratory study 

Healthy adults (age 21±0.5 years) 

N=10 ...90% of participa

breathe easier on The present study receptor stimulatioinhaled menthol dairway respiration] subjects. 

Reitzel LR, Li Y, Stewart DW, Cao Y, Wetter DW, Waters AJ, Vidrine JI. 

Race moderates the effect of menthol cigarette use on short-term smoking abstinence. 

2013 NIH Grant; CDC grant, 

The University of Texas MD Anderson Cancer Center 

Cohort study Current smokers (age 

18-65), smoking ≥5 cpd for at least a year, willingness to quit 

N=183 The main effects o

continuous short-tnot significant... Menthol use was sshort-term continuamong White partWhite menthol uselikely to maintain cthan White nonme95% CI = 0.05–0.9

Reitzel LR, 2011 NIH Grants Clinical trial Women who smoked N= 123 White menthol use

Nguyen N, Cao Race/ethnicity prior to pregnancy and menthol continuous abstineY, Vidrine JI, moderates the quit either during smokers, users. Daza P, Mullen effect of pregnancy or within 2 121 PD, Velasquez prepartum months of becoming nonmenthol MM, Li Y, menthol cigarette pregnant smokers Cinciripini PM, use on postpartum Cofta-Woerpel smoking L, Wetter DW. abstinence. Rosenbloom J, A cross-sectional 2012 NIH Grant, the Harvard Cross-sectional Women smokers N=198 A greater proportio

Rees VW, Reid study on tobacco School Office for study African their first cigarette K, Wong J, use and Enrichment Programs and American, (p < 0.01)... Kinnunen T. dependence the Harvard School of N=730 White 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

among women: Does menthol matter? 

Dental Medicine The ANOVAs cond

menthol preferencper day, age of sm

Rostron B. 

NNAL exposure by race and menthol cigarette use among US smokers. 

2012 (epub) 

No funding source(s). 

Author affiliated with FDA 

Nationally representative survey (NHANES) 

NHANES smoker participants from 2007­2010 (age ≥20) 

N=1614 Menthol cigarette 

NNAL concentratioThis difference waNNAL concentratiocompared with noWhite smokers. Nicotine and carciby NNAL and cotinCPD across race/esmokers. 

Rostron B. 

Lung cancer mortality risk for U.S. menthol cigarette smokers. 

2012 No funding source(s). 

Author affiliated with FDA 

Nationally representative survey (NHISCCS) 

Adult participants (age 

≥ 18) who were smokers identified with either menthol or nonmenthol preference (pack verified) 

N=4832 The HR for lung ca

smokers at ages 5(95% CI = 0.37 – 0

Sarkar M, Wang J, Liang Q 

Metabolism of nicotine and 4­(methylnitrosamin o)-1-(3-pyridyl)-lbutanone (NNK) in menthol and non-menthol cigarette smokers 

2013 No funding source(s). 

Authors affiliated with Altria Client Services 

Multi-center, cross-sectional study (TES) 

Adult participants (age 

≥21) who reported smoking ≥1cpd for at least the past 12 months 

N=1044 menthol; 2297 nonmenthol 

Race, machine-smage interaction terfactors for the 3OHThe biomarkers of carboxyhemoglobnot statistically sig

Strasser AA, Ashare RL, Kaufman M, Tang KZ, Mesaros AC, Blair IA. 

The effect of menthol on cigarette smoking behaviors, biomarkers and subjective responses. 

2013 NIH Grants Human 

laboratory study 

Adult smokers (age 21­

65); smoke ≥10 cpd, smoke menthol cigarettes at least 80% of the time 

N=32 ...the experimenta

increase in total pbrand) to period 2 period 2 (menthol) 0.06) and a signifi1 and 3 (P = 0.02)There was a signif

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

from period 1 (basmean difference=1but there was no dand 3 (non-menthoexperimental grouCotinine values hanicotine values; theffects or interactio

Topp R, Winchester L, Mink AM, Kaufman JS, Jacks DE. 

Comparison of the effects of ice and 3.5% menthol gel on blood flow and muscle strength of the lower arm. 

2011 No funding(s) sources. 

Authors affiliated with the University of Louisville 

Human laboratory study 

Healthy adults (mean age 24.4) 

N=17 ...at 5 minutes afte

gel blood flow signartery by 42%. 

Topp R, Winchester LJ, Schilero J, Jacks D. 

Effect of topical menthol on ipsilateral and contralateral superficial blood flow following a bout of maximum voluntary muscle contraction. 

2011 University of Louisville 

Foundation, Hygienic Research Fund 

Human laboratory study 

Healthy adults (average age 24.19±2.97) 

N=16 ...the application o

gel or 10% menthoblood flow... 

The application of menthol wipe reduon the side receivi

Valero ML, Mello de Queiroz F, Stühmer W, Viana F, Pardo LA. 

TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells. 

2012 Financed by the MaxPlanck Society and grants 

SAF2010-14990 and PROMETEO2010-046, and a predoctoral fellowship from the Spanish government. 

Nonclinical Three human prostate 

cell lines (normal and cancerous) 

N/A We observed no c

growth after stimumenthol... 

Villanti AC, 

Giovino GA, Barker DC, 

Menthol brand switching among adolescents and 

2012 Schroeder Institute for 

Tobacco Research and Policy Studies at Legacy 

Longitudinal random-digit telephone 

Smokers (age 16-24) who had ever smoked 20 lifetime cigarettes 

N=1045 After 2 years, prop

menthol smokers cigarettes (15.0%; 

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

Mowery PD, Sevilimedu V, Abrams DB. 

young adults in the National Youth Smoking Cessation Survey. 

survey and had smoked within 

the past 30 days 

than baseline non

to menthol brands 

Vozoris NT. 

Mentholated cigarettes and cardiovascular and pulmonary diseases: a population-based study. 

2012 No funding source(s). 

Author affiliated with Kingston General Hospital; Queen’s University 

National representative survey (2001­2008 NHANES) 

Current smokers (age ≥20) with ascertained menthol smoker status 

N=5028 After also controlli

diagnosed, self-rediabetes mellitus, stroke remained sall (OR, 2.19; 95% 3.54; 95% CI, 1.60American (OR, 3.0mentholated cigarnonmentholated c

Widome R, Brock B, Noble P, Forster JL. 

The relationship of neighborhood demographic characteristics to point-of-sale tobacco advertising and marketing. 

2013 Grant from the Robert 

Wood Johnson Foundation; Minnesota Department o fHealth 

Cross-sectional study with US Census 

Licensed tobacco vendors in St. Paul, MN 

N=654 stores 

...higher minority pareas were more lof ads for menthol Stores in block groproportions of AfriBlacks, Asians, peunder the age of 1have more mentho

Willis DN, Liu B, Ha MA, Jordt SE, Morris JB. 

Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. 

2011 NIH Grants and the 

American Asthma Foundation 

Nonclinical mice N/A ...counterirritant e

model are appareequal to those presmoke. 

Wilson N, Weerasekera D, Peace J, Edwards R. 

Smokers have varying misperceptions about the harmfulness of menthol cigarettes: 

2011 Health Research Council 

of New Zealand 

Cross-sectional analysis of ITC (International Tobacco Control Policy Evaluation Survey) data 

Adult smokers from the 

2008/2009 wave who participated in this telephone survey 

N=923 ...some groups of 

users and Pacific ssmoking menthol cthan regular cigare

* Note: these statements are taken directly from articles and may not include all rele
Reference Addendum 

Author Article Title Year Funded By Type of Study Subject Description Sample Authors’ ResultsName(s) Pub. (Including Special Size (N) Menthol* 

Population(s)) (excerpted direc

national survey data. 

Wise PM, Breslin PA, Dalton P. 

Sweet taste and menthol increase cough reflex thresholds. 

2012 NIH Grants and Kraft 

Foods 

Human laboratory study 

Healthy adults (age 23­

36); 12 nonsmokers, 1 light smoker 

N=13 Inhalation of head

decreased cough concentration of cacough, relative to a solvent blank. 

Wise PM, Preti G, Eades J, Wysocki CJ. 

The effect of menthol vapor on nasal sensitivity to chemical irritation. 

2011 Institutional funds from the 

Monell Chemical Senses Center 

Human laboratory study 

Healthy adults (age 21­

46 

N=22 Pretreatment with 

sensitivity to nasa(participants requilateralize) but increisothiocyanate (lowrequired). 

Wu X, Desai KG, Mallery SR, Holpuch AS, Phelps MP, Schwendeman SP. 

Mucoadhesive fenretinide patches for sitespecific chemoprevention of oral cancer: enhancement of oral mucosal permeation of fenretinide by coincorporation of propylene glycol and menthol. 

2012 Fanconi Anemia Research 

Fund and NIH grants 

Nonclinical (porcine buccal preparation) 

N/A N/A vitro and in vivo re

was not significantcoincorporation of indicating that masand not the patch, the permeation rat

Yerger VB. 

Menthol's potential effects on nicotine dependence: a tobacco industry perspective. 

2011 DHHS Contract Documents 

research 

N/A N=309 

documents 

The tobacco indusoverrides the harsalleviates nicotinesynergistically intethe trigeminal nervfor a tobacco prodnicotine tobacco psmokers than nonproducts. 

* Note: these statements are taken directly from articles and may not include all rele