Disturbing Menthol Findings

A May 28, 2010 study in Nicotine and Tobacco Research examines the ability of menthol in tobacco products to increase mouth tissue penetration of nicotine and NNN, one of nicotine's cancer causing metabolites.  It concluded that "menthol enhances penetration of NNN and nicotine ... even after brief exposure." 

The study found that within 30 of applying  menthol to tissues that it allowed 6% more nicotine to penetrate floor of mouth tissues, with 29% greater penetration of cheek (buccal mucosa) tissue penetation.  As for the carcinogen NNN, within 30 minutes of applying menthol to tissues that NNN penetration was 19% greater in floor of mouth tissues and 29% greater in cheek tissues.  

Researchers knew prior to the study that:

1.  Menthol is the major component of peppermint oil.
2.  Menthol creates a minty flavor, aroma, and cooling sensation when it contacts skin and mucous membranes.
3.  Since 1926 menthol has been used to mask the bitterness and harshness of cigarette smoke.
4.  Today, 26% of cigarettes sold are menthols.
5.  Today, 66% of black male smokers smoke menthols, 73% of black female smokers, 27% of adult white female smokers as compared to only 18% of adult white male smokers.
6.  Oral cancers account for only 2% of all cancers yet roughly 80% of all oral cancers occur in smokers, and their rate of oral cancer is 5 to 9 times higher than in non-smokers.
7.  Today black men have the highest risk for developing oral cancer of any ethnic group, roughly 20% higher than for white males.

Exactly how menthol increases absorption remains unclear.  What has researchers concerned is that the evidence is building that menthol may actually be responsible for increasing disease risks, and the risk of nicotine dependency, at least in allowing youth and new smokers to tolerate inhaled smoke's harshness.  But how?  Is increased disease primarily due to the fact that menthol brands normally have greater tar and nicotine levels, that menthol allows users to suck those higher levels harder, deeper and hold them longer, to the tissue penetrating properties found in this study, or a combination?

Right now the U.S. Food and Drug Administration is examining the issue of menthol and the possibility of ordering its removal from all U.S. cigarette brands.   The FDA has selected a panel of experts to review the question.  That panel includes both cigarette industry representatives and pharmaceutical industry consultants for both Pfizer, with its menthol flavored nicotine inhaler, and GlaxoSmithKline, with its menthol flavored nicotine gum and lozenge.  In that powerful  economic interests could be in play, a shadow watchdog panel has been established to shadow or mirror analysis by the real panel and I was asked to be a part of that group.  Although we'll have no real authority, we're going to evaluate  the same evidence as the real panel and prepare our own FDA recommendation which we hope will at least be considered. 

Below is the study abstract (summary) from the paper.  Remember, if a former menthol brand user, all these menthol issues need no longer be your concern so long as all nicotine remains on the outside.  Still just one guiding principle for each of us ... no nicotine today!

Breathe deep, hug hard, live long,

John (Gold x11)

Effect of menthol on the penetration
of tobacco carcinogens  and nicotine
across porcine oral mucosa ex vivo

Nicotine & Tobacco Research Advance Access published online on May 28, 2010

Christopher A. Squier, Ph.D., D.Sc., Mary J. Mantz, M.S. and Philip W. Wertz, Ph.D.


Introduction: Menthol is a flavored tobacco additive claimed to mask the bitter taste and reduce the harshness of cigarette smoke. (Azzi, C., Zhang, J., Purdon, C. H., Chapman, J. M., Nitcheva, D., Hebert, J. R., et al., 2006, Permeation and reservoir function of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P) across porcine esophageal tissue in the presence of ethanol and menthol. Carcinogenesis, 27, 137–145). have shown that menthol increased the flux of tobacco carcinogens (TC) across porcine esophagus. As oral mucosa is exposed to both smoke and smokeless tobacco in tobacco users, the objective of this study was to determine whether menthol influenced the penetration of the TC nitrosonornicotine (NNN) across porcine buccal (BM) and floor of mouth (FM) mucosa.

Methods: Porcine BM and FM were collected at slaughter, mounted in perfusion chambers (n = 7/group), and exposed to tritiated NNN (3H-NNN; Amersham, activity 1 µCi/ml) and tritiated nicotine (3H-nicotine; Sigma) in 3% nicotine/phosphate-buffered saline (0.01 M, pH 7.4) containing 0.01% unlabeled NNN (National Cancer Institute Chemical Carcinogen Repository) ± 0.08% menthol for 0.5, 1, 2, or 12 hr. Kp values (cm/min) were determined and statistically analyzed (analysis of variance, Tukey’s, p < .05).

Results: FM and BM permeability to both 3H-NNN and 3H-nicotine was significantly increased (p < .05) with addition of menthol over that of nicotine alone regardless of exposure times. Even short 30-min menthol exposure significantly increased the flux of both compounds, and this was maintained throughout the experiment.

Discussion: Menthol enhances penetration of NNN and nicotine through FM and BM in vitro, even after short exposure. This may reflect loading of a superficial epithelial reservoir (Squier, C. A., Kremer, M. J., Bruskin, A., Rose, A., & Haley, J. D., 1999. Oral mucosal permeability and stability of transforming growth factor beta-3 in vitro. Pharmaceutical Research, 16, 1557–1563.), thus delivering menthol and enhancing flux for several hours. Practical implications are for a potentially increased oral exposure to carcinogens among users of menthol-flavored cigarettes and chewing tobacco.



Edited 2 times by JohnPolito May 31 10 2:24 PM.