Researchers at the University of Connecticut School of Pharmacy and Yale University have found that the cooling properties of menthol suppress the respiratory system’s natural response to the irritants found in cigarette smoke, increasing the likelihood that people who smoke mentholated cigarettes will become addicted to them and suffer future health problems.

The findings are particularly important for younger smokers, the researchers warn, because they tend to prefer menthol cigarettes over non-menthol brands. As an additive to cigarettes, menthol stimulates cold receptors, giving the sensation of coolness in the mouth, pharynx, and lungs.

The study appears online in the Journal of the Federation of American Societies for Experimental Biology (FASEB).

Menthol, the natural cooling agent in peppermint, is present in almost all commercially-sold cigarettes in varying degrees, even those not marketed as mentholated. While there has been much debate about the harmful effects of menthol cigarettes, the UConn-Yale study is the first to confirm menthol’s pharmacological effects on smokers and its potential connection to addiction and smoking-related disease.

The UConn-Yale research team found that in mice, vaporized menthol immediately blocked the response in airway receptors that promote sensations of irritation to protect the respiratory system. The mouse equivalent of a “smoker’s cough” was almost completely blocked when mice inhaled menthol and tobacco irritants together.

“The irritant sensations produced by smoke warn people they are inhaling something dangerous,” says UConn Board of Trustees Distinguished Professor of Pharmacology & Toxicology John B. Morris, the study’s senior author.

“By blocking these important warning signs, mentholated cigarettes are easier to smoke and, therefore, are much more hazardous,” says Morris, assistant dean for research at the UConn School of Pharmacy and an expert in the toxicity of inhaled irritant vapors.

“This may be especially true for young people who are just starting to smoke for the first time.”

Adolescents 12 to 17 years old smoke menthol cigarettes at a higher rate than any other age group, according to a report by the Food and Drug Administration’s Tobacco Products Scientific Advisory Committee (TPSAC) released in March. About half of middle school smokers and 45% of high school smokers said they usually smoke a menthol brand, the report says.

“Studies indicate that most young people smoke menthol cigarettes,” says Sven-Eric Jordt, associate professor of pharmacology at Yale School of Medicine and co-principal investigator on the study with Morris.  “So they are being exposed to higher levels of nicotine and other toxic substances at a young age, which may lead to rapid addiction and, ultimately, the development of smoking-related disease.”

The findings add another dimension to the ongoing debate over the potential health

hazards presented by mentholated cigarettes. In 2009, Congress passed the Family Smoking Prevention and Tobacco Control Act, which outlawed flavored tobacco additives such as cloves, cinnamon, candy, chocolate or fruit flavors; but exempted menthol.

Earlier this year, the FDA’s Tobacco Products Scientific Advisory Committee, after a year-long review, acknowledged that it is “biologically plausible” that adding menthol to cigarettes may make them more addictive. But the committee deferred on making a recommendation to include menthol in the tobacco additives ban. While primarily used as a flavoring agent in menthol cigarettes, menthol can also be found in small quantities in non-menthol cigarettes where it is sometimes used as a flavor enhancer, as part of other commercial flavors or is an incidental byproduct of the tobacco manufacturing process, the committee’s report said. The FDA is currently re-evaluating scientific data on menthol in cigarettes, including the TPSAC report.

“Menthol is present in 90 percent of the commercial cigarettes in the U.S. including brands not marketed as being mentholated,” says Morris. “This is of great concern if menthol is acting as a drug to suppress protective respiratory tract responses.  Our study is novel in that it shows than menthol, at the levels in cigarette smoke, does, in fact, dramatically suppress respiratory tract irritation responses.”

Other researchers involved in the study were doctoral graduate students Michael A. Ha and Daniel N. Willis of the UConn School of Pharmacy’s toxicology program, and Boyi Liu of Yale.

This study was supported by the National Institutes of Health and the American Asthma

Foundation.