March 2002

From American Chemical Society

Nicotine patches and gum may pose health hazards

The probable cause: a nicotine metabolite acting as catalyst

Nicotine patches and gum, designed to help smoker's quit, may be hazardous to your health. The finding is reported in the March 27 print issue of the Journal of the American Chemical Society, a peer-reviewed publication of the American Chemical Society, the world's largest scientific society. The article was published initially March 8 on the journal's Web site.

Widely believed to be safe, the patches and gum deliver nicotine to the system to quell the body's craving for it. But researchers at The Scripps Research Institute in La Jolla, Calif., report learning, for the first time, that a breakdown product of nicotine, called nornicotine, has the ability to interfere with a broad range of chemical reactions in the body and that this interaction has the potential to trigger adverse health effects.

The study suggests that those who take medications while smoking or using nicotine patches or gum may be at greater risk for potentially adverse drug interactions. Nornicotine could modify these drugs, possibly reducing drug potency and causing side effects, according to the researchers.

While patches and gum can vary in nicotine content, those who continue to smoke while using these products subject themselves to higher health risks by getting extra nicotine, they said.

They caution that their results are preliminary and limited to laboratory observations. The compound is undergoing further testing to determine its specific effects in animals and humans, but results are not yet available, the researchers added.

The study also implies that nornicotine adds to the health dangers of smoking itself. Although nicotine has been shown to be a dangerous chemical in addition to its known addictive properties, this is the first demonstration of the chemical potential of a nicotine metabolite, they said.

"This represents another potentially adverse chemical found in tobacco that's coming from nicotine itself," said the study's lead author, Kim D. Janda, Ph.D. "We've got to be more aware of this."

The addictive effects of nicotine have been known for some time. Nornicotine, also a natural constituent of tobacco, was thought to be a minor player in addiction. While investigating ways to treat nicotine addiction, Janda and graduate student Tobin Dickerson conducted a detailed chemical analysis of the breakdown of nicotine.

They found that nornicotine is not just an innocent bystander: it catalyzes certain reactions that play major roles in processing chemicals that circulate in the body, whereas nicotine itself has no effect on these chemical reactions.

The finding was surprising because it was believed that, under conditions found in the body, only certain enzymes were able to catalyze these reactions, and nornicotine is not an enzyme. The compound, which differs from nicotine by a single carbon atom, is the first example of a metabolite that acts as a catalyst for chemical reactions, the researchers said.

The researchers demonstrated that nornicotine could interact with many important chemical reactions, including the conversion of glucose into energy. Impairment of glucose metabolism has been linked to a broad range of potentially adverse disease conditions, they said.

They also identified certain medications, including steroids and antibiotics, which are likely to interact with nornicotine. This drug interaction could trigger potentially adverse health effects in humans. Tests are currently underway to determine specific drugs that may put smokers and other users of nicotine products at increased health risks.

How the compound works in the body and its specific health effects are unknown. But its ability to catalyze reactions in a laboratory setting calls into question its safety and underscores the need to avoid tobacco products containing nicotine, the researchers said.

Those who want to quit smoking may wish to consider treatments that don't involve nicotine, he added. "Unfortunately, although some nicotine-free treatments are currently undergoing testing, to our knowledge there are no nicotine-free treatments for smoking cessation therapies currently available over-the-counter," Janda said.

This study was funded by the Skaggs Institute for Chemical Biology.

-- Mark T. Sampson

The online version of the research paper cited above was initially published March 8 on the journal's Web site. Journalists can arrange access to this site by sending an e-mail to newsroom@acs.org or calling the contact person for this release.

Kim D. Janda, Ph.D., is a professor in the Department of Chemistry at The Scripps Research Institute in La Jolla, Calif.











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