Genetic sensitivity to bitter tastes may impact adherence to oral smoking cessation products

"Tobacco companies have amassed a wonderful database exploring the genetics of taste and its impact on a person's smoking experience," says Karen Ahijevych, PhD, a researcher at The Ohio State University College of Nursing. "We thought it would be interesting to reapply some of that knowledge to see if taste sensitivities impact adherence to oral NRT- which is often a first-line therapy for smoking cessation."

Nicotine has a bitter component. For the study, Ahijevych tested smokers to determine their threshold for detecting a bitter chemical called n-6-propylthiouracil (PROP). PROP taste thresholds vary widely, but are generally due to a sequence variation in the bitter receptor gene TAS2R38.Previous research indicates that about 25 percent of people have a TAS2R38 variant that makes them ultra-sensitive to bitter flavors. These "super-tasters" are also less likely to be nicotine dependent.

"We know NRT is effective at reducing cigarette consumption, but super-tasters may not be the best candidates because they can really taste the bitterness in oral NRT products," said Ahijevych, whose research was supported by a grant from Ohio State's Center for Clinical and Translational Science and the National Institute on Drug Abuse. "Knowing the degree of a person's bitterness sensitivity could help a clinician choose a more effective smoking cessation plan."

To identify super-tasters from moderate and non-tasters, Ahijeyvch had participants rate the intensity of tiny paper discs infused with a specific amount of PROP. Participants that ranked PROP as having the "strongest oral sensation imaginable" were labeled as super-tasters. Additional genetic sequencing was done on each participant to verify that the results of their "taste test" correlated with the presence of the bitter receptor gene TASR38 and its variants. The groups were randomized to use one week of oral NRT lozenges and one week of a nicotine inhaler and encouraged to remain smoke free. Smoking status was assessed throughout the study.

Mirroring a scale that tobacco companies use when testing new cigarette products, Ahijevych also quizzed participants about the two forms of oral NRT. She asked smokers about the strength of mouth sensation, product likeability, and level of satisfaction with the NRT therapies.

Ultimately, Ahijevych did not find a strong correlation between bitter sensitivity phenotype and a reduced use of oral NRT. While non-tasters used more lozenges than super-tasters, all of the study volunteers used considerably fewer lozenges or nicotine inhaler puffs than prescribed, making it difficult to draw a conclusion. However, she says that the study did find other evidence about taste perceptions that could impact the way clinicians prescribe NRT.

"We found that menthol cigarette users consistently reported experiencing stronger mouth sensations than other users. This could indicate that the use of menthol has primed them to expect sensations that may make them better oral NRT candidates," said Ahijevych. "We also found that after just two weeks of using NRT, non-tasters who reduced or eliminated cigarette consumption started becoming more sensitive to bitter tastes."

Anecdotally smokers experience tastes and smells differently, likely because smoke changes the taste perception. In Ahijevych's study, 30 percent of people who were initially identified as non-tasters were more sensitive to bitter flavors after using the oral NRT therapies for two weeks, suggesting that when people reduce smoking, their taste sensitivities begin to recover.

Ahijevych notes that her study used nicotine replacement therapies with no flavor. Like tobacco companies, companies that make oral NRT products are also experimenting with flavors like coffee and menthol. But even a sweet or savory flavor may not be enough to trick a bitter super-taster.

"Clearly, the sensitivity to bitterness is not set in stone. It's a snapshot of a moment, and can change over time, particularly when smoking is reduced," said Ahijevych. "I think taste perception is something that clinicians could explore with patients to help make sure they are getting the most out of a smoking cessation program."

Ahijevych thinks that someday the PROP-infused discs that were used to evaluate subjects' level of bitterness sensitivity could be developed into a simple, inexpensive point of care test. That way, clinicians could know immediately if their patient may respond more favorably to smoking cessation medications that bypass taste. An in-office test would also allow clinicians to monitor how a patient's taste sensitivities were changing over time, and modify the intervention accordingly.

While Ahijevych didn't find the link between bitter phenotype and oral NRT avoidance she was looking for -- the study did have at least one huge impact. Even with being on a sub-therapeutic dose of NRT, study participants ultimately reduced their cigarette consumption from an average of 15 a day to just 4 a week within a two week timeframe.

"NRT definitely works if people can stick with it as part of a larger plan," said Ahijevych, who is currently part of the NIH-funded Ohio State University Center of Excellence for Tobacco Regulatory Science. "The tobacco companies have spent considerable time understanding what sensations and tastes it takes to get people hooked on smoking. We can use the same strategies along with new research to help curb that interest and reduce smoking-related death and illness."