The Bitter Truth: The Taste of Some Medications Depends on Variations in Bitter Receptor Genes

AMHERST, Mass. – “Good medicine tastes bitter,” the Chinese saying goes. Mary Poppins had a cure for that in the timeless tune: “Just a spoonful of sugar helps the medicine go down.”

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Now, University of Massachusetts Amherst sensory scientist Alissa Nolden has a scientific explanation for those truisms. Her new research, published in a special Nutrigenomics issue of Frontiers in Genetics, shows that the degree of bitterness for two common antibiotics relates to genetic differences in people’s TAS2R bitter taste receptors.

How medicine – especially in oral liquid form – tastes is important because it’s thought to be associated with whether patients appropriately take and complete their medication regimen. “Taste can be a real issue,” says Nolden, assistant professor of food science. “It’s something that everyone has experienced, and it can lead to rejection or low compliance. But there are very few studies that are published on the sensory profile of any antibiotics.”

Humans have 25 bitter taste receptors (TAS2Rs) – which are now known to be located throughout the body, not just on the tongue, and serve various non-tasting roles. The TAS2R receptors are thought to have evolved as warning signs for toxic foods and substances. The idea is not to make medicine taste yummy because that could attract children or otherwise encourage dangerous misuse.

“There’s a fine line between acceptable and aversive,” Nolden says. “The goal isn’t to taste good.”

For the study, 143 participants rated the intensity of taste sensations, including bitterness. Nolden, who collected the study’s data while completing her Ph.D. at Pennsylvania State University, focused on the bitterness ratings of two antibiotics – chloramphenicol and ofloxacin. Bitterness was the dominant sensation for both drugs, and on average was rated near moderate intensity. However, not all participants experienced the same bitterness intensity.

“Bitterness intensity is strongly associated with genetic mutations in our bitter taste receptors,” Nolden explains. One of the most studied bitter taste receptor mutations is associated with the bitterness perception of propylthiouracil, a thyroid medication, and phenylthiocarbamide, a chemical compound found in cruciferous vegetables. In general, among a Caucasian population, about 50 percent of people will experience moderate bitterness; 25 percent will have a more functional phenotype and taste bitterness more intensely; and 25 percent will have a less functional genetic difference, experiencing a reduced sense of bitterness.

“We anticipated finding individual variability, with some individuals perceiving high bitterness and some individuals perceiving lower bitterness of these antibiotics,” Nolden says. “We also investigated whether or not this variability would be associated with genetic mutations in our bitter taste receptor genes. We were successful in examining the sensory profile of these antibiotics and linking individual variability in bitterness intensity with two different bitter taste receptor mutations.”

Ultimately, medication taste may fall in the realm of personalized medicine – the idea that medical treatments are customized based on a person’s genetic makeup. Screening medications taking into account the common genetic differences in bitter taste receptors may enhance the effectiveness of prescription drugs.

“This is just the beginning,” says Nolden, emphasizing that research is needed to expand data on the genetic profiles of bitter taste receptors among different racial and ethnic groups. “The take-home message is that drugs are often bitter, and they haven’t been investigated in terms of individual variability in sensory perception.”

She concludes in her paper, “Improved understanding of individualized barriers to patient compliance, especially for oral formulations, can guide future efforts to optimize delivery systems for improved compliance.”