Bad bitterness made better for everyone: Global taste differences in the flavor of medicines

A global study published in Chemical Senses and led by the Monell Chemical Senses Center examined the bitterness intensity of five medicines and two bitter modifiers in 338 adults of European descent and recent US and Canadian immigrants from Asia, South Asia, and Africa. They found bitterness ratings differed by ancestry for two of the five drugs and the effectiveness of some modifiers. They also found genetic variants that explain some population differences in reaction to bitter tastes.

“This is the first study to compare participants from diverse ancestries tasting different bitter medicines,” said first author Ha Nguyen, PhD, the Carol M. Christensen Postdoctoral Fellow at Monell.

Specifically, the tasting panel included five bitter-tasting medicines — tenofovir alafenamide (TAF; for HIV), moxifloxacin (for tuberculosis), praziquantel (for schistosomiasis, a type of worm), amodiaquine (for malaria), and propylthiouracil (PROP; for hyperthyroidism). Other solutions were tested, too: TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness) and sucralose alone.

A global study led by the Monell Chemical Senses Center examined the bitterness intensity of five medicines and two bitter modifiers in adults of European descent and recent US and Canadian immigrants from Asia, South Asia, and Africa.

Big Differences in Bitterness

Large person-to-person differences in bitterness ratings were found for all medicines in all ancestry groups. Within each group, some people rated the medicines at the top of the bitter scale, indicating intense bitterness, whereas others rated it as weak as water. Despite this wide range of responses within each group, 40 percent of the medicines differed by ancestry group. On average, PROP was more bitter for people of Asian ancestry than other ancestries, and amodiaquine was more bitter for people of European ancestry than people of African ancestry.

The differences in PROP bitterness among ancestries confirmed earlier knowledge regarding the distribution of TAS2R38 taste receptor genetic variants among different global regions. There were also ancestry differences in the bitterness of TAF when sucralose was added. When sucralose was added as a sweetener to modify bitterness, it worked better for Africans than Asians.

“Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them,” said Nguyen.

The Benefits of Making Bitter Better

Bitterness is not always bad; it can be helpful when added to products to prevent accidental poisonings. “However, bitter avoidance doesn’t help when patients reject medicines,” said senior author Dani Reed, PhD, Monell Chief Science Officer. “From my own experience, it can be embarrassing to explain to a doctor that I did not give my child the full dose of medicine because they refused to take it because of the taste.”

Many clinicians know that a drug’s poor palatability is a barrier to completing and adhering to treatment, and this non-adherence is consequential in low-resource places where every dose of medicine is vital.

“These medicines have added ingredients like sweeteners to reduce bitterness, but often these additions are only partially effective at improving taste,” said Nguyen. “By learning about differences among people and groups, we are working on bitter-blocking strategies to improve the taste of medicines for everyone so that all who need them can more easily take them.”

This work was supported by funding from the National Institutes of Health (R42 DC017693), the Gates Foundation (INV-005381), the Monell Chemical Senses Center’s Carol M. Christensen Postdoctoral Fellowship in Human Chemosensory Science Fund; and Monell Chemical Senses Center Institutional Funds.