Age-Related Differences in Bitter Taste and Efficacy of Bitter Blockers

Abstract

BackgroundBitter taste is the primary culprit for rejection of pediatric liquid medications. We probed the underlying biology of bitter sensing and the efficacy of two known bitter blockers in children and adults.MethodsA racially diverse group of 154 children (3-10 years old) and their mothers (N = 118) evaluated the effectiveness of two bitter blockers, sodium gluconate (NaG) and monosodium glutamate (MSG), for five food-grade bitter compounds (quinine, denatonium benzoate, caffeine, propylthiouracil (PROP), urea) using a forced-choice method of paired comparisons. The trial was registered at clinicaltrials.gov (NCT01407939).ResultsThe blockers reduced bitterness in 7 of 10 bitter-blocker combinations for adults but only 3 of 10 for children, suggesting that efficacy depends on age and is also specific to each bitter-blocker combination. Only the bitterness of urea was reduced by both blockers in both age groups, whereas the bitterness of PROP was not reduced by either blocker in either age group regardless of TAS2R38 genotype. Children liked the salty taste of the blocker NaG more than did adults, but both groups liked the savory taste of MSG equally.Conclusions and RelevanceBitter blocking was less effective in children, and the efficacy of blocking was both age and compound specific. This knowledge will pave the way for evidence-based strategies to help develop better-tasting medicines and highlights the conclusion that adult panelists and genotyping alone may not always be appropriate in evaluating the taste of a drug geared for children.

The sweetness and bitterness of childhood: Insights from basic research on taste preferences

“…To examine age-related efficacy of bitter blockers (both sodium salts and sucrose), we conducted basic research studies using PROP and the generally recognized as safe (GRAS) bitter agents urea, caffeine, quinine, denatonium benzoate (a compound typically added to detergents to deter ingestion by children), and tetralone (i.e., iso-alpha acids commonly found in beer) as test stimuli. The ability of two sodium salts (sodium gluconate and monosodium glutamate) to block bitter taste was both compound specific, consistent with adult studies [75, 78], and age specific [77, 78]. In general, if the sodium salt worked in blocking (or enhancing) bitterness for a given bitter ligand in children, it also worked for adults, but not vice versa (Table 1).…”

“… PROP, 6- n -propylthiouracil; ↓, decreased bitterness; ↑, increased bitterness; ↔, no effect; NA, not assessed. a Adapted from Mennella et al [45, 77, 78]. …”

“…In recent years, we have developed methods to conduct basic research on bitter taste in children to determine whether the same methods that work in the blocking or suppression of bitter taste in adults also work for children [45, 77, 78]. To examine age-related efficacy of bitter blockers (both sodium salts and sucrose), we conducted basic research studies using PROP and the generally recognized as safe (GRAS) bitter agents urea, caffeine, quinine, denatonium benzoate (a compound typically added to detergents to deter ingestion by children), and tetralone (i.e., iso-alpha acids commonly found in beer) as test stimuli.…”

Influences of weight, age, gender, genetics, diseases, and ethnicity on bitterness perception: a narrative review of current methodological aspects

“…The method using forced choice of paired comparisons intends to obtain more concise and valid results [10]. Tests with 6-n-propylthiouracil (PROP) seeking to detect "non-taster" and "taster" subjects are commonly employed in children because they do not require reading skills [11].…”

Proceedings of the 2015 ASPEN Research Workshop—Taste Signaling

“…Children have sensory systems that detect and prefer the once rare calorie‐ and mineral‐rich foods that taste sweet or salty, 101 while rejecting the potentially toxic ones that taste bitter 102 , 103 . Such age‐related changes in taste perception and preference, documented by experimental research during the past century, 102 indicate that the rewarding properties of sweeteners and salt and the aversive properties of bitter‐tasting compounds are more pronounced during childhood.…”