Subject characteristics, dietary intake, and completion of psychophysical tasks by age group.

a<p>Categories to classify BMI are from the Centers for Disease Control and Prevention for children <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092201#pone.0092201-Kuczmarski1" target="_blank">[44]</a> and standard BMI categories for mothers.</p>b<p>Intake data are averaged from the 2 testing days and were collected and analyzed using the Automated Self-Administered 24-Hour Recall, beta version (2009).</p>c<p>One teaspoon of added sugar is 4 g; adapted from the National Cancer Institute.</p>d<p>Income level is in US dollars; one mother did not report her income (n = 75).</p

Effect of <i>TAS2R38</i> genotype on sensitivity to the bitter taste of PROP.

<p>The cumulative percentage of children (top) and mothers (bottom) in each of the three allele groups (AA, AP, PP) who first detected a bitter or “yucky” taste when sampling 56, 180 and 560 µM PROP or who never detected a bitter taste when sampling each of these PROP solutions (“none tasted bitter”). *Significantly different from adults of same <i>TAS2R38</i> genotype (p<0.05).</p

Multivariate models.

<p>η², proportion of variance accounted for; <i>F</i>, Fisher value; df, degrees of freedom. Only children with complete data for these variables were included in the analysis (e.g., n = 78 for Model 1). Variables shown in boldface made a significant contribution to the model.</p

Subject characteristics and completion of psychophysical tasks by age group.

<p>Abbreviations: MSG, monosodium glutamate; NaG, sodium gluconate; PROP, propylthiouracil; SEM, standard error of the mean. ¹Not all 118 mothers and 154 children participated in both sets of blocker paired comparisons.</p

Associations between sweet and salty taste preferences and height, percent body fat, and NTx.

<p>Panels show associations between most preferred levels of sweet (left) and salty (right) tastes and height (top), percent body fat (middle), and NTx (bottom). Three outlying values of NTx (open data points) were removed for most analyses but are shown here for comparison.</p

Univariate analysis of generation (mother vs. child) effects on sweet and salty taste preferences and genotype-related effects on sweet taste preferences.

a<p>Post-hoc analysis; different symbols (*,†) denote genotype groups with sucrose preference values significantly different from each other. For siblings, one child was picked randomly for this analysis so that all children were unrelated.</p

Correlation between salt and sugar intake and preferences.

<p>(A) Reported sugar and sodium intake correlated in children (p<0.01) and in mothers (p<0.001). (B) Daily sodium intake was associated with preferred salt level in broth in children (p<0.05) but not in mothers. (C) Daily added sugar intake was not related to preferred sucrose levels.</p

Summary of efficacy of NaG and MSG in reducing bitterness in adult and pediatric populations: analysis of the ranking data.

<p>Abbreviations: MSG, monosodium glutamate; NaGlu, sodium gluconate; PROP, propylthiouracil. ↓ signifies the blocker significantly reduced bitterness of a particular bitter agent as determined by Friedman statistical tests of ranks. ↔ signifies the blocker did not significantly reduce bitterness.</p

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

<div><p>Background</p><p>Bitter 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.</p><p>Methods</p><p>A 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).</p><p>Results</p><p>The 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 <i>TAS2R38</i> genotype. Children liked the salty taste of the blocker NaG more than did adults, but both groups liked the savory taste of MSG equally.</p><p>Conclusions and Relevance</p><p>Bitter 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.</p></div

Efficacy of blockers: summary of post hoc analyses* from bitter rankings in the paired-comparison test ¹ by <i>TAS2R38</i> genotype for each of the two blockers when combined with PROP in each of the two groups: children and adults (means ± SEM).

<p>Abbreviations: PROP, propylthiouracil; SEM, standard error of the mean. Putative bitter blockers—NaG, 0.3 M sodium gluconate; MSG, 0.1 M glutamate. Rankings for bitterness range from 1 (least) to 4 (most); see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103107#pone.0103107.s001" target="_blank">Table S1</a> for ranking procedure. Different letters indicate rankings that are statistically different from each other within each row. Genotypes (AA, AP, PP) refer to the bitter-sensitive (P) and bitter-insensitive (A) forms of A49P alleles of the <i>TAS2R38</i> bitter receptor gene.¹All Friedman statistical tests of rank tests were significant at p≤0.05.</p