RELATIONSHIPS BETWEEN BITTER TASTE SENSITIVITY AND CONSUMPTION OF BITTER SUBSTANCES

The effect of consumption of bitter taste substances (caffeine and beer) to bitter taste sensitivity was examined by 19 healthy adults. For individual taste sensitivity, detection thresholds were used on 6 bitter substances (caffeine, iso-alpha-acids: beer bittering agents, quinine sulfate, L-tryptophan, L-phenylalanine and glycyl-L-phenylalanyl-L-phenylalanine) and 3 non-bitter substances (L-aspartic acid, aspartame and NaCl). Nonusers of caffeine had significantly higher sensitivity (lower threshold) for caffeine compared to moderate and heavy users. Slight consumers of beer had significantly higher sensitivity for iso-alpha-acids relative to heavy users of beer, Iso-alpha-acids were not detected in saliva in acute dosing test by using 6 subjects. The correlations between thresholds of 6 bitter substances were calculated. Significant correlations (p < 0.01) were noted in 2 cases between caffeine and quinine, and iso-alpha-acids and L-trypothan. These data suggest the significant relation between individual bitter taste sensitivity and the consumption of caffeine and beer (iso-alpha-acids).     

Bitter taste thresholds, numbers and diameters of circumvallate papillae and their relation with age in a Turkish population

Objectives: This study analyses the relationship between the sense of bitter taste and age. The relationships between these and the numbers and diameters of Circumvallate Papillae (CP) are also analysed. Subjects: Twenty-four elderly subjects (from 65 to 85 years) and 30 young subjects (from 17 to 25 years) were studied. Method: Bitter taste thresholds were determined by the three drop method with an ascending series of concentrations. The numbers and diameters of CP were observed by direct naked eye observation using a wooden tongue depressor, a gauge and a light source. Results: The bitter taste acuity was significantly poorer in the older sample. There was no relationship between the bitter taste acuity and number of papillae but an inverse relationship was observed between the bitter taste acuity and diameters of papillae, thus lower acuity was associated with larger papillae. It was also observed that the diameters of papillae were inversely related to the numbers of CP. The distribution of numbers and diameters of CP were not significantly different between these samples with age.     

Taste Sensitivity and Aging: High Incidence of Decline Revealed by Repeated Threshold Measures

Contrary to what has often been said about the subject, declinein taste sensitivity with aging characterizes virtually everybodyand is not the artificial result of averaging large losses ofa minority with negligible losses of a majority. This assertionis supported by six repeated measures of sucrose thresholdsin each of 15 older (over 64 years) and 15 younger (under 27years) adult subjects. Threshold was determined by a proceduresimilar to past studies and with the same results: much scatterand considerable overlap between the thresholds of younger andolder subjects. A quite contrasting picture emerges, however,when each subject's six threshold determinations are averaged.Averaging shrinks the individual differences among subjects,as well as the over-lap between younger and older subjects.Although virtually all elderly subjects now revealed taste weakness,reliable individual differences in degree of weakness aboundamong them, suggesting various individual rates of physiologicalaging. In contrast young persons exhibit greater uniformityof sensitivity. These findings were brought out by inter-testcorrelations, which were much higher for the older subjects;i.e. an older subject who tended to score high (low) on onetest tended to score high (low) on the other tests. The studyconfirms the tenuous nature of brief threshold tests as indicesof personal sensitivity as found earlier also in olfactory thresholdsand in concurrent measurement of two-point touch thresholdsin the present study. This revealed correlated losses betweenrepeated taste and touch thresholds from the same 15 older subjects,unrelated to their exact chronological age. Chem. Senses 20:451–459, 1995.     

Genetic Sensitivity to 6-n-Propylthiouracil (PROP) and Hedonic Responses to Bitter and Sweet Tastes

Genetically mediated sensitivity to the bitter taste of 6-n-propylthiouracil(PROP) has been associated with greater acuity for bitter andfor some sweet tastes. Thus far, few studies have explored therelationship between PROP taste sensitivity and hedonic responsesto bitter and sweet. In this study, 87 normal-weight young womenwere divided into PROP non-tasters (n = 18), regular tasters(n = 49), and supertasters (n = 20), based on their PROP detectionthresholds and the scaling of five suprathreshold solutionsof PROP and NaCl. Non-tasters had thresholds >1.8 x 10^–4mol/l PROP. Supertasters had thresholds <3.2 x 10^–5mol/l PROP and PROP/NaCl ratios >1.70. As expected, dislikeof the bitter taste of PROP was determined by its perceivedintensity, which was greater among supertasters than among regulartasters or non-tasters. Significant correlations were observedbetween PROP taste thresholds and the sum of intensity ratings(r = –0.61) and between summed intensity and summed hedonicratings (r = –0.80). PROP taste sensitivity was weaklylinked to enhanced perception of sweet taste, but did not predicthedonic responses to sucrose or to saccharin solutions. Giventhat the dislike of PROP solutions is determined by their perceivedintensity, hedonic responses to PROP solutions may provide arapid way of screening for PROP taster status. Chem. Senses22: 27–37, 1997.     

Genetic analysis of a complex trait in the Utah Genetic Reference Project: a major locus for PTC taste ability on chromosome 7q and a secondary locus on chromosome 16p

The ability to taste phenylthiocarbamide (PTC) shows complex inheritance in humans. We obtained a quantitative measure of PTC tasting ability in 267 members of 26 large three-generation families that were part of a set of CEPH families that had been used for genetic mapping. Significant bimodality was found for the distribution of age and gender adjusted scores (P<0.001), with estimated means of 3.16 (SD=1.80) and 9.26 (SD=1.54). Using the extensive genotyping available in these families from the genetic mapping efforts, we performed a genome scan by using 1324 markers with an average spacing of 4 cM. Analyses were first carried out with a recessive genetic model that has traditionally been assumed for the trait, and a threshold score of 8.0 delineating tasters from non-tasters. In this qualitative analysis, the maximum genome-wide lod score was 4.74 at 246 cM on chromosome 7; 17 families showed segregation of the dichotomous PTC phenotype. No other lod scores were significant; the next highest score was on chromosome 10 (lod=1.64 at 85 cM), followed by chromosome 3 (lod=1.29 at 267 cM). Because PTC taste ability exhibited substantial quantitative variation, the quantitative trait was also analyzed by using a variance components approach in SOLAR. The maximum quantitative genome-wide lod score was 8.85 at 246 cM on chromosome 7. Evidence for other possible quantitative loci was found on chromosomes 1 (lod=2.31 at 344 cM) and 16 (lod=2.01 at 14 cM). A subsequent two-locus whole-genome scan conditional on the chromosome 7 quantitative trait locus identified the chromosome 16 locus (two-locus lod=3.33 at 14 cM).     

Effect of chorda tympani nerve transection on salt taste perception in mice

Effects of gustatory nerve transection on salt taste have been studied extensively in rats and hamsters but have not been well explored in the mouse. We examined the effects of chorda tympani (CT) nerve transection on NaCl taste preferences and thresholds in outbred CD-1 mice using a high-throughput phenotyping method developed in our laboratory. To measure taste thresholds, mice were conditioned by oral self-administration of LiCl or NaCl and then presented with NaCl concentration series in 2-bottle preference tests. LiCl-conditioned and control NaCl-exposed mice were given bilateral transections of the CT nerve (LiCl-CTX, NaCl-CTX) or were left intact as controls (LiCl-CNT, NaCl-CNT). After recovery from surgery, mice received a concentration series of NaCl (0-300 mM) in 48-h 2-bottle tests. CT transection increased NaCl taste thresholds in LiCl-conditioned mice and eliminated avoidance of concentrated NaCl in control NaCl-exposed mice. This demonstrates that in mice, the CT nerve is important for detection and recognition of NaCl taste and is necessary for the normal avoidance of high concentrations of NaCl. The results of this experiment also show that the method of high-throughput phenotyping of salt taste thresholds is suitable for detecting changes in the taste periphery in mouse genetic studies.     

Comparing sensory experience in bitter taste perception of phenylthiocarbamide within and between human twins and singletons: intrapair differences in thresholds and genetic variance estimates

BACKGROUND: Quantitative genetic studies revealed that not all of the phenotypic variance in PTC taste perception is heritable. AIM: To study quantitative variations in PTC tasting ability in twins and to estimate heritability of PTC taste perception on the taste of twin data on males and females sexes separately. SUBJECTS AND METHODS: The data for PTC taste sensitivity following the classic method of Harris & Kalmus (1949) were collected on a sample of 141 twin pairs (66 MZ and 75 DZ) and 275 singletons (128 males and 147 females) from Chandigarh, India. Genetic analyses were performed following Christian (1979), Donner (1986) and Sham (1998). RESULTS: Frequency of non-tasters was similar in twins (33 %) and singletons (32 %), but significant sex differences were observed. No differences were found between zygosities for mean thresholds. Similarly, no evidence of variance heterogeneity and environmental covariance was seen between zygosities. Since no basic assumption of the twin method was found violated, within-pair estimates of genetic variance would be unbiased. These estimates were highly significant in both males and females. However, dominance and additive components of genetic variance were found to differ between sexes. CONCLUSION: PTC thresholds do not seem to be significantly affected by environmental factors as no variance inequality was observed between twin zygosities. Intensity of bitterness (scalar dimensions) of PTC is a separate trait having no commonality with the genetic basis of recognition threshold for PTC tasting ability. The receptors recognizing bitter taste are different from the receptors determining intensity of taste. The absolute difference between co-twins in PTC thresholds can be used as a simple tool in the twin zygosity diagnosis. The results show that none of the MZ co-twins had manifested difference of more than 3 in their PTC threshold.     

Taste thresholds and above-threshold responses to fructose solution in relation to diet in Callitrichidae primates]

Taste thresholds and consumption responses to above-threshold concentrations of fructose solutions were determined in eight callitrichid primate species using the "two-bottle preference test". Although taste thresholds are relatively similar across species, above-threshold responses may differ considerably between marmosets and tamarins. As fructose concentration increases, the rate of consumption increases less for most marmoset species (Cebuella and Callithrix spp.) than for Goeldi's monkey (Callimico) and tamarins (Saguinus and Leontopithecus spp.). It is proposed that distinct shapes of the curves illustrating these responses characterize species in terms of global taste system adaptations to different diets.     

Effects of linoleic acid on sweet, sour, salty, and bitter taste thresholds and intensity ratings of adults

Evidence supporting a taste component for dietary fat has prompted study of plausible transduction mechanisms. One hypothesizes that long-chain, unsaturated fatty acids block selected delayed-rectifying potassium channels, resulting in a sensitization of taste receptor cells to stimulation by other taste compounds. This was tested in 17 male and 17 female adult (mean +/- SE age = 23.4 +/- 0.7 yr) propylthiouracil tasters with normal resting triglyceride concentrations (87.3 +/- 5.6 mg/day) and body mass index (23.3 +/- 0.4 kg/m(2)). Participants were tested during two approximately 30-min test sessions per week for 8 wk. Eight stimuli were assessed in duplicate via an ascending, three-alternative, forced-choice procedure. Qualities were randomized over weeks. Stimuli were presented as room-temperature, 5-ml portions. They included 1% solutions of linoleic acid with added sodium chloride (salty), sucrose (sweet), citric acid (sour), and caffeine (bitter) as well as solutions of these taste compounds alone. Participants also rated the intensity of the five strongest concentrations using the general labeled magnitude scale. The suprathreshold samples were presented in random order with a rinse between each. Subjects made the ratings self-paced while wearing nose clips. It was hypothesized that taste thresholds would be lower and absolute intensity ratings or slopes of intensity functions would be higher for the stimuli mixed with the linoleic acid. Thresholds were compared by paired t-tests and intensity ratings by repeated measures analysis of variance. Thresholds were significantly higher (i.e., lower sensitivity) for the sodium chloride, citric acid, and caffeine solutions with added fatty acid. Sweet, sour, and salty intensity ratings were lower or unchanged by the addition of a fatty acid. The two highest concentrations of caffeine were rated as weaker in the presence of linoleic acid. These data do not support a mechanism for detecting dietary fats whereby fatty acids sensitize taste receptor cells to stimulation by taste compounds.     

Is There Any Effect on Smell and Taste Functions with Levothyroxine Treatment in Subclinical Hypothyroidism?

Subclinical hypothyroidism has been accused for coronary heart disease, lipid metabolism disorders, neuropsychiatric disorders, infertility or pregnancy related problems with various strength of evidence. Currently there is insufficient knowledge about olfaction and taste functions in subclinical hypothyroidism. Aim of the present study is to investigate the degree of smell and taste dysfunction in patients with subclinical hypothyroidism. 28 subclinical hypothyroid patients, and 31 controls enrolled in the prospective study in Istanbul, Turkey. Subclinical hypothyroid patients were treated with L-thyroxine for 3 months. Psychophysiological olfactory testing was performed using odor dispensers similar to felt-tip pens (“Sniffin’ Sticks”, Burghart, Wedel, Germany). Taste function tests were made using "Taste Strips" (Burghart, Wedel, Germany) which are basically tastant adsorbed filter paper strip. Patients scored lower on psychophysical olfactory tests than controls (odor thresholds:8.1±1.0 vs 8.9±1.1, p = 0.007; odor discrimination:12.4±1.3 vs 13.1±0.9, p = 0.016; odor identification:13.1±0.9 vs 14.0±1.1, p = 0.001; TDI score: 33.8±2.4 vs 36.9±2.1, p = 0.001). In contrast, results from psychophysical gustatory tests showed only a decreased score for “bitter” in patients, but not for other tastes (5.9±1.8 vs 6.6±1.0, p = 0.045). Three month after onset of treatment olfactory test scores already indicated improvement (odor thresholds:8.1±1.0 vs 8.6±0.6, p<0.001; odor discrimination:12.4±1.31 vs 12.9±0.8, p = 0.011; odor identification:13.1±0.9 vs 13.9±0.8, p<0.001; TDI scores:33.8±2.4 vs 35.5±1.7, p<0.001) respectively. Taste functions did not differ between groups for sweet, salty and, sour tastes but bitter taste was improved after 3 months of thyroxin substitution (patients:5.9±1.8 vs 6.6±1.2, p = 0.045). Correlation of changes in smell and taste, with thyroid function test were also evaluated. TSH, fT4 were found have no correlation with smell and taste changes with treatment. However bitter taste found positively correlated with T3 with treatment(r: 0.445, p: 0.018). Subclinical hypothyroid patients exhibited a significantly decreased olfactory sensitivity; in addition, bitter taste was significantly affected. Most importantly, these deficits can be remedied on average within 3 months with adequate treatment.     

Propylthiouracil Tasting: Determination of Underlying Threshold Distributions using Maximum Likelihood

The ability to taste low concentrations of propylthiouracil(PROP) and related bitter compounds is heritable. The currentanalysis determines whether the distribution of PROP taste thresholdsis consistent with an additive or a dominant mode of Mendeliantransmission. To that end, the lowest concentration of PROPdetectable was determined for 1015 subjects and models of bi-or tri-modal distributions of PROP taste thresholds were tested.The model with the greatest likelihood had three distributionsand followed an additive model of PROP taste sensitivity ifthe variances associated with the distributions were assumedto be equal. However, if the taste thresholds were transformedto remove skewness, or if the variances were unequal, then three-or two-distribution models were equally likely. Resolution ofthe mode of inheritance for bitter taste perception awaits additionalfamily studies and the characterization of the molecular basisof taste perception for these bitter compounds. Chem. Senses20: 529–533, 1995.     

Decline in taste and odor discrimination abilities with age, and relationship between gustation and olfaction

It is important to learn about changes in both taste and odor perceptions with increasing age, because the taste of foods we encounter in our daily life is strongly affected by their smell. This study discusses the difference in qualitative taste and odor discrimination between the elderly and the young. Tastants and odorants used in this study were presented not as single stimuli but as a taste mixture (sucrose and tartaric acid) and an odor mixture (beta-phenylethyl alcohol and gamma-undecalactone). The results showed that quality discrimination abilities of the elderly subjects for both taste and odor were significantly lower than those of the young subjects, indicating a decline in quality discrimination abilities related to age. Also, a moderate but significant correlation was observed between the taste discrimination ability and the odor discrimination ability. We measured thresholds for single-taste and odor components in mixtures and compared them between the elderly and the young to investigate the cause for these findings.     

The effect of age on the recognition thresholds of three sweeteners: sucrose,saccharin and aspartame

It iS believed that people's sensitivity to taste declines with age but the evidence is inconclusive. This study was designed to test the hypothesis that taste recognition thresholds (TRTs) for sweetness are higher in older than in younger individuals, using groups of 16 younger subjects (18–30) and 16 older subjects (60–85). Three test substances were used: sucrose, aspartame and saccharin. A questionnaire recorded variables which might have affected TRTs, but data failed to show any trend that might have biased the principle variate-age. There was a significant alteration with age of recognition thresholds, at least for sucrose and saccharin. The differences between the groups for the three sweeteners were due to the fact that all the very sensitive subjects were young. None of the older subjects had particularly poor discrimination: all but one had TRTs within the range of younger subjects. Although there are age-related taste changes, they are much less dramatic than commonly occurs with other senses, such as sight and hearing. The findings of this study have implications for institutional catering and the dietary management of older people using non-sugar sweeteners.     

Oral amiloride treatment decreases taste sensitivity to sodium salts in C57BL/6J and DBA/2J mice

Sodium taste transduction is thought to occur via an amiloride-sensitive, sodium-selective pathway and an amiloride-insensitive, cation nonselective, anion-dependent pathway(s). It has been shown by others that amiloride, an epithelial sodium channel (ENaC) blocker, significantly reduces the chorda tympani nerve response to lingually applied NaCl in C57BL/6 (B6) mice but not in DBA/2 (D2) mice, suggesting that the latter strain might not possess functional ENaCs in taste receptor cells. We psychophysically measured and compared taste detection thresholds of NaCl and sodium gluconate (NaGlu) prepared with and without 100 microM amiloride in these two strains (eight/strain). Mice were trained and tested in a two-response operant signal detection procedure conducted in a gustometer. Surprisingly, no strain effect was found for the detection thresholds of both salts (approximately 0.05-0.06 M). Moreover, these thresholds were increased by almost an order of magnitude by amiloride adulteration of the solutions. This marked effect of amiloride on sodium detection thresholds suggests that ENaCs are necessary for normal sensitivity to sodium salts in both strains. In addition, because NaGlu is thought to stimulate primarily the amiloride-sensitive pathway, especially at low concentrations, the similarity of NaCl and NaGlu thresholds (r > 0.81 both strains) suggests that ENaCs are also sufficient to support the detection of sodium in weak solutions by B6 and D2 mice.     

Genetic and Molecular Basis of Individual Differences in Human Umami Taste Perception

Umami taste (corresponds to savory in English) is elicited by L-glutamate, typically as its Na salt (monosodium glutamate: MSG), and is one of five basic taste qualities that plays a key role in intake of amino acids. A particular property of umami is the synergistic potentiation of glutamate by purine nucleotide monophosphates (IMP, GMP). A heterodimer of a G protein coupled receptor, TAS1R1 and TAS1R3, is proposed to function as its receptor. However, little is known about genetic variation of TAS1R1 and TAS1R3 and its potential links with individual differences in umami sensitivity. Here we investigated the association between recognition thresholds for umami substances and genetic variations in human TAS1R1 and TAS1R3, and the functions of TAS1R1/TAS1R3 variants using a heterologous expression system. Our study demonstrated that the TAS1R1-372T creates a more sensitive umami receptor than -372A, while TAS1R3-757C creates a less sensitive one than -757R for MSG and MSG plus IMP, and showed a strong correlation between the recognition thresholds and in vitro dose - response relationships. These results in human studies support the propositions that a TAS1R1/TAS1R3 heterodimer acts as an umami receptor, and that genetic variation in this heterodimer directly affects umami taste sensitivity.     

A RESEARCH NOTE: COMPARISON OF TIME-INTENSITY AND THRESHOLD MEASURES FOR DETERMINING BITTER TASTE SENSITIVITY OF CAFFEINE USER AND NONUSER

Two taste sensitivity measures (detection threshold and time-intensity [T/I]) were applied to evaluate bitter taste sensitivity of caffeine in both caffeine nonusers (n = 12) and users (n=12, caffeine consumption level; > 300mg/day). Taste thresholds of caffeine were significantly different between nonusers and users in two test sessions (p < 0.01 in first and p < 0.05 in second). In T/I measures, only the difference in peak height was observed between the two groups in one of two test sessions. The other two measures, half width and area of T/I curves showed no significant difference.     

Formulation and Evaluation of Taste Masked Oral Reconstitutable Suspension of Primaquine Phosphate

The purpose of this research was to mask the intensely bitter taste of primaquine phosphate (PRM) and to formulate suspension powder (cachets) of the taste masked drug. Taste masking was done using beta-cyclodextrin. To characterize and formulate taste masked cachets of PRM, the 1:25 M physical mixture was selected based on bitterness score. Phase solubility studies, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. Cachets were evaluated for angle of repose, sedimentation characterization and pH. In vitro drug release studies for physical mixture and kneaded system were performed at pH, 1.2 and 6.8. Bitterness score was evaluated using gustatory sensation test. Phase solubility studies showed weak interaction between PRM and CD. The FTIR, DSC and XRPD studies indicated inclusion complexation in physical mixture and kneaded system. In addition, kneaded system and physical mixture exhibited better drug release at pH 1.2 and negligible effect at pH 6.8. Cachets prepared using physical mixture, (DS24), showed complete bitter taste masking and easy redispersibility. Taste evaluation of cachets in human volunteers rated tasteless with a score of 0 to DS24 and 3 to DS25. Thus, results conclusively demonstrated successful taste masking and formulation of cachets with taste masked drug.     

Comparison of visual and CAS-200 quantitation of immunocytochemical staining in breast carcinoma samples.

Using the CAS-200 image analysis system, we compared the relationship between semiautomated computer measurements (QIC score) and visual scoring (H score) on 30 breast cancer fine needle aspirates (FNAs) and corresponding tissue specimens stained by the estrogen receptor immunocytochemical assay. These results were compared to the corresponding biochemistry assays for ER. We also investigated whether the computerized system could decrease false-negative staining for ER in 32 cryostat sections. QIC scores were generated using fixed nuclear and antibody thresholds after standardizing the illumination. Computer quantitation was essentially as precise as visual semiquantitation for FNAs: a small but significant correlation was found between tumor ER content and QIC score (r = .504, P less than .02) as compared with H score and ER content (rs = .55, P less than .005). The computerized system did not decrease the false-negative rate in cryostat sections. In all, computerized quantitation was no better than visual analysis of ER staining in these breast carcinomas.     

Perception of sweet taste is important for voluntary alcohol consumption in mice

To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: α-gustducin ( Gnat3 ), Tas1r3 or Trpm5 . Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.     

Taste sensitivity to phenylthiourea (PTC) in the rhesus monkey (Macaca mulatta)

The hypothesis that the distribution of thresholds of taste sensitivity to phenylthiourea (PTC) is unimodal was tested in a group of 367 rhesus monkeys. The distribution was found to be unimodal and highly skewed. The regression of taste thresholds of offspring on that of their father was 0.840±0.34. This estimate is consistent with an hypothesis of essentially no environmental influence. It was concluded that phenotypic variability at the PTC tasting locus in rhesus monkeys is almost totally determined by the non-additive influences of several genes on taste sensitivity.