Valerie B. Duffy

PTC/PROP tasting : anatomy, psychophysics, and sex effects

Taste worlds of humans vary because of taste blindness to phenylthiocarbamide (PTC) and its chemical relative, 6-n-propylthiouracil (PROP). We review early PTC studies and apply modern statistical analyses to show that a higher frequency of women tasted PTC crystals, and were tasters (threshold classification). In our laboratory, scaling of PROP bitterness led to the identification of a subset of tasters (supertasters) who rate PROP as intensely bitter. Supertasters also perceive stronger tastes from a variety of bitter and sweet substances, and perceive more burn from oral irritants (alcohol and capsaicin). The density of taste receptors on the anterior tongue (fungiform papillae, taste buds) correlate significantly with perceived bitterness of PROP and support the supertaster concept. Psychophysical data from studies in our laboratory also show a sex effect; women are supertasters more frequently. The anatomical data also support the sex difference; women have more fungiform papillae and more taste buds. Future investigations of PTC/PROP tasting and food behaviors should include scaling to identify supertasters and separate sex effects.

Bitter taste markers explain variability in vegetable sweetness, bitterness, and intake

Intake of vegetables falls short of recommendations to lower risk of chronic diseases. Most research addresses bitterness as a sensory deterrent to consuming vegetables. We examined bitter and sweet sensations from vegetables as mediators of vegetable preference and intake as well as how these tastes vary with markers of genetic variation in taste (3.2 mM 6-n-propylthiouracil bitterness) and taste pathology (1.0 mM quinine bitterness, chorda tympani nerve relative to whole mouth). Seventy-one females and 39 males (18-60 years) reported prototypical tastes from and preference for Brussels sprouts, kale and asparagus as well as servings of vegetables consumed, excluding salad and potatoes. Intensity and hedonic ratings were made with the general Labeled Magnitude Scale. Data were analyzed with multiple linear regression and structural equation modeling. Vegetable sweetness and bitterness were independent predictors of more or less preference for sampled vegetables and vegetable intake, respectively. Those who taste PROP as most bitter also tasted the vegetables as most bitter and least sweet. The spatial pattern of quinine bitterness, suggestive of insult to chorda tympani taste fibers, was associated with less bitterness and sweetness from vegetables. Via structural equation modeling, PROP best explained variability in vegetable preference and intake via vegetable bitterness whereas the quinine marker explained variability in vegetable preference and intake via vegetable bitterness and sweetness. In summary, bitterness and sweetness of sampled vegetables varied by taste genetic and taste function markers, which explained differences in preference for vegetables tasted in the laboratory as well as overall vegetable intake outside the laboratory.

Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake

BACKGROUND Phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), chemically related compounds, are probes for genetic variation in bitter taste, although PROP is safer with less sulfurous odor. Threshold for PROP distinguishes nontasters (increased threshold) from tasters (lower threshold); perceived intensity subdivides tasters into medium tasters (PROP is bitter) and supertasters (PROP is very bitter). Compared with supertasters, nontasters have fewer taste papillae on the anterior tongue (fungiform papillae) and experience less negative (e.g., bitterness) and more positive (eg, sweetness) sensations from alcohol. We determined whether the TAS2R38 gene at 7q36 predicted PROP bitterness, alcohol sensation and use. METHODS Healthy adults (53 women, 31 men; mean age 36 years)--primarily light and moderate drinkers--reported the bitterness of five PROP concentrations (0.032-3.2 mM) and intensity of 50% ethanol on the general Labeled Magnitude Scale. PROP threshold and density of fungiform papillae were also measured. Subjects had common TAS2R38 gene haplotypes [alanine-valine-isoleucine (AVI) and proline-alanine-valine (PAV)]. RESULTS PROP bitterness varied significantly across genotypes with repeated measures ANOVA: 26 AVI/AVI homozygotes tasted less bitterness than either 37 PAV/AVI heterozygotes or 21 PAV/PAV homozygotes. The PAV/PAV group exceeded the PAV/AVI group for bitterness only for the top PROP concentrations. The elevated bitterness was musch less than if we defined the groups using psychophysical criteria. With multiple regression analyses, greater bitterness from 3.2 mM PROP was a significant predictor of greater ethanol intensity and less alcohol intake--effects separate from age and sex. Genotype was a significant predictor of alcohol intake, but not ethanol intensity. With ANOVA, AVI/AVI homozygotes reported higher alcohol use than either PAV/AVI heterozygotes or PAV/PAV homozygotes. When age effects were minimized, PROP bitterness explained more variance in alcohol intake than did the TAS2R38 genotype. CONCLUSIONS These results support taste genetic effects on alcohol intake. PROP bitterness serves as a marker of these effects.

Psychophysics of sweet and fat perception in obesity: problems, solutions and new perspectives

Psychophysical comparisons seem to show that obese individuals experience normal sweet and fat sensations, they like sweetness the same or less, but like fat more than the non-obese do. These psychophysical comparisons have been made using scales (visual analogue or category) that assume intensity labels (e.g. extremely) which denote the same absolute perceived intensity to all. In reality, the perceived intensities denoted by labels vary because they depend on experiences with the substances to be judged. This variation makes comparisons invalid. Valid comparisons can be made by asking the subjects to rate their sensory/hedonic experiences in contexts that are not related to the specific experiences of interest. Using this methodology, we present the evidence that the sensory and hedonic properties of sweet and fat vary with body mass index. The obese live in different orosensory and orohedonic worlds than do the non-obese; the obese experience reduced sweetness, which probably intensifies fat sensations, and the obese like both sweet and fat more than the non-obese do. Genetic variation as well as taste pathology contribute to these results. These psychophysical advances will impact experimental as well as clinical studies of obesity and other eating disorders.

Supertasting and PROP Bitterness Depends on More Than the TAS2R38 Gene

Polymorphisms in the TAS2R38 gene provide insight to phenotypes long associated 6-n-propylthiouracil (PROP) and phenylthiocarbamide bitterness. We tested relationships between TAS2R38 genotype, taste phenotype, and fungiform papillae (FP) number in 139 females and 59 males (age range 21-60 years), primarily of European ancestry. DNA was analyzed for 3 polymorphic sites, identifying common (alanine-valine-isoleucine [AVI/AVI], heterozygotes, proline-alanine-valine [PAV/PAV]) and rare (proline-valine-isoleucine, alanine-alanine-valine, AAI) forms. Individuals with PROP threshold >0.15 mM were almost exclusively AVI/AVI; those with threshold <0.1 mM could have any genotype. PAV/PAVs were more difficult to identify with PROP taste measures, although perceived bitterness of moderate PROP concentrations (0.32, 1 mM) had better correspondence with genotype than did threshold. For AVI/AVIs, increases in bitterness from 1 to 3.2 mM PROP nearly paralleled those of TAS2R38 heterozygotes and PAV/PAVs. Some bitterness gains were related to FP number sampled from a standard area on the tongue tip, yet the PROP bitterness-FP relationship differed across genotype. Among homozygotes, FP was a significant determinant of PROP bitterness; heterozygotes showed a flat relationship. Those tasting concentrated PROP as more bitter also tasted concentrated sucrose, citric acid, sodium chloride, and quinine as more intense, even after statistically controlling for TAS2R38 genotype, FP, and intensity of tones (nonoral standard). To summarize, although PROP threshold generally exhibited single-gene complete dominance, PROP bitterness may involve additional bitter receptors as evidenced by misclassification of some nontaster homozygotes and the bitterness functions for concentrated PROP. Variability in receptor expression may explain attenuated bitterness-FP relationships. PROP bitterness does associate with heightened taste sensations (i.e., supertasting), but this is not due to TAS2R38 polymorphisms.

Labeled scales (e.g., category, Likert, VAS) and invalid across-group comparisons: what we have learned from genetic variation in taste

Direct comparisons of sensory or hedonic perceived intensities across individuals are impossible since we cannot share experiences. However, experiences can be compared indirectly if we can identify a standard assumed to be equal, on average, to groups compared. Sensory standards (i.e., magnitude matching) have proved very useful. Intensity adjectives/adverbs have also been used as standards (e.g., This tastes very strong to me; is it very strong to you?). We argue these labels often refer to experiences of different absolute intensity to the groups of interest making the comparisons invalid. An early solution rested on the assumption that the maximum intensity perceivable was equal for all sensory domains and individuals. Comparisons were then possible because all judgments could be made on a zero to maximum scale. We present data showing this assumption is not true.

Genetic variation and inferences about perceived taste intensity in mice and men.

The study of genetic variation in taste produces parallels between mice and men. In mice, genetic variation across strains has been documented with psychophysical and anatomical measures as well as with recordings from whole nerves. In humans, the variation has been documented with psychophysical and anatomical measures. Whole-nerve recordings from animals and psychophysical ratings of perceived intensities from human subjects have a similar logical limitation: absolute comparisons across individuals require a standard stimulus that can be assumed equally intense to all. Comparisons across whole-nerve recordings are aided by single-fiber recordings. Comparisons across psychophysical ratings of perceived intensity have been aided by recent advances in methodology; these advances now reveal that the magnitude of genetic variation in human subjects is larger than previously suspected. In females, hormones further contribute to variation in taste. There is evidence that the ability to taste (particularly bitter) cycles with hormones in women of child-bearing age, rises to a maximum early in pregnancy and declines after menopause. Taste affects food preferences, which in turn affect dietary behavior and thus disease risks. Valid assessment of taste variation now permits measurement of the impact of taste variation on health. Advances in psychophysical methodology were essential to understanding genetic variation in taste. In turn, the association of perceived taste intensities with tongue anatomy now provides a new tool for psychophysics. The ability of a psychophysical scale to provide across-subject comparisons can be assessed through its ability to show the fungiform papillae density-taste association.

Allelic variation in TAS2R bitter receptor genes associates with variation in sensations from and ingestive behaviors toward common bitter beverages in adults.

The 25 human bitter receptors and their respective genes (TAS2Rs) contain unusually high levels of allelic variation, which may influence response to bitter compounds in the food supply. Phenotypes based on the perceived bitterness of single bitter compounds were first linked to food preference over 50 years ago. The most studied phenotype is propylthiouracil bitterness, which is mediated primarily by the TAS2R38 gene and possibly others. In a laboratory-based study, we tested for associations between TAS2R variants and sensations, liking, or intake of bitter beverages among healthy adults who were primarily of European ancestry. A haploblock across TAS2R3, TAS2R4, and TAS2R5 explained some variability in the bitterness of espresso coffee. For grapefruit juice, variation at a TAS2R19 single nucleotide polymorphism (SNP) was associated with increased bitterness and decreased liking. An association between a TAS2R16 SNP and alcohol intake was identified, and the putative TAS2R38-alcohol relationship was confirmed, although these polymorphisms did not explain sensory or hedonic responses to sampled scotch whisky. In summary, TAS2R polymorphisms appear to influence the sensations, liking, or intake of common and nutritionally significant beverages. Studying perceptual and behavioral differences in vivo using real foods and beverages may potentially identify polymorphisms related to dietary behavior even in the absence of known ligands.

Sweet and bitter tastes of alcoholic beverages mediate alcohol intake in of-age undergraduates.

Alcoholic beverages are complex stimuli, giving rise to sensations that promote or inhibit intake. Previous research has shown associations between 6-n-propylthiouracil (PROP) bitterness, one marker of genetic variation in taste, and alcohol behaviors. We tested the PROP bitterness and alcohol intake relationship as mediated by tastes of sampled alcoholic beverages. Forty-nine undergraduates (mean age=22 years) participated. According to the Alcohol Use Disorders Identification Test (AUDIT), only 3 of 49 subjects reported patterns indicating problematic drinking. Participants used the general Labeled Magnitude Scale to rate PROP bitterness and tastes from and preference for Pilsner beer, blended scotch whiskey, instant espresso and unsweetened grapefruit juice. Alcohol intake was reported over a typical week. Regression analysis tested the hypothesis that PROP bitterness influenced alcohol bitterness and sweetness, which in turn predicted alcohol intake. Those who tasted less PROP bitterness tasted all beverages as less bitter and more preferred. Sweetness of scotch was significantly greater in those who tasted PROP as least bitter. For scotch, greater sweetness and less bitterness from sampled scotch were direct predictors of greater alcohol intake. For beer, preference ratings were better predictors of alcohol intake than the bitter or sweet tastes of the sampled beer. These findings support that PROP bitterness predicts both positive and negative tastes from alcoholic beverages and that those tastes may predict alcohol intake. The college environment may attenuate direct effects of PROP bitterness and intake. Here, PROP bitterness does not predict alcohol intake directly, but acts instead through sweet and bitter tastes of alcoholic beverages.

Explaining variability in sodium intake through oral sensory phenotype, salt sensation and liking.

Our sodium-rich food supply compels investigation of how variation in salt sensation influences liking and intake of high-sodium foods. While supertasters (those with heightened propylthiouracil (PROP) bitterness or taste papillae number) report greater saltiness from concentrated salt solutions, the non-taster/supertaster effect on sodium intake is unclear. We assessed taster effects on salt sensation, liking and intake among 87 healthy adults (45 men). PROP bitterness showed stronger associations with perceived saltiness in foods than did papillae number. Supertasters reported: greater saltiness in chips/pretzels and broth at levels comparable to regular-sodium products; greater sensory and/or liking changes to growing sodium concentration in cheeses (where sodium ions mask bitterness) and broths; and less frequently salting foods. PROP effects were attenuated in women. Compared with men, women reported more saltiness from high-sodium foods and greater liking for broth at salt levels comparable to regular-sodium products. Across men and women, Structural Equation Models showed PROP and papillae number independently explained variability in consuming high-sodium foods by impacting salt sensation and/or liking. PROP supertasters reported greater changes in sensation when more salt was added to broth, which then associated with greater changes in broth liking, and finally with more frequent high-sodium food intake. Greater papillae number was associated with less frequent high-sodium food intake via reduced liking for high-fat/high-sodium foods. In summary, variation in sensations from salt was associated with differences in hedonic responses to high-sodium foods and thus sodium intake. Despite adding less salt, PROP supertasters consumed more sodium through food, as salt was more important to preference, both for its salty taste and masking of bitterness.