Sweet taste and chorda tympani transection alter capsaicin-induced lingual pain perception in adult human subjects.

Sweetness signals the nutritional value of food and may moreover be accompanied by a sensory suppression that leads to higher pain tolerance. This effect is well documented in infant rats and humans. However, it is still debated whether sensory suppression is also present in adult humans. Thus, we investigated the effects of sweet taste on the perception of the painful trigeminal stimulus capsaicin in two groups of healthy adult human subjects. A solution of 100 µM capsaicin was applied to the tip of the subject's tongues in order to stimulate trigeminal Aδ- and C-fiber nociceptors. When swallowed, 1M sucrose reduced the capsaicin-induced burning sensation by 29% (p ≤ 0.05) whereas a solution of similar taste intensity containing 1 µM quinine did not. Similarly, sucrose application to the frontal hemitongue suppressed the perception of the burning sensation induced by contralaterally applied capsaicin by 25% (p ≤ 0.01). We furthermore investigated the effects of documented unilateral transection of the chorda tympani nerve on capsaicin perception. In accordance with the ipsi-to-contralateral effect of sucrose on capsaicin perception in healthy subjects, hemiageusic subjects were more sensitive for capsaicin on the tongue contralateral to the taste nerve lesion (+38%; p ≤ 0.01). Taken together, these results argue I) for the existence of food intake-induced sensory suppression, if not analgesia, in adult humans and II) a centrally mediated suppression of trigeminal sensation by taste inputs that III) becomes disinhibited upon peripheral taste nerve lesion.

Otitis media and associations with overweight status in toddlers.

INTRODUCTION: Otitis media (OM) is a significant disease that affects nearly all children early in life. Recently, childhood overweight has become an epidemic. Past research has demonstrated that a history of OM is related to food preferences and overweight through proposed physiological mechanisms. The purpose of this study was to explore the relationship between recurrent OM (ROM)/tympanostomy tube treatment and overweight status. METHODS: Data were analyzed from a prospective cohort of mothers and children recruited from 1991-1996 from a local health maintenance organization. ROM and tympanostomy tube status were obtained through a combination of physical exam and medical record abstraction. ROM and tympanostomy tube status were analyzed as categorical variables with weight-for-length (WFL) data from well child checks. Chi-square and logistic regression for univariate and multivariate analyses were performed. RESULTS: 11.4% of children had a WFL measure at two years of age ≥ 95 th percentile. Those children with a history of tympanostomy tube treatment had a significantly increased risk of having a WFL ≥ 95 th percentile after controlling for birth weight, maternal prenatal smoking, maternal education, and family income (OR 3.32, 95% CI 1.43-7.72). The alternative hypothesis that children with larger WFL at two month of age would have a greater number of OM episodes by two years of age was not significant. CONCLUSION: The findings of this study are consistent with the hypothesis and prior research that OM treated with tympanostomy tubes is associated with overweight status.

Measuring taste impairment in epidemiologic studies: the Beaver Dam Offspring Study.

Taste or gustatory function may play an important role in determining diet and nutritional status and therefore indirectly impact health. Yet there have been few attempts to study the spectrum of taste function and dysfunction in human populations. Epidemiologic studies are needed to understand the impact of taste function and dysfunction on public health, to identify modifiable risk factors, and to develop and test strategies to prevent clinically significant dysfunction. However, measuring taste function in epidemiologic studies is challenging and requires repeatable, efficient methods that can measure change over time. Insights gained from translating laboratory-based methods to a population-based study, the Beaver Dam Offspring Study (BOSS) will be shared. In this study, a generalized labeled magnitude scale (gLMS) method was used to measure taste intensity of filter paper disks saturated with salt, sucrose, citric acid, quinine, or 6-n-propylthiouracil, and a gLMS measure of taste preferences was administered. In addition, a portable, inexpensive camera system to capture digital images of fungiform papillae and a masked grading system to measure the density of fungiform papillae were developed. Adult children of participants in the population-based Epidemiology of Hearing Loss Study in Beaver Dam, Wisconsin, are eligible for this ongoing study. The parents were residents of Beaver Dam and 43-84 years of age in 1987-1988; offspring ranged in age from 21-84 years in 2005-2008. Methods will be described in detail and preliminary results about the distributions of taste function in the BOSS cohort will be presented.

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.

Valid across-group comparisons with labeled scales: the gLMS versus magnitude matching.

Labeled scales are commonly used for across-group comparisons. The labels consist of adjective/adverb intensity descriptors (e.g., "very strong"). The relative distances among descriptors are essentially constant but the absolute perceived intensities they denote vary with the domain to which they are applied (e.g., a "very strong" rose odor is weaker than a "very strong" headache), as if descriptors were printed on an elastic ruler that compresses or expands to fit the domain of interest. Variation in individual experience also causes the elastic ruler to compress or expand. Taste varies genetically: supertasters perceive the most intense tastes; nontasters, the weakest; and medium tasters, intermediate tastes. Taste intensity descriptors on conventional-labeled scales denote different absolute perceived intensities to the three groups making comparisons across the groups invalid. Magnitude matching provides valid comparisons by asking subjects to express tastes relative to a standard not related to taste (e.g., supertasters match tastes to louder sounds than do nontasters). Borrowing the logic of magnitude matching, we constructed a labeled scale using descriptors unrelated to taste. We reasoned that expressing tastes on a scale labeled in terms of all sensory experience might work. We generalized an existing scale, the Labeled Magnitude Scale (LMS), by placing the label "strongest imaginable sensation of any kind" at the top. One hundred subjects rated tastes and tones using the generalized LMS (gLMS) and magnitude matching. The two methods produced similar results suggesting that the gLMS is valid for taste comparisons across nontasters, medium tasters, and supertasters.

Comparing sensory experiences across individuals: recent psychophysical advances illuminate genetic variation in taste perception.

Modern psychophysics has traveled considerably beyond the threshold measures that dominated sensory studies in the first half of this century. Current methods capture the range of perceived intensity from threshold to maximum and promise to provide increasingly accurate comparisons of perceived intensities across individuals. The application of new psychophysical tools to genetic variation in taste allowed us to discover supertasters, individuals who live in particularly intense taste worlds. Because of the anatomy of the taste system, supertasters feel more burn from oral irritants like chili peppers, more creaminess/ viscosity from fats and thickeners in food and may also experience more intense oral pain. Not surprisingly, these sensory differences influence food choices and thus health. A discussion of the milestones on the road to understanding genetic variation in taste must include discussion of some potholes as well. Often our failures have been as instructive as our successes in the effort to evaluate the impact of genetic variation in taste.

Food acceptance and genetic variation in taste.

OBJECTIVE: To determine if individuals who taste 6-n-propylthiouracil (PROP), one marker of genetic variation in taste, as exceptionally bitter can also perceive sugars as sweeter, other bitters as more intense, and dietary fats as more creamy and/or viscous than do individuals who taste PROP as weakly bitter. This study examined the association between genetic variation in taste and acceptance for sweet, high-fat, and bitter foods and beverages. DESIGN: Genetic variation was measured by perceived bitterness of PROP (influenced by genetic, hormonal, and pathologic factors) and density of fungiform papillae on the anterior portion of the tongue (influenced primarily by genetic factors). Four sweet, 3 fat, and 3 bitter groups were derived from principal components analyses of questionnaire items. SUBJECTS: Convenience sample of healthy adults (24 women, 22 men; mean age +/- standard deviation = 21 +/- 6 years) who did not report high dietary restraint. STATISTICAL ANALYSES: Pearson product moment correlations between genetic taste measures and food and beverage groups. RESULTS: The sample showed diversity in genetic taste measures: perceived bitterness of 0.0032 mol/L PROP ranged from "weak" to well above "very strong"; fungiform papillae densities ranged from 33 to 156 papillae per square centimeter. Distribution of perceived bitterness of PROP and fungiform papillae density differed in women and men. The association between genetic taste measures and acceptance of sweet and high-fat groups differed in women and men. In women, liking of sweet and high-fat food and beverage groups decreased with increasing perceived bitterness of PROP. In men, liking of these foods and beverages increased but with increasing papillae densities. Genetic taste measures were not associated with a dislike of bitter food and beverage groups. APPLICATIONS: The influence of genetic variation in taste on food intake depends on how perceptible sweet, fat, or bitter components are in foods and beverages, as well as the value of sensory factors vs other factors (e.g., health, convenience) on personal dietary choices. Female supertasters of PROP bitterness may avoid high-fat or sweet foods because these oral sensations are too intense and thus less pleasant. Supertasters may taste more bitterness in vegetables but still enjoy eating them because of their healthfulness and because condiments (especially those that are salt based) can block bitterness.

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.

Anesthesia of the chorda tympani nerve and taste phantoms.

The chorda tympani nerve innervates the anterior two-thirds and the glossopharyngeal nerve, the posterior one-third, of each side of the tongue. Previous work showed that anesthesia of one chorda tympani increased the perceived intensity of quinine applied to an area innervated by the contralateral glossopharyngeal nerve, but decreased the perceived intensity of NaCl applied to an area innervated by the ipsilateral glossopharyngeal nerve. The data presented here corroborate that earlier finding and show that if both chorda tympani nerves are anesthetized, the taste of quinine is intensified and the taste of NaCl diminished at areas innervated by the glossopharyngeal on both sides of the tongue. In about 40% of the subjects, tastes occurred in the absence of stimulation (we call these tastes phantoms). The phantoms were usually localized to the posterior tongue contralateral to the anesthesia and they were abolished when a topical anesthetic was applied to the area where they were perceived. Phantoms like these may be a source of clinical dysgeusia in patients with localized taste damage. The phantoms may result because the anesthesia releases inhibition normally occurring between the central projection areas of different taste nerves.

PROP (6-n-propylthiouracil) supertasters and the saltiness of NaCl.

Taste blindness to phenylthiocarbamide (PTC) and its chemical relative 6-n-propylthiouracil (PROP) was discovered in the 1930s. Family studies showed that those who could not taste PTC/PROP (nontasters) carried two recessive alleles. In recent years, we have classified tasters into two groups: medium (PROP is moderately bitter) and supertasters (PROP is intensely bitter). With our classification, approximately 25% of Americans are nontasters, 50%, medium tasters, and 25%, supertasters. Studies showed that supertasters form a cohesive group. Anatomical studies showed that supertasters have the most fungiform papillae. Psychophysical studies showed that supertasters perceive the most intense bitterness and sweetness from a variety of compounds, the most intense burn from oral irritants, and the most intense tactile sensations from viscous solutions. Oral burn and touch are presumably perceived to be the most intense to supertasters because taste buds in fungiform papillae are innervated by the trigeminal nerve (pain, touch) as well as the chorda tympani nerve (taste). The psychophysical scaling method used was magnitude matching with NaCl as the control modality. With this method, subjects rated the intensities of a series of NaCl and PROP solutions. The assumption that the taste of NaCl did not vary with PROP status allowed comparisons of the bitterness of PROP across subjects. Early magnitude matching studies, using sound as the control, had suggested that this assumption was reasonable. However, recent studies challenged that conclusion. Larger samples with more diverse populations, using sound as the control, showed that the taste of NaCl varied with PROP bitterness; supertasters perceived the strongest taste and nontasters, the weakest. Thus our earlier conclusions were conservative because differences between nontasters, medium tasters, and supertasters were concealed by using NaCl as a standard. Using magnitude matching with sound as the standard, or using the Green scale, which employs intensity labels, we found that the differences between PROP groups are larger. Note that the association between PROP status and salt taste is interesting in itself, since variability in salt taste may have important nutritional consequences.

Taste changes across pregnancy.

UNLABELLED: We examined taste intensity and preference in 46 pregnant and 41 healthy female controls enrolled in the Yale Pregnancy Study (J. Rodin, PI). Pregnant females were tested non-pregnant (non-pg) and during the first, second and third trimesters; controls, at corresponding time intervals. Subjects rated intensity of and preference for a three-member concentration series of NaCl, sucrose, citric acid (CA), and quinine hydrochloride (QHCl) on a labeled line ('nothing' at the left, 'extremely' at 80%). Variance differences between groups were tested with the F distribution (p < 0.05). Controls had significantly greater variance among overall intensity ratings than pregnant females, most pronounced for QHCl. Controls did not have highest variance among overall hedonic ratings, but did have highest variance for sweet and QHCl ratings. Within pregnancy analyses were tested with the Friedman two-way ANOVA. Significant intensity changes occurred for moderate NaCl and QHCL concentrations (p < 0.005). For NaCl, intensity fell from non-pg and first trimester to second and third trimesters. For QHCl, intensity rose from non-pg to first trimester, and fell from first to second and third trimesters. In the hedonic ratings, significant changes occurred for top concentrations of NaCl (p < 0.05) and 0.001 M CA (p < 0.001), and moderate QHCl (p < 0.005). NaCl preference rose from non-pg to third trimester. Preference for CA fell from non-pg to first trimester and then rose from first to second and third trimesters. QHCl became less disliked from non-pg and first trimester to third trimester. SUMMARY: taste intensity and hedonic variance in controls may associate with menstrual hormone fluctuations. Pregnant women were aligned in pregnancy stage which may explain the lower variance. Taste intensity and hedonic changes across pregnancy could serve to support healthy pregnancy outcomes: increases in bitter intensity in first trimester to protect against ingesting poisons; changes in NaCl, sour and bitter preference later in pregnancy to support ingesting a varied diet.

Comparison of the Green scale versus magnitude estimation for taste perception.

The Green scale is a new psychophysical method that is simple for subjects to use, but its relation with magnitude estimation has yet to be fully characterized. In comparing the consistency between the Green scale and magnitude estimation, we found that the former seems to provide a psychological oral sensation measurement that is different from the latter method. A simple correction formula can be derived.

Psychophysical measurement of 6-n-propylthiouracil (PROP) taste perception.

The ability to taste 6-n-propylthiouracil (PROP) is genetically determined. PROP tastes moderately bitter to 'medium tasters' (MT), intensely bitter to 'supertasters' (ST), and tasteless to 'nontasters' (NT). The psychophysical method used to characterize PROP status should capture the entire range of perception, while minimizing context, ceiling and other effects. Magnitude estimation successfully captures the variability in PROP perception, but requires normalization and may be difficult to conduct in industrial settings. Two labeled scales were tested as part of three separate studies (S1, S2 and S3) to measure perceived intensity of PROP and sweeteners. All studies included reportedly healthy volunteers aged 21-62 years recruited at Cultor Food Science in Groton, CT. In S1 [n = 163 (55 males, 108 females)], subjects rated perceived intensity of PROP-saturated paper and sucrose (1.0 M) on the Labeled Magnitude (Green) Scale (LMS) [labeled line with descriptors (no taste--strongest imaginable)]. In S2 [n = 152 (49 males, 103 females)], subjects rated perceived intensity of sucrose (1.0 M) and PROP solutions (0.001 M, 0.0032 M) on the LMS. In S3 [n = 136 (48 males, 88 females)], subjects rated perceived intensity of sucrose (1.0 M) and PROP solutions (0.001 M, 0.0032 M) on a 9-point category scale (1 = not at all; 9 = extremely). In all experiments, water rinses were included between each tastant and PROP was the final stimulus. Statistical analyses included descriptive statistics, regression analysis, and ANOVA. In S1 and S2, those with higher PROP perception perceived sucrose more intensely [(S1: r = 0.32; p < 0.001); (S2: r = 0.25; p < 0.01)]. A higher frequency of females were ST than males. Also, the PROP effect on sweet perception was most evident in female ST. This apparent sex difference may be the result of hormonal variation associated with menstruation. As well, in S1 and S2 subjects aged 20-40 years, females had significantly greater variance among sucrose intensity ratings than males (F = 3.66; p < 0.01), which may be due to hormonal changes with menses. The S3 results failed to show either the positive correlation between PROP and sucrose perception or the sex difference. Thus of the two labeled scales, the LMS appears to be better for assessing PROP perception, as it is continuous and also minimizes ceiling effects. Future research will extend these studies by including sucrose and high intensity sweetener concentration series.

Supertasting, earaches and head injury: genetics and pathology alter our taste worlds.

Family studies using thresholds showed that PROP (6-n-propylthiouracil) tasting is produced by a dominant allele, T. Nontasters have two recessive alleles and tasters have one or two dominant alleles. The bitterness of suprathreshold PROP and anatomical criteria subdivide tasters into medium and supertasters. Supertasters may be TT tasters, but this has yet to be demonstrated. Supertasters preceive the greatest bitterness and sweetness from many stimuli as well as the greatest oral burn from alcohol and capsaicin. Women are more likely than men to be supertasters. Otitis media and head trauma can alter taste and thus PROP classifications, complicating studies on PROP genetics. Some subjects with a history of otitis media show taste reductions, but others show enhanced tastes and appear to have more taste buds per fungiform papilla. Subjects with head trauma show reduced tastes on some oral loci, but there is evidence that severe reductions on the front of the tongue ameliorate reductions at the circumvallate papillae on the back of the tongue by a release of inhibition mechanism.

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 current analysis determines whether the distribution of PROP taste thresholds is consistent with an additive or a dominant mode of Mendelian transmission. To that end, the lowest concentration of PROP detectable 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 distributions and followed an additive model of PROP taste sensitivity if the variances associated with the distributions were assumed to be equal. However, if the taste thresholds were transformed to remove skewness, or if the variances were unequal, then three- or two-distribution models were equally likely. Resolution of the mode of inheritance for bitter taste perception awaits additional family studies and the characterization of the molecular basis of taste perception for these bitter compounds.

Effect of anesthesia of the chorda tympani nerve on taste perception in humans.

Individuals who have sustained considerable damage to parts of the taste system often fail to experience changes in everyday taste experience. The two halves of the tongue are independently innervated: the chorda tympani (branch of the facial or VIIth cranial nerve) innervating the anterior two-thirds and the glossopharyngeal (IXth cranial nerve) innervating the posterior one-third. Anesthesia of the chorda tympani nerve on one side produced increased taste intensities for some stimuli on the area innervated by the glossopharyngeal nerve on the other side. Because this effect occurs across the midline and taste projects ipsilaterally, the effect must occur in the central nervous system (CNS). This supports Halpern and Nelson's release-of-inhibition hypothesis that the area to which the chorda tympani projects in the CNS must normally inhibit that of the glossopharyngeal nerve. Anesthesia of the chorda tympani abolishes that inhibition and leads to perception of increased taste intensities from areas innervated by the glossopharyngeal nerve.

Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy/radiation therapy.

Pain from oral mucositis afflicts from 40% to 70% of patients receiving chemotherapy or radiation therapy. Current methods of clinical pain management (for example, topical anesthetics, systemic analgesics) have limited success. In a pilot study, we examined the ability of oral capsaicin to provide temporary relief of oral mucositis pain. Capsaicin, the active ingredient in chili peppers, desensitizes some neurons and has provided moderate pain relief when applied to the skin surface. Oral capsaicin in a candy (taffy) vehicle produced substantial pain reduction in 11 patients with oral mucositis pain from cancer therapy. However, this pain relief was not complete for most patients and was only temporary. Additional research is needed to fully utilize the properties of capsaicin desensitization and thus optimize analgesia.