Taste dysfunction: a practical guide for oral medicine.

Dental practitioners are often the first clinicians to be presented with complaints about changes in taste. This raises a problem in terms of appropriate evaluative response. It is a difficult issue both because of the common confusion between smell and taste problems (with smell being the more vulnerable sense and contributing substantially to the flavor of food that most patients equate with 'taste'), and because of the lack of widely accepted standardized techniques to assess true taste function. This brief review provides a summary of some of the problems associated with assessing taste function in a clinical setting and of patient management options available to the practitioner of oral medicine.

Salty taste acceptance by infants and young children is related to birth weight: longitudinal analysis of infants within the normal birth weight range.

BACKGROUND: Birth weight and sodium intake are both associated with risk for hypertension. It is not known whether birth weight influences response to salty taste. OBJECTIVE: To assess the relationship between birth weight and salty taste acceptance of infants and young children. DESIGN: Acceptance of salty taste was assessed at 2 (n = 80) and 6 (n = 76) months in infants (birth weight >2.5 kg) enrolled in a prospective cohort study. Acceptance was expressed as proportional intake following 1-min ingestion tests with water and salt solutions (0.17 and 0.34 mol/l NaCl, in water). Birth weight was obtained by maternal report. Questionnaires completed by mothers and food-ranking procedures performed by children evaluated salt liking and preference in a subset (n = 38) of subjects at preschool age (36 or 48 months). SETTING: Nonprofit basic research institute in Philadelphia, PA, USA. RESULTS: Regression analysis revealed significant negative associations between birth weight and acceptance of salty taste at 2 months (0.17 mol/l, P < 0.0001; 0.34 mol/l, P < 0.01) but not at 6 months. Relationships were not affected by adjustment for potential confounders. In preschoolers, greater liking of (P < 0.05) and preference for (P < 0.01) salty foods was associated with lower birth weight in simple, but not adjusted, models. CONCLUSION: Measures related to salty taste preference were inversely related to birth weight over the first 4 years of life. Additional studies should substantiate these findings and explore whether early response to salty taste predicts future sodium intake, blood pressure, or other public health-related outcomes. SPONSORSHIP: National Institutes of Health (DC 00882).

Modulation of odor-induced increases in [Ca(2+)](i) by inhibitors of protein kinases A and C in rat and human olfactory receptor neurons.

Protein kinases A and C have been postulated to exert multiple effects on different elements of signal transduction pathways in olfactory receptor neurons. However, little is known about the modulation of olfactory responses by protein kinases in intact olfactory receptor neurons. To further elucidate the details of the modulation of odorant responsiveness by these protein kinases, we investigated the action of two protein kinase inhibitors: H89, an inhibitor of protein kinase A, and N-myristoylated EGF receptor, an inhibitor of protein kinase C, on odorant responsiveness in intact olfactory neurons. We isolated individual olfactory neurons from the adult human and rat olfactory epithelium and measured responses of the isolated cells to odorants or biochemical activators that have been shown to initiate cyclic AMP or inositol 1,4,5-trisphospate production in biochemical preparations. We employed calcium imaging techniques to measure odor-elicited changes in intracellular calcium that occur over several seconds. In human olfactory receptor neurons, the protein kinase A and C inhibitors affected the responses to different sets of odorants. In rats, however, the protein kinase C inhibitor affected responses to all odorants, while the protein kinase A inhibitor had no effect. In both species, the effect of inhibition of protein kinases was to enhance the elevation and block termination of intracellular calcium levels elicited by odorants. Our results show that protein kinases A and C may modulate odorant responses of olfactory neurons by regulating calcium fluxes that occur several seconds after odorant stimulation. The effects of protein kinase C inhibition are different in rat and human olfactory neurons, indicating that species differences are an important consideration when applying data from animal studies to apply to humans.

The addition of CO2 to traditional taste solutions alters taste quality.

Previous studies of the effect of carbonation on taste perception have suggested that it may be negligible, manifesting primarily in increases in the perceived intensity of weak salt and sour stimuli. Assuming CO2 solutions in the mouth stimulate only trigeminal nerve endings, this result is not altogether surprising; however, there are neurophysiological data indicating that CO2 stimulates gustatory as well as trigeminal fibers. In that case, carbonation might alter the quality profile of a stimulus without producing substantial changes in overall taste intensity--much as occurs when qualitatively different taste stimuli are mixed. To address this possibility, subjects were asked to rate the total taste intensity of moderate concentrations of stimuli representing each of the basic tastes and their binary combinations, with an without added carbonation. They then subdivided total taste intensity into the proportions of sweetness, saltiness, sourness, bitterness and 'other taste qualities' they perceived. The addition of carbonation produced only small increases in ratings of total taste intensity. However, rather dramatic alterations in the quality profiles of stimuli were observed, particularly for sweet and salty tastes. The nature of the interaction is consistent with a direct effect of carbonation/CO2 on the gustatory system, although the possibility that at least some of the observed effects reflect trigeminal-gustatory interactions cannot be ruled out.

The use of olfactory receptor neurons (ORNs) from biopsies to study changes in aging and neurodegenerative diseases.

A gradual loss of olfactory capability with age and in a number of neurodegenerative diseases is common, and mechanisms underlying these losses are not understood. We determined the feasibility of using ORNs obtained from olfactory epithelial biopsies to identify possible changes in ORN function that may contribute to olfactory impairment in these individuals. ORNs from nine healthy subjects (66-84 yr), three patients with Alzheimer's disease and one with multi-infarct dementia were studied with calcium imaging techniques and two odorant mixtures. Seventy-five viable ORNs were studied; 53% of these were odorant responsive, and twenty percent of these responded to both odorant mixtures. In contrast, 25% of 173 ORNs from younger subjects were odorant responsive, and none of these responded to both odorant mixtures. The proportion of cells responding to each of the odorant mixtures also differed between older and younger subjects. These studies demonstrate the feasibility of this approach to examine age or disease-associated changes in neuronal function. Further, age-related changes in ORN selectivity may contribute to changes in olfactory performance.

Clinical disorders of smell and taste.

Renewed attention to chemosensory dysfunction has revealed that a substantial portion of the population are affected during their lives, many simply as a result of aging. The authors discuss terminology, assessment, etiology, and prognosis and compare current understanding with that presented by Mackenzie in 1884.

Selectivity and response characteristics of human olfactory neurons.

Transduction mechanisms were investigated in human olfactory neurons by determining characteristics of odorant-induced changes in intracellular calcium concentration ([Ca2+]i). Olfactory neurons were freshly isolated from nasal biopsies, allowed to attach to coverslips, and loaded with the calcium-sensitive indicator fura-2. Changes in [Ca2+]i were studied in response to exposure to individual odors, or odorant mixtures composed to distinguish between transduction pathways mediated by adenosine 3'5'-monophosphate (cAMP; mix A) or inositol 1,4,5-trisphosphate (InsP3; mix B). Overall, 52% of biopsies produced one or more odorant-responsive olfactory neurons, whereas 24% of all olfactory neurons tested responded to odorant exposure with a change in [Ca2+]i. As in olfactory neurons from other species, the data suggest that odorant exposure elicited calcium influx via second-messenger pathways involving cAMP or InsP3. Unlike olfactory neurons from other species that have been tested, some human olfactory neurons responded to odorants with decreases in [Ca2+]i. Also in contrast with olfactory neurons from other species, human olfactory neurons were better able to discriminate between odorant mixtures in that no neuron responded to more than one type of odor or mixture. These results suggest the presence of a previously unreported type of olfactory transduction mechanism, and raise the possibility that coding of odor qualities in humans may be accomplished to some degree differently than in other vertebrates, with the olfactory neuron itself making a greater contribution to the discrimination process.

Increased liking for salty foods in adolescents exposed during infancy to a chloride-deficient feeding formula.

In a model selected for its similarity to the hormonal consequences of sodium deficiency, food choices of 169 adolescents exposed during infancy to a chloride-deficient feeding formula were compared to those of their closest-aged siblings. Questionnaires completed by parents were used to assess food likes and dislikes. When a salty food was mentioned by parents as one craved by either child, exposed children were more likely than siblings to crave that food (p = 0.005). Frequencies of two of four salt-related dietary behaviors [adding salt to food before tasting (p = 0.03) and to atypical foods (p = 0.05)] were higher in exposed adolescents than in siblings, while frequencies of parallel sugar-related behaviors did not differ between the groups. Foods classified as being lower in saltiness were disliked by exposed children relative to siblings (p = 0.003), although ratings of foods higher in saltiness did not differ. Finally, when asked to rank eight foods in order of preference, ranks assigned by exposed children to salty foods tended (p = 0.07) to be higher than those of siblings. The data suggest a persistent effect of early experience on human salt preference. Additional studies are needed to determine whether salt intake is increased in this and other populations that suffer electrolyte depletion during early development.

Evaluating the 'Labeled Magnitude Scale' for measuring sensations of taste and smell.

The Labeled Magnitude Scale (LMS) is a semantic scale of perceptual intensity characterized by a quasi-logarithmic spacing of its verbal labels. The LMS had previously been shown to yield psychophysical functions equivalent to magnitude estimation (ME) when gustatory, thermal and nociceptive stimuli were presented and rated together, and the upper bound of the LMS was defined as the 'strongest imaginable oral sensation'. The present study compared the LMS to ME within the more limited contexts of taste and smell. In Experiment 1, subjects used both methods to rate either taste intensity produced by sucrose and NaC1 or odor intensity produced by acetic acid and phenyl ethyl alcohol, with the upper bound of the LMS defined as either the 'strongest imaginable taste' or the 'strongest imaginable odor'. The LMS produced psychophysical functions equivalent to those produced by ME. In, Experiment 2 a new group of subjects used both methods to rate the intensity of three different taste qualities, with the upper bound of the LMS defined as the 'strongest imaginable [sweetness, saltiness, or bitterness]'. In all three cases the LMS produced steeper functions than did ME. Experiment 3 tested the hypothesis that the LMS yields data comparable to ME only when the perceptual domain under study includes painful sensations. This hypothesis was supported when the LMS again produced steeper functions that ME after subjects had been explicitly instructed to omit painful sensations (e.g. the 'burn' of hot peppers) from the concept of 'strongest imaginable taste'. We conclude that the LMS can be used to scale sensations of taste and smell when they are broadly defined, but that it should be modified for use in scaling specific taste (and probably odor) qualities. The implications of these results for theoretical issues related to ME, category-ratio scales and the size of the perceptual range in different sensory modalities are discussed.

Functionally mature olfactory neurons from two anosmic patients with Kallmann syndrome.

Patients with Kallmann syndrome (KS) exhibit hypogonadotropic hypogonadism and anosmia [Kallmann et al., Am. J. Mental Def., 48 (1944) 203-236] secondary to failure of gonadotropin-releasing hormone (GnRH)-producing neurons to migrate from the olfactory placode to the brain, and to agenesis of the olfactory bulbs. It has been hypothesized that olfactory neurons (ON) from individuals with KS are immature partly on the basis of studies in animals showing that lack of synaptic connection of ON with the olfactory bulb results in expression of immature ON [Schwob et al., J. Neurosci., 12 (1979) 880-883]. To test this assumption, we obtained olfactory tissue samples from two males diagnosed with KS on the basis of medical history and MRI studies. Both patients were anosmic. The functioning of cells isolated from biopsies taken from the upper middle turbinate and septum was studied by measuring changes in intracellular Ca2+ concentration ([Cai]) using dual excitation fluorescence microscopy. Biopsies from both patients yielded cells that morphologically appeared to be ON. Seven of 16 cells that morphologically resembled ON responded with a change in [Cai] upon stimulation with an odorant mixture. These studies show that at least some ON in KS individuals are functionally mature and suggest that complete development of the olfactory bulbs is not required for differentiation of mature human ON.

Bitter taste in aging: compound-specific decline in sensitivity.

Threshold sensitivity to and the perceived intensity of two bitter compounds, quinine sulfate and urea, were assessed in 52 young adults and 60 elderly adults. Consistent with previous literature, age-related declines in sensitivity to the bitterness of quinine were observed at both threshold and suprathreshold levels. In contrast, the same young and elderly subjects showed comparable sensitivity to the bitterness of urea. These results provide further support for the existence of multiple bitter taste transduction sequences in humans, and indicate that they may be differentially affected by aging.

Infant salt taste: developmental, methodological, and contextual factors.

Two studies investigated the human infant's response to salt during development. In the first study, measures of intake and sucking were obtained from two groups of infants, newborns and 4- to 8-month-olds, in response to brief presentations of two concentrations of salt (0.2 or 0.4 M) and water. For several measures of sucking and for intake, there were significant age and concentration effects. Generally, newborn infants tended to reject saline relative to water more than did 4- to 8-month-old infants. This result, consistent with previously published research, suggests a developmental change in salt acceptability and, probably, sensitivity in the human infant. In the second longitudinal study, the response to salted (0.15 M) versus unsalted formulas was evaluated monthly in infants 2 to 7 months of age. Again, a developmental change was observed: Based on some sucking measures, younger infants appeared to be indifferent to the salted formula relative to the unsalted formula whereas older infants tended to reject the salted formula, presumably because either it was less sweet than the unsalted formulas or because it was novel. These data are consistent with the hypothesis developed from animal model studies that during early human postnatal development, transductive elements sensitive to saltiness mature.

Hepatic lipid profiles in miniature pigs after alcohol feeding.

Changes in lipid profiles have not been reported for the known increases in total lipid content in livers of alcoholics. We have reported a lowering of the beta-oxidative capacity of alcoholic livers, and therefore would expect a lower turnover of fatty acids in these livers, and thus a change in lipid profile. The percentage composition of saturated and unsaturated fatty acids in the liver of alcohol-fed miniature pigs versus the controls, as well as the function of distance from the main hepatic vein, have both been determined in this study involving the feeding of ethanol for one year. Livers of alcohol-fed miniature pigs contained more total lipids than those of controls. Results also indicated significantly higher percentages of free fatty acids and triglycerides in the alcohol-fed miniature pigs, and also an increase in percentage total neutral lipids. The effect of distance from the main blood source (and therefore oxygenation) gave a fatty acid profile that showed an increase in the ratio of saturated to unsaturated fatty acids with increasing distance from the right hepatic vein. This change in ratio was independent of alcohol feeding.

Dietary assessment of patients with chemosensory disorders.

OBJECTIVE: To identify individuals who are at nutritional risk because of taste and/or smell disorders. DESIGN: Patients referred by a private physician for evaluation of a chemosensory complaint underwent an extensive battery of taste and smell tests, otorhinolaryngologic tests, and, in some cases, periodontal examinations and completed a dietary/health questionnaire, a 24-hour recall, and a 2-day diet record. SETTING: Patients were interviewed at the Monell-Jefferson Chemosensory Clinical Research Center, Philadelphia, Pa. SUBJECTS: We studied 310 patients (142 men and 168 women) with a primary complaint of chemosensory disorder. Mean age was 50.5 +/- 15.7 (range = 15 to 93 years). Normative data were provided by an additional 79 healthy control subjects (42 men and 37 women) with no taste or smell complaint. Their mean age was 48.8 +/- 18.8 years (range = 20 to 83 years). MAIN OUTCOME MEASURES: Chemosensory disorder-related changes in food habits (determined by questionnaire responses), nutrient intake (analysis of 3-day food records), and body weight (self-reported). STATISTICAL ANALYSES: Analysis of covariance, followed by post hoc analysis of adjusted means with the Tukey honestly significant difference test, was used to explore group differences in nutrient intake and body weight. chi 2 Analysis and the Pearson correlation coefficient were used to evaluate relationships between variables. RESULTS: When groups were classified according to chemosensory diagnosis, group differences were observed on global appetitive questions, but complaints were high in all groups. Approximately 65% (203 of 310) of patients had self-reported body weights within 5% of their predisorder weight, but clinically meaningful weight gains or losses were observed in each group. Patients with multiple chemosensory disorders were most likely to lose weight, whereas the incidence of weight gain was highest in patients with anosmia. Patient report of a change in eating patterns was the best predictor of weight change among the variables examined. CONCLUSIONS: Dietary responses to chemosensory disorders vary widely and may place patients at nutritional risk. Until better prognostic indexes are identified, dietitians should query patients about disorder-related alterations in eating patterns and provide appropriate individualized counseling.

Human olfactory neurons respond to odor stimuli with an increase in cytoplasmic Ca2+.

The sense of smell allows terrestrial animals to collect information about the chemical nature of their environment through the detection of airborne molecules. In humans smell is believed to play an important role in protecting the organism from environmental hazards such as fire, gas leaks and spoiled food, in determining the flavor of foods, and perhaps in infant-parent bonding. In addition, the study of human olfaction is relevant to a number of medical problems that result in olfactory dysfunction, which can affect nutritional state, and to the study of the etiology of neurodegenerative diseases which manifest themselves in the olfactory epithelium. Although much is known about behavioral aspects of human olfaction, little is understood about the underlying cellular mechanisms in humans. Here we report that viable human olfactory neurons (HON) can be isolated from olfactory tissue biopsies, and we find that HON respond to odorants with an increase in intracellular calcium concentration ([Cai]).

Hyposmia in allergic rhinitis.

BACKGROUND: The association between nasal allergy and loss or diminution of smell is frequently alluded to in the literature; however, neither the true prevalence of hyposmia in individuals with allergic rhinitis nor its bases have been established. METHODS: We assessed olfactory threshold for phenylethyl alcohol in 91 patients with symptoms of allergic rhinitis and 80 nonatopic control subjects. To determine the degree to which nasal congestion contributes to hyposmia in allergic rhinitis, total nasal resistance was measured in 64 of the patients and 72 of the control subjects. RESULTS: Olfactory thresholds were significantly higher in allergic patients than in control subjects (p < 0.001), with 23.1% of the patients demonstrating a clinically significant smell loss (defined as threshold at or above the 2.5th percentile of control values). Although nasal resistance was significantly higher among patients than among controls (p < 0.001), it was not related to olfactory threshold in either group. Clinical or radiographic evidence of sinusitis or nasal polyps or both in allergy patients was found to be significantly associated with hyposmia (p < 0.006). CONCLUSIONS: The observed prevalence of hyposmia among patients with allergic rhinitis suggests that this is a major etiologic factor contributing to smell disorders. Sinusitis or nasal polyps or both may underlie many cases of allergy-related hyposmia.

Non-oral etiologies of oral malodor and altered chemosensation.

A number of non-oral causes for oral malodor have been discussed. Several well documented etiologies for non-oral malodor include renal failure, cirrhosis of the liver, and diabetes mellitus. Each of these conditions has been examined using analytical instrumentation. In addition there appear to be several other metabolic conditions involving enzymatic and transport anomalies (such as trimethylaminuria) which lead to the systemic production of volatile malodors that manifest themselves as halitosis and/or altered chemoreception. Our studies include patients who have been referred to us after being examined by numerous clinical specialists with no identification or relief from their problem. This is due in part to the intermittent nature of many of these problems as well as an apparent lack of knowledge concerning many of these metabolic problems and their relation to oral symptoms.

Early developmental change in bitter taste responses in human infants.

Human newborns (birth-6 days) and older infants (14-180 days) were allowed to ingest both urea (0.12-0.24 M) in a mildly sweet diluent and the diluent alone, and multiple measures of responsivity were obtained (relative intake, sucking behavior, and hedonic ratings based on facial expressions and body movements). For newborns, there was no indication of rejection of urea relative to the diluent in measures of intake or sucking behavior; rather, their responses were predominantly controlled by the order of presentation of the two tastes. In contrast, older infants tended to reject all concentrations of urea according to these measures. Hedonic ratings provided an indication of limited rejection of the bitter taste by newborns, but older infants were still found to respond more consistently. These data suggest there is an early developmental change in bitter taste perception.

Dietary evaluation of patients with smell and/or taste disorders.

The impact of smell and taste disorders on dietary habits and nutritional status has received limited research attention. This paper reports findings obtained from questionnaires and diet records completed by 40 healthy subjects and 118 patients with chemosensory dysfunction. Chemosensory disorders were frequently associated with decreases in food acceptability. Although dietary responses to these dysfunctions varied greatly, patients with distorted or phantom smell and/or taste sensations tended to report weight loss whereas those with simple sensory loss were more likely to report weight gain. Indices derived from diet records did not indicate that either group of patients was at substantial nutritional risk, but food frequency responses and estimates of body mass index were consistent with patient reports of changes in dietary patterns and weight. In addition, marked weight change and aberrant dietary practices were noted in individual patients. Thus, there were indications that chemosensory dysfunction may be associated with nutritionally important dietary alterations.