Tolerance of bitter stimuli and attenuation/accumulation of their bitterness in humans.

Some components of bitterness make key flavor contributions to promote the palatability of foods, whereas other components are recognized as aversive signals to avoid consuming harmful substances. These contradictory behaviors suggest that humans tolerate tastes of bitterants based on certain criteria. Here, we investigated human taste tolerance and sensory cues leading to diverse taste tolerance of bitter compounds. Tolerance of eight bitter compounds, which are typically contained in foods, was evaluated by measuring detection and rejection thresholds. The results revealed that the level of tolerance of each compound was variable, and some compounds showed an acceptable concentration regarding the suprathreshold intensity. Tolerance did not depend on the nutritive value or attenuation and accumulation characteristics of bitterness and bitter taste receptors. These results suggest that the criteria controlling tolerance of bitter compounds may be derived from a complex relationship between the taste quality and cognitive process.

Genetic analysis of chemosensory traits in human twins.

We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h(2) from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype-phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways.

Inhibitory effects of benzyl benzoate and its derivatives on angiotensin II-induced hypertension.

Hypertension is a lifestyle-related disease which often leads to serious conditions such as heart disease and cerebral hemorrhage. Angiotensin II (Ang II) plays an important role in regulating cardiovascular homeostasis. Consequently, antagonists that block the interaction of Ang II with its receptors are thought to be effective in the suppression of hypertension. In this study, we searched for plant compounds that had antagonist-like activity toward Ang II receptors. From among 435 plant samples, we found that EtOH extract from the resin of sweet gum Liquidambar styraciflua strongly inhibited Ang II signaling. We isolated benzyl benzoate and benzyl cinnamate from this extract and found that those compounds inhibited the function of Ang II in a dose-dependent manner without cytotoxicity. An in vivo study showed that benzyl benzoate significantly suppressed Ang II-induced hypertension in mice. In addition, we synthesized more than 40 derivatives of benzyl benzoate and found that the meta-methyl and 3-methylbenzyl 2'-nitrobenzoate derivatives showed about 10-fold higher activity than benzyl benzoate itself. Thus, benzyl benzoate, its derivatives, and benzyl cinnamate may be useful for reducing hypertension.

Innate and acquired tolerance to bitter stimuli in mice.

Tolerance to bitter foods and its potentiation by repetitive exposure are commonly experienced and potentially underlie the consumption of bitter foods, but it remains unknown whether permissive and adaptive responses are general phenomena for bitter-tasting substances or specific to certain substances, and they have not been rigorously studied in mice. Here, we investigated the effects of prolonged exposure to a bitter compound on both recognition and rejection behaviors to the same compound in mice. Paired measurements of rejection (RjT) and apparent recognition (aRcT) thresholds were conducted using brief-access two-bottle choice tests before and after taste aversion conditioning, respectively. First, RjT was much higher than aRcT for the bitter amino acids L-tryptophan and L-isoleucine, which mice taste daily in their food, indicating strong acceptance of those familiar stimuli within the concentration range between RjT and aRcT. Next, we tested five other structurally dissimilar bitter compounds, to which mice were naive at the beginning of experiments: denatonium benzoate, quinine-HCl, caffeine, salicin, and epigallocatechin gallate. RjT was moderately higher than aRcT for all the compounds tested, indicating the presence of innate acceptance to these various, unfamiliar bitter stimuli in mice. Lastly, a 3-week forced exposure increased RjT for all the bitter compounds except salicin, demonstrating that mice acquire tolerance to a broad array of bitter compounds after long-term exposure to them. Although the underlying mechanisms remain to be determined, our studies provide behavioral evidence of innate and acquired tolerance to various bitter stimuli in mice, suggesting its generality among bitterants.

Oral Carbonation Attenuates Feeling of Hunger and Gastric Myoelectrical Activity in Young Women.

We previously reported that carbonated water ingestion induced fullness and gastric motility. In order to determine whether such satiating effects occur through oral carbonic stimulation alone, we conducted modified sham-feeding (SF) tests (carbonated water ingestion (CW), water ingestion (W), carbonated water sham-feeding (CW-SF), and water sham-feeding (W-SF)), employing an equivalent volume and standardized temperature of carbonated and plain water, in a randomized crossover design. Thirteen young women began fasting at 10 p.m. on the previous night and were loaded with each sample (15ºC, 250 mL) at 9 a.m. on separate days. Electrogastrography (EGG) recordings were obtained from 20 min before to 45 min after the loading to determine the power and frequency of the gastric myoelectrical activity. Appetite was assessed using visual analog scales. After ingestion, significantly increased fullness and decreased hunger ratings were observed in the CW group. After the load, transiently but significantly increased fullness as well as decreased hunger ratings were observed in the CW-SF group. The powers of normogastria (2-4 cpm) and tachygastria (4-9 cpm) showed significant increases in the CW and W groups, but not in the CW-SF and W-SF groups. The peak frequency of normogastria tended to shift toward a higher band in the CW group, whereas it shifted toward a lower band in the CW-SF group, indicating a different EGG rhythm. Our results suggest that CO2-induced oral stimulation is solely responsible for the feeling of satiety. Moreover, different gastric-contraction rhythms (slow or fast) were induced by oral carbonic stimulation alone and carbonated water ingestion.

Oral Cooling and Carbonation Increase the Perception of Drinking and Thirst Quenching in Thirsty Adults.

Fluid ingestion is necessary for life, and thirst sensations are a prime motivator to drink. There is evidence of the influence of oropharyngeal stimulation on thirst and water intake in both animals and humans, but how those oral sensory cues impact thirst and ultimately the amount of liquid ingested is not well understood. We investigated which sensory trait(s) of a beverage influence the thirst quenching efficacy of ingested liquids and the perceived amount ingested. We deprived healthy individuals of liquid and food overnight (> 12 hours) to make them thirsty. After asking them to drink a fixed volume (400 mL) of an experimental beverage presenting one or two specific sensory traits, we determined the volume ingested of additional plain, 'still', room temperature water to assess their residual thirst and, by extension, the thirst-quenching properties of the experimental beverage. In a second study, participants were asked to drink the experimental beverages from an opaque container through a straw and estimate the volume ingested. We found that among several oro-sensory traits, the perceptions of coldness, induced either by cold water (thermally) or by l-menthol (chemically), and the feeling of oral carbonation, strongly enhance the thirst quenching properties of a beverage in water-deprived humans (additional water intake after the 400 ml experimental beverage was reduced by up to 50%). When blinded to the volume of liquid consumed, individual's estimation of ingested volume is increased (~22%) by perceived oral cold and carbonation, raising the idea that cold and perhaps CO2 induced-irritation sensations are included in how we normally encode water in the mouth and how we estimate the quantity of volume swallowed. These findings have implications for addressing inadequate hydration state in populations such as the elderly.

The effects of carbonated water upon gastric and cardiac activities and fullness in healthy young women.

Although previous reports suggested that carbonated water drinking was effective against gastrointestinal symptoms, there is little information about the effects of carbonated water on gastric and appetite sensation. We therefore investigated the effect of carbonated water on short-term fullness with respect to gastric and cardiac responses in 19 healthy young women. Each subject was tested on three separate days at approximately 9 a.m. after an overnight fast. Gastric motility, evaluated by electrogastrography (EGG) and heart rate (HR), was measured for 20 min in the fasting state and 40 min after ingestion of water. Preloads consisted of an equivalent amount (250 mL) of water (W) or carbonated water (CW) and no drinking (blank). Fullness scores were measured using visual analog scales. To determine gastric motility, we assessed the component of bradygastria (1-2 cycles/min [cpm]), normogastria (2-4 cpm), tachygastria (4-9 cpm), and dominant frequency of the EGG power spectrum. After ingestion of CW, significant increases in fullness scores were observed compared with W. All postprandial EGG powers were significantly greater than preprandial, but no group difference was found. However, a dominant frequency tended to shift toward a lower band after ingestion of W. A significantly higher HR was found following consumption of CW as opposed to W. Multiple regression analysis revealed that increased HR was a significant variable contributing to the variances in fullness after ingestion of CW at 40 min. Our data suggest that CW may induce a short-term, but significant, satiating effect through enhanced postprandial gastric and cardiac activities due possibly to the increased sympathetic activity and/or withdrawal of parasympathetic activity.

Opponency of astringent and fat sensations.

In most cultures, people ingest a variety of astringent foods and beverages during meals, but the reasons for this practice are unclear. Many popular beliefs and heuristics, such as high tannin wines should be balanced with fatty foods, for example 'red wine with red meat', suggest that astringents such as pickles, sorbets, wines, and teas 'cleanse' the palate while eating. Oral astringents elicit 'dry, rough' sensations [1], in part, by breaking down mucinous lubricating proteins in saliva [2,3]. The introduction of oral lubricants, including fats, partially diminishes strong astringent sensations [4,5]. Thus, it appears that astringency and fattiness can oppose each other perceptually on an oral rheological spectrum. Most teas, wines, and 'palate cleansers', however, are only mildly astringent and an explanation of how they could oppose the fattiness of meals is lacking. Here, we demonstrate that weakly astringent stimuli can elicit strong sensations after repeated sampling. Astringency builds with exposures [6] to an asymptotic level determined by the structure and concentration of the compound. We also establish that multiple sips of a mild astringent solution, similar to a wine or tea, decrease oral fat sensations elicited by fatty food consumption when astringent and fatty stimuli alternate, mimicking the patterning that occurs during a real meal. Consequently, we reveal a principle underlying the international practice of 'palate cleansing'. Repeatedly alternating samples of astringent beverages with fatty foods yielded ratings of fattiness and astringency that were lower than if rinsing with water or if presented alone without alternation.