Genetic Variation in Taste Sensitivity to 6-n-Propylthiouracil and Its Relationship to Taste...

INTERNATIONAL SYMPOSIUM ON OLFACTION AND TASTE

Genetic Variation in Taste Sensitivityto 6-n-Propylthiouracil and Its Relationship

to Taste Perception and Food SelectionBeverly J. Tepper,a Elizabeth A. White,a Yvonne Koelliker,a

Carmela Lanzara,b Pio d’Adamo,b and Paolo Gasparinib

aDepartment of Food Science, School of Environmental and Biological Sciences,

Rutgers University, New Brunswick, New Jersey, USAbDepartment of Reproductive and Developmental Sciences, IRCCS Burlo Garofolo,

University of Trieste, Trieste, Italy

The ability to taste bitter thiourea compounds and related chemicals is a well-knownhuman trait. The majority of individuals perceive these compounds, typified by the bit-terness of 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC), as moderately-to-extremely bitter. Approximately 30% of the population is taste blind to these sub-stances. It has been hypothesized that PROP/PTC tasters are more sensitive to otherbitter tastes, sweet taste, the pungency of chili peppers, the astringency of alcohol, andthe texture of fats. Tasters may also show lower preferences for foods with these tastequalities than nontasters who show the opposite set of responses (i.e., lower taste sensi-tivities and higher preferences for these sensory qualities). This pathway is illustratedin the following model:

PROP Sensitivity → Food Perception → Preference → Selection

Robust associations between PROP status and taste perceptions have been well doc-umented. However, subsequent links to food preferences and diet selection have beenmore difficult to demonstrate. This is not surprising given the complexity of human in-gestive behavior that is influenced by numerous factors including health attitudes, per-sonality traits, and cultural norms. Our laboratory has been using PROP screening toinvestigate individual differences in the selection of bitter foods, especially bitter tastingvegetables and fruits that may have long-term health implications. This chapter will dis-cuss new and recent findings addressing the following issues: 1) whether PROP-relateddifferences in perception of bitter compounds predict the perception and liking of bitterfoods; 2) the role of bitter taste modifiers; and 3) the influence of personal characteristicssuch as food attitudes and cultural background on PROP-related food preferences.

Key words: 6-n-propylthiouracil; bitter taste; taste modification; food preference

Introduction

A vast number of structurally diverse com-pounds elicit bitter taste in humans and manybitter substances can be detected at concen-trations roughly 1000-fold lower than sub-

Address for Correspondence: Beverly J. Tepper, Ph.D., Rutgers Univer-sity, Department of Food Science, School of Biological and EnvironmentalSciences, 65 Dudley Road, New Brunswick, NJ 08901-8520. Voice: 732-932-9611x221; fax: 732-932-6776. [email protected]

stances that stimulate the other basic tastes.1

Since many bitter substances are either poi-sonous or toxic, the ability of humans to de-tect even trace amounts of bitterness in foodsmay have conferred important survival ad-vantages throughout human evolution. It isnot surprising, then, that humans exhibit astrong innate aversion to strong bitter taste.2

Nevertheless, there are large individual differ-ences in the perception of bitterness amongpeople that are well known. The best-known

International Symposium on Olfaction and Taste: Ann. N.Y. Acad. Sci. 1170: 126–139 (2009).doi: 10.1111/j.1749-6632.2009.03916.x c© 2009 New York Academy of Sciences.

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Tepper et al.: PROP Bitterness & Food Selection 127

example of this variation is the genetic abil-ity to taste the synthetic compounds phenyl-thiocarbamide (PTC) and 6-n-propylthiouracil(PROP).

PTC and PROP taste moderately-to-intensely bitter to the majority of individualsacross the globe.3 Approximately 70% of Cau-casians of Western European origin are consid-ered “tasters” whereas the remaining 30% aretaste-blind to these compounds and are consid-ered “nontasters.” Bartoshuk and colleagues4

showed that this large group of tasters canbe subdivided into medium tasters and super-tasters, with the latter group showing the mostextreme sensitivity to PTC/PROP. Thus, thepopulation distribution of nontasters, mediumtasters and supertasters approximates 30%,50%, and 20%, respectively.4 However, thesepercentages vary as a function of age, gender,and ethnicity, which can modify the expres-sion of the trait.3–5 The terms “low-taster (orresponder)” and “high-taster (or responder)”have sometimes been used,6 but there is nogeneral agreement as to the meaning of theseterms. In general, tasters can be distinguishedfrom nontasters based on their threshold sen-sitivities to PTC/PROP. However, thresholdmethods cannot separate medium tasters fromsupertasters, hence suprathreshold intensityratings are used for this purpose. Several validand reliable suprathreshold methods are avail-able and have been used extensively (for re-view see Tepper7). The studies described laterin this chapter utilize suprathreshold methodsthat were developed and tested in our labora-tory and make use of empirically derived cutoffscores to identify taster groups.8 Supertastersalso have a high density of fungiform papillaeon the anterior surface of the tongue support-ing the idea that supertasters are anatomicallydistinct from medium tasters.4,9,10

The gene responsible for variation in PTC/PROP sensitivity is TAS2R38 which resideson human chromosome 7.11 Three single nu-cleotide polymorphisms of this gene resultin three amino acid substitutions at positionsP49A, A262V, and V296I and give rise to

two common haplotypes, PAV (the taster vari-ant) and AVI (the nontaster variant). PROP-sensitive individuals possess one or two domi-nant alleles (PAV/PAV or PAV/AVI), whereasinsensitive individuals are recessive for the trait(AVI/AVI).11,12 The occurrence of other vari-ants is either rare (AAV and PVI) or is limitedto specific populations (AAI in Sub-SaharanAfricans).13

Data from human experiments and cell-based assays suggest that this receptor respondsto PTC and PROP but not to other structurallyrelated compounds that lack the thiourea (N-C = S) moiety.12 This implies that TAS2R38may be narrowly tuned and selective for thisspecific subset of compounds. This specificitycould have important nutritional implicationssince high concentrations of goitrogens (typifiedby the class of compounds known as glucosi-nolates) in traditional human diets are knownto interfere with the utilization of iodine andcompromise thyroid function.14 It has beensuggested that the PTC polymorphism is con-served in human beings as a protective mech-anism against the overconsumption of dietarygoitrogens.15 In support of this notion, a recentstudy showed that greater sensitivity to PROPwas associated with increased bitterness per-ception from glucosinolate-producing vegeta-bles but not from nonglucosinolate-producingvegetables.16

On the other hand, numerous psychophys-ical studies suggest that PTC/PROP tastersare more sensitive to a variety of bitter sub-stances found in foods that are unrelated to thegoitrogens including caffeine,17,18 quinine,18–20

naringin,21 and isohumolones.22 Negative find-ings for caffeine19,23 and quinine23–25 have alsobeen reported.

Food preference studies involving sampledfoods or reported food likes and dislikeshave generally shown that PROP tasters showgreater dislike of certain bitter vegetables andstrong-tasting fruits. Differences in liking havebeen observed for broccoli, brussels sprouts,cabbage, kale, asparagus, and spinach,26–30 aswell as for grapefruit and grapefruit juice,21,31

128 Annals of the New York Academy of Sciences

and soy products.32 However, findings are notalways uniform across the studies. Two reportsfound no relation between PROP status and ac-ceptance of broccoli,28,33 although one of theaforementioned studies found a relationship be-tween PROP status and liking of spinach.28

PROP status has also been associated withgreater perceived intensity of other oral sensa-tions including sweetness,34 irritation from cap-saicin and alcohol,35,36 and the texture of liquidfats.9,37 These observations imply that this traitmight serve as an index of general taste ability,an idea that has been suggested previously.38

This possibility could have broad implicationsfor food selection and nutritional status sincenumerous studies have reported that PROPtasters express lower liking for sweet taste34

(except for PROP-tasting children who showthe opposite response39,40), salad dressings,41

sweetened milks,42 pungent foods,43 and alco-holic beverages.44

Several recent investigations of reported foodintakes have also shown that PROP tastersconsume fewer vegetables30,45,46 and addedfats27 than nontasters. One study directly mea-sured short-term vegetable intake in preschool-ers who were given a choice of different veg-etables as a snack.29 Results showed that tasterchildren consumed approximately half as manyvegetables as nontaster children. Furthermore,32% of the taster children consumed no veg-etables during snack time as compared to 8%of the nontaster children. Despite these posi-tive findings, there are also studies reportingno association between PROP status and likingand/or intake of these classes of foods.47,48 Thereader is referred to Tepper7 for a comprehen-sive review of the role of PROP status in foodpreference and dietary behavior.

The lack of concordance among studies sug-gests that the relationship between the abilityto taste PROP and the perception and liking ofbitter and other strong-tasting foods is com-plex and not completely understood. More-over, linking PROP status with food selection,dietary patterns, and ultimately to nutritionaloutcomes may be a difficult task because hu-

man eating is a complex behavior with multipledeterminants. These determinants include, butare not limited to, age, gender, ethnicity andculture, prior experiences with foods, personal-ity traits, and attitudes about nutrition, health,and body weight. Relatively few studies have ex-amined these variables as potential mediators ofthe association between PROP status and nutri-tional endpoints. Studies that have consideredone or more of these variables have generallyproduced positive results.27,42,43

Our laboratory has been studying the roleof the PROP bitter taste phenotype in dietarybehavior and health outcomes, such as bodyweight. The following sections will discuss newand selected, earlier findings from our work ex-amining associations between PROP and bittertaste perception and selection of bitter foods.

Does PROP Status Influence thePerception of Chemically Diverse

Bitter Substances?

Experiments were designed to determinewhether PROP supertasters would perceivemore bitterness than nontasters from chemi-cally diverse bitter compounds in aqueous so-lutions. Five bitter compounds found in foodsas well as PROP were tested. Figure 1 showsthat PROP supertasters gave higher bitternessratings than nontasters to caffeine, epicatechin,and PROP across all concentrations as well ashigher ratings to naringin and L-phenlyalanineacross most concentrations. PROP status hadonly a weak influence on the intensity of qui-nine which was rated higher in bitterness bysupertasters than nontasters at only the high-est quinine concentration (0.08 mM). Tasteintensity for PROP was moderately corre-lated with the ratings for caffeine, epicatechin,and L-phenylalanine (Pearson r = 0.42–0.54;P < 0.004 after Bonferroni correction), but notfor quinine (r = 0.29; ns) or naringin (r = 0.32;ns). These findings suggest that PROP super-tasters perceive greater intensity from a diver-sity of bitter substances, but the strength of


Figure 1. Mean (± SE) bitterness intensity of six compounds across concentrations byPROP nontasters (n = 30) and supertasters (n = 30). The labeled magnitude scale (0 = “barelydetectable” to 100 = “strongest imaginable oral sensation”) was used to collect the ratings.The compounds were: caffeine, quinine HCl, 6-n-2-propylthiouracil, -(-)epicatechin, naringin,and L-phenylalanine. All were laboratory grade except for naringin, which was food gradeand was donated by International Flavors and Fragrances, Union Beach, NJ. ∗P < 0.05;∗ ∗P < 0.01.

this effect is not identical across compounds.These results support the notion that PROPstatus serves as a general marker for bittertaste perception rather than a specific markerfor thiourea compounds as other studies havesuggested.18,49 The reasons for these opposingfindings are unknown at this time, hence furtherinvestigation of this question seems warranted.

Subjects were also characterized forTAS2R38 genotypes and the data were rean-alyzed to determine if the results of the studyremained the same. Although there are threevariant sites in this gene (P49A, V262A, and

V291I), the last two are in perfect linkage dis-equilibrium. Therefore, subjects were groupedby the first and second variant site. Fifty-threesubjects provided DNA samples and they weregrouped as having two bitter-insensitive alleles(AV/AV; n = 20) or at least one bitter-sensitiveallele (AV/PA or PA/PA; n = 28). We notethat a large proportion (10/14) of the super-tasters in our sample were also heterozygousfor TAS2R38, which has been reported pre-viously.12 This outcome was anticipated sincevariation in TAS2R38 accounts for a largeportion, but not all of the variation in taste


sensitivity to PROP,13,49 and there is signifi-cant overlap in PROP taste intensity betweenAV/PA and PA/PA groups.12 An additional fivesubjects possessed an uncommon form of thegene (AA) and were eliminated from the sta-tistical analyses. Overall, the relationship be-tween phenotypic group (nontaster or super-taster) and allelic group (AV/AV or AV/PAand PA/PA combined) was strong (Spearmanr = 0.72; P ≤ 0.001).

When the bitterness ratings were reanalyzedcontrasting subjects with the AV/AV form tothose with the PA/AV or PA/PA form (com-bined), the results were virtually identical tothose obtained when subjects were classified asphenotypic nontasters and supertasters. Thus,PROP phenotype and TAS2R38 haplotypeprovided similar information about the bitter-ness of the samples.

Does PROP Status InfluenceResponses to These Same Bitter

Substances in Foods?

A second experiment investigated whetherPROP supertasters would perceive great in-tensity from representative foods that naturallycontained the same bitter compounds testedin the previous study. Liking ratings were alsocollected to determine if PROP-related differ-ences in bitterness perception influenced theacceptance of these foods.

As shown in Figure 2, PROP status influ-enced the perception of black coffee (represen-tative of caffeine) and dark chocolate ganache(epicatechin), but not tonic water (quinine) orwhite grapefruit juice (naringin). Specifically,supertasters perceived more coffee flavor andoverall flavor, as well as more bitter persis-tence from black coffee than nontasters. su-pertasters also perceived more chocolate fla-vor and more overall flavor from the darkchocolate than nontasters. Despite noticeabledifferences in the perception of coffee andchocolate, there were no differences in overall

liking of any of the foods by PROP status (seeFig. 2).

There are relatively few studies examiningthe influence of PROP status on the sensoryresponses to foods (or model foods) that con-tained the same bitter compounds that weretested here. For example, one study reportedthat supertasters discriminated added caffeinein orange juice and both medium and super-tasters discriminated caffeine in cream cheesebetter than nontasters.50 In another study, caf-feine solutions were judged as more bitter byPROP tasters than nontasters, but the ad-dition of a non-nutritive sweetener (neohes-peridin dihydrochalcone) to caffeine solutionsdecreased bitterness intensity and increasedhedonic scores of both groups to a similarlevel.51 The latter study also reported no dif-ferences among taster groups in the sensoryresponses to chocolate (white, milk, or darkchocolate).51 PROP status did not influencethe intensity or liking of grapefruit juice in thepresent study. These findings conflict with ear-lier observations from our laboratory showingthat taster children gave lower hedonic rat-ings to a grapefruit/orange juice blend at a3:1 ratio,31 but not at a 1:1 ratio.27 In con-trast, another study reported that supertastersgave lower hedonic rating than nontasters tonaringin solutions lightly sweetened with su-crose (4%) and that greater sensitivity to PROPwas associated with lower reported preferencesfor grapefruit juice.21

Mattes52 has argued that genetically medi-ated differences in bitterness perception maynot be sufficient to alter food acceptability,since bitterness represents only one facet of thecomplex sensory profile of a food. Our find-ings lend partial support to this assertion. su-pertasters perceived more bitterness than non-tasters from most of the compounds we testedwhen dissolved in aqueous solutions but notwhen these same substances were present inreal foods. Moreover, PROP status did not in-fluence acceptability of these foods. As statedpreviously, it is also important to considerthe role of cultural norms, eating attitudes


Figure 2. Mean (± SE) intensity ratings (left panel) and liking ratings (right panel) forattributes of four bitter foods by PROP nontasters (n = 24) and supertasters (n = 24). Data werecollected using 15-cm linear scales with anchors “none” to “strong” for intensity, and “dislikeextremely” to “like extremely” for acceptance. The foods were: black coffee (Nescafe ClassicInstant Coffee, Nestle USA); 100% juice, no sugar added white grapefruit juice (Ocean Spray,Lakeville-Middleboro, MA); dark chocolate ganache (standard household recipe); and tonicwater (Schweppes, Dr. Pepper/Seven Up Inc., Plano, TX). ∗P < 0.05; ∗ ∗P < 0.01.

and health beliefs in food acceptability, whichwere not measured here. These factors willbe discussed in a subsequent section of thischapter.

Is There a Role for Bitter TasteModification? A Case Study

Dislike of bitter taste is the primary reasonthat consumers give for rejecting certain foods,

such as fruits and vegetables, whole grain prod-ucts, and soy.53 Thus, the food and pharmaceu-tical industries are highly motivated to controlbitterness in their products. Common meth-ods for modifying bitterness include selectiveplant breeding, the use of encapsulation to iso-late bitter ingredients from the food matrix,or the addition of salt, sweeteners, and addedflavors.53

A novel approach to controlling bitternessis to utilize compounds that directly modify


the activity of bitter taste cells. The 5′-nucleotides including adenosine 5′ monophos-phate (AMP), guanidine 5′ monophosphate,inosine 5′ monophosphate, among others,are known to block bitter taste perceptionin rodents by inhibiting taste cell signalingpathways.54 The exact mechanism by whichthis inhibition occurs is unknown. One reportin humans showed that AMP reduced the bit-terness of oral pharmaceuticals as well as qui-nine and urea, and was more effective thansodium chloride.55 As part of the same exper-iments described above, we also determined ifAMP reduced the bitterness of aqueous bittersolutions and bitter foods, and whether super-tasters were more sensitive to this effect thannontasters.

These experiments used adenosine 5′

monophosphate sodium salt (Redpoint BioCorp., Cranbury, NJ) henceforth referred to asAMP. Pilot tests showed that AMP at 10 μMand 20 μM reduced the bitterness of the testsolutions but did not impart “umami” (savory)flavor or other side tastes that are commonlyassociated with the 5′ nucleotides.56,57 Thus,AMP was used at concentrations of 0, 10, and20 μM.

As shown in Figure 3, AMP at both concen-trations reduced the bitterness of caffeine atall caffeine concentrations. Overall, AMP ledto a 27% reduction in the bitterness of caf-feine. In addition, AMP at 20 μM, but not at10 μM reduced the bitterness of quinine at thehighest quinine concentration. AMP did notreduce the bitterness of the other compoundstested. These data suggest that AMP selec-tively inhibited the perceived intensity of thebitter alkaloids caffeine and quinine, and hada more pronounced effect on the former thanon the latter compound. Previous experimentswith AMP have not investigated its effects oncaffeine.55 Thus, to our knowledge, the presentfinding of a robust inhibition of the bitternessof caffeine by AMP is novel, and not previouslyreported.

The exact molecular mechanisms by whichAMP reduces bitterness perception has yet to

be fully elucidated. But strong evidence sug-gests that AMP inhibits the α-gustducin sig-naling pathway either at cell-surface receptorsor at downstream elements of the signalingcascade.54 In the present experiments, AMPspecifically reduced the bitterness of caffeineand (to a lesser extent) quinine, molecules thatare amphipathic and capable of rapidly pene-trating membrane.58 Indeed, quinine has beenshown to activate G proteins directly, bypassingmembrane receptors.59 Caffeine is a potent in-hibitor of phosphodiesterase, a major enzymeimplicated in gustducin-mediated signal trans-duction.60 Thus, it is conceivable that AMPreduces the bitterness of compounds that ac-tivate a common signaling pathway. Since bit-ter taste is thought to be mediated by multi-ple receptor/transduction mechanisms,61 it ispossible that the other bitter substances acti-vate AMP-resistant bitter transduction path-ways and therefore AMP was not effective in re-ducing the bitterness of these other compounds.This possibility deserves further attention. Ourresults differ from those of previous studiessuggesting that AMP acts as a broad-basedbitterness inhibitor in mice and humans.54,55

However, we used much lower concentrationsof AMP than in previous experiments, whichmight explain our findings.

There were no significant interactions be-tween PROP status and AMP concentrationon the perception of bitterness in caffeine orquinine (data not shown). That is, althoughsupertasters gave higher bitterness ratings tocaffeine (and to a lesser extent quinine) thandid nontasters (see Fig. 1), both groups experi-enced proportionally similar reductions in bit-ter intensity with AMP. Thus, on a comparativebasis, AMP was as effective in reducing the bit-terness of caffeine and quinine for supertastersas it was for nontasters. These data imply thatPROP status influences an individual’s overallbitter taste responsiveness and that AMP in-hibits bitterness through mechanisms that aredistinct from those involved in PROP tasting.This distinction is further supported by resultsshowing that AMP did not reduce the bitterness


Figure 3. Mean (± SE) bitterness intensity of six compounds with 0, 10, or 20 μM AMP.The samples and procedures were the same as those shown in Figure 1. Subjects were alsothe same as those shown in Figure 1 with nontasters (n = 30) and supertasters (n = 30)combined into a single group (total n = 60). ∗∗P < 0.01.

of PROP when PROP was tasted as a separatestimulus (Fig. 3).

AMP was also added to the same four foodstested previously. Following pilot testing, AMPwas used at either 0 or 100 μM/L of sam-ple in black coffee and chocolate ganache andat either 0 or 350 μM/L of sample in grape-fruit juice and tonic water. Thus, two samplesof each food (with and without AMP) wereevaluated. When added to black coffee, AMPreduced mean bitterness ratings from 12.6 ±0.4 cm to 10.9 ± 0.5 cm (on a 15-cmscale) as well as persistence of bitterness from10.9 ± 0.6 cm to 9.2 ± 0.6 cm (P ≤ 0.05). AMP

did not alter the perception of any of the otherfoods. These findings agree with our results inaqueous solutions showing that AMP stronglyreduced the bitterness of caffeine solutions. Theobserved potency of AMP in coffee is intriguingbecause coffee contains a variety of other bit-ter compounds (e.g., polyphenols, quinic acid,caffeic acid) that may make a greater contri-bution to coffee bitterness than caffeine62 (alsosee Hofmann, this volume63). AMP did not al-ter liking ratings of black coffee. However, oursubjects did not habitually consume their coffeeblack, which might have contributed to the lowoverall liking ratings for this sample (< 3 points).


Figure 4. Influence of food adventurousness on liking of food groups as a function ofPROP taster status. Data represent the mean (± SE) number of foods liked per food group byPROP nontasters (n = 67) and tasters (medium and supertasters combined; n = 165). Likingresponses (“like” or “dislike”) were analyzed by factor analysis to organize the foods intogroups; separate models were calculated for nontasters and tasters. Numbers appearing inparentheses after the food group labels indicate the total number of foods in the group basedon the factor analysis. Statistical comparisons are between food adventurous and nonfoodadventurous subjects within each taster group. ∗∗P < 0.01; ∗∗∗P < 0.001. (Adapted from Ref.43 with permission from Elsevier.)

Future studies will have to determine if AMPis useful for modifying bitterness in caffeine-containing foods. On the other hand, AMPmay be a useful laboratory tool for prob-ing the molecular and psychophysical basis oftaste.

Do Food Attitudes and CulturalNorms Play a Role?

With a few notable exceptions,30,43,64 studieshave not examined the role of personal char-acteristics in the relationship between PROPstatus and food selection, and this involvementcould be significant. For example, we previouslyidentified a variable called “food adventurous-ness” (defined as the self-reported frequency oftrying new foods) that helped to clarify the foodpreferences of PROP taster groups.43 Briefly,232 American consumers completed a 75-item food preference checklist that was heav-ily weighted toward bitter and strong-tastingfoods. Subjects were classified as nontasters ortasters (medium and supertasters combined)

and their preference ratings (like or dislike foreach food) were analyzed by factor analysis toorganize the foods into groups (fruits; vegeta-bles; nonfat condiments including hot peppers,raw garlic and onions, pickles, etc.; and alco-holic beverages). Separate models were devel-oped for tasters and nontasters. Subjects werealso characterized as being high or low in foodadventurousness.

As shown in Figure 4, PROP tasters whowere food adventurous liked more foods perfood group than tasters who were not foodadventurous. In contrast, food adventurous-ness had no influence on the number of foodsliked from each of the food groups for non-tasters. Thus, characterizing subjects by theirself-described food adventurousness unmaskedtwo subgroups of PROP tasters—those wholiked a broad range of foods and those withmore narrow food preferences. Classifying sub-jects by PROP status alone or food adventur-ousness alone did not provide meaningful in-sights into the reported food preferences ofthese individuals. It seems likely that otherpersonal characteristics interact with PROP


status to influence food likes and dislikes.Identifying and incorporating these variablesinto future studies will lead to a more com-plete understanding of food preferences andselection patterns than examining PROP sta-tus in isolation.

It is noteworthy that most of the availabledata on PROP tasting and food preferenceshave been collected in mainstream consumergroups or students living in North America,Western Europe, or Australia.7 It has been as-sumed that PROP status has a similar influenceon food preferences across different ethnic andcultural groups, but this might not be the case.One study showed no influence of PROP sta-tus on general food preferences in Tunisians,65

but data are lacking in other cultures. As partof an ongoing investigation on the genetics ofmultifactorial diseases, we have been studyingthe village of Carlantino, a genetically and ge-ographically isolated community located in themountains of Southern Italy. We administereda food preference questionnaire to 535 volun-teers from this village who were 15–89 yearsof age (mean age = 52.0 ± 0.8 years). Thequestionnaire was based on the food preferencechecklist from our food adventurousness study(see above) but modified to include foods com-monly consumed in Italy. The response cate-gories of the questionnaire were also expandedto a 9-point liking scale.

As shown in Figure 5, there was a high de-gree of liking for vegetables in Carlantino withratings > 7 on the 9-point scale for the majorityof the items. However, liking of these foods didnot vary by PROP taster group. We speculatethat in a food culture where the overall ac-ceptance of vegetables is high, the influence ofPROP status on vegetable liking may be weakor absent. We did not collect information onfood preparation. However, in Italy, vegetablesare more commonly eaten cooked than raw,which reduces bitterness. Thus, another poten-tial explanation for our findings is that culi-nary traditions overshadowed the influence ofgenetic taste variation on vegetable acceptance,which has been suggested previously.52

Figure 5. Mean (± SE) liking ratings for vegeta-bles as a function of PROP taster status by partici-pants in the Village of Carlantino (n = 535). Datawere collected using a 9-point liking scale (1 = dis-like extremely and 9 = like extremely). No significantdifferences were found by PROP status.

Figure 6. Mean (± SE) liking ratings for pun-gent foods and alcohol as a function of PROP tasterstatus by participants in the Village of Carlantino(n = 535). Data were collected using a 9-point likingscale (1 = dislike extremely and 9 = like extremely).Mean values for individual foods with different super-script letters are significantly different by PROP tasterstatus. P < 0.001.

A very different picture emerged for the de-gree of liking for pungent and spicy foods, andalcoholic beverages. Figure 6 shows that super-tasters expressed lower liking for most of these


items in comparison to nontasters. These re-sults are intriguing because these foods stimu-late trigeminal sensations. Capsaicin from chilipepper and isothiocyantes from raw garlic andonion elicit oral irritation, and alcohol producesastringency.66 These results support the generalpremise of this chapter, that PROP status playsa role in the acceptance of strong-tasting foodsthat elicit oral sensations outside the realm ofbitter taste. Interestingly, food adventurousnesshad no influence on food acceptance in Car-lantino volunteers.

Conclusions and Future Directions

More than four decades ago, early re-searchers suggested that PROP status playeda role in guiding general food preferences suchthat tasters had more overall food dislikes thannontasters.67 Since then, steady progress hasbeen made in establishing the links betweenthe ability to taste PROP and a variety of nutri-tional outcomes including food preference andselection, and dietary intake.7 However, thelarge number of contradictory reports in thisliterature has raised doubts about the signifi-cance of this phenotype in human nutrition.52

The viewpoint advanced here is that many ofthe factors influencing the pathway betweenthe ability to taste PROP and nutritional end-points are not presently known, and efforts toidentify these factors should be an ongoing goalfor progress in the field to continue.

Until recently, TAS2R38 was considered theonly bitter-taste gene that exhibits prominentphenotypic variation in humans. Consequently,all of the research on genetic variation in bit-ter taste was focused on this trait. However,data are accumulating on the contribution ofother taste genes to individual differences intaste perception and food selection. Recent ex-amples include TAS2R43 and TAS2R44 whichhave been associated with the bitter taste of sac-charin,68 and TAS2R16 which has been impli-cated, along with TAS2R38, in behavioral re-sponses to alcohol.69 Thus, it seems likely that

the examination of multiple taste phenotypeswill provide a more complete understandingof human eating behavior than a single tastephenotype.

Finally, a recent report70 questioned whetherPROP sensitivity is the best general index ofheightened sensitivity to oral sensations. In acommentary to that paper, Reed71 coined thephrase “general supertaster” to describe indi-viduals who respond with heightened sensitivityto all or most stimuli, without regard to theirgenetic sensitivity to PROP. This novel conceptuncouples the term “supertaster” from its pre-sumed genetic link with PROP. Indeed, emerg-ing evidence suggests that greater responsive-ness to PROP as well as greater responsivenessto thermal taste (a taste phantom associatedwith warming and cooling of the tongue)72 bothserve as markers for enhanced global sensoryacuity.73 The concept of general supertastingis intriguing and awaits additional empiricalsupport.

Acknowledgments

The authors thank Dr. Danielle Reed andMs. Kirsten J. Mascioli of the Monell Chemi-cal Senses Center for performing the genotypeanalyses. These studies were supported, in part,by Redpoint Bio Corp. (formerly LinguagenCorp.), Cranbury, NJ (to B.J.T.) and the ItalianMinistry of Research and the Italian Ministryof Health (to P.G.).

Disclosures: The authors have no other fi-nancial relationship with Redpoint Bio Corp.Redpoint Bio Corp. holds a patent on theuse of the common nucleotide, adenosine 5′

monophosphate (CAS # 61-19-8) as a bitterblocker in foods. Redpoint Bio Corp. has nopatent claim on the synthesis or experimentaluse of this agent.

Conflicts of Interest

These studies were supported, in part,by Redpoint Bio Corp. (formerly LinguagenCorp.), Cranbury, NJ. The authors have no


other financial relationship with Redpoint BioCorp. that holds a patent on the use of the com-mon nucleotide, adenosine 5’ monophosphate(CAS # 61-19-8) as a bitter blocker in foods.Redpoint Bio Corp. has no patent claim on thesynthesis or experimental use of this agent.

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