Background On Taste

Taste acts as an end behaviour checkpoint to either accept or reject food, enabling individuals to distinguish nutrient rich foods from noxious substances. There is a great variability amongst taste sensitivity in individuals, which can strongly influence food preferences, nutritional status and health. Taste is one of our five senses and is important in identifying both nutrients and potentially harmful substances and humans are able to discriminate five tastes; sweet, umami, sour, salty, bitter. Salts are recognised by salty ion channel receptors; acids by sour ion channel receptors; carbohydrates, sweeteners and protein receptors are detected by the type 1 family of taste receptors (T1Rs) and the bitter taste, which detects a variety of compounds including potential toxins, is mediated by the type 2 family of taste receptors (T2Rs).   

TAS2R38, Haplotypes And Bitterness Sensitivity

TAS2R38 is a member of the TAS2 bitter taste receptor gene family, which, in humans, consists of 25 functional genes and 11 pseudogenes. Three of these SNPs i.e. 145 C>G (Pro49Ala), 785 C>T (Ala262Val) and 886 G>A (Val296Iso), result in three non -synonymous amino acid substitutions i.e. alanine for proline (Proline49Alanine), valine for alanine (Alanine262Valine) and isoleucine for valine (Valine296Isolecuine).  These SNPs represent the most common variant alleles of TAS2R38 and are primarily responsible for the phenotype seen i.e. the individual’s ability to perceive bitter taste. These amino acid substitutions give rise to common haplotypes which are strongly associated with bitter sensitivity i.e. PAV (Proline, Alanine, Valine), considered to be the taster variation, associated with bitter sensitivity and AVI (Alanine, Valine, Isoleucine), considered to be the non-taster variation, associated with bitter insensitivity.  A substantial proportion of differences in PTC/ PROP sensitivity is explained by these haplotypes, with various combinations of variants being strongly associated with bitter perception. Two rare haplotypes (AAV and AAI) and two extremely rare haplotypes (PAI and PVI) with frequencies of <5% and <1% respectively have also been identified.

Individuals who are homozygous for PAV (PAV/PAV) are classified as super tasters as they have a high perceived PROP intensity and are more sensitive towards bitter taste and those who are heterozygous for PAV (PAV/AVI) are classified just as tasters as they have a moderate perceived PROP intensity and therefore a moderate sensitivity towards the bitter taste.  Non-tasters have a low perceived PROP intensity and are therefore not sensitive towards bitter tastes.

Intake Of Vegetables

PROP tasters have been found to have lower intake of certain vegetables, such as cruciferous vegetables, which contain bitter compounds such as isothiocyanates.

Tasters have been hypothesized to have lower acceptance and intake of bitter tasting fruits and vegetables (grapefruit juice, cruciferous vegetables), on the basis of earlier studies which found a relationship showing positive association between PROP taste sensitivity and perceived bitterness in certain compounds such as caffeine, quinine and naringin (the bitter compound in grapefruit). Many bitter tasting foods are anticarcinogenic (e.g. flavonoids, glucosinolates and phenols) and so these findings may have important health implications.

In a study of the bitter taste perception of food, PAV homozygotes rated vegetables containing glucosinolate (a natural bitter tasting compound present in cruciferous vegetables) as 60% more bitter than AVI homozygotes did, whereas PAV/AVI heterozygotes gave most glucosinolate-generating vegetables intermediate scores of bitterness.   An analysis of food selection in an Italian population showed that AVI/AVI non-taster homozygotes consumed more cruciferous vegetables than individuals carrying a single copy of the PAV taster haplotype.

Effect On Sweet Taste

It appears that super tasters might have a reduced intake of high sugar foods however there are contradictory results in studies with respect to PROP status and sweet taste in adults.

Results on PROP taster sensitivity and intake of high sugar foods are mixed. In children, several studies have found increased intake of sweet foods amongst PROP tasters, however some reports show individuals who perceive PROP as extremely bitter (PROP taster) to avoid strong tasting versions of foods that don’t contain thiourea groups, including sweets and reporting PROP super tasters to have a reduced intake of high fat and high sugar foods.

Variations in the TAS2R38 gene may explain individual differences in sweet preferences among children. In a study by Joseph et al, no relationship was found with sweet genotypes, however sucrose detection thresholds were related to variations in the bitter taste receptor gene TAS2R38 amongst children. This gene partially explains why children differ in their ability to perceive the bitter compound propylthiouracil as well as their individual differences in sweet preferences.  Several studies in adults have also linked the perception of bitter ligands on this receptor to sucrose or sweet tastes in adults. Joseph et al. carried out a study to understand how variations in children’s sucrose detection thresholds relate to their age, gender, taste genotype, body composition and dietary intake of added sugars. Sucrose detection thresholds were tested individually in 7-14-year-old children, five genetic variants of taste genes were assayed i.e. sweet genes TAS1R3 and GNAT3 and the three variants on the bitter receptor gene TAS2R38. Body weight and height were taken in all children.

The study found that children with a bitter- sensitive allele of TAS2R38 reported consuming more added sugar than those with the less sensitive allele. These results are consistent with previous reports from Menella et al. (2005) that children with a bitter sensitive allele preferred cereal and beverages with higher sugar content than those without.

Effect On Fat

Non-tasters tend to be less sensitive to the texture of fats which may result in higher overall intakes of fats and super tasters tend to have a reduced intake of high fat foods.  In a review by Tepper et al., most, but not all studies, reported PROP non-tasters to have a lower ability to distinguish fat content and creaminess in certain fatty foods.  PROP non-tasters have shown higher preferences for dietary fats (full fat milk, high fat salad dressings, sweet-fat dairy mixtures) and have also been found to consume more servings of discretionary fats and high energy foods than tasters.  PROP tasters have given higher taste intensity ratings for the essential fatty acid linoleic acid, compared with non-tasters.  It is possible that non -tasters are better able to tolerate higher fat foods compared to tasters because they are less sensitive to unpleasant chemo sensory effects, imparted by free fatty acids.

Several studies have also reported associations between PROP status and liking/intake of fat containing foods in children, with non-tasters showing a preference to/ increased intake for fat, however some studies found no association.  Keller discussed that for sweet and fatty foods, the relationship between perception and taste is likely an inverse U-shaped curve, where the optimal preferred concentration depends on age, developmental and genetic factors. 

Effect On BMI/Weight And Eating Behaviours

There is conflicting evidence around inverse correlations between PROP tasters and calorie consumption/BMI/weight status.  Some findings support this and others don’t, suggesting a multifactorial role in the pathway linking PROP tasting and food perception and preference with feeding behaviour and body weight.  There is evidence that the ability to taste, especially bitter taste, may affect food preferences, which in turn may impact dietary behaviour and therefore risk of metabolic conditions such as obesity and diabetes. Some findings contradict this. Whilst the haplotypes that comprise bitter taste and TAS2R38 functionality may in part influence an individual’s eating behaviour and weight influence, certain other factors such as gender, aging and smoking status may diminish the taste of food, modify fat deposition and alter antimicrobial sensing profile.  

Genetic Variations Of TAS2R38 And Innate Defence System

Ortega et al evaluated the haplotypes of bitter taste receptor TAS2R38 in an identification sample of 210 Caucasian women in different weight conditions, which included anorexia nervosa (52 participants) and obesity (72 participants) compared to 82 healthy matched controls. In an extended sample of 1319 participants, an increased frequency of obesity was found in subjects carrying the AVI/AVI haplotype. This was more robust in women over 40 years of age.

The association of surfactant protein D (SPD) and manna binding lectin (MBL) was also tested in an independent sample, of 534 people, picturing the general population. SPD and MBL are proteins that are involved in the innate immune defence system. Increased SPD and MBL concentrations were found in non smoking AVI carriers.  

It is possible that in the context of obesity associated impairment of circulating MBL and SPD, subjects with AVI haplotype may be more susceptible to host pathogen interactions and increased low grade inflammation, however more in-depth research is needed to determine if the link between TAS2R38 and the release of immunological agents have clinical implications.

Alcohol And Smoking

Tobacco smoke contains a complex mixture of chemical substances of varying structure and functionality, some of which activate different taste receptors. Bitter taste has evolved to identify potentially toxic compounds to protect individuals against harmful foods and so an aversion to this taste may prevent smoking and dependence on nicotine. Non-taster individuals are thought to be more likely to smoke because of their inability to taste bitter compounds in tobacco smoke, however results on this are conflicting. Risso et al. examined the association between TAS2R38 PAV, AVI and rarer haplotypes and cigarette smoking in a large number of individuals from three independent cohorts of both European American (EA) and African American (AA) individuals.  Data were collected on tobacco use and all participants were genotyped for TAS2R38 polymorphisms. Results showed a significant association between common TAS2R38 haplotypes and smokers in EAs where carriers of the taster PAV haplotype and PTC tasters were significantly less likely to be current smokers. Carriers of the non-taster AVI haplotype and PTC non-tasters were significantly more likely to be regular smokers.  On the contrary, in two large samples of African Americans, including a total of over 7000 participants, no association was found between the major TAS2R38 haplotypes and smoking status.

The study concluded that TAS2R38 haplotypes are associated with smoking status in European- Americans but not African-American populations and PTC taster status may play a role in protecting individuals from cigarette smoking in certain populations. Mangold et al. (2008) observed a higher smoking quantity among non-tasters vs. tasters.

 Colon Cancer Risk

Bitter taste receptors are also expressed in other parts of the GIT and evidence has shown a higher incidence of colonic neoplasms in PROP tasters, however results from Carrai contradict this .  

In the study by Basson et al (2005), 251 men who underwent screening lower endoscopy, were tested for the associations between bitterness of PROP (a measure of taste genetics) and the number of colonic polyps (a measure of colon cancer risk).  A subset of 86 patients reported weekly vegetable intake, excluding salads or potatoes. A significant correlation was seen between PROP bitterness (rated by the patients) and polyp number (independent from the age associated increased in number of polyps). Men over 66 years of age saw the strongest PROP-polyp relationship and older men with polyps were more likely to be overweight or obese. Amongst the subset reporting vegetable intake, there was a lower vegetable consumption amongst men who tasted PROP as more bitter. These preliminary findings suggested that colon cancer risk may be affected by taste genetics, possibly through intake of vegetables.

Change In Taste Sensitivity With Age 

Several studies suggest that taste sensitivity diminishes with increasing age. 

In a study by Menella et al., to determine how age interacts with diplotype to affect PROP taste perception, they found that the association between TAS2R38 genotype and PROP taste sensitivity phenotype was resilient against effects of race/ethnicity (amongst all ages) and sex (in children and adolescents) but age was a modifier of the association, especially amongst AVI/PAV heterozygotes.  Children heterozygote for AVI/PAV haplotype were more sensitive to the bitterness of PROP than adults with the same diplotype and adolescents were intermediate.  

Individuals carrying the haplotype PAV for TAS2R38 are considered to be bitter tasters and those carrying the AVI genotype are considered to be non-tasters for bitter compounds, with carriers of the PAV/PAV diplotype considered to be super tasters, those with the PAV/AVI diplotype considered to be ‘tasters’ (rather than super tasters) and those with the AVI/AVI diplotype non-tasters.

Tasters i.e. individuals with TAS2R38 PAV genotype are more likely to have a reduced intake of Brassica and cruciferous vegetables. These vegetables offer important nutrients and health benefits and people with this high bitter tasting phenotype should look at ways to mask the bitterness of their vegetables e.g. cooking them, serving them with dips, adding other flavours and making milder juices/smoothies to encourage increased intake.

They may also have a high intake of sweet and sugary foods, especially in children, although this is controversial as mixed results have been seen. Monitoring of their sugar intake is recommended and ways to reduce this if intake is found to be high.

Figure 1 – Theoretical pathway linking PTC genoptype (TAS2R38) and PROP phenotype to chronic health.

Keller KL, Adise S. Variation in the ability to taste bitter thiourea compounds: implications for food acceptance, dietary intake and obesity risk in children. Annu Rev Nutr. 2016. 36: 6.1-6.27.