Bitterness has the simplest relationship with food intake: What is bitter is bad, and what tastes bad is not eaten. Because poisons can kill quickly, their detection in food is paramount. And many poisons are bitter, a taste quality that evokes a classic rejection response.23,24
This rejection is assumed to be inborn and unlearned because it is apparent in human infants and in nonhuman primates.25
Furthermore, because it is also present in rodents that have had their neural connection between the brain stem and cortex severed, the rejection of bitterness could even be considered a reflex.26
Many people assume that all poisons are bitter, but this viewpoint depends upon the definition of poison. Toxicologists view all chemicals as potentially poisonous—the key issue is determining the relationship between dosage and lethality. Because every chemical is a potential poison but not every chemical is bitter, not all poisons are bitter. From the viewpoint of taste and food intake, a poison is defined as a chemical in a food that is liable to cause illness or death when eaten in sufficient quantity. Even with this narrow and unconventional definition of poison, it is not known how many chemicals are poisons and what proportion of them are bitter. However, when people are offered a range of chemicals to taste, they are overwhelmingly accurate at guessing the toxicity of given compounds using only taste as a guide.27
The following are common poisonous plants: castor beans contain ricin, a compound that causes red blood cells to clump together; turnips contain progoitrin, which inhibits thyroid hormones; cassava contains cyanide, which interrupts the ability of cells to make ATP; soybeans contain saponin, which is poorly absorbed into the body but when present in the bloodstream causes red cells to burst. All these chemicals—ricin, progoitrin, cyanide, and saponin—are bitter.28
We can see from these examples that many poisonous plant compounds are bitter and that the taste system developed in part to detect and avoid them. However, the relationship between the detection of bitterness of a chemical and its lethality is a puzzle, because some bitter chemicals that are not harmful to humans can nonetheless be perceived at low concentrations.29
So the ability to sense bitterness may serve other purposes in addition to poison detection. For instance, when proteins are fermented, some of the protein products are bitter,30
so the bitter taste system may also detect decayed proteins.
Typically, infants and primates immediately and automatically reject bitter stimuli. But for adult humans, the decision about what to do when bitterness is perceived is more complex. Adults sometimes eat foods and drink beverages that are bitter because they contain chemicals that increase feelings of wellbeing; the most obvious examples are the psychoactive drugs caffeine and alcohol. How much the person likes the effects of the bitter drugs, despite their taste, largely determines whether people ingest them.31
Even for bitter foods and drinks that offer pharmacological incentives, people often mask the bitterness, for instance adding cream and sugar to coffee. But if adults ingest bitter foods and drinks only when they contain drugs, then we must explain the willingness of people to drink decaffeinated coffee, which is still bitter but contains much less caffeine than regular coffee.32
It is possible that the overall sensory qualities of coffee become associated with the effect of caffeine33
and that even during extinction (i.e., when the stimulus is no longer followed by the rewarding response), the association is sufficient to maintain the behavior. Or it could be that the small amounts of caffeine are enough to maintain the consumption of this bitter beverage. But even if bitter substances are willingly ingested for their pharmacological benefit, we still need to explain why some people eat bitter melon (a plant commonly eaten in Asia) or other bitter plants that have no obvious drug-like properties.
This paradox—people eat bitter foods that contain no known psychoactive drug—might be resolved if the bitter compounds make people feel better in other ways. Recent studies suggest that bitter melon may contain secondary chemicals that have favorable metabolic effects, including reducing blood sugar in people with diabetes.34
Thus, bitter foods might contain healthful compounds that blur the line between nutrient and drug. If bitter-tasting chemicals in plant foods have health benefits, then removing these compounds (through manufacturing of processed foods or selectively breeding plants for low bitterness) may have negative consequences. The harmful effect of increased sugar and fat in the modern human diet has been widely discussed, but the loss of bitter compounds may also contribute to diseases associated with the modern diet, such as obesity and diabetes. Our bitter detection system seems to balance rejection and acceptance for bitterness in order to avoid poisons and to get enough—but not too much—of the bitter substances that make us feel good.
Tests often ask people to sample bitter chemicals dissolved in water, and because these chemicals must be safe to ingest (even so, subjects are usually asked not to swallow the samples), the number of bitter chemicals tested in a laboratory does not reflect the wide range of bitter compounds we could potentially taste. The selection of chemicals tested is further biased towardthose that have been previously used for sensory testing, so that data can be compared across studies and because their safe use already has been documented. Some of the frequently tested bitter compounds include quinine (found in the bark of the cinchona tree and used to treat malaria), caffeine (found in coffee beans and widely consumed for its stimulant properties), epicatechin (found in tea), tetralone (found in hops and, by extension, in beer), l-phenylalanine (an amino acid), magnesium sulfate (a mineral found in Epsom salts), urea (a product of nitrogen metabolism), naringin (a compound found in grapefruit), sucrose octaacetate (an acetylated derivative of sucrose), denatonium benzoate (used in consumer products to discourage accidental poisoning), and propylthiouracil (a sulfur-containing drug used to treat hyperthyroid disease). People exhibit marked differences in perceiving these chemicals18,35,36
: Some find bitter compounds to be very bitter, whereas others experience the same concentration of the same chemical as much less intense.
We know that the origin of these individual differences, at least for most compounds listed above, is partially genetic because people with genetic makeups that are very similar (e.g., identical twins) are more alike in bitter perception than people who differ (e.g., fraternal twins).37,38
For the least lethal bitter chemicals, which are the most studied in humans, genetic variation is a moderate to strong determinant of how well a person can perceive them. For the most lethal poisons, less individual variation might be expected because people who have lost their ability to taste these chemicals might experience more accidental poisoning, so their genes would be less represented in the population. On the other hand, sensory variation in the worldwide population might be greatest for poisonous chemicals in plants that are found only in some geographic regions. But whether there is greater or lesser individual variation in the perception of lethal bitter chemicals has gone unanswered—ethical concerns obviously prevent testing with these poisons in people. Cell-based assays with one or two human bitter receptors can be used to test the response to a wide range of poisons,39
but this method provides only a partial answer to the question because artificial systems may not recreate the human taste experience.
In at least one case, a gene’s participation in bitter perception is well understood. The inability of some people to taste phenylthiocarbamide (PTC) was discovered in the 1930s by a DuPont chemist named Arthur Fox.18
It was soon determined that the trait was heritable (i.e., transmitted in families),40
and 70 years later the responsible gene and allele were identified.41
The gene, called TAS2R38, is a member of the bitter taste receptor family TAS2R. Three alleles in TAS2R38 account for the bitter-blindness to PTC—they combine to form a haplotype that leads to reduced ability to perceive PTC (and its chemical relative propylthiouracil, one of the commonly studiedbitters listed above). The TAS2R38 haplotype determines most of the variation in people, but alleles in other genes,42,43
and even age44
also contribute to variations in PTC perception. The study of the genetics of this trait is useful because it straddles the divide between the single-gene mode of inheritance found in diseases such as cystic fibrosis and the interactions of many genes found in a complex trait like obesity. Thus, PTC genetics is a useful model for studying genotype/phenotype effects and the influences that modify them.
Genetic differences in bitter taste perception might modify food preferences and intake in a complex manner. Although PTC was first created in a chemistry laboratory and is probably not found in plants, there are many chemical relatives of PTC that stimulate the TAS2R38 bitter taste receptor.39,46,47
At least one of these compounds is found in plant food (turnips),48
and less similar but still related compounds are found in other plant species.49
People with taster and nontaster alleles of TAS2R38 differ in their perception of vegetables (like watercress) that contain these PTC-like compounds.50
From here, it is a short step to hypothesize that genetically insensitive people would eat more of these vegetables than would people who find them to be bitter.
If people differ in their intake of some vegetables, bitter perception might ultimately influence body weight, as suggested by some investigators.51-54
However, a direct relationship between TAS2R38 genotype, food intake, and body weight has not been detected in epidemiological studies55,56
or in genome-wide studies of association with body mass index, a measure of obesity.10,57,58
Thus, if alleles of this bitter receptor gene can directly affect food intake or body weight, they are too weak to be detected in the population as a group. Progress toward understanding genotype/phenotype relationships for PTC taste-blindness and food intake will require narrowing the focus to vegetables that contain these specific compounds. In addition, instead of relying on indirect information about the chemical constitution of vegetables, concentrations of these bitter chemicals should be directly measured in vegetables, because amounts can differ depending on which cultivar is tested or the composition of the soil in which it was grown.
A related point to consider is which aspect of receptor function is most affected by alleles of TAS2R38. While it is often referred to as a “bitter taste receptor,” this receptor and other bitter receptors are also found in the gut59-61
and in nasal airways, where they detect molecules secreted by bacteria.62
The expression of the gene TAS2R38 in the gut is regulated by the amount of cholesterol in the diet, and its expression is highest when cholesterol is low.63
The interpretation of this observation is that gene expression of bitter receptors is increased when plant foods are consumed, which is logical because bitter compounds are more concentrated in plants than in other foods, like meats. It is therefore reasonable to assume that bitter taste receptors are intimately related to vegetable intake, because vegetables taste bitter and gene expressionin the gut is tied to the intake of diets high in plant food. However, the regulation of bitter receptors in the tongue (or the gut) in response to changes in diet had not yet been studied. This is a gap in our knowledge.
A convincing argument can be made that a specific bitter receptor and its alleles might affect food intake, especially of vegetables. But it is important to put these details in context. Although people differ in their ability to taste many bitter chemicals,36
the complete loss of bitter perception for a particular chemical like PTC is probably rare. (It might be misleading to call this a complete loss because the nontaster form of the receptor might detect different bitter molecules.64
) Current studies suggest that PTC is unusual because only one of the 25 known bitter receptors is strongly stimulated by it, so the loss of this one receptor (TAS2R38) is consequential.39
Other bitter molecules stimulate multiple receptors, and the loss of one may decrease but not eliminate the ability to detect that particular bitter molecule.30,39,47,65-73
The perception of PTC is probably an extreme case of individual variation in bitter perception.