The curious connection between cocktails and covid
Humans have a complex relationship with bitter substances. We simultaneously seek out the bitterness of coffee and beer, while breeding it out of modern vegetable varieties. Whether you love them or hate them may well be genetic and is likely to predict how ill you get from diseases like Covid-19.
A historical view from medicine to hedonism
Bitter plants have a medicinal history as digestive tonics to either calm or increase absorption of nutrients, or to fortify those who needed a little boost. By the late 19th Century, alcoholic bitter tonics had become a popular cocktail ingredient. But increasing amounts of research in the last 20 years is showing us that these complex and grimace-inducing foods contain interesting compounds that are interacting with our bodies in complex ways.
Bitter receptors
Evolutionarily, our bitter taste receptors have provided helpful ways for us to spot a poisonous plant or toxic substance, and extremely bitter substances are likely to trigger vomiting. While common bitters like nicotine and strychnine are toxic, there are many bitter tasting compounds that appear to have no adverse action beyond leaving a nasty taste in the mouth (Tuzim & Korolczuk, 2021). Logic would suggest that bitterness would cause us to all avoid any bitter foods, but that turns out to not be the case. Repeated exposure and experience that a specific bitter food is actually safe means that some acclimatisation can occur, and those most sensitive to the bitterness of caffeine tend to drink more coffee (Ong et al, 2018).
Digging a little deeper highlights that not only are there many different types of bitter compound, there are multiple bitter receptors. There are thought to be around 25 different taste receptors that respond to bitters (TAS2Rs), they are located throughout the digestive system and, despite our association of tasting things with the mouth, they are most dense in the large intestine (Turner et al, 2018).
Some bitter compounds only bind to one of the receptors, but others seem to spread themselves around indiscriminately. Amarogentin from the plant gentian (Gentiana lutea L., image on the left ©2003 Dr. Amadej Trnkoczy CalPhotos database) is one of the key bitter compounds found in the popular cocktail ingredient Angostura bitters. It has been found to bind to five of our bitter taste receptors (TAS2R1, TAS2R38, TAS2R39 and TAS2R46) (Wooding et al, 2021; Wölfe et al, 2017). Quinine, the bitter compound from Cinchona bark used to flavour tonic and treat malaria has been found to activate nine different TAS2Rs (Wooding et al, 2021).
Non-tasters and super tasters, and unexpected effects
As far back as 1932, it was discovered that people either find bitter foods intensely unpleasant (super-tasters), edible (tasters) or quite palatable (non-tasters). As with many scientific findings, it happened quite by chance. A chemist called Arthur Fox (a non-taster) accidentally spilt the chemical phenylthiocarbamide (PTC) and dust billowed out into the lab. Arthur was surprised to find that his colleague (a taster or super-taster) complained of a bitter taste that he was unable to detect. PTC is not found in foods, but being a super-taster of PTC is predictive of sensitivity to other bitter compounds (Kim & Drayner, 2005).
The sensitivity to bitter tastes is linked to varied genotypes in the genes for TAS2Rs. The relationship between taste receptor genotypes, food preferences and potentially corelated health impacts is complex and we are far from unravelling it all. However, an important connection was highlighted by research during the Covid-19 pandemic, which found that non-tasters were significantly more likely to test positive for SARS-Cov-2 than tasters or super-tasters (Barham et al, 2021). They were also more likely to be hospitalised and suffer from their symptoms for longer, indicating an unexpected immune benefit from an aversion to eating bitter greens (or those who find things bitter, but love to eat them anyway). TAS2Rs are not only found in the digestive system, but appear on a variety of cells in the body. As with the TAS2Rs in the gut, those found in the airways and cells of the immune system can recognise harmful triggers, such as microbial pathogens, and people with sensitive receptors are better at mounting an innate immune response.
Actions other than improving a cocktail or protecting against covid
As well as determining food preferences, bitter receptors are involved in blood sugar regulation, appetite and digestive function. TAS2Rs modulate release of metabolism-regulating molecules in the body, indicating a potential role for bitter foods in metabolic disorders like diabetes and obesity (Turner et al, 2018). However, we have a long way to go before the picture is clear enough for firm recommendations.
These molecular effects would indicate that super-tasters may be less likely to eat bitter vegetables and therefore, more likely to have a higher body mass index (BMI), however, some research shows that non-tasters are more likely to have a higher BMI (Feeney et al, 2010). Results should be taken with a pinch of salt, as a number of studies find no impact of taster status on food preferences or BMI, indicating that other environmental or genetic factors are more important.
Not so bitter prospects
In a world recovering from the after effects of the Covid-19 pandemic and still very much suffering from problems of metabolic disorders like obesity and diabetes, the possibility that we could harness the interaction of cocktail ingredients with our taste buds to improve health is an enticing idea.
References:
Barham HP, Taha MA, Broyles ST, Stevenson MM, Zito BA, Hall CA. Association Between Bitter Taste Receptor Phenotype and Clinical Outcomes Among Patients With COVID-19. JAMA Netw Open. 2021;4(5):e2111410. Published 2021 May 3. doi:10.1001/jamanetworkopen.2021.11410
Feeney E, O’Brien S, Scannell A, Markey A, Gibney ER. Genetic variation in taste perception: does it have a role in healthy eating? Proceedings of the Nutrition Society. 2011;70(1):135-143. doi:10.1017/S0029665110003976
Kim UK, Drayna D. Genetics of individual differences in bitter taste perception: lessons from the PTC gene. Clin Genet. 2005 Apr;67(4):275-80. doi: 10.1111/j.1399-0004.2004.00361.x. Erratum in: Clin Genet. 2005 Jun;67(6):534. PMID: 15733260.
Ong, JS., Hwang, LD., Zhong, V.W. et al. Understanding the role of bitter taste perception in coffee, tea and alcohol consumption through Mendelian randomization. Sci Rep 8, 16414 (2018). https://doi.org/10.1038/s41598-018-34713-z
Turner A, Veysey M, Keely S, Scarlett C, Lucock M, Beckett EL. Interactions between Bitter Taste, Diet and Dysbiosis: Consequences for Appetite and Obesity. Nutrients. 2018; 10(10):1336. https://doi.org/10.3390/nu10101336
Tuzim K, Korolczuk A. An update on extra-oral bitter taste receptors [published correction appears in J Transl Med. 2021 Nov 26;19(1):478]. J Transl Med. 2021;19(1):440. Published 2021 Oct 21. doi:10.1186/s12967-021-03067-y
Wölfle U, Haarhaus B, Seiwerth J, et al. The Herbal Bitter Drug Gentiana lutea Modulates Lipid Synthesis in Human Keratinocytes In Vitro and In Vivo. Int J Mol Sci. 2017;18(8):1814. Published 2017 Aug 22. doi:10.3390/ijms18081814
Wooding SP, Ramirez VA, Behrens M. Bitter taste receptors: Genes, evolution and health. Evol Med Public Health. 2021;9(1):431-447. Published 2021 Oct 13. doi:10.1093/emph/eoab031