Popular Beverages Stimulate Oropharyngeal and Gut Receptors Eliciting Modulation of the Upper Digestive Processes

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Michael Kevin McMullen


This paper reports clinical studies on the effect of agonists of taste and chemethesis receptors in the oropharyngeal cavity and the gut. The peripheral nerve system plays a vital role in our selection or rejection of what we eat and drink. Although the degree to which it is hard-wired has not been determined, it is known that our food and drink choices change with age.  Scientific studies on the impact of food and drink on the body have been concerned predominantly with nutritional factors and, more recently, impacts on cholesterol and blood sugar levels. On the other hand, the sensations we experience during eating and drinking have long been regarded, perhaps even dismissed, as purely hedonistic. The idea that foods and drinks may actually influence digestion is a novel one and is based on the discovery 20 years ago of taste buds, innervated by the vagi, in stomach and intestinal tissues. Studies indicate some of our most popular drinks modulate both postprandial hyperaemia and gastric emptying. It is proposed that the bitter taste experienced with some foods and drinks promotes increased blood flow to the splanchnic circulation and slows the flow of chyme to the small intestine. In cases of toxicity, these actions promote emesis whereas at non-toxic levels, bitter substances promote digestion by increasing postprandial hyperaemia and slowing gastric emptying. Additionally, chemethesis agonists can act on the oropharyngeal receptors resulting in a slower gastric emptying. These effects may lead to a learned behaviour and subsequent enjoyment of bitter tastants, rather than their rejection, amongst those with reduced digestive capacity. It provides a rationale for the popularity of certain bitter tasting aperitifs and digestive alcoholic beverages originating in southern Europe.

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MCMULLEN, Michael Kevin. Popular Beverages Stimulate Oropharyngeal and Gut Receptors Eliciting Modulation of the Upper Digestive Processes. Medical Research Archives, [S.l.], v. 10, n. 12, dec. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3418>. Date accessed: 17 june 2024. doi: https://doi.org/10.18103/mra.v10i12.3418.
Review Articles


1. Wu SV, Rozengurt N, Yang M, Young SH, Sinnett-Smith J, Rozengurt E. Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc Natl Acad Sci U S A. 2002;99(4):2392-7. doi:10.1073/pnas.042617699
2. Roper SD. TRPs in taste and chemesthesis. Handb Exp Pharmacol. 2014;223:827-71. doi:10.1007/978-3-319-05161-1_5
3. Spector AC, Travers SP. The representation of taste quality in the mammalian nervous system. Behav Cogn Neurosci Rev. Sep 2005;4(3):143-91. doi:10.1177/1534582305280031
4. Small DM. Flavor is in the brain. Physiol Behav. 2012;107(4):540-52. doi:10.1016/j.physbeh.2012.04.011
5. Someya N, Endo MY, Fukuba Y, Hayashi N. Blood flow responses in celiac and superior mesenteric arteries in the initial phase of digestion. Am J Physiol Regul Integr Comp Physiol. 2008;294(6):R1790-6. doi:10.1152/ajpregu.00553.2007
6. Hlebowicz J, Darwiche G, Björgell O, Almér L-O. Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects. Am J Clin Nutr. 2007;85(6):1552-1556. doi:10.1093/ajcn/85.6.1552
7. Hlebowicz J, Hlebowicz A, Lindstedt S, et al. Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin concentrations in healthy subjects. Am J Clin Nutr. 2009;89(3):815-821. doi:10.3945/ajcn.2008.26807
8. Beejmohun V, Peytavy-Izard M, Mignon C, et al. Acute effect of Ceylon cinnamon extract on postprandial glycemia: alpha-amylase inhibition, starch tolerance test in rats, and randomized crossover clinical trial in healthy volunteers. BMC Complement Altern Med. 2014;14:351. doi:10.1186/1472-6882-14-351
9. Markey O, McClean CM, Medlow P, et al. Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast. Cardiovasc Diabetol. 2011;10(1):78. doi:10.1186/1475-2840-10-78
10. Wickenberg J, Lindstedt S, Berntorp K, Nilsson J, Hlebowicz J. Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance. Br J Nutr. 2012;107(12):1845-1849. doi:10.1017/S0007114511005113
11. Magistrelli A, Chezem JC. Effect of ground cinnamon on postprandial blood glucose concentration in normal-weight and obese adults. J Acad Nutr Diet. 2012;112(11):1806-9. doi:10.1016/j.jand.2012.07.037
12. Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. BMJ. 1990;300(6719):230-235. doi:10.1136/bmj.300.6719.230
13. Shang C, Lin H, Fang X, et al. Beneficial effects of cinnamon and its extracts in the management of cardiovascular diseases and diabetes. Food Funct. 2021;12(24):12194-12220. doi:10.1039/d1fo01935j
14. Sharma S, Mandal A, Kant R, Jachak S, Jagzape M. Is cinnamon efficacious for glycaemic control in type-2 diabetes mellitus? J Pak Med Assoc. 2020;70(11):2065-2069. PMID: 33341863
15. Franke A, Nakajima IA, Schneider A, Harder H, Singer MV. The effect of ethanol and alcoholic beverages on gastric emptying of solid foods in humans. Alcohol Alcohol. 2005;40(3):187-193. doi:10.1093/alcalc/agh138
16. Franke A, Teyssen S, Harder H, Singer MV. Effect of ethanol and some alcoholic beverages on gastric emptying in humans. Scand J Gastroenterol. 2004;39(7):638-644. doi:10.1080/00365520410005009
17. Heinrich H, Goetze O, Menne D, et al. Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial. BMJ. 2010;341:c6731. doi:10.1136/bmj.c6731
18. Kasicka-Jonderko A, Jonderko K, Bożek M, Kamińska M, Mgłosiek P. Potent inhibitory effect of alcoholic beverages upon gastrointestinal passage of food and gallbladder emptying. J Gastroenterol. 2013;48(12):1311-1323. doi:10.1007/s00535-013-0752-y
19. Kasicka-Jonderko A, Jonderko K, Gajek E, Piekielniak A, Zawislan R. Sluggish gallbladder emptying and gastrointestinal transit after intake of common alcoholic beverages. J Physiol Pharmacol. 2014;65(1):55-66. PMID: 24622830
20. Gonzalez Z, Herlihy D, Phan C, Diaz J, Dominguez K, McCallum R. Alcohol and gastric motility: pathophysiological and therapeutic implications. J Investig Med. 2020;68(5):965-971. doi:10.1136/jim-2020-001327
21. Chou CC, Coatney RW. Nutrient-induced changes in intestinal blood flow in the dog. Br Vet J. 1994;150(5):423-437. doi:10.1016/S0007-1935(05)80192-7
22. Mehta G, García-Pagán J-C, Bosch J. Physiology of the splanchnic and hepatic circulations. In: Ginès P, Kamath PS, Arroyo V, eds. Chronic Liver Failure: Mechanisms and Management. Humana Press; 2011:77-90.
23. Trahair LG, Horowitz M, Jones KL. Postprandial hypotension: A systematic review. J Am Med Dir Assoc. 2014;15(6):394-409. doi:10.1016/j.jamda.2014.01.011
24. McMullen MK, Whitehouse JM, Whitton PA, Towell A. Bitter tastants alter gastric-phase postprandial haemodynamics. J Ethnopharmacol. 2014;154(3):719-727. doi:10.1016/j.jep.2014.04.041
25. Tian J, Li M, Liao J, Li J, Tong X. Chinese herbal medicine banxiaxiexin decoction treating diabetic gastroparesis: A systematic review of randomized controlled trials. Evid Based Complement Alternat Med. 2013;2013:749495. doi:10.1155/2013/749495
26. Tian JX, Li M, Liao JQ, Liu WK, Tong XL. Xiangshaliujunzi decoction for the treatment of diabetic gastroparesis: a systematic review. World J Gastroenterol. 2014;20(2):561-8. doi:10.3748/wjg.v20.i2.561
27. Doi H, Sakakibara R, Sato M, et al. Dietary herb extract rikkunshi-to ameliorates gastroparesis in Parkinson's disease: a pilot study. Eur Neurol. 2014;71(3-4):193-5. doi:10.1159/000355608
28. Meyerhof W, Batram C, Kuhn C, et al. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses. 2009;35(2):157-170. doi:10.1093/chemse/bjp092
29. Behrens M, Gu M, Fan S, Huang C, Meyerhof W. Bitter substances from plants used in traditional Chinese medicine exert biased activation of human bitter taste receptors. Chem Biol Drug Des. 2018;91(2):422-433. doi:10.1111/cbdd.13089
30. Dragos D, Gilca M. Taste of phytocompounds: A better predictor for ethnopharmacological activities of medicinal plants than the phytochemical class? J Ethnopharmacol. 2018;220:129-146. doi:10.1016/j.jep.2018.03.034
31. Frank O, Zehentbauer G, Hofmann T. Bioresponse-guided decomposition of roast coffee beverage and identification of key bitter taste compounds. Eur Food Res Technol. 2005;222(5):492. doi:10.1007/s00217-005-0143-6
32. Lang R, Klade S, Beusch A, Dunkel A, Hofmann T. Mozambioside Is an arabica-specific bitter-tasting furokaurane glucoside in coffee beans. J Agric Food Chem. 2015;63(48):10492-10499. doi:10.1021/acs.jafc.5b04847
33. Lang T, Lang R, Di Pizio A, et al. Numerous compounds orchestrate coffee’s bitterness. J Agric Food Chem. 2020;68(24):6692-6700. doi:10.1021/acs.jafc.0c01373
34. McMullen MK, Whitehouse JM, Shine G, Whitton PA, Towell A. The immediate and short-term chemosensory impacts of coffee and caffeine on cardiovascular activity. Food Funct. 2011;2(9):547-54. doi:10.1039/c1fo10102a
35. McMullen MK, Whitehouse JM, Shine G, Whitton PA, Towell A. Caffeine in hot drinks elicits cephalic phase responses involving cardiac activity. 10.1039/C2FO00002D. Food Funct. 2012;3(9):931-940. doi:10.1039/C2FO00002D
36. McMullen MK. Neural transmission from oropharyngeal bitter receptors to the medulla is partially or completely labelled-Line. Nat Prod Commun. 2016;11(8):1201-1204. doi:10.1177/1934578X1601100841
37. Liszt KI, Ley JP, Lieder B, et al. Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells. Proceedings of the National Academy of Sciences. 2017;114(30):E6260-E6269. doi:doi:10.1073/pnas.1703728114
38. Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 23rd ed. New York: McGrawHill Medical. 26 ed. McGrawHill Medical.; 2019:752.
39. Douglas BR, Jansen JB, Tham RT, Lamers CB. Coffee stimulation of cholecystokinin release and gallbladder contraction in humans. Am J Clin Nutr. 1990;52(3):553-556. doi:10.1093/ajcn/52.3.553
40. Adan A, Prat G, Fabbri M, Sànchez-Turet M. Early effects of caffeinated and decaffeinated coffee on subjective state and gender differences. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(7):1698-703. doi:10.1016/j.pnpbp.2008.07.005
41. Quinlan P, Lane J, Aspinall L. Effects of hot tea, coffee and water ingestion on physiological responses and mood: the role of caffeine, water and beverage type. Psychopharmacology (Berl). 1997;134(2):164-73. doi:10.1007/s002130050438
42. Leslie FC, Thompson DG, McLaughlin JT, Varro A, Dockray GJ, Mandal BK. Plasma cholecystokinin concentrations are elevated in acute upper gastrointestinal infections. QJM. 2003;96(11):870-1. doi:10.1093/qjmed/hcg140
43. Akimoto K, Inamori M, Iida H, et al. Does postprandial coffee intake enhance gastric emptying?: a crossover study using continuous real time 13C breath test (BreathID system). Hepatogastroenterology. 2009;56(91-92):918-920. PMID: 19621729
44. Boekema PJ, Lo B, Samsom M, Akkermans LM, Smout AJ. The effect of coffee on gastric emptying and oro-caecal transit time. Eur J Clin Invest. 2000;30(2):129-134. doi:10.1046/j.1365-2362.2000.00601.x
45. Lien HC, Chen GH, Chang CS, Kao CH, Wang SJ. The effect of coffee on gastric emptying. Nucl Med Commun. 1995;16(11):923-926. doi 10.1097/00006231-199511000-00008
46. Schubert MM, Grant G, Horner K, et al. Coffee for morning hunger pangs. An examination of coffee and caffeine on appetite, gastric emptying, and energy intake. Appetite. 2014;83:317-326. doi:10.1016/j.appet.2014.09.006
47. Nehlig A. Effects of coffee on the gastro-intestinal tract: A narrative review and literature update. Nutrients. 2022;14(2):399. doi:10.3390/nu14020399
48. Franke A, Harder H, Orth AK, Zitzmann S, Singer MV. Postprandial walking but not consumption of alcoholic digestifs or espresso accelerates gastric emptying in healthy volunteers. J Gastrointestin Liver Dis. 2008;17(1):27-31. doi:10.3390/nu14020399
49. Lovick TA. CCK as a modulator of cardiovascular function. J Chem Neuroanat. 2009;38(3):176-84. doi:10.1016/j.jchemneu.2009.06.007
50. Crespi F. On the role of cholecystokinin (CCK) in fear and anxiety: A review and research proposal. J Human Psych. 2019;1(2):1-10. doi:10.14302/issn.2644-1101.jhp-19-2766
51. Durrant KL. Known and hidden sources of caffeine in drug, food, and natural products. J Am Pharm Assoc (Wash). 2002;42(4):625-637. doi:10.1331/108658002763029607
52. Childs E, de Wit H. Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users. Psychopharmacology. 2006;185(4):514-523. doi:10.1007/s00213-006-0341-3
53. Rezaie P, Bitarafan V, Horowitz M, Feinle-Bisset C. Effects of bitter substances on GI function, energy intake and glycaemia-Do preclinical findings translate to outcomes in humans? Nutrients. 2021;13(4):1317. doi:10.3390/nu13041317
54. Peyrot des Gachons C, Beauchamp GK, Stern RM, Koch KL, Breslin PAS. Bitter taste induces nausea. Curr Biol. 2011;21(7):R247-R248. doi:10.1016/j.cub.2011.02.028
55. Deloose E, Janssen P, Corsetti M, et al. Intragastric infusion of denatonium benzoate attenuates interdigestive gastric motility and hunger scores in healthy female volunteers. Am J Clin Nutr. 2017;105(3):580-588. doi:10.3945/ajcn.116.138297
56. Little TJ, Gupta N, Case RM, Thompson DG, McLaughlin JT. Sweetness and bitterness taste of meals per se does not mediate gastric emptying in humans. Am J Physiol Regul Integr Comp Physiol. 2009;297(3):R632-R639. doi:10.1152/ajpregu.00090.2009
57. Andreozzi P, Sarnelli G, Pesce M, et al. The bitter taste receptor agonist quinine reduces calorie intake and increases the postprandial release of cholecystokinin in healthy subjects. J Neurogastroenterol Motil. 2015;21(4):511-9. doi:10.5056/jnm15028
58. Bitarafan V, Fitzgerald PCE, Little TJ, et al. Intragastric administration of the bitter tastant quinine lowers the glycemic response to a nutrient drink without slowing gastric emptying in healthy men. Am J Physiol Regul Integr Comp Physiol. 2020;318(2):R263-R273. doi:10.1152/ajpregu.00294.2019
59. Wicks D, Wright J, Rayment P, Spiller R. Impact of bitter taste on gastric motility. Eur J Gastroenterol Hepatol. 2005;17(9)doi:10.1097/00042737-200509000-00012
60. Rose BD, Bitarafan V, Rezaie P, Fitzgerald PCE, Horowitz M, Feinle-Bisset C. Comparative effects of intragastric and intraduodenal administration of quinine on the plasma glucose response to a mixed-nutrient drink in healthy men: Relations with glucoregulatory hormones and gastric emptying. J Nutr. 2021;151(6):1453-1461. doi:10.1093/jn/nxab020
61. Walker EG, Lo KR, Pahl MC, et al. An extract of hops (Humulus lupulus L.) modulates gut peptide hormone secretion and reduces energy intake in healthy-weight men: a randomized, crossover clinical trial. Am J Clin Nutr. 2022;115(3):925-940. doi:10.1093/ajcn/nqab418
62. van Avesaat M, Troost FJ, Ripken D, Peters J, Hendriks HF, Masclee AA. Intraduodenal infusion of a combination of tastants decreases food intake in humans. Am J Clin Nutr. 2015;102(4):729-35. doi:10.3945/ajcn.115.113266
63. Xie C, Wang X, Young RL, Horowitz M, Rayner CK, Wu T. Role of intestinal bitter sensing in enteroendocrine hormone secretion and metabolic control. Review. Front Endocrinol (Lausanne). 2018;27(9):576 -583. doi:10.3389/fendo.2018.00576