The Traditional View of Bitter Tonics

Bitter-tasting herbs have a long tradition of use. The pre-dinner drink (aperitif) had its origin in the Roman practice of drinking wine infused with bitter herbs to help ensure efficient digestion.¹ In Western herbal medicine bitters are used to stimulate the appetite and digestive enzymes and to treat associated conditions such as dyspepsia, indigestion, sluggish gallbladder function, and food intolerance.² Bitters were also regarded as having tonic and wider applications, such as to treat fatigue and debilitated conditions affecting the whole body.^3-5 Bitter compounds are detected and tasted in the mouth via the bitter taste-sensing type 2 receptors named TAS2Rs.⁵ However modern research shows that bitter herbs work through mechanisms far beyond taste alone.

TAS2R Activation: What are TAS2 Receptors?

TAS2Rs are also present on other tissues in the body, including the gastrointestinal mucosa (particularly enteroendocrine cells), the skin, lungs and reproductive system. Because the sensing of taste is not required in these extra-oral tissues, other physiological actions must be involved.⁵

There are about 25 functional TAS2Rs in humans (more, but some are nonfunctional), some can only be activated by a few bitter compounds, while others respond to several or many bitter agonists.^5-7 Bitter substances from a range of bitter herbs have been shown to activate TAS2Rs, including Hops, Feverfew, Gentian, Wormwood, Tangerine, Andrographis, and Phellodendron.^8-10

When bitter compounds activate certain TAS2Rs, enteroendocrine cells release hormones such as glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY).^5,6

Metabolic Effects of Incretins

GLP-1, CCK and PYY modulate appetite and satiety, and enhance insulin secretion and bile acid release, potentially leading to healthier blood glucose control and lipid profiles.¹¹

Effects of Gut Hormones

• GLP‑1: reduces appetite, promotes satiety, stimulates insulin secretion, suppresses glucagon release, increases insulin release, slows gastric emptying

• CCK: suppresses appetite (signalling fullness during meals), slows gastric emptying

• PYY: decreases appetite, reduces gastric emptying, improves insulin sensitivity

Clinical Evidence for Bitter Herbs, Incretin Secretion, and Appetite Control

A systemic review and meta-analysis found bitter tastants were the most potent influencers of eating behaviour. Pooled effects of bitter tastants showed a statistically significant reduction in energy intake of 54.62 kcal (p=0.0014).¹²

The strongest clinical evidence for bitter herbs modulating incretins, appetite and body composition is on Hops. In a randomised controlled trial, administration of a Hops extract prior to eating significantly increased the natural secretion of GLP-1, CCK and PYY. Additionally, Hops treatment significantly decreased plasma concentrations of insulin, glucose dependent insulinotropic polypeptide and pancreatic polypeptide, after lunch, compared to placebo. These gut hormone changes were accompanied by a significant reduction in energy intake, compared to placebo (approximately 17%): 4473 kJ (gastric delivered Hops), 4439 kJ (duodenal delivered Hops) and 5383 kJ (placebo), respectively (p=0.006).¹³

In two randomised cross-over studies, the administration of Hops extract during a 24 hour fast significantly reduced perceived hunger and food cravings. In one of these studies, this reduction in hunger was accompanied by a reduction in energy intake at the fast-break meal (-14% lower than placebo).^14,15

Other studies have found Hops extract supplementation resulted in improvements in glycaemic control, BMI, and total fat area in patients with prediabetes,¹⁶  and in visceral fat, body fat ratio and energy intake in overweight healthy people.¹⁷  

Gentian,¹⁸ Andrographis,¹⁹ and Curcumin²⁰ have also been demonstrated to increase GLP-1 secretion in humans. Gentian administration was also associated with reduced energy intake,¹⁸ and Curcumin supplementation also significantly reduced hepatic fat content, body weight and body mass index.²⁰

Utilising Bitter Herbs for Metabolic Support

These scientific studies demonstrate that bitter herbs can be an important part of a holistic prescription for metabolic health. Incorporating bitter herbs as both supplements and foods may help to increase natural incretin secretion, modulate appetite, and reduce energy intake, thereby improving glycaemic control and body composition.

References

¹ Janssen S, Depoortere I. Nutrient sensing in the gut: new roads to therapeutics? Trends Endocrinol Metab 2013; 24(2):92-100. DOI: 10.1016/j.tem.2012.11.006

² Mills SY. The Essential Book of Herbal Medicine. Penguin Arkana (Penguin), London, 1991

³ Weiss RF. Herbal Medicine, translated by Meuss AR from the 6th German Edition of Lehrbuch der Phytotherapie. Beaconsfield Publishers, Beaconsfield, 1988

⁴ Cook WH. The Physio-medical Dispensatory. First published 1869, reprinted Eclectic Medical Publications, Portland, 1985.

⁵ Descamps-Solà M, Vilalta A, Jalsevac F, Blay MT, Rodríguez-Gallego E, Pinent M, et al. Bitter taste receptors along the gastrointestinal tract: comparison between humans and rodents. Front Nutr. 2023 Aug 30;10:1215889. DOI: 10.3389/fnut.2023.1215889.

⁶ Wang Q, Liszt KI, Depoortere I. Extra-oral bitter taste receptors: new targets against obesity? Peptides. 2020 May;127:170284. DOI: 10.1016/j.peptides.2020.170284.

⁷ Behrens M, Schaefer S. Bitter taste receptors. Chem Senses. 2025 Jan 22;50:bjaf064. DOI: 10.1093/chemse/bjaf064.

⁸ Meyerhof W, Batram C, Kuhn C et al. The molecular receptive ranges of human TAS2R bitter taste receptors Chem Senses 2010; 35(2):157-170. DOI: 10.1093/chemse/bjp092

⁹ Brockhoff A, Behrens M, Massarotti A et al. Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium.J Agric Food Chem 2007; 55(15):6236-6243. DOI: 10.1021/jf070503p

¹⁰ Narukawa M, Noga C, Ueno Y et al. Biochem Biophys Res Commun 2011; 405(4): 620-625

¹¹ Chou WL. Therapeutic potential of targeting intestinal bitter taste receptors in diabetes associated with dyslipidemia. Pharmacol Res. 2021 Aug;170:105693. DOI: 10.1016/j.phrs.2021.105693.

¹² Klaassen T, Keszthelyi D, Troost FJ, Bast A, Masclee AAM. Effects of gastrointestinal delivery of non-caloric tastants on energy intake: a systematic review and meta-analysis. Eur J Nutr. 2021 Sep;60(6):2923-2947.

¹³ Walker EG, Lo KR, Pahl MC, Shin HS, Lang C, Wohlers MW, 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 Mar 4;115(3):925-40. DOI: 10.1093/ajcn/nqab418.

¹⁴ Walker E, Lo K, Tham S, Pahl M, Lomiwes D, Cooney J, et al. New Zealand bitter hops extract reduces hunger during a 24 h water only fast. Nutrients. 2019 Nov 13;11(11):2754. DOI: 10.3390/nu11112754.

¹⁵ Walker E, Lo K, Gopal P. Gastrointestinal delivery of bitter hop extract reduces appetite and food cravings in healthy adult women undergoing acute fasting. Obes Pillars. 2024 Jun 20;11:100117. DOI: 10.1016/j.obpill.2024.100117.

¹⁶ Obara K, Mizutani M, Hitomi Y, Yajima H, Kondo K. Isohumulones, the bitter component of beer, improve hyperglycemia and decrease body fat in Japanese subjects with prediabetes. Clin Nutr. 2009 Jun;28(3):278-84. DOI: 10.1016/j.clnu.2009.03.012.

¹⁷ Morimoto-Kobayashi Y, Ohara K, Ashigai H, Kanaya T, Koizumi K, Manabe F,et al. Matured hop extract reduces body fat in healthy overweight humans: a randomized, double-blind, placebo-controlled parallel group study. Nutr J. 2016 Mar 9;15:25. DOI: 10.1186/s12937-016-0144-2.

¹⁸ Mennella I, Fogliano V, Ferracane R, Arlorio M, Pattarinio F, Vitaglione P. Microencapsulated bitter compounds (from Gentiana lutea) reduce daily energy intakes in humans. Br J Nutr. 2016 Nov 10: 1-10. DOI: 10.1017/S0007114516003858.

¹⁹ Tarigan TJE, Purwaningsih EH, Yusra, Abdullah M, Nafrialdi, Prihartono J, et al. Effects of Sambiloto (Andrographis paniculata) on GLP-1 and DPP-4 concentrations between normal and prediabetic subjects: a crossover study. Evid Based Complement Alternat Med. 2022 Jan 15;2022:1535703. DOI: 10.1155/2022/1535703.

²⁰ He Y, Chen X, Li Y, Liang Y, Hong T, Yang J, et al. Curcumin supplementation alleviates hepatic fat content associated with modulation of gut microbiota-dependent bile acid metabolism in patients with nonalcoholic simple fatty liver disease: a randomized controlled trial. Am J Clin Nutr. 2024 Jul;120(1):66-79. doi: 10.1016/j.ajcnut.2024.05.017.