Many cultures (and indeed herbal clinicians) around the world have long respected the role of bitter herbs and foods for promoting digestion. For example, aperitifs – drinks consumed before a meal to stimulate appetite and digestion – were originally derived from bitter herbs.

And a traditional Dutch early evening food, bitterballen, was often consumed by the elderly with failing digestion.

Bitterballen isn't usually bitter tasting anymore, and certainly the modern way is to avoid bitter-tasting foods. We even now associate the word bitter with negative emotions and experiences. However, modern research has confirmed that optimizing the bitter taste function is essential for good health, and this is not just confined to the digestive tract. As busy clinicians, you might be wondering how this research can help you achieve better outcomes with your patients. Here's how.

At one time, it was thought bitters primarily acted to stimulate the digestive processes of the upper gastrointestinal tract by a reflex initiated from the bitter taste buds on the tongue. In other words, the interaction of the bitter-tasting phytochemicals in the herb with receptors on the tongue stimulated nervous impulses to the brain, which in turn initiated facilitatory signals via the vagus nerve to the upper digestive organs, especially the stomach.

Hence, tasting a bitter herb before eating was felt to be essential for its activity. Bitters were seen to prime the digestion by this reflex process through stimulating the release of gastric acid, digestive enzymes and bile.

Since then, there have been several important new discoveries. First, we know much more about the bitter taste receptors themselves. A family of around 30 receptors (denoted as TAS2R, previously T2R) has been identified.¹ Most TAS2Rs are broadly tuned to each detect a range of bitter substances, explaining how we can recognize hundreds of bitter compounds with only this limited set of receptors.

In addition, some extremely bitter molecules simultaneously stimulate more than one receptor. For example, amarogentin from gentian stimulates seven receptors: TAS2R1, 4, 39, 43, 46, 47 and 50; Absinthin from wormwood stimulates four: TAS2R10, 14, 46 and 47.² This could explain why herbs such as gentian and wormwood are particularly good at boosting digestion.

The most intriguing new discovery is that bitter taste receptors are not restricted to the mouth.³ There are numerous reports of TAS2Rs being present farther down in the gut in certain cells lining the gastrointestinal wall, including in the stomach. Cells with these receptors appear to be wired to elicit an aversive behavior, probably as a defensive mechanism, because many toxic chemicals are bitter in taste.¹ As a result of this defensive response of the digestive system, bitter taste receptors in the gastrointestinal tract appear to upregulate several metabolic and digestive functions.

In particular, bitter receptors have been found on enteroendocrine cells, the specialized hormone-releasing cells of the upper digestive tract.⁴ When stimulated, these cells release a variety of gut hormones, but in particular, cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1). CCK has numerous important functions in the digestive tract: It promotes secretion of pancreatic enzymes and bile, slows down stomach emptying, increases gastric digestive mixing and secretions, and creates a sense of fullness so you stop eating.

GLP-1 also slows gastric emptying and creates a sense of fullness, but most importantly, it stimulates the release of insulin. In fact, there is a new class of diabetes drugs (the gliptins) based on enhancing the action of GLP-1. We now know bitters can stimulate the release of these important hormones from enteroendocrine cells.

This new research suggests bitters can create a sense of fullness (satiety) and hence might actually help with weight loss. How does this sit with the traditional notion that bitters improve appetite? The answer is there is no contradiction, because bitters only seem to promote appetite when it is below par.⁵

The discovery that bitter receptors occur throughout the gastrointestinal tract and appear to regulate a number of physiological functions has the potential to change our understanding of bitter herbs. First, it means bitter herbs do not need to be tasted to boost upper digestive function. While tasting may be desirable for optimum effects, it is not essential. In fact, clinical research on gentian dating from 19986 supports this concept, but now we understand why. This means tablets or capsules containing bitter herbs will be clinically active, although higher doses are probably necessary.

As noted above, support for this concept of direct activity in the stomach also comes from a multicenter, uncontrolled study of gentian capsules involving 205 patients.⁶ Patients took on average about five capsules per day, each containing 120 mg of a 5:1 dry extract of gentian root, and achieved rapid and dramatic relief of symptoms including constipation, flatulence, appetite loss, vomiting, heartburn, abdominal pain and nausea.

As early as 1956, Wolf and Mack carried out an excellent case study on the direct action of various bitters on the stomach of their patient Tom (who had an occluded esophagus and a gastric fistula), with goldenseal (Hydrastis canadensis) proving to be the most potent direct-acting bitter.⁷

Research has shown that the capacity to sense bitterness varies from person to person. Some people are highly sensitive, known as “supertasters.” Since the stimulation of bitter receptors could exert a range of important health benefits, could people who have a low sensitivity to bitters be at a health disadvantage? Epidemiological research suggests this could be the case. In fact, functional variants in bitter taste receptor sensitivity have been linked to alcohol dependency,⁸ adiposity,⁹ eating behavior disinhibition¹⁰ and high body-mass index (BMI).¹¹ People with a lower bitter tasting sensitivity exhibited the poorer health measure.

The new research also suggests a role for bitter herbs in blood sugar control and managing insulin resistance. In support of this, 94 patients with prediabetes exhibited improvements in BMI, blood glucose control and body fat when given just 16-48 mg/day of isohumulones (hop bitter acids) as capsules in a double blind, placebo-controlled clinical trial.¹²

Blending bitters together will have more clinical impact, as a wider range of bitter receptors will be stimulated. This will help to overcome the genetic variations in a person's capacity to taste and respond to bitters. For example, a combination of gentian, wormwood and feverfew will stimulate 12 out of the known 29 human bitter taste receptors.

In a sense, with our modern dietary focus on sweet, sour, savory and salty foods, bitter has become the neglected taste. The latest research provides a compelling argument that we can all benefit from adding bitter herbs and foods back into our diet. Perhaps by including bitterness in our diet, we might avoid bitterness in our life (in terms of physical health)?

References

1. Meyerhof W. "Elucidation of mammalian bitter taste." Rev Physiol Biochem Pharmacol, 2005;154:37-72.
2. Meyerhof W, Batram C, Kuhn C, et al. "The molecular receptive ranges of human TAS2R bitter taste receptors." Chemical Senses, 2010; 35(2):157-170.
3. Behrens M, Meyerhof W. "Gustatory and extragustatory functions of mammalian taste receptors." Physiology Behavior, 2011;105(1):4-13.
4. Valussi M. "Functional foods with digestion-enhancing properties." International Journal of Food Sciences and Nutrition, 2012;63(Suppl 1):82-89.
5. Mills SY, Bone KM. Chapter 2: "Principles of Herbal Pharmacology." Principles and Practice of Phytotherapy: Modern Herbal Medicine, 1st Edition. Edinburgh: Churchill Livingstone, 2000.
6. Wegener T. "Anwendung eines Trockenextraktes Augentianae luteae radix bei dyspeptischem Symptomkomplex." Z Phytother, 1998;19:163-164.
7. Wolf S, Mack M. "Experimental study of the action of bitters on the stomach of a fistulous human subject." Drug Standards, 1956;24(3):98-101.
8. Wang JC, Hinrichs AL, Bertelsen S, et al. "Functional variants in TAS2R38 and TAS2R16 influence alcohol consumption in high-risk families of African-American origin." Alcoholism Clinical and Experimental Research, 2007;31(2):209-215.
9. Tepper BJ, Koelliker Y, Zhao L, et al. "Variation in the bitter-taste receptor gene TAS2R38, and adiposity in a genetically isolated population in Southern Italy." Obesity, 2008;16(10):2289-2295.
10. Dotson CD, Shaw HL, Mitchell BD, et al. "Variation in the gene TAS2R38 is associated with the eating behavior disinhibition in Old Order Amish women." Appetite, 2010;54(1):93-99.
11. Feeney E, O'Brien S, Scannell A, et al. "Genetic variation in taste perception: does it have a role in healthy eating?" The Proceedings of the Nutrition Society, 2011;70(1):135-143.
12. Obara K, Mizutani M, Hitomi Y, et al. "Isohumulones, the bitter component of beer, improve hyperglycemia and decrease body fat in Japanese subjects with prediabetes." Clinical Nutrition, 2009;28(3):278-284.

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Kerry Bone is a practicing herbalist; co-founder and head of research and development at MediHerb; and principal of the Australian College of Phytotherapy. He also is the author of several books on herbs and herbal therapy, including Principles and Practice of Phytotherapy and The Essential Guide to Herbal Safety.

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