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Digestive bitter formulas or tonics, comprised of plants such as gentian, ginger, wormwood, and dandelion, have been traditionally used to support digestive function for millennia. (1

Deficient in most modern diets, which lean heavily toward overly sweet or salty foods, digestive bitter herbs and plants were regularly consumed in ancestral diets. Digestive bitters are most effective when taken 10-15 minutes before a meal or with a meal.

For over a century now, two herbs in particular, gentian and skullcap, have been routinely combined and used as an herbal digestive bitter formulation to treat indigestion and heartburn. (2)

The doctor who pioneered this formulation is the late, great naturopathic physician, Dr. O.G. Carroll, said to be the most famous doctor west of the Mississippi in his time, operated a large clinical practice for decades out of Spokane, Washington. Dr. Carroll called his herbal formulation fifty-fifty caps because they were said to be approximately half gentian and half skullcap. (3

More can be learned about Dr. Carroll’s legacy, such as the Carroll Food Intolerance Method, at The Carroll Institute of Healing

It is a well-known fact that gastroesophageal reflux disease (GERD) is strongly associated with a condition called hypochlorhydria, wherein the pH of the stomach, which normally is around 1.5 to 3.5, is too high and so the stomach acid, responsible for activating a cascade of enzymatic and hormonal activity in the gut, is abnormally low. (4

It can be argued that modern diets tend to prolong acid suppression and lead to hypochlorhydria, impairing vitamin B12, calcium, and iron absorption, as well as leading to increased infectious risks over the long term. Also, it has been hypothesized that the intraluminal environment is altered and small intestinal bacterial overgrowth (SIBO) is promoted. As a result of SIBO, excessive fermentation occurs and leads to symptoms such as bloating, abdominal discomfort, and diarrhea. (5)

Evidence abounds that the lower esophageal sphincter will loosen and open if the acidic environment of the GI tract is not sufficient, hence, the acidic contents of the gut will reflux up into the esophagus and cause the symptoms of heartburn. (6)

The Science of Digestive Bitters

Scientists are split as to the mechanism of digestive bitters: a cephalic elicited vagal response involving the enteric nervous system versus a purely local response in the gastrointestinal tract. The truth is that it’s both. (7)

Our human genome contains 29 bitter taste receptors (T2Rs), which are responsible for all bitter ligands and stimulated when ingesting bitter foods, transferring information from our vagus nerve to our digestive organs and promoting an optimal pH in the gut. (8) In mouse models, bitter compounds have been shown to activate the T2Rs and stimulate the secretion of the hunger hormone ghrelin, which makes us feel satiated. (9)


The herb, gentian (Gentiana lutea), also known as bitter root, is known to help keep the pH in the gut optimal as well as upregulate gut function and the ability to break down foodstuff entering the gut. (10)

As a result, enzymatic activity fires on all cylinders in the gut and adequate secretion delivers appropriate catabolic activity, facilitating breakdown and absorption. The microflora stays balanced, as well, disallowing pathogenic bacteria to take hold and engender dysbiosis. Conditions such as fungal overgrowth and ulcers associated with H. pylori bacteria overgrowth would be much less likely to occur. (11, 12)

Bitter glycoside compounds, such as secoiridoid monoterpenes, are what give gentian its bitter taste, but it also contains triterpenoids, xanthones, and other constituents. (13)

Gentian has analgesic, anti-inflammatory, and antioxidant effects. The root of gentian is used more commonly than the bark in herbal remedies. Gentian has been used for digestive disorders, such as loss of appetite, bloating, diarrhea, fullness, flatulence, and acid reflux. It has also been used for alleviating fever as well as preventing muscle spasms.


The herb, skullcap (Scutellaria laterifllora), soothes the digestive lining of the gut and supports gut healing, operating as a nervine, thereby calming the nervous system and helping to regulate the gut-brain axis as well as the vagus nerve connecting the brain to the gut. (14)

Skullcap possesses anxiolytic, sedative, anti-inflammatory, and antispasmodic properties. Skullcap contains flavonoids, lignins, resins, and tannins. (15)


As a naturopathic physician, digestive bitters are my first line of treatment, as we start with getting gut function improved. One of my favorite bitter tonics is gentian and skullcap digestive capsules.

Remember to consult your naturopathic doctor, or your integrative medicine practitioner, regarding the role that digestive bitters can play in your health, as there may be contraindications to adding them to your regimen.


  1. McMullen MK, Whitehouse JM, Towell A. Bitters: Time for a New Paradigm. Evid Based Complement Alternat Med. 2015;2015:670504. doi: 10.1155/2015/670504. Epub 2015 May 14. PMID: 26074998; PMCID: PMC4446506. https://pubmed-ncbi-nlm-nih-gov.liboff.ohsu.edu/26074998/
  2. Editor1. (2015, December 17). The Carroll Food Intolerance Evaluation and Its Applications. Retrieved January 11, 2021, from https://ndnr.com/autoimmuneallergy-medicine/the-carroll-food-intolerance-evaluation-and-its-applications/
  3. Zap Indigestion with #50 Capsules. (n.d.). Retrieved January 11, 2021, from https://www.holistichealthpc.com/blog/zap-indigestion-with-50-capsules
  4. Kellerman R, Kintanar T. Gastroesophageal Reflux Disease. Prim Care. 2017 Dec;44(4):561-573. doi: 10.1016/j.pop.2017.07.001. Epub 2017 Oct 5. PMID: 29132520.
  5. Surdea-Blaga T, Negrutiu DE, Palage M, Dumitrascu DL. Food and Gastroesophageal Reflux Disease. Curr Med Chem. 2019;26(19):3497-3511. doi: 10.2174/0929867324666170515123807. PMID: 28521699.
  6. Reebs, D., & *, N. (2018, June 19). The Myth of GERD: It’s Not the Acid, Stupid! Dr. Ben Reebs. Retrieved January 11, 2021, from https://www.drreebs.com/the-myth-of-gerd-its-not-the-acid-stupid/
  7. McMullen MK, Whitehouse JM, Towell A. Bitters: Time for a New Paradigm. Evid Based Complement Alternat Med. 2015;2015:670504. doi: 10.1155/2015/670504. Epub 2015 May 14. PMID: 26074998; PMCID: PMC4446506. https://pubmed-ncbi-nlm-nih-gov.liboff.ohsu.edu/26074998/
  8. Bloxham CJ, Foster SR, Thomas WG. A Bitter Taste in Your Heart. Front Physiol. 2020 May 8;11:431. doi: 10.3389/fphys.2020.00431. PMID: 32457649; PMCID: PMC7225360.
  9. Janssen S, Laermans J, Verhulst PJ, Thijs T, Tack J, Depoortere I. Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2094-9. doi: 10.1073/pnas.1011508108. Epub 2011 Jan 18. PMID: 21245306; PMCID: PMC3033292.
  10. Levy, J. (2019, September 10). The Ancient Herb that Aids Digestion, Wound Healing & More. Retrieved January 11, 2021, from https://draxe.com/nutrition/gentian/
  11. Beasley DE, Koltz AM, Lambert JE, Fierer N, Dunn RR. The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome. PLoS One. 2015 Jul 29;10(7):e0134116. doi: 10.1371/journal.pone.0134116. PMID: 26222383; PMCID: PMC4519257.
  12. Sarker SA, Ahmed T, Brüssow H. Hunger and microbiology: is a low gastric acid-induced bacterial overgrowth in the small intestine a contributor to malnutrition in developing countries? Microb Biotechnol. 2017 Sep;10(5):1025-1030. doi: 10.1111/1751-7915.12780. Epub 2017 Jul 17. PMID: 28714103; PMCID: PMC5609274.
  13. Mirzaee F, Hosseini A, Jouybari HB, Davoodi A, Azadbakht M. Medicinal, biological and phytochemical properties of Gentiana species. J Tradit Complement Med. 2017 Jan 28;7(4):400-408. doi: 10.1016/j.jtcme.2016.12.013. PMID: 29034186; PMCID: PMC5634738.
  14. Awad R, Arnason JT, Trudeau V, Bergeron C, Budzinski JW, Foster BC, Merali Z. Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties. Phytomedicine. 2003 Nov;10(8):640-9. doi: 10.1078/0944-7113-00374. PMID: 14692724.
  15. Shang X, He X, He X, Li M, Zhang R, Fan P, Zhang Q, Jia Z. The genus Scutellaria an ethnopharmacological and phytochemical review. J Ethnopharmacol. 2010 Mar 24;128(2):279-313. doi: 10.1016/j.jep.2010.01.006. Epub 2010 Jan 11. PMID: 20064593.