Detoxification: The Importance of Moving Bile with a Bigger Bitter
Bile. It doesn’t have the best reputation. You know it as that bitter fluid you burp up on occasion. It’s also a synonym for spite and malice. As an adjective—bilious—it means spiteful and ill-tempered.
So, you might be surprised to know that bile is, metabolically, like precious gold. The smooth flow of that dark green to yellowish brown liquid produced by your liver and stored in your gallbladder is a key player in detoxification, proper digestion, an intact gut lining, healthy small intestine flora, normal cholesterol and blood sugar levels, and perhaps even the proper function of neurons in the brain.1,2,3,4 Bile salts can modify lipids, destroy bacterial endotoxins, and function as an antimicrobial.5,6
In many people, however, bile flow is impaired, leading to stagnation.7 That stagnation can have profound health consequences. Stagnant bile flow impairs the movement of toxins, which flow with the bile out of the liver into the gallbladder, and then into the digestive tract for excretion.8 The lack of bile flow can also contribute to gastrointestinal dysbiosis and small intestinal bacteria overgrowth (SIBO). 9,10 Endotoxin, associated with dysbiosis and gram-negative flora, irritates the mucosal lining of the gastrointestinal tract and increases inflammation.11 An inflamed and “leaky” gut then lets bacterial and other toxins slip into the bloodstream, triggering a systemic inflammatory response.12 That inflammatory response can further impair liver and gallbladder function and inhibit bile flow, contributing to what is known as cholestasis.13
As if that’s not enough, endotoxins downregulate critical pumps (called Phase III transporters) that transport toxins out of our cells.14 This stepwise buildup of toxins depletes our most potent antioxidant, glutathione--further stressing the liver, which relies heavily on glutathione in detoxification reactions.15,16 In addition, a gut inflamed by endotoxin renders the liver more susceptible to damage by xenobiotics, chemicals foreign to our body, found in our environment.17
Let it flow, then. Bile flow is supremely important to overall health. And if there is one simple and powerful way to assist the healthy flow of bile, it is the classic bitter herbs that have been part of our medicine chest for centuries. These herbs long ago migrated from the apothecary to the cocktail bar, transforming into cherished aperitifs and digestifs that are taken before or after meals to stimulate appetite and digestion. These bitter substances offer the body not only support for digestion, but have an impact on the function of many other systems. Receptors for bitter cover not only the back of the tongue, but are also found in the lungs, ovaries, pancreas and other tissues. They can trigger numerous biological processes including regulation of blood sugar and activation of the immune system in response to infections.18,19,20,21
Bitters inherently turn on the digestive processes, but there are some bitter herbs that are more targeted for supporting the movement of bile, and toxins, from the liver and out through the gallbladder. Here are four such bitters:
*Dandelion (Taraxacum officinale). Dandelions produce bright yellow flower that turn to wispy puffs. The leaves are grooved and the brown roots fleshy, filled with a bitter, milky material. The pleasant (to some!) bitter taste in the leaves and root are due to molecules called sesquiterpene lactones that increase bile production and stimulate digestion.22,23 Dandelion stimulates the flow of bile into the duodenum (cholagogue) and simultaneously stimulates the production of bile by the liver (choleretic). It increases the activity of glutathione (GSH) and GSH-related enzymes in the liver.24 It is a diuretic and supports elimination of toxins through the urine.25 The long-chain saccharides in dandelion also have anti-inflammatory effects, possibly due to its inhibition of nitric oxide production and COX-2 expression (cyclooxygenase, or COX, an enzyme that produces prostaglandins that promote inflammation, pain, and fever).26,27
*Gentian (Gentianinae, family of 400 species). Well known as one of the strongest bitter herbs—or the most bitter bitter—gentian stimulates digestive secretions of all kinds, including saliva and bile flow.28 It modulates stomach acid secretion, increasing it in a state of deficiency, yet protecting stomach tissues against gastritis or gastric ulcers, possibly by regulating inflammatory prostaglandin pathways.29 Gentian is hepatoprotective, and as a liver protective agent has been observed to increase levels of catalase, superoxide dismutase and reduced GSH.30 Gentian has been observed in animal studies to increase GSH, GSH peroxidase, and superoxide dismutase levels in the setting of alcohol or acetaminophen-induced oxidative damage—and in this way, supporting and protecting the liver.31,32
*Goldenrod (Solidago canadensis) is a classic herb that supports the urinary system, promotes urination and thus the elimination of toxins.33 This helps support the liver, as some toxins, once conjugated, may be more efficiently drained through the kidneys. At the same time, flavonoids from solidago help activate GSH-S-transferase, a critical enzyme in phase II detoxification, which also brings relief to the liver.34
*Myrrh (Commiphora myrrha). Myrrh is a resinous exudate from trees of Commiphora species. It contains many highly bioactive molecules such as terpenoids and sesquiterpenoids as well as furanosesquiterpenoids, which have antifungal, antibacterial, anti-inflammatory, and smooth-muscle relaxing action.35
Myrrh strongly promotes healthy bile flow, and it has microbial-balancing qualities as well.36,37 Myrrh is popular in both Ayurvedic and Chinese medicine, and is considered a primary detoxifier that is both tonifying and strengthening. Its reputation for moving stagnant blood, including menstrual blood, leads to its popular use as a female remedy.38 Myrrh, like its popular Ayurvedic herbal cousin guggul, contains molecules called sterones that have impressively diverse biological activity. They can increase iodine uptake in the thyroid, and inhibit the inflammation triggered by endotoxin-induced nitric oxide production, having even more potent activity than curcumin.39
Just as significant, these sterones help turn on the bile salt export pump (Bsep).40 Bsep is located on the cell surfaces which connect the hepatocytes (liver cells) to the bile canaliculus, which drains bile from the liver to the gallbladder. This is one of the mechanisms by which guggul may have cholesterol-lowering effects, as the conversion of cholesterol to bile acids in the liver helps eliminate excess cholesterol, but also supports the movement of bile out of the liver, reducing cholestasis.
This blend of bitter herbs (dandelion, goldenrod, gentian, and myrrh) brings together the traditional use of bitters from multiple medicine systems, supported by research, to support gastrointestinal function and the processes of detoxification, more strongly than any other bitter combination. It’s bigger. It’s better. It’s badder. It’s bitter!
1 Lefebvre P, Cariou B, Lien F et al. Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev. 2009 Jan;89(1):147-91 View Abstract
2 Gadaleta RM, Oldenburg B, Willemsen EC et al. Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine. Biochim Biophys Acta. 2011 Aug;1812(8):851-8 View Abstract
3 Sharma R, Long A, Gilmer JF. Advances in Bile Acid Medicinal Chemistry. Curr Med Chem. 2011;18(26):4029-52 View Abstract
4Islam KB, Fukiya S, Hagio M Bile acid is a host factor that regulates the composition of the cecal microbiota in rats.Gastroenterology. 2011 Nov;141(5):1773-81. View Abstract
5 Fernandesa CF, Shahani KM, Amer MA. Effect of Nutrient Media and Bile Salts on Growth and Antimicrobial Activity of Lactobacillus acidophilus. Journal of Dairy Science Volume 71, Issue 12, December 1988, Pages 3222-32299. View Abstract
6 D'Aldebert E, Biyeyeme Bi Mve MJ, Mergey M et al. Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology. 2009 Apr;136(4):1435-43. View Abstract
7 Dietrich CG, Geier A, Wasmuth HE Influence of biliary cirrhosis on the detoxification and elimination of a food derived carcinogen. Gut. 2004 Dec;53(12):1850-5. View Full Paper
8 Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation.
Physiol Rev. 2003 Apr;83(2):633-71. View Full Paper
9 Islam KB, Fukiya S, Hagio M, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011 Nov;141(5):1773-81.
10 Hellström PM, Nilsson I, Svenberg T. Role of bile in regulation of gut motility. J Intern Med. 1995 Apr;237(4):395-402.
11 Awad WA, Hess C, Hess M. Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens. Toxins (Basel). 2017 Feb 10;9(2). View Abstract
12 Ahmad R, Sorrell MF, Batra SK, et al. Gut permeability and mucosal inflammation: bad, good or context dependent. Mucosal Immunol. 2017 Mar;10(2):307-317 View Abstract
13 Whiting JF, Green RM, Rosenbluth AB et al. Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis. Hepatology. 1995 Oct;22(4 Pt 1):1273-8. View Abstract
14 Kalitsky-Szirtes J, Shayeganpour A, Brocks DR et al. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos. 2004 Jan;32(1):20-7. View Abstract
15 Kaplowitz N. The importance and regulation of hepatic glutathione. Yale J Biol Med. 1981 Nov-Dec; 54(6): 497–502. View Full Paper
16 Carbonell LF, Nadal JA, Llanos MC, et al. Depletion of liver glutathione potentiates the oxidative stress and decreases nitric oxide synthesis in a rat endotoxin shock model. Critical care medicine. 2000 Jun 1;28(6):2002-6. View Abstract
17 Ganey PE, Roth RA. Concurrent inflammation as a determinant of susceptibility to toxicity from xenobiotic agents. Toxicology. 2001 Dec 28;169(3):195-208. View Abstract
18 Yu Y, Hao G, Zhang Q, Hua W, Wang M, Zhou W, Zong S, Huang M, Wen X. Berberine induces GLP-1 secretion through activation of bitter taste receptor pathways. Biochem Pharmacol. 2015 Sep 15;97(2):173-7. View Abstract
19Shaik FA, Singh N, Arakawa M, Duan K, Bhullar RP, Chelikani P. Bitter taste receptors: Extraoral roles in pathophysiology. Int J Biochem Cell Biol. 2016 Aug;77(Pt B):197-204. View Abstract
20 Lee RJ, Cohen NA. The emerging role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis. Am J Rhinol Allergy. 2013 Jul-Aug;27(4):283-6. View Abstract
21 Gaida MM, Dapunt U, Hänsch GM. Sensing developing biofilms: the bitter receptor T2R38 on myeloid cells. Pathog Dis. 2016 Apr;74(3). View Full Paper
22 You Y, Yoo S, Yoon HG et al. In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress.Food Chem Toxicol. 2010 Jun;48(6):1632-7. View Abstract
23 Park CM, Cha YS, Youn HJ Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in Sprague-Dawley rats. Phytother Res. 2010 Sep;24(9):1347-53 View Abstract
24 Ung-Kyu C, Ok-Hwan L, Joo Hyuk Y et al. Hypolipidemic and Antioxidant Effects of Dandelion (Taraxacum officinale) Root and Leaf on Cholesterol-Fed Rabbits Int J Mol Sci. 2010 Jan; 11(1): 67–78. View Full Paper
25 Clare BA, Conroy RS, Spelman K. The Diuretic Effect in Human Subjects of an Extract of Taraxacum officinale Folium over a Single Day J Altern Complement Med. 2009 Aug; 15(8): 929–934. View Full Paper
26 Park CM, Cho CW, Song YS. TOP 1 and 2, polysaccharides from Taraxacum officinale, inhibit NFκB-mediated inflammation and accelerate Nrf2-induced antioxidative potential through the modulation of PI3K-Akt signaling pathway in RAW 264.7 cells. Food Chem Toxicol. 2014 Apr;66:56-64. View Abstract
27 Jeon HJ, Kang HJ, Jung HJ et al. Anti-inflammatory activity of Taraxacum officinale. J Ethnopharmacol. 2008 Jan 4;115(1):82-8. View Abstract
28 P Oztürk N, Herekman-Demir T, Oztürk Y et al. . Choleretic activity of Gentiana lutea ssp. symphyandra in rats.Phytomedicine. 1998 Aug;5(4):283-8 View Abstract
29 Niiho Y, Yamazaki T, Nakajima Y, Yamamoto T, Ando H, Hirai Y, Toriizuka K, Ida Y. Gastroprotective effects of bitter principles isolated from Gentian root and Swertia herb on experimentally-induced gastric lesions in rats. Journal of natural medicines. 2006 Jan;60(1):82-8. View Abstract
30 Mihailović V, Mihailović M, Uskoković A et al. Hepatoprotective effects of Gentiana asclepiadea L. extracts against carbon tetrachloride induced liver injury in rats. Food Chem Toxicol. 2013 Feb;52:83-90. View Abstract
31 Lian LH, Wu YL, Song SZ, Wan Y, Xie WX, Li X, Bai T, Ouyang BQ, Nan JX. Gentiana manshurica Kitagawa reverses acute alcohol-induced liver steatosis through blocking sterol regulatory element-binding protein-1 maturation. J Agric Food Chem. 2010 Dec 22;58(24):13013-9. View Abstract
32 Wang AY, Lian LH, Jiang YZ, Wu YL, Nan JX. Gentiana manshurica Kitagawa prevents acetaminophen-induced acute hepatic injury in mice via inhibiting JNK/ERK MAPK pathway. World J Gastroenterol. 2010 Jan 21;16(3):384-91. View Abstract
33 Melzig MF. [Goldenrod--a classical exponent in the urological phytotherapy]. Wien Med Wochenschr. 2004 Nov;154(21-22):523-7. View Abstract
34 Apáti P, et al. In-vitro effect of flavonoids from Solidago canadensis extract on GSH S-transferase. J Pharm Pharmacol. 2006 Feb;58(2):251-6. View Abstract
35 Shen T, Lou, HX. Bioactive Constituents of Myrrh and Frankincense, Two Simultaneously
Prescribed Gum Resins in Chinese Traditional Medicine. Chemistry & Biodiversity. 2008; 5: 541-543
36 Dolara P, Corte B, Ghelardini C, Pugliese AM, Cerbai E, Menichetti S, Lo Nostro A. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh. Planta Med. 2000 May;66(4):356-8. View Abstract
37 Sheir Z, Nasr AA, Massoud A, Salama O, Badra GA, El-Shennawy H, Hassan N, Hammad SM. A safe, effective, herbal antischistosomal therapy derived from myrrh. Am J Trop Med Hyg. 2001 Dec;65(6):700-4. View Full Paper
38 Engels G, Brinckmann J. Myrrh. American Botanical Council. 2012. [Cited October 9, 2017] Available at: cms.herbalgram.org/herbalgram/issue93/HERBPRO_myrrh.html
39 Frawley D, Lad V. The Yoga of Herbs: An Ayurvedic Guide to Herbal Medicine. Lotus Press, 1986.
40 Cui J, Huang L, Zhao A, et al. Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. J Biol Chem. 2003 Mar 21;278(12):10214-20. View Abstract