Bitters: Balancing Agents for the Gut, and Support for Liver/Kidney Detoxification
Herbal bitters have a long history of use, and are commonly used in cocktails known as aperitifs and digestifs which are served before and after meals to stimulate appetite and digestion. However, bitter herbs act far beyond the digestive system, and broadly impact the liver, kidneys, skin, immune system, and detoxification pathways.
Bitter herbs broadly encompass many botanicals, and are most often thought of as herbs with effects on the digestive system. Herbal bitters have a long history of use, and are commonly served in cocktails known as aperitifs and digestifs before or after meals to stimulate appetite and digestion. Strong bitter herbs like gentian stimulate stomach acid and other accompanying digestive secretions, while slightly milder bitters such as sweet orange essential oil also calms digestive upset and balances the central nervous system. Bitter herbs act far beyond the digestive system however, and broadly impact the liver, kidneys, skin, immune system, and detoxification pathways. Bitter taste receptors exist not only on the back of the tongue but also throughout the digestive system and beyond. They have been shown to trigger a wide variety of biological processes including regulation of blood sugar and activation of the immune system in response to infections.,,
The impact of liver, kidney, and gastrointestinal function on detoxification
Although the process of detoxification occurs in every cell of the body, organs in which detoxification occurs at a higher level are the liver and kidneys. It is well known that in individuals with compromised liver or kidney function, dosages of many medications must be altered. The small intestine mucosa also plays an important role in detoxification, as proteins important for all phases of detoxification are expressed at a high level here., When any of these organs (liver, kidneys, intestines) experience less than optimal function, a backup in processing of toxins will occur. With understanding of this, it is easy to see the importance of an integrated process where the intestines, liver, and kidneys are all functioning in an optimal fashion simultaneously.
Gastrointestinal inflammation also effects detoxification, increasing susceptibility of the organism to toxicity from external and internal agents. Leaky gut and damage to the gastrointestinal barrier allows endotoxin, also known as lipopolysaccharide (LPS), to be released into circulation. Exposure to endotoxin effects the other stages of detoxification, downregulating expression of some of the drug and toxin-metabolizing enzymes and Phase III transporters.,
The broad impact of the bitter herbs in Dr. Shade’s Bitters No. 9
The proprietary bitters combination of Dr. Shade’s Bitters No. 9 includes dandelion, milk thistle, solidago (goldenrod), gentian, burdock, and essential oils of sweet orange, myrrh, juniper, and clove, which are delivered along with phospholipids that comprise the liposomes in which these herbs are carried. The combination of these herbs is thoughtfully selected to support the gastrointestinal tract, liver, and kidneys in their necessary functions for health and detoxification. Just a small snippet of the vast amounts of research
on these herbs is highlighted below.
Dandelion is known for its action on the liver and gallbladder, but also acts as an antioxidant and anti-inflammatory, and may have cholesterol lowering effects.,, In animal models, supplementation with dandelion leaf extract has been shown to alleviate hepatic inflammation associated with a high-fat diet, and protect the liver from alcohol-induced oxidative stress., In the setting of alcohol injury, supplementation with dandelion root extract was observed to increase hepatic antioxidant activity, including glutathione (GSH), GSH-S-transferase, GSH reductase, and GSH peroxidase.
Milk thistle has been vastly studied for its antioxidative, anti-inflammatory, and hepatoprotective effects in settings including acetaminophen, radiation, iron overload, alcohol and Amanita phalloides (also known as “death cap” mushroom) induced liver damage. Silymarin is the active complex extracted from the seeds of the plant, with the flavonolignan silybin being the most biologically active moiety comprising 50% to 70% of silymarin. Silybin has been observed to inhibit human intestinal β-glucuronidase, blocking the release and reabsorption of free xenobiotics and their metabolites from their glucuronide conjugates. Silymarin acts as an antioxidant, enhancing hepatic and intestinal GSH levels, and stabilizing membranes by inhibiting membrane peroxidation.,
Solidago Solidago, commonly known as goldenrod, is known for its action on the urinary tract, and is classically used for infections, inflammation, and prevention of kidney stones. Solidago is rich in compounds including flavonoids, phenolic acids, sesquiterpenes, diterpenes, saponins, and several caffeoylquinic acids., Solidago acts as an anti-inflammatory, antimicrobial, diuretic, antispasmodic, and analgesic due to these many compounds found within it. Research has also shown that the flavonoids from solidago have an activating effect on GSH-S-transferases, a critical enzyme in phase II detoxification, in a dose-dependent fashion.
Gentian Gentian is one of the strongest herbal bitters most often utilized in digestive bitter formulations. Gentian is a digestive toner and modulator of stomach acid secretion, improving function in a state of deficiency but also having a protective effect on conditions such as gastritis or gastric ulcers possibly through prostaglandin pathways. Gentian also acts beyond the digestive system, as the compounds in it exhibit hypoglycemic, hepatoprotective, anti-inflammatory, antioxidant, antimicrobial, immunomodulatory, and adaptogenic properties., As a liver protective agent, gentian has been observed to increase levels of reduced GSH, catalase, superoxide dismutase and GSH peroxidase in various settings of toxin-induced oxidative damage.,,
Burdock root is commonly utilized in digestive and metabolic balancing formulas, with hypoglycemic, antioxidant, anti-inflammatory, hepatoprotective, and antimicrobial actions. Burdock root has been observed to reverse decreases in GSH and increases in malondialdehyde (a marker of oxidative stress) induced by toxin exposure. Caffeoylquinic acid derivatives from burdock root have been observed to have a strong antioxidant effect, greater than that of α-tocopherol. Burdock extract has been shown to inhibit lipoprotein oxidation while increasing GSH, GSH reductase, GSH peroxidase, GSH-S-transferase and catalase levels.
Essential oils of sweet orange, myrrh, juniper, and clove
Each of these oils contains many active compounds, a sense of which we only begin to have from the aromatic expression of its essence. Sweet orange essential oil is derived from the outer peel of the orange, which anyone who has tasted is familiar with its bitter nature. Sweet orange essential oil has been observed to have antibacterial, antifungal, and antioxidant effects., Myrrh has a long history of medicinal use, and is perhaps most recognized for its antimicrobial effects., Additionally, myrrh has been used as an anesthetic, anti-inflammatory, antioxidant, and cholesterol lowering agent.
Juniper essential oil also has been shown to have broad antimicrobial action, with traditional use as an antiseptic, antidiarrheal, anti-inflammatory, and astringent, with an affinity for the urinary tract. , Juniper also acts as an antioxidant, with metal chelating, free radical, superoxide anion radical, and hydrogen peroxide scavenging activities., Finally, clove essential oil also has antimicrobial, antiviral, antiulcer, anti-inflammatory and antioxidant properties., As an antioxidant it has a
significant inhibitory effect against hydroxyl radicals and forms complexes with reduced metals.,,
 You Y, 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
 Niiho Y, et al. 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
 Lian LH, et al. 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
 Wang AY, et al. 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
 Maruta Y, Kawabata J, Niki R. Antioxidative caffeoylquinic acid derivatives in the roots of burdock (Arctium lappa L.). Journal of Agricultural and Food Chemistry. 1995 Oct;43(10):2592-5. View Abstract
 Wang BS, et al. Protective effects of burdock (Arctium lappa Linne) on oxidation of low-density lipoprotein and oxidative stress in RAW 264.7 macrophages. Food Chemistry. 2007 Dec;101(2):729-38. View Abstract
 Miceli N, et al. Comparative analysis of flavonoid profile, antioxidant and antimicrobial activity of the berries of Juniperus communis L. var. communis and Juniperus communis L. var. saxatilis Pall. from Turkey. J Agric Food Chem. 2009 Aug 12;57(15):6570-7. View Abstract
 Santin JR, et al. Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models. Naunyn Schmiedebergs Arch Pharmacol. 2011 Feb;383(2):149-58. View Abstract
 Chaieb K, et al. The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): a short review. Phytother Res. 2007 Jun;21(6):501-6. View Abstract