Licorice (Glycyrrhiza glabra L.) and DGL (deglycyrrhizinated licorice)
  
Licorice (Glycyrrhiza glabra L.) and DGL (deglycyrrhizinated licorice)
Background
Licorice is harvested from the root and dried rhizomes of the low-growing shrub Glycyrrhiza glabra . Currently, most licorice is produced in Greece, Turkey, and Asia.
Licorice was used in ancient Greece, China, and Egypt, primarily for gastritis and ailments of the upper respiratory tract. Ancient Egyptians prepared a licorice drink for ritual use to honor spirits of the pharaohs. Its use became widespread in Europe and Asia for numerous indications.
During World War II, the Dutch physician F.E. Revers observed improvements in patients' peptic ulcer disease from a licorice preparation. He also noted facial and peripheral edema, sparking scientific investigation into licorice's properties and adverse effects. In the 1950s, there were reports of patients with Addison's disease 'craving' licorice candy, viewed by some as early evidence of steroid modulating properties.
In addition to its medicinal uses, licorice has been used as a flavoring agent, valued for sweetness (glycyrrhizin, a component of licorice, is 50 times sweeter than table sugar). The generic name "glycyrrhiza" stems from ancient Greek, meaning "sweet root." It was originally used as flavoring for licorice candies, although most licorice candy is now flavored with anise oil. Licorice is still used in sub-therapeutic doses as a sweetening agent in herbal medicines, lozenges, and tobacco products (doses low enough that significant adverse effects are unlikely).
Licorice has a long history of medicinal use in Europe and Asia. At high doses, there are potentially severe side effects, including hypertension (high blood pressure), hypokalemia (low blood potassium levels) and fluid retention. Most adverse effects have been attributed to the chemical component glycyrrhiza (or glycyrrhizic acid). Licorice can be processed to remove the glycyrrhiza, resulting in DGL (deglycyrrhizinated licorice), which does not appear to share the metabolic disadvantages of licorice.
In Europe, licorice has most often been used to treat cough, bronchitis, gastritis, and peptic ulcer disease. In Chinese medicine, it is felt to benefit Qi , reduce "Fire Poison" (sore throat, skin eruptions), and diminish "Heat." Specific conditions treated by Chinese herbalists include gastric and duodenal ulcers, abdominal pain, pharyngitis, malaria, tuberculosis, abscesses and sores. In Ayurveda, licorice is felt to be effective in the treatment of constipation, inflamed joints, peptic ulcer disease, and diseases of the eye.
Synonyms
Bois doux, fabaceae, gan cao, glucoliquiritin , glycyrrhetenic acid, glycyrrhiza, Glycyrrhiza glabra , Glycyrrhiza uralensis , glycyrrhizin, kanzo, Lakrids, Lakritzenwurzel, leguminose, licorice root, Liquiritiae radix, Liquiritia officinalis, liquirizia, liquorice, prenyllicoflavone, Radix glycyrrhizae, réglisse, Suβholzwurzel, sweet root, sweet wood.
Evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Uses based on scientific evidenceGrade*Apthous ulcers / canker sores
Some research suggests that licorice extracts, DGL and carbenoxolone may provide benefits for treating cankers sores. However, studies have been small, with flaws in their designs. The safety of DGL makes it an attractive therapy if it does speed healing of these sores, but it is not clear at this time whether there is truly any benefit.
C
Bleeding stomach ulcers caused by aspirin
Although there has been some study of DGL in this area, it is not clear what effects DGL has on gastrointestinal bleeding.
C
Familial Mediterranean Fever (FMF)
A small clinical pilot study and laboratory study of a multi-ingredient preparation containing licorice, called Immunoguard, suggests possible effects in managing FMF. Well-designed study of licorice alone is necessary before a recommendation can be made.
C
Herpes simplex virus
Laboratory studies have found that DGL may hinder the spread and infection of herpes simplex virus. Studies in humans have been small, but they suggest that topical application of carbenoxolone cream may improve healing and prevent recurrence.
C
High potassium levels resulting from abnormally low aldosterone levels
In theory, because of the known effects of licorice, there may be some benefits of licorice for high potassium levels caused by a condition called hypoaldosteronism. There is early evidence in humans in support of this use. However, research is preliminary and a qualified health care provider should supervise treatment.
C
Peptic ulcer disease
Licorice extracts, DGL and carbenoxolone have been studied for treating peptic ulcers. DGL (but not carbenoxolone) may offer some benefits. However, these studies have been small, with flaws in their designs, and results of different studies have disagreed with each other. Therefore, it is unclear whether there is any benefit from licorice for this condition.
C
Viral hepatitis
The licorice extracts DGL and carbenoxolone have been proposed as possible therapies for viral hepatitis. Animal studies have investigated the mechanism of licorice in hepatitis, and studies in humans have shown some benefits with a patented intravenous licorice preparation that is not available in the United States. Studies using oral licorice have been small, with flaws in their designs. Therefore, it is not clear whether there is any benefit from oral licorice for hepatitis treatment.
C
Genital herpes
Available studies have not found any benefit from carbenoxolone cream when applied topically to the skin to treat genital herpes infections.
D
* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).
Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Adrenal insufficiency (Addison's disease), antimicrobial, antioxidant, antispasmodic, aplastic anemia, asthma, bacterial infections, bad breath, body fat reducer, bronchitis, cancer, chronic fatigue syndrome, colitis, colorectal cancer, constipation, coronavirus, cough, dental hygiene, depression, detoxification, diabetes, diuretic, diverticulitis, dropped head syndrome, eczema, Epstein-Barr virus, fever, gastroesophageal reflux disease, gentamicin induced kidney damage, graft healing, high cholesterol, HIV, hormone regulation, inflammation, inflammatory skin disorders, laryngitis, liver protection, lung cancer, menopausal symptoms, metabolic abnormalities, methicillin-resistant staphylococcus aureus, muscle cramps, obesity, osteoarthritis, plaque, polycystic ovarian syndrome, rheumatoid arthritis, SARS, skin disorders, sore throat, stomach upset, urinary tract inflammation.
Dosing
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Standardization:
The expert panel German Commission E recommends that licorice be used for only four to six weeks unless under direct medical supervision. However, this is based on the use of relatively large daily doses (five to 15 grams per day). Many experts believe that extended treatments may be safe if lower doses are used. In a four-week study in healthy individuals, recommended doses were well tolerated, with few adverse effects. There are no standard or well-studied doses of licorice, and many different doses are used traditionally.
Adults (18 years and older):
Licorice powdered root (4 percent to 9 percent glycyrrhizin): Doses of one to four grams taken by mouth daily, divided into three or four doses, have been used.
Licorice fluid extract (10 percent to 20 percent glycyrrhizin): Doses of two to four milliliters per day have been taken by mouth.
DGL extract tablets: Doses of 380 to 1140 milligrams three times daily taken by mouth 20 minutes before meals have been used.
Carbenoxolone gel or cream: A 2 percent cream or gel has been applied five times a day for seven to 14 days for herpes simplex virus skin lesions.
Children (younger than 18 years):
There is not enough scientific evidence to recommend licorice for use in children, and licorice is not recommended due to potential side effects.
Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Allergies
People should avoid licorice if they have a known allergy to licorice, any component of licorice or any member of the Fabaceae ( Leguminosae ) plant family (pea family). There is a report of rash after applying a cosmetic product containing licorice to the skin.
Side Effects and Warnings
Licorice contains a chemical called glycyrrhizic acid, which is responsible for many of the reported side effects. DGL (deglycyrrhizinated licorice) has had the glycyrrhizic acid removed, and therefore is considered safer for use.
Many of the adverse effects of licorice result from actions on hormone levels in the body. By altering the activities of certain hormones, licorice may cause electrolyte disturbances. Possible effects include sodium and fluid retention, low potassium levels, and metabolic alkalosis.
Licorice has been reported to cause high blood pressure, including dangerously high blood pressure with symptoms such as headache, nausea, vomiting, and hypertensive encephalopathy with stroke-like effects (for example, one-sided weakness).
Electrolyte abnormalities may also lead to irregular heartbeats, heart attack, kidney damage, muscle weakness, or muscle breakdown. Licorice should be used cautiously by people with congestive heart failure, coronary heart disease, kidney or liver disease, fluid retention (edema), high blood pressure, underlying electrolye disturbances, hormonal abnormalities, or those taking diuretics.
Hormonal imbalances have been reported with the use of licorice, such as abnormally low testosterone levels in men or high prolactin levels and estrogen levels in women. These adverse effects may reduce fertility or cause menstrual abnormalities.
Reduced body fat mass has been observed wit the use of licorice.
High doses of licorice may cause temporary vision problems or loss.
Pregnancy and Breastfeeding
Licorice cannot be recommended during pregnancy and breast-feeding due to possible alterations of hormone levels and the possibility of premature labor.
Hormonal imbalances reported with the use of licorice include abnormally low testosterone levels in men and high prolactin levels/estrogen levels in women.
References
1. Amaryan G, Astvatsatryan V, Gabrielyan E, et al. Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. And Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever. Phytomed 2003;10(4):271-285.
2. Arase Y, Ikeda K, Murashima N, et al. The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 1997;79(8):1494-1500.
3. Carbonell-Barrachina AA, Aracil P, Garcia E, Burlo F, et al. Source of arsenic in licorice confectionery products. J Agric Food Chem 2003;51(6):1749-1752.
4. Cinatl J, Morgenstern B, Bauer G, et al. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003;361 (9374) :2045-2046.
5. Elinav E, Chajek-Shaul T. Licorice consumption causing severe hypokalemic paralysis. Mayo Clin Proc 2003;78(6):767-768.
6. Eriksson JW, Carlberg B, Hillorn V. Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia. J Intern Med 1999;245(3):307-310.
7. Fujioka T, Kondou T, Fukuhara A, et al. Efficacy of a glycyrrhizin suppository for the treatment of chronic hepatitis C: a pilot study. Hepatol Res 2003;26(1):10-14.
8. Harada T, Ohtaki E, Misu K, et al. Congestive heart failure caused by digitalis toxicity in an elderly man taking a licorice-containing chinese herbal laxative. Cardiology 2002;98(4):218.
9. Hinoshita F, Ogura Y, Suzuki Y, et al. Effect of orally administered shao-yao-gan-cao-tang (Shakuyaku-kanzo-to) on muscle cramps in maintenance hemodialysis patients: a preliminary study. Am J Chin Med. 2003;31(3):445-53.
10. Hughes J, Sellick S, King R, et al. Re: "preterm birth and licorice consumption during pregnancy". Am J Epidemiol. 2003 Jul 15;158(2):190-1; author reply 191.
11. Kamei J, Nakamura R, Ichiki H, et al. Antitussive principles of Glycyrrhizae radix, a main component of the Kampo preparations Bakumondo-to (Mai-men-dong-tang). Eur J Pharmacol. 2003 May 23;469(1-3):159-63.
12. Kang DG, Sohn EJ, Mun YJ, Woo WH, Lee HS. Glycyrrhizin ameliorates renal function defects in the early-phase of ischemia-induced acute renal failure. Phytother Res 2003;17(8):947-951.
13. Kang DG, Sohn EJ, Lee HS. Effects of glycyrrhizin on renal functions in association with the regulation of water channels. Am J Chin Med 2003;31(3):403-413.
14. Lin JC. Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro. Antiviral Res. 2003 Jun;59(1):41-47.
15. Liu J, Manheimer E, Tsutani K, et al. Medicinal herbs for hepatitis C virus infection: a Cochrane hepatobiliary systematic review of randomized trials. Am J Gastroenterol. 2003;98(3):538-544.
16. Nokhodchi A, Nazemiyeh H, Ghafourian T, et al. The effect of glycyrrhizin on the release rate and skin penetration of diclofenac sodium from topical formulations. Farmaco 2002;57(11):883-888.
17. Ofir R, Tamir S, Khatib S, Vaya J. Inhibition of serotonin re-uptake by licorice constituents. J Mol Neurosci 2003;20(2):135-140.
18. Oganesyan KR. Antioxidant effect of licorice root on blood catalase activity in vibration stress. Bull Exp Biol Med 2002;134(2):135-136.
19. Russo S, Mastropasqua M, Mosetti MA, et al. Low doses of liquorice can induce hypertension encephalopathy. Am J Nephrol 2000;20(2):145-148.
20. Sasaki H, Takei M, Kobayashi M, et al. Effect of glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV-seropositive patients. Pathobiol 2002-2003;70(4):229-236.
21. Serra A, Uehlinger DE, Ferrari P, et al. Glycyrrhetinic Acid decreases plasma potassium concentrations in patients with anuria. J Am Soc Nephrol 2002;13(1):191-196.
22. Sigurjonsdottir HA, Manhem K, Axelson M, et al. Subjects with essential hypertension are more sensitive to the inhibition of 11 beta-HSD by liquorice. J Hum Hypertens 2003;17(2):125-131.
23. Sohn EJ, Kang DG, Lee HS. Protective effects of glycyrrhizin on gentamicin-induced acute renal failure in rats. Pharmacol Toxicol 2003;93(3):116-122.
24. Strandberg TE, Andersson S, Jarvenpaa AL. Risk factors for preterm delivery. Lancet 2003;361(9355):436; author reply 436-437.
25. van Rossum TG, Vulto AG, Hop WC, et al. Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C. Am J Gastroenterol 2001;96(8):2432-2437.
January 01, 2004 
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