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Licorice (Glycyrrhiza glabra L.) and DGL (deglycyrrhizinated licorice)

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Licorice and DGL
Licorice and DGL

BackgroundReturn to top

The medicinally used part of licorice is the root and dried rhizome of the low-growing shrub  Glycyrrhiza glabra . Currently, most licorice is produced in Greece, Turkey, and Asia.

Licorice has been used in ancient Greece, China, and Egypt, primarily for gastritis (inflammation of the stomach) 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.

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.

SynonymsReturn to top

Alcacuz (Portuguese), alcazuz (Spanish), asam boi, bois doux (French), carbenoxolone, Chinese licorice, deglycyrrhizinised liquorice, deglycyrrhizinized succus Liquiritiae, duogastrone, Fabaceae (family), gan cao, gan zao, glabrene, glabridin, glucoliquiritin, glycyrrhetenic acid,  Glycyrrhiza ,  Glycyrrhiza glabra ,  Glycyrrhiza uralensis  Fisher, glycyrrhizin, isoflavan, isoliquiritigenin, kanzo (Japanese), LA, Lakrids (Danish), lakritze, Lakritzenwurzel (German), Leguminoseae (family), licochalcone-A, licorice root, Liquiritiae radix,  Liquiritia officinalis , liquirizia (Italian), liquorice, orozuz, phytoestrogen, Persian licorice, prenyllicoflavone, radix glycyrrhizae, réglisse (French), regliz, Russian licorice, Shakuyanu-kanzo-tou, shao-yao-gan-cao-tang, STW 5-11 (extracts from bitter candy tuft, matricaria flower, peppermint leaves, caraway, licorice root, and lemon balm), Suβholzwurzel, sweet root, sweet wood, yashimadhu (Sanskrit), Yo Jyo Hen Shi Ko (Japanese).

EvidenceReturn to top

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*
Adrenal insufficiency (Addison's disease)

Addison's disease is a relatively common disorder to endocrinologists, but is rare and potentially fatal when presenting acutely. Treatment now involves replacement of glucocorticoids and mineralocorticoids with synthetic compounds, although historically patients took common salt and plant-based preparations, including licorice.
C
Aplastic anemia

Limited study suggests that licorice may be beneficial in aplastic anemia, but results are inconclusive.
C
Apthous ulcers / canker sores

Some research suggests that licorice extracts, DGL, and the drug 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
Atopic dermatitis

Topical licorice extract gel has been shown to be effective in the treatment of atopic dermatitis in preliminary human study. Further research is needed to confirm these results.
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
Dental hygiene

Further studies are needed prior to recommending for or against the use of glycyrrhizin in dental hygiene.
C
Familial Mediterranean fever (FMF)

Early 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
Functional dyspepsia

Early studies indicate that the herbal preparation STW 5, which contains licorice among many other herbal extracts, may help improve symptoms in patients with functional dyspepsia.
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
HIV

Early studies suggest that glycyrrhizin may inhibit HIV replication in patients with AIDS. However, human reports are lacking. Additional study is needed to make a firm recommendation.
C
Hyperprolactinemia (neuroleptic-induced)

Shakuyaku-kanzo-to, an herbal medicine containing licorice, has been used for neuroleptic-induced hyperprolactinemia. However, additional studies are needed in this area.
C
Idiopathic thrombocytopenic purpura

Early study has suggested that recombinant roasted licorice decoction combined with low-dose glucocorticoids may be more effective than glucocorticoids alone in treating idiopathic thrombocytopenic purpura. This combination has also shown a lower adverse effect rate than glucocorticoids alone.
C
Inflammation

Many medical conditions are marked by inflammation. Because licorice can affect the metabolism of steroids, licorice is sometimes used to help decrease inflammation. Additional study is needed to make a firm recommendation.
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, most studies are poorly designed and some results conflict. Therefore, it is unclear whether there is any benefit from licorice for this condition.
C
Polycystic ovarian syndrome

Spironolactone is a synthetic steroid that is commonly used as a diuretic in women with polycystic ovary syndrome. Licorice has been used in combination with spironolactone to reduce side effects related to the diuretic activity of spironolactone.
C
Reducing body fat mass

Preliminary data shows that licorice may reduce body fat mass. Further research is needed to confirm these results.
C
Upper respiratory tract infections (common cold)

Historically, licorice has been used for its expectorant and anti-tussive effects. The herbal combination product, KanJang®, has been studied for the treatment of uncomplicated upper respiratory tract infections. Results are mixed, and additional study is needed.
C
Viral hepatitis

The licorice extracts DGL and carbenoxolone have been proposed as possible therapies for viral hepatitis. Further research is needed before a recommendation can be made.
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;
F: Strong scientific evidence against this use.

Grading rationale

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.

Allergies, antimicrobial, antioxidant, antiparasitic, antispasmodic, antitumor, asthma, bacterial infections, bad breath, blood disorders, breast cancer, bronchitis, burns, cancer, chronic fatigue syndrome, colitis, colorectal cancer, constipation, coronavirus, cough, cysts, depression, detoxification, diabetes, diuretic, diverticulitis, dysmenorrhea (painful menstruation), Epstein-Barr virus, fever, fibromyalgia, gastroesophageal reflux disease, gentamicin induced kidney damage, graft healing, heartburn, Helicobacter pylori infection, hepatoma, high cholesterol, hormone regulation, hot flashes, hyperpigmentation disorders, immune system stimulation, indigestion, infertility, inflammatory skin disorders, laryngitis, liver cancer, liver protection, lung cancer, melanoma, melasma, menopausal symptoms, metabolic abnormalities, methicillin-resistant Staphylococcus aureus (MRSA), muscle cramps, non-ulcer dyspepsia, obesity, osteoarthritis, postherpetic neuralgia, postural hypotension, premenstrual syndrome, prostate cancer, pruritus (rash), rheumatoid arthritis, RSV, SARS, skin disorders, sore throat, systemic lupus erythematosus, urinary tract inflammation, weight loss.

DosingReturn to top

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.

Adults (18 years and older)
Carbenoxolone gel or cream: A 2% cream or gel has been applied five times a day for 7-14 days for herpes simplex virus skin lesions.

Commercial preparation :  3.5 grams a day of a commercial preparation of licorice has been studied for body fat mass reduction.

DGL extract tablets: Doses of 380-1,140 milligrams three times daily taken by mouth 20 minutes before meals have been used.

Licorice fluid extract (10 percent to 20 percent glycyrrhizin): Doses of 2-4 milliliters per day have been taken by mouth.

Licorice powdered root (4 percent to 9 percent glycyrrhizin): Doses of 1-4 grams taken by mouth daily, divided into three or four doses, have been used.

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.

SafetyReturn to top

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.

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 electrolyte 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. However, study results conflict. These adverse effects may reduce fertility or cause menstrual abnormalities.

Reduced body fat mass has been observed with the use of licorice, but weight gain is also possible. Acute pseudo-aldosteronism syndrome has been associated with licorice. Paralysis has been reported in a patient taking licorice that contributed to low potassium levels. Thyrotoxic periodic paralysis (TPP) has been associated with licorice. Metabolic alkalosis and seizure has been reported from licorice in antacid.

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).

High doses of licorice may cause temporary vision problems or loss. Ocular side effects have been reported. Central retinal vein occlusion has been associated with licorice. A case report exists of licorice-induced hypokalemia associated with dropped head syndrome (DHS).

Pregnancy and Breastfeeding
Licorice cannot be recommended during pregnancy and breastfeeding 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. However, study results conflict. 17-OHP and LH levels may also be affected.

InteractionsReturn to top

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. 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.

Interactions with Drugs
In general, prescription drugs should be taken one hour before licorice or two hours after licorice because licorice may increase the absorption of many drugs. Increased absorption may increase the activities and side effects of some drugs (for example, nitrofurantoin). Phosphate salts have been shown to increase licorice absorption. Liver metabolism of certain drugs may be affected by licorice but further study is needed before a conclusion can be drawn.

Because the toxicity of digoxin (Lanoxin®) is increased when potassium levels are low, people who take digoxin and are interested in using licorice should discuss this with their healthcare provider. Increased monitoring may be necessary. Other drugs that may increase the tendency for irregular heart rhythms are also best avoided when using licorice.

Licorice may reduce the effects of blood pressure or diuretic (urine-producing) drugs, including hydrochlorothiazide and spironolactone. Use of licorice with the diuretics hydrochlorothiazide or furosemide (Lasix®) may cause potassium levels to fall very low and lead to dangerous complications. Other drugs that can also cause potassium levels to fall too low and are best avoided when using licorice include insulin, sodium polystyrene (Kayexalate®), and laxatives. Chewing tobacco may increase the toxicity of licorice gums by causing electrolyte disturbances.

Licorice may increase the adverse effects associated with corticosteroids such as prednisolone and monoamine oxidase inhibitors such as isocarboxazid (Marplan®), phenelzine (Nardil®), or tranylcypromine (Parnate®). Agents acting on serotonin may also interact with licorice.

Licorice may reduce the effects of birth control pills, hormone replacement therapies, or testosterone therapy.

In theory, licorice may increase the risk of bleeding when used with anticoagulants (blood thinners) or antiplatelet drugs. Examples include warfarin (Coumadin®), heparin, clopidogrel (Plavix®), or aspirin.

Licorice may also interact with glucocorticoids, ulcer medications, interferon, or lithium.

Interactions with Herbs and Dietary Supplements
Herbs with potential laxative properties may add to the potassium-lowering effects of licorice.

Herbs with potential diuretic properties may increase adverse effects associated with licorice.

Herbs and supplements that lower blood pressure may add to the blood pressure-lowering effects of licorice.

Herbs with monoamine oxidase inhibitor activity may worsen side effects when used at the same time as licorice. Agents acting on serotonin may also interact with licorice.

In theory, herbs and supplements that increase the risk of bleeding may further increase the risk of bleeding when taken with licorice.

Liver metabolism of certain herbs and supplements may be affected by licorice but further study is needed before a conclusion can be drawn.

Licorice may interact with herbs or supplements used for heart disorders. It may also interact with other herbs or supplements with hormonal effects.

Methodology Return to top

This information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Tracee Rae Abrams, PharmD (University of Rhode Island); Ethan Basch, MD (Memorial Sloan-Kettering Cancer Center); Stephen Bent, MD (University of California, San Francisco); Tracy Ha, PharmD (Massachusetts College of Pharmacy); Dana A. Hackman, BS (Northeastern University); David Kroll, PhD (Duke University); Katie Nummy, BS (Northeastern University); Michael Smith, M.R.PharmS., ND (Canadian College of Naturopathic Medicine); David Sollars, MAc (Merrimack College); Isabel Sylesky, PharmD (Northeastern University); Phillipe Szapary, MD (University of Pennsylvania); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Sarah Taylor, PharmD (University of Pittsburgh); Natasha Tiffany, MD, PhD (Harvard Medical School); Verda Tunaligil, MD, MPH (Harvard School of Public Health); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Minney Varghese, BS (Northeastern University); Mamta Vora, PharmD (Natural Standard Research Collaboration); Wendy Weissner, BA (Natural Standard Research Collaboration); Peter Wolsko, MD (Harvard Medical School).

Methodology details

Selected references Return to top

  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. Phytomedicine 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. Armanini D, Castello R, Scaroni C, et al. Treatment of polycystic ovary syndrome with spironolactone plus licorice. Eur J Obstet Gynecol Reprod Biol 2007 Mar;131(1):61-7.
  4. Chande N, Laidlaw M, Adams P, et al. Yo Jyo Hen Shi Ko (YHK) improves transaminases in nonalcoholic steatohepatitis (NASH): a randomized pilot study. Dig Dis Sci 2006 Jul;51(7):1183-9.
  5. Cheng TO. Herbal interactions with cardiac drugs. Arch Intern Med 2000;160(6):870-871.
  6. 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.
  7. Elinav E, Chajek-Shaul T. Licorice consumption causing severe hypokalemic paralysis. Mayo Clin Proc 2003;78(6):767-768.
  8. 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.
  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):445-453.
  10. 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;469(1-3):159-163.
  11. Kobayashi H, Mizuno N, Teramae H, et al. The effects of Hochu-ekki-to in patients with atopic dermatitis resistant to conventional treatment. Int J Tissue React 2004;26(3-4):113-117.
  12. 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.
  13. Strandberg TE, Andersson S, Jarvenpaa AL, et al. Preterm birth and licorice consumption during pregnancy. Am J Epidemiol 2002;156(9):803-805.
  14. Tsukamoto S, Aburatani M, Yoshida T, et al. CYP3A4 inhibitors isolated from Licorice. Biol Pharm Bull 2005 Oct;28(10):2000-2.
  15. van Uum SH. Liquorice and hypertension. Neth J Med 2005;63(4):119-120.

February 01, 2008.


Natural Standard Logo This evidence-based monograph was prepared by the Natural Standard Research Collaboration. The information provided should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. Talk to your health care provider before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Copyright© 2009 Natural Standard (www.naturalstandard.com). All Rights Reserved.