About Herbs

Bottom Line: Licorice may be helpful in treating peptic ulcers, but it should not be used to treat cancer, hormonal diseases, or any other serious medical condition.

In traditional Chinese medicine, licorice is thought to affect the activities of the adrenal glands. In fact, experiments in animals and humans show this to be true, as licorice can mimic the effects of steroid hormones such as aldosterone and estrogen. The substance in licorice that scientists think is responsible for these effects is called glycyrrhizin, a molecule that: (1) inhibits the breakdown of cortisol, which, in turn, increases the loss of potassium in the urine and the retention of sodium in the body, and (2) binds to estrogen receptors at high concentrations. This may explain its ability to decrease the levels of testosterone circulating in the blood. (Note: Because glycyrrhizin causes undesirable side effects, it is often removed from licorice products during processing.)

Other than glycyrrhizin, physiological activity has been reported for several other compounds in licorice. Isoflavone compounds also mimic estrogens in the human body, and can kill several strains of bacteria and viruses on contact. Other compounds act as blood thinners and inhibit the process of inflammation. In humans, the compound carbenoxolone has been used to treat stomach and esophageal ulcers, with positive effects. Scientists think that it exerts this effect by increasing blood flow to and the amount of mucus lining the stomach.

Almost all of the clinical trials studying licorice have used it in combination with other herbs, such as PC-SPES for prostate cancer.

A number of clinical trials have used deglycyrrhizinated licorice to treat stomach ulcers, with favorable results.

Licorice may interfere with a number of lab values, such as:
Increased blood pressure
Decreased blood potassium levels
Elevated blood sodium levels
Decreased testosterone levels

Glycyrrhiza glabra, Glycyrrhiza uralensis

Gan cao, sweet root, glycyrrhiza, Radix liquiritiae, liquorice

Derived from the root of the plant. Licorice is used extensively in traditional Chinese medicine for a variety of conditions and ailments. Almost all clinical studies on licorice have been performed in combination with other herbs ⁽¹⁷⁾. Alone, licorice is used primarily to manage gastric complaints. A number of active chemicals are thought to account for its biologic activity. Due to the adverse reaction profile of licorice, many studies have been performed using the deglycyrrhizinated licorice (DGL) extract, which is free of glycyrrhizin and has had no significant reported adverse effects. Adverse effects from glycyrrhizin are primarily related to possible changes in electrolytes causing hypokalemia, hypernatremia, pseudo-hyperaldosteronism, decreased libido in men ⁽⁶⁾, and paralysis ⁽¹³⁾. Drugs that interact with licorice containing glycyrrhizin include diuretics, cardiac glycosides, insulin, and corticosteroids, all of which are related to changes in electrolytes. Other possible drug interactions with any licorice product include potentiation of anticoagulants and possible interference with hormonal therapy due to estrogenic activity of licorice ^{(2) (10)}.

Flavoring agent.

Glycyrrhizin has been reported to bind to glucocorticoid and mineralocorticoid receptors with moderate affinity, and to estrogen receptors, sex-hormone-binding globulin and corticosteroid-binding globulin with very weak affinity. The anti-estrogenic action documented for glycyrrhizin at high concentration has been associated with glycyrrhizin binding at estrogen receptors. However, estrogenic activity has also been reported for licorice and is attributed to its isoflavone constituents ^{(2) (14)}.

It has been suggested that glycyrrhizin may exert its mineral-corticoid effect via an inhibition of 11B-hydroxysteroid dehydrogenase. Long-term ingestion of licorice has been shown to cause secondary hypertension and hypokalemia resulting in paralysis ⁽¹³⁾. The coumarin constituent has antiplatelet activity. Anti-inflammatory action is exhibited by glycyrrhetinic acid against UV erythema. Antimicrobial activity is attributed to the isoflavonoid constituents. Carbenoxolone, an ester derivative of glycyrrhetinic acid, has been used in the treatment of gastric and esophageal ulcers; it is thought to exhibit a mucosal protectant effect by beneficially interfering with gastric prostanoid synthesis and increasing both mucous production and regional blood flow. Data show suppression of both plasma renin activity and aldosterone secretion. Also, a decrease in serum testosterone and an increase in 17-hydroxyprogesterone have been shown ⁽³⁾. Licorice has recently been shown to have chemopreventive effects in human breast cancer cells ⁽¹⁵⁾ and colon carcinogenesis ⁽¹⁶⁾.

Administration of licorice after meals delays the time (Tmax) to peak concentration, but does not affect maximum concentration (Cmax) or area-under-the-curve (AUC) ⁽⁷⁾. Elimination half-life is approximately 5 hours following intravenous administration ⁽⁹⁾. Primary route of excretion is in bile ⁽⁸⁾.

Due to the adverse reaction profile of licorice, many studies have been performed using the deglycyrrhizinated licorice (DGL) extract. Deglycyrrhizinated licorice is free of glycyrrhizin and has had no reported significant adverse effects.

Licorice should not be consumed by those with renal or liver dysfunction, or women who are pregnant or breast-feeding.

Hypertension, lethargy, muscle pain, cardiac arrhythmias, sodium retention, hypokalemia, hyper-mineralcorticoidism, pseudo-hyperaldosteronism, decreased libido in men, and suppression of scalp sebum secretion
⁽⁶⁾

Cardiac glycosides: Licorice may potentiate toxicity.
Stimulant laxatives: Chronic use of licorice may increase loss of potassium.
Diuretics: Chronic use of licorice may increase loss of potassium.
Spironolactone / Amiloride: Licorice should not be used simultaneously due to effects on sodium and potassium excretion.
Corticosteroids: Concomitant use with licorice might potentiate the duration of activity.
Aspirin: Licorice may reduce ulcer formation from aspirin and possibly provide protection from gastric mucosal damage.
Insulin: Licorice may have a synergistic effect possibly causing hypokalemia and sodium retention with concomitant use.
Hormonal therapy: Licorice may interfere with the activity of hormonal therapy due to its estrogenic or anti-estrogenic properties.
Anticoagulant/Antiplatelet Drugs: Licorice may potentiate activity due to coumarin constituent.
MAO-inhibitors (MAO-I): Licorice may potentiate activity of MAO-Is.
^{(2) (10)}

Secondary hypertension
Potassium levels may be decreased.
Sodium levels may be elevated.
Testosterone levels may be decreased.

The only studies in humans showing positive results have used deglycyrrhizinated licorice as a single agent in peptic ulcers. Studies of licorice in combination with other herbs has shown favorable results, such as PC-SPES for prostate cancer.

Madisch A, et al. Treatment of Functional Dyspepsia with a Herbal Preparation. A Double- Blind, Randomized, Placebo-Controlled, Multicenter Trial. Digestion 2004;69:45-52.
This study was aimed at determining the efficacy and safety of STW 5-II, an herbal preparation containing extracts of licorice root as one of the major ingredients as well as matricaria flower, peppermint leaves, caraway, lemon balm, and bitter candy tuft. 120 patients with functional dyspepsia were randomly assigned to 4 treatment groups and treated over a 12-week period. Patients received either STW 5-II or placebo for 8 weeks. Treatment during the last 4-week period was determined by the investigator based on symptom relief in patients. The outcome measure was the standardized gastrointestinal symptom score (GIS). There was a significant decrease in GIS in patients treated with STW 5-II compared to those on placebo during the first 4 weeks. Symptoms improved further in patients who continued treatment during the second 4 weeks. After 8 weeks, 43.3% patients on active treatment and 3.3% patients on placebo reported total symptom relief. The authors suggest that STW 5-II significantly improves symptoms of dyspepsia as compared to a placebo. However, since STW 5-II contains other herbs, the extent to which licorice contributes to relieving dyspeptic symptoms is not clear from this study.