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Licorice Std. Extract

Also known as: Licorice, licorice root extract, deglycyrrhizinated licorice, DGL, Glycyrrhiza glabra

Overview

Licorice extract is derived from the root of *Glycyrrhiza glabra*, a plant traditionally used in herbal medicine for a variety of conditions. Its primary bioactive compounds include glycyrrhizin (glycyrrhizic acid), glycyrrhetic acid, isoliquiritigenin, and glabridin. These compounds contribute to its recognized anti-inflammatory, antioxidant, antimicrobial, and anticancer properties. Historically, licorice has been employed for respiratory, gastrointestinal, liver, and inflammatory conditions. While research maturity is moderate to advanced, with numerous clinical trials and systematic reviews, the evidence quality varies, and heterogeneity in study designs can complicate interpretation. Deglycyrrhizinated licorice (DGL) is a modified form often used to mitigate some of the adverse effects associated with glycyrrhizin.

Benefits

Licorice extract offers several evidence-based benefits. Its anti-inflammatory and antioxidant properties are well-documented, with compounds inhibiting inflammatory pathways and reducing oxidative stress markers, which can help mitigate tissue damage. Meta-analyses of randomized controlled trials (RCTs) suggest that licorice can enhance liver function, improving liver enzyme profiles and demonstrating hepatoprotective effects, though results vary due to study heterogeneity. Components like isoliquiritigenin and glabridin have shown promising anticancer activity in vitro and in some clinical contexts by inhibiting cancer cell proliferation and metastasis. Deglycyrrhizinated licorice (DGL) is particularly effective in protecting the gastrointestinal tract, treating gastric ulcers, and alleviating mucosal damage, including chemotherapy-induced gastrointestinal toxicity. Furthermore, a meta-analysis of 26 clinical trials indicated that licorice consumption could lead to statistically significant, albeit modest, reductions in body weight. Secondary benefits include antimicrobial activity and potential uses in skin disorders and oral health. Cancer patients may benefit from licorice-containing herbal formulas to reduce chemotherapy side effects, and individuals with liver dysfunction may see improved biochemical markers.

How it works

Licorice's primary mechanism involves its active compound, glycyrrhizin, which is metabolized to glycyrrhetic acid. Glycyrrhetic acid inhibits 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), leading to mineralocorticoid-like effects. Its anti-inflammatory actions stem from the inhibition of NF-κB and a reduction in pro-inflammatory cytokines. The anticancer effects are mediated by compounds like isoliquiritigenin and glabridin, which modulate cell cycle regulators, induce apoptosis, promote autophagy, and inhibit angiogenesis. Antioxidant activity is achieved through scavenging reactive oxygen species and enhancing endogenous antioxidant enzymes. The bioavailability of glycyrrhizin depends on its conversion to glycyrrhetic acid by intestinal microflora. Deglycyrrhizinated extracts are designed to reduce the mineralocorticoid side effects by removing most of the glycyrrhizin.

Side effects

While generally safe at recommended doses, chronic or high-dose use of licorice can lead to serious adverse effects. Common side effects, occurring in over 5% of users, include sodium retention, hypertension, hypokalemia (low potassium), muscle pain, and lethargy, primarily due to its mineralocorticoid-like activity. Uncommon side effects (1-5%) can include cardiac arrhythmias, metabolic alkalosis, and adrenal crisis, especially in sensitive individuals or cases of overdose. Rare but severe side effects (less than 1%) reported include intracranial hemorrhagic stroke, cerebral microbleeds, severe refractory hypokalemia, and an increased risk of early preterm births associated with heavy licorice use during pregnancy. Licorice has significant drug interactions, particularly with antihypertensives, diuretics, corticosteroids, and medications affecting potassium levels. It is contraindicated in individuals with hypertension, heart disease, renal impairment, and pregnancy due to the risk of preterm birth. Pregnant women and individuals with cardiovascular or renal disease should avoid licorice or use it with extreme caution and medical supervision.

Dosage

The minimum effective dose of licorice extract is variable, but clinical trials often utilize standardized extracts containing 100-200 mg of glycyrrhizin daily. Optimal dosage ranges typically fall between 100-400 mg of glycyrrhizin per day. For gastrointestinal benefits, deglycyrrhizinated licorice (DGL) is commonly used in doses of 380-760 mg daily. The maximum safe dose for chronic intake is generally considered to be below 100 mg of glycyrrhizin per day, as doses exceeding this can increase the risk of adverse effects. Doses above 300 mg/day require medical supervision. Oral administration with food may improve tolerance. DGL is preferred for GI indications to minimize mineralocorticoid side effects. Absorption is dependent on gut microflora conversion, which can lead to variability among individuals. No specific cofactors are required, but monitoring electrolyte levels is advised during prolonged use.

FAQs

Is licorice safe for long-term use?

Long-term use of licorice, especially with high glycyrrhizin content, can cause serious mineralocorticoid-related side effects like hypertension and hypokalemia. Monitoring and dose limitation are essential for safety.

Can licorice help with weight loss?

Evidence suggests licorice may contribute to modest weight reduction, as shown in a meta-analysis. However, it is not considered a primary weight loss agent and should be used cautiously due to potential side effects.

Does licorice interact with blood pressure medications?

Yes, licorice can significantly raise blood pressure and counteract the effects of antihypertensive medications. Individuals on blood pressure medication should avoid licorice or consult a doctor.

Is deglycyrrhizinated licorice (DGL) safer?

Yes, DGL is generally considered safer because the glycyrrhizin, responsible for mineralocorticoid side effects like hypertension and hypokalemia, has been largely removed. It's often preferred for GI issues.

How soon do the effects of licorice appear?

Gastrointestinal benefits from licorice, particularly DGL, can often be observed within days to a few weeks. However, effects related to liver function or weight management typically take several weeks to months to manifest.

Research Sources

https://pmc.ncbi.nlm.nih.gov/articles/PMC8703329/ – This comprehensive review explores the pharmacological effects of licorice extracts, detailing their anticancer, anti-inflammatory, and antioxidant activities. It highlights isoliquiritigenin and glabridin as key bioactive compounds and provides mechanistic insights, drawing from both preclinical and some clinical data, though noting a lack of large-scale RCTs.
https://www.liebertpub.com/doi/full/10.1089/jmf.2019.4459?doi=10.1089%2Fjmf.2019.4459 – This meta-analysis of 26 clinical trials investigates licorice's impact on body weight reduction and its anti-inflammatory properties. It discusses glycyrrhizin metabolism and its mineralocorticoid effects leading to adverse events, providing quantitative effect sizes for weight loss while also emphasizing variability and safety concerns.
https://onlinelibrary.wiley.com/doi/10.1002/ptr.8288 – This systematic review and meta-analysis focuses on the hepatoprotective effects of licorice, synthesizing data from randomized controlled trials. Despite observed heterogeneity, the study concludes that licorice significantly improves liver function markers, while also calling for further high-quality trials to address language bias and study variability.
https://www.mskcc.org/cancer-care/integrative-medicine/herbs/licorice – This review from Memorial Sloan Kettering Cancer Center summarizes systematic reviews indicating that licorice-containing formulas can reduce chemotherapy-induced gastrointestinal toxicity. It also issues strong warnings about serious adverse effects like hypertension and hypokalemia, recommending deglycyrrhizinated forms for enhanced safety.