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Liquorice root

Also known as: Liquorice root, licorice, Glycyrrhiza, Glycyrrhizic acid, Glycyrrhiza glabra

Overview

Liquorice root, primarily derived from the Glycyrrhiza glabra plant, is a traditional herbal supplement known for its bioactive compounds, particularly glycyrrhizic acid and triterpenes. Historically, it has been utilized for various ailments, including liver diseases, gastrointestinal disorders, and inflammatory conditions. Its primary applications in modern supplementation focus on its anti-inflammatory, hepatoprotective, and gastrointestinal protective properties. While preclinical research is robust, especially concerning its anti-inflammatory effects in conditions like ulcerative colitis and its hepatoprotective actions, clinical evidence, though emerging, can be limited by methodological issues. The overall research maturity is moderate, with several systematic reviews and meta-analyses supporting its potential benefits, particularly in liver health. However, it's crucial to note its potential to influence blood pressure due to mineralocorticoid-like effects, which is a significant safety consideration.

Benefits

Liquorice root offers several evidence-based benefits, primarily driven by its active compound, glycyrrhizic acid. It demonstrates significant anti-inflammatory and gastrointestinal protective effects, with preclinical models of ulcerative colitis showing reduced inflammation and potential for mucosal healing. For liver health, glycyrrhizic acid has been shown to significantly reduce markers of liver fibrosis, such as TGF-β1 mRNA expression, hydroxyproline levels, and liver enzymes (e.g., alanine aminotransferase), indicating strong hepatoprotective effects in patients with liver disease. In liver fibrosis, studies observed a reduction in TGF-β1 mRNA expression by approximately 2.9-fold and a significant decrease in liver enzymes (mean difference of -18.12 U/L for alanine aminotransferase). While not a primary benefit, licorice components can modulate blood pressure, typically causing an increase due to mineralocorticoid-like effects, which is a clinically relevant secondary effect. Potential antioxidant and immune-modulatory effects have also been suggested but require further clinical validation. Patients with liver fibrosis or chronic liver disease, as well as individuals with inflammatory bowel disease (ulcerative colitis) based on preclinical evidence, may benefit most. Improvements in liver fibrosis have been observed over weeks to months, while gastrointestinal effects are suggested during active treatment phases in preclinical models.

How it works

Liquorice root exerts its therapeutic effects through several key mechanisms. Its hepatoprotective action primarily involves the inhibition of pro-fibrotic cytokines, such as TGF-β1, and the modulation of downstream Smad signaling pathways, thereby reducing the progression of liver fibrosis. The anti-inflammatory effects are mediated by modulating immune responses and reducing oxidative stress, particularly in gastrointestinal tissues. Glycyrrhiza also interacts with mineralocorticoid receptors, which can lead to sodium retention and potassium loss, consequently affecting electrolyte balance and blood pressure. The main active compound, glycyrrhizic acid, is metabolized in the gut to glycyrrhetinic acid, which is the form primarily absorbed and responsible for systemic activity. Its molecular targets include TGF-β1, Smads, and various inflammatory mediators, as well as mineralocorticoid receptors.

Side effects

While generally safe at moderate doses, liquorice root can cause significant adverse effects, primarily related to its mineralocorticoid-like activity. The most common side effects, occurring in over 5% of users, include hypertension (high blood pressure), hypokalemia (low potassium levels), and edema (fluid retention) due to its impact on electrolyte balance. Less common side effects (1-5%) may include headache, fatigue, and muscle weakness. Rare but severe side effects (less than 1%) can involve severe electrolyte imbalance and cardiac arrhythmias, particularly in susceptible individuals or with high doses. Liquorice root can interact significantly with various medications, including antihypertensives, diuretics, corticosteroids, and any drugs that affect potassium levels, potentially exacerbating their effects or leading to dangerous imbalances. It is strictly contraindicated in patients with uncontrolled hypertension, heart failure, kidney disease, or pre-existing hypokalemia. Special caution is advised for pregnant and breastfeeding women due due to potential hormonal effects, and it should be avoided in these populations. The elderly and individuals with pre-existing cardiovascular risk factors should also exercise extreme caution and ideally avoid its use due to the risk of blood pressure elevation and electrolyte disturbances.

Dosage

For therapeutic effects, particularly in liver disease, clinical studies have utilized glycyrrhizic acid doses ranging approximately from 60 to 240 mg per day. The optimal dosage range is typically considered to be 100-200 mg of glycyrrhizic acid daily. Prolonged intake exceeding 100 mg/day of glycyrrhizic acid may increase the risk of adverse effects, and doses above 300 mg/day are generally not recommended due to heightened safety concerns. To improve tolerance and absorption, doses are often recommended to be divided and taken with meals. It is crucial to use standardized extracts with a known glycyrrhizic acid content to ensure consistent dosing. The gut microbiota plays a role in converting glycyrrhizic acid to its active form, glycyrrhetinic acid, influencing its absorption and bioavailability. While no specific cofactors are required, monitoring electrolyte levels, especially potassium, is highly advisable during supplementation.

FAQs

Is licorice root safe for long-term use?

Long-term use of licorice root, especially at high doses, is generally not recommended due to the increased risk of adverse effects like hypertension and hypokalemia.

Can licorice root lower blood pressure?

No, licorice root typically raises blood pressure due to its mineralocorticoid-like effects, which can lead to sodium retention and potassium loss.

How soon can benefits be expected?

Benefits related to liver health may take weeks to months to become apparent. Gastrointestinal effects, primarily observed in preclinical studies, would likely occur during active treatment.

Does licorice interact with medications?

Yes, licorice can interact significantly with medications, particularly those affecting blood pressure (e.g., antihypertensives) and potassium levels (e.g., diuretics, corticosteroids).

Is deglycyrrhizinated licorice (DGL) safer?

DGL has had most of the glycyrrhizic acid removed, making it safer with fewer side effects related to blood pressure and potassium. However, its efficacy for liver fibrosis may be reduced.

Research Sources

https://pubmed.ncbi.nlm.nih.gov/35671864/ – This systematic review and meta-analysis of preclinical studies investigated the effects of licorice extract on ulcerative colitis. It found that licorice significantly reduced inflammation in animal models, providing a strong rationale for future clinical trials, though direct human evidence is still lacking.
https://www.mdpi.com/2072-6643/16/21/3768 – This systematic review and meta-analysis of clinical trials examined the effect of licorice intake on blood pressure. It concluded that licorice consistently raises blood pressure due to its mineralocorticoid activity, highlighting important safety considerations for its use.
https://www.scielo.br/j/cta/a/8BkTCwd3yPd43tqdpQ3f9NQ/ – This systematic review and meta-analysis focused on the effects of glycyrrhizic acid on liver fibrosis. It included four clinical studies and found that glycyrrhizic acid significantly decreased TGF-β1 mRNA expression and liver enzyme levels, demonstrating its hepatoprotective potential.