How does licorice consumption affect mast cell function?

Licorice and Mast Cell Function

Licorice components, particularly glycyrrhizic acid and liquiritigenin, demonstrate significant mast cell stabilizing effects by inhibiting degranulation and calcium influx, but patients with mast cell disorders should exercise caution due to licorice's mineralocorticoid activity and potential drug interactions. 1, 2

Anti-Mast Cell Effects of Licorice

Direct Mast Cell Stabilization

• Glycyrrhizic acid (GA) and licorice chalcone A (LA) potently inhibit mast cell degranulation in both RBL-2H3 cells and mouse peritoneal mast cells, reducing histamine and TNF-α release. 1

• Liquiritigenin and 18β-glycyrrhetinic acid are the most potent components for preventing IgE-mediated mast cell degranulation and compound 48/80-induced activation. 2

• These compounds inhibit calcium influx into mast cells, a critical step in the degranulation cascade. 1

• LA appears to function as a potential ligand of MRGPRX2 (MAS-related G protein-coupled receptor-X2), a pivotal receptor for pseudo-allergic reactions. 1

Anti-Allergic Clinical Effects

• Licorice components demonstrate anti-scratching behavior effects and reduce passive cutaneous anaphylactic reactions in animal models. 2

• Glycyrrhizin and liquiritigenin inhibit IgE production in ovalbumin-induced asthma models, suggesting benefit for IgE-mediated allergic diseases including dermatitis and asthma. 2, 3

• The anti-inflammatory mechanisms involve reduction of pro-inflammatory mediator synthesis that activates eosinophils, basophils, and mast cells, preventing Th2 cell differentiation. 3

Critical Safety Concerns for Mast Cell Disorder Patients

Mineralocorticoid Activity

• Licorice causes excess mineralocorticoid activity through inhibition of 11β-hydroxysteroid dehydrogenase (11β-HSD2) and direct mineralocorticoid receptor binding. 4, 5

• This leads to sodium retention, hypervolemia, hypokalemia, hypertension, and edema development—particularly problematic for patients with systemic mastocytosis who may already have cardiovascular instability. 4

• Long-term use with high doses causes hypertension and hypokalemic-induced secondary disorders. 4

Drug Interactions

• Glycyrrhetinic acid (GA) induces CYP3A activity, creating significant drug-drug interactions with medications metabolized by this pathway, including cyclosporine A. 4

• Concurrent use with methotrexate increases mean retention time of methotrexate. 4

• Combination with cilostazol causes pseudoaldosteronism. 4

• These interactions are particularly concerning for mast cell disorder patients who may be on immunosuppressive therapy or cytoreductive agents. 4

Clinical Recommendations

For Patients with Mast Cell Disorders

• Patients with systemic mastocytosis, particularly those with cirrhosis or on immunosuppressive medications, should avoid licorice consumption due to mineralocorticoid effects and drug interactions. 4

• The salt and water retaining effects contradict standard management principles for mast cell activation syndrome, where trigger avoidance is paramount. 6, 7

• While licorice has theoretical anti-mast cell properties, the cardiovascular risks (hypertension, fluid retention) outweigh potential benefits in patients already at risk for anaphylaxis and hypotensive episodes. 4

Safer Alternatives for Mast Cell Stabilization

• H1 and H2 antihistamines remain first-line therapy for mast cell activation symptoms, with doses potentially 2-4 times FDA-approved levels. 6, 7, 8

• Oral cromolyn sodium is the preferred mast cell stabilizer for gastrointestinal symptoms without the mineralocorticoid risks of licorice. 6

• For patients seeking natural anti-inflammatory options, other Ramadan drinks (tamarind, carob, hibiscus) lack the contraindications associated with licorice. 4

Common Pitfalls to Avoid

• Do not recommend licorice as a "natural" mast cell stabilizer without considering the patient's complete medication list and comorbidities, particularly cardiovascular status and liver function. 4

• Avoid assuming that anti-mast cell effects demonstrated in vitro translate to safe clinical use—the systemic mineralocorticoid effects create unacceptable risks for most mast cell disorder patients. 1, 2, 5

• Do not overlook that patients may consume licorice in candy, herbal supplements, or traditional beverages without recognizing it as a medication with significant pharmacologic effects. 5