Liquorice Safety in Rheumatoid Arthritis
Liquorice (licorice) can be used cautiously in patients with rheumatoid arthritis as a complementary therapy, but requires careful monitoring for cardiovascular and metabolic side effects, particularly hypertension, hypokalemia, and edema.
Evidence for Potential Benefits
The active components of liquorice—glycyrrhizin (GL) and glycyrrhetinic acid (GA)—demonstrate anti-inflammatory effects through suppression of the COX-2/thromboxane A2 (TxA2) pathway, which is a crucial mechanism in RA pathogenesis 1.
Liquorice may serve as an add-on therapy that could potentiate therapeutic effects and decrease adverse effects of NSAIDs or DMARDs by targeting the COX-2/TxA2 pathway, which is not addressed by standard RA medications 1.
Clinical evidence from 120 RA patients showed that compound decoction of Tripterygium wilfordii combined with liquorice achieved an 89.8% efficacy rate with significantly lower adverse reaction incidence compared to Tripterygium wilfordii alone (P < 0.01), demonstrating toxicity attenuation effects 2.
Liquorice extract has been documented as possessing anti-inflammatory and anti-arthritic properties through multiple phytochemicals including phenolic acids, triterpene glycosides, and flavonoids 3, 4.
Critical Safety Concerns
Cardiovascular risks: Liquorice can cause pseudohyperaldosteronism, leading to hypertension, fluid retention, and hypokalemia through mineralocorticoid effects—particularly concerning since RA patients already have elevated cardiovascular risk 1.
Drug interactions: Patients taking DMARDs, biologics, or NSAIDs must be monitored closely, as liquorice may alter drug metabolism and electrolyte balance 4.
Monitoring requirements: Regular assessment of blood pressure, serum potassium levels, and signs of fluid retention is essential when using liquorice in RA patients 4.
Clinical Decision Algorithm
For RA patients considering liquorice:
Contraindications: Avoid in patients with uncontrolled hypertension, heart failure, renal disease, or those taking digoxin or diuretics 4.
Dosing considerations: Limit glycyrrhizin intake to <100 mg/day (approximately 50-100g of liquorice root) to minimize mineralocorticoid effects 4.
Baseline assessment: Check blood pressure, serum potassium, and renal function before initiating liquorice supplementation 4.
Follow-up monitoring: Reassess blood pressure and electrolytes every 2-4 weeks initially, then monthly if stable 4.
Integration with Standard RA Treatment
Liquorice should only be considered as complementary therapy alongside evidence-based RA management, not as monotherapy 1, 3.
Standard DMARD therapy (methotrexate as first-line) remains the cornerstone of RA treatment per ACR guidelines, with liquorice serving only as potential adjunctive support 5.
The European League Against Rheumatism emphasizes that any supplement use, including herbal products, should be discussed with the rheumatologist, particularly when starting new treatments 6.
Common Pitfalls to Avoid
Underestimating mineralocorticoid effects: Even "natural" liquorice preparations can cause significant electrolyte disturbances and cardiovascular complications 4.
Assuming safety due to herbal origin: Liquorice has well-documented adverse effects that require the same vigilance as pharmaceutical agents 4.
Neglecting drug-supplement interactions: Liquorice may interact with immunosuppressive medications commonly used in RA management 3, 4.