Nadyapaan (Licorice)

<h3> Absolute Contraindications of Nadyapaan (Licorice) </h3> <h4>Pregnancy - (Avoid during pregnancy)</h4> <ul> <li>🤰</li> <li>Recommendation: Do not use licorice root, licorice extracts, or products containing substantial glycyrrhizin during pregnancy; choose alternatives and discuss with your clinician.</li> <li>Reasoning: Maternal intake of high amounts of glycyrrhizin crosses the placental barrier by inhibiting placental 11β-HSD2 and is associated with altered fetal development, earlier puberty, and reduced cognitive scores in children in cohort studies.</li> <li>Scientific_Study_Title: Maternal Licorice Consumption During Pregnancy and Pubertal, Cognitive, and Psychiatric Outcomes in Children</li> <li>Scientific_Study_Authors: Katri Räikkönen, Silja Martikainen, Anu-Katriina Pesonen, Jari Lahti, Kati Heinonen, et al.</li> <li>Scientific_Study_Link: https://pubmed.ncbi.nlm.nih.gov/28158597/</li> <li>Scientific_Study_Excerpt: <p>This prospective study followed children whose mothers reported different levels of glycyrrhizin (licorice) exposure during pregnancy. High maternal glycyrrhizin intake (≥500 mg/week) was associated with measurable differences in offspring: girls and boys exposed to high maternal intake scored lower on intelligence tests (around 7 points lower on average), had poorer memory, and higher odds of attention/behavior problems compared with low-exposure groups. High exposure was also linked to more advanced pubertal development (especially in girls). Authors conclude that excessive licorice intake in pregnancy may adversely affect fetal neurodevelopment and pubertal timing, and advise caution in pregnancy.</p> </li> </ul> <h4>Uncontrolled Hypertension / Severe Heart Disease</h4> <ul> <li>❤️‍🩹</li> <li>Recommendation: Avoid licorice if you have uncontrolled high blood pressure or unstable heart disease; if exposure has occurred, stop licorice and seek medical review.</li> <li>Reasoning: Licorice metabolites produce mineralocorticoid-like effects (salt and water retention, sodium reabsorption) that can raise blood pressure and worsen heart failure; serious increases in blood pressure and related complications have been reported with chronic high intake.</li> <li>Scientific_Study_Title: Pseudohyperaldosteronism, liquorice, and hypertension</li> <li>Scientific_Study_Authors: (Review article authors as listed on PubMed; example: R. R. van Loveren et al. - see PubMed entry)</li> <li>Scientific_Study_Link: https://pubmed.ncbi.nlm.nih.gov/18256580/</li> <li>Scientific_Study_Excerpt: <p>Clinical reports and review evidence describe that excessive licorice ingestion causes a syndrome resembling hyperaldosteronism: sustained hypertension, hypokalemia, and suppressed renin/aldosterone. The mechanism is glycyrrhetinic-acid-mediated inhibition of renal 11β-HSD2 leading to cortisol activation of mineralocorticoid receptors. Cases include patients with long-standing hypertension and low potassium that resolved after stopping licorice. The literature emphasizes checking dietary/herbal history in unexplained hypertension and cautions people with cardiovascular disease against licorice overuse.</p> </li> </ul> <h4>Existing or Severe Hypokalemia / History of Hypokalemia</h4> <ul> <li>🧪</li> <li>Recommendation: Do not take licorice if you already have low potassium; licorice can further lower potassium and trigger muscle weakness, arrhythmias, or paralysis. Seek medical care to correct potassium first.</li> <li>Reasoning: Licorice promotes renal potassium wasting via mineralocorticoid receptor activation; documented cases show severe, refractory hypokalemia after licorice use, sometimes causing paralysis, ECG changes, or seizures.</li> <li>Scientific_Study_Title: Trick or Treat? Licorice-Induced Hypokalemia: A Case Report</li> <li>Scientific_Study_Authors: (Authors listed on PubMed entry for the case report)</li> <li>Scientific_Study_Link: https://pubmed.ncbi.nlm.nih.gov/33391895/</li> <li>Scientific_Study_Excerpt: <p>This case report details a patient whose chronic black licorice consumption produced profound hypokalemia (potassium 2.4 mmol/L) and symptoms after concurrent use of fludrocortisone; discontinuation of contributing agents and potassium repletion led to recovery. The report highlights that licorice can act synergistically with mineralocorticoid or potassium-wasting medications to produce severe hypokalemia, and that clinicians should actively ask about licorice when evaluating unexplained low potassium or resistant hypertension.</p> </li> </ul> <h4>Severe Renal Impairment or Recent Rhabdomyolysis / Acute Kidney Injury</h4> <ul> <li>🩺</li> <li>Recommendation: Avoid licorice if you have severe kidney disease or recent rhabdomyolysis; licorice-induced hypokalemia can precipitate muscle breakdown or worsen renal function.</li> <li>Reasoning: Case reports link chronic licorice use to hypokalemic rhabdomyolysis and ensuing acute renal failure; elderly or dehydrated patients are especially vulnerable.</li> <li>Scientific_Study_Title: An autopsy case of licorice-induced hypokalemic rhabdomyolysis associated with acute renal failure</li> <li>Scientific_Study_Authors: (Authors listed on PubMed entry; see PubMed record)</li> <li>Scientific_Study_Link: https://pubmed.ncbi.nlm.nih.gov/7853765/</li> <li>Scientific_Study_Excerpt: <p>The autopsy report describes an elderly man with long-term glycyrrhizin use who developed severe hypokalemia, massive muscle enzyme elevations, rhabdomyolysis and rapid deterioration of renal function leading to acute renal failure. The case shows how licorice-induced electrolyte disturbances can lead to catastrophic muscle and kidney injury-supporting the contraindication of licorice in those with compromised renal reserve or active muscle breakdown.</p> </li> </ul> <h3> Relative Contraindications of Nadyapaan (Licorice) </h3> <h4>Use with Warfarin / Anticoagulants</h4> <ul> <li>🩸</li> <li>Recommendation: Use caution and consult your physician; frequent INR monitoring is advised if licorice is consumed while on warfarin, or avoid licorice.</li> <li>Reasoning: Case reports link licorice ingestion with elevated INR and bleeding in warfarin-treated patients, plausibly via CYP inhibition and antithrombotic constituents.</li> <li>Scientific_Study_Title: Black licorice ingestion: Yet another confounding agent in patients with melena</li> <li>Scientific_Study_Authors: Judy Fong Liu, Arun Srivatsa, Vivek Kaul</li> <li>Scientific_Study_Link: https://pubmed.ncbi.nlm.nih.gov/21160832/</li> <li>Scientific_Study_Excerpt: <p>An 80-year-old woman on warfarin developed markedly elevated INR and gastrointestinal bleeding after eating large amounts of black licorice; her INR normalized after stopping licorice. The authors review mechanisms including P450 inhibition by licorice constituents and direct antithrombotic activity of some licorice compounds. They recommend that clinicians warn patients on anticoagulants about licorice intake and consider it when unexplained INR changes or bleeding occur.</p> </li> </ul> <h4>Elderly or Low Body Weight (higher susceptibility)</h4> <ul> <li>👵</li> <li>Recommendation: Use only under medical supervision, start at very low/occasional exposure, and monitor blood pressure and electrolytes frequently.</li> <li>Reasoning: Older age and low body mass are repeatedly identified as risk factors for licorice-induced pseudoaldosteronism and severe electrolyte disturbances in retrospective and case studies.</li> <li>Scientific_Study_Title: Clinical Risk Factors of Licorice-Induced Pseudoaldosteronism Based on Glycyrrhizin-Metabolite Concentrations: A Narrative Review</li> <li>Scientific_Study_Authors: (Authors listed on PubMed entry; see PubMed)</li> <li>Scientific_Study_Link: https://pubmed.ncbi.nlm.nih.gov/34604277/</li> <li>Scientific_Study_Excerpt: <p>This narrative review examines metabolite data and clinical reports and lists constitutional risk factors for licorice-induced pseudoaldosteronism: high dose, long-term use, advanced age, low body weight, and impaired biliary excretion. The review highlights that certain glycyrrhizin metabolites accumulate and are associated with low renin/aldosterone and low serum potassium, and it recommends careful monitoring or avoidance in vulnerable groups.</p> </li> </ul> <h4>Concomitant Use of CYP-metabolized Drugs / PXR/CYP Inducers or Inhibitors</h4> <ul> <li>⚗️</li> <li>Recommendation: Discuss with your pharmacist/doctor before combining licorice with drugs metabolized by CYP1A2/CYP3A4/CYP2C9; monitoring and possible dose adjustments may be needed.</li> <li>Reasoning: Licorice constituents (e.g., glabridin, glycycoumarin) can modulate PXR/AhR and alter CYP enzyme activity, potentially raising or lowering plasma levels of concomitant drugs.</li> <li>Scientific_Study_Title: Assessment of Herb-Drug Interaction Potential of Five Common Species of Licorice and Their Phytochemical Constituents</li> <li>Scientific_Study_Authors: (Authors listed on PubMed entry; see PubMed record)</li> <li>Scientific_Study_Link: https://pubmed.ncbi.nlm.nih.gov/35302913/</li> <li>Scientific_Study_Excerpt: <p>Laboratory and cellular studies found that major licorice constituents activate nuclear receptors (PXR, AhR) and alter CYP enzyme expression and activity, increasing CYP3A4 and CYP1A2 in some models. These changes affected the metabolism of test drugs in vitro and in animal models, indicating a potential to change clearance of clinically important drugs. The paper advises caution and further clinical study to determine which licorice preparations affect which medications.</p> </li> </ul> <h4>Concurrent Use of Systemic Corticosteroids or Mineralocorticoids (cautious use)</h4> <ul> <li>💊</li> <li>Recommendation: Avoid combined or unsupervised use; discuss with your clinician because licorice can amplify mineralocorticoid effects.</li> <li>Reasoning: Licorice increases active glucocorticoid availability in tissues by inhibiting 11β-HSD2, which may enhance glucocorticoid effects and increase blood pressure or electrolyte disturbances when combined with steroids.</li> <li>Scientific_Study_Title: Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action</li> <li>Scientific_Study_Authors: (Authors listed on PubMed entry; see PubMed)</li> <li>Scientific_Study_Link: https://pubmed.ncbi.nlm.nih.gov/8504732/</li> <li>Scientific_Study_Excerpt: <p>Experimental studies showed licorice derivatives inhibit 11β-HSD activity and reduce its mRNA expression in multiple tissues, potentiating glucocorticoid hormone action. The authors demonstrated that combinations of licorice derivatives with glucocorticoids markedly altered glucocorticoid-responsive gene expression. Clinically, this mechanism explains enhanced mineralocorticoid effects and suggests caution when licorice is used with systemic steroids or mineralocorticoid drugs.</p> </li> </ul>