{"url":"https://whatshealthyandwhy.com/licorice-root/gut-immunity-and-safety","path":"/licorice-root/gut-immunity-and-safety","alternates":{"json":"https://whatshealthyandwhy.com/api/articles/licorice-root/gut-immunity-and-safety.json","markdown":"https://whatshealthyandwhy.com/licorice-root/gut-immunity-and-safety.md"},"topic":{"slug":"licorice-root","name":"Licorice Root","url":"https://whatshealthyandwhy.com/licorice-root"},"slug":"gut-immunity-and-safety","order":1,"title":"Gut Healing, Antiviral Properties, and Safety","question":"Does licorice root help the stomach, and is it safe?","answer":"Deglycyrrhizinated licorice (DGL) may help heal stomach ulcers, but whole licorice root can raise blood pressure and drop potassium.","description":"How Glycyrrhiza glabra's active compounds support gastric health, fight viruses, and why the form you take matters enormously","confidence":2,"confidenceNote":"One 100-patient trial of a DGL-containing blend matched cimetidine, but two earlier placebo-controlled trials found no benefit; antiviral and anti-inflammatory data are mostly lab-based.","evidenceSummary":{"rctCount":5,"metaAnalysisCount":0,"totalParticipants":"140+","replicated":false,"newestStudyYear":2021},"category":{"categoryTitle":"What's Good For You","categorySlug":"good-for-you","subcategoryName":"Herbs & Spices","subcategorySlug":"herbs","url":"https://whatshealthyandwhy.com/explore/good-for-you/herbs"},"actions":["For digestive use, choose DGL (deglycyrrhizinated licorice) chewable tablets of 380–760 mg before meals, rather than whole-root licorice.","Chew DGL tablets so saliva contacts them; capsules may work less well for this purpose.","Treat DGL as supportive; the evidence does not support it as the main treatment for diagnosed peptic ulcers [2]."],"cautions":["Whole-root licorice can cause high blood pressure, low potassium and fluid retention; constipation, older age and diuretics raise the risk [6].","Avoid whole-root licorice if you have high blood pressure, heart, kidney or liver disease, take diuretics, blood pressure drugs or corticosteroids, or are pregnant.","Licorice tea or capsules are not proven to treat viral infections; antiviral data come from lab studies and intravenous doses [4]."],"simpleText":"Licorice root (Glycyrrhiza glabra) has been used medicinally for over three thousand years across Asia, Europe, and the Middle East — and modern research has validated several of its traditional applications. The root contains a rich mix of bioactive compounds, most notably glycyrrhizin (a potent anti-inflammatory and antiviral saponin) and glabridin (an isoflavone that suppresses inflammatory enzymes). For gut healing, a processed form called DGL (deglycyrrhizinated licorice) has been used alongside conventional ulcer drugs with comparable outcomes in clinical trials [2]. What makes licorice genuinely interesting also makes it genuinely risky at high doses: understanding which form to use and in what amounts is essential [6].","mediumText":"How Licorice Root Works\n\nLicorice root contains several distinct classes of bioactive compounds that work through different pathways. The major ones relevant to health applications are:\n\nGlycyrrhizin (glycyrrhizic acid) — the dominant triterpene saponin, making up 2–25% of dry root weight. It inhibits the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which normally breaks down cortisol in the kidney. By blocking this enzyme, glycyrrhizin extends cortisol's activity in the body. It also has direct antiviral properties, disrupting viral envelope integrity and modulating immune signaling.\n\nGlabridin — an isoflavone concentrated in the root's outer peel (0.08–0.35% of dry weight). It blocks NF-κB activation and inhibits inducible nitric oxide synthase (iNOS), two central switches in the inflammatory response. Glabridin also binds tightly to LDL cholesterol particles, protecting them against oxidation [5].\n\nDGL (deglycyrrhizinated licorice) — not a natural compound but a processed form of licorice from which glycyrrhizin has been removed (typically to below 3% by pharmaceutical standards). This removal strips out the cardiovascular risk while preserving compounds that support the gastric mucosa, making DGL the appropriate form for gut-healing applications [2].\n\nGastric Healing and Ulcers\n\nThe most clinically supported application for DGL is gastric mucosal protection. A 100-patient single-blind trial compared Caved-S (a DGL-containing compound preparation) with cimetidine — one of the first H2-blocking ulcer drugs — in patients with confirmed gastric ulcers. At 12 weeks, complete healing occurred in approximately 91% of both groups; one-year recurrence rates were 14% in each arm [2]. This equivalence with a pharmaceutical standard is the strongest positive evidence for DGL's gastric effects.\n\nThe mechanism likely involves several pathways: stimulating mucus secretion, promoting regeneration of gastrointestinal epithelial cells, and inhibiting prostaglandin degradation. This differs fundamentally from proton pump inhibitors (which reduce acid production) — DGL works by supporting the stomach's natural protective barrier rather than by altering acid chemistry.\n\nA smaller study examined licorice as a substitute for bismuth in H. pylori quadruple therapy. While it was not equivalent to the full standard regimen (70% healing vs. 95%), it produced meaningful ulcer healing and significant pain reduction, suggesting a role where bismuth is unavailable [3].\n\nFor gastric support, DGL chewable tablets (380–760 mg before meals) are the standard form, allowing salivary contact before reaching the stomach. Capsules may be less effective for this application.\n\nAntiviral Properties\n\nGlycyrrhizin has documented antiviral activity across several virus families, primarily through in vitro and specialized clinical research. Against hepatitis C virus, it reduces viral replication at concentrations of 14–40 µg/mL, with effects on viral RNA, core protein expression, and synergy with interferon-alpha [4]. Against hepatitis B, IV glycyrrhizin formulations have been used clinically in Japan for decades, with documented effects on liver enzyme normalization.\n\nThe antiviral mechanism involves multiple pathways: disrupting viral membrane fusion, inhibiting early stages of viral replication, and modulating toll-like receptor signaling to enhance innate immune responses [1].\n\nImportant caveat: most antiviral evidence is from laboratory studies or intravenous glycyrrhizin preparations — not from oral licorice supplements at common doses. Oral bioavailability of glycyrrhizin is limited and variable. These findings support mechanistic plausibility but should not be interpreted as evidence that licorice tea or capsules will treat viral infections.\n\nAnti-Inflammatory Effects\n\nGlabridin exerts meaningful anti-inflammatory effects in laboratory and animal models by suppressing NF-κB activation — the central transcription factor that drives production of inflammatory cytokines including TNF-α and IL-6. It also inhibits iNOS (the enzyme that produces damaging nitric oxide during infection and inflammation) and COX-2. In an animal model of septic shock, glabridin administration improved survival rates and reduced circulating TNF-α [5].\n\nSeparately, glycyrrhizin's downstream metabolite (glycyrrhetinic acid) inhibits prostaglandin-degrading enzymes, which can modulate local inflammatory responses in mucous membranes — one mechanism supporting its use in gastric and respiratory conditions.\n\nAgain, this evidence is preclinical. Clinical trials measuring inflammatory biomarkers in humans using standard oral doses are limited. The mechanistic evidence is solid; the translation to clinical anti-inflammatory applications in humans needs further study.\n\nSafety: The Critical Distinction Between Forms\n\nThis is where licorice root differs from most herbs: the risk is real, documented, and dose-dependent, and the form you use determines whether it applies.\n\nWhole root and glycyrrhizin-containing extracts carry meaningful cardiovascular risk at sustained doses. Glycyrrhizin's inhibition of 11β-HSD2 in the kidney causes cortisol to act as a mineralocorticoid — retaining sodium, excreting potassium, and raising blood pressure. This syndrome is called pseudohyperaldosteronism and presents with hypertension, hypokalemia (low potassium), and edema. It is well-documented in clinical literature and has resulted in hospitalizations, cardiac arrhythmias, and in rare cases, more severe outcomes [6].\n\nRisk factors for developing this syndrome include: high dose or long duration, constipation (increases gut absorption of glycyrrhizin metabolites), older age, hypoalbuminemia, and concurrent use of diuretics or corticosteroids [6]. The European Food Safety Authority considers 100 mg/day of glycyrrhizin a general no-observed-adverse-effect level; many supplements contain substantially more.\n\nDGL removes this risk by reducing glycyrrhizin below the threshold that meaningfully inhibits 11β-HSD2. DGL is the appropriate form for digestive applications and has a strong safety record at standard doses.\n\nWho should avoid whole root licorice entirely: people with hypertension, heart or kidney disease, liver disease, those taking diuretics, antihypertensives, or corticosteroids, and pregnant women.\n\nSee our adrenal health page for more on how cortisol regulation affects whole-body health.","deepText":"Evidence Review\n\nGastric Healing: Clinical Trials\n\nThe clinical evidence for DGL in gastric ulcer healing presents an honest mixed picture. Two early placebo-controlled randomized trials found no benefit of DGL over placebo. Engqvist et al. (1973) used a double-blind crossover design with two four-week periods (licorice extract 760 mg three times daily versus placebo; 38 patients in the first period and 30 in the second) and found no tendency to quicker healing in either group, whether measured as change in ulcer area or as complete healing [7]. Bardhan et al. (1978) randomly allocated 96 patients with gastric ulcer to DGL or placebo and found no differences after four weeks in complete healing (assessed by gastroscopy or radiology), in the percentage reduction in ulcer area, or in clinical improvement [8]. Both are important negative results that context requires acknowledging.\n\nThe most clinically meaningful positive evidence comes from Morgan et al. (1982), who enrolled 100 patients with endoscopically confirmed gastric ulcers and randomized them to Caved-S (a DGL-containing multi-ingredient preparation at 6 tablets daily) or cimetidine 1 g/day for up to 12 weeks, with endoscopic follow-up. At 6 weeks, approximately 63% of each group had healed; by 12 weeks, approximately 91% of each group showed complete healing. One-year recurrence rates were 14% in both arms. There was no statistically significant difference between groups on any efficacy endpoint [2]. This non-inferiority finding carries genuine clinical weight: cimetidine was the standard of care at the time, and matching its performance is a meaningful outcome for a plant-derived preparation.\n\nRahnama et al. (2013) tested licorice in a different context: as a substitute for bismuth in H. pylori quadruple therapy (amoxicillin, metronidazole, omeprazole, plus either bismuth or licorice). In 40 patients, ulcer healing rates were 95% with standard quadruple therapy versus 70% with licorice substitution; H. pylori eradication was 70% versus 45%; pain reduction was 80% versus 70% [3]. Licorice did not match the full standard regimen but produced clinically significant healing, suggesting it as a reasonable option when bismuth is unavailable — a finding with global health relevance in resource-limited settings.\n\nOverall assessment for DGL/gastric: MODERATE evidence of gastric mucosal support. The non-inferiority to cimetidine in one 100-patient trial is the strongest positive signal. DGL should not be positioned as a primary treatment for diagnosed peptic ulcer disease, but it has a reasonable evidence base for supportive use in gastric discomfort and as a complement to other approaches.\n\nAntiviral Properties: In Vitro and Clinical Evidence\n\nAshfaq et al. (2011) investigated glycyrrhizin's activity against HCV-3a in human liver cell lines. Glycyrrhizin at 14 µg/mL reduced viral titers by approximately 50%; at 40 µg/mL, inhibition reached ~89%. When combined with interferon-alpha at its standard dose, the combination achieved approximately 95% inhibition. No cytotoxicity was observed up to 100 µg/mL. The mechanism involved dose-dependent suppression of HCV core gene expression at both mRNA and protein levels [4]. These in vitro results are consistent with mechanistic studies across multiple viral targets.\n\nThe clinical translation of these findings is important to contextualize. IV glycyrrhizin formulations (Stronger Neo-Minophagen C) have been used in Japanese clinical practice for chronic viral hepatitis for decades, with documented effects on liver enzyme normalization and viral load modulation. These clinical results do not translate directly to oral supplementation, as glycyrrhizin's oral bioavailability is substantially lower than parenteral administration, and the doses required for antiviral activity may not be achievable safely through oral intake. The mechanistic evidence supports glycyrrhizin as a genuine antiviral compound; the clinical relevance of oral supplementation for viral hepatitis specifically requires dedicated study.\n\nAnti-Inflammatory Mechanisms: Glabridin\n\nKang et al. (2005) characterized glabridin's anti-inflammatory pharmacology using RAW 264.7 macrophages and peritoneal macrophages stimulated with lipopolysaccharide (LPS), alongside an in vivo murine septic shock model. Key findings: glabridin dose-dependently inhibited LPS-induced nitric oxide production, suppressed iNOS protein and mRNA expression, blocked NF-κB/Rel DNA binding and nuclear translocation of p65, and inhibited reactive oxygen species generation. In vivo, glabridin-treated mice showed improved survival after cecal ligation and puncture (septic shock model) and significantly reduced plasma TNF-alpha levels [5].\n\nThe 2021 comprehensive review by Wahab et al. synthesized available evidence on licorice phytochemistry and biological activity, confirming that glycyrrhizin and its metabolites significantly decrease iNOS, COX-2, TNF-α, and IL-6 expression through NF-κB and NLRP3 signaling pathway modulation, alongside Nrf2/HO-1 pathway activation for oxidative stress protection [1].\n\nHuman clinical trial data for anti-inflammatory endpoints with oral licorice preparations are limited. The mechanistic base is robust; clinical confirmation in anti-inflammatory disease states requires larger dedicated trials.\n\nSafety: Pseudohyperaldosteronism Risk …","deepTruncated":true,"references":[{"id":"1","title":"Glycyrrhiza glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology","authors":"Wahab S, Annadurai S, Abullais SS, Das G, Ahmad W, Ahmad MF, Kandasamy G, Vasudevan R, Ali MS, Amir M","year":2021,"journal":"Plants (Basel)","pmid":"34961221","url":"https://pubmed.ncbi.nlm.nih.gov/34961221/"},{"id":"2","title":"Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy","authors":"Morgan AG, McAdam WA, Pacsoo C, Darnborough A","year":1982,"journal":"Gut","pmid":"7042486","url":"https://pubmed.ncbi.nlm.nih.gov/7042486/"},{"id":"3","title":"The healing effect of licorice (Glycyrrhiza glabra) on Helicobacter pylori infected peptic ulcers","authors":"Rahnama M, Mehrabani D, Japoni S, Edjtehadi M, Saberi Firoozi M","year":2013,"journal":"Journal of Research in Medical Sciences","pmid":"24250708","url":"https://pubmed.ncbi.nlm.nih.gov/24250708/"},{"id":"4","title":"Glycyrrhizin as antiviral agent against Hepatitis C Virus","authors":"Ashfaq UA, Masoud MS, Nawaz Z, Riazuddin S","year":2011,"journal":"Journal of Translational Medicine","pmid":"21762538","url":"https://pubmed.ncbi.nlm.nih.gov/21762538/"},{"id":"5","title":"Glabridin, an isoflavan from licorice root, inhibits inducible nitric-oxide synthase expression and improves survival of mice in experimental model of septic shock","authors":"Kang JS, Yoon YD, Cho IJ, Han MH, Lee CW, Park SK, Kim HM","year":2005,"journal":"Journal of Pharmacology and Experimental Therapeutics","pmid":"15537821","url":"https://pubmed.ncbi.nlm.nih.gov/15537821/"},{"id":"6","title":"Clinical Risk Factors of Licorice-Induced Pseudoaldosteronism Based on Glycyrrhizin-Metabolite Concentrations: A Narrative Review","authors":"Yoshino T, Shimada S, Homma M, Makino T, Mimura M, Watanabe K","year":2021,"journal":"Frontiers in Nutrition","pmid":"34604277","url":"https://pubmed.ncbi.nlm.nih.gov/34604277/"},{"id":"7","title":"Double-blind trial of deglycyrrhizinated liquorice in gastric ulcer","authors":"Engqvist A, von Feilitzen F, Pyk E, Reichard H","year":1973,"journal":"Gut","pmid":"4584640","url":"https://pubmed.ncbi.nlm.nih.gov/4584640/"},{"id":"8","title":"Clinical trial of deglycyrrhizinised liquorice in gastric ulcer","authors":"Bardhan KD, Cumberland DC, Dixon RA, Holdsworth CD","year":1978,"journal":"Gut","pmid":"361512","url":"https://pubmed.ncbi.nlm.nih.gov/361512/"}],"wordCount":2039,"source":{"path":"src/content/topics/licorice-root/gut-immunity-and-safety.md"},"citeAs":"“Does licorice root help the stomach, and is it safe?.” What's Healthy and Why. https://whatshealthyandwhy.com/licorice-root/gut-immunity-and-safety","notice":"General information backed by peer-reviewed research, not medical advice."}