Gut Healing, Antiviral Properties, and Safety

Evidence Review

Gastric Healing: Clinical Trials

The clinical evidence for DGL in gastric ulcer healing presents an honest mixed picture. Two early placebo-controlled RCTs (Engqvist et al., 1973; Bardhan et al., 1978) found no statistically significant difference between DGL and placebo in endoscopically confirmed ulcer healing — both are important negative results that context requires acknowledging.

The 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.

Rahnama 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.

Overall 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.

Antiviral Properties: In Vitro and Clinical Evidence

Ashfaq 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.

The 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.

Anti-Inflammatory Mechanisms: Glabridin

Kang 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].

The 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].

Human 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.

Safety: Pseudohyperaldosteronism Risk

The safety literature on whole-root licorice is well-developed and unambiguous about the mechanism. Yoshino et al. (2021) conducted a narrative review specifically examining clinical risk factors for licorice-induced pseudohyperaldosteronism, using pharmacokinetic data on glycyrrhizin metabolite concentrations. The review identified a consistent set of patient-level and situational risk factors: prolonged or high-dose exposure, constipation (which extends colonic transit time, increasing gut bacterial conversion of glycyrrhizin to the more absorbable glycyrrhetinic acid), hypoalbuminemia, elevated bilirubin (impairing hepatic elimination), older age, and concurrent medications that compound electrolyte effects [6].

The syndrome presents as apparent mineralocorticoid excess: hypertension, hypokalemia (sometimes severe, with associated muscle weakness), and sodium retention. Hypokalemia in the range that licorice can produce is associated with cardiac arrhythmia risk, which explains documented case reports of serious cardiovascular events. The mechanism is well-established: glycyrrhetinic acid inhibits 11β-HSD2 in the kidney collecting duct, allowing cortisol — which circulates at much higher concentrations than aldosterone — to bind mineralocorticoid receptors and drive sodium-potassium exchange.

DGL's safety advantage is mechanistically sound: without glycyrrhizin reaching systemic circulation at meaningful concentrations, the 11β-HSD2 inhibition driving pseudohyperaldosteronism does not occur. At standard supplemental doses, DGL has not been associated with blood pressure or electrolyte effects in published clinical data.

Evidence Summary Table

Licorice root occupies a legitimate place in evidence-based herbal medicine — but only when the right form is matched to the right application, and with clear-eyed understanding of where its risks arise. For gastric support, DGL is a well-tolerated option with meaningful clinical backing. Whole-root preparations deserve more caution than their ubiquity in wellness products might suggest.