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Licorice Root for Health & Longevity

Evidence Review created on 10/22/2026 using AI4L / Opus 5.5

Also known as: Licorice, Liquorice, Liquorice Root, Glycyrrhiza glabra, Glycyrrhiza uralensis, Glycyrrhiza inflata, Glycyrrhizae Radix, Sweet Root, Gan Cao, Chinese Licorice, Mulethi, Yashtimadhu, Deglycyrrhizinated Licorice, DGL

Motivation

Licorice root (Glycyrrhiza glabra) is the sweet root behind black licorice candy, many herbal teas, and a long list of traditional remedies. Its main sweet compound changes how the body handles salt and the stress hormone cortisol, while other compounds in the root are studied for anti-inflammatory activity. For health-focused adults, that makes licorice an unusual case: a familiar food flavoring that is also an active substance.

The root has been part of Egyptian, Greek, Chinese, and Indian medicine for thousands of years, mainly as a soothing remedy for the stomach. Today it is sold as a supplement for digestive comfort, appears in many Japanese and Chinese herbal formulas, and flavors candy and tobacco. It has also drawn medical attention through case reports involving heavy candy and tea consumption, which keeps blood pressure at the center of its safety discussion.

This review examines what human studies show about licorice root for longevity-minded adults: the benefits tested, the risks tied to its sweet compound, how forms with that compound removed differ, the doses studied, and the monitoring described in the research.

Benefits - Risks - Protocol - Conclusion

This section lists expert commentary and narrative reviews that give a high-level overview of licorice root’s benefits, risks, and longevity relevance.

  • How Much Licorice Is Safe? - Michael Greger

    Michael Greger reviews trials showing that glycyrrhizin (licorice’s main sweet compound) trims body fat slightly while retaining water and raising blood pressure, and asks how much intake stays safe.

  • Licorice - Alzheimer’s Drug Discovery Foundation

    A brain-health evidence report finding antioxidant and anti-inflammatory activity in laboratory work but no cognitive benefit in clinical studies, with a detailed safety and dosing discussion.

  • Licorice: From Pseudohyperaldosteronism to Therapeutic Uses - Sabbadin et al., 2019

    The Padua endocrinology group explains pseudohyperaldosteronism (a state mimicking excess aldosterone, the salt-retaining adrenal hormone, with high blood pressure and low potassium) and uses such as polycystic ovary syndrome.

  • Liquorice Toxicity: A Comprehensive Narrative Review - Ceccuzzi et al., 2023

    Reviews 104 published case reports of licorice toxicity, including arrhythmias (irregular heart rhythms), paralysis, and rhabdomyolysis (muscle breakdown), and examines which patient features predicted harm.

No dedicated content was found from Rhonda Patrick, Peter Attia, Andrew Huberman, Chris Kresser, Life Extension Magazine, or Lifespan.io: they mention licorice only in passing (Attia, Kresser, and Huberman, whose podcast episodes briefly touch on its cortisol and blood-pressure effects) or not at all (Patrick), Life Extension covers licorice only in a short product-oriented post on deglycyrrhizinated licorice and as one ingredient in multi-nutrient stomach-health articles, and Lifespan.io covers only a cell-culture study of one licorice compound. Only four sources met the overview standard, so four are listed.

Grokipedia

Liquorice

An encyclopedic overview of liquorice botany, chemistry, traditional uses, clinical evidence, and safety; useful for orientation, though its claims need checking against primary studies.

Examine

Licorice

Examine grades human trial outcomes for licorice condition by condition and summarizes dosage and safety, separating glycyrrhizin-containing products from deglycyrrhizinated (glycyrrhizin-removed) ones.

ConsumerLab

Licorice and DGL Supplements, Candies, and Tea Review

Independent tests of 11 licorice and DGL (deglycyrrhizinated licorice, with glycyrrhizin removed) products measured glycyrrhizic acid (glycyrrhizin) per serving; three DGL products held more than expected.

Systematic Reviews

This section lists systematic reviews and meta-analyses (analyses pooling results of multiple studies) covering licorice root’s main benefits and its principal blood-pressure and potassium risk.

Mechanism of Action

Two groups of compounds explain most of licorice root’s effects:

  • Glycyrrhizin: Gut bacteria convert it to glycyrrhetinic acid, which blocks 11β-HSD2 (11β-hydroxysteroid dehydrogenase type 2, the kidney enzyme that inactivates cortisol). Cortisol then activates mineralocorticoid receptors (salt-retaining receptors normally reserved for aldosterone), causing sodium retention, potassium loss, and higher blood pressure (Ploeger et al., 2001). Glycyrrhizin also binds HMGB1 (high-mobility group box 1, an inflammation-driving danger signal from damaged cells) (Mollica et al., 2007) and partly blocks testosterone-producing enzymes (Armanini et al., 2004).
  • Flavonoids (glabridin, liquiritigenin, isoliquiritigenin, licochalcone A): These provide antioxidant, anti-inflammatory, and estrogen-like activity (Alzheimer’s Drug Discovery Foundation, ADDF). Deglycyrrhizinated licorice keeps the flavonoids. Separately, root polysaccharides block Helicobacter pylori (an ulcer-causing stomach bacterium) adhesion in laboratory tests (Wittschier et al., 2009).
  • Pharmacology: Glycyrrhetinic acid, 200 to 1,000 times more potent than glycyrrhizin at blocking 11β-HSD2, concentrates in the liver, is conjugated by several UGT enzymes, most actively UGT1A3 (a liver enzyme that tags compounds for excretion) (Lu et al., 2009), and recycles through bile, delaying clearance (Ploeger et al., 2001); glabridin’s half-life is about 10 hours in a study by its oil’s maker, Kaneka (Aoki et al., 2007). Glycyrrhizin modestly induces CYP3A4 (the liver enzyme metabolizing roughly half of prescription drugs) (Tu et al., 2010).
  • Competing explanations: Weight effects are attributed to blocked cortisol activation in fat or to flavonoids, while water retention can mask fat loss. Blood pressure rises with glycyrrhizin but not with flavonoid-dominated extracts (Wu et al., 2024).

Historical Context & Evolution

  • Original use: Licorice appears in Assyrian, Egyptian, Greek, Chinese, Tibetan, and Indian medicine, used for coughs, asthma, wound healing, and lung, liver, and artery diseases, according to the US National Center for Complementary and Integrative Health (NCCIH). In Chinese medicine (where it is called gan cao) it remains a common ingredient of multi-herb formulas.
  • Ulcer therapy and hormone discovery: Research on licorice’s hormone-like effects, including salt retention, cortisol potentiation, and testosterone lowering, developed through the twentieth century alongside its use for stomach ulcers (Armanini et al., 2002). Deglycyrrhizinated licorice, promoted for ulcers, did not speed gastric-ulcer healing in a 1973 controlled trial (Engqvist et al., 1973). Detailed metabolic studies then traced the salt-retaining effect to cortisol (Farese et al., 1991).
  • Japanese liver use: Intravenous glycyrrhizin has been used in Japan for chronic hepatitis since 1977; in long-term follow-up, users developed cirrhosis (liver scarring) and liver cancer less often than controls (Kumada, 2002), a different route from oral supplements.
  • Health-optimization interest: Glycyrrhizin-depleted flavonoid extracts were later developed for digestion and body fat, and laboratory aging findings drew longevity interest.
  • How opinion changed: The 100 mg/day glycyrrhizic acid level that JECFA (the Joint Expert Committee on Food Additives of the United Nations food and health agencies) judged unlikely to harm most adults (JECFA) is now questioned after a 2024 trial measured blood-pressure rises at that dose (af Geijerstam et al., 2024), while benefit claims remain supported mainly by small trials.

Expected Benefits

High 🟩 🟩 🟩

Relief of Throat and Mouth Soreness (Topical Use) ⭕️ Not Central to Health & Longevity

Licorice gargles and other topical forms used before surgery reduce sore throat after breathing-tube placement, and licorice rinses, patches, and pastes shorten painful canker sores, through local anti-inflammatory action. A meta-analysis of five randomized trials (Kuriyama & Maeda, 2019) includes independent trials by Agarwal in India (Agarwal et al., 2009) and Ruetzler in Austria (Ruetzler et al., 2013); a systematic review of six canker-sore trials agrees (Dorsareh et al., 2023). This bears on short-term comfort, not on lifespan or chronic disease.

Magnitude: Postoperative sore throat at 24 hours: risk ratio (the event rate with licorice divided by the rate in controls) 0.44 (95% confidence interval, CI, the range likely to contain the true effect: 0.28 to 0.69) versus non-analgesic controls; severity standardized mean difference (SMD, effect size in standard-deviation units) −0.69 (95% CI −0.96 to −0.43) (Kuriyama & Maeda, 2019).

Medium 🟩 🟩

Upper Digestive Symptom Relief (Indigestion and Reflux)

A flavonoid-rich, low-glycyrrhizin extract (GutGard) reduced functional dyspepsia (chronic indigestion without visible cause) symptoms versus placebo in 50 patients (Raveendra et al., 2012) and eased heartburn and regurgitation in 200 adults with reflux (Raj et al., 2025). A Cochrane review rated the indigestion evidence moderate certainty from that single trial (Báez et al., 2023). The 2012 trial included researchers from the extract’s manufacturer, Natural Remedies. Proposed mechanisms are protection of the stomach lining and anti-inflammatory flavonoids.

Magnitude: Indigestion symptom score SMD −1.86 (95% CI −2.54 to −1.19) versus placebo after 30 days (1 trial, 50 participants) (Báez et al., 2023).

Helicobacter pylori Suppression

Adding licorice to clarithromycin-based triple therapy (two antibiotics plus an acid reducer) raised H. pylori eradication in 120 patients (Hajiaghamohammadi et al., 2016), and licorice matched bismuth within quadruple (four-drug) therapy (Momeni et al., 2014). Alone, GutGard 150 mg/day cleared stool antigen more often than placebo in a trial sharing authors with the manufacturer-affiliated 2012 study (Puram et al., 2013). A meta-analysis of polyphenol compounds, licorice among them, found higher eradication as add-ons (Wang et al., 2023). Root polysaccharides block bacterial adhesion in laboratory tests (Wittschier et al., 2009).

Magnitude: Eradication 83.3% with licorice plus triple therapy versus 62.5% with triple therapy alone (Hajiaghamohammadi et al., 2016); stool antigen negative in 56% versus 4% with placebo after 60 days (Puram et al., 2013).

Lower Liver Enzymes and Liver Fat in Fatty Liver Disease

Oral licorice root extract, 2 g/day for 2 months, lowered ALT (alanine aminotransferase, a liver-injury enzyme) in 66 fatty-liver patients (Hajiaghamohammadi et al., 2012), and 1 g/day for 12 weeks with diet improved ALT and ultrasound liver-fat grade in 60 women (Rostamizadeh et al., 2022). A meta-analysis of 15 trials found larger effects with purified glycyrrhizin compounds, with preparations varying widely (Giangrandi et al., 2024). Proposed mechanisms are anti-inflammatory and antioxidant liver protection; no trial measured cirrhosis or liver events.

Magnitude: ALT −15.63 U/L (95% CI −25.08 to −6.18) and AST (aspartate aminotransferase, a second liver enzyme) −7.37 U/L (95% CI −13.13 to −1.61) versus controls across mixed preparations in patients with various primary liver diseases, not fatty liver alone (Giangrandi et al., 2024).

Fewer Menopausal Hot Flashes

Licorice root extract, 330 mg three times daily for 8 weeks, reduced hot-flash frequency versus placebo in 90 Iranian women, with symptoms recurring after stopping (Nahidi et al., 2012); its abstract claims lower severity, but the full text shows severity also fell with placebo in week 1. A second trial in 60 women found licorice 1,140 mg/day similar to low-dose hormone therapy for frequency but weaker for severity (Menati et al., 2014). Estrogen-like flavonoids such as liquiritigenin are the proposed mechanism (ADDF). Both trials are small and short.

Magnitude: Daily hot flashes fell from 7.70 to 6.43 after 8 weeks with licorice versus 7.73 to 7.75 with placebo (week-8 group means compared at P < 0.001, P being the probability of such a difference by chance; no difference figure reported) (Nahidi et al., 2012).

Eczema Symptom Relief (Topical Gel) ⭕️ Not Central to Health & Longevity

In a double-blind trial in atopic dermatitis (eczema, an itchy inflammatory skin condition) with 30 patients per group, licorice extract gel applied for 2 weeks was compared with a base gel; 2% gel reduced redness, swelling, and itching more than 1% gel (Saeedi et al., 2003). Local anti-inflammatory action is the proposed mechanism. This is a single small trial, and NCCIH calls the evidence preliminary (NCCIH). This bears on skin comfort, not on lifespan or chronic disease.

Magnitude: Redness, swelling, and itching scores fell more with 2% than with 1% gel over 2 weeks (P < 0.05); the trial abstract reports no outcome figure, including versus the base gel (Saeedi et al., 2003).

Small Reductions in Body Weight and Body Fat ⚠️ Conflicted

A meta-analysis of 26 trials (985 participants) found licorice products slightly lowered body weight and BMI (body mass index, weight relative to height) (Luís et al., 2018). Much evidence uses licorice flavonoid oil from researchers linked to its maker, Kaneka (Aoki et al., 2007; Tominaga et al., 2009). Root extract did not change BMI in a fatty-liver trial (Hajiaghamohammadi et al., 2012). Proposed mechanisms are reduced cortisol activation in fat or flavonoid action. Net reading: a real but very small weight effect, partly offset by water retention.

Magnitude: Body weight −0.43 kg (95% CI −0.68 to −0.18) and BMI −0.15 kg/m² (95% CI −0.24 to −0.06) versus controls (Luís et al., 2018).

Low 🟩

Improved Blood Lipids and Insulin Sensitivity ⚠️ Conflicted

Licorice extract plus dieting lowered cholesterol and insulin resistance versus placebo plus dieting in 66 women with polycystic ovary syndrome (Hooshmandi et al., 2024); evidence is indirect, tested only with diet. A licorice-candy trial found no lipid or blood-sugar change (Åstrand et al., 2026). Net reading: benefit remains unconfirmed.

Magnitude: LDL cholesterol (low-density lipoprotein, artery-clogging cholesterol) fell from 121.1 to 81.1 mg/dL with licorice versus 101.0 to 105.6 mg/dL with placebo, and HOMA-IR (an insulin-resistance index) from 2.38 to 1.23 versus 2.54 to 2.55 (between-group P ≤ 0.01; no difference figure reported) (Hooshmandi et al., 2024).

Adjunct Improvement of Parkinson’s Disease Symptoms

Licorice syrup (about 12 mg glycyrrhizic acid twice daily) added to standard care for 6 months improved rating-scale scores, daily activities, and tremor versus placebo in 39 Parkinson’s patients (Petramfar et al., 2020). Evidence is indirect: one small trial, tested only alongside standard Parkinson’s medication.

Magnitude: Total Parkinson’s rating-scale score, daily activities, and tremor improved versus placebo from week 6; the published abstract reports no between-group outcome figure (Petramfar et al., 2020).

Peptic Ulcer Healing (Deglycyrrhizinated Licorice) ⚠️ Conflicted

Chewable deglycyrrhizinated licorice healed gastric ulcers about as often as cimetidine (an acid-reducing medicine) in 100 patients (Morgan et al., 1982). Placebo-controlled trials found no faster healing of gastric (Bardhan et al., 1978) or duodenal ulcers (Feldman & Gilat, 1971). Net reading: placebo-controlled trials show no healing benefit.

Magnitude: Gastric-ulcer healing about 63% at 6 weeks and 91% at 12 weeks with both deglycyrrhizinated licorice and cimetidine, no significant difference (Morgan et al., 1982); no difference from placebo in complete healing after 4 weeks, with no outcome figure in the abstract (Bardhan et al., 1978).

Muscle Mass and Balance in Older Adults

Licorice flavonoid oil, 300 mg/day for 16 weeks, increased trunk muscle in 50 older rehabilitation patients (Kinoshita et al., 2017) and prolonged one-leg standing in 73 exercising women (Kinoshita et al., 2021), possibly via antioxidant muscle protection. Evidence is indirect: a glycyrrhizin-free flavonoid concentrate, not whole root, from one group.

Magnitude: One-leg standing rose from 73.9 to 93.5 seconds with flavonoid oil versus 82.8 to 87.1 seconds with placebo (between-group P = 0.03; no difference figure reported) (Kinoshita et al., 2021).

Adjunct Relief of Depressive Symptoms

Purified glycyrrhizic acid added to standard antidepressants relieved depressive symptoms more than placebo over 4 weeks in 56 patients, mainly in those with high inflammation (Cao et al., 2020). Evidence is indirect: one small trial of an isolated compound, tested only alongside antidepressants.

Magnitude: Greater symptom relief at week 4 (P = 0.016), with higher response and remission rates; the trial abstract reports no outcome figure (Cao et al., 2020).

Lower Androgen Levels in Women ⭕️ Not Central to Health & Longevity

Licorice 3.5 g/day, probably by blocking testosterone-producing enzymes, lowered total testosterone in nine healthy women over two cycles, reversing after stopping (Armanini et al., 2004). Data are uncontrolled, from one group, and hormonal only. This bears on androgen-excess conditions such as PCOS (polycystic ovary syndrome) and hirsutism (excess body hair).

Magnitude: Total testosterone fell from 27.8 to 17.5 ng/dL after 2 months (no control group) (Armanini et al., 2004).

Antiviral Effects Against Respiratory Viruses ⚠️ Conflicted

Glycyrrhizin inhibited SARS (severe acute respiratory syndrome) coronavirus in cells (Cinatl et al., 2003). As add-on COVID-19 (coronavirus disease 2019) care, licorice shortened hospital (Soleiman-Meigooni et al., 2022) and intensive-care stays (Alikiaie et al., 2023), not clinical measures (Ameri et al., 2023). Net reading: small, inconsistent trials leave benefit unproven.

Magnitude: Hospital stay 5.24 days with licorice syrup plus standard care versus 7.14 days with standard care alone (Soleiman-Meigooni et al., 2022); no between-group difference in oxygen saturation, body temperature, or breathing rate after 7 days, with no outcome figure in the abstract (Ameri et al., 2023).

Speculative 🟨

Slowing of Aging Pathways

Licorice extract extended worm lifespan 14% (Reigada et al., 2020) and improved aging markers in mice (Yu et al., 2025). Basis is animal and cell data only; no human aging outcome exists.

Cancer Prevention

Licochalcones inhibit growth, migration, and invasion of cancer cells through several signaling pathways (Deng et al., 2023). Basis is cell and animal data; no controlled human cancer-prevention data exist.

Dental Caries Prevention ⭕️ Not Central to Health & Longevity

Licorice lollipops, gums, and gels lowered counts of the cavity-causing bacterium Streptococcus mutans in children (Tharakan et al., 2020). Basis is a bacterial-count marker only; no adult cavity outcome exists. It bears on oral health.

Benefit-Modifying Factors

  • Genetic polymorphisms: No validated gene variant predicts benefit. CYP2C19 (a liver enzyme that metabolizes omeprazole) genotype did not change glycyrrhizin’s effect on omeprazole metabolism (Tu et al., 2010); gut-bacteria differences drive individual variation in glycyrrhizin handling instead (Yoshino & Makino, 2026).
  • Baseline biomarkers: Benefits appeared in people with abnormal starting values: elevated ALT in fatty liver, active H. pylori infection, frequent hot flashes, or overweight. No trial shows benefit in people whose values are already normal.
  • Sex: Hot-flash and androgen-lowering data come from women only (Nahidi et al., 2012); in men, androgen lowering would be an adverse effect rather than a benefit.
  • Pre-existing health conditions: Trials found effects in indigestion, reflux, H. pylori infection, fatty liver, and Parkinson’s disease. People with hypertension gain less net benefit because glycyrrhizin raises their pressure more (Sigurjonsdottir et al., 2003).
  • Age: Most trials enrolled adults under 60; flavonoid-oil trials in 54- to 90-year-olds are the main older-adult data (Kinoshita et al., 2017), and older adults’ proposed greater glycyrrhizin sensitivity, unconfirmed in a case-report review (Ceccuzzi et al., 2023), narrows whole-root margins.

Potential Risks & Side Effects

High 🟥 🟥 🟥

Blood Pressure Elevation (Glycyrrhizin-Containing Forms) ⚠️ Conflicted

Glycyrrhetinic acid blocks 11β-HSD2, so cortisol retains sodium and water. A meta-analysis of 18 studies found dose-dependent rises (Penninkilampi et al., 2017), confirmed in trials by Sigurjónsdóttir in Iceland and Sweden (Sigurjónsdóttir et al., 2001) and af Geijerstam in Sweden at 100 mg/day (af Geijerstam et al., 2024). A trial at about 24 mg/day found no change (Petramfar et al., 2020), and flavonoid-dominated extracts showed none (Wu et al., 2024). Net reading: glycyrrhizin raises pressure dose-dependently, with little effect at low doses or without glycyrrhizin.

Magnitude: Home systolic pressure changed +3.1 mmHg (95% CI 0.8 to 5.4) during 2 weeks of licorice versus −0.3 mmHg (95% CI −1.8 to 1.3) during the control period (P = 0.018) (af Geijerstam et al., 2024); pooled change from baseline +5.45 mmHg systolic (95% CI 3.51 to 7.39), no control group (Penninkilampi et al., 2017).

Low Potassium and Severe Pseudohyperaldosteronism ⚠️ Conflicted

Cortisol-activated kidney receptors also excrete potassium: the meta-analysis found potassium, renin (a kidney enzyme), and aldosterone fell (Penninkilampi et al., 2017), confirmed in Epstein’s and Bernardi’s trials (Epstein et al., 1977; Bernardi et al., 1994). Hukkanen saw low potassium only with added thiazide (a urine-increasing diuretic) (Hukkanen et al., 2009); a low-dose trial found none (Petramfar et al., 2020). Case reports document arrhythmias and paralysis (Ceccuzzi et al., 2023); one man died (Edelman et al., 2020). Net reading: potassium loss is reversible and becomes severe mainly with sustained high intake.

Magnitude: Plasma potassium pooled change from baseline −0.33 mmol/L (the abstract prints the 95% CI as −0.42 to 0.23), no control group (Penninkilampi et al., 2017); low potassium in 2 of 10 volunteers with licorice plus hydrochlorothiazide versus 0 of 10 with licorice alone (Hukkanen et al., 2009).

Medium 🟥 🟥

Harm to Pregnancy and Offspring

In Finnish studies, heavy maternal glycyrrhizin intake (at least 500 mg/week) was linked to preterm birth (Strandberg et al., 2002) and, in a Helsinki birth cohort (a group followed from birth) examined at age 12, to lower IQ (intelligence quotient), poorer memory, more ADHD (attention-deficit/hyperactivity disorder) problems, and earlier puberty in girls (Räikkönen et al., 2017). The proposed mechanism is blocked placental 11β-HSD2, exposing the fetus to maternal cortisol. Data are observational from one research network.

Magnitude: Early preterm birth (under 34 weeks) odds ratio (OR, relative odds versus lower intake) 3.07 (95% CI 1.17 to 8.05) (Strandberg et al., 2002); IQ 7 points lower (95% CI 3.1 to 11.2) versus children of mothers consuming 249 mg/week or less (Räikkönen et al., 2017).

Low 🟥

Lower Testosterone in Men ⚠️ Conflicted

Licorice 7 g/day, proposed to block testosterone-producing enzymes, lowered serum testosterone in healthy men within a week in an uncontrolled study (Armanini et al., 2003), but two salivary-testosterone replication attempts found no fall (Josephs et al., 2001). Net reading: a possible modest, reversible drop at high glycyrrhizin doses remains unconfirmed.

Magnitude: Total testosterone −26% after one week (no control group) (Armanini et al., 2003).

Fluid Retention and Cardiac Strain

Sodium retention can cause edema (tissue swelling) and cardiac strain, seen mainly in uncontrolled case reports (Ceccuzzi et al., 2023). In the Swedish trial, NT-proBNP (a heart-strain blood marker) rose only in the quarter with strongest hormone suppression (af Geijerstam et al., 2024), a subgroup finding.

Magnitude: NT-proBNP +204.1% during licorice versus +72.4% during control in that quarter (P = 0.016) (af Geijerstam et al., 2024).

Speculative 🟨

Stimulation of Hormone-Sensitive Tissues

Licorice has estrogen-like activity (Sabbadin et al., 2019), partly from liquiritigenin (ADDF). Relevance to breast or endometrial cancer risk is untested; the basis is mechanistic only.

Risk-Modifying Factors

  • Genetic polymorphisms and gut bacteria: No validated gene variant predicts risk; some people’s gut bacteria turn glycyrrhizin into 3-epi-glycyrrhetinic acid, which resists liver clearance and accumulates, explaining toxicity at low doses (Yoshino & Makino, 2026).
  • Baseline biomarkers: Low-normal potassium and low albumin raise risk; low albumin increases free glycyrrhetinic acid reaching the kidney (Yoshino & Makino, 2026).
  • Sex: Women reported more symptoms than men at the same dose (Sigurjonsdottir et al., 2003), although a review of 104 case reports did not identify female sex as a risk factor (Ceccuzzi et al., 2023).
  • Pre-existing health conditions: Hypertension amplified the systolic rise (15.3 versus 3.5 mmHg) (Sigurjonsdottir et al., 2003); slow gut transit allows accumulation (Ploeger et al., 2001); heart and kidney disease raise risk (NCCIH).
  • Age: Declining 11β-HSD2 activity and kidney excretion may make older adults more susceptible (Yoshino & Makino, 2026), yet old age was not a risk factor in 104 case reports (Ceccuzzi et al., 2023).

Key Interactions & Contraindications

Prescription drugs:

  • Thiazide and loop diuretics (urine-increasing medicines: hydrochlorothiazide, indapamide, furosemide): Avoid with glycyrrhizin-containing forms (loop diuretics theoretical); additive potassium loss. Hydrochlorothiazide plus licorice caused low potassium in 2 of 10 volunteers within a week (Hukkanen et al., 2009). Weekly potassium checks are usual when combined.
  • Corticosteroids (anti-inflammatory steroid medicines: prednisolone, hydrocortisone): Caution; oral glycyrrhizin increased prednisolone exposure and slowed its clearance (Chen et al., 1991), intensifying steroid effects and potassium loss. Blood pressure and potassium are typically monitored.
  • CYP3A4-cleared drugs (midazolam, alprazolam, simvastatin): Monitor; 14 days of glycyrrhizin lowered midazolam exposure about 23% (Tu et al., 2010), risking reduced effect. Effects on other drugs cleared by this enzyme are extrapolated (theoretical); a glycyrrhizin-depleted extract showed no relevant interaction (Liu et al., 2023).
  • Digoxin and QT-prolonging antiarrhythmics (heart-rhythm medicines: digoxin, sotalol, amiodarone): Avoid (theoretical); licorice-induced low potassium raises digoxin toxicity and arrhythmia risk with drugs that prolong the QT interval (the heart’s electrical recovery time). Potassium is typically checked before and during use.
  • P-glycoprotein substrates (drugs pumped out of cells by the P-glycoprotein transporter: talinolol, dabigatran, digoxin): No interaction found; 6 days of glycyrrhizin left talinolol exposure unchanged (Yan et al., 2013), so no transporter-related effect is expected. Digoxin’s separate potassium-related risk still applies.
  • Antihypertensives (blood-pressure medicines: lisinopril, amlodipine, losartan): Caution (theoretical); glycyrrhizin’s salt retention opposes blood-pressure lowering, and hypertensive patients show larger rises (Sigurjonsdottir et al., 2003). Home blood pressure is typically rechecked within 2 weeks.
  • Mineralocorticoid antagonists (aldosterone-blocking diuretics: spironolactone, eplerenone): Caution; licorice reduced spironolactone’s renin-aldosterone activation and volume-depletion symptoms in women with PCOS (Armanini et al., 2007), implying blunted diuretic and blood-pressure effects.
  • CYP2C9-cleared drugs (warfarin, glipizide): Monitor (theoretical); licorice extracts inhibited CYP2C9 (a warfarin-metabolizing enzyme) in laboratory assays (Li et al., 2017), possibly raising bleeding risk; a human study found no clinically relevant tolbutamide interaction (Liu et al., 2023). INR (a clotting test) is typically monitored.
  • Estrogen-containing therapies (ethinyl estradiol, conjugated estrogens): Caution (theoretical); estrogen-like flavonoids may add to or compete with hormonal effects. No human interaction study exists.

Over-the-counter medications:

  • Proton-pump inhibitors (stomach-acid reducers: omeprazole, esomeprazole): Monitor; glycyrrhizin 150 mg twice daily for 14 days lowered omeprazole levels through CYP3A4 induction (Tu et al., 2010), possibly reducing acid control.
  • Stimulant laxatives (bisacodyl, senna): Avoid regular combination (theoretical); additive potassium loss raises arrhythmia and muscle-weakness risk.
  • NSAIDs (nonsteroidal anti-inflammatory drugs: ibuprofen, naproxen): Caution (theoretical); both promote sodium retention, adding to blood-pressure rise.

Supplements:

  • Other glycyrrhizin sources (licorice tea, candy, Kampo formulas such as shakuyakukanzoto): Avoid stacking; glycyrrhizin doses add up, and two Kampo (Japanese herbal medicine) formulas together caused severe low potassium (Arai et al., 2023).
  • Stimulant-laxative herbs (senna, cascara, aloe latex): Avoid regular combination (theoretical); additive potassium loss.
  • Blood-pressure-raising supplements (caffeine, bitter orange, yohimbine): Caution (theoretical); additive blood-pressure rise, typically tracked with home readings.
  • Diuretic herbs (dandelion leaf, horsetail): Caution (theoretical); additive potassium and fluid shifts.
  • Estrogenic botanicals (red clover, soy isoflavones, hops): Caution (theoretical); additive estrogen-like activity.

Other interventions:

  • High-sodium diet: Caution; salt intake worsens glycyrrhizin’s adverse effects (NCCIH). Lowering sodium reduces the blood-pressure rise.
  • Prolonged heavy sweating (endurance exercise in heat): Caution (theoretical); sweat potassium losses add to licorice losses, raising cramp and rhabdomyolysis risk.

Populations who should avoid Licorice Root:

  • Pregnant women: heavy intake of at least 500 mg glycyrrhizin per week was linked to preterm birth (Strandberg et al., 2002) and offspring harm (Räikkönen et al., 2017); about 250 g licorice per week is considered unsafe in pregnancy (NCCIH)
  • People with hypertension, heart conditions, or kidney conditions (glycyrrhizin-containing forms) (NCCIH)
  • People with existing low potassium or on potassium-wasting diuretics (Hukkanen et al., 2009)
  • People with low blood albumin, such as advanced cirrhosis (Yoshino & Makino, 2026)
  • People with hormone-sensitive cancers (theoretical)

Risk Mitigation Strategies

Doses, timings, and thresholds below follow common practice unless cited.

  • Glycyrrhizin-depleted forms for digestive goals: Deglycyrrhizinated or flavonoid-dominated extracts did not raise blood pressure (Wu et al., 2024), preventing hypertension and potassium loss.
  • Cap on total glycyrrhizic acid: Common practice keeps intake below 100 mg/day, the level judged unlikely to harm most adults (JECFA), and lower with hypertension, since 100 mg/day still raised pressure (af Geijerstam et al., 2024).
  • Counting every source: A licorice tea serving held 46 mg glycyrrhizic acid and capsules up to 29.7 mg (ConsumerLab); tallying candy, tea, and formulas prevents unintended overdose.
  • Early blood pressure and potassium checks: Daily home readings for 2 weeks, when the rise plateaus (Sigurjónsdóttir et al., 2001), and a potassium test at 2 to 4 weeks catch pseudohyperaldosteronism early.
  • Stop thresholds: Common stop points are potassium below 3.5 mmol/L or a home systolic rise of 10 mmHg or more above baseline, preventing arrhythmia and sustained hypertension.
  • Stopping with warning symptoms: Muscle weakness, cramps, palpitations, or swelling preceded severe cases (Ceccuzzi et al., 2023); stopping and seeking evaluation prevents progression to paralysis or cardiac events.
  • Limited whole-root courses: Glycyrrhizin-containing forms are commonly used in 4- to 6-week courses with breaks, limiting cumulative accumulation and blood-pressure effects.
  • Lower sodium and higher potassium intake: Reducing salt limits glycyrrhizin’s adverse effects (NCCIH); potassium-rich foods offset part of the potassium loss.
  • Avoidance during pregnancy: Abstaining prevents the preterm-birth and offspring risks linked to heavy intake (Räikkönen et al., 2017).

Therapeutic Protocol

Timing, cycling, titration, and other parameters below reflect common practice unless cited.

  • Conventional approach: NCCIH finds insufficient high-quality evidence for any condition and considers deglycyrrhizinated oral products possibly safe for up to 4 months (NCCIH); conventional practice limits glycyrrhizin.
  • Traditional and integrative approach: Licorice is a standard ingredient of Kampo and Chinese multi-herb formulas, where pseudohyperaldosteronism is the recognized limiting effect (Yoshino & Makino, 2026).
  • Whole-root extract: 1 g/day for 12 weeks (Rostamizadeh et al., 2022) or 2 g/day for 2 months (Hajiaghamohammadi et al., 2012) for fatty liver; 330 mg three times daily for hot flashes (Nahidi et al., 2012).
  • Low-glycyrrhizin extract (GutGard): 75 mg twice daily for indigestion (Raveendra et al., 2012); 150 mg once daily for H. pylori (Puram et al., 2013); popularized by its developer, Natural Remedies of Bangalore.
  • Chewable deglycyrrhizinated licorice: 760 mg three times daily was the regimen in the gastric-ulcer trial (Engqvist et al., 1973); integrative practitioners use chewable tablets before meals for reflux.
  • Licorice flavonoid oil: 300 mg/day (Kinoshita et al., 2021) up to 900 mg/day (Tominaga et al., 2009), an ingredient developed by Kaneka.
  • Topical gargle: 0.5 g licorice in 30 mL water, gargled 5 minutes before anesthesia (Agarwal et al., 2009; Ruetzler et al., 2013).
  • Time of day: Digestive extracts are taken before or with meals; no study has compared morning and evening dosing of any form.
  • Half-life: Glabridin’s half-life is about 10 hours (Aoki et al., 2007); glycyrrhetinic acid recycles through bile, so effects outlast dosing and accumulate with slow gut transit (Ploeger et al., 2001).
  • Single or split dosing: Most trials split doses two or three times daily; flavonoid oil was taken once daily and reached stable blood levels within 2 weeks (Aoki et al., 2007).
  • Genetic polymorphisms: No pharmacogenetic dosing guide exists; CYP2C19 genotype did not alter glycyrrhizin’s metabolic effect (Tu et al., 2010), and the gut-bacteria accumulation trait cannot be tested routinely.
  • Sex differences: Women reported more symptoms at the same glycyrrhizin dose (Sigurjonsdottir et al., 2003); men face possible testosterone lowering at high doses (Armanini et al., 2003).
  • Age: Older adults may be more sensitive to glycyrrhizin (Yoshino & Makino, 2026), though a case-report review found no age effect (Ceccuzzi et al., 2023); glycyrrhizin-depleted forms and lower whole-root doses are common choices after 60.
  • Baseline biomarkers: Elevated blood pressure or low-normal potassium favors glycyrrhizin-depleted forms; elevated ALT or a positive H. pylori test marks the populations in which trials found effects.
  • Pre-existing conditions: Hypertension, heart disease, and kidney disease restrict use to glycyrrhizin-depleted forms; indigestion, reflux, and fatty liver are the conditions most studied.

Discontinuation & Cycling

  • Short-term, not lifelong: Trials ran 4 to 26 weeks, and none supports lifelong glycyrrhizin intake; deglycyrrhizinated products are considered possibly safe for up to 4 months (NCCIH).
  • Withdrawal effects: No withdrawal syndrome is described, but benefits fade; hot flashes returned 2 weeks after stopping (Nahidi et al., 2012).
  • Reversal of adverse effects: Testosterone returned to baseline after stopping (Armanini et al., 2004); blood pressure and potassium normalize after discontinuation (Ceccuzzi et al., 2023).
  • Tapering: Not required; glycyrrhizin-related toxicity is managed by stopping abruptly and correcting potassium (Ceccuzzi et al., 2023).
  • Cycling: Glycyrrhizin-containing forms are commonly used in 4- to 6-week blocks with 2- to 4-week breaks; no trial tested whether cycling preserves efficacy.

Sourcing and Quality

  • Glycyrrhizin content varies widely: ConsumerLab found 23.8 to 29.7 mg glycyrrhizic acid per serving in root capsules, 14.5 to 31.6 mg in candies, 46 mg in tea, and under 0.3 to 7.6 mg in deglycyrrhizinated products (ConsumerLab).
  • Deglycyrrhizinated is not always glycyrrhizin-free: Three deglycyrrhizinated products contained more glycyrrhizic acid than expected (ConsumerLab); third-party verification matters for people avoiding glycyrrhizin.
  • Species matters: Glycyrrhiza glabra, Glycyrrhiza uralensis, and Glycyrrhiza inflata differ in flavonoids and drug-enzyme inhibition (Li et al., 2017); quality labels name the species.
  • “Licorice” candy may contain none: Many US licorice-flavored products use anise oil instead (NCCIH), whereas European black licorice often contains real root extract.
  • Standardized extracts: GutGard is standardized to at least 3.5% glabridin and at most 3.0% glycyrrhizin (Raj et al., 2025); licorice flavonoid oil is standardized to glabridin (Aoki et al., 2007).
  • Tested brands and third-party seals: ConsumerLab tested products from Natural Factors, Nature’s Way, NOW, Pure Encapsulations, Swanson, Traditional Medicinals, Vital Nutrients, Panda, and Wiley Wallaby, finding heavy metals generally very low; USP (United States Pharmacopeia) or NSF (NSF International) seals verify contents.

Practical Considerations

  • Time to effect: Sore-throat prevention works the same day; indigestion and reflux relief appeared within 2 weeks (Raj et al., 2025); liver enzymes changed over 8 to 12 weeks; blood-pressure rises peak within 2 weeks (Sigurjónsdóttir et al., 2001).
  • Common pitfalls: Assuming natural means harmless, stacking tea, candy, and supplements, trusting “deglycyrrhizinated” labels without testing, and using licorice for “adrenal fatigue” (a contested diagnosis of stress-related exhaustion) without checking blood pressure and potassium.
  • Regulatory status: In the US, licorice is listed by the Food and Drug Administration (FDA) as a GRAS (generally recognized as safe) flavoring under the federal food regulation 184.1408 (FDA); supplements are not FDA-approved before sale (NCCIH); JECFA set no acceptable daily intake (JECFA).
  • Cost and payer incentives: Licorice products are inexpensive and widely available. Conventional comparators such as acid reducers and hormone therapy are also low-cost, so payer incentives are unlikely to explain the evidence gap; much trial funding comes from extract makers.

Interaction with Foundational Habits

  • Sleep: None established (direct). Glycyrrhizin prolongs cortisol’s tissue action by blocking its inactivation, a theoretical influence on evening arousal, but no trial measured sleep. Taking glycyrrhizin-containing forms earlier in the day is a common precaution without supporting data.
  • Nutrition: Potentiating. High sodium intake worsens glycyrrhizin’s adverse effects (NCCIH), while potassium-rich foods (leafy greens, beans, potatoes) may offset part of the potassium loss (theoretical). Licorice candy adds sugar; digestive extracts are taken with meals, and licorice teas count toward glycyrrhizin intake.
  • Exercise: Potentiating for flavonoid oil, which improved balance alongside a strength program in older women (Kinoshita et al., 2021). Indirect risk for glycyrrhizin forms (theoretical): heavy sweating adds potassium loss, and licorice-related low potassium with a diuretic has caused rhabdomyolysis (Horwitz et al., 2015). No data exist on blunted muscle growth from training.
  • Stress management: Indirect. Glycyrrhizin extends cortisol’s action, which is why it is marketed for “adrenal fatigue,” a contested diagnosis without a validated test. No trial shows improved stress resilience; a glycyrrhetinic acid depression trial is pending (NCT05570110).

Monitoring Protocol & Defining Success

Baseline testing before starting glycyrrhizin-containing licorice covers home blood pressure (a one-week average), serum potassium, kidney function, and any condition-specific marker, such as ALT for fatty liver or a breath test for H. pylori. Deglycyrrhizinated or flavonoid-oil products need only the condition-specific marker and a baseline blood pressure.

Ongoing monitoring follows a set cadence: home blood pressure daily for the first 2 weeks, then weekly; potassium at 2 to 4 weeks, then every 3 months while use continues; condition-specific markers at 8 to 12 weeks. Success means the targeted symptom or marker improves while blood pressure and potassium stay at baseline.

Biomarker Optimal Functional Range Why Measure It? Context/Notes
Home blood pressure No established target; track change from own pre-licorice average Safety check: a sustained rise stops or changes use Seated morning readings; glycyrrhizin rises plateau within 2 weeks (Sigurjónsdóttir et al., 2001)
Serum potassium 3.5 to 5.0 mmol/L (standard reference range) Safety check: a fall stops use Pair with sodium and creatinine; delayed processing can falsely raise potassium; no fasting needed
Plasma renin and aldosterone Within laboratory limits for posture and sodium intake (standard reference range); track suppression from own baseline Expected to change: suppression confirms glycyrrhizin effect Morning, seated sampling; suppression appeared at 100 mg/day (af Geijerstam et al., 2024)
Creatinine and eGFR Within laboratory limits (standard reference range) Safety check: impaired kidney function excludes glycyrrhizin forms eGFR (estimated glomerular filtration rate, a kidney-filtration estimate); baseline, then with potassium checks
ALT Below the laboratory upper limit (standard reference range) Expected to change: falls in fatty liver Fasting not required; repeat at 8 to 12 weeks (Rostamizadeh et al., 2022)
H. pylori breath or stool antigen test No established target; track conversion from a positive to a negative test Expected to change: clearance confirms effect Tested at least 4 weeks after therapy, with acid reducers paused 2 weeks before
Total testosterone (men) Within laboratory limits (standard reference range) Expected to change: a fall at high doses changes use Morning, fasting sample; reported falls are conflicted (Armanini et al., 2003)

Qualitative markers:

  • Digestive comfort (heartburn, bloating, fullness)
  • Hot-flash frequency and severity
  • Swelling of ankles or hands
  • Muscle weakness, cramps, or palpitations
  • Headaches suggesting rising pressure

Emerging Research

  • Glycyrrhizin in prostate cancer: A phase 2 pre-surgery trial (NCT06378346) randomizes 60 men to 75 or 150 mg glycyrrhizin or observation before prostate removal; the primary endpoint is change in PSA (prostate-specific antigen, a tumor marker); completion March 2027. Positive results would give a first human anticancer signal; null results keep anticancer claims preclinical.
  • Glycyrrhetinic acid in depression: A trial of enoxolone (glycyrrhetinic acid) in 80 patients (NCT05570110) measures aldosterone/cortisol ratio, CRP (C-reactive protein, an inflammation marker), blood pressure, and depression. Registered completion (June 2026) has passed; status still reads recruiting, without posted results. Positive results would suggest a mood-related use; null results change nothing here.
  • Multi-herb fatty-liver trial: A phase 2 trial (NCT06798948) tests artichoke, milk thistle, turmeric, and licorice in 100 patients, measuring MRI (magnetic resonance imaging) liver-fat fraction, completion December 2027. A positive result would support combination products but cannot isolate licorice; a null result would weaken the fatty-liver item.
  • Licorice in H. pylori dual therapy: A 374-patient trial (NCT06881524) compares licorice-and-lotus-root powder with low-dose amoxicillin against high-dose amoxicillin. Its registered completion (August 2025) has passed while status still reads not yet recruiting; no results are posted. Positive results would strengthen the H. pylori item; null results would weaken it.
  • Fermented deglycyrrhizinated licorice for nerve damage: A completed trial in 83 diabetic patients (Massoud et al., 2026) improved nerve conduction versus placebo with an enzyme-rich fermented extract; independent replication would be needed before it bears on licorice root itself.
  • Safety thresholds and individual sensitivity: The 2024 Swedish trial (af Geijerstam et al., 2024) and the gut-bacteria accumulation phenotype (Yoshino & Makino, 2026) point to research that could lower the accepted safe intake or identify people who tolerate more.
  • Glabridin metabolic effects: A secondary analysis found licorice candy blunted a CRP rise but improved no metabolic marker (Åstrand et al., 2026), suggesting trials of glabridin-rich, glycyrrhizin-free extracts as the stronger test of metabolic benefit.

Conclusion

Licorice root is a common food flavoring that also acts as a drug. Its main sweet compound changes how the kidneys handle salt and potassium, while its plant pigments calm inflammation in laboratory work.

For health-focused adults, the clearest benefits are local and short-term: soothing a sore throat or mouth sores, and easing indigestion and reflux with extracts that have the sweet compound removed. Smaller, less certain benefits appear for stomach-bacteria control, fatty-liver blood tests, menopausal hot flashes, and slight weight loss. Evidence that licorice slows aging or prevents cancer comes only from animal and cell studies.

The risks are better established than most of the benefits. Regular intake of the sweet compound raises blood pressure and lowers potassium, even at amounts once considered safe, and heavy use has caused dangerous heart rhythms and paralysis. People with high blood pressure, heart or kidney problems, people taking medicines that increase urine output, and pregnant women face the greatest harm; whether older age adds risk remains unsettled. Forms without the sweet compound avoid most of this risk.

The evidence base is thin. Most benefit trials are small, short, and run by single groups, and key digestive and weight-loss data come partly from studies involving the makers of two branded extracts. For people pursuing a longer, healthier life, the sweet compound’s effect on blood pressure outweighs its modest benefits, while purified extracts offer a narrower, safer profile.

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