Deglycyrrhizinated licorice

Licorice/Drug Interactions:

  • GeneralGeneral: As one of the most widely sold herbal medicines, the interaction between licorice herb and the absorption of drugs and other agents has been reviewed (232; 233). The enhancing activity of dipotassium glycyrrhizinate on the intestinal absorption of drugs has been demonstrated in animal and in vitro research (234). The in vivo enhancing-activity of dipotassium glycyrrhizinate in the absorption of drugs is dependent on glycyrrhetinic acid, a hydrolysis product of dipotassium glycyrrhizinate resulting from the action of beta-glucuronidase in intestinal flora. Thus, in general, prescription drugs should be taken one hour before licorice or two hours after licorice. Increased absorption may increase the activities and side effects of some drugs.
  • Adrenal agentsAdrenal agents: Licorice has been used traditionally as a treatment for adrenal insufficiency (83; 84; 85).
  • AlcoholAlcohol: In a case report, concomitant intake of licorice and alcohol plus the adoption of a low carbohydrate diet and a spinning exercise regimen has yielded life-threatening results (235).
  • Aldose reductase inhibitorsAldose reductase inhibitors: Licorice contains isoliquiritigenin, an aldose reductase inhibitor (236).
  • Aldosterone receptor antagonistsAldosterone receptor antagonists: In human research, excess consumption of glycyrrhetinic acid may produce an acquired form of apparent mineralocorticoid excess syndrome, which results in hypokalemia and suppression of the renin-angiotensin-aldosterone system (86; 54; 87; 88; 89; 90; 91; 92). Pseudohyperaldosteronism secondary to licorice use has also been noted in case reports (142; 143; 144; 145; 146).
  • AnalgesicsAnalgesics: In human research, dissolved licorice powder and mixed ingredient herbal diets and formulations containing licorice (e.g. Tsumura TJ-68, shakuyakukanzoto, shao-yao-gan-cao-tang) ameliorated pain associated with cancer, intubation, and muscle cramps (237; 116; 185; 75; 238).
  • Angiotensin converting enzyme (ACE) inhibitorsAngiotensin converting enzyme (ACE) inhibitors: Based on mechanism of action, licorice and ACE inhibitors may have opposite effects on the action of 11 beta-hydroxysteroiddehydrogenase, suggesting the potential for opposite effects in humans.
  • Antiarrhythmic agentsAntiarrhythmic agents: In human research, Chinese licorice preparations (e.g. Zhi Gan Cao Tang) have demonstrated beneficial effects in patients with severe arrhythmias, including the prolongation of P-R and Q-T intervals (94; 110). Therefore, concurrent use may result in diminished effects of antiarrhythmic medications.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Anecdotally, the coadministration of licorice and various other herbs as part of the traditional herbal mixture, Ankaferd blood stopper (ABS), has been used to stop bleeding. In postsurgical dental patients with increased bleeding tendency, ABS effectively controlled bleeding in most cases (239). In humans, fecal blood loss induced by oral aspirin was reduced DGL was given with each aspirin dose (67). In patients with idiopathic thrombocytopenic purpura, the coadministration of recombinant roasted licorice decoction (RRLD) and low-dose glucocorticoids increased the number of thrombocytes vs. glucocorticoids alone (240). The licorice derivative isoliquiritigenin has been found to have in vitro anti-platelet activity (38).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIsAntidepressant agents, monoamine oxidase inhibitors (MAOIs): In animal research, the antidepressant-like effect of licorice extract may be due to an increase of brain norepinephrine and dopamine, but not due to an increase of serotonin (100). Thus, licorice may have additive effects with antidepressant agents. Theoretically, some licorice constituents may inhibit MAO effects, thereby increasing the effects of MAOIs.
  • Antidepressant agents, selective serotonin reuptake inhibitors (SSRIs)Antidepressant agents, selective serotonin reuptake inhibitors (SSRIs): In animal research, the antidepressant-like effect of licorice extract may be due to an increase of brain norepinephrine and dopamine, but not due to an increase of serotonin (100). Thus, licorice may have additive effects with antidepressant agents. Theoretically, licorice may interact with SSRIs.
  • Antidiabetic agentsAntidiabetic agents: In animals, licorice increased or decreased blood glucose (194; 195).
  • AntiemeticsAntiemetics: In case reports and clinical trials, gastric discomfort, poor appetite, nausea, vomiting, and loose stools have been associated with the consumption of licorice, foods high in glycyrrhizic acid, or DGL (157; 87; 65; 35; 10; 66).
  • AntihypertensivesAntihypertensives: In human research, licorice may increase blood pressure (132; 163; 150), although in some research decreased systolic blood pressure has been observed (113; 114). In human research, a combination of licorice and spironolactone reduced the blood pressure-lowering effect of spironolactone (115).
  • Anti-inflammatory agentsAnti-inflammatory agents: In cellular, animal, and human research, licorice alone, its bioactive constituents, or coadministered with other herbs (e.g. TJ-109), has demonstrated anti-inflammatory effects (29; 241; 242; 99). In a preliminary scientific study, beta-glycyrrhetinic acid, the aglycone derivative of glycyrrhizin, inhibited human complement activity (82). In vitro, glycyrrhizin decreased neutrophil-generated O2, H2O2 and OH in a dose-dependent manner, exerting anti-inflammatory actions in some but not all studies (243; 244). Based on in vitro research, the inhibition of hydrocortisone metabolism by 11 beta-HSD may partially explain the known anti-inflammatory actions of orally administered glycyrrhetinic acid (245).
  • Antilipemic agentsAntilipemic agents: In animal and human research, licorice alone or as part of a polyherbal formulation was shown to have hypocholesterolemic effects (246; 113; 114; 247).
  • Antimicrobial agentsAntimicrobial agents: Licorice contains constituents such as glabridin, glabrol, and 3-hydroxyglabrol, which possess antimicrobial activity in vitro (248).
  • Antineoplastic agentsAntineoplastic agents: In vitro, licorice and several of its bioactive constituents (e.g. glycyrrhetinic acid, dibenzoylmethane, glabridin) have demonstrated anti-cancer effects, including cytotoxicity, angiogenesis inhibition, and modulation of cancer cell signaling (249; 9; 250). In human ressearch, a combination product including licorice was used to reduce PSA levels (7). In animal research, the administration of a licorice extract significantly inhibited tumor growth in BALB/C mice inoculated with CT-26 colon cancer cells (251).
  • Antiobesity agentsAntiobesity agents: A dose of 3.5g licorice daily reduced body fat mass in human research, potentially due to the inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 at the level of fat cells (120). However, in other human research, licorice flavonoids (GlavonoidT) lacked effect on anthropometric variables (108).
  • Antiulcer agentsAntiulcer agents: Traditionally, licorice has been used for ulcer symptom reduction. In human research, oral licorice patches have demonstrated a greater percentage reduction in ulcer size and reductions in the diameter of necrosis, although its effects on pain symptoms have been contradictory (121; 122).
  • Antiviral agentsAntiviral agents: In cellular, animal, and human research, licorice and its bioactive constituents have demonstrated antiviral effects against a variety of microorganisms (4). In human research, glycyrrhizin may inhibit HIV-1 replication (106). In vitro, glycyrrhizin was shown to bind to hepatocytes modifying the expression of hepatitis B virus-related agents on the hepatocytes and suppressing sialylation of hepatitis B surface antigen (252). In vitro, glycyrrhizic acid inhibited the replication of the Epstein-Barr virus (253).
  • BenzodiazepinesBenzodiazepines: Licorice is used in patients undergoing withdrawal from benzodiazepines (254).
  • Cardiac glycosides, digoxinCardiac glycosides, digoxin: Theoretically, concurrent use of licorice and cardiac glycosides may increase the risk of hypokalemia.
  • Cardiovascular agentsCardiovascular agents: In human research, the coadministration of glycyrrhiza, ginseng, and oriental bezoar as part of a traditional Kampo formulation potentiated parasympathetic nervous activity, as evidenced by increased HF power (high frequency component in heart rate variability [HRV]) and decreased heart rate (255; 256). In experimental models of ocular neovascularization, licorice root-derived isoliquiritigenin demonstrated antiangiogensis effects (257).
  • CisplatinCisplatin: In animal research, a combination of licorice and cisplatin diminished the therapeutic efficacy of cisplatin (251). Thus, this combination should be avoided.
  • CorticosteroidsCorticosteroids: In case reports, licorice raised blood levels in persons taking oral corticosteroids and increased hydrocortisone activity (93; 94; 95; 88; 96). Based on observation in rat liver, the administration of glycyrrhetinic acid or glycyrrhizin may suppress the activity of 5(-reductase and may result in a delay in the clearance of corticosteroids and a prolonged half-life of cortisol (258). In humans, oral administration of glycyrrhizin increased the plasma prednisolone concentrations and influenced its pharmacokinetics by inhibiting its metabolism, but not by affecting its distribution (94). In patients with Addison's disease, licorice increased the median area under the curve for serum cortisol for up to 2.6 hours post-ingestion of cortisone acetate and increased the median urinary cortisol: cortisone ratio (259). Cortisone and licorice have shown synergistic actions in patients with Addison's and Simmond's diseases, according to a case report (260).
  • Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: In laboratory research, constituents of licorice have been isolated that have inhibited the cytochrome P450 enzyme (261). However, other preclinical and clinical research has suggested that glycyrrhizin modestly induces CYP3A (101; 102).
  • Dental and periodontal agentsDental and periodontal agents: In human research, a licorice-containing starch gel lacked effect on dental plaque or oral bacterial growth (22). In other preclinical and clinical research, licorice extract alone or coadministered with conventional dental agents has demonstrated antibacterial and anticaries effects (6; 262; 263; 264).
  • Dermatologic agentsDermatologic agents: In human research, a licorice containing gel and mixed ingredient TCM formulations containing licorice (e.g. Zemaphyte) have demonstrated some efficacy at reducing symptoms of dermatitis (105; 265; 266; 218; 267). Beneficial symptom-reducing and disease-modifying effects have also been observed for the treatment of melasma (172) and psoriasis (268).
  • DiureticsDiuretics: Concurrent use of licorice and diuretics may lead to additive electrolyte effects and toxicity. A case of licorice-induced hypokalemic myopathy precipitated with concurrent use of bendrofluazide was reported (74). In a separate case report, hypokalemic rhabdomyolysis occurred with myoglobulinuria, due to licorice ingestion and diuretic treatment (269). In human research, the coadministration of licorice and hydrochlorothiazide significantly increased the risk of hypokalemia vs. licorice alone, as indicated by decreased plasma potassium level, increased plasma renin activity, and reduced weight (270).
  • Gastrointestinal agentsGastrointestinal agents: In animal and preliminary human research, DGL may reduce gastric bleeding caused by aspirin; human fecal blood loss induced by aspirin was less when DGL was also provided in combination with aspirin (67). In human research, TJ-68, containing licorice constituents, inhibited colonic spasms during colonoscopy (3).
  • HepatotoxinsHepatotoxins: In animal research, glycyrrhizic acid was protective against carbon tetrachloride-induced liver injury (271). In human research, licorice root decreased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in individuals with non-alcoholic fatty liver disease (NAFLD) (107).
  • Hormonal agentsHormonal agents: In human study, licorice alone, its constituents, or in combination with other herbs (e.g. peony) have reduced testosterone (60; 221; 63) and prolactin hormone levels (222; 272) and increased serum parathyroid hormone (273). Licorice has demonstrated estrogenic effects, including interaction with the estrogen receptor and enhancement of endogenous estrogen activity (64). Beta-glycyrrhetinic acid has been previously reported to have anti-estrogenic activity (223). In human research, licorice and its constituents may increase the risk of swelling and hypertension when taken with estrogen hormonal agents (104; 224).
  • ImmunomostimulantsImmunomostimulants: In human research, a licorice herbal tincture stimulated immune cells as quantified by CD69 expression on CD4 and CD8 T cells (17). In preliminary scientific research, beta-glycyrrhetinic acid, the aglycone derivative of glycyrrhizin, inhibited human complement activity (82).
  • InsulinInsulin: Theoretically, licorice and insulin may be synergistic in lowering serum potassium and levels should be monitored.
  • InterferonsInterferons: In human research, the licorice component glycyrrhizin may enhance the effectiveness of interferon used in treating hepatitis C (274).
  • Iron saltsIron salts: In human research, licorice promoted the absorption of iron (275).
  • Kayexalate (sodium polystyreneKayexalate (sodium polystyrene): Theoretically, licorice and kayexalate may be synergistic in lowering serum potassium and levels should be monitored.
  • LaxativesLaxatives: Theoretically, the concurrent use of licorice and laxatives may lead to additive hypokalemia.
  • LithiumLithium: Anecdotal reports have mentioned the possibility of an interaction between lithium and licorice.
  • Nephrotoxic agentsNephrotoxic agents: In a case study, a patient with a history of anorexia nervosa developed licorice-induced hypokalemic myopathy and hypokalemic renal tubular damage (103).
  • NitrofurantoinNitrofurantoin: In human research, a combination of licorice and nitrofurantoin resulted in lower side effects and a lack of effect on urinary recovery (276). It has been noted anecdotally that DGL may increase bioavailability of nitrofurantoin by 50%. However, it has also been noted that licorice may increase the excretion of nitrofurantoin.
  • Nonsteroidal anti-inflammatory agents (NSAIDs)Nonsteroidal anti-inflammatory agents (NSAIDs): In humans, fecal blood loss induced by oral aspirin was reduced when DGL was given with each aspirin dose (67). The licorice derivative isoliquiritigenin has been found to have in vitro anti-platelet activity (38).
  • PhosphatesaltsPhosphatesalts: Based on anecdotal reports, phosphate salts increased licorice absorption.
  • Potassium depleting agentsPotassium depleting agents: In human research and case reports, licorice may have additive effects with other agents that lower blood potassium levels (54; 55; 37; 36).
  • QT prolonging agents (Loratadine, Terfenadine)QT prolonging agents (Loratadine, Terfenadine): In human research, a Chinese licorice preparation has been reported to prolong P-R and Q-T intervals (94).
  • Ursodeoxycholic acidUrsodeoxycholic acid: In human research, a combination of glycyrrhizin and ursodeoxycholic acid (UDCA) resulted in a greater decrease in AST compared with glycyrrhizin alone (277).

    • Licorice/Herb/Supplement Interactions:

  • GeneralGeneral: As one of the most widely sold herbal medicines, the interaction between licorice herb and the absorption of drugs and other agents has been reviewed (232; 233).
  • Adrenal herbs and supplementsAdrenal herbs and supplements: Licorice has been used traditionally as a treatment for adrenal insufficiency (83; 84; 85).
  • Aldose reductase inhibitorsAldose reductase inhibitors: Licorice contains isoliquiritigenin, an aldose reductase inhibitor (236).
  • Aldosterone receptor antagonistsAldosterone receptor antagonists: In human research, excess consumption of glycyrrhetinic acid may produce an acquired form of apparent mineralocorticoid excess syndrome, which results in hypokalemia and suppression of the renin-angiotensin-aldosterone system (86; 54; 87; 88; 89; 90; 91; 92). Pseudohyperaldosteronism secondary to licorice use has also been reported in case reports (142; 143; 144; 145; 146).
  • AnalgesicsAnalgesics: In human research, dissolved licorice powder and mixed ingredient herbal diets and formulations (e.g. Tsumura TJ-68, shakuyakukanzoto, shao-yao-gan-cao-tang) containing licorice ameliorated pain associated with cancer, intubation, and muscle cramps (237; 116; 185; 75; 238).
  • Angiotensin converting enzyme (ACE) inhibitorsAngiotensin converting enzyme (ACE) inhibitors: Based on mechanism of action, licorice and ACE inhibitors may have opposite effects on the action of 11 beta-hydroxysteroiddehydrogenase suggesting the potential for opposite effects in humans.
  • AntiarrhythmicsAntiarrhythmics: In human research, Chinese licorice preparations (e.g. Zhi Gan Cao Tang) have demonstrated beneficial effects in patients with severe arrhythmias, including the prolongation of P-R and Q-T intervals (94; 110). Therefore, concurrent use may result in diminished effects of antiarrhythmic agents.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Anecdotally, the coadministration of licorice and various other herbs as part of the traditional herbal mixture, Ankaferd blood stopper (ABS), has been used to stop bleeding. In postsurgical dental patients with increased bleeding tendency, ABS effectively controlled bleeding in most cases (239). In humans, fecal blood loss induced by 975mg oral aspirin given three times daily was reduced when 350mg DGL was given with each aspirin dose (67). In patients with idiopathic thrombocytopenic purpura, the coadministration of recombinant roasted licorice decoction (RRLD) and low-dose glucocorticoids increased the number of thrombocytes vs. glucocorticoids alone (240). The licorice derivative isoliquiritigenin has been found to have in vitro anti-platelet activity (38).
  • Antidepressant herbs and supplements, monoamine oxidase inhibitors (MAOIs)Antidepressant herbs and supplements, monoamine oxidase inhibitors (MAOIs): In animal research, the antidepressant-like effect of licorice extract may be due to an increase of brain norepinephrine and dopamine, but not due to an increase of serotonin (100). Thus, licorice may have additive effects with antidepressant agents. Theoretically, some licorice constituents may inhibit MAO effects, thereby increasing the effects of MAOIs.
  • Antidepressant herbs and supplements, selective serotonin reuptake inhibitors (SSRIs)Antidepressant herbs and supplements, selective serotonin reuptake inhibitors (SSRIs): In animal research, the antidepressant-like effect of licorice extract may be due to an increase of brain norepinephrine and dopamine, but not due to an increase of serotonin (100). Thus, licorice may have additive effects with antidepressant agents. Theoretically, licorice may interact with SSRIs.
  • AntiemeticsAntiemetics: In case reports and clinical trials, gastric discomfort, poor appetite, nausea, vomiting, and loose stools have been associated with the consumption of licorice, foods high in glycyrrhizic acid, or DGL (157; 87; 65; 35; 10; 66).
  • Anti-inflammatory herbs and supplementsAnti-inflammatory herbs and supplements: In cellular, animal, and human research, licorice alone, its bioactive constituents, or coadministered with other herbs (e.g. TJ-109), has demonstrated anti-inflammatory effects (29; 241; 242; 99). In preliminary scientific research, beta-glycyrrhetinic acid, the aglycone derivative of glycyrrhizin, inhibited human complement activity (82). In vitro, glycyrrhizin decreased neutrophil-generated O2, H2O2 and OH in a dose-dependent manner, exerting anti-inflammatory actions in some but not all studies (243; 244). Based on in vitro research, the inhibition of hydrocortisone metabolism by 11 beta-HSD may partially explain the known anti-inflammatory actions of orally administered glycyrrhetinic acid (245).
  • AntilipemicsAntilipemics: In animal and human research, licorice alone or as part of a polyherbal formulation was shown to have hypocholesterolemic effects (246; 113; 114; 247).
  • AntimicrobialsAntimicrobials: Licorice contains constituents such as glabridin, glabrol, and 3-hydroxyglabrol, which possess antimicrobial activity in vitro (248).
  • AntineoplasticsAntineoplastics: In vitro, licorice and several of its bioactive constituents (e.g. glycyrrhetinic acid, dibenzoylmethane, glabridin) have demonstrated anti-cancer effects, including cytotoxicity, angiogenesis inhibition, and modulation of cancer cell signaling (249; 9; 250). In human research, a combination product including licorice was used to reduce PSA levels (7). In animal research, the administration of a licorice extract significantly inhibited tumor growth in BALB/C mice inoculated with CT-26 colon cancer cells (251).
  • Antiobesity herbs and supplementsAntiobesity herbs and supplements: A dose of 3.5g licorice daily reduced body fat mass in human research, potentially due to the inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 at the level of fat cells (120). However, in other human research, licorice flavonoids (GlavonoidT) lacked effect on anthropometric variables (108).
  • AntioxidantsAntioxidants: Antioxidant constituents have been isolated from the roots and stolons of licorice (278). In cellular and animal research, licorice was shown to have antioxidant effects (279; 246). In human research, supplementation with licorice root extract or a methanol extract of glycyrrhizin-free licorice root containing glabridin has been shown to reduce plasma susceptibility to oxidation, decrease oxidative stress level and plasma low-density lipoprotein (LDL) oxidation, and increase plasma LDL resistance to oxidation, aggregation, and retention (1; 2; 114).
  • Antiulcer and gastric acid-reducing herbs and supplementsAntiulcer and gastric acid-reducing herbs and supplements: Traditionally, licorice has been used for ulcer symptom reduction. In human research, oral licorice patches have demonstrated a greater percentage reduction in ulcer size and reductions in the diameter of necrosis, although its effects on pain symptoms have been contradictory (121; 122).
  • Antiviral herbs and supplementsAntiviral herbs and supplements: In cellular, animal, and human research, licorice and its bioactive constituents have demonstrated antiviral effects against a variety of microorganisms (4). In human research, glycyrrhizin may inhibit HIV-1 replication (106). In vitro, glycyrrhizin was shown to bind to hepatocytes modifying the expression of hepatitis B virus-related agents on hepatocytes and suppressing sialylation of hepatitis B surface antigen (252). In vitro, glycyrrhizic acid inhibited the replication of the Epstein-Barr virus (253).
  • Cardiac glycosidesCardiac glycosides: Theoretically, the concurrent use of licorice and cardiac glycosides may increase the risk of hypokalemia.
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: In human research, the coadministration of glycyrrhiza, ginseng, and oriental bezoar as part of a traditional Kampo formulation potentiated parasympathetic nervous activity, as evidence by increased HF power (high frequency component in heart rate variability [HRV]) and decreased heart rate (255; 256). In experimental models of ocular neovascularization, licorice root-derived isoliquiritigenin demonstrated antianiogenesis effects (257).
  • Cytochrome P450 metabolized herbs and supplementsCytochrome P450 metabolized herbs and supplements: In laboratory research, constituents of licorice have been isolated that have inhibited the cytochrome P450 enzyme (261). However, other preclinical and clinical research has suggested that glycyrrhizin modestly induces CYP3A (101; 102).
  • Dental and periodontal herbs and supplementsDental and periodontal herbs and supplements: In human research, a licorice-containing starch gel lacked effect on dental plaque or oral bacterial growth (22). In other preclinical and clinical research, licorice extract alone or coadministered with conventional dental agents has demonstrated antibacterial and anticaries effects (6; 262; 263; 264).
  • Dermatological agentsDermatological agents: In human research, a licorice containing gel and mixed ingredient TCM formulations containing licorice (e.g. Zemaphyte) have demonstrated some efficacy at reducing symptoms of dermatitis (105; 265; 266; 218; 267). Beneficial symptom-reducing and disease-modifying effects have also been observed for the treatment of melasma (172) and psoriasis (268).
  • DiureticsDiuretics: Concurrent use of licorice and diuretics may lead to additive electrolyte effects and toxicity. A case of licorice-induced hypokalemic myopathy precipitated with concurrent use of bendrofluazide was reported (74). In a separate case report, hypokalemic rhabdomyolysis occurred with myoglobulinuria, due to licorice ingestion and diuretic treatment. (269). In human research, the coadministration of licorice and hydrochlorothiazide significantly increased the risk of hypokalemia vs. licorice alone, as indicated by decreased plasma potassium level, increased plasma renin activity, and reduced weight (270).
  • Foxglove (Digitalis purpurea)Foxglove (Digitalis purpurea): Theoretically, the concurrent use of licorice and cardiac glycosides may increase the risk of hypokalemia.
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: In animal and preliminary human research, DGL may reduce gastric bleeding caused by aspirin; human fecal blood loss induced by aspirin was less when DGL was also provided (67). In human research, TJ-68, containing licorice constituents, inhibited colonic spasms during colonoscopy (3). In individuals with constipation-dependent irritable bowel syndrome or functional dyspepsia, mixed ingredient herbal formulations containing licorice (e.g. STW 5-II) have improved stool consistency, increased bowel movement frequency, and decreased symptoms of abdominal pain, bloating, and straining (280; 281).
  • Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: In animal research, glycyrrhizic acid was protective against carbon tetrachloride-induced liver injury (271). In human research, licorice root decreased levels of ALT and AST in individuals with NAFLD (107).
  • Hormonal herbs and supplementsHormonal herbs and supplements: In human research, licorice alone, its constituents, or in combination with other herbs (e.g. peony) have reduced testosterone (60; 221; 63) and prolactin hormone levels (222; 272) and increased serum parathyroid hormone (273). Licorice has demonstrated estrogenic effects, including interaction with the estrogen receptor and enhancement of endogenous estrogen activity (64). Beta-glycyrrhetinic acid has been previously reported to have anti-estrogenic activity (223). In human research, licorice and its constituents may increase the risk of swelling and hypertension when taken with estrogen hormonal agents (104; 224).
  • HypoglycemicsHypoglycemics: In animals, licorice increased or decreased blood glucose (194; 195).
  • HypotensivesHypotensives: In human research, licorice may increase blood pressure (132; 163; 150), although in some research decreased systolic blood pressure has been observed (113; 114). In human research, a combination of licorice and spironolactone reduced the blood pressure-lowering effect of spironolactone (115).
  • Immunomomodulatory herbs and supplementsImmunomomodulatory herbs and supplements: In human research, a licorice herbal tincture stimulated immune cells as quantified by CD69 expression on CD4 and CD8 T cells (17). In preliminary scientific research, beta-glycyrrhetinic acid, the aglycone derivative of glycyrrhizin, inhibited human complement activity (82). Thus, licorice may interact with immunomodulatory agents.
  • Iron containing herbs and supplementsIron containing herbs and supplements: In human research, licorice promoted the absorption of iron (275).
  • LaxativesLaxatives: Theoretically, the concurrent use of licorice and laxatives may lead to additive hypokalemia.
  • Nephrotoxic herbs and supplementsNephrotoxic herbs and supplements: In a case study, a patient with a history of anorexia nervosa developed licorice-induced hypokalemic myopathy and hypokalemic renal tubular damage (103).
  • NicotineNicotine: Theoretically, licorice may interact with nicotine.
  • PhosphatesaltsPhosphatesalts: Based on anecdotal reports, phosphate salts have been shown to increase licorice absorption.
  • PhytoestrogensPhytoestrogens: In human research, licorice or its constituents reduced testosterone levels (60; 221). Beta-glycyrrhetinic acid has been previously reported to have anti-estrogenic activity (223). In human research, licorice and its constituents may increase the risk of swelling and hypertension when taken with estrogen hormonal agents (104; 224).
  • Potassium lowering herbs and supplementsPotassium lowering herbs and supplements: In human research and case reports, licorice may have additive effects with other agents that lower blood potassium levels (54; 55; 37; 36).

    • Licorice/Food Interactions:

  • AlcoholAlcohol: In a case report, concomitant intake of licorice and alcohol plus the adoption of a low carbohydrate diet and a spinning exercise regimen has yielded life-threatening results (235).
  • Chewing tobaccoChewing tobacco: Both licorice and chewing tobacco may contain glycyrrhetinic acid or derivatives, which may lead to additive electrolyte imbalances or toxicity (282).
  • GrapefruitGrapefruit: Naringen, found in grapefruit juice, may enhance mineralocorticoid activities of licorice, due to its ability to inhibit 11 beta-hydroxysteroid dehydrogenase activity in human and in vitro research (283; 284).
  • Iron containing foodsIron containing foods: In human research, licorice promoted the absorption of iron (275).
  • Phosphatecontaining foodsPhosphatecontaining foods: Based on anecdotal reports, phosphate salts increased licorice absorption.
  • Potassiumcontaining foodsPotassiumcontaining foods: In human research and case reports, licorice may have additive effects with other agents that lower blood potassium levels (54; 55; 37; 36).
  • SodiumSodium: In human research, the consumption of licorice resulted in sodium retention (214; 219).

    • Licorice/Lab Interactions:

  • 17-hydroxyprogesterone17-hydroxyprogesterone: In human research, licorice increased serum 17-hydroxyprogesterone concentrations (60)
  • Alanine aminotransferase (ALT)Alanine aminotransferase (ALT): In human research, significant reductions were seen in ALT concentrations with licorice use or SNMC injections (10; 36; 35; 126; 107).
  • AlbuminAlbumin: In human research, injection with SNMC normalized of albumin levels (126).
  • AldosteroneAldosterone: In human research, licorice consumption increased plasma aldosterone (219).
  • Alkaline phosphataseAlkaline phosphatase: In human research, licorice was shown to affect ALT, AST, and GTP concentrations (10) and therefore it may be possible that alkaline phosphatase may also be affected.
  • Aspartate aminotransferase (AST)Aspartate aminotransferase (AST): In human research, significant reductions were seen in AST concentrations with licorice use (10; 107).
  • Blood cell countBlood cell count: In human research, treatment with a combination product containing licorice or a licorice decoction resulted in a significant increase in blood cells, as measured by hemoglobin, white blood cell count, and platelets (285; 240). The percentage of CD3 and CD4 were significantly increased and CD8 was reduced.
  • Blood glucoseBlood glucose: In animals, licorice increased or decreased blood glucose (194; 195).
  • Blood ironBlood iron: In human research, licorice promoted the absorption of iron (275).
  • Blood pHBlood pH: In human research, licorice may result in metabolic alkalosis (54; 92).
  • Blood pressureBlood pressure: In human research, licorice may increase blood pressure (132; 163; 150), although in some research decreased systolic blood pressure has been observed (113; 114).
  • Cortisol concentrationCortisol concentration: In case reports, licorice and its constituents raised blood levels in persons taking or not taking oral corticosteroids and to increase hydrocortisone activity (93; 94; 95; 88; 219; 111; 96). In patients with Addison's disease, licorice increased the median area under the curve for serum cortisol for up to 2.6 hours post-ingestion of cortisone acetate and increased the median urinary cortisol: cortisone ratio (259). Based on observation in rat liver, the administration of glycyrrhetinic acid or glycyrrhizin may suppress the activity of 5(-reductase and may result in a delay in the clearance of corticosteroids and a prolonged half-life of cortisol (258).
  • ECGECG: In human research, Chinese licorice preparations (e.g. Zhi Gan Cao Tang) have demonstrated beneficial effects in patients with severe arrhythmias, including the prolongation of P-R and Q-T intervals (94; 110). In human research, the coadministration of glycyrrhiza, ginseng, and oriental bezoar as part of a traditional Kampo formulation potentiated parasympathetic nervous activity, as evidence by increased HF power (high frequency component in heart rate variability [HRV]) and decreased heart rate (255; 256).
  • EstrogenEstrogen: Licorice has demonstrated estrogenic effects, including interaction with the estrogen receptor and enhancement of endogenous estrogen activity (64). In vitro, beta-glycyrrhetinic acid, a constituent of licorice, had anti-estrogenic activity (223).
  • Gamma-glutamyltransferase (GGT)Gamma-glutamyltransferase (GGT): In human research, significant reductions were seen in gamma-GTP concentrations with licorice use (10).
  • Lactate dehydrogenase (LDH)Lactate dehydrogenase (LDH): In human research, licorice was shown to affect ALT, AST, and GTP concentrations (10) and therefore it may be possible that LDH may also be affected.
  • Lipid panelLipid panel: In animal and human research, licorice alone and as part of a polyherbal formulation was shown to have hypocholesterolemic effects (246; 113; 114; 247).
  • Parathyroid hormoneParathyroid hormone: In human research, licorice increased serum parathyroid hormone (273).
  • Plasma reninPlasma renin: In human research, plasma renin decreased following the consumption of licorice candy bars over a seven-year period (92).
  • Plasma sodium concentrationPlasma sodium concentration: In human research, the consumption of licorice resulted in sodium retention (214; 219).
  • Platelet countPlatelet count: The licorice derivative isoliquiritigenin has been found to have in vitro anti-platelet activity (38).
  • PotassiumconcentrationPotassiumconcentration: In case reports and clinical trials, hypokalemia, increased urinary potassium, and decreased plasma potassium has been associated with licorice use (186; 54; 55; 37; 36; 219; 112; 270).
  • ProlactinProlactin: In human research, licorice alone, its constituents, or in combination with other herbs (e.g. peony) have reduced prolactin hormone levels (222; 272).
  • Prothrombin timeProthrombin time: In human research, injection with SNMC resulted in the normalization of prothrombin time (126).
  • TestosteroneTestosterone: In human research, licorice or its constituents reduced testosterone levels (60; 221; 63).
  • Total bilirubinTotal bilirubin: In human research, licorice was shown to affect ALT, AST, and GTP concentrations (10) and therefore it may be possible that total bilirubin may also be affected.
  • Urine outputUrine output: Urine flow rates in glycyrrhizin-treated rats were decreased significantly (286).
  • Viral loadViral load: In cellular, animal, and human research, licorice and its bioactive constituents have demonstrated antiviral effects against a variety of microorganisms (4). Based on human research, glycyrrhizin may inhibit HIV-1 replication (106). In vitro, glycyrrhizin was shown to bind to hepatocytes modifying the expression of hepatitis B virus-related agents on hepatocytes and suppressing sialylation of hepatitis B surface antigen (252). In vitro, glycyrrhizic acid was shown to inhibit the replication of the Epstein-Barr virus (253).