Glycamil

Other Names

(+)-Glycyram18β-Glycyrrhizic Acid Monoammonium Salt3-O-(2-O-β-D-Glucopyranuronosyl-α-D-glucopyranuronosyl)-18β-glycyrrhetinic acid ammonium salt30-NoroleananeAMGZAmmonium GlycyrrhizateAmmonium GlycyrrhizinateGlycyminGlycyron Ammonium SaltGlycyron Monoammonium SaltGlycyrramGlycyrrhizic Acid Ammonium SaltGlycyrrhizic Acid Monoammonium SaltGlycyrrhizinGlycyrrhizin Ammonium SaltGlycyrrhizin Monoammonium SaltGlycyrrhizinateMonoammonium 18β-glycyrrhizinateMonoammonium GlycyrrhizateMonoammonium Glycyrrhizinate

Synopsis

Glycamil (Monoammonium Glycyrrhizinate / Ammonium Glycyrrhizinate)

1. Identity, Nomenclature, and Chemical Nature

Glycamil is a registered trade and common name for Monoammonium Glycyrrhizinate (MAG), the monoammonium salt of glycyrrhizic acid (glycyrrhizin). It is also known by synonyms including Ammonium Glycyrrhizinate, Glycyrram, Monoammonium Glycyrrhizate, Amgz, Ammoniated Glycyrrhizin, Glycyrrhizic Acid Ammonium Salt, and Glycyrrhizic Acid Monoammonium Salt, among others, with a molecular formula of C₄₂H₆₅NO₁₆ and a molecular weight of 840.0 g/mol.

Glycyrrhizin is found in the licorice root of a small leguminous shrub, Glycyrrhiza glabra L., native to Europe and Central Asia. Chemically, glycyrrhizin — or 20-β-carboxy-11-oxo-30-norolean-12-en-3β-yl-2-O-β-D-glucopyranurosyl-α-D-glucopyranosiduronic acid (C₄₂H₆₂O₁₆, MW 822.92) — is a triterpenoide glycoside (saponin) with a glycyrrhetinic acid aglycone condensed with two glucuronic acid residues. Glycamil/MAG is the corresponding monoammonium salt of this compound, formed by combining the free acid with one equivalent of ammonia.

Glycyrrhiza glabra, commonly known as liquorice, contains several bioactive compounds such as flavonoids, sterols, triterpene, and saponins; among which glycyrrhizic acid, an oleanane-type saponin, is the most abundant component in liquorice root. Glycamil is classified as an oleanolic acid-type compound from Glycyrrhiza that has some antiallergic, antibacterial, and antiviral properties; it is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation.

After harvest, the roots are dried to 10% moisture, shredded, extracted with aqueous ammonia, concentrated in vacuum evaporators, precipitated with sulfuric acid, and crystallized with 95% alcohol, providing a crude ammonium glycyrrhizin (AG). This process gives rise to Glycamil as the direct ammonium salt product. Glycyrrhizin as the ammonium salt is soluble in both hot and cold water and is stable in its dry form.

The ammonium salt of glycyrrhizin is approved as a flavoring and flavor enhancer in the USA. Glycyrrhizic acid is extracted from the root of the licorice plant (Glycyrrhiza glabra), and when extracted from the plant, it can be obtained in the form of ammonium glycyrrhizin and mono-ammonium glycyrrhizin. Glycyrrhizic acid has been developed in Japan and China as a hepatoprotective drug in cases of chronic hepatitis, and from January 2014, glycyrrhizic acid as part of the licorice extract was approved by the FDA as an existing food sweetener.

Common Forms and Preparations

Oral pharmaceutical dosage forms: capsules, tablets, and liquid preparations used particularly in Asian clinical settings for liver disease.
Intravenous formulations: Licorice and its extracts, especially glycyrrhizin, can be taken orally, through the skin (in the form of gels and oils), and intravenously.
Topical/cosmetic forms: 18β-glycyrrhetinic acid and its derivatives exhibit a broad spectrum of biological and pharmacological activities relevant to skin applications; the aim of dermatological research has been to characterize the anti-inflammatory, antioxidant and antimicrobial activities applicable in dermatology and cosmetology.
Food ingredient: Glycyrrhizin is used in Japan and other countries as a sweetening agent; in the USA, it is approved for use as a flavor and flavor enhancer.

2. Traditional and Historical Use

The historical record of licorice root — the natural source of Glycamil/monoammonium glycyrrhizinate — extends across multiple ancient civilizations over millennia. Licorice has a history of medicinal and culinary use going back thousands of years in many ancient cultures, including Egypt, China, and India.

Ancient Egypt and the Mediterranean

In ancient times, liquorice roots were a staple in traditional medicine; the ancient Egyptians, including reportedly Cleopatra, used liquorice for its health benefits, believing it could soothe digestive issues and relieve respiratory conditions like bronchitis. It was also described in Assyrian herbals as one of the most essential herbs (c. 2000 BC), and Hippocrates (400 BC) suggested it as a treatment for ulcers and thirst.

Traditional Chinese Medicine (TCM)

Liquorice has a long history of use in traditional Chinese, Ayurvedic, and herbal medicine. Derived from the root of the plant, licorice is used to flavor foods; it is also used in traditional Chinese medicine to detoxify and enhance or balance the effects of other components in herbal formulations. In Traditional Chinese Medicine, liquorice has been a key component, considered to have antiviral and anti-inflammatory properties, and TCM practitioners used it to treat ailments such as gastritis and bronchitis and to enhance the potency of other herbs in complex formulations.

The radices of Glycyrrhiza uralensis Fisch. and herbal preparations containing Glycyrrhiza spp. have been used for thousands of years as an herbal medicine for the treatment of viral-induced cough, viral hepatitis, and viral skin diseases like ulcers in China. In TCM pharmacopeia, the plant — known as "Gancao" — was described as the "great harmonizer," routinely added to multi-herb decoctions to moderate the harsh properties of other ingredients and to harmonize the formula as a whole.

Ayurveda and Indian Traditional Medicine

In Ayurveda, licorice is used as a tonic, an expectorant, and as a demulcent. In Ayurveda generally, licorice is used as a rejuvenator and aphrodisiac, as well as for boosting memory, complexion, sound quality, dental health, vision, lactation, and healing of cancer, ulcers, and wounds. Traditionally, it has been used as a medicine in Ayurveda for rejuvenation; in Sanskrit, it is called "Yastimadhu."

In later medieval texts like the Bhavaprakasha (16th century), licorice was combined with herbs such as Yashtimadhu and Kutaja to create potent decoctions for jaundice and hepatic support. In recent decades, standardized licorice extracts with defined glycyrrhizin content have been developed, bridging classical Ayurvedic insights with modern pharmacognosy.

European Traditions

During the Middle Ages in Europe, apothecaries used liquorice in various remedies; it was often employed to treat sore throats and coughs, and this period saw the rise of liquorice-making for medicinal purposes, signalling its importance in traditional medical practices. Liquorice has been used in TCM to alleviate pain and in traditional herbal medicine as a treatment for kidney, lung, and liver ailments, gastric discomfort, arthritis, and infections.

3. Key Constituents and Active Compounds

Glycamil is itself a defined single chemical entity — monoammonium glycyrrhizinate — but occurs as the primary bioactive salt form extracted from a plant matrix that contains multiple active compounds.

Glycyrrhizic Acid / Glycyrrhizin

Glycyrrhizic acid or glycyrrhizin is the main active component extracted from the glycyrrhiza root, consisting of a triterpenoid pentacyclic glucoside. Glycyrrhizic acid is an amphiphilic molecule: the hydrophilic part is represented by the glucuronic acid residues, and the hydrophobic part is the glycyrrhetic acid residue.

Glycyrrhetinic Acid (the primary metabolite)

Glycyrrhizin is cleaved to glycyrrhizic acid, which is subsequently converted to glycyrrhetic acid by human intestinal microflora. Glycyrrhetic acid is a potent inhibitor of 11β-hydroxysteroid dehydrogenase (11β-HSD) and performs a range of corticosteroid-like activities. During metabolism in the plant by glucuronidase, or by intestinal bacteria after oral ingestion, glycyrrhizin is hydrolyzed into two pentacyclic triterpenoids, which are stereoisomers: 18α- and 18β-glycyrrhetinic acids.

Other Bioactive Constituents of Glycyrrhiza glabra

The active ingredients of licorice include glycyrrhizic acid (also known as glycyrrhizin), 18β-glycyrrhetinic acid (the major metabolite), glabrin A and B, isoflavones, and others, all of which have been demonstrated to have different pharmacological activities. The liquorice plant contains numerous bioactive compounds, including triterpenes, flavonoids, and secondary metabolites, with glycyrrhizin being the main active compound.

4. Established Mechanisms of Action

4.1 Anti-Inflammatory Mechanisms

Glycyrrhizin has long been known as a compound with many biological effects: anti-inflammatory, antiulcer, antianaphylaxis, antioxidant, immunoregulatory, membrane stabilization, antiviral, and anticancer activities. In particular, the anti-inflammatory activity of glycyrrhizic acid has been well studied; several in vitro studies have shown that glycyrrhizic acid can inhibit the production of the most proinflammatory cytokines such as TNF-α, interleukins IL-1β, and IL-6.

Glycyrrhizin, a triterpene of licorice, shows marked analgesic and anti-inflammatory effects through decreasing the expression levels of TNF-α, IL-6, iNOS, and COX-2. Due to its ability to bind the COX/mPGEs pathway for a long time, ammonium glycyrrhizinate exhibited antinociceptive and anti-inflammatory activity until 24–48 hours after a single administration.

Docking studies suggest that ammonium glycyrrhizinate's effects on inflammation and nociception may also depend upon interaction with mPGES-1/2, COX-1/2, and 5-LO. AG interacted with key amino acids of mPGES-2 and COX-2, highlighting a preferential binding with these two isoforms. AG appears to locate better in the binding pocket of COX-2, interacting with key amino acids like Trp387, Ser530 (H-bonds), and Arg120 (salt bridge).

Its anti-inflammatory effect may also be mediated through inhibition of phospholipase A2 activity. Glycyrrhizin has an anti-inflammatory and antiphlogistic action; glycyrrhetic acid inhibits the conversion of cortisol into cortisone by 11-beta hydroxysteroid dehydrogenase and inhibits the production of inflammatory cytokines such as TNF-α and IL-1β.

MAG suppresses activation of the NF-κB signaling pathway induced by LPS in lung tissue, and the therapeutic mechanism of MAG on acute lung injury may be attributed to the inhibition of this NF-κB signaling pathway.

A further mechanism responsible for the antiphlogistic action of this drug is the capacity of glycyrrhizin to inhibit the production of free radicals, a class of powerful inflammatory agents, by neutrophils.

4.2 Inhibition of 11β-Hydroxysteroid Dehydrogenase (Corticosteroid-Like Activity)

Licorice demonstrates mineralocorticoid-like activity not only by inhibiting 11β-HSD2, but also by binding to a mineralocorticoid receptor, leading to potentially adverse risks of mineralocorticoid-like overactivity. This mechanism underlies both some therapeutic properties (reducing inflammation in a cortisol-sparing manner) and the major adverse effects profile of the compound (see Safety section).

4.3 Antiviral Mechanisms

Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice; glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG) is the active metabolite of GL. GL and its metabolites have a wide range of antiviral activities against viruses such as the hepatitis virus, herpes virus, and SARS-CoV-2; although their antiviral activity has been widely reported, the specific mechanism of action involving multiple links such as the virus itself, cells, and immunity are not clearly established.

GL has been reported to have the ability to bind to ACE2, which can prevent SARS-CoV-2 infection; virtual screening also revealed that GL is effective against the target proteins of SARS-CoV-2, potentially serving as an inhibitor of the ACE2-specific receptor binding domain (RBD) on the spike glycoprotein of SARS-CoV-2.

4.4 Hepatoprotective Mechanisms

The multi-target pharmacological mechanisms of glycyrrhizin preparations comprise anti-inflammatory, membrane-stabilizing, antioxidant, anti-apoptotic, immunomodulatory, and anti-fibrotic effects that collectively underpin their hepatoprotective activity. Monoammonium glycyrrhizinate, as used in compound glycyrrhizin preparations, is widely used clinically to treat drug-induced liver injury by protecting hepatocyte membranes, exerting anti-inflammatory and immunomodulatory effects, and demonstrating corticosteroid-like actions that promote hepatocyte repair, enhance hepatic protein synthesis, prevent fibrosis, and strengthen anti-allergic and detoxification capacities.

4.5 Antioxidant Mechanisms

Pretreatment with MAG prior to LPS administration significantly induced a decrease in lung wet weight/dry weight ratio and in total leukocyte number; at the same time, pretreatment with MAG also significantly improved superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) content in bronchoalveolar lavage fluid. MAG exerts its therapeutic effects through multiple mechanisms, including suppression of microglia-induced neuroinflammation and oxidative stress, stabilization of mitochondrial membrane potential (ΔΨm), and preservation of mitochondrial bioenergetic function.

4.6 Neuroprotective Mechanisms

Ammonium glycyrrhizinate, as analyzed on an in vitro neuroblastoma cell line (SH-SY5Y), was able to prevent the cytotoxic effect and mitochondrial fragmentation that occurs after high-glucose administration. Monoammonium glycyrrhizinate (MAG), a bioactive liquorice-derived compound, exhibits anti-inflammatory and antioxidant properties with potential effects on microglial mitochondria.

4.7 Gap Junction Modulation

Glycyrrhetinic acid and its derivatives can block gap junction function, and monoammonium glycyrrhizinate is a clinically available oral medicine for chronic hepatitis, dermatitis, or stomatitis through this and other mechanisms.

5. Scientific Evidence by Area of Use

5.1 Liver Disease and Hepatoprotection

Hepatoprotection is the most extensively studied and clinically established application of glycyrrhizin preparations, including monoammonium glycyrrhizinate (Glycamil). Glycyrrhizin preparations derived from Glycyrrhiza uralensis (licorice) are widely used hepatoprotective agents in clinical practice; their primary active components, 18α- and 18β-glycyrrhetinic acid (GA), are represented by formulations including diammonium glycyrrhizinate (DG), compound glycyrrhizin (CG), and magnesium isoglycyrrhizinate (MgIG), and extensive reviews address their multi-target pharmacological mechanisms and anti-inflammatory, membrane-stabilizing, antioxidant, anti-apoptotic, immunomodulatory, and anti-fibrotic effects that collectively underpin hepatoprotective activity.

The well-established liver-protective efficacy of monoammonium glycyrrhizinate (MONO), diammonium glycyrrhizinate (DIAM), and magnesium isoglycyrrhizinate (MAGN) has been translated into clinical practice, though their clinical differentiation remains elusive owing to their structural similarities and overlapping therapeutic effects. Findings from comparative research reveal that both DIAM and MAGN exhibit superior bioavailability and hepatoprotective profiles compared to MONO.

Diammonium glycyrrhizinate (DG) is a popular drug in traditional Chinese medicine that slowly metabolizes into glycyrrhetic acid, which plays a role in detoxification, immune regulation, and liver cell membrane protection; while a number of studies indicated the efficiency of DG for the prevention of anti-tuberculosis drug-induced liver injury, there is still not enough evidence to support its routine prescription to prevent liver damage in people on tuberculosis treatment.

Clinical evidence across major liver diseases, including viral hepatitis, drug-induced liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, and autoimmune hepatitis, has been evaluated, though heterogeneity in study designs and the geographical concentration of evidence are noted limitations.

Evidence strength: The hepatoprotective evidence is strongest for drug-induced liver injury and chronic viral hepatitis, primarily from Asian (Chinese and Japanese) clinical trials. Most studies are conducted in Asia; large-scale randomized controlled trials from Western populations are limited. Evidence is supportive but the quality of individual studies varies.

5.2 Anti-Inflammatory and Analgesic Effects

Monoammonium glycyrrhizinate (MAG), as a derivative of glycyrrhizic acid, has anti-inflammatory, anti-allergic, anti-tumour, antimicrobial, antioxidant, anti-diabetic, anti-ulcer, and hepatoprotective effects.

MAG was investigated for its anti-inflammatory activity on hapten-induced experimental colitis; MAG in doses of 30 and 50 mg/kg body weight was injected intraperitoneally for 6 days, starting one day before inducing colitis. This is a preclinical animal study; human trials for inflammatory bowel conditions are not yet available.

In an LPS-induced acute lung injury mouse model, MAG attenuated histopathological changes in the lung and decreased the infiltration of inflammatory cells, especially neutrophils. Monoammonium glycyrrhizinate also significantly reduced the wet/dry weight ratio of lungs, and MAG inhibited the production of TNF-α, IL-1β, and protein in the bronchoalveolar lavage fluid.

Recent evidence confirms the anti-inflammatory and antinociceptive effectiveness of glycyrrhizin and suggests that these effects depend upon the inhibition of microglial high-mobility group box 1 protein (HMGB1). Glycyrrhizin, its metabolite glycyrrhetic acid, and other liquorice-derived compounds such as isoflavonoids and trans-chalcones exert potent anti-inflammatory effects via a wide range of mechanisms including HMGB1 inhibition, gap junction blockade, and α_2A-adrenoceptor antagonism; these properties, together with an increasing body of preclinical studies and a long history of use in herbal medicine, suggest that liquorice constituents may be useful for pain management.

Evidence strength: Predominantly preclinical (animal and in vitro). Clinical human evidence for anti-inflammatory endpoints specifically attributable to monoammonium glycyrrhizinate (as distinct from the parent glycyrrhizin) is limited. Whether liquorice plant-derived compounds represent a novel class of analgesics is yet to be established.

5.3 Antiviral Activity

The pharmacologic effects of licorice contribute to its anti-inflammatory, antioxidative, anti-allergenic, and antimicrobial properties. Glycyrrhizin and licorice extract have a wide range of pharmacological activities including anti-inflammatory, antioxidative, antiviral, anticancer, antimicrobial, antidiabetic, immunomodulatory, acute lung injury prevention, cardioprotective, and hepatoprotective activities.

GL and its metabolites have a wide range of antiviral activities against viruses such as the hepatitis virus, herpes virus, and SARS-CoV-2. Clinical investigations in China have verified the effects of diammonium glycyrrhizinate–vitamin C tablets on common COVID-19 pneumonia, and its metabolite GA, which is structurally similar to corticosteroids, may act as a glucocorticoid-like drug, helping to enhance immune regulation against cytokine storms and reduce inflammation.

Evidence strength: Antiviral activity is well-documented in vitro and in preclinical models. Clinical data specifically for monoammonium glycyrrhizinate as an antiviral agent in well-designed, adequately powered randomized controlled trials (independent of its liver-protective role in viral hepatitis) remains limited. Although antiviral activity has been widely reported, the specific mechanism of action involving multiple links such as the virus itself, cells, and immunity are not clearly established.

5.4 Neuropathic Pain and Diabetic Peripheral Neuropathy

In in vitro work, ammonium glycyrrhizinate was analyzed in a neuroblastoma cell line (SH-SY5Y), and was found to be able to prevent the cytotoxic effect and mitochondrial fragmentation observed after high-glucose administration. In an in vivo experiment, a short-repeated treatment with ammonium glycyrrhizinate was able to attenuate neuropathic hyperalgesia in streptozotocin-induced diabetic mice.

The authors concluded that ammonium glycyrrhizinate could ameliorate diabetic peripheral neuropathy, counteracting both in vitro and in vivo effects induced by high glucose, and might represent a complementary medicine for the clinical management of diabetic peripheral neuropathy.

Evidence strength: This area is very preliminary, based on in vitro cell lines and animal models only. No clinical trials in human patients with diabetic peripheral neuropathy using Glycamil/MAG specifically have been identified in the published literature.

5.5 Spinal Cord Injury and Neuroinflammation

Substantial evidence indicates that glycyrrhizic acid and its derivatives confer therapeutic benefits across diverse pathologies by targeting core inflammatory and oxidative pathways; experimental evidence shows that MAG attenuates microglia-mediated neuroinflammation, thereby promoting neural tissue preservation and enhancing motor function recovery in a murine model of spinal cord injury.

Evidence strength: Preclinical (animal) only at present. Human clinical data are absent.

5.6 Respiratory and Pulmonary Applications

Pharmacological activities of ammonium glycyrrhizinate have been proven including antitussive, antidiabetic, hepatoprotective, antimicrobial, antiulcer, antiviral, and anticancer effects. Regarding respiratory health specifically: the anti-inflammatory effects of MAG on LPS-induced acute lung injury in mice were investigated; pretreatment with MAG prior to LPS administration significantly reduced lung wet weight/dry weight ratio, total leukocyte number, and neutrophil percent in the bronchoalveolar lavage fluid, and myeloperoxidase (MPO) activity in the lung in a dose-dependent manner.

Evidence strength: Primarily animal model data. Traditional use for cough and bronchitis is longstanding, and the parent glycyrrhizin is used as an expectorant in some pharmacopeias, but controlled human trial data for MAG specifically in respiratory disease are very limited.

5.7 Dermatological Applications

Attention has been focused on identifying natural herbal compounds with high biological activity, especially antioxidative, anti-inflammatory, and antimicrobial properties, for preventing and controlling various skin conditions, including inflammation-related diseases such as atopic dermatitis and UV-induced skin photoaging; one key active plant ingredient is 18β-glycyrrhetinic acid (GA), the main metabolite of glycyrrhizin, obtained from licorice root.

Licorice has been used to treat liver disease, gastrointestinal disorders, oral disease, and various skin disorders. Ongoing clinical investigation of topical glycyrrhetinic acid-based formulations in human dermatitis is evidenced by active clinical trial designs evaluating topical formulations containing lower and higher concentrations of 18β-glycyrrhetinic acid for their dose-dependent effects on intact skin parameters and whether a higher dose enhances anti-inflammatory and barrier-restoring effects.

Evidence strength: Cosmetic/topical use is well-established in practice and supported by mechanistic research and preclinical data. Controlled clinical trial evidence specifically for topical MAG in named dermatological conditions is limited but growing.

5.8 Gastrointestinal Applications

In the pharmacological field, glycyrrhizin and its salt forms are used as expectorants and as gastroprotective agents in cases of peptic ulcers. Glycyrrhiza glabra has been studied for a variety of pharmacological properties including ulcer healing, anti-ulcerogenic, anti-bacterial, and antioxidant potential activity.

Evidence strength: Traditional use for gastrointestinal conditions (peptic ulcers, gastritis) is extensive and supported by multiple preclinical studies. Deglycyrrhizinated licorice (DGL) forms have more human trial data for ulcer relief specifically; the glycyrrhizin-containing forms (including MAG) have less direct human clinical evidence for GI endpoints in isolation.

6. Body Systems and Health Areas Associated with Glycamil

Hepatic (Liver): Licorice has been used to treat liver disease, most prominently chronic viral hepatitis and drug-induced liver injury.
Immune System: Immunomodulatory effects are documented as part of the multi-target pharmacological mechanism of glycyrrhizin preparations.
Inflammatory Pathways / Musculoskeletal: Liquorice constituents have been found to have anti-inflammatory, antioxidant, antiviral, anticancer, hepatoprotective, and neuroprotective properties.
Neurological: Liquorice constituents appear to have antidepressant actions and effects on morphine tolerance.
Endocrine / Metabolic: Licorice demonstrates mineralocorticoid-like activity by inhibiting 11β-HSD2 and binding to a mineralocorticoid receptor.
Respiratory: Licorice supplements are promoted for cough and bacterial and viral infections.
Integumentary (Skin): Glycamil has some antiallergic, antibacterial, and antiviral properties and is used topically for allergic or infectious skin inflammation.
Cardiovascular (adverse effect monitoring): Due to its mineralocorticoid-like activity, blood pressure and electrolyte homeostasis are relevant systems affected by chronic use.

7. Dosage Forms and Reported Study Dosages

Dosages reported in the scientific literature vary by condition, formulation, and route of administration. The following information is drawn directly from source-cited data only.

Animal anti-inflammatory study (colitis model): MAG in doses of 30 and 50 mg/kg body weight was injected intraperitoneally for 6 days in experimental colitis.
Animal acute lung injury study: Acute lung injury was induced in BALB/c mice by intratracheal instillation of LPS, and MAG was injected intraperitoneally 1 h prior to LPS administration. Specific mg/kg doses were investigated in a dose-dependent manner across multiple experimental groups.
Oral traditional use (safety reference dose, crude drug): Orally, intake of large doses (>50 g crude drug per day) for a prolonged period leads to hypokalaemia, hypernatraemia, oedema, hypertension, and cardiac disorder.
Pharmaceutical clinical use (hepatitis, general): Licorice and its extracts, especially glycyrrhizin, can be taken orally, through the skin (in the form of gels and oils), and intravenously. Specific clinical dosages for oral MAG preparations are not uniformly established in Western regulatory contexts and vary by Asian national formularies.
Food/flavoring use (USA): The ammonium salt of glycyrrhizin is approved as a flavoring and flavor enhancer in the USA, with use levels governed by GRAS (Generally Recognized As Safe) provisions of the FDA.

No single standardized therapeutic dose for Glycamil (MAG) as a dietary supplement has been established in peer-reviewed systematic reviews or in formal WHO/ESCOP/EMA monographs as of the available literature. Dosages used in clinical and experimental settings vary substantially and must be interpreted in the context of the specific formulation and route of administration studied.

8. Safety Considerations and Drug Interactions

8.1 Mineralocorticoid-Like Adverse Effects

The most clinically significant and well-documented safety concern with Glycamil/MAG is pseudo-aldosteronism arising from inhibition of 11β-HSD2. Moderate chronic or high acute exposure to glycyrrhizic acid, ammonium glycyrrhizate, and their metabolites have been demonstrated to cause transient systemic alterations, including increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin–angiotensin–aldosterone system, hypertension, and muscular paralysis, possibly through inhibition of 11β-hydroxysteroid dehydrogenase-2 (11β-OHSD2) in the kidney.

Chronic use of licorice can lead to hypokalemia and hypertension, and some people are more sensitive to licorice exposure. The compound glycyrrhizin can cause potassium levels to temporarily drop, leading to abnormal heart rhythms, high blood pressure, swelling, and lethargy; in extreme cases, or if inappropriately high doses are used, it can lead to heart failure in some people.

8.2 Hypokalemia

Orally, intake of large doses (>50 g crude drug per day) for a prolonged period leads to hypokalaemia, hypernatraemia, oedema, hypertension, and cardiac disorder; hypokalemia is the greatest threat when liquorice preparations high in glycyrrhizin are prescribed for prolonged periods. A literature analysis of severe hypokalemia induced by glycyrrhizin preparations reported a median serum potassium level of 1.8 mmol/L; severe hypokalemia occurred at a median of 60 days after treatment initiation (range 4 days to over 1 year), and recovery was achieved at a median of 7 days after drug discontinuation and potassium supplementation.

8.3 Gastrointestinal Effects

While monoammonium glycyrrhizinate is generally considered to be safe, common side effects include gastrointestinal issues such as nausea, vomiting, and diarrhea; some individuals may also experience allergic reactions characterized by symptoms like itching, rash, and swelling.

8.4 Contraindicated Conditions

One of the drawbacks of using glycyrrhetinic derivatives is that they tend to induce hypertension and hypokalemia, especially in the elderly. Contraindications for the use of MAG include conditions such as hypertension, chronic kidney disease, and hypokalemia. Special precautions should be taken with elderly patients with hypertension or cardiac, renal, or hepatic conditions.

8.5 Drug Interactions

Long-term use of MAG, especially in high doses, can lead to more severe side effects such as hypertension, hypokalemia, and water retention; these side effects are primarily due to the compound's mineralocorticoid-like effects, which can disrupt electrolyte balance and fluid regulation in the body. The inhibition of 11β-HSD2 also means that MAG can potentiate the systemic activity of corticosteroid medications, and concurrent use with loop diuretics or thiazide diuretics (which also lower potassium) carries an additive risk of hypokalemia. Side effects, typically involving cardiac dysfunction, edema, and hypertension, have been reported among subjects receiving high doses of glycyrrhizin-based pharmaceuticals or consuming large amounts of licorice-containing confectionery or health products over a prolonged period.

8.6 Regulatory Status of the Ammonium Salt Form

Ammonium glycyrrhizate (also known as glycyrrhizin, ammoniated) was investigated to be safe and is used as an ingredient in the formulation of makeup, fragrance, hair care, skin care, shaving, personal hygiene, and suntan products. Diammonium glycyrrhizinate has no current US brand names, but is widely used in Asian and European markets under various regional names (e.g., Ganli); in the United States, it is considered an investigational or dietary component depending on the formulation.

References

Health Conditions

Health conditions that Glycamil may help support.

No conditions available.

Body Systems

Body systems that Glycamil may help support.

No body systems available.