Glyceryl Glycyrrhetinate

What Is It?

Glycyrrhetinic Acid and Glycyrrhizic Acid are specific compounds isolated from licorice plants. Glycyrrhizic Acic is a conjugate of Glycyrhetinic Acid and two molecules of glucuronic acid, a carbohydrate. Potassium Glycyrrhetinate, Sodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate and Stearyl Glycyrrhetinate are salts and esters of Glycyrrhetinic Acid.

Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate and Potassium Glycyrrhizinate are salts and esters of Glycyrrhizic Acid. In cosmetics and personal care products, these ingredients are used in the formulation of makeup, fragrance, hair care, skin care, shaving, personal hygiene and suntan products.

Why Is It Used?

These ingredients are used to enhance the appearance of dry or damaged skin by reducing flaking and restoring suppleness. They are also used to impart a flavor to cosmetics and personal care products.

Scientific Facts

Glycyrrhetinic Acid is an organic compound derived from shredded licorice roots and Glycyrrhizic Acid is a natural material isolated from the licorice plant, Glycyrrhiza glabra.

Safety Information

The Food and Drug Administration (FDA) includes licorice and licorice derivatives on its list of substances considered Generally Recognized As Safe (GRAS) as direct food ingredients with some restrictions on the levels of Glycyrrhizic Acid in certain types of foods.

Glycyrrhizic Acid is not permitted as a non-nutritive sweetener in sugar substitutes. The safety of Glycyrrhetinic Acid, Glycyrrhizic Acid and their salts and esters has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.

The CIR Expert Panel evaluated the scientific data and concluded that Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Sodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate and Potassium Glycyrrhizinate were safe for use in cosmetic and personal care products.

CIR Safety Review: The CIR Expert Panel reviewed data indicating that while Glycyrrhizic Acid was poorly absorbed by the intestinal tract, it was hydrolyzed to Glycyrrhetinic Acid by a beta-glucuronidase produced by intestinal bacteria. In the blood, Glycyrrhetinic Acid and Glycyrrhizic Acid were bound to albumin and were well absorbed into tissues.

Glycyrrhetinic Acid and Glycyrrhizic Acid and metabolites were mostly excreted in the bile, with very little excreted in urine. Dipotassium Glycyrrhizate was undetectable in the receptor chamber when tested for penetration through skin. 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-angiotensis-aldosterone system, hypertension and muscular paralysis.

Little short-term, subchronic, or chronic toxicity were seen when Ammonium, Dipotassium, or Disodium salts of Glycyrrhizic Acid were administered. Glycyrrhetinic Acid was not irritating to shaved skin, but was considered slightly irritating in an in vitro test. Glycyrrhetinic Acid inhibited the mutagenic activity of benzo[a]pyrene and inhibited tumor initiation and promotion by other agents. Glycyrrhizic Acid inhibited tumor initiation by another agent, but did not prevent tumor promotion.

Ammonium Glycyrrhizate was not genotoxic in cytogenetics assays, the dominant lethal assay, a bacterial assay and heritable translocation tests. Disodium Glycyrrhizate was not carcinogenic in a drinking water study at exposure levels up to 12.2 mg/kg/day for 96 weeks. Glycyrrhizate salts produced no reproductive or developmental toxicity, except for a dose-dependent increase in a skeletal variation (at 238.8 and 679.9 mg/kg/day) in one study. Sedation, hypnosis, hypothermia, and respiratory depression were seen after administration of 1250 mg/kg Glycyrrhetinic Acid intraperitoneally.

No treatment related effects in motor function tests were seen after exposure to a powdered diet containing up to 4% Ammonium Glycyrrhizate, but active avoidance was facilitated at 4%, unaffected at 3%, and depressed at 2%. In a study of 39 healthy volunteers, a no effect level of 2 mg/kg/day was determined for Glycyrrhizic Acid given orally. Glycyrrhetinic Acid at concentrations up to 6% was not a skin irritant or a sensitizer in clinical tests. Neither Glycyrrhizic Acid, Ammonium Glycyrrhizate, nor Dipotassium Glycyrrhizate at 5% were phototoxic agents or photosensitizers. Birth weight and maternal blood pressure were unrelated to the level of consumption of Glycyrrhizic Acid in 1049 Finnish women with infants, but babies whose mother consumed greater than 500 mg/week were more likely to be born before 38 weeks. The CIR Expert Panel notes that the ingredients in this safety assessment are specific chemical species that may be isolated from the licorice plant.

Because these chemicals may be isolated from plant sources, steps should be taken to assure that pesticide and toxic metal residues are below acceptable levels. Glycyrrhetinic Acid is described as at least 98% pure, Ammonium Glycyrrhizate is at least 98% pure, and Dipotassium Glycyrrhizate is at least 95% pure. The CIR Expert Panel advised the industry that total PCB/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and that toxic metal levels must not contain more than 3 mg/kg of arsenic (as As), not more than 0.002% heavy metals, and not more than 1 mg/kg of lead (as Pb).

While the CIR Expert Panel noted that Glycyrrhizic Acid is cytotoxic at high doses and ingestion can have physiological effects, there is little acute, short-term, subchronic, or chronic toxicity and these ingredients are poorly absorbed through the skin. These ingredients are not considered to be irritants, sensitizers, phototoxic agents, or photosensitizers at the current maximum concentration of use. Within the overall pattern of use at the time of the evaluation, the CIR Expert Panel considered all ingredients in this group to be safe.

Link to FDA Code of Federal Regulations for licorice and licorice derivatives…

Glycyrrhetinic Acid and Glycyrrhizic Acid and their salts and esters may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Regulation of the European Union.

Link to the EU Cosmetic Regulation:…

The European Commission’s Scientific Committee on Food (SCF) advised that regular daily ingestion of Glycyrrhizic Acid and Ammonium Glycyrrhizate from all food products should not exceed an Upper Use Level of 100 mg/day.