Usnic Acid

Several cases of clinically apparent acute liver injury have been attributed to commercial dietary supplements that contain usnic acid. “LipoKinetix” was one such supplement advertised as a weight loss and body building supplement. Each tablet contained sodium usniate (100 mg), norephedrine (25 mg), diiodothyronine (100 mg), yohimbine (3 mg) and caffeine (100 mg). The product has been linked to multiple instances of acute liver injury. The time to onset was 2 to 12 weeks and the clinical presentation resembled acute viral hepatitis with onset of fatigue and nausea, followed by jaundice. The pattern of serum enzyme elevations was hepatocellular, with marked elevations in serum ALT and minimal increases in alkaline phosphatase levels. Liver biopsy demonstrated acute hepatocellular necrosis and inflammation. Immunoallergic features (fever, rash and eosinophilia) were not common and autoantibodies were usually not present. Recovery was rapid with stopping the dietary supplement, but some cases were severe and led to acute liver failure and either death or need for emergency liver transplantation. Instances of acute hepatitis have also been reported with other multi-ingredient dietary supplements that contain usnic acid, but much more rarely than with LipoKinetix which was withdrawn from distribution after a FDA warning letter. Rare instances of hepatotoxicity have also been reported with use of lichen based teas known as Kombucha tea, but whether these were due to usnic acid or another contaminant of the tea was not shown.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=125-46-2]

Usnic acid is one of the most common and abundant lichen metabolites.

Usnic acid is widely distributed in species of Cladonia (Cladoniaceae),Usnea (Usneaceae), Lecanora (Lecanoraceae), Ramalina (Ramalinaceae), Evernia, Parmelia (Parmeliaceae) and other lichen species.

/HUMAN EXPOSURE STUDIES/ ... Usnic acid gave negative patch test reactions in subjects found to be allergic to lichen substances. ... Positive test reactions against usnic acid in 0.35% of tested patients.

/HUMAN EXPOSURE STUDIES/ Two forest workers affected with allergic contact dermatitis, which occurred only during work in forest areas, showed positive patch test reactions to lichens containing usnic acid and to isolated usnic acid. Lichens are plants composed of fungi living in symbiosis with algae. Usnic acid, one of the lichenic acids which accumulates in lichenized fungi, is a monobasic acid with dibenzofuran structure and antibiotic properties. Dibenzofuran is chemically related to furocoumarans. Lichens are plentiful in temperate zone forests and allergy to usnic acid represents some part of the "cedar-poisoning" problem in British Columbia. Geographical distribution of lichens containing usnic acid suggests that allergy to usnic acid will be found to be more common than presently recognized.

/SIGNS AND SYMPTOMS/ The only reported adverse effects /concerning usnic acid toxicity in humans/ are local irritation and allergic contact dermatitis, sometimes accompanied by conjunctivitis.

/SPECIAL STUDIES/ In vitro challenges were /conducted/ on primary and continuously cultured cells /to determine/ the cytotoxic action of usnic acid alone or as a component of oral care formulations. The cell strains KB human epidermoid and gingival keratinocytes and fibroblasts (taken from human biopsies), usnic acid alone or as part of a formulation did not /result/ in any sign of cytotoxicity. ...

For more Human Toxicity Excerpts (Complete) data for USNIC ACID (6 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ The sensitizing potency of the most common lichen substances were determined in Guinea pigs by a modified Freunds' complete adjuvant (FCA) test. ... The sensitizing potency of (-) and (+)-usnic acid was weak. The (-) stereoisomer was found to be twice as active as its counterpart.

/LABORATORY ANIMALS: Acute Exposure/ Sodium usneate administered iv to anesthetized cats at doses of 10 mg/kg led to an augmented rate of metabolism with symptoms such as hyperventilation, increased oxygen consumption and rise in body temperature. /Sodium usneate/

/LABORATORY ANIMALS: Acute Exposure/ Mice were treated orally with aqueous suspensions of (+)-usnic acid in a single dose of either 100 or 200 mg/kg. The effects on femur cells and proteins and on nucleic acids of liver cells were studied 24-72 hr after treatment. (+)-Usnic acid was found to affect the proliferation of polychromatic erythrocytes possibly by interference with RNA biosynthesis. The slight increase in the micronucleated polychromatic erythrocytes without affecting DNA synthesis suggests an effect of usnic acid on spindle apparatus.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Feeding experiments in ... animals have shown usnic acid to be toxic in high doses. The development of ataxia in sheep and cattle, leading to paralysis of the extremities in severe cases, was attributed to usnic acid following consumption of lichen Parmelia molliuscula.

For more Non-Human Toxicity Excerpts (Complete) data for USNIC ACID (7 total), please visit the HSDB record page.

/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

LD50 Dog iv 40 mg/kg

LD50 Rabbit iv 30 mg/kg

LD50 Rat iv 30 mg/kg

LD50 Rabbit oral 500 mg/kg

For more Non-Human Toxicity Values (Complete) data for USNIC ACID (6 total), please visit the HSDB record page.