Kava and Kava Hepatotoxicity: Requirements for Novel Experimental, Ethnobotanical and Clinical Studies Based on a Review of the Evidence

• Published in: Phytotherapy research 2011-09, Vol.25 (9), p.1263-1274
• Main Authors: Teschke, Rolf, Qiu, Samuel X, Xuan, Tran Dang, Lebot, Vincent
• Format: Article
• Language: English
• Subjects: adulterated products; aflatoxicosis; aflatoxin B1; Aflatoxins - toxicity; Animals; anxiety; anxiety disorders; Aspergillus; Beverages - toxicity; bioavailability; Biological and medical sciences; Chemical and Drug Induced Liver Injury; clinical trials; cultivars; drug induced liver injury; drying; Ethnobotany; fungi; General pharmacology; hepatotoxicity; hepatotoxins; herbal hepatotoxicity; Humans; humidity; kava; Kava - chemistry; Kava - toxicity; kava hepatotoxicity; liver; liver function; Medical sciences; ochratoxin A; Pacific Islands; patients; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Piper methysticum; Plant Extracts - chemistry; pollutants; raw materials; rhizomes; risk; roots; Toxicity Tests
• ISSN: 0951-418X; 1099-1573; 1099-1573
• DOI: 10.1002/ptr.3464

Kava hepatotoxicity is a well described disease entity, yet there is uncertainty as to the culprit(s). In particular, there is so far no clear evidence for a causative role of kavalactones and non‐kavalactone constituents, such as pipermethystine and flavokavain B, identified from kava. Therefore, novel enzymatic, analytical, toxicological, ethnobotanical and clinical studies are now required. Studies should focus on the identification of further potential hepatotoxic constituents, considering in particular possible adulterants and impurities with special reference to ochratoxin A and aflatoxins (AFs) producing Aspergillus varieties, which should be urgently assessed and published. At present, Aspergillus and other fungus species producing hepatotoxic mycotoxins have not yet been examined thoroughly as possible contaminants of some kava raw materials. Its occurence may be facilitated by high humidity, poor methods for drying procedures and insufficient storage facilities during the time after harvest. Various experimental studies are recommended using aqueous, acetonic and ethanolic kava extracts derived from different plant parts, such as peeled rhizomes and peeled roots including their peelings, and considering both noble and non‐noble kava cultivars. In addition, ethnobotanical studies associated with local expertise and surveillance are required to achieve a good quality of kava as the raw material. In clinical trials of patients with anxiety disorders seeking herbal anxiolytic treatment with kava extracts, long‐term safety and efficacy should be tested using traditional aqueous extracts obtained from peeled rhizomes and peeled roots of a noble kava cultivar, such as Borogu, to evaluate the risk: benefit ratio. Concomitantly, more research should be conducted on the bioavailability of kavalactones and non‐kavalactones derived from aqueous kava extracts. To be on the side of caution and to ensure lack of liver injury, kava consuming inhabitants of the kava producing or importing South Pacific islands should undergo assessment of their liver function values and serum aflatoxin levels. The primary aim is to achieve a good quality of kava raw material, without the risk of adulterants and impurities including ochratoxin A and AFs, which represent the sum of aflatoxin B1, B2, G1 and G2. Although it is known that kava may naturally be contaminated with AFs, there is at present no evidence that kava hepatotoxicity might be due to aflatoxicosis. However, approp