Kava and kava hepatotoxicity: requirements for novel experimental, ethnobotanical and clinical studies based on a review of the evidence.

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, appropriate studies have yet to be done and should be extended to other mould hepatotoxins, with the aim of publishing the obtained results. It is hoped that with the proposed qualifying measures, the safety of individuals consuming kava will substantially be improved.