Herbal hepatotoxicity by kava: Update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits

Digestive and Liver Disease

Articles in Press

Rolf Teschkea, Samuel X. Qiub, Vincent Lebotc

Received 2 December 2010; accepted 25 January 2011. published online 07 March 2011.
Corrected Proof

Abstract

Herbal hepatotoxicity by the anxiolytic kava (Piper methysticum Forst. f.) emerged unexpectedly and was observed in a few patients worldwide. Liver injury occurred after the use of traditional aqueous kava extracts in the South Pacific region and of acetonic and ethanolic extracts in Western countries in rare cases, suggesting that the solvents used play no major causative role. In this review, we discuss actual pathogenetic issues of kava hepatotoxicity with special focus on developments regarding pipermethystine, flavokavain B, and mould hepatotoxins as possible culprits. There is abundant data of in vitro cytotoxicity including apoptosis by pipermethystine and flavokavain B added to the incubation media, yet evidence is lacking of in vivo hepatotoxicity in experimental animals under conditions similar to human kava use. Furthermore, in commercial Western kava extracts, pipermethystine was not detectable and flavokavain B was present as a natural compound in amounts much too low to cause experimental liver injury. There is concern, however, that due to high temperature and humidity in the South Pacific area, kava raw material might have been contaminated by mould hepatotoxins such as aflatoxins after harvest and during storage. Whether kava hepatotoxicity may be due to aflatoxicosis or other mould hepatotoxins, requires further studies.

Keywords: Drug induced liver injury, Herbal hepatotoxicity, Herbs induced liver injury, Kava, Kava hepatotoxicity, Piper methysticum

a Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Goethe University of Frankfurt/Main, Germany
b Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, China
c CIRAD, Port-Vila, Vanuatu

Corresponding author at: Department of Internal Medicine II, Klinikum Hanau, Teaching Hospital of the Goethe University of Frankfurt/Main, Leimenstrasse 20, D-63450 Hanau, Germany. Tel.: +49 6181 2964200; fax: +49 6181 2964211.

PII: S1590-8658(11)00048-X
doi:10.1016/j.dld.2011.01.018
© 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Inc All rights reserved.

Source