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

[Guest guest]

http://www.dldjournalonline.com/article/PIIS159086581100048X/abstract?rss=yes

JOURNAL OF DIGESTIVE AND LIVER DISEASE

Herbal hepatotoxicity by kava: Update on pipermethystine, flavokavain B, and

mould hepatotoxins as primarily assumed culprits

Rolf Teschkea, X. Qiub, 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.

a Department of Internal Medicine II, Division of Gastroenterology and

Hepatology, Klinikum Hanau, Teaching Hospital of the Goethe University of

furt/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 furt/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

[Guest guest]

http://www.dldjournalonline.com/article/PIIS159086581100048X/abstract?rss=yes

JOURNAL OF DIGESTIVE AND LIVER DISEASE

Herbal hepatotoxicity by kava: Update on pipermethystine, flavokavain B, and

mould hepatotoxins as primarily assumed culprits

Rolf Teschkea, X. Qiub, 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.

a Department of Internal Medicine II, Division of Gastroenterology and

Hepatology, Klinikum Hanau, Teaching Hospital of the Goethe University of

furt/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 furt/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