Excerpts taken from the article: German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics
Until the year 2002, extracts of the rhizome and roots of the Melanesian plant kava [Piper methys- ticum G. Forst. (Piperaceae)] were marketed in Germany and other countries in the form of me- dicinal products licensed for the treatment of situational anxiety. After receiving a series of case reports concerning alleged liver toxicity, the German regulatory authority BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte; Federal Institute for Drugs and Medical Devices) decided in the summer of 2002 to cancel all drug registrations for all medicinal products containing kava by a simple administration decision, with the exception of homeopathic dilutions of 4D (1 : 10 000) or higher. Formally, the benefit-risk ratio was declared negative. Other regulators outside Germany soon followed this decision. The consequences of this ban were felt worldwide and led to an economic disaster in many South Pacific states. Within Europe, the kava ban deprived physicians of an effective and comparatively safe medication, creating a “therapeutic gap nobody wished for” .
– A ban that has been contested because of the poor evidence of risks related to kava. Only recently, two German administrative courts decided that the decision of the regulatory authority to ban kava as a measure to ensure consumer safety was inappropriate and even associated with an increased risk due to the higher risk inherent to the therapeutic alternatives. This ruling can be considered as final for at least the German market, as no further appeal has been pursued by the regulatory authorities. However, in order to prevent further misunderstandings, especially in other markets, the current situation calls for a comprehensive presentation of the cardinal facts and misconceptions concerning kava and related drug quality issues.
Possible Theories Concerning the Perceived Liver Damage
The analysis of the case reports by Teschke had revealed only very few case reports with a relatively high probability of having been caused by kava, among them one report with a proven allergic reaction to the product , and thus a type of reaction which must be assessed apart from the issue of typically dose-de- pendent toxic reactions. Although the number of cases seems in- significant when compared with the known exposure data (450 million daily doses in ten years according to IMS data), the ob- served cases still demand a pharmacological explanation. Thus, over the past twelve years, several theories have been published, which, all in all, can be summed up in five major lines of thought:
” The “human genetic variability theory”: According to this school of thought, kava preparations are completely harmless to the general population. However, there is a small subgroup of the European Caucasian population lacking the metabolizing liver enzyme cytochrome P450 subtype 2D6 (CYP 2D6), as ob- served in one case report . This mutation might lead to an unusual metabolic pattern in these patients, resulting in the transformation of the normally harmless constituents of kava into toxic metabolites in the liver. This theory suffers from the fact that this would be a typical dose-dependent toxicity. With approximately 7–9% of Caucasians being CYP 2D6-deficient, a much higher number of case reports would be expected not only in Germany, but in all Caucasian populations. This was quite obviously not the case; the observations were almost exclusively restricted to Germany and Switzerland, with the latter country using kava products of German origin.