Acute liver failure associated with the use of herbal preparations containing black cohosh

To the Editor: We wish to comment on the case report by Lontos and colleagues on the proposed causal relationship between the herb black cohosh (Cimicifuga racemosa) and acute hepatic failure.1 One other case has been reported in Australia,2 and the evidence linking black cohosh to liver toxicity was weak and contested.3

The medication in the case report presented by Lontos and colleagues1 included a herb (ground ivy) containing a known liver toxin (pulegone). Pulegone is considered a strong hepatotoxin and should not be dismissed, even though it was reported that there was less pulegone in ground ivy than in pennyroyal.

The authors do not indicate the daily dose of the pulegone ingested. The Therapeutic Goods Administration (TGA) made only qualitative analyses of three of the five herbs in the mixture. In our opinion the most suspect ingredient was ground ivy, and it was not assayed. The argument that the TGA could not find a standard for pulegone or ground ivy is untenable given the level of expertise and the capacity of the TGA and its laboratories.

Was the supply company asked to provide analytical evidence of the contents of the herbal extracts? Ground ivy is not known to be hepatotoxic, but it is possible that the extract could have contained ground ivy with pennyroyal, which might explain the hepatoxicity of the mixture. Although uncertain without thoroughly investigating all ingredients in the herbal mixture, this alternative is a possibility. Without thorough investigation of herbal preparations, adverse events attributed to certain herbs remain dubious at best.

Black cohosh has a very good safety record. There is a large body of clinical evidence and research which suggests that this herb has no hepatotoxic effects. Indeed, a German manufacturer has sold more than 350 million daily doses of black cohosh preparations worldwide since the pharmacovigilance system was introduced, and no comparable cases have been reported until these two reports in Australia. An Ames test (salmonella microsomal assay) showed no in-vitro evidence of mutagenic potential of an extract of black cohosh,4 and no chemical or organ toxicities were observed in Wistar rats given up to 5000 mg of a Cimicifuga racemosa extract granulate per kilogram body weight for 26 weeks.5

What may also be of concern is that the TGA may not have the full capabilities to test ingredients used in Australian herbal products. That substitution of herbs with potentially toxic herbs may be a common event, and that neither the TGA nor the manufacturers may have the expertise to prevent deleterious contaminants, is of even greater concern.