Volume 190 - Issue 2
Liver failure associated with the use of black cohosh for menopausal symptoms
Authors: Elizabeth C-Y Chow, Marcus Teo, John A Ring and John W Chen
Med J Aust 2009; 190 (2): 99-100. || doi: 10.5694/j.1326-5377.2009.tb02294.x
Published online: 19 January 2009
Published online: 19 January 2009
In reply: Teschke questions the temporal sequence in our reported case1 by raising an ambiguity in dates. We wish to clarify: when the patient first presented on 23 May 2006, lethargy, arthralgia and nausea had been present for only about 3 weeks. This was well after the dose increase in black cohosh in March 2006. As such, the dose escalation definitely preceded the patient’s symptoms and liver failure.
To further explore causality would require rechallenge with black cohosh, which we consider dangerous and unethical. Other unlikely causes of liver failure raised by Teschke, although theoretically possible, were not evident. The clinical course and histological findings in the pretransplant biopsy and explanted liver categorically excluded alcoholic cirrhosis and non-alcoholic steatohepatitis as causes of the liver failure. We also reiterate that there was no previous history of liver disease or other medication use.
Increasing numbers of case reports are being published showing evidence of hepatotoxicity in patients taking black cohosh. Two well documented cases of seriously deranged liver function in patients taking black cohosh, which resolved on ceasing its use, have just been reported.2 Teschke concedes that four other cases have been reported where some causality between black cohosh and hepatotoxicity was evident.3
Neither Teschke nor Naser and Liske offer any reassurance on the long-term safety or lack of toxicity of black cohosh by referencing any properly conducted safety study. Certainly, there is recent in-vitro and in-vivo evidence in a rat model that black cohosh is toxic to hepatocyte mitochondria and impairs oxidative phosphorylation, resulting in apoptotic hepatocyte death.4
It is notable that, based on available evidence, the Australian Therapeutic Goods Administration requires preparations containing black cohosh to carry a warning of potential liver toxicity, stating that “there appears to be an association between the use of black cohosh and liver damage, but that it is very rare”.5 Furthermore, in the United Kingdom, the Medicines and Healthcare Products Regulatory Agency stated, “Warnings regarding rare adverse reactions in the liver should be added to the product information for black cohosh for both licensed and unlicensed products”.6 Government authorities in Europe3 and Canada7 have raised similar concerns. Long-term studies as well as further animal studies would be welcome in this area.
References
- Chow ECY, Teo M, Ring JA, Chen JW. Liver failure associated with the use of black cohosh for menopausal symptoms. Med J Aust 2008; 188: 420-422.
- Joy D, Joy J, Duane P. Black cohosh: a cause of abnormal postmenopausal liver function tests. Climacteric 2008; 11: 84-88. 0_CBBGJBFD
- European Medicines Agency, Committee on Herbal Medicinal Products (HMPC). Assessment of case reports connected to herbal medicinal products containing Cimicifugae racemosae rhizoma (black cohosh, root). London: EMEA, 2007. http://www.emea.europa. eu/pdfs/human/hmpc/26925806en.pdf (accessed Oct 2008).
- Lüde S, Török M, Dieterle S, et al. Hepatic effects of Cimifuga racemosa extract in vivo and in vitro. Cell Mol Life Sci 2007; 64: 2848-2857. 0_pgfId-1605693
- Australian Government Department of Health and Ageing Therapuetic Goods Administration. Required advisory statements for medicine labels. Proposed update 3.1, consultation document. Canberra: Australian Government, 2007. http://www.tga.gov.au/meds/drrasmlupd3-1.pdf (accessed Oct 2008).
- Medicines and Healthcare Products Regulatory Agency. Black cohosh. UK Public Assessment Report, 31 Jul 2006. http://www.mhra.gov.uk/home/groups/es-herbal/documents/websiteresources/con2024279.pdf (accessed Oct 2008).
- Health Canada. Health Canada is advising consumers about a possible link between black cohosh and liver damage [advisory]. Ottawa: Health Canada, 2006. http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2006/2006_72_e.html (accessed Sep 2006).