Terra Sigillata

We’ve discussed previously the use of herbal extracts from black cohosh (Actea racemosa) for relief from hot flashes and other vasomotor symptoms of menopause and perimenopause. A clinical trial in Annals of Internal Medicine last December, showed that one black cohosh extract was no better than placebo for this indication. Lack of efficacy has been shown in other settings yet black cohosh remains one of the most popular herbal products in North America.

Regardless of whether it works, black cohosh has been investigated by Health Canada for its link to rare but serious cases of liver damage. The outcome of their deliberations is that there is not enough evidence of causality to remove the product from the market but it will be sold with a warning about the potential for liver injury.

Health Canada is being urged to issue stronger safety warnings about the potentially dangerous sideeffects of a popular herbal remedy that’s predominantly marketed to menopausal women after reports that it could be linked to liver damage.

Sporadic reports of liver damage associated with black cohosh use began around 2003. Forty-seven of those cases were reported in Australia, leading that country’s Therapeutic Goods Adminstration to require warnings on product labels. Similar reports, also rare, have also been reported in England. A medicinal chemistry group at the University of Illinois has detected the in vitro formation of chemically-reactive metabolites of black cohosh extract but concluded from clinical trials results that these metabolites are unlikely to be of danger to women taking “moderate” doses of the supplement. NIH’s NCCAM convened a special conference in late 2004 on black cohosh safety in clinical trials and concluded that, in some cases, there was a causal relationship between the herb and cases of liver failure. However, the meeting report also noted:

Hepatotoxicity covers a spectrum of liver disease. Making the connection between drug or botanical use and liver disease is very difficult and mostly relies on a diagnosis by exclusion. Dr. [Leonard] Seeff [of NIDDK] reminded participants that some forms of drug-induced liver injury depend on the dose and total amount of drug taken. Others are referred to as idiosyncratic and immunologically based. The latter are rare events, even with conventional drugs. A major problem in assigning blame is that often multiple drugs or herbs are being taken. Today the most common cause of fulminant hepatitis is use of acetaminophen.

Studying drug-induced liver injury is extremely challenging because of its often idiosyncratic, or unpredictable, nature. However, FDA notes that drug-induced liver injury has now become the leading cause of acute liver failure in the US. Drug-induced liver injury is also a major cause of drugs failing during clincial development or being pulled from the market after approval. The NIDDK Drug-Induced Liver Injury Network (DILIN) website gives some of these examples.

But back to black cohosh – if it shows no efficacy in clinical trials, why expose oneself to even a low risk of hepatotoxicity. Proponents of black cohosh cite the fact that we now know hormone-replacement therapy (HRT) has its own risks of increased cardiovascular disease in certain populations. While this is most certainly true and using HRT is a decision to be made on a case-by-case basis, black cohosh is not a substitute for HRT. As I have said before,

Let’s not forget, however, that another reason to take HRT is to prevent severe osteoporosis, a claim that has never been made for black cohosh.

Of course as noted earlier, alcohol and acetaminophen are the major causes of liver damage.

But the jury remains out on black cohosh whose problems are likely too rare to track given current reporting mechanisms.