Kava: The Present European Situation

A look at the controversy.

By Joerg Gruenwald and Janine Freder

For several decades kava products have been used as registered drugs for the treatment of anxiety problems in Europe, especially in Germany and Switzerland. In 1990 the German Commission E issued a positive monograph for dosages of 60-120 mg kava pyrones and limited their use to three months without medical advice. The interactions, specifically with alcohol, barbiturates and psychopharmacological agents, were clearly indicated. We estimate an annual use of over approximately 70 million daily doses in Germany and over 100 million daily doses in Europe based on the sales figures of kava products. In the international context, this usage is only a small percentage compared to the local use of kava in Polynesia, where approximately 70-80% of all consumption is estimated to take place.

Based on these figures, kava belongs to the group of most used herbal medicinal products worldwide that have been regarded for a long time as safe when used as directed. The efficacy is well proven in many properly per­formed placebo-controlled double-blind studies and the positive effects on mental health problems, especially anxiety, are well documented.

The risk-benefit relationship has been under discussion recently, when producers of kava products and companies that wanted to register new kava products in Germany were in­formed of possible side effects.

On November 8, 2001 the German Federal Institute of Drugs and Medical Devices issued a letter to all manufacturers of herbal medicinal products containing kava manufactured and marketed in Germany. The Institute disclosed its intention to possibly withdraw the market authorization of these products. Companies were given limited time to respond to this notice. This activity was based on adverse event reports concerning possible liver-toxic effects of kava. To our knowledge, at least 30 cases have occurred in Germany so far. Unfortunately, most of these reports have not been published, nor is the data readily accessible for review. Furthermore, most publications do not give the full picture; often, the case history is incomplete. The few available case reports in the literature range from credible to inconclusive. However, one exitus, four liver transplants and several cases of hepatitis and jaundice have been linked to kava use, a matter which cannot be taken lightly and needs thorough investigation.

While the first reports of a possible connection between kava and liver problems are reported in the PDR for Herbal Medicines from 1988 (Australia) and 1998 (Germany), recent findings came from Switzerland, followed by Germany. In eight cases, side effects (four serious cases) were recorded that could be related to kava intake at dosages of 140-210 mg kavalactones per day. Most of these patients took acetone extracts. This led to the withdrawal of kava preparations based on acetone extracts in Switzerland, whereas ethanolic extracts were still on the market. The Swiss IKS was the first national authority to prohibit the marketing of certain kava preparations.

The list of available cases in Germany (Table 1) suffers from several shortcomings. Of the 30 cases, eight reports (27%) do not state the duration of kava intake until the appearance of the first symptoms. In 11 cases (37%) kava was taken for a longer period than the recommended three months; three people took kava preparations in very high dosages for more than a year. In nine cases (30%), not even the dosage is given. Fourteen patients (47%) took higher dosages than the recommended daily dosage—in some cases up to four times that of the highest recommended dosage. Furthermore, half of the patients were over 60, which implies a certain susceptibility to multi-morbidity.

The liver is a very sensitive organ that—especially in the Western world—has to deal with a lot of toxins during one’s lifetime. A diet rich in fats, the consumption and perhaps misuse of alcohol and nicotine, as well as modern medications and chemical pollutants, have done their share in weakening the detoxification unit of the body. In the case of the patient who died during kava treatment, the liver was probably damaged by alcohol abuse, as stated in the report. One of the patients receiving a liver transplant also reported “mild alcohol use,” which leads to one of the problems with case history. People tend to either deliberately withhold information about their alcohol intake or to underestimate it. Furthermore, co-medication was not thoroughly investigated, which leads to a distorted physiological picture.

The withdrawal of the marketing authorization would only be reasonable when it is assumed that kava has no benefit and the side effects are so severe that the benefit-risk-ratio is infinitely negative. The 30 cases listed by the German Federal Institute of Drugs and Medical Devices demonstrate that it is of paramount importance to conduct further investigations on the mechanisms of the as­sumed hepatotoxic effects of kava. The data at hand is not completely conclusive. Even if, in some cases, liver transplants have been deemed necessary, more than 100 million single daily doses have been sold every year only in Europe.

A recent evaluation reported an incidence of hepatotoxity with kava use of 0.23 cases per 1 million daily doses. The causality in most cases remains questionable due to co-medication (other drugs including Paracetamol), a history of alcohol abuse or viral infections, all known to possibly interfere with liver function. Other psychotropic agents like benzo-diazepines, neuroleptics or anti-depressants are known to have similar or higher incidents of hepatotoxic adverse effects.

Kava preparations have been demonstrated to be effective anxiolytics. For patients suffering from panic attacks or anxiety, taking kava preparations is often the first step towards a “normal,” anxiety-free life. Afterwards, other forms of therapy, such as psychotherapy or authogenic training, are effective. The prescription of chemico-synthetic medications such as benzodiazepines seems to be a questionable alternative as these medications have side effects and, more importantly, may lead to dependence. Thorough research into kava is necessary to gain information about the pharmacokinetics, distribution, met­abolism and hepatic elimination mechanisms as well as the mechanism of liver toxicity itself. Only when the evidence is there can valid statements be made about the safety concerns regarding kava. Better labeling is clearly required regarding co-medication, alcohol usage, etc. A physician should be consulted when other drugs are taken or when the user has severe diseases.NW