Kava May Be Linked To Liver Problems
1 February 2002
by Wyn Snow, Managing Editor

A new controversy is brewing over kava (Piper methysticum) and possible liver toxicity. Kava is popular with consumers, ranking ninth among herbal supplements and accounting for $15 million in sales through mainstream retail stores. Sales in health food stores, multi-level marketing companies, mail order and sales by health professionals may constitute an additional $15 million.

On 8 November 2001, the German government reported that over the past several years, 24 cases in Germany and 5 cases in Switzerland may indicate a connection between kava and liver toxicity -- including hepatitis, cirrhosis and liver failure. In 18 of these cases, pharmaceutical drugs with known or potential liver toxicity were also being used, a fact that obscures the role that kava may or may not have played. Among these 18 cases are 1 death and 4 liver transplants.

Kava has been used as a social and ceremonial beverage among South Pacific Islanders (Fiji, Vanuatu, Samoa, Tonga) for as long as two or three millenia. Kava is known to have side effects, including yellowing skin, sensitivity to light and impaired motor control, but these are usually associated with high levels of intake. Other side effects can include upset stomach, diarrhea, headaches and bad taste in the mouth.

Swift response from government

As a result of recently reported cases, Switzerland now prohibits the sale of kava. Germany issued a preliminary ban on the sale of kava except in products containing only minute amounts. The United Kingdom is asking manufacturers and retailers to temporarily stop selling kava while it reviews the safety data. Richard Woodfield, head of herbal policy at Britain's Medicines Control Agency, told the BBC that this was a precautionary measure.

On December 18, the US Food and Drug Administration (FDA) issued a letter asking health professionals to review their cases of liver toxicity in order to collect information on whether kava may have been involved. The letter says the FDA has received "several reports of serious injury allegedly associated with the use of kava-containing dietary supplements, with at least one report of hepatic failure requiring liver transplantation in a previously healthy young female."

German manufacturers appeal ban

Manufacturers are complying with governmental requests. In late December, however, 50 companies in Germany that produce kava appealed the ban through the German Medicines Manufacturer's Association (BAH).

The appeal claims that no evidence links the 24 cases of severe side effects to kava use. Bernd Eberwein, executive director of the Bonn-based BAH, told Reuters Health that the person who died was an elderly woman already suffering from a variety of complications with "significant risk factors."

Eberwein acknowledged that the incidence of side effects rises with higher dosages. "A majority of experts say the potential side effects are dose dependent,'' he said. Most German kava products give a daily dosage level of 60 to 120 mg of kavapyrones, and doctors may recommend dosages as high as 240 mg per day, yet three of the four people who received liver transplants were taking more than 240 mg per day.

Kava affects the liver by causing a shift in enzymes, especially cytochrome P450. However, this enzyme shift is not unusual -- it occurs after every meal. Even a glass of grapefruit juice causes a similar shift.

Botanical organizations organize scientific investigation

A coalition of four botanical trade organizations is moving swiftly to investigate the scientific evidence -- the American Herbal Products Association (AHPA), the Council for Responsible Nutrition (CRN), the National Nutritional Foods Association (NNFA), and the Utah Natural Products Alliance (UNPA).

"Safety is our first concern," according to Michael McGuffin, President of the American Herbal Products Association. "The industry coalition has initiated an expert scientific evaluation of all of the adverse event reports. We believe it is critical that kava's long history of safe use be reaffirmed by a review of the information."

The Council for Responsible Nutrition (CRN) agrees. According to John Cardellina, PhD, Vice President for Botanical Science, "We are actively proceeding with a number of initiatives on this issue, both within and outside the industry, working jointly with regulators and the scientific community to learn as much as we can about these adverse events and the safety of kava."

The American Botanical Council (ABC) also recommends scientific review of the evidence. Mark Blumenthal, ABC's executive director, says, "An expert evaluation of the medical reports and all relevant scientific literature is needed to determine the extent of the problem and the appropriate steps for the proper labeling of kava." Blumenthal also says, "The scientific literature does not show much basis for concern about potential liver toxicity. These cases in Europe are relatively recent."

These five organizations have retained a professional toxicologist from a leading university to investigate whether the scientific evidence supports a connection between kava intake and liver disease.

Previous evidence underscores safety of kava

The German government's Commission E examined the scientific and medical research evidence for kava's safety and efficacy. In 1990, they approved the use of kava as an over-the-counter herbal remedy for anxiety, stress, and restlessness. The German Commission E is comprised of herbal experts, both for medical use and pharmacology.

The safety and effectiveness of kava for relieving anxiety was supported by a meta-analysis published in 2000 that examined seven clinical trials in the Journal of Clinical Psychopharmacology, and by a similar critical review published in 2001. These reviews found no adverse effects related to liver toxicity.

Jerry Cott, PhD, former Chief of the Psychopharmacology Research Program at the National Institute of Mental Health, also pointed out that a small clinical study from Duke University published in October 2001 showed no adverse effects from kava on the liver.

However, liver toxicity is a long-term, subtle-onset effect that may not show up in short-term trials. Since liver toxicity can be lethal, prudence is called for.

Botanical groups urge consumers to use caution

The American Botanical Council and American Herbal Products Association may recommend expanding the cautionary information placed on kava labels. Based on the limited data now available, ABC's Blumenthal says consumers should use extra caution until this evidence can be evaluated. In particular . . .

• Do not use kava if you have liver problems, drink alcohol regularly, or take pharmaceutical drugs that affect the liver (ask your doctor).

• Do not use kava on a daily basis for more than 4 weeks (all the adverse reports are associated with chronic use).

• Stop taking kava if you experience any symptoms of jaundice (such as dark urine, yellowing of the eyes).

• If you have a history of liver problems or suspect that you might, consult your doctor before using or continuing to use kava.

Blumenthal says, "These cautions represent a prudent approach to the information presently available."

According to the American Botanical Council, "The primary adverse effects of kava reported in the literature are relatively minor and are usually associated with highly excessive intake. These effects include the occasional yellowing and scaling of skin, which returns to normal after discontinuation of the herb. Other effects associated with high doses include slow adjustments of the eyes to changes in light and impaired motor control (related to kava's action of relaxing skeletal muscles, one of the reasons it is used for treating mild cases of anxiety)."

Putting risk in perspective

Side effects are common among pharmaceutical drugs, both prescription and over-the-counter. In fact, deaths associated with properly prescribed drugs are among the top ten causes of death in the US.

Cott says, "If the incidence of liver toxicity for kava is correct, then according to German researchers it is very similar to that of conventional pharmaceutical anti-anxiety and antidepressant prescription drugs." These small risks are generally considered acceptable in the risk-to-benefit analysis used in evaluating toxicity risks of pharmaceutical medicines.

Consumers need to be aware that despite having a remarkably good safety record, all dietary supplements carry some risk of side effects, especially if taken in high dosages.

Botanical products in particular are likely to have side effects, for they are derived from the folk remedies and medical knowledge of indigenous cultures. Trends to concentrate substances into pills and manipulate ingredients to create standardized dosages have contributed to higher rates of side effects than are seen with the traditional teas and infusions of folk medicine.

Sources

American Botanical Council. "American Botanical Council Announces New Safety Information On Kava." Healthy.net website, 20 December 2001. healthy.net/asp/templates/news.asp?Id=3814.

American Herbal Products Association. "Dietary Supplement Associations Undertake Scientific Evaluation of Kava." AOL health news via PRNewswire, 20 December 2001.

Ned Stafford, Reuters Health. "Manufacturers Appeal Germany's Kava Kava Ban." Yahoo Health News, 20 December 2001.

Natural Products Insider. "Kava Possibly Linked to Liver Toxicity; Many Governments Considering Bans." Natural Products Insider website, 2 January 2002. www.naturalproductsinsider.com/hotnews/21h294743.html.

Christine Lewis Taylor, PhD, Director, Office of Nutritional Products, Labeling and Dietary Supplements, Center for Food Safety and Applied Nutrition, US Food and Drug Administration. "Letter to Health Care Professional Colleague." FDA website, 18 December 2001. www.cfsan.fda.gov.