n December 2000, a 14-year-old American girl developed persistent nausea, vomiting, fatigue, weight loss and loss of appetite–a constellation of symptoms that suggested acute hepatitis. She saw a doctor, who prescribed rest and liver-function tests. The test results showed much more liver damage than hepatitis typically causes. The girl was hospitalized with liver failure and received an emergency liver transplant.
Liver failure is extremely rare in otherwise healthy teenagers. This girl did not use alcohol, which in large amounts is toxic to the liver, and she took no medications implicated in liver damage, just ibuprofen occasionally. However, she had taken kava (Piper methysticum) for 44 days to treat anxiety.
Alarming Reports from Around the World
This case was just one of approximately 82 reports from around the world of kava users developing liver disease ranging from mild impairment of liver function (elevated liver enzymes) to jaundice, hepatitis and even acute liver failure requiring a transplant in an estimated 12 patients. Nine of these people died.
By early 2001, these reports generated international headlines. USA Today: “Herb Kava Linked to Liver Problems.” The New York Times: “Questions About Kava’s Safety.” They also prompted several countries to ban the herb: Germany, Austria, Canada, France, Ireland, Singapore, Switzerland and the U.K. Kava was not banned in the United States, but the Food and Drug Administration (FDA) warned consumers about the possibility of life-threatening liver damage.
Kava sales plummeted–by 50 percent, according to one estimate published in Market Research Updates. As sales fell, so did reports of kava-induced liver damage. The controversy became old news–though not to herb researchers. Studies continued. Some studies made the herb look dirty for liver damage. Others made the safety scare look more like a tempest in a teapot–or in a traditional Polynesian kava bowl. In 2005, the German counterpart of the FDA repealed its kava ban. But soon after, the U.K. decided to uphold its ban on kava products.
Based on research to date, kava cannot be called completely safe. Like most pharmacologically active substances, it has benefits and risks. By the same token, it’s an overstatement to call this herb hazardous. The truth lies somewhere in between. Bottom line: Most people can use kava safely in recommended amounts. But kava consumers should be well informed about this herb because its downside–liver damage–though rare, is potentially life-threatening.
Is Kava Inherently Hazardous?
According to distinguished German herb researcher Mathias Schmidt, an expert on kava, the answer is no. Many of the case reports of kava-related liver damage turned out to be less than compelling. Researchers at the University of Munster, Germany, analyzed 78 European case reports of alleged kava toxicity. Only four could be persuasively linked to kava alone. Schmidt’s own analysis knocks that number down to three. The tiny number of European kava-related problems, Schmidt says, “stand against 450 million doses of kava taken in Europe during the 10 years before the German ban.” An analysis by the University of Sydney, Australia, researchers concurs: “Only a negligible fraction of the case reports are attributable to kava.”
Even if every case report were attributable to kava, that works out to 0.3 cases per 1 million doses, a rate of serious side effects comparable with many FDA-approved drugs.
In most case reports of kava toxicity, the herb was just one of many drugs taken that can harm the liver, among them alcohol, aspirin, Prozac, Paxil and birth control pills.
Furthermore, according to a report in the German Pharmacists Journal, kava has been used throughout Polynesia for at least 1,500 years with few reports of significant side effects and no reports in the ethnopharmacological literature of liver damage, e.g., jaundice.
Finally, various research reports show that the traditional water extract of the herb (powdered kava root mixed with water) is not toxic to the liver in rats and causes no toxicity in isolated human liver cells.
However, many drugs considered safe in recommended amounts can cause liver damage when taken in large amounts, for example, acetaminophen (Tylenol). Two studies have looked at kava use among Australia’s aboriginal population. Heavy users have developed elevated liver enzymes, the first sign of liver damage. But none developed liver failure–and the native Australians were using at least four ounces of kava a week for decades, thousands of times more than the typical American user.
Four Possible Reasons for Kava-Induced Liver Damage
If kava is reasonably safe when typical amounts are ingested, why have more than 80 people around the world developed liver disease while taking it? Researchers have identified four possible reasons:
1. As already mentioned, most of those who developed liver disease were also taking other drugs that can cause liver toxicity. It’s possible that kava increases the likelihood of such damage.
2. Kava is a fairly slow-growing herb. It takes four to five years for the root/rhizome to mature enough to be harvested for sale. Kava’s popularity as an herbal tranquilizer dates from the late 1990s. At that time, demand for the herb grew faster than its supply. There were reports that some growers stretched their supply by including not just root material but also the aerial parts–the leaves and stem peelings–of the plant. The aerial parts contain an alkaloid, pipermethystine, that is toxic to the liver. It’s possible that contamination of the root with stem and leaf material containing pipermethystine is responsible for the liver toxicity.
Despite its problems, kava is an effective herbal tranquilizer.
The contamination theory dovetails with the timeline of problems with kava. The first report of liver toxicity was published in 1998. The story became news in 2001. Reports of liver toxicity peaked in 2002. Since then they have fallen off, in part because kava consumption has fallen. As that happened, there was less pressure to stretch supply, so it’s likely there was less contamination of root material with the liver-toxic aerial parts of the plant.
3. Polynesians pound kava root into a powder and mix it with water, then drink the cloudy white liquid. Western commercial extracts do not use water, but alcohol, acetone or methanol. This results in different concentrations of the herb’s bioactive constituents (kavalactones). It’s possible that the difference between traditional and commercial kava preparations plays a role in liver damage. In addition, water extracts of kava contain glutathione, a potent antioxidant that helps prevent liver toxicity. Commercial preparations don’t contain glutathione, which might increase the risk of liver problems.
4. Kava is one of a great many drugs and herbs that affect the body’s cytochrome P450 system. This system, little known outside of professional medicine, involves a group of 50 enzymes, six of which are involved in the metabolism of 90 percent of drugs, including medicinal herbs. When drugs and herbs that affect the cytochrome P450 enzyme system are taken simultaneously, liver damage or potentially problematic interactions are possible. Cytochrome P450 problems are most likely in those with a genetic deficiency in a certain enzyme, CYP2D6. This deficiency is rare in Polynesians. But an estimated 8 percent of people of European descent have it. A CYP2D6 deficiency might increase susceptibility to liver damage and, at the same time, explain why kava toxicity has not been observed in traditional kava-using cultures.
The situation is confusing, Schmidt says, though there is “a high probability that the problem was caused by bad-quality kava.”
Recommendations for Safe Kava Use
Despite the reported problems, kava is an effective herbal tranquilizer (see “The Latest Research on Kava’s Benefits“). Compared with pharmaceuticals with similar qualities, such as Valium, kava is safer. German researchers estimate that kava produces 0.008 adverse event reports per million doses. Valium produces 2.12; however, Valium does not cause liver failure.
The American Botanical Council in Austin, Texas, the nation’s leading herb education organization, has developed a series of guidelines for safe use of kava:
• Don’t use kava if you have been diagnosed with liver disease or have a history of liver disease.
• Don’t use it if you take drugs with potential liver toxicity, including alcohol. Take a list of your medications to your physician or pharmacist and ask if any might cause liver toxicity. If so, do not take kava.
• Kava-related liver damage is associated with long-term use of the herb. Don’t take it daily for more than four weeks without consulting a medical professional for a liver-function test. “Periodic liver-function tests are required for those who take statin drugs to lower cholesterol,” says Mark Blumenthal, founder and executive director of the American Botanical Council. “I’d recommend them for long-term users of kava.”
• Stop taking kava if you notice nausea, vomiting, unusual fatigue, loss of appetite, darkening of urine or yellowing of the eyes. These all are symptoms of liver disease. If you develop these symptoms, consult a physician promptly.
In addition, here are other prudent suggestions.
• Look for products that specify only root/rhizome material. This is no guarantee you’ll get only root/rhizome material. But care in labeling often indicates care in harvesting.
• If you have had unusual reactions to other drugs, you might have a CYP2D6 enzyme deficiency. Recently a test became available, but it costs $500 and most health insurers do not cover it. At this price, it’s probably more cost-effective to use other herbal tranquilizers–such as chamomile (Matricaria recutita), hops (Humulus lupulus) and passionflower (Passiflora incarnata)–instead of kava.
Michael Castleman is a widely published health writer. Visit his website atwww.MCastleman.com.
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