As a near decade-long ban of kava (Piper methysticum) continues in 5 major Western countries, an international group of scientists is encouraging the reintroduction of the anti-anxiety herb into the global market.1 Though many in the kava industry have been calling for the herb’s reintroduction for some time—as its ban was widely seen as unjustified—these recent articles define a clear and detailed plan for how to safely reimplement the herb considering its complicated history.
Beginning in 2002, kava’s use was banned in Germany, the United Kingdom, Switzerland, France, Canada, and other countries following reports that it was associated with serious toxic liver injury. The UK health authorities reviewed its kava prohibition in 2005, but decided to uphold it.2 Kava has never been banned in the United States, where it continues to be sold as a dietary supplement, although at much lower levels since the US Food and Drug Administration advised consumers on the potential liver hepatotoxicity issue in 2002.3
Australia’s Therapeutic Goods Administration (TGA) issued a voluntary recall of all registered products containing kava following a liver failure-related death of a woman who had been taking a kava medicine. After ordering and analyzing a safety review on the plant, however, the TGA amended its regulations to approve water-soluble kava extracts and dried kava rhizome for use in tea bags for over-the-counter medicinal use in 2005, thus restricting use of alcoholic and/or acetonic kava extracts.4 Various clinical trials and a 2006 systematic review by the Cochrane Collaboration have shown that kava shows efficacy in treating symptoms associated with generalized anxiety disorders.5
Experts on kava have noted that the rare cases of liver adverse events are not reflective of traditional kava use in the South Pacific—which has a history of safety—nor with widespread European use.5,6 They have suggested that these events were instead likely caused by the use of poor quality raw kava material or incorrect kava cultivars and/or plant parts in the manufacture of a few extracts.7
Writing in recent issues of the British Journal for Clinical Pharmacology and Phytomedicine, leading kava experts in Australia and Germany suggest reestablishing the legal use of kava according to traditional use “for the sake of the patients and the South Pacific Economy,” as these bans have significantly damaged the South Pacific communities that serve as main sources of cultivated kava.5 The experts’ 6-point plan for safe kava reintroduction includes the following points:1,8
1) Ideally use one of several noble kava cultivars (those having a certain chemotype signature and high amounts of kavain and dihydrokavain and low amounts of methysticin and desmethoxyyangonin) that have a history of safe traditional use and are at least 5 years old. Make regulatory kava standardizations for the best noble cultivars mandatory.
2) Use only the peeled and dried rhizome and underground roots of the kava plant, as opposed to its leaves and/or aerial parts. Establish legislation to ensure that only these are exported for use in kava medicines and dietary supplements, and ensure that requirements for use in the South Pacific and in international exports are the same.
3) Give water-soluble kava extracts preference over those extracted using alcohol or a chemical solution.
4) Define and establish standards for a recommended daily dosage of kavalactones (the primary active compounds) and duration of treatment.
5) Conduct systematic and rigorous research into kava’s safety issues, such as using poorly stored and manufactured kava material and/or incorrect cultivar and plant material, and conduct human clinical trials using noble cultivars prepared through good pharmaceutical manufacturing practices.
6) Implement and strictly enforce a Pan-Pacific quality control system.
Global Response
The United Kingdom
When asked if it would review its ban on kava, based on the kava experts’ recent recommendations, Richard Woodfield, head of Herbal Policy at the UK Medicines and Healthcare products Regulatory Agency (MHRA) sent the following statement: “The MHRA were unaware of the BJCP article. Having reviewed it, we do not believe that it presents anything new in terms of scientific support for the safe use of kava. For example, the lack of hepatotoxicity reports when there was no process for [gathering] does not provide reassurance that the traditional products are safe. Similarly, the suggestion that introducing quality controls and reverting to traditional methods on the basis that these are safe equally would not provide a sufficient basis on which the Agency could justify lifting the ban on Kava.
“It should also be kept in mind,” Woodfield continued, “that with the introduction of the Traditional Herbal Medicinal Products Directive [THMPD], any kava based products would have to apply for at traditional herbal registration (THR) or a full marketing authorisation (MA). The MHRA does not think that the points outlined in the report to support the return of Kava to the worldwide market would address the requirements which are necessary for a THR or MA application/approval” (e-mail, March 14, 2011).
Germany
The situation in Germany could depend on the ability of a group of kava manufacturers to communicate a solution for efficacy and safety concerns with the German Federal Institute for Drugs and Medical Devices (BfArM).
“This is why these new papers are so important,” said Mathias Schmidt, PhD, a pharmacist with HERBResearch Germany who has long-term experience with kava research (e-mail, March 7-29, 2011). However, Dr. Schmidt and the kava steering group that he scientifically consults disagree with several aspects of the authors’ 6 key recommendations. They think the first point should recommend using cultivars that are exclusively of a noble cultivar, as opposed to ideally; and that the use of ethanol extracts should not be discouraged, as there is “a history of more than 100 years of safe use in Europe” and it seems that the choice of cultivar impacts eventual toxicity. Also, Dr. Schmidt said that future dosage recommendations should consider that kavalactones from noble kava “have never been shown to be toxic” because “the difference is in the kavalactone distribution (relative quantities of the six individual compounds) and in the presence of other secondary plant metabolites such as flavokavins.”
Dr. Schmidt noted that the push for kava reintroduction in Germany won’t be imminently successful. “The situation has always been a political issue,” he said, “not a scientific one. And believe me, this is politics at its worst.”
According to Dr. Schmidt, the kava steering group has a long and difficult history of attempting to resolve the kava situation with BfArM. It began in 2001, when there were 8 cases of severe liver toxicity in Switzerland, said Dr. Schmidt. “BfArM [informed] the press about the dangers of kava, and a multitude of very poorly documented case reports [flowed] in.” BfArM then claimed that kava extracts registered in Germany had never been shown to be efficacious. Based on this purported lack of efficacy and the reported adverse reactions, BfArM banned the herb in 2002.
The 9 years since the ban, said Dr. Schmidt, have consisted of BfArM’s issuing ambiguous requirements for data, rejecting proposals, and canceling meetings—the most recent of which was set to take place in April of 2011 but was recently canceled by BfArM. Though BfArM repealed its ban on kava products in 2005, all kava registrations have been inactivated indefinitely until further notice.9
According to Dr. Schmidt, the German Commission E—a panel of federally appointed experts who advise BfArM—had voted to switch kava to prescription status and “clearly spoke against a ban.” When BfArM ignored the recommendation and banned kava, “Commission E members were very angry and published a corresponding statement in favor of kava,” said Dr. Schmidt. Additionally, an independent expert report by Phytopharm Consulting later criticized BfArM for fostering an inaccurate and negative kava reputation through its ignoring and/or misinterpreting of important scientific data.10
“We have now been presenting BfArM with scientific data for 10 years, but they don’t want to listen,” said Dr. Schmidt. “The ban was fully based on formal grounds, not on a scientific debate. Scientists were never heard in the process.”
Due to years of delay the kava steering group would like to sue the government agency, according to Dr. Schmidt. Usually, pharmaceutical companies can sue BfArM only over a decision, but no decision has been made with the kava case. “Our only chance would be to sue them for inactivity, and then for having built a very sloppy case against kava,” he said. “I do not see a change coming so soon.” So why would BfArM be politically invested in maintaining the kava ban? “Probably there is no secret power behind the story, just an authority anxious not to admit that they were dead wrong,” said Dr. Schmidt, noting that the media would either fiercely attack the BfArM for lifting the ban or question its methods and reasoning for implementing the ban.
This current situation could change due to a recent decision by German kava manufacturers to alter the dosing of their banned kava products so that it corresponds with efficacious dosing used in clinical trials, Dr. Schmidt continued. “This effectively takes away BfArM’s major argument. They say, ‘As kava is not efficacious, we do not need to discuss the safety.’ However, if kava is efficacious, BfArM must look into the safety situation.”
The United States
In the United States, kava dietary supplements almost always contain label warnings about potential liver injury, recommending discontinuation of use if certain symptoms appear which are associated with liver dysfunction.
One of the authors of the recent papers encouraging kava reintroduction, Rolf Teschke, MD, wrote a review article in the March 2011 AHPA Report of the American Herbal Products Association (AHPA), in which he reiterated his reasoning for supporting a lift of kava bans across the world.11 In a following news release, AHPA’s Chief Science Officer, Steven Dentali, PhD, said Dr. Teschke’s article “underscores the fact that there isn't enough information to say that the safety issue with kava is likely supposed toxicity associated with its constituent kavalactones, a possible purported basis for many of the bans and restrictions on kava products.”
“Case reports can only serve as sentinel events,” continued Dr. Dentali. “In the absence of an immediate health hazard, an understanding of the materials involved, their chemical constituents, possible mechanisms of action, and other considerations are needed to properly evaluate sentinel events before bans are implemented against potentially useful remedies.”
—Lindsay Stafford
References
1. Experts propose global guidelines for safe use and production of Kava. The University of Melbourne Newsroom. February 27, 2011. Available at: http://newsroom.melbourne.edu/news/n-469. Accessed March 30, 2011.
2. Cavaliere C, Blumenthal B. UK expert committee upholds kava ban. HerbalGram. 2006;72:59. Available at: http://cms.herbalgram.org/herbalgram/issue72/article3045.html.
3. Consumer advisory: kava-containing dietary supplements may be associated with severe liver injury. US Food and Drug Administration. March 25, 2002. Available at: www.fda.gov/Food/ResourcesForYou/Consumers/ucm085482.htm. Accessed March 31, 2011.
4. Kava fact sheet. Australian Government Department of Health and Ageing Therapeutic Goods Administration website. April 2005. Available at: www.tga.gov.au/cm/kavafs0504.htm. Accessed March 31, 2011.
5. Teschke R, Sarris J, Glass X, Schulze J. Kava, the anxiolytic herb: back to basics to prevent liver injury? Br J Clin Pharmacol. 2011. 71;3:445–448.
6. Schmidt M. Quality criteria for kava. HerbalGram. 2007;73:44.
7. Teschke R. Kava and the risk of liver toxicity: past, current, and future. AHPA Report. 2011. 26(3).
8. Teschke R, Sarris J, Lebot V. Kava hepatotoxicity solution: A six-point plan for new kava standardization Phytomedicine. 2001. 18:96–103.
9. Blumenthal M. German government reconsiders kava. HerbalGram. 2005; 67:21-22. Available at: http://cms.herbalgram.org/herbalgram/issue67/article2844.html.
10. Gruenwald J. Kava stakeholders plan regulatory review and market return. HerbalGram. 2004;61:69-70. Available at: http://cms.herbalgram.org/herbalgram/issue61/article2651.html.
11. Kava trade and use restrictions may be based on inadequate information [press release]. American Herbal Products Association; Silver Spring, MD. March 8, 2011. Available at: www.ahpa.org/Default.aspx?tabid=69&aId=644. Accessed March 30, 2011.
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