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Second thoughts about kava

2002; Elsevier BV; Volume: 113; Issue: 4 Linguagem: Inglês

10.1016/s0002-9343(02)01204-4

1555-7162

Edzard Ernst,

Complementary and Alternative Medicine Studies

Kava (Piper methysticum) has long been used by the inhabitants of the South Pacific, mainly for making a recreational beverage. Its traditional indications include gonorrhea, syphilis, cystitis, weight reduction, muscle relaxation, and sleep induction (1Ernst E. Pittler M.H. Stevinson C. et al.The Desktop Guide to Complementary and Alternative Medicine. Mosby, Edinburgh, UK2001: 128-130Google Scholar). More recently, it has attracted considerable research interest for its alleged anxiolytic properties. Clinical trials of its efficacy have been undertaken, mostly in Germany. In 1990, the German Commission E issued a statement supporting the use of kava pyrones (60 to 120 mg) for self-medication for up to 3 months (2Blumenthal M. Goldberg A. Brinckmann J. Herbal Medicine Expanded Commission E Monographs. Integrative Medicine Communications, Austin, TX2000: 221-225Google Scholar). A recent meta-analysis reported that kava extracts (300 to 800 mg/d in divided doses) are relatively safe and more efficacious than placebo in the treatment of anxiety (3Pittler M.H. Ernst E. Efficacy of kava extract for treating anxiety systematic review and meta-analysis.J Clin Psychopharmacol. 2000; 20: 84-89Crossref PubMed Scopus (242) Google Scholar). Kava is believed to affect GABAA receptors in the hippocampus and amygdala complex (1Ernst E. Pittler M.H. Stevinson C. et al.The Desktop Guide to Complementary and Alternative Medicine. Mosby, Edinburgh, UK2001: 128-130Google Scholar), and perhaps dopamine D2 and histamine receptors as well (4Dinh L.D. Simmen U. Bueter K.B. et al.Interaction of various Piper methysticum cultivars with CNS receptors in vitro.Planta Med. 2001; 67: 306-311Crossref PubMed Scopus (40) Google Scholar). Based on encouraging scientific evidence and skillful marketing, kava products became a commercial success. An estimated 70 million daily doses have been consumed in Germany alone, although 70% to 80% of kava is consumed in Polynesia (5Gruenwald J. Freder J. Kava the present European situation.Nutraceuticals World. 2002; January/February: 22-24Google Scholar). In the United States, the total retail sale of kava was estimated at $17 million in 1998 (6Blumenthal M. Herbal market levels after five years of boom.Herbal Gram. 1999; 47: 64-65Google Scholar). These figures, however, are now likely to plummet because of second thoughts about the safety of this herbal medicine. During the last year, more cases of severe liver toxicity associated with kava use have been reported in Europe. A recent publication lists 30 European cases (Table) (5Gruenwald J. Freder J. Kava the present European situation.Nutraceuticals World. 2002; January/February: 22-24Google Scholar), and the Food and Drug Administration and other non-European agencies have also reported instances of liver toxicity (7Gruenwald J. International kava-alliance.Neutraceuticals World. 2002; April: 22-23Google Scholar). Causality has been difficult to establish, and it has been argued that part of the negative coverage of kava reflects a generally biased attitude toward herbal medicines (8Loew D.L. Kava kava extrakt.Dtsche Apotheker Zeitung. 2002; 141: 64-74Google Scholar). In addition to concerns about toxicity, kava was suspected to have caused parkinsonism in a 45-year-old woman who had taken a supplement containing kava extracts (65 mg/d) for 10 days (9Meseguer E. Taboada R. Sánchez V. et al.Life-threatening parkinsonism induced by Kava-Kava.Mov Disord. 2002; 17: 195-196Crossref PubMed Scopus (33) Google Scholar). Her severe and persistent parkinsonism responded to anticholinergics. The association between kava use and parkinsonism, however, could not be confirmed.TableOverview of 30 Cases of Kava-Related Liver Toxicity in Europe*From reference 5.DosageKava extract, 60 to 400 mg/d (sometimes within recommended range of 60 to 120 mg/d). Dosage not reported in 9 cases.Length of treatmentSeveral days to 2 years.Type of extractEthanolic extract (n = 13 cases), acetonic extract (n = 10), and pure kavain (n = 4). No information was given in remaining cases.Clinical outcomeDeath (n = 1), liver transplantation (n = 5), and liver damage ranging from increase of liver enzyme level to hepatic insufficiency in remaining patients.Concomitant therapyOther medication could have played a role in all but 4 cases; in 14 cases, multiple other drugs were administered.* From reference 5Gruenwald J. Freder J. Kava the present European situation.Nutraceuticals World. 2002; January/February: 22-24Google Scholar. Open table in a new tab Because of these reports, kava has all but disappeared from the markets. Withdrawal has been voluntary in some countries and enforced by regulatory authorities in others. In the United States, health authorities have alerted consumers and health care professionals to the risk of severe liver injury associated with kava (7Gruenwald J. International kava-alliance.Neutraceuticals World. 2002; April: 22-23Google Scholar). Such reactions are prudent first steps, but what should happen next? First, we need to understand if the cases of liver damage are incidental, if they are predictable, and how often they occur. Next, we need to view this data in relation to the known benefits of kava (3Pittler M.H. Ernst E. Efficacy of kava extract for treating anxiety systematic review and meta-analysis.J Clin Psychopharmacol. 2000; 20: 84-89Crossref PubMed Scopus (242) Google Scholar); for example, does kava do more good than harm? And finally, we need to compare the risk-benefit profile of kava with that of other similarly effective anxiolytic drugs. Preliminary data by Schulze et al., presented at the 2001 Annual Meeting of the Swiss Society of Pharmacology, suggest that the adverse effects associated with conventional anxiolytics may be greater than those of kava. If this is confirmed, perhaps we will see a return of kava.