Planta Med 2015; 81(18): 1647-1653
DOI: 10.1055/s-0035-1558295
Georg Thieme Verlag KG Stuttgart · New York

German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics

Kenny Kuchta
1   National Institute of Health Sciences, Division of Pharmacognosy, Phytochemistry and Narcotics, Setagaya-ku, Kamiyoga, Tokyo, Japan
Mathias Schmidt
2   HerbResearch Germany, Tussenhausen-Mattsies, Germany
Adolf Nahrstedt
3   Institut für Pharmazeutische Biologie und Phytochemie, Westf. Wilhelms-Universität, Münster, Germany
› Author Affiliations
Further Information

Publication History

received 08 September 2015
revised 19 October 2015

accepted 23 October 2015

Publication Date:
22 December 2015 (online)


Kava, the rhizome and roots of Piper methysticum, are one of the most important social pillars of Melanesian societies. They have been used for more than 1000 years in social gatherings for the preparation of beverages with relaxing effects. During the colonial period, extract preparations found their way into Western medicinal systems, with experience especially concerning the treatment of situational anxiety dating back more than 100 years. It therefore came as a surprise when the safety of kava was suddenly questioned based on the observation of a series of case reports of liver toxicity in 1999 and 2000. These case reports ultimately led to a ban of kava products in Europe – a ban that has been contested because of the poor evidence of risks related to kava. Only recently, two German administrative courts decided that the decision of the regulatory authority to ban kava as a measure to ensure consumer safety was inappropriate and even associated with an increased risk due to the higher risk inherent to the therapeutic alternatives. This ruling can be considered as final for at least the German market, as no further appeal has been pursued by the regulatory authorities. However, in order to prevent further misunderstandings, especially in other markets, the current situation calls for a comprehensive presentation of the cardinal facts and misconceptions concerning kava and related drug quality issues.

  • References

  • 1 Anonymous Kava-Kava: Eine Lücke, die keiner wollte. Interview mit Prof. Volker Faust. Natura Med 2002; 17: 14
  • 2 Ernst E. Marktrücknahme des pflanzlichen Anxiolytikums Kava: Nutzen unter-, Risiken überschätzt?. Münchn Med Wschr 2003; 144: 40
  • 3 Loew D, Gaus W. Kava-Kava. Tragödie einer Fehlentscheidung. Z Phytother 2002; 23: 267-281
  • 4 Loew D. Zum Widerruf von Kava-Extrakten. Politikum oder fachliche Fehlbeurteilung?. Ärzteztsch Naturheilverf 2003; 44: 884-896
  • 5 Loew D. Widerruf der Zulassung von Kava-Extrakten. War die Entscheidung des BfArM gerechtfertigt?. Dt Apotheker Ztg 2005; 145: 5362-5364
  • 6 Pittler MH, Ernst E. Kava extract for treating anxiety. Cochrane Database Syst Rev 2003; (1) CD003383
  • 7 Schmidt M, Nahrstedt A. Ist Kava lebertoxisch? Eine Analyse der bekannten Daten zum Leberrisiko von Kava-Präparaten. Dtsch Apoth Ztg 2002; 142: 1006-1011
  • 8 Schmidt M. Are kavalactones the hepatotoxic principle of kava extracts? The pitfalls of the glutathione theory. J Altern Complement Med 2003; 9: 183-187 author reply 187–188
  • 9 Stevinson C, Huntley A, Ernst E. A systematic review of the safety of kava extract in the treatment of anxiety. Drug Saf 2002; 25: 251-261
  • 10 Teschke R, Gaus W, Loew D. Kava extracts: safety and risks including rare hepatotoxicity. Phytomedicine 2003; 10: 440-446
  • 11 Teschke R. Kava-induzierte Leberschäden – Was ist gesichert?. Dtsch Apoth Ztg 2003; 143: 4011-4021
  • 12 Teschke R. Nicht einmal eine Verschreibungspflicht. FAZ 2003; 54: 8
  • 13 Singh YN, Devkota AK. Aqueous kava extracts do not affect liver function tests in rats. Planta Med 2003; 69: 496-499
  • 14 Bauer R, Kopp B, Nahrstedt A. Relevant hepatotoxic effects of kava still need to be proven. A statement of the Society for Medicinal Plant Research. Planta Med 2003; 69: 971-972
  • 15 Schmidt M. German court ruling reverses kava ban; German regulatory authority appeals decision. HerbalGram 2014; 103: 38-43
  • 16 Kraft K. Verwaltungsgericht Köln kippt das Kava-Verbot. Z Phytother 2014; 35: 186-189
  • 17 Sarris J, Kavanagh DJ, Byrne G, Bone KM, Adams J, Deed G. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum . Psychopharmacology (Berl) 2009; 205: 399-407
  • 18 Sarris J, Kavanagh DJ, Deed G, Bone KM. St. Johnʼs wort and Kava in treating major depressive disorder with comorbid anxiety: a randomised double-blind placebo-controlled pilot trial. Hum Psychopharmacol 2009; 24: 41-48
  • 19 Sarris J, Stough C, Bousman CA, Wahid ZT, Murray G, Teschke R, Savage KM, Dowell A, Ng C, Schweitzer I. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol 2013; 33: 643-648
  • 20 Sarris J, Stough C, Teschke R, Wahid ZT, Bousman CA, Murray G, Savage KM, Mouatt P, Ng C, Schweitzer I. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytother Res 2013; 27: 1723-1728
  • 21 Sarris J, Scholey A, Schweitzer I, Bousman C, Laporte E, Ng C, Murray G, Stough C. The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study. Hum Psychopharmacol 2012; 27: 262-269
  • 22 Schmidt M, Nahrstedt A, Lüpke NP. Piper methysticum (Kava) in der Diskussion: Betrachtungen zu Qualität, Wirksamkeit und Unbedenklichkeit. Wien Med Wochenschr 2002; 152: 382-388
  • 23 Teschke R, Schwarzenboeck A, Hennermann KH. Causality assessment in hepatotoxicity by drugs and dietary supplements. Br J Clin Pharmacol 2008; 66: 758-766
  • 24 Teschke R, Schwarzenboeck A, Hennermann KH. Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases. Eur J Gastroenterol Hepatol 2008; 20: 1182-1193
  • 25 Teschke R, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: challenges and pitfalls of causality assessment methods. World J Gastroenterol 2013; 19: 2864-2882
  • 26 Teschke R, Fuchs J, Bahre R, Genthner A, Wolff A. Kava hepatotoxicity: comparative study of two structured quantitative methods for causality assessment. J Clin Pharm Ther 2010; 35: 545-563
  • 27 Teschke R, Wolff A. Kava hepatotoxicity: regulatory data selection and causality assessment. Dig Liver Dis 2009; 41: 891-901
  • 28 Teschke R, Wolff A. Regulatory causality evaluation methods applied in kava hepatotoxicity: are they appropriate?. Regul Toxicol Pharmacol 2011; 59: 1-7
  • 29 Strahl S, Ehret V, Dahm HH, Maier KP. Nekrotisierende Hepatitis nach Einnahme pflanzlicher Heilmittel. Dtsch Med Wochenschr 1998; 123: 1410-1414
  • 30 Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity. Ann Intern Med 2001; 135: 68-69
  • 31 Johnson BM, Qiu SX, Zhang S, Zhang F, Burdette JE, Yu L, Bolton JL, van Breemen RB. Identification of novel electrophilic metabolites of Piper methysticum Forst (Kava). Chem Res Toxicol 2003; 16: 733-740
  • 32 Olsen LR, Grillo MP, Skonberg C. Constituents in kava extracts potentially involved in hepatotoxicity: a review. Chem Res Toxicol 2011; 24: 992-1002
  • 33 Hänsel R, Lazar J. Kawapyrone. Inhaltsstoffe des Rauschpfeffers in pflanzlichen Sedativa. Dtsch Apoth Ztg 1985; 125: 2056-2058
  • 34 Gaedcke F. SL-49: Pharmaceutical characterization of Kava-Kava extracts and their formulations. Phytomed 2000; 7 (Suppl. 02) 27
  • 35 Anonymous Assessment of the risk of hepatotoxicity with kava products. Geneva: World Health Organization; 2007
  • 36 Lewin L. Über Piper methysticum (Kawa-Kawa). Berl Klin Wschr 1886; 1: 7-10
  • 37 Zhou P, Gross S, Liu JH, Yu BY, Feng LL, Nolta J, Sharma V, Piwnica-Worms D, Qiu SX. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-kappaB and MAPK signaling pathways. FASEB J 2010; 24: 4722-4732
  • 38 Li X, Liu Z, Xu X, Blair CA, Sun Z, Xie J, Lilly MB, Zi X. Kava components down-regulate expression of ar and ar splice variants and reduce growth in patient-derived prostate cancer xenografts in mice. PLoS One 2012; 7: e31213
  • 39 Dragull K, Yoshida WY, Tang CS. Piperidine alkaloids from Piper methysticum . Phytochemistry 2003; 63: 193-198
  • 40 Nerurkar PV, Dragull K, Tang CS. In vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactones. Toxicol Sci 2004; 79: 106-111
  • 41 Lechtenberg M, Quandt B, Schmidt M, Nahrstedt A. Is the alkaloid pipermethystine connected with the claimed liver toxicity of Kava products?. Pharmazie 2008; 63: 71-74
  • 42 Teschke R, Qiu SX, Xuan TD, Lebot V. Kava and kava hepatotoxicity: requirements for novel experimental, ethnobotanical and clinical studies based on a review of the evidence. Phytother Res 2011; 25: 1263-1274
  • 43 Teschke R, Lebot V. Proposal for a kava quality standardization code. Food Chem Toxicol 2011; 49: 2503-2516
  • 44 Schmidt M, Carreno I, Vergano P. Technical assistance to the integration to the multilateral trading system and support to the integrated framework. Ref: 9 ACP RPR 140‐039/11: Establishment of health and safety standards for the production and export of kava-based products. Brussels: ACP-EU-TBT; 2012
  • 45 Lebot V. The quality of kava consumed in the South Pacific. HerbalGram 2006; 71: 34-37
  • 46 Schmidt M. Quality criteria for kava. HerbalGram 2007; 73: 44-49
  • 47 Lebot V, Merlin M, Lindstrom L. Kava, the Pacific elixir. New Haven: Yale University Press; 1992
  • 48 Siméoni P, Lebot V. Buveurs de kava. Port Vila, Vanuatu: Géo-consulte; 2014
  • 49 Lebot V. Kava in the Pacific. High Level Conference on Kava: Port Vila, Vanuatu; 2012
  • 50 Kaul PN, Joshi S. Alternative medicine: herbal drugs and their critical appraisal, Part II. Chapter 2: Kava-Kava. In: Jucker E, editor Progress in drug research, Vol. 57. Basel: Springer; 2001: 5-24
  • 51 Narayanapillai SC, Leitzman P, OʼSullivan MG, Xing C. Flavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice. Chem Res Toxicol 2014; 27: 1871-1876
  • 52 Lebot V, Do TK, Legendre L. Detection of flavokavins (A, B, C) in cultivars of kava (Piper methysticum) using high performance thin layer chromatography (HPTLC). Food Chem 2014; 151: 554-560
  • 53 Schmidt M. “Noble” vs. “Two-day” Phytochemical quality and analytical specifications. High Level Conference on Kava: Port Vila, Vanuatu; 2012
  • 54 Teschke R, Sarris J, Schweitzer I. Kava hepatotoxicity in traditional and modern use: the presumed Pacific kava paradox hypothesis revisited. Br J Clin Pharmacol 2012; 73: 170-174
  • 55 Kraft M, Spahn TW, Menzel J, Senninger N, Dietl KH, Herbst H, Domschke W, Lerch MM. Fulminant liver failure after administration of the herbal antidepressant kava-kava. Dtsch Med Wochenschr 2001; 126: 970-972