Publication Cover
Journal of Environmental Science and Health, Part C
Environmental Carcinogenesis and Ecotoxicology Reviews
Volume 26, 2008 - Issue 1
1,262
Views
63
CrossRef citations to date
0
Altmetric
Original Articles

Toxicity of Kava Kava

, , , &
Pages 89-112 | Published online: 05 Mar 2008

REFERENCES

  • Smith , R M , Thakrar , H , Arowolo , T A and Shafi , A A . 1984 . High-performance liquid chromatography of kava lactones from Piper methysticum . J Chromatog , 283 : 303 – 308 .
  • Lebot , V , Merlin , M and Lindstrom , L . 1992 . Kava: The Pacific Drug , 255 New Haven, CT : Yale University Press .
  • Dentali , S J . 1997 . Herb Safety Review. Kava. Piper methysticum Forster f. (Piperaceae) , 29 Boulder, CO : Herb Research Foundation .
  • Schulze , J , Raasch , W and Siegers , C P . 2003 . Toxicity of kava pyrones, drug safety and precautions—a case study . Phytomedicine , 10 ( Suppl4 ) : 68 – 73 .
  • Singh , Y N . 1992 . Kava: an overview . J Ethnopharmacol , 37 ( 1 ) : 13 – 45 .
  • Singh , Y N . 2005 . Potential for interaction of kava and St. John's wort with drugs . J Ethnopharmacol , 100 ( 1–2 ) : 108 – 13 .
  • Mirasol , F . 1998 . Botanicals industry posts strong growth in US. Chem . Market Rep , 28 ( 4 ) : 12 – 13 .
  • CFSAN. Center for Food Safety and Applied Nutrition(CFSAN) . March 25 2002 . Kava-containing dietary supplements may be associated with severe liver injury , March 25 , Rockville, Maryland : U.S. Department of Health and Human Services, Food and Drug Administration . (http://www.cfsan.fda.gov/∼dms/ds-warn.html):. 2002
  • CFSAN. Center for Food Safety and Applied Nutrition (CFSAN) . 2002 . Letter to health care professionals: FDA issues consumer advisory that kava products may be associated with severe liver injury (document issued March 25, 2002) , Rockville, Maryland : U.S. Department of Health and Human Services, Food and Drug Administration . (http://www.fda.gov/medwatch). 2002
  • Lim , S T , Dragull , K , Tang , C S , Bittenbender , H C , Efird , J T and Nerurkar , P V . 2007 . Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats . Toxicol Sci , 97 ( 1 ) : 214 – 21 .
  • He , X G , Lin , L Z and Lian , L Z . 1997 . Electrospray high performance liquid chromatography-mass spectrometry in phytochemical analysis of kava (Piper methysticum) extract . Planta Med , 63 ( 1 ) : 70 – 4 .
  • Clouatre , D L . 2004 . Kava kava: examining new reports of toxicity . Toxicol Lett , 150 ( 1 ) : 85 – 96 .
  • Shulgin , A T . 1973 . The narcotic pepper—the chemistry and pharmacology of Piper methysticum and related species . Bull Narc , 25 : 59 – 74 .
  • Israili , Z H and Smissman , E E . 1976 . Synthesis of kavain, dihydrokavain, and analogues . J Org Chem , 41 ( 26 ) : 4070 – 74 .
  • Norton , S A and Ruze , P . 1994 . Kava dermopathy . J Am Acad Dermatol , 31 ( 1 ) : 89 – 97 .
  • Jamieson , D D , Duffield , P H , Cheng , D and Duffield , A M . 1989 . Comparison of the central nervous system activity of the aqueous and lipid extract of kava (Piper methysticum) . Arch Int Pharmacodyn Ther , 301 : 66 – 80 .
  • Bilia , A R , Gallon , S and Vincieri , F F . 2002 . Kava-kava and anxiety: growing knowledge about the efficacy and safety . Life Sci , 70 ( 22 ) : 2581 – 97 .
  • Ernst , E . 2006 . Herbal remedies for anxiety—a systematic review of controlled clinical trials . Phytomedicine , 13 ( 3 ) : 205 – 8 .
  • Keledjian , J , Duffield , P H , Jamieson , D D , Lidgard , R O and Duffield , A M . 1988 . Uptake into mouse brain of four compounds present in the psychoactive beverage kava . J Pharm Sci , 77 ( 12 ) : 1003 – 6 .
  • Rasmussen , A K , Scheline , R R , Solheim , E and Hansel , R . 1979 . Metabolism of some kava pyrones in the rat . Xenobiotica , 9 ( 1 ) : 1 – 16 .
  • Duffield , A M , Jamieson , D D , Lidgard , R O , Duffield , P H and Bourne , D J . 1989 . Identification of some human urinary metabolites of the intoxicating beverage kava . J Chromatogr , 475 : 273 – 81 .
  • Zou , L , Harkey , M R and Henderson , G L . 2005 . Synthesis, in vitro, reactivity, and identification of 6-phenyl-3-hexen-2-one in human urine after kava-kava (Piper methysticum) ingestion . Planta Med , 71 ( 2 ) : 142 – 6 .
  • Johnson , B M , Qiu , S X , Zhang , S , Zhang , F , Burdette , J E , Yu , L , Bolton , J L and van Breemen , R B . 2003 . Identification of novel electrophilic metabolites of piper methysticum Forst (Kava) . Chem Res Toxicol , 16 ( 6 ) : 733 – 40 .
  • Jamieson , D D and Duffield , P H . 1990 . The antinociceptive actions of kava components in mice . Clin Exp Pharmacol Physiol , 17 ( 7 ) : 495 – 507 .
  • Kumar , V . 2006 . Potential medicinal plants for CNS disorders: an overview . Phytother Res , 20 ( 12 ) : 1023 – 35 .
  • Jussofie , A , Schmiz , A and Hiemke , C . 1994 . Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain . Psychopharmacology (Berl) , 116 ( 4 ) : 469 – 74 .
  • Almeida , J C and Grimsley , E W . 1996 . Coma from the health food store: interaction between kava and alprazolam . Ann Intern Med , 125 ( 11 ) : 940 – 1 .
  • Wu , D , Yu , L , Nair , M G , De Witt , D L and Ramsewak , R S . 2002 . Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots . Phytomedicine , 9 ( 1 ) : 41 – 7 .
  • Brauer , R , Pfab , R , Becker , K , Berger , H and Stangl , M . 2001 . Fulminantes leberversagen nach einnahme des pfalzlichen heimittels kava-kava . Z Gastroenterol , 39 : 491
  • Saß , M , Schnabel , S , Kröger , J , Liebe , S and Schareck , W D . 2001 . Acute liver failure from kavakava—a rare indication for liver transplantation . Z. Gastroenterol , 39 : 491
  • Humberston , C L , Akhtar , J and Krenzelok , E P . 2003 . Acute hepatitis induced by kava kava . J Toxicol Clin Toxicol , 41 ( 2 ) : 109 – 13 .
  • Russmann , S , Lauterburg , B H and Helbling , A . 2001 . Kava hepatotoxicity . Ann Intern Med , 135 ( 1 ) : 68 – 9 .
  • Russmann , S , Barguil , Y , Cabalion , P , Kritsanida , M , Duhet , D and Lauterburg , B H . 2003 . Hepatic injury due to traditional aqueous extracts of kava root in New Caledonia . Eur J Gastroenterol Hepatol , 15 ( 9 ) : 1033 – 6 .
  • 2002 . Kava kava may cause irreversible liver damage . S. Afr. Med. J. , 92 : 961
  • Anon . 2002 . Concerns over kava have the FDA's attention . Mayo Clin. Health Lett , 20 : 4
  • Anon . 2002 . Kava concerns. FDA, Botanical Council raises safety concerns . AWHONN Lifelines , 6 : 13 – 15 .
  • Anon . 2003 . From the Centers for Disease Control and Prevention. Hepatic toxicity possibly associated with kava-containing products-United States, Germany, and Switzerland, 1999–2002 . JAMA , 289 : 36 – 37 .
  • Campo , J V , McNabb , J , Perel , J M , Mazariegos , G V , Hasegawa , S L and Reyes , J . 2002 . Kava-induced fulminant hepatic failure . J Am Acad Child Adolesc Psychiatry , 41 ( 6 ) : 631 – 2 .
  • Parkman , C A . 2002 . Another FDA warning: Kava supplements . Case Manager , 13 ( 4 ) : 26 – 8 .
  • De Smet , P A . 2002 . Safety concerns about kava not unique . Lancet , 360 : 1336
  • Clough , A R , Bailie , R S and Currie , B . 2003 . Liver function test abnormalities in users of aqueous kava extracts . J Toxicol Clin Toxicol , 41 ( 6 ) : 821 – 9 .
  • Anke , J and Ramzan , I . 2004 . Kava Hepatotoxicity: Are we any closer to the truth? . Planta Med , 70 ( 3 ) : 193 – 6 .
  • Rietjens , I M , Martena , M J , Boersma , M G , Spiegelenberg , W and Alink , G M . 2005 . Molecular mechanisms of toxicity of important food-borne phytotoxins . Mol Nutr Food Res , 49 ( 2 ) : 131 – 58 .
  • Anke , J , Fu , S and Ramzan , I . 2006 . Kavalactones fail to inhibit alcohol dehydrogenase in vitro . Phytomedicine , 13 ( 3 ) : 192 – 5 .
  • Whitton , P A , Lau , A , Salisbury , A , Whitehouse , J and Evans , C S . 2003 . Kava lactones and the kava-kava controversy . Phytochemistry , 64 ( 3 ) : 673 – 9 .
  • Bujanda , L , Palacios , A , Silvarino , R , Sanchez , A and Munoz , C . 2002 . [Kava-induced acute icteric hepatitis] . Gastroenterol Hepatol , 25 ( 6 ) : 434 – 5 .
  • Stickel , F , Baumuller , H M , Seitz , K , Vasilakis , D , Seitz , G , Seitz , H K and Schuppan , D . 2003 . Hepatitis induced by Kava (Piper methysticum rhizoma) . J Hepatol , 39 ( 1 ) : 62 – 7 .
  • Escher , M , Desmeules , J , Giostra , E and Mentha , G . 2001 . Hepatitis associated with Kava, a herbal remedy for anxiety . Bmj , 322 ( 7279 ) : 139
  • Kraft , M. T.W. S. , Menzel , J , Senninger , N , Dietl , K H , Herbst , H , Domschke , W and Lerch , M M . 2001 . Fulminant liver failure after administration of the herbal antidepressant Kava-Kava . Dtsch Med Wochensch , 126 : 970 – 972 .
  • Thomsen , M , Vitetta , L , Schmidt , M and Sali , A . 2004 . Fatal fulminant hepatic failure induced by a natural therapy containing kava . Med J Aust , 180 ( 4 ) : 198 – 9 . author reply 199
  • Gow , P J , Connelly , N J , Hill , R L , Crowley , P and Angus , P W . 2003 . Fatal fulminant hepatic failure induced by a natural therapy containing kava . Med J Aust , 178 ( 9 ) : 442 – 3 .
  • Ruze , P . 1990 . Kava-induced dermopathy: a niacin deficiency? . Lancet , 335 ( 8703 ) : 1442 – 5 .
  • Norton , S A . 1998 . Herbal medicines in Hawaii from tradition to convention . Hawaii Med. J. , 57 : 383 – 386 .
  • Mathews , J D , Riley , M D , Fejo , L , Munoz , E , Milns , N R , Gardner , I D , Powers , J R , Ganygulpa , E and Gununuwawuy , B J . 1988 . Effects of the heavy usage of kava on physical health: summary of a pilot survey in an aboriginal community . Med J Aust , 148 ( 11 ) : 548 – 55 .
  • Schelosky , L , Raffauf , C , Jendroska , K and Poewe , W . 1995 . Kava and dopamine antagonism . J Neurol Neurosurg Psychiatry , 58 ( 5 ) : 639 – 40 .
  • Pfeiffer , C C , Murphree , H B and Goldstein , L . 1967 . “ Effects of kava in normal subjects and patients ” . In Ethnopharmacologic Search for Psychoactive Drugs , Edited by: Efron , D H , Holmstedt , B and Kline , N S . 155 – 161 . Public Health Service Publication . No. 1645, Proceedings of a symposium held in San Francisco, Ca. January 28-30, 1967
  • Dragull , K , Yoshida , W Y and Tang , C S . 2003 . Piperidine alkaloids from Piper methysticum . Phytochemistry , 63 ( 2 ) : 193 – 8 .
  • Smith , K K , Dharmaratne , H R , Feltenstein , M W , Broom , S L , Roach , J T , Nanayakkara , N P , Khan , I A and Sufka , K J . 2001 . Anxiolytic effects of kava extract and kavalactones in the chick social separation-stress paradigm . Psychopharmacology (Berl) , 155 ( 1 ) : 86 – 90 .
  • Nerurkar , P V , Dragull , K and Tang , C S . 2004 . In vitro toxicity of kava alkaloid, pipermethystine, in Hep G2 cells compared to kavalactones . Toxicol Sci , 79 ( 1 ) : 106 – 11 .
  • Hsu , S Y , Lin , M H , Lin , L C and Chou , C J . 1994 . Toxicologic studies of dihydro-5,6-dehydrokawain and 5,6-dehydrokawain . Planta Med , 60 ( 1 ) : 88 – 90 .
  • Duffield , P H and Jamieson , D . 1991 . Development of tolerance to kava in mice . Clin Exp Pharmacol Physiol , 18 ( 8 ) : 571 – 8 .
  • Jhoo , J W , Freeman , J P , Heinze , T M , Moody , J D , Schnackenberg , L K , Beger , R D , Dragull , K , Tang , C S and Ang , C Y . 2006 . In vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum) . J Agric Food Chem , 54 ( 8 ) : 3157 – 62 .
  • Jhoo , J , Ang , C YW , Mei , N , Chen , T , Dragull , K and Tang , C . 2006 . “ Kava (Piper methysticum) Safety issues and studies for cytotoxicity and mutagenicity of pipermethystine ” . In American Chemistry Society Book Series: Dietary Supplements , Edited by: Ho , C. New York, NY : Oxford University Press, Inc. .
  • Kaplowitz , N . 1997 . Hepatotoxicity of herbal remedies: insights into the intricacies of plant-animal warfare and cell death . Gastroenterology , 113 ( 4 ) : 1408 – 12 .
  • Eichelbaum , M , Kroemer , H K and Fromm , M F . 1997 . Impact of P450 genetic polymorphism on the first-pass extraction of cardiovascular and neuroactive drugs . Adv Drug Deliv Rev , 27 ( 2–3 ) : 171 – 199 .
  • Strahl , S , Ehret , V , Dahm , H H and Maier , K P . 1998 . [Necrotizing hepatitis after taking herbal remedies] . Dtsch Med Wochenschr , 123 ( 47 ) : 1410 – 4 .
  • Russmann , S , Lauterburg , B H , Barguil , Y , Choblet , E , Cabalion , P , Rentsch , K and Wenk , M . 2005 . Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: Protective effect against environmental carcinogens? . Clin Pharmacol Ther , 77 ( 5 ) : 453 – 4 .
  • Raucy , J L . 2003 . Regulation of CYP3A4 expression in human hepatocytes by pharmaceuticals and natural products . Drug Metab Dispos , 31 ( 5 ) : 533 – 9 .
  • Gibson , G G , Plant , N J , Swales , K E , Ayrton , A and El-Sankary , W . 2002 . Receptor-dependent transcriptional activation of cytochrome P4503A genes: induction mechanisms, species differences and interindividual variation in man . Xenobiotica , 32 ( 3 ) : 165 – 206 .
  • Meijerman , I , Beijnen , J H and Schellens , J H . 2006 . Herb-drug interactions in oncology: focus on mechanisms of induction . Oncologist , 11 ( 7 ) : 742 – 52 .
  • Hodgson , E and Philpot , R M . 1974 . Interaction of methylenedioxyphenyl (1,3-benzodioxole) compounds with enzymes and their effects on mammals . Drug Metab Rev , 3 ( 2 ) : 231 – 301 .
  • Murray , M and Reidy , G F . 1989 . In vitro formation of an inhibitory complex between an isosafrole metabolite and rat hepatic cytochrome P-450 PB-B . Drug Metab Dispos , 17 ( 4 ) : 449 – 54 .
  • Murray , M , Wilkinson , C F , Marcus , C and Dube , C E . 1983 . Structure-activity relationships in the interactions of alkoxymethylenedioxybenzene derivatives with rat hepatic microsomal mixed-function oxidases in vivo . Mol Pharmacol , 24 ( 1 ) : 129 – 36 .
  • Unger , M , Holzgrabe , U , Jacobsen , W , Cummins , C and Benet , L Z . 2002 . Inhibition of cytochrome P450 3A4 by extracts and kavalactones of Piper methysticum (Kava-Kava) . Planta Med , 68 ( 12 ) : 1055 – 8 .
  • Cote , C S , Kor , C , Cohen , J and Auclair , K . 2004 . Composition and biological activity of traditional and commercial kava extracts . Biochem Biophys Res Commun , 322 ( 1 ) : 147 – 52 .
  • Zou , L , Harkey , M R and Henderson , G L . 2002 . Effects of herbal components on c DNA-expressed cytochrome P450 enzyme catalytic activity . Life Sci , 71 ( 13 ) : 1579 – 89 .
  • Mathews , J M , Etheridge , A S and Black , S R . 2002 . Inhibition of human cytochrome P450 activities by kava extract and kavalactones . Drug Metab Dispos , 30 ( 11 ) : 1153 – 7 .
  • Mathews , J M , Etheridge , A S , Valentine , J L , Black , S R , Coleman , D P , Patel , P , So , J and Burka , L T . 2005 . Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro . Drug Metab Dispos , 33 ( 10 ) : 1555 – 63 .
  • Bressler , R . 2005 . Herb-drug interactions: interactions between kava and prescription medications . Geriatrics , 60 ( 9 ) : 24 – 5 .
  • Hu , Z , Yang , X , Ho , P C , Chan , S Y , Heng , P W , Chan , E , Duan , W , Koh , H L and Zhou , S . 2005 . Herb-drug interactions: a literature review . Drugs , 65 ( 9 ) : 1239 – 82 .
  • Anke , J and Ramzan , I . 2004 . Pharmacokinetic and pharmacodynamic drug interactions with Kava (Piper methysticum Forst. f.) . J Ethnopharmacol , 93 ( 2–3 ) : 153 – 60 .
  • Clayton , N P , Yoshizawa , K , Kissling , G E , Burka , L T , Chan , P C and Nyska , A . 2007 . Immunohistochemical analysis of expressions of hepatic cytochrome P450 in F344 rats following oral treatment with kava extract . Exp Toxicol Pathol , 58 ( 4 ) : 223 – 36 .
  • Poolsup , N , Li Wan Po , A and Knight , T L . 2000 . Pharmacogenetics and psychopharmacotherapy . J Clin Pharm Ther , 25 ( 3 ) : 197 – 220 .
  • Wanwirolmuk , S , Bhawan , S , Coville , P and Chalcroft , S . 1998 . Genetic polymorphism of debrisoquine (CYP2D6) and proguanil (CYP2C19) in south Pacific Polynesian populations . Euro J Clin Pharmacol , 54 : 431 – 435 .
  • Liu , L L , Gong , L K , Qi , X M , Cai , Y , Wang , H , Wu , X F , Xiao , Y and Ren , J . 2005 . Altered expression of cytochrome P450 and possible correlation with preneoplastic changes in early stage of rat hepatocarcinogenesis . Acta Pharmacol Sin , 26 ( 6 ) : 737 – 44 .
  • Gurley , B J , Swain , A , Barone , G W , Williams , D K , Breen , P , Yates , C R , Stuart , L B , Hubbard , M A , Tong , Y and Cheboyina , S . 2007 . Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans . Drug Metab Dispos , 35 ( 2 ) : 240 – 5 .
  • Folmer , F , Blasius , R , Morceau , F , Tabudravu , J , Dicato , M , Jaspars , M and Diederich , M . 2006 . Inhibition of TNFalpha-induced activation of nuclear factor kappa B by kava (Piper methysticum) derivatives . Biochem Pharmacol , 71 ( 8 ) : 1206 – 18 .
  • Knight , E V , Kimball , J P , Keenan , C M , Smith , I L , Wong , F A , Barrett , D S , Dempster , A M , Lieuallen , W G , Panigrahi , D and Powers WJ and others . 1996 . Preclinical toxicity evaluation of tepoxalin, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, in Sprague-Dawley rats and beagle dogs . Fundam Appl Toxicol , 33 ( 1 ) : 38 – 48 .
  • Reilly , T P , Brady , J N , Marchick , M R , Bourdi , M , George , J W , Radonovich , M F , Pise-Masison , C A and Pohl , L R . 2001 . A protective role for cyclooxygenase-2 in drug-induced liver injury in mice . Chem Res Toxicol , 14 ( 12 ) : 1620 – 8 .
  • Kaplowitz , N . 2001 . Causality assessment versus guilt-by-association in drug hepatotoxicity . Hepatology , 33 ( 1 ) : 308 – 10 .
  • Croom , E MJ and Walker , L . 1995 . Botanicals in the pharmacy: New life for old remedies . Drug Top , 139 : 84 – 93 .

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.