title: Evaluation of commercial kava extracts and kavalactone standards for mutagenicity and toxicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells.
abstract: Kava (Piper methysticum) is a member of the pepper family and has been cultivated by South Pacific islanders for centuries and used as a social and ceremonial drink. Traditionally, kava extracts are prepared by grinding or chewing the rhizome and mixing with water and coconut milk. The active constituents of kava are a group of approximately 18 compounds collectively referred to as kavalactones or kava pyrones. Kawain, dihydrokawain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin are the six major kavalactones. Kava beverages and other preparations are known to be anxiolytic and are used for anxiety disorders. Dietary supplements containing the root of the kava shrub have been implicated in several cases of liver toxicity in humans, including several who required liver transplants after using kava supplements. In order to study the toxicity and mutagenicity, two commercial samples of kava, Kaviar and KavaPure, and the six pure kavalactones including both D-kawain and DL-kawain, were evaluated in L5178Y mouse lymphoma cells. Neither the kava samples nor the kavalactones induced a mutagenic response in the L5178Y mouse lymphoma mutation assay with the addition of human liver S9 activation.
authors.affiliation: Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Parkway, HFS-717, College Park, MD 20740-3835, USA. paul.whittaker@fda.hhs.gov
authors.forename: Paul
authors.initials: P
authors.lastname: Whittaker
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Clarke
authors.forename: Richard H C
authors.initials: RH
authors.lastname: San
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Betz
authors.forename: Harold E
authors.initials: HE
authors.lastname: Seifried
authors.forename: Lowri S
authors.initials: LS
authors.lastname: de Jager
authors.forename: Virginia C
authors.initials: VC
authors.lastname: Dunkel
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003603:Cytotoxins / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D020901:Kava / Q000737:chemistry / Q000633:toxicity*; D007783:Lactones / Q000737:chemistry / Q000633:toxicity*; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008223:Lymphoma / Q000235:genetics; D013058:Mass Spectrometry; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D010936:Plant Extracts / Q000633:toxicity; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure