Toxicokinetics of kava

Abstract

Kava is traditionally consumed by South Pacific islanders as a drink and became popular in Western society as a supplement for anxiety and insomnia. Kava extracts are generally well tolerated, but reports of hepatotoxicity necessitated an international reappraisal of its safety. Hepatotoxicity can occur as an acute, severe form or a chronic, mild form. Inflammation appears to be involved in both forms and may result from activation of liver macrophages (Kupffer cells), either directly or via kava metabolites. Pharmacogenomics may influence the severity of this inflammatory response.

Figure 1

Structures of the six main kavalactones (1–6), Pipermethysticine (7), and Flavokavain B (8). The chemical formulae are kavain (C₁₄H₁₄O₃), 7,8-dihydrokavain (C₁₄H₁₆O₃), methysticin (C₁₅H₁₄O₅), 7,8-dihydromethysticin (C₁₅H₁₆O₅), yangonin (C₁₅H₁₄O₄), desmethoxyyangonin (= 5,6-dehydrokavain = C₁₄H₁₂O₃), pipermethystine (C₁₆H₁₇NO₄), and flavokavain B (C₁₇H₁₆O₄).