What long-term side effects are associated with kava?

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    Last Updated: October 13, 2024

    There are clinical reports of herb-induced liver injury with kava use, especially when taken consistently for longer than a month.[1] Prolonged kava use has been associated with lower body weight and depressed markers of immune function similar to those seen in alcoholics.[2][3] Reports of multiple adverse events, liver dysfunction (e.g., hepatotoxicity, hepatitis, hepatic failure), and, in some instances, death have also been reported, but the dose and duration of kava aren’t always consistent or clearly stated in these reports.[4][5][6][7][8]

    These accounts, however, may be mistaken in the assumption that kava alone is to blame. While some adverse event reports identify the use of individual kavalactones (rather than a whole root extract), other reports note that kava was taken in addition to another substance with the potential for hepatotoxicity.[4][9][6]

    Additionally, no controlled trials using a standardized kava intervention (i.e, 200–300 mg of standardized extracts, taken for less than 2 months) have reported liver toxicity with the use of moderate dosing. However, not all studies measure liver enzymes or function either.[10][11] Regardless of whether kava alone or in combination with other factors is to blame for adverse events, caution is advised until clearer evidence is established.

    Higher doses of kava (greater than 1,000 mg/day of root extract over 4 weeks) are associated with an increased risk of impaired cytochrome P450 (CYP450) function.[12] Inhibition of CYP450 is possibly due to kava containing methysticin, as demonstrated by in vitro studies.[13] In vitro studies have also identified that some kavalactones (desmethoxyyangonin, methysticin, and dihydromethysticin) could inhibit liver enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP4A9/11.[14][15][16] However, the kavalactone kavain is not yet known to inhibit liver enzymes.[14]

    References

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    2. ^Cairney S, Clough AR, Maruff P, Collie A, Currie BJ, Currie JSaccade and cognitive function in chronic kava users.Neuropsychopharmacology.(2003-Feb)
    3. ^Cairney S, Maruff P, Clough AR, Collie A, Currie J, Currie BJSaccade and cognitive impairment associated with kava intoxication.Hum Psychopharmacol.(2003-Oct)
    4. ^Ulbricht C, Basch E, Boon H, Ernst E, Hammerness P, Sollars D, Tsourounis C, Woods J, Bent SSafety review of kava (Piper methysticum) by the Natural Standard Research Collaboration.Expert Opin Drug Saf.(2005-Jul)
    5. ^Gow PJ, Connelly NJ, Hill RL, Crowley P, Angus PWFatal fulminant hepatic failure induced by a natural therapy containing kava.Med J Aust.(2003-May-05)
    6. ^Clouatre DLKava kava: examining new reports of toxicity.Toxicol Lett.(2004-Apr-15)
    7. ^Russmann S, Lauterburg BH, Helbling AKava hepatotoxicity.Ann Intern Med.(2001-Jul-03)
    8. ^Humberston CL, Akhtar J, Krenzelok EPAcute hepatitis induced by kava kava.J Toxicol Clin Toxicol.(2003)
    9. ^Olsen LR, Grillo MP, Skonberg CConstituents in kava extracts potentially involved in hepatotoxicity: a review.Chem Res Toxicol.(2011-Jul-18)
    10. ^Pittler MH, Ernst EKava extract for treating anxietyCochrane Database Syst Rev.(2003)
    11. ^Zhang W, Yan Y, Wu Y, Yang H, Zhu P, Yan F, Zhao R, Tian P, Wang T, Fan Q, Su ZMedicinal herbs for the treatment of anxiety: A systematic review and network meta-analysis.Pharmacol Res.(2022-May)
    12. ^Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah AIn vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes.Clin Pharmacol Ther.(2005-May)
    13. ^Zhang Q, Liu H, Wu D, Yu H, Wang K, Jiao W, Zhao XMethysticin Acts as a Mechanism-Based Inactivator of Cytochrome P450 2C9.Chem Res Toxicol.(2022-Jun-20)
    14. ^James M Mathews, Amy S Etheridge, Sherry R BlackInhibition of human cytochrome P450 activities by kava extract and kavalactonesDrug Metab Dispos.(2002 Nov)
    15. ^L Zou, G L Henderson, M R Harkey, Y Sakai, A LiEffects of kava (Kava-kava, 'Awa, Yaqona, Piper methysticum) on c-DNA-expressed cytochrome P450 enzymes and human cryopreserved hepatocytesPhytomedicine.(2004)
    16. ^Unger M, Holzgrabe U, Jacobsen W, Cummins C, Benet LZInhibition of cytochrome P450 3A4 by extracts and kavalactones of Piper methysticum (Kava-Kava).Planta Med.(2002-Dec)