Role of ethanol in kava hepatotoxicity

@article{Li2010RoleOE,
  title={Role of ethanol in kava hepatotoxicity},
  author={X. Z. Li and Iqbal Ramzan},
  journal={Phytotherapy Research},
  year={2010},
  volume={24}
}
Kava is known for its recreational, ceremonial and medicinal use in the Pacific. The aqueous non‐alcoholic drink of kava rhizome produces intoxicating, relaxing and soothing effects. While kava's medicinal effects receive worldwide recognition, kava‐containing products came under scrutiny after over 100 reports of spontaneous adverse hepatic effects. Many mechanisms have been postulated to explain the unexpected toxicity, one being pharmacokinetic interactions between kavalactones and co… 
Kava hepatotoxicity: pathogenetic aspects and prospective considerations
  • R. Teschke
  • Medicine
    Liver international : official journal of the International Association for the Study of the Liver
  • 2010
TLDR
By improving kava quality and adherence to therapy recommendation under avoidance of comedication, liver injury by kava should be a preventable disease, at least to a major extent.
The sub-acute toxicity of kavalactone in rats: a study of the effect of oral doses and the mechanism of toxicity in combination with ethanol.
TLDR
Results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity, and supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner.
Re-introduction of kava (Piper methysticum) to the EU: is there a way forward?
TLDR
The Kava Anxiety-Lowering Medication (KALM) project uses an aqueous rhizome extract of a noble cultivar of kava in participants with generalised anxiety and Generalised Anxiety Disorder, potentially providing an important step in the way forward with kava.
Contaminant Hepatotoxins as Culprits for Kava Hepatotoxicity – Fact or Fiction?
TLDR
This work proposes the ‘working hypothesis’ that contaminant hepatotoxins including moulds might have caused rare kava hepatotoxicity in humans, and suggests that kavalactones daily for acute or intermittent use could be a preventable disease.
Kava hepatotoxicity solution: A six-point plan for new kava standardization.
Kava and Kava Hepatotoxicity: Requirements for Novel Experimental, Ethnobotanical and Clinical Studies Based on a Review of the Evidence
TLDR
There is at present no evidence that kava hepatotoxicity might be due to aflatoxicosis, however, appropriate studies have yet to be done and should be extended to other mould hepatotoxins, with the aim of publishing the obtained results.
Proposal for a kava quality standardization code.
  • R. Teschke, V. Lebot
  • Medicine
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2011
Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytes
TLDR
Flavokawains promote an adaptive cellular response that protects hepatocytes against oxidative stress and it is proposed that FKA has potential as a chemopreventative or chemotherapeutic agent.
Herbal Highs: Review on Psychoactive Effects and Neuropharmacology
TLDR
Some “herbal highs” should be classified as harmful drugs since chronic administration has been linked with addiction and cognitive impairment; for some others taking into consideration only the recent trends of abuse, studies investigating these aspects are lacking.
...
...

References

SHOWING 1-10 OF 40 REFERENCES
Toxicity of Kava Kava
TLDR
The present review focuses on the recent findings on kava toxicity and the mechanisms by which kava induces hepatotoxicity.
Hepatic injury due to traditional aqueous extracts of kava root in New Caledonia.
TLDR
It is concluded that not only commercially available, but also traditionally prepared kava extracts may rarely cause liver injury and the increased activity of gamma glutamyl transferase in heavy kava consumers in the presence of normal or minimally elevated transaminases is probably not a sign of liver injury, but rather reflects an induction of CYP450 enzymes.
Aqueous kava extracts do not affect liver function tests in rats.
TLDR
Kava ( Piper methysticum Forst. f., Piperaceae), prepared as the traditional aqueous infusion, was tested in the rat for possible effects on liver function tests and showed the lack of a toxic effect by kava on the liver.
Kava Hepatotoxicity: Are we any closer to the truth?
TLDR
In this article the major theories as to the mechanism of kava hepatotoxicity are summarized and there is still no satisfactory answer.
Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats.
TLDR
PM-treated rats demonstrated a significant increase in hepatic glutathione, cytosolic superoxide dismutase (Cu/ZnSOD), tumor necrosis factor alpha mRNA expression, and cytochrome P450 (CYP) 2E1 and 1A2, suggesting adaptation to oxidative stress and possible drug-drug interactions.
A re-evaluation of kava (Piper methysticum).
  • E. Ernst
  • Medicine
    British journal of clinical pharmacology
  • 2007
TLDR
The UK government prohibited the sale of kava (Piper methysticum), a popular and effective herbal anxiolytic drug, marketed in Britain as unlicensed herbal products or food supplements in 2003, because of an unacceptable risk of hepatotoxicity.
Safety review of kava (Piper methysticum) by the Natural Standard Research Collaboration
TLDR
A recommendation is made to consolidate and analyse available reports and to continue postmarket surveillance in an international repository to prevent duplicates and promote collection of thorough details at the time of each report so that any association with kava is clearly defined.
In vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactones.
Kava herbal supplements have been recently associated with acute hepatotoxicity, leading to the ban of kava products in approximately a dozen countries around the world. It is suspected that some
...
...