"The extraction process (aqueous vs. acetone in the two types of preparations) is responsible for the difference in toxicity as extraction of glutathione in addition to the kava lactones is important to provide protection against hepatotoxicity"
http://www.sciencedirect.com/science/article/pii/S0031942203003819
"However, several reports of hepatotoxicity have been linked to the consumption of kava extracts in Western countries, where mainly ethanolic or acetonic extracts are used. The mechanism of toxicity has not been established, although several theories have been put forward.
The composition of the major constituents, the kava lactones, varies according to preparation method and species of kava plant, and thus, the toxicity of the individual lactones has been tested in order to establish whether a single lactone or a certain composition of lactones may be responsible for the increased prevalence of kava-induced hepatotoxicity in Western countries.
http://www.ncbi.nlm.nih.gov/pubmed/21506562
"Some manufacturers highly concentrate the lactone content in their extracts.
As a consequence, important compounds are left out and the effects are different from those produced by the traditional juice beverage.
An unfortunate example of the “different effects” would be those resulting in the liver toxicity that has been reported to occur with use of commercially concentrated extracts made with chemical solvents."
"The extraction process utilizes acetone or alcohol and produces a sticky paste, which has little resemblance to the natural form of Kava in use in the South Pacific.
It is possible that the recently developed chemical processing introduces compounds into the standardized product that can affect the liver.
Another possibility is that the chemical solvents used do not extract the same compounds as the natural water extracts in traditional use. The extraction process may exclude important modifying constituents soluble only in water."
"These Aboriginal individuals consumed approximately 375 grams of dried whole root of Kava as a beverage in water per week. Generally, available Kava averages about 9% kavalactones and as a water extract 5% would be made available in the prepared beverage.
Therefore, the assumption can be made that 2700 milligrams (over 12 times the recommended dose) of total kavalactones was consumed daily for 6 years and these people had no liver symptoms but did have a liver enzyme elevation.
Compare this to one death and multiple liver transplants with patients who used standardized extracts. These patients had used those standardized products for less than a year and only marginally exceed the recommended dose of 210 mg/day.
Another smaller group of Aboriginals consumed about 100 grams per week (which is 3 times the suggested dose of the standardized extract) and had no symptoms. These individuals were former abusers of alcohol and in poor health when the study began.
This study supports the use of Kava as a water extract as compared to the liver toxicity
associated with standardized extract form."
"The German medical literature also reports a standardized ethanolic extract of kava with concentrated lactones, was the probable cause of hepatitis in another woman who required a liver transplant. [3]"
[3]. Kraft M, Spahn TW, Menzel J et al. Fulminant liver failure after administration of the herbal
antidepressant Kava-Kava. Dtsch. Med. Wschr., 126:970-972, 2001 [in German]
http://www.eclecticherb.com/kava/pdf/4page.pdf
"A recent WHO risk assessment concluded that “clinical trial of kava have not revealed hepatoxicity as a problem5 suggesting that “water extracts are devoid of toxic effects” [6] and recommending that “products should be developed from water-based suspensions of kava” [7]."
[6] WHO (2007): Assessment of the risk of hepatotoxicity with kava products, p. 59
[7] WHO (2007): Assessment of the risk of hepatotoxicity with kava products, p. 62
"In 2005, Food Safety Australia and New Zealand reported the health risk assessment of kava and the associated hepatoxicity from commercial acetonic or ethanolic kava extract marketed [...]"
http://www.kavaforums.com/forum/attachments/codex-madang-na12_kava_draft-pdf.64/
"It is important to note that although Western “industrial” kava preparations are mainly extracted with organic solvents (e.g., ethanol,acetone), traditional kava drinks are prepared by dipping the kava roots/rhizomes in water or coconut juice with an apparently safe history"
"We report herein that organic solvent-extracted kava root extracts contain high levels of FKB that induce severe hepatocellular toxicity through inducing oxidative stress, modulating IKK/NF-κB and MAPK signaling pathways.It is therefore concluded that FKB is the major, and perhaps the exclusive, chalcone contributing to the hepatotoxicity of kava extracts, and its levels should be tightly monitored and controlled during preparation of kava root extracts if organic solvents are used for extraction."
"Traditionally, extraction of these compounds is performed using aqueous solutions, yielding relatively low levels of kavalactones (~4.6%, Table 1). Modern extraction techniques using organic solvents (e.g., acetone, ethanol) yield significantly higher levels of kavalactones (~45–55%, Table 1), and dramatically higher levels of lipophilic chalcones in the extract (~160-fold for FKB, Table 1).
Recently organic extracts of kava root rhizomes, sold as over-the-counter herbal supplements, were reported to induce severe hepatotoxicity."
"In agreement with this in vivo observation, our data (Fig. 1A) showed that indeed kavalactones had no significant effects on the viability of selected liver cell lines.
On the other hand, we show here that chalcones, compounds that are dramatically enriched in organic solvent-based extractions (Table 1), were accountable for the observed hepatotoxicity (Fig. 1)."
"In summary, we showed that in organic solvent-extracted kava root extracts, chalcones, and especially FKB are dramatically enriched. We also demonstrated that FKB is a potent hepatotoxin that induces hepatocellular apoptosis."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992378/
"FKB was also present in ethanolic extracts of roots of the two-days cultivar Palisi from Vanuatu with a ten-fold higher amount compared to the noble cultivar Ava La’au from Samoa (DiSilvestro, Zhang, & DiSilvestro, 2007). In dried roots of an unknown cultivar from Vanuatu, analysis by gas-chromatography–mass spectrometry (GC–MS) showed for FKB peak areas of 0.1% and 0.5% for aqueous and acetonic extracts respectively (Xuan et al.,2008)."
"Kavalactones were then extracted using organic solvents but alkaloids were most likely extracted too and so probably were flavokavins (Teschke et al., 2009)."
http://www.ncbi.nlm.nih.gov/pubmed/24423570
"In 2003, cases of hepatotoxicity in connection with the use of Western acetonic and ethanolic kava products were reported; at the same time, it was observed that liver toxicity had not been documented with traditional water-based kava extracts used in Pacific countries, such as the South Pacific Islands and Australia [
6,
7]."
"Therefore, the five studies all showed either normal or slightly increased ALT and AST values, and in none of these studies was there evidence for clinically relevant hepatocellular injury [
14–
18]. This is in contrast to high ALT and AST values observed in patients who used ethanolic or acetonic kava extracts [
12,
13].
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269575/