Hey sorry been outta ton, the concern of hepatotoxicity intrigues me, there are some strategies i think you guys have discussed that might mitigate the effect, however, the exact mechanism hasn't been elucidated. However, the best thought mechanism i can clean is reactive species inducing GSH depletion. This isn't an uncommon thing, acetaminophen induces similar changes, and after reading more papers Some of the constituents of kava remind me of unsaturated pyrrolizidine alkaloids found in things like borage and butterbur. As for the alcohol angle, i see no reason in the data to consume ethanol extracts, however, there is not enough evidence to conclude small amounts found in a tincture will have a huge impact, if anyone has in vivo studies examining this id love to have them
with the regenerative capabilities of the liver i would behard pressed to say that a healthy person consuming normal(not recreational) amounts could induce hepatic insult. However, i would try and mitigate this as much as possible. The below study suggests that GSH reduces cytotoxicity or in this case injury to hepatocytes via correction of GSH depletion through redox. GSH sucks orally, its bioavailibility is garbage, as previously suggested N-acetyl cysteine(antidote for acetaminophen OD) could help correct this problem, and is a viable option to take with your kava, it also regulates glutamate as an NMDA antagonist such that it could help with anxiety and OCD, issues people use kava for anyway. Milk thistle might not be a good idea do to substate issues. Another study (murine model) showed kavain was inherently hepatotoxic, i have no doubt kava is bad for the liver, but its quantity and to what degree. Insulting the liver is like walking down the street with your girlfriend, you can look at other woman and been fine for life but once you go all out and sleep with one,you are done, fibrosis.
i honestly have no idea about the chemistry question, not my field, sorry.
Chem Res Toxicol. 2011 Jul 18;24(7):992-1002. Epub 2011 May 3.
Constituents in kava extracts potentially involved in hepatotoxicity: a review.
Olsen LR, Grillo MP, Skonberg C.
Source
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark.
[email protected]
Abstract
Aqueous kava root preparations have been consumed in the South Pacific as an apparently safe ceremonial and cultural drink for centuries. 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. However, no such conclusion has been made on the basis of current data. Inhibition or induction of the major metabolizing enzymes, which might result in drug interactions, has also gained attention, but ambiguous results have been reported. On the basis of the chemical structures of kava constituents, the formation of reactive metabolites has also been suggested as an explanation of toxicity. Furthermore, skin rash is a side effect in kava consumers, which may be indicative of the formation of reactive metabolites and covalent binding to skin proteins leading to immune-mediated responses. Reactive metabolites of kava lactones have been identified in vitro as glutathione (GSH) conjugates and in vivo as mercapturates excreted in urine. Addition of GSH to kava extracts has been shown to reduce cytotoxicity in vitro, which suggests the presence of inherently reactive constituents. Only a few studies have investigated the toxicity of the minor constituents present in kava extract, such as pipermethystine and the flavokavains, where some have been shown to display higher in vitro cytotoxicity than the lactones. To date, there remains no indisputable reason for the increased prevalence of kava-induced hepatotoxicity in Western countries.
Br J Clin Pharmacol. 2011 Jul 29. doi: 10.1111/j.1365-2125.2011.04070.x. [Epub ahead of print]
Kava hepatotoxicity in traditional and modern use: The presumed Pacific kava paradox hypothesis revisited.
Teschke R, Sarris J, Schweitzer I.
Source
Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Goethe University of Frankfurt/ Main, Germany Department of Psychiatry, Faculty of Medicine, University of Melbourne, Australia Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia.
Abstract
What this paper adds Kava is a Pacific herb consumed worldwide and used for recreational purposes and to treat general anxiety. Kava use is associated with rare hepatotoxicity. The previously proposed Pacific kava paradox was based on kava hepatotoxicity, not observed following traditional aqueous extracts in the Pacific region but restricted to Western acetonic and ethanolic extracts. Cases of the WHO revealed that also traditional aqueous extracts used in New Caledonia, Australia, the US, and Germany may be hepatotoxic. Hence, there is no more a basis to sustain the previously proposed Pacific kava paradox. It appears that the primary cause of toxicity may be attributed to poor quality of the raw material by mould hepatotoxins. ABSTRACT: Kava, a Pacific herb consumed worldwide for medicinal, recreational and cultural purposes, has been associated with rare hepatotoxicity, and there is the current critical need to determine this causation. The previously proposed Pacific kava paradox was based on the theory that kava hepatotoxicity was not observed following traditional aqueous extracts in the Pacific region, but restricted to Western acetonic and ethanolic extracts. Subsequent cases of the WHO revealed that traditional aqueous extracts used in New Caledonia, Australia, the US, and Germany may also be hepatotoxic; thus there is no more a basis to sustain the previously proposed Pacific kava paradox. It appears that the primary cause of toxicity may reside in the time before the preparation of the various kava extracts, possibly attributed to poor quality of the raw material by mould hepatotoxins. Rigorous testing of kava raw material is urgently advised, in addition to Pan-Pacific kava manufacturing quality standards
Food Chem Toxicol. 2011 Nov;49(11):2820-9. Epub 2011 Aug 18.
Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed to Kava Kava.
Behl M, Nyska A, Chhabra RS, Travlos GS, Fomby LM, Sparrow BR, Hejtmancik MR, Chan PC.
Source
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Abstract
Kava Kava is an herbal supplement used as an alternative to antianxiety drugs. Although some reports suggest an association of Kava Kava with hepatotoxicity , it continues to be used in the United States due to lack of toxicity characterization. In these studies F344/N rats and B6C3F1 mice were administered Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or two years. Results from prechronic studies administered Kava Kava at 0.125 to 2g/kg body weight revealed dose-related increases in liver weights and incidences of hepatocellular hypertrophy. In the chronic studies, there were dose-related increases in the incidences of hepatocellular hypertrophy in rats and mice administered Kava Kava for up to 1g/kg body weight. This was accompanied by significant increases in incidences of centrilobular fatty change. There was no treatment- related increase in carcinogenic activity in the livers of male or female rats in the chronic studies. Male mice showed a significant dose-related increase in the incidence of hepatoblastomas. In female mice, there was a significant increase in the combined incidence of hepatocellular adenoma and carcinoma in the low and mid dose groups but not in the high dose group. These findings were accompanied by several nonneoplastic hepatic lesions
this study is just ridiculous, incredible conclusions without even mentioning the population that consumes the beverage.
Aust N Z J Public Health. 2011 Oct;35(5):427-33. doi: 10.1111/j.1753-6405.2011.00737.x. Epub 2011 Sep 12.
Kava drinking associated with suicidal behaviour among young Kanaks using kava in New Caledonia.
Vignier N, Lert F, Salomon C, Hamelin C.
Source
Inserm U1018, Centre for Epidemiology and Population Health, Occupational and social determinants of health, Villejuif, France and Université de Versailles St-Quentin, France.
Abstract
Objective : To examine associations between recreational use of kava and indicators of suicidal behaviour among youth in New Caledonia. Methods : This cross-sectional community-based survey was administered to 1,400 young people aged 16-25 years. A multivariate analysis tested for associations between lifetime kava use and lifetime suicidal ideation and attempts. Because ethnicity affected the correlation between kava use and suicidal behaviour, data were analysed separately for Kanak youth and youth of other ethnic communities. Results : Overall, 42% of respondents reported any lifetime kava use, 34% reported past suicidal ideation and 12% any suicide attempts. Among Kanak youth, kava use increased the likelihood of reporting both suicidal ideation (aOR = 2.40, 95% CI: 1.58-3.66) and suicide attempts (aOR = 1.98, 95% CI: 1.11-3.52). No such association was found in the non-Kanak group. Conclusions : The discrepancy between the effects of kava drinking on suicidal behaviour between Kanak youth and youth of other ethnic groups may be related to differences in patterns and quantity of kava use. In view of the paucity of data on the effects of kava on mental health in young people, further investigation is required. Implications : The results call for an increased awareness of the potential adverse health effects of kava consumption in New Caledonia where it has spread in recent times and among communities where previously it was never used.
