Hepatocellular toxicity of kava leaf and root extracts
Kava extracts are used widely for different purposes and were thought to be safe. Recently, several cases of hepatotoxicity have been published.
To explore possible mechanisms of kava hepatotoxicity, we prepared and analyzed three different kava extracts (a methanolic and an acetonic root and a methanolic leaf extract), and investigated their toxicity on HepG2 cells and isolated rat liver mitochondria.
All three extracts showed cytotoxicity starting at a concentration of 50 μg/ml (lactate dehydrogenase leakage) or 1 μg/ml (MTT test). The mitochondrial membrane potential was decreased (root extracts starting at 50 μg/ml) and the respiratory chain inhibited and uncoupled (root extracts) or only uncoupled (leaf extract) at 150 μg/ml, and mitochondrial β-oxidation was inhibited by all extracts starting at 100 μg/ml.
The ratio oxidized to reduced glutathione was increased in HepG2 cells, whereas the cellular ATP content was maintained. Induction of apoptosis was demonstrated by all extracts at a concentration of 150 μg/ml.
These results indicate that the kava extracts are toxic to mitochondria, leading to inhibition of the respiratory chain, increased ROS production, a decrease in the mitochondrial membrane potential and eventually to apoptosis of exposed cells. In predisposed patients, mitochondrial toxicity of kava extract may explain hepatic adverse reactions of this drug.
University of Sydney researchers find new evidence linking kava to liver damage
In recent years, serious concerns about the dangers of kava and the effects on the liver have resulted in regulatory agencies, such as the US Food and Drug Administration and Australia's Therapeutic Goods Administration, banning or restricting the sale of kava and kava products.
Originally from Fiji, where kava drinking is common, Professor Iqbal Ramzan, Dean of Pharmacy at the University of Sydney, Australia, had previously published articles on the adverse effects of kava, and wanted to investigate further the effects kava had on the liver.
His findings are published in the January 28, 2008 edition of the World Journal of Gastroenterology. Leading a team of researchers from the University of Sydney, Professor Ramzan spent one year investigating the cellular effects of kava on the liver. Kava has been used in ceremonies and for recreational and social purposes in the South Pacific since ancient times, much like alcohol, tea or coffee is in other societies today.
In the 1980s other medicinal uses for kava began to emerge and it was marketed in herbal form as a natural way to treat conditions such as anxiety, insomnia, tension and restlessness, particularly in Europe and North America.
More recently, evidence began to emerge about the adverse affect kava could have on the liver.
To test these theories, the University of Sydney study focused on the major kavalactone (the ingredient in kava believed to affect the liver) -- kavain -- and investigated the effects it had on the ultrastructure (or biological structure) of the liver.
This required the use of electron microscopes (which enable the examination of the interior of cells) provided by the Australian Key Centre for Microscopy and Microanalysis at the University of Sydney under the direction of its Deputy Director, Professor Filip Braet.
The study found that following kavain treatment the liver tissue displayed an overall change in structure, including the narrowing of blood vessels, the constriction of blood vessel passages and the retraction of the cellular lining.
Interestingly, kavain also adversely affected certain cells which function in the destruction of foreign antigens (such as bacteria and viruses), which make up part of the body's immune system.
In other words, the kavain treatment disturbed the basic structure of the liver, consequently seriously impacting the normal functioning of the liver.
The results of the University of Sydney's study clearly support earlier literature observations on kava's adverse affects on the functioning of the liver in general.
However, additional investigations into the effects of other major kavalactones on the liver, as well as studies on whether the effects of kava are reversible, are urgently needed.
Thaks for this information, Harry. As my husband sometimes uses Kava kava capsules when he is in an insomniac spell, I don't know whether to interfere with his use of something which helps him. Given his age and condition (almost 80, cancer and osteoporosis) it is tempting to thing "Let him carry on with it."
As it is something which has been used for generations in the areas where it grows, how big is the risk, I wonder? Then again, alcohol has been used for generations, and we know what effects that has!
My father also uses one capsule of kava, on an almost daily-basis, to help with some minor anxiety issues.
My opinion, based on what is known at the moment, is that low-to-moderate use is unlikely to cause problems for most people.
I do think it's wise to periodically have liver-function tests conducted - which my father has done on a yearly-basis ... as part of his yearly physical. So far, for him, there is no evidence of any liver inflammation.
I also think it's wise to choose the purest possible kava product. There is some concern that certain manufacturers utilize other parts of the kava plant, besides the root, and that that may potentially increase the risk.
The way the kava is extracted may play a role in it's toxicity-profile as well. If there are caustic-solvents used in the extraction of the kava principles ... they may still be present, in small quantities, in the final product and (potentially) cause harm.
Finally, keep in mind that these studies are quite experimental in nature. It's hard to say if the results will apply to actual human beings consuming low-to-moderate amounts of commercially-available kava extracts.
I'm just putting this information out there in case there are kava users that may want to monitor any possible side-effects that may result from chronic-use. It's just a precaution that hopefully has no practical application in the real world.
Thanks Harry, I had been considering it along those lines.
On "the other fourm" a poster has described how she uses Kava kava root and makes her own tincture. I have been thinking of doing something similar, so at least, I know what went into the making of it! Trouble is, we don't have Everclear here. I think there is a polish spirit around 98% proof - that would be the nearest I could get.
If your father has been using it, low key and long term, he must find it beneficial too? Where does he buy his supply from?
My father reports that it mellows him out. I think he only uses one capsule, on stressful days, in the morning. He used it more when he was working ... less now - because he's recently retired.
If I had my way, I'd have him use one of these two products:
Check out the "product review" section. You'll find that a few people claim to have used kava for several years with no ill-effect.
My dad is a very thrifty-shopper. I try to emphasize how important quality is, especially in this industry, but ultimately he usually errs on the side of saving money.
So, I think he's using this product (which is less-expensive):
Harry, you gem! I have just ordered the Nakamal product, from the second link you posted. They will ship to UK.
The third one, which your father uses now - that looks like the Now foods company - which reminds me of my first rice bran oil order, and all that info from Rosie, so long ago!
Thanks for the memories.
Kava Caution
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