I've found this super strange quote:
"A poisoning by synthetic enantiomers could also be a possible cause, as a dissertation published in 2011 shows. The drugs produced in Germany (such as, for example, the drug Laitan) contained not only natural substances but also, for cost reasons, synthesized Kavain . [21] Artificially produced Kavain is a racemic mixture of (+) - Kavain and (-) - Kavain (also referred to as DL- Kaavain). Kava Kava contains only (+) - Kavain. The work has shown that the synthetic (-) - kavain is degraded to harmful para-hydroxy compounds. This would explain why hepatotoxic cases have mainly occurred in the German-speaking world, while the hepatotoxicity in the Pacific region is virtually unknown. The present differences to the hepatotoxicity in the scientific literature could also be understood, since the authors do not explicitly state whether the examined kavain is synthetic or originates from the kava kava."
?! Has anyone else read about synthetic kavain being used in the manufacturing of the German extracts?
@verticity ?
Henry, thanks for posting this, I never ever knew that they were making their own Kavain. I wonder if Dr. Schmidt knows about this?
I will have to ask him, thanks again for sharing this information. Aloha.
Chris
I think this is well known in Germany. There were at least two drugs containing synthetic Kavain:
Kavaform and Neuronika. As far as I know, Laitan was made of natural Kava. There was also an article in german:
https://www.deutsche-apotheker-zeitung.de/daz-az/2000/daz-29-2000/uid-6989
I have never heard of that. Where did you find that quote, @Henry ?
In general it is difficult to synthesize enantiomerically pure chemicals using conventional chemistry, but plants and animals naturally do it all the time. Normally one of the enantiomers is biologically active, and the other form is just inert: it doesn't do anything useful, but is very difficult to separate.I have never heard of one enantiomer being toxic while the other one is not. That is indeed very strange.
OK, there actually was one notorious example of a drug where one optical isomer is a useful drug, but the other one is toxic: thalidomide. (That was also another notorious example of a failure by German pharmaceutical companies.) Unfortunately in that case the two forms can spontaneously interconvert so it is impossible to make a pure form. (That is not the case for kavain: naturally occuring (+)-kavain can't change to (-)-kavain):
http://www.avericadiscovery.com/blog/why-thalidomide-is-important-to-chiral-separation/
"Kavalactone biosynthesis in Piper methysticum
Kava is a beloved plant of the Polynesian peoples because it produces a number of polyketides collectively known as the kava lactones. We are currently testing a number of candidate genes that were sequenced from the PhytoMetaSyn project (http://phytometasyn.ca/) that may encode the biosynthetic enzymes that produce the major kava lactones. "
http://www.sciencedirect.com/science/article/pii/S0040403906019769
Huh interesting, I think back when the liver concerns first started they were linked to people in Germany having liver failure due to kava.
It was originally a poor translation from a random German article. But I've found the original source. It was written by Dr Barguil in his PhD thesis (chemistry):
"Cependant, certains travaux se heurtent à des obstacles méthodologiques : plusieurs étudesutilisent en effet, en complément ou en substitut à l’extrait de kava, le mélange racémique quiconstitue la kavaïne de synthèse. C’est ce mélange de produits naturels et du produit de synthèsequi est le principe actif essentiel d’une série de produits pharmaceutiques allemands autorisésjusqu’en 2000. Or on sait que les isomères (+) des kavalactones (les seuls présents dans la plante)sont actifs sur le plan thérapeutique. Doper l’extrait naturel de kava par un produit synthétiqueétait un moyen économique pour les pharmacologues allemands d’accroître la quantité de produitsactifs (au risque d’y introduire un produit étranger). De plus, l’activité du kava naturel n’est pasdue à une seule kavalactone, mais à la synergie de l’ensemble des kavalactones qui sont présentesen proportions très variables selon le cultivar. Tester un mélange de kava naturel et de kavaïne desynthèse équivaut à tester simultanément des kavalactones naturelles et l’isomère (-) kavaïneétranger à la plante.Il convient donc de rester prudent face aux résultats d’auteurs qui ne précisent pas lanature de l’extrait ou de la substance qu’ils ont utilisés, parfois une kavalactone naturelle pure,parfois une molécule provenant d’une synthèse racémique, parfois même des extraits de kava dontla provenance, le mode de préparation et la concentration en kavalactone(s) ne sont pas précisés.Nous avons chaque fois tenté de connaître la nature du produit utilisé sous le terme de « kava » ousous celui de « kavaïne » "
https://kavalogue.files.wordpress.com/2011/11/these-doctorat-kava-yann-barguil-2011.pdf
You can google translate it, should be pretty accurate. But let me know if it's not clear, I can help to translate it.
He argues that synthetic kavain was present in a range of German products up until 2000.
But I'm still not finding the research where they find that (-)-kavain is toxic.
"A poisoning by synthetic enantiomers could also be a possible cause, as a dissertation published in 2011 shows. The drugs produced in Germany (such as, for example, the drug Laitan) contained not only natural substances but also, for cost reasons, synthesized Kavain . [21] Artificially produced Kavain is a racemic mixture of (+) - Kavain and (-) - Kavain (also referred to as DL- Kaavain). Kava Kava contains only (+) - Kavain. The work has shown that the synthetic (-) - kavain is degraded to harmful para-hydroxy compounds. This would explain why hepatotoxic cases have mainly occurred in the German-speaking world, while the hepatotoxicity in the Pacific region is virtually unknown. The present differences to the hepatotoxicity in the scientific literature could also be understood, since the authors do not explicitly state whether the examined kavain is synthetic or originates from the kava kava."
?! Has anyone else read about synthetic kavain being used in the manufacturing of the German extracts?
@verticity ?
Henry, thanks for posting this, I never ever knew that they were making their own Kavain. I wonder if Dr. Schmidt knows about this?
I will have to ask him, thanks again for sharing this information. Aloha.
Chris
I think this is well known in Germany. There were at least two drugs containing synthetic Kavain:
Kavaform and Neuronika. As far as I know, Laitan was made of natural Kava. There was also an article in german:
https://www.deutsche-apotheker-zeitung.de/daz-az/2000/daz-29-2000/uid-6989
So strange! This seems like a very important piece of info and yet it doesn't even get mentioned in any of these comprehensive lit reviews. I've found another source (in French) claiming that laitan also contained synthetic kavain..I think this is well known in Germany. There were at least two drugs containing synthetic Kavain:
Kavaform and Neuronika. As far as I know, Laitan was made of natural Kava. There was also an article in german:
https://www.deutsche-apotheker-zeitung.de/daz-az/2000/daz-29-2000/uid-6989
I have never heard of that. Where did you find that quote, @Henry ?
In general it is difficult to synthesize enantiomerically pure chemicals using conventional chemistry, but plants and animals naturally do it all the time. Normally one of the enantiomers is biologically active, and the other form is just inert: it doesn't do anything useful, but is very difficult to separate.
OK, there actually was one notorious example of a drug where one optical isomer is a useful drug, but the other one is toxic: thalidomide. (That was also another notorious example of a failure by German pharmaceutical companies.) Unfortunately in that case the two forms can spontaneously interconvert so it is impossible to make a pure form. (That is not the case for kavain: naturally occuring (+)-kavain can't change to (-)-kavain):
http://www.avericadiscovery.com/blog/why-thalidomide-is-important-to-chiral-separation/
There is also The Stout Labs" in Canada who have this going-- interesting.So strange! This seems like a very important piece of info and yet it doesn't even get mentioned in any of these comprehensive lit reviews. I've found another source (in French) claiming that laitan also contained synthetic kavain..
"Kavalactone biosynthesis in Piper methysticum
Kava is a beloved plant of the Polynesian peoples because it produces a number of polyketides collectively known as the kava lactones. We are currently testing a number of candidate genes that were sequenced from the PhytoMetaSyn project (http://phytometasyn.ca/) that may encode the biosynthetic enzymes that produce the major kava lactones. "
There are methods to synthesize pure (+)-kavain. One method uses enzymes. But I don't think any of these methods were known in 2000 when these products were made.There is also The Stout Labs" in Canada who have this going-- interesting.
"Kavalactone biosynthesis in Piper methysticum
Kava is a beloved plant of the Polynesian peoples because it produces a number of polyketides collectively known as the kava lactones. We are currently testing a number of candidate genes that were sequenced from the PhytoMetaSyn project (http://phytometasyn.ca/) that may encode the biosynthetic enzymes that produce the major kava lactones. "
http://www.sciencedirect.com/science/article/pii/S0040403906019769
Huh interesting, I think back when the liver concerns first started they were linked to people in Germany having liver failure due to kava.
It was originally a poor translation from a random German article. But I've found the original source. It was written by Dr Barguil in his PhD thesis (chemistry):
"Cependant, certains travaux se heurtent à des obstacles méthodologiques : plusieurs étudesutilisent en effet, en complément ou en substitut à l’extrait de kava, le mélange racémique quiconstitue la kavaïne de synthèse. C’est ce mélange de produits naturels et du produit de synthèsequi est le principe actif essentiel d’une série de produits pharmaceutiques allemands autorisésjusqu’en 2000. Or on sait que les isomères (+) des kavalactones (les seuls présents dans la plante)sont actifs sur le plan thérapeutique. Doper l’extrait naturel de kava par un produit synthétiqueétait un moyen économique pour les pharmacologues allemands d’accroître la quantité de produitsactifs (au risque d’y introduire un produit étranger). De plus, l’activité du kava naturel n’est pasdue à une seule kavalactone, mais à la synergie de l’ensemble des kavalactones qui sont présentesen proportions très variables selon le cultivar. Tester un mélange de kava naturel et de kavaïne desynthèse équivaut à tester simultanément des kavalactones naturelles et l’isomère (-) kavaïneétranger à la plante.Il convient donc de rester prudent face aux résultats d’auteurs qui ne précisent pas lanature de l’extrait ou de la substance qu’ils ont utilisés, parfois une kavalactone naturelle pure,parfois une molécule provenant d’une synthèse racémique, parfois même des extraits de kava dontla provenance, le mode de préparation et la concentration en kavalactone(s) ne sont pas précisés.Nous avons chaque fois tenté de connaître la nature du produit utilisé sous le terme de « kava » ousous celui de « kavaïne » "
https://kavalogue.files.wordpress.com/2011/11/these-doctorat-kava-yann-barguil-2011.pdf
You can google translate it, should be pretty accurate. But let me know if it's not clear, I can help to translate it.
He argues that synthetic kavain was present in a range of German products up until 2000.
Clear enough:...You can google translate it, should be pretty accurate. ...
"Some studies, however, encounter methodological obstacles: several studies use, in addition or as a substitute to the extract of kava, the racemic mixture which synthesizes kavain. It is this mixture of natural products and the synthetic product which is the essential active ingredient of a series of German pharmaceutical products authorized until 2000. It is known that the (+) isomers of kavalactones (the only ones present in the plant) Are therapeutically active. Doping the natural extract of kava with a synthetic product was an economical way for German pharmacologists to increase the quantity of active products (at the risk of introducing a foreign product). Moreover, the activity of the natural kava is not due to a single kavalactone, but to the synergy of all the kavalactones which are present in very variable proportions according to the cultivar. Testing a mixture of natural kava and kavain desynthesis is equivalent to simultaneously testing natural kavalactones and the (-) kavain-strange isomer to the plant. It is therefore advisable to remain cautious with the results of authors who do not specify the nature of the extract Or of the substance which they have used, sometimes a pure natural kavalactone, sometimes a molecule derived from a racemic synthesis, sometimes even kava extracts whose origin, method of preparation and concentration in kavalactone (s) are not Each time we tried to know the nature of the product used under the term "kava" or under the term "kavain""
But I'm still not finding the research where they find that (-)-kavain is toxic.
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