Which specific CYP450 enzymes does Kava inhibit/induce?

[verticity]

Is it possible to split this into a new thread? Who is the moderator, @kavadude?

kavadude is a moderator, but you can do it yourself; just create a new thread, and copy the stuff that should be part of it.

I would also like to say: It is great to gather anecdotal evidence about kava-drug interactions, but since not everyone in the target audience here is familiar with how scientific research works, it should be prefaced with a clear disclaimer about the limitations and pitfalls of anecdotal evidence, especially anecdotal evidence gathered anonymously over the Internet. Basically: the fact that someone here claimed that some drug they were taking interacted with kava should be taken with a huge grain of salt: They could have other medical conditions they don't mention or are not aware of; they could be 100 years old; they could be 12 years old; they could be on other meds (legal, or illegal) that they don't mention; or they could possibly even be liars/trolls (this is the Internet afterall).

 

[verticity]

I just found this short paper which has some additional information for the discussion of which liver enzymes kava inhibits. It's from 2005, so not new, but new to me. This was a small human study that found that kava inhibited CYP450 1A2, but did not inhibit 2E1 or any others significantly. The way they figured that out was by looking at how regular kava drinkers metabolized caffeine before and after a period of abstinence. So this was a measure of a long term effect in people drinking traditional style kava in New Caledonia.
Russmann, S., Lauterburg, B. H., Barguil, Y., Choblet, E., Cabalion, P., Rentsch, K., & Wenk, M. (2005). Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: Protective effect against environmental carcinogens?. Clinical Pharmacology & Therapeutics, 77(5), 453-454.
(PDF attached)

This is a different result from the other human study I had been aware of that found kava only inhibited 2E1 and not the others.

(The paper also speculates that this inhibition could have some kind of cancer protective effect. As indicated by the question mark in the title of the article that part is just a couple highly speculative sentences in the article and is in no way proven. A later highly speculative paper by Barguil also hypothesized with no proof that CYP450 1A2 inhibition could cause "sudden death" by depleting nitric oxide, proving that when you read scientific papers like these you need to be careful to separate the actual experimental results from the speculative discussion about what those results could imply.)

This is actually a followup to this old locked thread which maybe a moderator would be kind enough to merge this with so that we can have this info in one place..
http://kavaforums.com/forum/threads/which-specific-cyp450-enzymes-does-kava-inhibit-induce.7084/

 

[Alia]

I just found this short paper which has some additional information for the discussion of which liver enzymes kava inhibits. It's from 2005, so not new, but new to me. This was a small human study that found that kava inhibited CYP450 1A2, but did not inhibit 2E1 or any others significantly. The way they figured that out was by looking at how regular kava drinkers metabolized caffeine before and after a period of abstinence. So this was a measure of a long term effect in people drinking traditional style kava in New Caledonia.
Russmann, S., Lauterburg, B. H., Barguil, Y., Choblet, E., Cabalion, P., Rentsch, K., & Wenk, M. (2005). Traditional aqueous kava extracts inhibit cytochrome P450 1A2 in humans: Protective effect against environmental carcinogens?. Clinical Pharmacology & Therapeutics, 77(5), 453-454.
(PDF attached)

This is a different result from the other human study I had been aware of that found kava only inhibited 2E1 and not the others.

(The paper also speculates that this inhibition could have some kind of cancer protective effect. As indicated by the question mark in the title of the article that part is just a couple highly speculative sentences in the article and is in no way proven. A later highly speculative paper by Barguil also hypothesized with no proof that CYP450 1A2 inhibition could cause "sudden death" by depleting nitric oxide, proving that when you read scientific papers like these you need to be careful to separate the actual experimental results from the speculative discussion about what those results could imply.)

This is actually a followup to this old locked thread which maybe a moderator would be kind enough to merge this with so that we can have this info in one place..
http://kavaforums.com/forum/threads/which-specific-cyp450-enzymes-does-kava-inhibit-induce.7084/

I am not reading in the Russmann portion whether the "6 healthy subjects frrom New Caledonia" consumed alcohol separate from the kava. There are details of these studies that bother me, or at least missing...such as the way the kava was prepared, fresh, dry, how it was cleaned, grown. I am neither agreeing nor disagreeing and I sincerely appreciate your summary and thought-provoking content. It is also great that they throw in the broccoli...I like broccoli.
Then we get to "Tylenol" . I am sure someone has already compared "Tylenol-liver-issues" with "Kava-liver-issues" it would be interesting to review how often in each.
How often folks have liver issues with tylenol compared to kava.

 

[verticity]

I am not reading in the Russmann portion whether the "6 healthy subjects frrom New Caledonia" consumed alcohol separate from the kava. There are details of these studies that bother me, or at least missing...such as the way the kava was prepared, fresh, dry, how it was cleaned, grown. I am neither agreeing nor disagreeing and I sincerely appreciate your summary and thought-provoking content. It is also great that they throw in the broccoli...I like broccoli.
Then we get to "Tylenol" . I am sure someone has already compared "Tylenol-liver-issues" with "Kava-liver-issues" it would be interesting to review how often in each.
How often folks have liver issues with tylenol compared to kava.

Yes there absolutely are a lot of issues with this study, not least that 6 subjects is a very small number.
Re the broccoli part (in the ichthyosis paper) yes I like how he's ambiguous about whether eating broccoli will save you or kill you lol.

 

[Alia]

Yes there absolutely a lot of issues with this study, not least that 6 subjects is a very small number.
Re the broccoli part (in the ichthyosis paper) yes I like how he's ambiguous about whether eating broccoli will save you or kill you lol.

After I wrote above I went and found Dr. Aporosas' - De-Mythologizing and Re-branding of Kava (2019). It looks like that paper is a free download
and you and others may already be familiar with it. The Liver part is pretty extensive and very interesting to review.

 

[TheKavaSociety]

Yann Barguil's work has been discussed here before. He was the guy who claimed that the extracts involved in liver damage in Europe contained synthetic kavain (presumably toxic).

In general though, he seems to have an attitude to kava that for most people it seems to be perfectly benign or even healthy, but for a tiny tiny minority it can be deadly for reasons that are at present somewhat poorly understood. He claimed once that maybe 1 in 175,000 Europeans can't metabolise kava (due to their genetic susceptibility) and who may hence experience nasty stuff. But the rest can down bucketloafs of the stuff daily with no apparent harm

 

[verticity]

After I wrote above I went and found Dr. Aporosas' - De-Mythologizing and Re-branding of Kava (2019). It looks like that paper is a free download
and you and others may already be familiar with it. The Liver part is pretty extensive and very interesting to review.

That looks like a good one. I had not seen it before.
https://journals.sagepub.com/doi/full/10.1177/2050324519876131
I had been looking up Barguil out of curiosity because of @Henry's comment in another thread and found an earlier article by Aporosa where he also expresses his disdain for Barguil's "sudden death" theory in no uncertain terms, calling it "the ultimate kava lie, the biggest kava myth".
https://researchcommons.waikato.ac.nz/bitstream/handle/10289/12255/Demythifying kava (USP Tonga 2017).pdf

 

[TheKavaSociety]

That looks like a good one. I had not seen it before.
https://journals.sagepub.com/doi/full/10.1177/2050324519876131
I had been looking up Barguil out of curiosity because of @Henry's comment in another thread and found an earlier article by Aporosa where he also expresses his disdain for Barguil's "sudden death" theory in no uncertain terms, calling it "the ultimate kava lie, the biggest kava myth":
https://researchcommons.waikato.ac.nz/bitstream/handle/10289/12255/Demythifying kava (USP Tonga 2017).pdf

I ve read Barguil's work in French. He strikes me as a sensible scholar trying to understand how come an extremely tiny number of people seem to be literally dying after what we would all consider a miniscule amount of kava. He doesnt call kava toxic, he has spoken publicly about the fact that for the overwhelming majority of the population it is safe and certainly not helatotoxic. But for a few people it proves harmful, most likely due to their genetic susceptibility.

The problem I see with his work is that he underestimates the quality and food safety aspects of kava consumption. He talk of kava in general, but in reality that's like talking about the safety of drinking water without specifying whether one means rain water, well water, boiled water or sewage water.
Food safety aspects of kava are important beyond measure.

 

[kasa_balavu]

found an earlier article by Aporosa where he also expresses his disdain for Barguil's "sudden death" theory in no uncertain terms, calling it "the ultimate kava lie, the biggest kava myth"

Relevant snippet:

And finally we have what I call the ultimate kava lie, the biggest kava myth, and that is, “post-kava session sudden death syndrome”. The idea that kava might cause ischaemic heart disease (IHD) and result in “post-kava session sudden death syndrome” was first studied by Prof. Alan Clough in 2004. At the end of that study, Prof. Clough reported that “There is no clear evidence for an association between kava use and IHD”. Additionally, he said that “kava has been used for centuries by Pacific peoples with no evidence for an association with heart disease.”
So it is clear, kava does not cause ischaemic heart disease and “post-kava session sudden death syndrome”. But jump forward 9 years to a researcher called Barguil. In his paper about kava dermopathy he makes a brief but sensational claim. He says that kava causes “post-kava session sudden death syndrome” and he backed this up by sighting Prof. Alan Clough. So Barguil made up a lie about kava and then he used Prof. Alan Clough to support his lie, even though Prof. Clough said kava did not cause sudden death. Then Barguil added that 9 people had died as a result of “post-kava session sudden death syndrome” over a 13 year period in New Caledonia. He added, “No autopsies were carried out” and 6 of the 9 had been “heavy smokers, [had] severe hypertension, sleep apnoea, cardiac arrhythmia, asthma, [and/or a] family history of sudden death”. So what did these people really die of? No one knows.
It seems like Barguil just doesn’t like kava and decided to make up a story that kava causes death. The sad thing is, this lie was published in a peer reviewed journal, so people are reading this and believing a lie.