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Dangerous to combine Rue and Milk Thistle? Options
 
RhythmSpring
#1 Posted : 3/29/2019 2:32:55 AM

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Someone correct me if I'm wrong, but my rough understanding is that they both require the CYP3A4 liver enzyme to be broken down, or both reduce it, or something like that.

So if they are both in the body at the same time, wouldn't that create an unhealthful circumstance? Or would one potentiate the other?

Wut?
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downwardsfromzero
#2 Posted : 3/29/2019 3:42:54 AM

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The actual enzyme dynamics of the two combined depends on whether either of them induces the CYP3A4 besides merely being competitive substrates. It might be helpful to be clearer about what you think is going on (you must have a source?) because one possible interpretation is that one or the other of these plants downregulates production of the enzyme.

Considering it's rue alkaloids you're talking about, it's worth considering that there have been claims that harmaline is harder on the liver than THH or harmine. In that case the milk thistle might prove to be beneficial. It's not clear how or whether harmaline exerts any hepatotoxic effect but if it's oxidised to a toxic metabolite by one of the cytochrome P450 enzymes - as is the case with the toxic pyrrolizidine alkaloids - then taking something that blocks that metabolic pathway would potentially be a good thing. More research is necessary.

And while it could be said that prudence would dictate not adding grapefruit to the mix, grapefruit reduces hepatotoxicity of pyrrolizidine alkaloids by around 70% (in rats) by blocking their CYP3A4 mediated toxification. (Reference will follow.) IIRC, at least some of the harmala alkaloids are broken down by CYP2D6 as well so there are other routes for their elimination.

A significant amount of harmala alkaloids are excreted in the urine. Some proportion of them appears to get demethylated to harmol etc. judging by the shift in colour of their fluorescence. Maybe we can start sending Endlessness or Benzyme some harmalated urine samples for analysis, on top of everything else, to confirm this hypothesis. Off the top of my head it's not possible for me to recall which of the CYP family would be responsible for this O-demethylation, but it is definitely one of them - maybe even CYP3A4.




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ShamensStamen
#3 Posted : 3/29/2019 6:07:43 PM
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Not a problem in my experience, i was taking Milk Thistle extract for a bit there, and still took Rue here and there, even mixed the two together on a few occasions, no negative interactions noticed. Harmalas are primarily metabolized by CYP2D6, which Harmalas inhibit, they also inhibit CYP1A2, haven't heard much about Harmalas inhibiting CYP3A4 though. And Rue isn't hard on the liver in my experience, i took it daily/near daily for 4 years, and then daily for 8 months straight, usually in high to heavy dosages, no negative health effects noticed.
 
RhythmSpring
#4 Posted : 4/2/2019 11:46:38 PM

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Thanks, guys.

I took the two together and it was fine. And from what I read here, perhaps the Milk Thistle makes it even safer by protecting the liver.

Although I will say that my heart gets jumpy when I chew the raw Syrian rue seeds, leading me to believe that Harmaline is a bit more risky to mix with things than Harmine/THH. Syrian Rue that I've boiled for an hour feels a lot smoother and easier on my system than raw or boiled for 5 minutes.
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Auxin
#5 Posted : 4/6/2019 10:14:52 PM

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For clarity, I'm curious. Did you consume ground/chewed milk thistle seeds or an extract?
When ShamensStamen said he experienced no bad interaction with milk thistle extract it didnt surprise me at all since such an extract should be free of amines, but the actual seed would have many compounds not contained in a silymarin focused extract.
Thanks for posting your experiences Smile
 
RhythmSpring
#6 Posted : 4/6/2019 11:26:35 PM

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I consumed an extract of Milk Thistle with the boiled (1hr) Rue seeds, although to be fair, it was around .7g of the seeds. Still, it felt safe. I'm pretty sensitive.
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