Well, yes. But the opposite conclusion might be reached too. The fact that a given drug, in this case rapamycin has a different pathway through oral vs transdermal (or rectal/colonic) absorbtion might mean that it undergoes different processing resulting in different health impact. We know this to be true to some degree, because we’ve had studies where rapamycin was delivered through injection (in mice) and having a non-equivalent impact. It reminds me of various arguments I read about how curcumin is not absorbed into the blood plasma and therefore is an inert molecule in the human body. Except the action of curcumin was not through direct effect, but through the metabolites that arose as a result of being processed through the microbiome. The manner of deliverance matters, and not just through bioavailability of the molecule itself. Most studies of rapamycin were conducted in models where the method of delivery was oral (and some injection). That to me is a salient point, and not something to gloss over as you rush to a conclusion based on a completely different mode of delivery, with potentially completely different processing and discrete effects all along the way.
It’s the old black box problem. Inputs → processing inside the black box → outputs. You cannot expect to change the input and then have the exact same output because you have speculated or assumed what goes on inside the box. You want the same output? Make sure it’s the same input. You have just changed the input from oral to rectal. Bzzt! Wrong. You are assuming that the change of delivery method - i.e. what happens inside the black box - will nonetheless deliver exactly the same output as in the studies where we have reached conclusions based on oral delivery. I have spent enough years reading biological studies to know that such assumptions are dangerous in the extreme.
Now, you may be right, and it makes no difference except for the differences you outlined - but that’s an assumption that needs to be proven. I don’t know. I don’t assume or claim anything. I just demand that you show it, because there are no studies that I am aware of which examined the effects of rectal delivery of rapamycine. Maybe you are right, but then you must show your work. You have not done so, instead you made a series of unproven assumptions. A hightly dangerous thing in medicine, that has lead to many faulty outcomes. Mechanistic reasoning at its worst. Show me the outcomes, and then we’ll talk.
Meanwhile, I’ll stick to taking rapamycin in the way studies have shown - oral. Those are the outcomes, and that’s what I’ll do, based on studies. So I’m going by the study protocols - you are not. Until you have proven otherwise I don’t see your approach as well founded. YMMV.
vongehr
#22
going rather strong again are we? Did you not just recently go of the rails while discussing here? Hypertension? It is you who made the unbased assumption of that the rapa just treats my ass. I have not made any of the claims you ascribe to me! I proposed the rectal route, started trying, asked others to please help establishing blood work. Now take some deep breaths and consider the longevity due to loving kindness.
Eh? I made concrete points about biological pathways, in response I got a lot of odd statements not focused on the issues at hand. And therefore, there is no need for me to comment - let them shine on their own for all to see. No advantage in any further interaction. All the best!
vongehr
#24
you are abrasive and can’t give constructive criticism all over this forum, and others told you so. Once more, calm down, or you gonna cut down on your lifespan no matter where you put the rapamycine.
vongehr
#25
Also the rectal area evolved to counter entering poisons by absoption into the “first pass liver” metabolism, via HPV (hepatic portal vein duct) and IVC (inferior vena cava), as in this picture.
Therefore, also rectal application occurs 2h after ingestion of a grapefruit, after 50 mg acarbose.
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vongehr
#26
Good news, more info I found on this great forum, so people here knew, but instead opted to clutter the thread with silly nonsense. Why is that???
Anyways, CYP3A4 already acts in the intestine walls, not just the liver (“first pass”). Thus, it being highly likely that there is less CYP3A4 in the rectum, the rectal route still has all the originally claimed advantages, even though blood still goes to the liver (which is prepared by grapefruit ingestion).
