See this thread: Possible Rapamycin Risks for Healthy Humans (Part 2)
you are on the ball RapAdmin- thank you very much.
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What’s the source for the table and the graphs? If it’s not open access, can you make the pdf available?
Are you talking about the images in the first post of this thread?
Also,
From the matt kaeberlein talk yesterday:
- Matt Kaeberlein mentioned there is unpublished data that shows that everolimus increased lifespan in mice (not sure what lab or who did it).
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Yes: I was replying directly to that post. Does the platform not show that?
It was Stephen Spindler who showed that everolimus robustly extends lifespan:
The money shot is at 10:42, but the whole thing is worth a watch.
With all the other stuff that he showed doesn’t work and his strong methodology, this is an important result.
Lots of other mouse data on everolimus and aging outcomes, though not as much as rapamycin.
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Here is some of the source data for the first post (it was over a year ago when I posted it, so I can’t find the exact same paper for the Everolimus chart - but there is a close one here:
Klawitter, Jost; Nashan, Björn; Christians, Uwe (2015). Everolimus and sirolimus in transplantation-related but different. Expert Opinion on Drug Safety, 14(7), 1055–1070. doi:10.1517/14740338.2015.1040388
Full Paper here: Sci-Hub | Everolimus and sirolimus in transplantation-related but different | 10.1517/14740338.2015.1040388
The Rapamycin / sirolimus half-life curve is from the paper below, which is included the bottom of the first post in this thread: What is the Rapamycin Dose / Dosage for Anti-Aging or Longevity?
Pharmacokenetics and Safety of a Single Dose of Rapamycin (sirolimus) in Healthy Males
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Just one thing to note that I found as I was looking at these papers again… Everolimus seems to have a different response to being taken with a high fat meal than rapamycin / sirolimus … see table below from this paper:
Everolimus and Sirolimus in Transplantation-Related but Different
Link to exact table in paper.
And, the Pharmacokinetics of Sirolimus vs. Everolimus:
From this direct link to the table
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Oral everolimus is absorbed rapidly, and reaches peak concentration after 1.3–1.8 hours. Steady state is reached within 7 days, and steady-state peak and trough concentrations, and area under the concentration-time curve (AUC), are proportional to dosage. In adults, everolimus pharmacokinetic characteristics do not differ according to age, weight or sex, but bodyweight-adjusted dosages are necessary in children.
Lipid Increase with Everolimus:
I found this interesting:
Source: Clinical Pharmacokinetics of Everolimus
Full paper (PDF) below:
00003088-200443020-00002.pdf (160.5 KB)
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I read elsewhere you want a fast peak with rapamycin, taking it with a high fat meal lower the peak (Cmax), and increases AUC.
I spoke with rapamycin researcher Adam Salmon this morning… he’s doing the marmoset lifespan studies. I’ll post more when I have time to do a writeup on my interview, but in short, yes, high fat is good to take with rapamycin. Adam believes that all the data strongly suggests that its the AUC that matters most for longevity- all the biggest lifespan increases in mice have been daily dosing.
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Okay, interesting, that makes sense as the mice did have rapa continuously.
A decrease in AUC with fatty meals for everolimus seems important.
Now I just need to know how everolimus reacts with GFJ to try an el cheapo approach.
But if everolimus need to dose twice as high as rapa, it isn’t so lucrative.
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I think we’ve identified a blood everolimus test above in this thread - please report if you do use it and the cost, and best places to get it.
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I found the original paper for the comparison table from that first post:
Long-term outcome of everolimus treatment in transplant patients
Thanks for digging up these resources. From a quick glance, some frustrating inconsistencies.
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For what it’s worth, I’ve also tried chewing everolimus and and swishing it in my mouth for up to a minute, and then swallowing it. It doesn’t have an unpleasant taste, and I’ve noticed subjective effects within minutes! I limit this method of administration to no more than 5mg everolimus at the moment however.
Interesting. But i wonder if everolimus is like rapamycin and has to be protected from stomach acid so it gets into the small intestine and absorbed. Chewing could break the barrier that provides the protection against the stomach acid.
The study they cite for this is:
This is an in vitro study testing a standard concentration of each drug on primary human aortic endothelial cells (HAEC) after one-time exposure. As many people will know, rapa does not acutely inhibit mTORC2, but somehow destabilizes it after prolonged exposure: that’s part of the rationale for intermittent dosing. So I don’t think this study should be relied on too much as regards the relative effects of the two drugs on it.
The basis for Dr. Stanfield’s statement that everolimus inhibits mTORC2 more than rapa here is not clear; no citation is given.
On the other hand, the Lamming study found that everolimus is less prone to inhibit mTORC2 after long-term administration is in vivo — at least in the liver. It is in mice — but so are nearly all the other studies on which we’re pinning possible human use. This is the same study cited for saying everolimus is less prone to inhibiting mTORC2 as cited in the Wikipedia article.
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I guess chewing and swishing results in something like a sublingual administration which may be the reason for the quick effects. But yeah, i don’t know what happens in the stomach.
Did you ever contact them? What did they say?
I have not yet ordered any everolimus or spoken to Life Extension about the potential for a lower cost version of the everolimus blood test.
Last year when I emailed them about the sirolimus blood test I just contacted them as a concerned customer… so if anyone is interested in a lower cost everolimus blood test i encourage you to contact them and tell them there is a growing interest and demand in this test, just like the blood sirolimus test. Here was my original contact effort towards their lab customer support: How to get a Rapamycin (sirolimus) Blood Level Test
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Oh — really? You were indicating you would do so back last summer. What changed your mind or caused you to delay commencement?