#5

Is Everolimus a better mTOR inhibitor than Rapamycin?

  • Everolimus has shorter half-life, which means fewer side effects and shorter rest periods ?

  • Everolimus inhibit mTORC2 more or less? (Inhibit MTORC2 is usually considered harmful)

  • Everolimus has better oral bioavailability(20%) than Rapamycin(14%) ?

  • Everolimus is easier to cross BBB(brain blood barrier) than Rapamycin, which means better effects on the aging brain ?

  • 10mg Everolimus equal to 6mg Rapamycin ?

  • 20mg/week Everolimus is reasonable?

  • Which indian manufacturer of Everolimus is the best quality? Glenmark?

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#6

Hard to say if it’s better as much less researched, but possibly. Best brands probably zydus and glenmark. See this thread Everolimus instead of Sirolimus / Rapamycin? Anyone else trying?

I recently purchased a bunch of Glenmark Everolimus thinking that it might be much more package efficient (given the 10mg tablets), but the packaging on these is quite large, taking must as much space as probably 10X1mg rapamycin tablets.

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#7

Everolimus is easier to cross BBB(brain blood barrier) than Rapamycin, which means better effects on the aging brain ?

Curious question, where have you found the data that Everolimus crosses the BBB easier than Rapamycin? Do you have any study to refer to?

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#8

Now that is going into uncharted territory. Way off my comfort zone. I’m happy to stick to regular rapamycin for now.

#9

The paper just went live on the preprint server

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#10

@Krister_Kauppi

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#11

Here is a link to the webinar on Youtube where Sajad Zalzala, Girish Harinath and Stefanie Morgan from AgelessRx go through the Rapamycin bioavailability study.

And here is the study.

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#12

A question that is controversial and perhaps a bit off topic but on everyone’s mind…

Is Rapa AUC or peak more important for longevity and immune function impact of Rapa? IE, should a person aim for a high peak (bbb?) but a short residence time (clear quickly) to reduce side effects…via taking a higher dose of Rapa on empty stomach, for example?

Or should a person aim for slow absorption and long residence time even at the cost of lower peak rapa in blood, possibly by taking a lower dose of rapa (perhaps two doses in short sequence) with a fatty meal?

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#13

Adam Salmon’s response to this question:

Speaker 2 12:24
Okay, do you have any sense on longevity purposes, whether it’s AUC?, CMax?, what do you think are key factors in in the effectiveness of rapamycin?

Speaker 1 12:36
So, you know, you you raise this point, I’ll have to come back to the mouse, because we don’t know. My general feeling is it’s probably something like the AUC and this is based on the fact that, you know, despite what some people might say, the chronic rapamycin treatment has still been the most consistent effect. And the one test that really go did it same time. Test different ways to do it, by the ITP every day in the diet, still did the best.

Source: Adam Salmon's Marmoset Longevity Study - #4 by RapAdmin

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#14

Yes, I saw that before; good interview. I’m still gathering data (opinions) before I adjust my methods. It’s nice to get multiple points of view. I already know that there isn’t a clear answer, but I’ll go with the dominant leaning among the smartest people once I know what that is.

#15

Yes that would be good for those people that can take blood tests. However, the answer to that question would not be simple and would differ depending on the frequency of dosing.

#16

tomorrow I will take 10mg with GFJ. At the moment I am doing it once every 2 weeks. :wink:

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#17

I can get pure rapamycin in powder form. Does that format, powder, affect bioavialability?

#18

I’m not sure where you would get the pure powder form from. However, I would assume it would have the same bioavailability as the compounded versions since the compounding pharmacies use a powder form when mixing up their capsules or tablets
To my knowledge, compounding pharmacies measure out the rapamycin powder, add an excipient/filler/binder, and make up the capsule or tablets that way.

#19

The paper here indicate that compounded Rap is not as bio-available, not sure why that would be. Unless the actual amount indicated of the active ingredient is not in the pill/cap? and that paper only shows the blood level from the compounded version but not the generic version so one cannot tell from that paper what is actually happening.

I get >99% Rap for about $0.50 a mg. Dosing 6mg of powder is not a problem for me but for most people, it would be.

#20

The commercially available tablets use some form of encapsulation or absorption enhancement materials to improve the absorption. Since ingesting the compounded form, which would be the same as the raw powder form from a practical perspective, does not have the encapsulation, therefore there’s lower absorption and bioavailability.

AgelessRx had worked with a compounding pharmacy partner to include ingredients to enhance absorption. But then we realize the cost of doing so made it far more expensive than it’s worth (It doubled or tripled the cost of the compounded capsule, whereby tripling the amount of rapamycin in a capsule only increases the cost marginally or a 15mg capsule is only slightly more expensive than 5 mg capsule)

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#21

Steve - this issue has been covered before in these discussions - I recommend you check them out:

here: Rapamycin enteric coating vs powder bioavailability

here: How many are making their own solutions from powder?

here: New Peter Attia interview w/Matt Kaeberlein, inferior bioavailability of encapsulated rapa

related Sirolimus Powder - 3rd party analysis

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#22

Thanks, that is what I thought. Enteric coating is the only “improvement” to enable better absorption in the lower digestive tract as opposed to the stomach. And there appears to be a bit of a stability issue to look into.

Fortunately I have enteric caps in stock and the ability to fill them accurately.

To date I’ve just been using the powder for skin care.

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#24

Just take it 3 hours after a meal. The stomach acid should be the lowest by then. I get the best blood result like that.

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#25

I was approved for the compounded rapamycin just this week by the ageless group.
I started on the sirolimus 1mg about 3 weeks ago, then upped to 2mg last week.

Has anyone been using the compounded rapamycin from the ageless team?

I’ve been taking the sirolimus just once a week. I’m also on Diltiazem which somewhat acts like grapefruit juice I’ve learned.

Thanks!

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Cardiac disease and use of rapamycin