What is the Rapamycin Dose / Dosage for Anti-Aging or Longevity?

Ah those “human impediments”…remember, biology does not care!

The activity on brain microglia. That’s a very big deal in regards to neuroinflammation and neurodegenerative diseases which we really don’t want.

tacrolimus is a completely different class of drugs than sirolimus and everolimus though, it’s a calcineurin inhibitor, not mtor inhibitor

Matt doesn’t see much difference in the two drugs:

rapaOrEverolimus2

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I think he’s thinking of Temsirolimus - Temsirolimus - Wikipedia

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I guess my thinking is that by using both you’re getting the known/proven longevity benefits of rapamycin, alternating with the potential different tissue distribution, shorter half-life (lower mTOR2 risk?), slightly lower side effect profile, increased BBB penetration of everolimus.

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Not reported…can we assume a non issue, certainly would be part of every blood panel, at least fasting glucose. But the study only dosed for 6 weeks…A1C needs at least 12 weeks to reconfigure right?

If I were to switch, I’d do an all-in Everolimus trial…no way to separate signal by mixing both. Maybe at the other end, could revisit remixing.

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Not sure what signals to watch for.
Lowering of lipids and glucose maybe.
Weight loss.
Energy?

All of the above yes, but one needs a reference time zero. How would tease out rapamycin and/or everolimus on a dual dose intervention?

To get true insight, would need the blood tests to try and ascertain the therapeutic intervention (eg. trough, AUC). Was I able to increase say trough/AUC but fewer side effects?

Yes - I agree with you @MAC you need to do the blood tests at your target dose of rapamycin, then zero out on the existing rapamycin, do blood tests again, then slowly ramp up the everolimus to the equivalent therapeutic dose as was with sirolimus, then do blood tests again, to see the difference.

At some point I will do this mini clinical trial. Afterwards, I would try to phase in the sirolimus again, testing different dosing protocols - perhaps take them at the same time, or perhaps alternating them. And blood tests as I go along.

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I have taken my third dose of 3 mg of rappa, I’m 78 years old and female so I’m not sure what dose I should take and for how long. I checked my glucose level 4 days ago and it was elevated, I took Metformin twice daily after the spike and my glucose level fell by 20 points . I am pre diabetic some of the time but often reduce glucose level to normal range by diet and Metformin.

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I still haven’t been able to figure out the effect on my blood glucose, if any. Since I have started taking rapamycin I almost never have it go below 70. Before it often would. But that’s not bad, that’s good. Looking at my CGM readings for the last 14 days my average is 104. My average for the last 90 days (about 50% pre-rapamycin) is 95. But this could be because I have been eating more carbohydrates.

Seems like taking Rapamycin is actually good for your glucose levels, unfortunately I have been around 100 for years so any spike is not good , I have now bought a Genteel blood suction device as there is no pain so I will experiment with glucose levels pre and post Rapamycin

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I am a little concerned by the 14 day #. Trying to avoid spikes is why I have a cgm. Easier said than done!

If you do this, since you already have your rapa data, you can generate data on everolimus and then, ideally, data on a a combination therapy.

In combination, because of the short half life, I was thinking:
Day 1 Rapa
Day 10 Ever
Day 14-17 ?? Rapa…

This would allow for a 2 week-ish rapa schedule with an Everolimus kicker timed when most of the rapa has cleared. If rapa is superior, you’re still getting a regular dosing regiment. If Ever proves better and provides penetration of the BBB, you’re getting that along with the rapa.

The delay between the Day10 Ever clearing and starting back rapa on Day 14-17 contemplates whether one would want days with both cleared from your system and, how many days one would want such a break inserted?

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Hey RapAdmin,

Just saw this now: “fully inhibited…” If that means complete inhibition, it’s inconsistent with everything I’ve read about rapamycin and everolimus. Massive doses of rapamycin in mice, for example (leading to sustained blood levels of around 60 ng/mL), inhibit TORC1 around 80%, not 100%, in certain parts of the brain. I’ve seen nothing in the Mannick papers indicating there was complete inhibition of TORC1.

Kind of what I’m now doing. Dewtails when I get a break from work (early Nov.)

By the way, pure everolimus in simple (what you find on Amazon) enteric coated capsules has massive bioavailability. Full report later.

One benefit of joining later than most is reading all of the past threads. Lots of good information in the old threads.

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I am going to start taking capers and cumin extract, both high in Kaempferol.

https://www.researchgate.net/publication/342413079_Evaluation_of_Kaempferol_as_AKT_Dependent_mTOR_Regulator_via_Targeting_FKBP-12_in_Hepatocellular_Carcinoma_An_In_silico_Approach

The docking studies support Kaempferol to be a potential ligand with docking score values of 33.4 (3CQU-3D structure of AKT1)] and 27.3 (2FAP-3D structure of FRB domain of mTOR) respectively as compared to that of standard drug Everolimus with 24.4 (3CQU-3D structure of AKT1) and 20.1 (2FAP-3D structure of FRB domain of mTOR) respectively. Docking studies along with ADMET results shows that Kaempferol has favorable drug likeliness properties and bind to the same active site (site1) of the targeted proteins (3CQU-3D structure of AKT1) and (2FAP-3D structure of FRB domain of mTOR) where the standard drug Everolimus is known to bind.

Conclusion The study exhibited that Kaempferol was having a better binding affinity towards the receptor FKBP12, a Rapamycin Binding Domain and AKT serine/threonine-protein kinase resulting in its better efficacy in the mTORC1 inhibition as when compared with standard drug Everolimus against HCC. To the best of our knowledge, no studies have been reported on Kaempferol as an mTORC1 inhibitor against Hepatocellular carcinoma.

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