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

On today’s new The Drive podcast, starting at about 1 hour 40 min, Matt Kaeberlein speaks about the poor bioavailability of rapa powder compared to tablets and doubles down on the view that compounded rapa probably won’t work nearly as well as branded or generic sirolimus tablets because stomach acid destroys the rapamycin.

This is such an absolutely hugely important topic for those who may THINK they are taking rapamycin but essentially aren’t, and are posting their experiences on effects, side effects, etc, which could skew our perceptions in so many wrong directions. Do we have a poll on percentages of people on this forum who take Rx tablets vs compounded or imported capsules/powder? I was giving my dog capsules from a veterinarian in California until I started reading about this issue a few months back. I actually decided to cough up the $600 and get him branded Rapamune and have started him on that recently.

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Yes, this issue first came up in june… See: Bioavailability of Rapamycin From Compounding Pharmacy

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Hopefully most are taking pills rather than capsules! Sounds like I wasted a LOT of money buying powdered capsules for my dog that likely weren’t helping him at all.

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I’m using 3mg capsules from Tailor Made Compounding:

Hope this doesn’t deserve a :frowning_face:

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I would do a blood sirolimus test a few hours after dosing to confirm

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The new part (for me at least) of the bioavailability discussion in the interview from today’s podcast was Matt’s discussion of the story behind development of “e-rapamycin”, encapsulated rapa that was designed specifically not to break down in the acidic environment of the mices’ stomachs despite being in their food, and that development of e-rapa took 18 months. They weren’t even going to be able to study rapa at ALL until they fixed this issue.
If this is the case, I don’t see how compounded rapa powder capsules could be anything other than a big waste of money unless the capsules are truly and effectively enteric coated.

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E-rapa was developed for animals. The Pharma companies have addressed the problems for humans, a variety of ways, using 3rd party technology like “nanocrystals”, etc. See this discussion thread and research: Rapamycin and NanoCrystal Formulations

Yes, I wasn’t suggestimg e-rapa is the only way to get absorbable rapamycin (branded or generic tablets may in fact be the only way).

From what MK is saying, it appears that rapa powder may not just be lower in absorption (which many including me had assumed based on what’s he’s said previously), but from this interview it seems essentially worthless, as in likely zero absorption.

Yes - that is what some of the doctors are saying on twitter - where their patients are taking rapamycin from compounded pharmacies (in capsules) and not showing any positive measures at all in the blood sirolimus tests… so yes, a big potential issue for anyone purchasing from compounding pharmacies.

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This was addressed by Dr. Green in the Kaberlain/Green/Blagosklonny podcast. Dr. Green uses compounded capsules for a topical blend, but not for mTor inhibition.

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Excellent points made! I started with generic, Dr. Reedy’s, Sirolimus. I did well and then switched to an equal dose of compounded. Symptoms of aging returned on the compounded form - sore joints after workouts and low back pain. I saw the previous thread about compounded forms not being well absorbed. I switched back to the Dr. Reedy form and symptoms resolved. Blood work would have been helpful from the objective side. Thanks for sharing the video. I like the points made about muscle mass decline accelerating age related issues and comments about higher protein diets not showing longevity issues that many think.

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@David did you try the strategy of placing the compounded capsule inside an enteric capsule? ( And yes, I followed the thread about whether the enteric capsule strategy works or not. ) Were you using capsules from TM? Just curious.

Is the Dr Reedy’s version a tablet?

I believe it was Matt K that said that compounded powders had lower efficacy in that Podcast. To add insult to injury, I paid more for the compounded powder capsules (for my skin cream) than I did for Dr. Reddy tablets.

So I mentioned this before, but what about the liquid oral Rapamune Oral Solution (that combines Rapamycin powder with ethanol, propylene glycol, and soya oil.) This solution is commonly prescribed to transplant patients also. Don’t we have any studies comparing the bioavailability of the oral solution with branded or generic Sirolimus tablets? That should give us somewhat of an answer, or not?

Yes, the Dr Reedy’s rapamycin is a tablet.

Yes, the oral liquid rapa solution is puzzling. Why doesn’t stomach acid destroy it in this formulation? I don’t think we ever arrived at a good answer for that.

This would actually be a great question for Matt Kaeberlein if we can get it to him.

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Lower bioavailability not no bioavailability, rapamune is available for transplant patients as a drink too but dosage is not compatible

The instructions for the drink are oddly specfic: to be mixed in a glass or plastic cup with 60 ml of either water or orange juice but nothing else, to be drunken immediately followed by either 120 ml of water or orange juice …

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I did not try that strategy after researching on how difficult it is to get good blood levels that were discussed in the first proposed mouse study detailed in your video. All of my personal data is just subjective, but for me, that’s the most important - to improve health span first and great if longevity is a side effect :cowboy_hat_face:

“Lower bioavailability not no bioavailability, rapamune is available for transplant patients as a drink too but dosage is not compatible”

As far as I’m aware this is the patent of the oral solution Rapamune Oral Solution - but correct me if I’m wrong:

It was invented especially to increase bioavailability. What I asked before - and am still wondering - is whether we have any studies comparing the bioavailabity of such an oral solution to the bioavailability of branded or generic Sirolimus tablets.

Anecdotally I use a bit of a similar approach to the approach described in the patent. I am in the unfortunate position that I can’t get a Sirolimus blood level test done where I live. However, anecdotally the side-effects I experience are so obvious that I would find it hard to imagine that the bioavailability is as low as is suggested here.

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