Rapamycin Half Life for Matt Kaeberlein Only 8 Hours?

Thanks for the explanation. I’ve been worrying about the possibility of a higher multiple. I’m glad to hear the range is narrow. I still might get a higher multiple since I eat 1 grapefruit 12 hours, 3 hours, and 1 minute before rapa. 4mg with a 14 day interval and a break after 2 cycles feels right. 5mg felt like too much, side effect wise. I don’t use fat or any other food, with a goal to get a higher peak and faster clearance (in theory).

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Do pomegranates have the same effect? I much prefer the taste of pomegranates to Grapefruits and my usual supplier of Pomelos seems to be unable to get them at the moment. Hence I bought a grapefruit yesterday for my planned Rapamycin tomorrow (my normal 21 day cycle).

However, if I could replace eating a grapefruit (or part) with Pomegranate that seems a much better option and also has the potential for urotlithin A (I don’t know if my microbiome creates it).

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An additional complication is that Rapamycin probably follows a two compartment model for elimination. This paper looks at that

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600722/

As far as I am personally concerned the main issue is that it hangs around a lot and hence
a) I should assume sleep disruption for a day or two
b) I should take it quite infrequently to allow time for my mTOR complexes to function normally.

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Very nice paper, thanks. The saturable oral absorption results in a less than proportional increase with higher doses in overall exposure for rapamycin. From a safety perspective, this is better than a higher than proportional increase in exposure with higher doses. There is a typo in Table 1 since Km units should be a concentration, not simply mg. I suspect the authors meant 13.8 micrograms/L Another commonly used drug that also has this property is gabapentin.

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Indeed, similar CYP3A4 inhibition. However, as with everything, test to see your personal result would be the sensible approach so that you understand your personal absorption and metabolism. It is easy to do as described, sadly not how Dr. Kaeberlein did it - get a level at 20 hrs and then 48 hours later. This usually makes the math really easy as your level 48 hours later will usually be close to 1/2 of your level at 20 hours making a rough estimate really simple.

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Can I ask what your dosing regimen is and how you worked it out? I understand if you would prefer not to share or if you have already given details then please point me there. Thanks.

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I have not found a route to getting blood levels measured in the UK. I have not tried that hard, however.

My decisionmaking process is based around taking a dose that does not produce too much of a negative side effect. The disruption of sleep is a negative side effect that I expect because of induced autophagy.

I am, however, hitting the protocol from multiple dimensions with attempts at combinatory effects. Only one of the interventions is rapamycin.

So - the data on sirolimus metabolism isn’t based on Dr. Green’s patients. There is no situation in which someone metabolizes rapamycin 4 times faster than the norm.
I have patients who are younger and healthier than Dr. K - and their metabolism is as expected. However, I measure it correctly. The issue isn’t whether he has a T1/2 of 8 hrs – it is plainly being done incorrectly.
When I was VP for Skyscape years ago, I authored widely used references of RxDrugs and Labs360. As part of that had a lot of interactions and discussions with PharmD’s and Laboratory medicine experts.
I’m not right all the time, and love to learn - but on this issue, there is a fundamental error, and it is a methodologic error, not that Dr. K’s liver is the most remarkable liver ever in a human being in regard to Rapamycin.
Dr. K is brilliant, love almost everything he has done … I wish I had an email for him to let him know he’d made an error before he put this out. Irrespective, there are times people think they understand things they don’t, and move forward with things they really could have used some expert advice on. This is sadly one of those cases. Couldn’t have happened to a nicer fellow … but he made an error and then did a podcast demonstrating his error, and still doesn’t know he’s made a mistake.

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https://www.optispan.life/contact

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OK, I am convinced. An error was made.

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Matt K. does follow rapamycin.news, so it’s very likely.he may see the information that you posted,

If you want to PM me a message and I can get you his email… to question him.

Or, just PM him on this site because he is a member.

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Excellent, well thought out post. Thank You!

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Thanks @Agetron - I’m glad you let me know this - I will be having a chat this week. A bit humbling to speak with a legend.

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Exactly, Matt K. Is one of the few knowledgable researchers without an agenda… except… wanting to explain what does the evidence point to… and is the work accurate using proper scientific methods. Very methodical and trusted.

And, geeky, funny and humble too.

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That’s very helpful. Thank you.