Matt Kaeberlein discussed half life on his YouTube channel about 8 months ago. the 63 hours was apparently derived from higher dose transplant patient data. Matt tested himself and got a much shorter half-life. He also showed data from Bryan Johnson who also had a shorter half-life (less than a day). Suggestive, not conclusive, that 63 hours might be taken with a grain of salt.
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For sure, rapamycin does NOT stick around for a 63hr half-life in healthy people using it intermittently.
Here’s what I know so far based on data we’ve collected at AgelessRx (we check everybody’s sirolimus levels but at random timings - we let people get their blood drawn whenever is convenient rather than time it for rapamycin):
- sirolimus levels seem to peak around 2 to 4 hours after ingestion
- there is a much smaller peak around 48 hours
- levels drop off around day 4 or 5
This is based on my observations of reviewing patient charts. I asked my research staff to see if we can analyze the data and make more concrete conclusions
Personally, I take my rapamycin on Tuesday around 1pm - maybe 30min after lunch.
I wait another 30min and take my other afternoon meds/supplement. Including 2.5mg tadalafil, 10mg atorvastatin, and a small dose of sublingual tirzapatide.
I avoid anything with curcumin on Tuesday since it’s thought to interfere with absorption.
Otherwise, I take my normal meds/supplement stack in the morning. This includes 1000mg of metformin ER.
Is it optimal? I have no idea…
But I recently did a metabolics test by Iollo (Mike Snyders group) and my rate of aging was very low (0.05 - whatever that means)
No, I haven’t done a Dunedin-Pace test recently to compare. Sorry
Remember , though, what works for me may not be appropriate for you!
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My high dose testing did seem to fit, however, with a long half life. It is quite likely a two compartment system anyway.
I did not, however, test for serum half life. Instead I tested for blood panels twice a week. The effect on Neutrophils is quite rapid. (because they have a really short half life).
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Beth
#13
NGUH, I’m just commenting to give you support!
I find all this information hard to digest as well!!! Because I don’t have a brain for science either, I rely on everyone’s help to figure it all out, so I’m glad you posted your question!
And PS, I don’t accept that you have lack of intellect… our brains are all wired differently and we have strengths and weaknesses in different areas. I’ve met brilliant CEO’s who can’t fight their way out of a paper bag 
And yes, the amount of money one can spend on all these supplements is staggering, so I understand the financial stress of it all. You are very smart not wanting to be wasteful.
I’ve learned some things from the answers here, so thanks again for your post.
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vongehr
#14
Big part of the confusion here seems to be that the half life itself is what varies between people and methods such as grapefruit (GF) ingestion.
It is not so that GF by some magic multiplies Rapamycin, and then comes the independent half life. Instead, and this is why I keep eating GF for a few days, GF slows hepatic removal of Rapamycin and thus increases the half life, especially soon after dosing in oral or rectal applications (because the blood from those places first goes through liver), but also later (blood always still hits the liver once in a while, even if you dose IM).
I agree with you that GFJ will also increase the half life. However, personally I don’t want to increase the half life.
cl-user
#16
Not really. This has been discussed here already. Here a ChatGPT summary:
Grapefruit juice is well known for inhibiting CYP3A4 in the intestinal wall, which reduces the first-pass metabolism of many drugs. Although grapefruit juice contains compounds such as furanocoumarins that can inhibit CYP3A4 in both the gut and the liver, the impact on hepatic CYP3A4 is much less pronounced. This is because the concentration of these inhibitory compounds is significantly higher in the gut, where they directly interact with the enzyme as the drug is absorbed, compared to what eventually reaches the liver.
In vitro studies have shown that grapefruit juice components can inhibit CYP3A4 in liver microsomes, but in vivo, the effect on hepatic CYP3A4 activity appears minimal and is not generally considered clinically significant. Most of the enhanced drug exposure and related interactions are therefore attributed to the inhibition of intestinal CYP3A4.
This distinction is important because it means that while grapefruit juice can markedly increase the bioavailability of drugs like sirolimus by reducing intestinal metabolism, it does not substantially alter liver metabolism of the drug.
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RapAdmin
split this topic
#17
Maxi
#18
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Maxi
#19
Yes, I measured my peak and half life (see post “Peak Values and Half Life”, unfortunately the graphs didnt come out) and found in multiple measurements a half life of 6-8 hrs, which is plausuîble as I am, according to my pharmacogenetic profile, a rapid metabolizer of 3A4. So I have a good peak but AUC is too low ! I want to increase half life, many 3A4 inhibitors available but problematic or difficult to dose. So i’ll try with GPJ by taking it 2.5 hrs after Rapa, which is where my peak lies. Any comments/suggestions on AUC improvement w/o increasing peak ?
59vw
#20
Maxi, this has been discussed previously here but if you are measuring T1/2 within the first 24-48 hours after taking rapa you are likely seeing an artifact of tissue uptake of rapamycin that reduces blood levels dramatically from about 2 -48 hours post ingestion of rapa. If you want an accurate T1/2 you should start your measurement at 48 hours and measure several times every 12 to 24 hours to generate a graph. I think you’ll find your T1/2 is closer to 50-60 hours. This is the same mistake that Kaeberlein made.
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Maxi
#22
Thank you. What dou you mean “an artifact of tissue uptake of rapamycin that reduces blood levels” , I have trouble understanding
Maxi
#23
Here is what I measured. The first graph is C (ug/l) after ingestion (14mg, no GPJ), the second C (in % of Peak) after Peak Time (several measurements). This checks with what you are saying, but for me hard to understand why this does not represent the usual metabolization and hence half tim. Could you please point me to more information (studies ?) . At 48 hrs I am at percentages of Peak, i.e. in the order of 1 ug/l. How can you measure for additional 48 hrs ? Or does C rise again ? Am I wrong ? Thank you for clarifying.
Pik 3 Curves 14 mg Feb March 2025.pdf (90.1 KB)
Sirolimus Half.Time Exp 15 03 2025.pdf (74.8 KB)
Yes Your model is visibly totally off:
what are the concentrations and time for those green points?
Maxi
#25
You are probably right. I’ll take more points downstream.
Just use the last 2 points to compute the half-life.
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59vw
#27
Agree with cl-user, just use the last two points and maybe a 72 hour point to compute the half life. The early blood concentrations are not showing steady state kinetics and will throw the entire model off. After about 48 hours you will be in steady state kinetics and several time points applied to the equations above will give you the T 1/2.
I have not really tried to get into this, but superficially a dimensional analysis gives ln time, not time which confuses me.
cl-user
#29
The formula I pasted is poorly formatted. It’s ln(2) * (t2 - t1) / ln(c1/c2) which gives the half life in the same unit as t2 and t1.
OK that’s dimensionally correct. I have not engaged brain to work out whether I agree with the formula or not,
