Timing of rapamycin dosing

I am a physician (anesthesia and critical care medicine) and my wife and I have been taking rapamycin for a little over a year. I am in my early 60’s and my wife is late 50’s. I’ll keep the post abbreviated for the sake of readability.
We are generally both fit, thin, healthy and exercise regularly with a very robust healthspan promoting lifestyle.
I have been taking metformin 500 mg BID for several years (had an A1c of 5.7 with a strong family h/o type 2 DM) as well as acarbose. Also generally try to eat a low(ish) carb diet. Wife is a vegan, I eat meat.
We had baseline labs drawn and have repeated them at about a year out.
We have been dosing rapamycin (sirolimus) 8mg/wk for 8 weeks for me (70kg ) And 6 mg/wk for 8 weeks for my wife who is 55 kg. We have alternated 8weeks on and 8 weeks off for the entire year. We did not ramp up the dosing but started at the above doses from day 1.
With the exception of aphthous ulcers ( I have had them twice and my wife once) there have been no significant side effects. Our labs are directionally very similar, a decrease in LDL cholesterol for both of us, an increase in A1c of 0.2 for both my wife and I. Otherwise no changes. TG are very low and HDL in the high 80’s.
We currently are considering changing a few things and am interested in thoughts from the group.
First I would love to check sirolimus levels (through Life-Extension) but wonder what the best timing of the lab draw would be based on the pharmacokinetics.As a corollary, I would love to determine the effect that grapefruit juice concentrate has and if I can measure the levels might consider using it to decrease the required oral dose to get the same levels.
Second I am considering doubling the dose but dosing every 2 weeks and taking shorter breaks. I think it is entirely reasonable based on what Matt Kaeberlein is seeing in the dog aging study to NOT take rapa constitutively but perhaps on a 8 weeks on 4 weeks off cycle to really make sure there is no TORC-2 inhibition. . In addition I am intrigued by the idea that higher doses might better penetrate the blood brain barrier. . I know Alan Green is dosing every 2 weeks but I haven’t seen any science to back it up. Not to say he is wrong but, as with so many things in this space, we are all just guessing much of the time and in my read, Dr Green’s practice is not always based on strong evidence.
Let me know your thoughts and thanks!


Hi and welcome to the site. We have a thread on getting blood sirolimus / rapamycin levels tested here: How to get a Rapamycin (sirolimus) Blood Level Test

There are a few different reasons to do this blood test… to test peak levels, to test trough levels, and to verify that your medication is not counterfeit (has sirolimus in it).

People here do peak levels also to see how things like grapefruit juice impact their AUC for the drug. But as you probably know - we really don’t know what the “right” or optimal peak level, or AUC is for rapamycin in longevity applications. We have a general heuristic that higher doses of rapamycin have, in mouse studies, generally led to longer lifespan improvements. But - as you get to higher and more frequent dosing you increase likelihood of mTORC2 inhibition and immune supression and thus the need for a balancing act.

While there seems to be some individual variability, generally peak levels seem to be achieved in the 1 to 3 hour window, and trough levels are tested on the last day before your next dose. Generally people are targeting a trough level of 1ng/ML to minimize mTORC2 inhibition risk, but other people are taking more risk… the choice is yours.

We have a long thread on the issue of Blood Brain Barrier penetration here: Rapamycin and the Issue of Getting Through the Blood Brain Barrier

I spoke recently with Adam Salmon who is running the marmoset rapamycin studies and he said they see reasonable BBB penetration by rapamycin into the marmoset brains. I’ll post the audio for that interview as soon as I can and I encourage you to listen to it.

Let us know what you decide on doing and your rationale!


Thank you for the links, they seem to be spot on.
I think testing of levels will be critical to get a sense for dosing, even if we don’t know the sweet spot for TORC1 but not TORC2 inhibition.

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The least expensive testing by LabCorp is through Marek Diagnostics $59.00

There is a discount code posted at the bottom of this posting.

I have no financial interest in Marek Diagnostics.

They are NOT allowed to sell direct testing in NY, NJ or RI


Discount code posted on 03/5/2023
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10% off any test


Thank you for the tip!

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I forgot to respond to this statement. I recommend you read this thread on the grapefruit juice / bioavailability action: Improve Bioavailability of Rapamycin (2)

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forget about doing grapefruit juice. do ketoconazole instead.

[quote=“dan_hayes, post:7, topic:6325”]
“Why is ketoconazole no longer used?
Ketoconazole may cause liver damage, sometimes serious enough to require liver transplantation or to cause death. Liver damage may occur in people who do not already have liver disease or any other conditions that increase the risk that they will develop liver damage.Sep 15, 2017”
Ketoconazole: MedlinePlus Drug Information.


Can you elaborate on what Matt Kaeberlein is seeing?

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So I haven’t recently followed up on the progress of the Dog Aging Study. I don’t think the final results have been published but the initial report to establish rapamycin dosing as safe was this:
GeroScience. 2017 Apr; 39(2): 117–127.
Published online 2017 Apr 3. doi: 10.1007/s11357-017-9972-z
PMCID: PMC5411365
PMID: 28374166
A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs
In this t study they administered the rapa to dogs for 10 weeks and observed persistent positive changes for up to a year in follow up (by his verbal report)
I have also heard matt himself is cycling the drug in an 8 week on and (i believe) 8 week off cycle similar to what Peter Attia has said he is doing (8weeks on/5 weeks off). In addition if you look at the work done by Joan Mannick of Novartis in 2014 with older individuals given a single 10 week course of Everolimus (a rapalog) the effects were measurable (in terms protection from respiratory infection) for up to a year suggesting that pulsing the dosing may be very effective and allow for a washout to ensure that TORC-2 activity is not suppressed.
Again much of this is unpublished but available in various forums where Matt has spoken.


I think the potential for hepatic toxicity would sway me away from ketoconazole.
If you can measure the effect grapefruit juice has on your own plasma levels and use this to determine a correct dose for yourself this might be useful.
I would consider doing a 2 hour post dose sirolimus level with and without GFJ and compare the peaks to determine the effect. Still coming up with the best time course but I will let you know what I find when I try.


Yes, you are correct.


Personally, I opted to buy the budget option from Kachhela (Siroboon) instead of using grapefruit juice to spike levels of Rapamune. A lot more pills for the same amount of money. I’m just not confortable using grapefruit juice in this manner. Perhaps if I went through the trouble of doing a blood test at least three times after using grapefruit juice I’d feel more confident in what level I’d be achieving every week. But I’m concerned that the levels of enzyme suppression could be variable. So I take pills with a similar meal each week.

Also, I take dozens of supplements, and there are many unknowns as to whether some of them may be affected by grapefruit consumption.

Of more concern to me though is frequency of dosing. It seems to be as much guesswork as it is scientific. Currently I have chosen to dose every eight days, reasoning that I wanted to make sure a full three half lives pass. One rapamycin researcher opined that five half lives should pass. My thinking was that if rapamycin levels are nearly abolished (five half lives), then recurrent or new side effects might be more likely.


I do think the timing issue is significant. Toxicity of rapamycin appears to be correlated most with trough levels. So directionally we might want to essentially reach a drug free state prior to redosing. That coupled with drug holidays are likely the key. That said although I am currently dosing 8mg 1x/wk for 8 weeks and then 8 weeks off, I am very seriously thinking about 16mg every 2 weeks for 8 weeks with 5-8 weeks off.
Again so much of this is guesswork and self experimentation. We are in need of a good marker for autophagy/ and a good RCT comparing the dosing regimens.


There is good information about rapamycin and the blood brain barrier in this video - I highly recommend people watch it:

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Welcome @Grabovac . . . If that’s a recent pic of you and your wife, you two look great for your ages! Keep us posted on your progress

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fyi, i checked my levels at 1h and 48h. it was still detectable at 48h but would’ve been gone by the next dose.

other random notes. about 50% people don’t experience negative or positive effects when on rapamycin (our studies and survey on this blog). Attia is one of them, so his cycling schedule is completely empirical.

Matt K had a strong positive response and he is cycling but not as regimented as 6 on 6 off etc.

Blagosklonnyi introduced the idea of doubling up on the dose every other week for BB permeability. He’s no longer doing that

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Thanks for posting. Are you concerned about your A1c rise of 0.2, despite Metformin and Acarbose, during your Rapamycin usage?

I just had labs and after only 8 months on Rapamycin (5mg weekly, 64Kg, age 62F, with an 8 wk break once every 4 mos), my A1c has risen from 5.6 to 5.8, despite eating low-carb to keto for years. Fasting Insulin wasn’t high at 6.5. I’m considering Metformin as the highs aren’t after eating.

There are others on the forum who don’t see A1c increases after Rapamycin, just wondering if you attribute it to the Rapa.

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I am not sure I would read anything into an A1c movement of 0.2 I copy below my A1c measurements. I do weekly blood tests, but not all labs do the A1c. Some do the percentage some do mmol/mol

There are issues with A1c that the labile element metabolises in a blood sample so if your lab is measuring both aldimine and ketoamine then a) you will have a higher figure, b) delays will matter (the labile element follows glucose by about 2 hours)

Finding out from labs exactly how they test A1c is sadly not as easy as it should be. For me the ones where I am in the 4.1-4.5 range I assume are excluding the labile part.

4.9 4.8 4.9 4.3 5 tested on second day 4.38 cvt 4.8 cvt 4.6 → 4.7 → 4.5 4.18 night time melatonin drives this down ->5.3 5.4 follows glucose by 2 hours 4.9 5.1 4.9 5 4.9 4.7 4.8 4.9 4.3 5
30 29 30 24 28.6 27.1 27.7 25.9 → 22 28.2 34 ->35 31 32 30 31 30 30.5 28 29 30 27.7 23.2 27.2 31 27.5 25.7

Really interesting question. Diving more deeply, I’ll say I am rather fanatical about blood glucose, I wear a CGM a couple of months a year and calibrate it daily (mostly a Dexcom G6). The Dexcom would indicate that my average blood glucose is in the 90’s while my A1c would imply numbers closer to 110 avg. that said there is a bit of a behavior modification effect when you put on a CGM so you are probably eating a bit differently when wearing it vs not.
That said A1c is not the best proxy for avg BG since it affected by RBC size and turnover. A well calibrated CGM is probably a better estimate of average BG all things equal.
In addition, I had been mostly very low carb but about a year ago my wife went vegan and since she does most of the cooking we are definitely eating more (complex and healthy) carbs than we used to. I still eat cheese, eggs meat but have added more carbs. So I attribute the rise in A1c to the increased carbs.
My fasting insulin was very low <7 mIU/ml but that was before the increased carbs and before the rapamycin. I will be doing an oral glucose tolerance test again soon with fasting insulin and glucose followed by post glucola insulin and glucose levels for a couple of hours to see how my insulin sensitivity really is.

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