The Key issue of Dosing Levels and Intervals for Best Rapamycin Outcomes

There is a lot of uncertainty right now with regard to the optimal dosing levels and schedules for rapamycin in humans (for anti-aging). Doctors and other people have generally standardized on the range of 3mg to 10mg a week in a single weekly dose, but there is little confidence that that is an optimal level and dosing protocol. The current standard dosing for rapamycin does seem to be a highly tolerable level in terms of side effects which is a great start. But - longer term it would be very valuable to better identify the benefits (and potential risks) more precisely of other dosing regimens.

Obviously, we really need to find out the optimal dosing levels and protocols for the best anti-aging effects. We get a hint on this issue from animal studies - so I think it would be good a good start for us to crowdsource all the animal data we can find in the research literature and try to convert it to dose equivalency in humans (to the degree possible).

And then over time we should also track the dosing levels being tested in different people (and outcomes) so we can all learn from past research and also from each other.

When we get all this information compiled we can dig in deeper on questions related to dose equivalency with the researchers to get a better understanding of how the doses map to each other (obviously very roughly) between species.

In this paper it was noted:

In most studies, mice were treated with 1.5–2 mg/kg rapamycin. Importantly, the clearance of rapamycin is much faster in mice than in humans. For example, in mice levels of rapamycin drop 20-folds the next day after injection,14 whereas in humans its terminal half-life is about 2.5 d.38,39 It was estimated that a 1.5 mg/kg injection in mice corresponds to the therapeutic oral dose in humans.

With regard to the half-life of rapamycin in mice - here is what the study mentioned above states:

Although these results showed that Ndufs4−/− mice benefit from rapamycin treatment, we noted that by 24 hours after injection, rapamycin levels in blood were reduced by more than 95% (fig. S3). We therefore performed a follow-up study delivering rapamycin (8 mg/kg) daily by intra-peritoneal injection starting at P10, which resulted in blood levels ranging from >1800 ng/ml immediately after injection to 45 ng/ml trough levels (fig. S3). For comparison, an encapsulated rapamycin diet that extends life span in wild-type mice by about 15% achieves steady-state blood levels of about 60 to 70 ng/ml, and trough levels between 3 and 30 ng/ml are recommended for [human organ transplant] patients receiving rapamycin.

Dudley Lamming’s lab reported this half-life for rapamycin in mice:

We calculate that the half-life of rapamycin in mouse blood is approximately 15 h , with blood levels of rapamycin reaching 4.9 nM 3 days after injection, a concentration capable of inhibiting mTOR signaling in tissue culture cell lines (Sarbassov et al., 2006)

And this paper provides a way to translate ppm (the dosing calculation provided in all the ITP studies on rapamycin in lifespan extension) to mg/kg:

Rapamycin is at 14 mg per kg (ppm) food, which is approximately equivalent to 2.24 mg/kg/mouse/day based on the assumption that an average mouse weighs 30 g and consumes 5 g of food per day.

Below is a summary of the dog and marmoset (monkey) studies with rapamycin, and the doses they’ve used. In the healthy dogs and marmosets, we see pretty high doses, with few side effects which suggests that healthy humans are likely to have similar outcomes. Also included below are the dosing used in transplant applications, just as a point of comparison:

Dose Equivalency Daily Dose (mg/kg) Dosing Sched. Total Dose mg/kg/wk Wkly Mg. Dose for 170lb/77kg
Dog Aging Project
Dogs - Low 0.05 M/W/F 0.15 11.55
Dogs - High 0.1 M/W/F 0.3 23.1
Pauloni study:
Low 0.08 Daily 0.56 43.12
Yi Study:
Med, .5mg/kg 0.5 Daily 3.5 269.5
Hi, 3 month, 1 Daily 7 539
Dose Equivalency Daily Dose (mg/kg) Dosing Sched. Total Dose/wk Wkly Mg Dose for 170lb/77kg
Marmosets 1 Daily (week days) 5 385
People: Dose (Mg/kg) Daily Dose (mg/kg) for 77kg person Dosing Sched. Total Dose mg/wk for 77kg person
Transplant w/Cyclosporin
Transplant - 2mg/day 0.03 2 Daily 14
Transplant - 5mg/day 0.07 5 Daily 35
Trans w/o Cyclosporin
Transplant (low) - 8mg/day 0.11 8 Daily 56
Transplant (Hi) - 20mg/day 0.29 20 Daily 140
Max - 40mg / day 0.57 40 Daily 280

Following is a link to a google spreadsheet I’ve created where people can add information.

Please join in and contribute on this small project:

Also - please post in a reply to this message your rapamycin dose right now and what it works out to mg/kg or mg/lb


This seems to be the dosing from the initial Dog Rapamycin trail done as part of the Dog Aging Project TRIAD program with rapamycin. I’ve calculated the dose equivalency in mg/week for a 170lb/70kg person for reference.

Dose Equivalency Dose (mg/kg) Dosing Sched. Total mg/kg Dose/wk Wkly Mg. Dose for 170lb/77kg
Dogs - Low 0.05 M/W/F 0.15 11.55
Dogs - High 0.1 M/W/F 0.3 23.1
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only 2 months of rap so far, ramping up. now: 2mg/week, taken with 6 oz grapefruit juice and fatty meal. Equivalent to (2mg/week)/70kg * (week/7 days) = 0.004mg/kg/day

Have you had any side effects yet?
Also - I’m confused by your dosing. You say 2mg/week - do you mean you are taking two mg of rapamycin / sirolimus. If you are also taking GFJ then your dose equivalence is really probably up around the 6mg/week level I think.

I’m trying out the “one dose every two week” scheduled right now - took 18mg on Tuesday. No noticeable side effects. I’m 75 kgs, so .24mg/kg daily dose equivalent.

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yes, 2 x 1mg pills of rapamycin. Yes, the equivalence might well be in the 6mg/week range. Possible side effects (though not definitely rapamycin-caused): 2 or 3 tiny red sores on the tip of my tongue, a small sore on the inner cheek caused by my biting myself but is surprisingly long-lasting, and a bruise under the base of one fingernail with accompanying damage to the base of the nail (I was not aware it had been injured). I think I’ll wait a few days extra for my next dose.

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I think using Grapefruit with a single dose does not increase the peak serum concentration. It just increases the halflife/clearance.


I guess that could be true - I haven’t studied the paper in depth. I think the key measure may be the AUC (Area under the curve) - i.e. how much exposure you get to the drug via the blood stream.

Whatever the case - the important point is that that you can get by with a lower dose of rapamycin and effectively get a higher dose - thus saving money and potentially decreasing side effects.

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Certainly more exposure. In this paper the patients are taking everyday, thus it’s building up with a lower clearance rate. I use grapefruit with my Sirolimus too. 15mg q 10 days.


Although popular science reporting like this might sometimes be inaccurate, this article clearly says the grapefruit increases absorption (thus peak levels?) and does not mention half-life. Another article quoted one of the scientists as saying the grapefruit effects were high within a few hours of consuming the juice, so I don’t think continually daily consumption is needed.

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I’ve been taking 30mg of CBD for the past year and started rapamycin last month increasing now to 6 mg/week. Some research has been published showing that CBD increases the blood level of rapa similar to grapefruit–to the extent of 200% or more. But they don’t talk of how much CBD does this. Does anyone have any input on how much CBD is needed to have this effect? I’m a patient of Dr Green & he thinks 30mg of CBD is not a problem but he didn’t have any direct knowledge of the issue. Any feedback would be appreciated as I’d like to keep taking CBD but don’t want to overdose on rapa. Thanks

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Hi Jim,
Welcome to the site, and thanks for posting on this. I had not heard of this - but a quick check on Pubmed shows you are absolutely right. I will dig deeper into this to see if I can find more and answer your questions - but you should definitely be careful:


Thanks! I’ve stopped taking CBD starting last week until I get more info. The best news would be that 30mg of CBD is reliably synergistic w/ rapa & consistently increases its biological effect by some known percentage. I could then continue w CBD & cut my rapa dose. But so many unknowns. Don’t want to overdose or underdose!


After reading the Dog aging project update recently, I took 13 mg Pfizer Rapamune (0,15 mg/ kg) at the start of a 3 day fast in the morning on an empty stomach with water and experienced no sides. In the past I also took 6 mg with 2 glasses grapefruit juice also without sides. I am 44 years old and exercise daily.


Looking to hear more. My issue with grapefruit juice is that it comes with a bunch of sugar

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Yes - I agree on the sugar issue. There is also the issue of the large amount of variability (in terms of its effectiveness in increasing the bioavailability) in the grape fruit juice that you buy.

When I have done the grapefruit with rapamycin dosing I eat the actual fruit an hour before I take the rapamycin. That seems like it might be better, and I’m guaranteed to get “fresh grapefruit juice” - and all the fiber from the fruit.

I have also done more research on the drug called “ketoconazole” that is mentioned in the same research study that used the grapefruit juice. This drug also is very good at increasing the bioavailability of the rapamycin - by a pretty consistent 5.6 X it says in the study. In the study they were giving it to cancer patients who were taking 90mg of rapamycin / Sirolimus a day - a huge amount, but with the ketoconazole they only needed to use 16mg / day to achieve the same blood Sirolimus levels.

ketoconazole is a cheap, and easily available generic medication - so if that is something that is of interest to you, talk to your doctor about it. The key issue the mention in the study that they were concerned about with regard to the ketoconazole, was toxicity or overdosing because they were using it every day. This wouldn’t be an issue in the sirolimus / anti-aging protocol I suspect because it would only be used once every week or two.

More information here:


Hi, my name is Ross Pelton and I am The Natural Pharmacist. I have written a book titled Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome which is in the final stages of editing and will soon be published.

Regarding “optimal” dose of rapamycin. I think this needs to be individualized. Everyone is different…ie. biochemical individuality.

I was taking 6 mg once weekly. My lab tests revealed that I had become anemic…so I have reduced my dose to 6 mg every other week. I just had a blood draw today. I will post the outcome when I get the results.


Welcome to the forum Dr. Ross. Please post a link to the book once its available. More information is great.

What is your opinion about doing peak and trough sirolimus blood level tracking or testing? Since there is quite a variation in half-lifes (between people) and dependent on diet, etc. - and the risk of mTORC2 inhibition over time.

Life Extension now offers a cheap $95 blood sirolimus test that we could use for this purpose.

I think testing peak and trough sirolimus would provide very important information for the LIfe Extension community. We are truly in the very beginning of this new frontier. I think ultimately, we will find that there is great biochemical individuality in what is the optimal dose and frequency for different individuals. I just made a comment earlier about reducing my dose from 6 mg weekly to 6 mg every other week…based on labs that revealed I had become anemic (low iron & hemoglobin). Lots to learn…Ross


Did switching to a 2 week interval reverse the anemia? Is your book out yet?

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What optimal iron/ferritin levels and hemoglobin levels do you aim for?