What most of us are doing here is starting low, slowly increasing, and doing regular blood testing to see how things are going (and hopefully working with your doctor to try to optimize things).
Could you please point to a post or thread that explains what blood testing will tell you? Do we in fact know what level of rapa in the blood is optimal? And how do we know that?
Not rapa, but my favorite goto on health in general:
Aerobic exercise provides at least a partial solution to sarcopenia as it ameliorates mitochondria-derived problems, and resistance exercise strengthens muscle mass and function.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165967/
Here is a good thread about rapamycin blood testing: How to get a Rapamycin (sirolimus) Blood Level Test
We do not know what the optimal dosing for rapamycin is for longevity. Its hard to do longevity studies of drugs because humans live so long, and the FDA doesn’t recognize aging as a disease so no drugs are going to be approved for “aging” anytime soon.
Additionally, rapamycin is a generic drug now (cheap) so nobody is going to invest the money for longer term clinical trials.
Generally, what we’ve seen in the mammal studies so far is the higher the dose, the longer the animal lives. See: List of all the Mouse Studies Showing Rapamycin Lifespan Extension
But mice live in pathogen-free cages, so what works for mice may not work for humans.
So - we are all working to figure this out ourselves.
Hi, Elizabeth, I couldn’t agree more.
Here’s an article from 2016 that looks at rapa among other interventions including exercise countering cachexia from colon cancer in mice. Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer | Scientific Reports
Cachexia, sarcopenia, and other muscle loss have in common the (upregulation?) of a couple ligases that are directly involved in protein degradation in skeletal muscle. Rapamycin significantly reduces the expression of these two. As did another intervention also tested that also targets AMPK. The article did spend a lot of time on voluntary exercise too.
Nevertheless, what 75-and-older humans may want to consume is what I’m going to keep thinking about. Similarly those coming back from significant health challenges. I think this will lead me into more cancer literature.
As far as I remember, female mice could overdose rapamycin, so there was a sweet spot for dosing.
Yes - In one study ( of the 45+ studies of rapamycin in mice) they did finally find an upper dose of rapamycin that no longer increased lifespan in those female mice. It was an extremely high dose though.
I should note that in mice there is a significant dose / response difference between male mice and female mice. This difference is not seen in humans.
Most of people currently using rapamycin seem to be (in mouse equivalent dosing) in the low levels tested (note: mice were dosed rapamycin in their food, daily, so that is another difference - vs. us using rapamycin dosed once weekly or so).
Here are the National Institutes on Aging Results from their rapamycin studies (these are the best rapamycin studies):
| Sirolimus Dose |
mg/kg/day Dose |
Blood/Sirolimus Level |
Male Median LS Increase | Female Median LS Increase |
|---|---|---|---|---|
| 4.7ppm | ∼2.24 | 3 to 4 ng/mL | 3% | 16% |
| 14ppm | ~6.67 | 9-16 ng/mL | 13% | 21% |
| 42ppm | ~20 | 23-80 ng/mL | 23% | 26% |
Here are results from all the higher dose studies I could find:
| Sirolimus Dose |
Mouse mg/kg/day Dose |
Mouse: Blood/Sirolimus Level |
Human mg/kg/day Dose |
Dose for 60kg Human | Daily Dose adjusted for longer half-life (/4) |
|---|---|---|---|---|---|
| 4.7ppm | ∼2.24 | 3 to 4 ng/mL | 0.182 mg/kg | 10.92 mg | 2.73 mg |
| 14ppm | ~6.67 | 9-16 ng/mL | 0.542 mg/kg | 32.54 mg | 8.135 mg |
| 42ppm | ~20 | 23-80 ng/mL | 1.626 mg/kg | 97.56 mg | 24.39 mg |
| 126ppm | ~60 | 4.878 mg/kg | 292.68 mg | 73.17 mg | |
| 378ppm | ~180 | 45 to 1800 ng/mL | 14.634 mg/kg | 878.04 mg | 218 mg |
Based on the FDA animal to human dosing conversion guide here.
Note: ½ life for sirolimus in mice is approx. 15 hours, vs. approx. 62 hours in humans. So, mice metabolize sirolimus approximately 4 times faster than humans.
What is the mouse equivalent of a human week? One day?
Based on the above half-life information, about 2 days mouse = 1 week human. So the mice were dosing 4x a week in human translation based on the half-life of Rapamycin. So for maximal longevity, should we even consider dosing every other day? The mice must have had their MTOR pathways completely shutdown.
That what I was thinking!
Based on my body weight (245 lb), at the lowest of the high dose ranges (4.7ppm ∼2.24 3 to 4 ng/mL 0.182 mg/kg 10.92 mg 2.73 mg), I should take 20 mg of sirolimus per week, divided by 4, so 5mg every other day. When you add grapefruit juice with each dose, I am guessing 2mg (roughly 3-6X) every other day? Very rough approximation and probably very incorrect
My target is 6 mg + GFJ each week to get 20 mg weekly equivalency. I also add EVOO and metformin which increase absorption beyond 3.5X.
Me too, same dose. I am not ready to go to every-other-day dosing unless I find some strong evidence.
Great minds think alike. 
More like look for the black cat in the dark room.
I have just upped my dosage to my target of 6 mg + GFJ + EVOO biweekly. I have been hit with euphoric fatigue after a few hours of dosing and it has continued for over 24 hours. It really helps with a good nights sleep. The best way to describe the feeling is that feeling you get after sex, when you just want to sleep yet feel so satisfied. Personally, its a good side effect and I hope it continues although I have less energy. Not sure whether I should hold at this level or reduce. This should be an equivalent of about 20 mg, IMHO.
I get this as well, with doses 6mg + , just feel tired but its a good tired and I do sleep well. Usually last 48 hours after dose, first 24 hours I have the most fatigue.
I think Dr. Green is back to lower doses on a weekly basis. One point to remember is that the bioavailability of rapamycin seems to be higher for females than males. This may also explain why it works better for females than males in some of the mouse studies.
I think Dr. Green is back to lower doses on a weekly basis.
Lower as in…?
So, as a female, age 62, are you taking ~16-18 mg weekly or biweekly? If you are, have you had side effects?
I’m an almost 59 y.o. female. I was going to work up to 5 or 6 mg weekly (side effects permitting). But without any clear mg per kg of body weight guidance it all seems like a shot in the dark. All of the comments so far have focused solely on the question of something like how much mTor suppression one requires. But no one seems to have any interest or insight into the metabolic question of absorption, immune-suppression and the wash-out process depending on body mass/fat composition and so forth.
So I just received the Rapa, and am diving back into the protocols. Thank you for sharing your experiences, it is very helpful to know when you upped your dosage and added GFJ. You may have seen this research regarding folks 65 starting on 5mg weekly with what looked to be de minimis side effects. (https://health.uconn.edu/aging/wp-content/uploads/sites/6/2016/04/mTOR-inhibition-improves-immune-function-in-the-elderly.pdf) The study lasted 6 weeks, there were 40+ subjects in the 5mg camp and 2 got a mouth ulcer.
I also found this i/v of Matt Kaeberlein extremely helpful as it just cut to the chase, Rapamycin and aging: Dosage, side effects, and success stories | Matt Kaeberlein - YouTube and particularly his comment that…“I’m just gonna say it, the side effects of rapa are less than exercise.” The other take-aways were: 1) Dosage 3mg-6mg reasonable (based on the Joan Mannick study of elderly participants taking 5mg weekly for 6m w/ few side effects (https://health.uconn.edu/aging/wp-content/uploads/sites/6/2016/04/mTOR-inhibition-improves-immune-function-in-the-elderly.pdf), this is probably more relevant to older folks as it appears there is a greater tolerance for rapa with age; 2) Most people don’t cycle. 3) Anecdotal evidence re: age-related physical complaints, including his frozen shoulder for which he took rapa weekly with plan to cycle at 10-12 weeks, but shoulder had cleared up with no side effects from rapa.
So based on the above, I am considering starting at 2mg/weekly and going from there. Re: my 18# 13Y old Chiwennie, who will be my co-pilot, I have calculated at .5mg weekly to start. I would be most grateful if anyone had any further insight regarding his dosage to share.