How Safe is Rapamycin (part 2)

Why do we bring the safety of rapamycin up? Because most medical professionals, if they have any experience with rapamycin at all, have that experience in the context of organ transplantation or cancer patients. These are very sick patients who use high daily doses of rapamycin along with many other drugs. In these scenarios the the side effects can be quite bad. In anti-aging applications people are using rapamycin with a pulsed dosing protocol (taking their rapamycin dose only once a week, or even once every two weeks) - which is very different from transplant or cancer applications.

A few points to note about rapamycin / sirolimus safety:

  1. Rapamycin is an FDA-approved drug that has been used for about 20 years in people, or hundreds of thousands, perhaps millions (my estimate) of people used daily for many years. In short, this is an old drug that has been used for a long time in people with generally positive effects.
  2. Rapamycin has almost seven years of clinical use in healthy humans by thousands of people without any serious reported adverse effects: From Dr. Alan Green interview, 2017:

"Back in December 2015, when I contemplated being the first person to use weekly rapamycin using the Koschei formula, as outlined by Blagosklonny in his 2014 paper, I too had some reservations…

However, after taking rapamycin for close to 4 years and treating over 360 patients over the past 2 years, I have the experience and knowledge to say that weekly rapamycin is a safe drug.

[Note: Dr. Alan Green, as of Oct. 2021, has over 760 patients on rapamycin for anti-aging.]
source: Dr. Green’s website]

  1. Rapamycin been used at extremely high dose (single dose) by a few people written about in case studies (see below) where the person tried to commit suicide by overdose using 103mg of rapamycin / sirolimus. The effects were minimal and not long lasting. So - the risk in the short term dosing seems to be extremely low.

There is no known LD/50 for rapamycin / sirolimus in humans (though some research suggests that consumption of over 800g/kg in rats may be an LD50, over 2500mg/kg in mice. So its a very non-toxic drug.

But, its also good to know that some people have pushed the limits (in a single dose) and that they’ve been ok. Here are the documented situations people have taken very high dosages of rapamycin / sirolimus.

Five cases of acute sirolimus overdose were reported – three in young children and two in adults. Four were accidental and one was with suicidal intent. Two patients developed symptoms probably related to sirolimus overdose: mild elevation of alkaline phosphatase, fever and gastroenteritis in a 2.5-year-old male who ingested 3 mg, and mild changes in total cholesterol in an 18-year-old female after ingestion of 103 mg. None of these events were life-threatening. Serial blood concentration measurements were performed starting 24 h after ingestion of 103 mg in a single case, and these followed a similar pharmacokinetic time-course to measurements taken after dosing in the therapeutic range.


Acute sirolimus overdose occurred accidentally in the majority of cases. Even large overdoses appeared to be well-tolerated, however children might be at greater risk of developing complications. Further study of sirolimus overdose is needed.

Other related readings:

The point, as Matt Kaeberlein, A professor at University of Washington focused on testing anti-aging drugs, is:

A Full Analysis of this Twitter Thread Here:

Additional Reading on this issue:

Defending and Explaining Rapamycin (Matt Kaeberlein on Twitter)

I hope I am not being redundant. I think this paper by Blagosklonny must have been cited on this site before. I imagine most of us have read it. Rapamycin for longevity: opinion article - PMC
Blagosklonny talks about the safety and risks of taking and NOT taking rapamycin. I am in agreement with everything he says in the paper. I particularly like this quote from the paper "Considered in those terms, one could say that in the elderly, not taking rapamycin may be even more “dangerous” than smoking.