Best Bets and Risk

Generally, yes - rapamycin by itself is very non-toxic to adult humans. There are no known overdoses on rapamycin, and people have tried (as much as 104 mg in a single dose I believe).

There are studies that have shown harm, but its due to the immune suppression issue, mostly in cancer studies where they are doing very high dosing of rapamycin or a rapalog (upwards of 10mg/day or as high as 45mg/day to 90mg/day…

Here is one such study, which Dudley Lamming pointed me towards. A young woman age 27 died in a clinical trail with everolimus when she was infected with sepsis:

In the short term dosing of rapamycin I think this safety profile is quite well documented, as covered in this paper that documented some people’s high dosings with no long term negative consqequences:

Please keep in mind that the longer term use of high dose rapamycin / everolimus has been identified as having some greater potential risk…

below are some examples in a high dose (e.g. 10mg/day) everolimus study for cancer patients (admitedly a serious and complex situation already, but … there was a death due to e-coli sepsis).

Rapamycin is not a risk-free drug, especially as you increase doses above the regular 5 to 8mg dosing once per week level.

The most common Adverse Effects (AEs) of everolimus therapy were laboratory abnormalities (100% of patients) and infection complications (83 episodes in 15 patients). Infectious episodes of pharyngitis (67%), diarrhea (44%), stomatitis (39%), and bronchitis (39%) were the most common infections. They were mostly mild or moderate in severity (grade 1–2).

In two cases, life-threatening conditions related to mTOR inhibitor treatment were encountered. The first was classified as grade 4 pleuropneumonia and Streptococcus pneumoniae sepsis, whereas the second was classified as death related to AE (grade 5) Escherichia coli sepsis.

A 27-year-old woman with TSC was started on everolimus
treatment because of AML of the left kidney
(60 Å~ 48 Å~ 36mm in size). The other signs of TSC were
facial angiofibroma, hypomelanotic macules of the skin,
and shagreen patch. The diagnosis of TSC was made
12 years earlier when the patient underwent nephrectomy
because of a large tumor of the right kidney. The
patient received everolimus at a dose 10 mg/day and the
trough concentrations of the drug ranged from 4.08 to
5.08 ng/ml. After 3 months of everolimus therapy, a
reduction in AML was observed (40 Å~ 31 Å~ 20mm in
size). During treatment, hypercholesterolemia (309 mg/
dl) and transient leukopenia (3.2 Å~ 109/l) with neutropenia
(1.34 Å~ 109/l) was observed. She also reported
oligomenorrhea. After a gynecological consultation, a
functional ovarian cyst was identified and contraceptives
were prescribed. However, 2 weeks later, she was
admitted to the gynecological unit because of subabdominal
pain and an ovarian cyst (64 Å~ 53mm in seize)
on ultrasound examination. Torsion of the ovarian cyst
was suspected. On the day of admission, WBC was
9.2 Å~ 109/l, the absolute neutrophil count (ANC) was
6.6 Å~ 109/l, the hemoglobin level was 10.8 mg/dl, the
PLT count was − 275 Å~ 109/l, and the C-reactive protein
concentration was 8.0 mg/dl (normal < 5.0 mg/dl). The
patient was advised to continue intake of contraceptives
and everolimus. The next day, the general condition of
the patient aggravated. Her blood pressure was low (85-
/50mmHg). Her WBC and ANC decreased (WBC
−2.4 Å~ 109/l, ANC − 1.8 Å~ 109/l), whereas the hemoglobin
level (11.0 g/dl), the PLT count (185 Å~ 109/l), and coagulation
tests were normal. Computed tomography of the
abdomen and pelvis showed AML of the left kidney (size
as in the previous examination), an ovarian cyst measuring
65 Å~ 50 Å~ 40 mm, and fluid in the retroperitoneal
space with density of the blood. Further aggravation of
her general condition was observed. The patient was
transferred to the ICU and she died after 2 h with
symptoms of shock and multiorgan failure. Blood and
urine cultures collected when she was in the ICU were
positive for Escherichia coli.

Complications of mammalian target of rapamycin inhibitor anticancer treatment among patients with tuberous sclerosis complex are common and occasionally life-threatening


Thank you! According to this table the smallest dose for 60 kg Human, when converted from mice, was 10.92 mg per day?

Yes - that is data from the ITP studies, but I don’t know how to factor in the shorter mouse half-life. A simplistic means of doing this would seem to be to divide by 4, but you have more expertise in this as you have medical training. What is your take on the 1/2 life variance?

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I have never encountered this parameter in my medical practice and don’t remember seeing references in the medical literature. There are formulas on line on variance calculator. The formulas look complex to me.
It looks like the smallest dose used in ITP studies was still too high for an average human.
P.S.Thank you for all the amazing work you have been doing!

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Perhaps you can ask some of your contacts at the Buck Institute when you have time?

It certainly seems like Rapa is generally safe. Not harmless though. If you search enough you can find significant adverse reactions. Most are reversible by stopping the Rapa. I found a couple cases with doses as low as 2 mg a day for 10 days.


Now that I understand the science of rapamycin, I am a firm believer, that there’s a much greater risk, and not taking rapamycin than there is in taking it. The first person I heard articulately express this was Mikhail Blagosklonny. I think easily available over the counter medication such as acetaminophen and ibuprofen, are far more dangerous than rapamycin when it is taken appropriately. So, from my perspective very little risk when taking rapamycin. Ross.

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Putting aside Rapamycin risks, what about the benefits in humans? Besides Joann Mannick’s study showing that mTOR inhibitors improve immune function in elderly is there anything else for healthy people? The evolution of of-label use in 333 adults study is interesting but in my mind doesn’t prove benefits yet. The benefits as a part of cancer treatment, organ rejection, stent coating are clear though.

Perhaps the best data we have on benefits for humans is here: Anti-aging Benefits of Rapamycin, Personal Experiences (part 2)

There have been very few large studies of rapamycin / rapalogs in healthy humans - really just the ResTORbio / Mannick studies (and likely won’t be any new ones, because rapamycin is off patent and thus no financial incentive to do so).

So, sadly we are not likely to ever get the really good clinical trial data that we want on rapamycin. There are some smaller clinical studies that are likely to be completed in the next few years, but for most clinicians the data won’t be enough to convince them that rapamycin is something they want to prescribe.

There is also the Dog Aging Study (TRIAD) with a few hundred dogs on rapamycin, that will be completed around 2026, and the Marmoset longevity study with something like 24 marmosets on Rapamycin that is ongoing (until they all die). The dog study may show some good results, but the marmoset one is obviously underpowered.

More information on the studies:

Here: New / Active Rapamycin Human Clinical Trials (related to Aging)

and: Update 13 key Rapamycin Studies and Clinical trials

and: Metabolic consequences of long-term rapamycin exposure on common marmoset monkeys (Callithrix jacchus) - PMC

More broadly, your comments related to the issue of why do we want to try longevity drugs based on just mouse data. This discsussion may be of interest: Most mouse research doesn't translate to humans - why do we think rapamycin is different?

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"Dogs can get cancer, and about 25% of dogs will develop some form of cancer in their lifetime. About 50% of dogs over the age of 10 will develop cancer. Cancer is the leading cause of death in pets beyond middle age. "
You would think even at this relatively early stage of the studies, a reduced cancer rate would start to show up.
Are any of these studies publishing ongoing results?