FWIW
I have stated this several time, the reality and fact is we{all of us using rapamycin for longevity] are all PFA* dosing. As of 2024 this is no “Clinical Trial” of rapymican effects on human aging/loginivity.
We all do this on a “leap of faith”{Peter Attia quote on one of his podcast his personal view on taking rapamycin for longevity]
*PFA is Plucked From Air.
There are so many variables to consider, but I don’t think weight is as important as age.
I think younger people need less of a dose than old people like me.
I think Dr.Blagosklonnyy’s theory that the highest dose that doesn’t produce unwanted side effects only applies to old people. After many months of experimenting with different doses, I have found that dose for me.
I agree with everything Dr. Fraser is saying here. In fact I think many of the protocols we’ve seen develop around rapamycin are mostly based on safety and risk mitigation with the hope of some of the benefits seen in animal lifespan / healthspan improvements in the longer term.
Thus - the typical dosing of around 5mg or 6mg once per week because it seems relatively safe from the only true clinical trial of rapamycin in healthy older adults (the 2014 Mannick Study). Side effects were mostly very minor, some benefit seen in a short term immune modulation endpoint.
This is sort of the baseline given the data we have. If I am tracking blood results regularly (every 1 to 3 months) and I don’t seen any negative changes, and you feel well, I suspect that I don’t need a “rapamycin vacation”. Most people on the site do not seem to do these Rapamycin vacations and I’m not aware of a any doctors prescribing them, but some people do them out of an abundance of caution.
If people have a year or more of time at 5mg/week or 6mg/week then we see people testing out higher doses to see how their body responds. As you can see in the forums, some people do fine with higher doses, some don’t.
Rapamycin is a more complex medication than something like acarbose who’s side effect really is just increase flatulence.
This is why I suggest to everyone who comes here with an interest in rapamycin spend at least a few months reading the Rapamycin FAQ, and following discussions, and getting as healthy as possible in terms of weight, lipids and blood glucose/insulin levels, C-reactive protein, and other standard blood measures of health (getting a good sense of baseline blood levels pre-treatment) before they move forward with taking rapamycin.
Rapamycin is not a silver bullet, but just one more arrow in the quiver (though it is probably the most powerful arrow we have at the moment).
Aim for 5mg once per week for 6-12 weeks on and 3 months off time!
This will minimise any potential side effects and maximise rapamycin effects!
Hi rapadmin,
have you changed you thoughts on vacations? as i was reading elswhere I came across a Oct 2021 post where you said it’s “probably wise to take periodic vacations.”
Not trying to stir the pot but just want to know if you have changed your mind since then due to more info. avail.
I don’t actively plan “rapamycin vacations” but I don’t take extreme measures to make sure I take each weekly dose all year, so “rapamycin vacations” happen for me as a side effect of a busy life. Sometimes I’m traveling and forget to bring my rapamycin, etc. - so I take a few weeks break.
In other words I don’t do any scheduled rapamycin breaks but breaks naturally happened a few times a year just as a result of me being busy with other priorities . As long as my blood work is fine, and I have no bothersome or noticeable side effects, I try to keep my schedule.
But I can see why people might want to take occasional breaks to minimize risk of mTORC2 inhibition, depending on your dose level and frequency. The higher the dose, the shorter the frequency, the greater the risk of mTORC2 inhibition.
I’ve probably softened my stance on rapamycin vacations since I started this site in October 2021. At that time Peter Attia and others were still talking a lot about breaks from dosing. I think we’ve seen since then that “most” people get by ok without breaks, but you have to track your blood test results to watch for lipid and blood glucose disregulation. If you’re not doing regular blood testing then “rapamycin vacations” may be a good idea just to minimize those risks.
Thx for the reply.
I really haven’t come across any info on male v.s. female dosing. I thought I read awhile ago that males were (on avg) doing 6mg/week and females 4mg/week? But I can’t find that post again. I think it was from one of the dr’s…?
My wife is thinking of dosing too although more for the dementia side than longevity as she’s in her early 80’s and we don’t “think” it would do a whole lot for longevity at her age; although we could be wrong. 
she has early stages of dementia (vascular). I’m quite a good bit younger than her so I’m doing it for the hopeful longevity results.
Yes - that sounds about right.
And I should correct myself regarding the weight / dosing issue. I just remembered that one of our community members mentioned that his provider (I think it was Healthspan ) gave him (or allowed him, upon asking) higher dosing levels per week because he was over 200lbs. So it seems that some providers are doing some basic levels of weight-adjusted dosing schedules. And I suppose that the male/female variation (higher dosing males, lower dosing females) is likely based on the same sort of thought process.
For older people who have chronic conditions I think that higher dosages of rapamycin would apply regardless of gender!
focus should be on the severity of the condition/symptoms and the ideal/effective doses of rapamycin which would be of benefit to the individual!
You can always taper down your dosages if experiencing any adverse side effects without having to cease treatment altogether and once a week dosing would be ideal!
Can you help us understand your perspective on this and rationale? Is this from personal experience, or have you read something that you can point to that helps us understand the rationale for that.
Things get complex quickly when you have older people with chronic conditions. I’ve tried to get my parents to take rapamycin, and they tried it for a while (a few months), but both my parents had chronic conditions and other medications they were taking, and the more complex things get the more drug monitoring you need to do, and likely more involvement and knowledgeable the doctors need to be to identify risks and confounding factors / drug drug interactions, etc. Where my parents live, they really didn’t have the level of medical support that would allow this greater monitoring.
I think the older the person is that is taking rapamycin, and especially if there are other medications or chronic conditions, the more complex it gets, and the more “hand holding” and monitoring that needs to be done.
Older people are more sensitive to things and not as resilient. The last thing you want to do is kill your parents by interjecting rapamycin into a already complex medical situation.
Yes I agree with you and in the past I have experimented with sheep placenta capsules using different brands/programs/dosages etc…which yielded very good results and especially lipids/bone profile!
The more you take the better the results would apply to chronic illnesses like Parkinson’s disease and dementia etc…
Was thinking that rapamycin is dose dependent so the more you take the better the overall results and the more severity of the conditions then higher amounts of rapamycin would apply!
Neal,
I think you’re pretty new here. So let me give you a little more information on our site.
We are a science-oriented site, with many doctors and scientists who participate. We try to have deeper discussions and be science-based so we like to see research studies and we discuss the relative merits of these studies carefully and from different perspectives. We also have a policy of not recommending a course of action to other people. Nobody here knows the other person’s situation, health, etc in any detail, so its not appropriate or reasonable for us to recommend any sort of medical course of action.
You can say what you would do in a given situation, but going beyond that could really be understood as “medical advice” and that is not something we support here.
Biology, and aging are both extremely complex topics that people spend a lifetime studying small aspects of and still are not experts. So we encourage humility when making statements and judgements, because there is always a reasonable chance you are wrong.
Let me give you an example.
You stated just now:
Was thinking that rapamycin is dose dependent so the more you take the better the overall results and the more severity of the conditions then higher amounts of rapamycin would apply!
Unfortunately that is definitely a wrong way to think about rapamycin - and its a mistake that could kill someone. Rapamycin is an immunomodulator drug; which means it can increase the strength of your immune system but it also means that it can decrease the strength of your immune system. At higher levels this drug was first approved for organ transplant (kidney, etc.) recipients, to weaken their immune system to that their body does not reject the new organ.
Rapamycin (and drugs that are almost identical to rapamycin and work the same way as rapamycin, called “rapalogs”, such as Everolimus) are also used in cancer treatments at high doses.
At high doses rapamycin and everolimus have been proven effective in some types of cancer treatments and tumors. The problem is that at these high doses you can also make the patient very susceptible to infections due to the greatly weakened immune system. With a greatly weakened immune system, your body has few defenses agains these infections.
So - with regard to rapamycin (and most drugs) “the more you take the better the overall results” is a really bad idea. Higher is not necessarily better with any drug, or chemical; most everything has a range that is helpful and a range that is unhelpful or harmful . I recommend you read this: Yes, the Dose Really Does Make the Poison (Skeptoid Blog)
This doesn’t happen very often, but it has happened: A few years ago a young woman age 27 was in a clinical trial taking higher doses of everolimus when she was infected with sepsis and died two hours later, probably because she had a weakened immune system.
Rapamycin is not a risk-free drug, especially as you increase doses above the regular 5 to 8mg dosing once per week level that is typically used in longevity applications.
In the study below I believe they were taking 10mg per day, so a very high dose compared to longevity applications.
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
Ok point taken but I have read somewhere that you can take antibiotics to counter the infections and rapamycin is even more safer than aspirin!
Maybe some of the side effects you mentioned in your article are overstated as well!
I would not say aspirin is “safe”. Aspirin has its good points and its bad points.
I’m also using test 250mg once per week so I have less immunity related problems associated with rapamycin!
I’m well protected!
Could you share a bit more about sheep placenta you use, and how to possibly select a trusted source? The link you shared in another post does not appear to be active but I got curious now
Dr. Green has suggested 2gr per week and I’ve been at it for a little over 3 months. I’ve organised the does on my running rest day and it seems ok. Gives me a day or 2 to manage some fatigue. But reading this I’m thinking I’m taking to little. Is this possible? Can’t say I’d be delighted to jump to a higher dose. Healthy, active 65yo. Views?
I believe that 6 mg would be just fine. Give it a try, and if it doesn’t work for you, go back to what does.
If you said 40 mg, I wouldn’t recommend that. 
According to the following article, life limitation is NOT aging but aging related diseases.
Currently, doses and schedules of rapamycin for longevity are based on the wrong objective: to avoid side effects. Nothing else. The doses of all other drugs are chosen to achieve therapeutic goals.
Side effects of rapamycin are not remarkable at all. They even less dangerous than the side effects of most other drugs.
what’s most significant is that many so-called “side” effects of rapamycin can actually be considered therapeutic effects themselves or indicative markers of therapeutic effects. For instance, mild anemia may be viewed as a marker for the cytostatic effect, which is critical in inhibiting tumor progression. This serves as an example of the latter. As for the former, rapamycin decreases levels of blood insulin, causing glucose intolerance. Most metabolic “side” effects of rapamycin are therapeutic and associated with increased lifespan in animals.
I have been very curious about Dr Green’s rationales for dosage based on factors like age etc. I found @Krister_Kauppi 's interview very valuable. (Profile - Krister_Kauppi - Rapamycin Longevity News) Alan Green on Rapamycin Master Series | Lessons learned from over 1200 patients
Generally Dr Green seem’s to shoot for 5-6 mg per week. Is he planning on titrating you up to that level over time? Or is he dosaging you based your running goals?
For myself, 2 years ago training for a summer sprint triathlon, I found my training and recovery going exceptionally well at a low dose of rapamycin. I was taking 6mg of rapamycin from a compounding pharmacy, but thought I was getting little benefit as this is not enteric coated. But somewhere on site a researcher revealed their research shows even compounding rapamycin leads to a substantial blood level. So perhaps I was benefiting at a low dose level. Last summer I trained with 6mg weekly of Zydus and felt it generally fatigued me and didn’t benefit recovery even after stopping a few weeks before event.
So I am back to training on low dose of 3mg Zydus rapamycin while training for this summer’s event. It would be great to know if Dr Green can give you feedback on older athlete’s training while on rapamycin.