Side Effects of Rapamycin (part 2)

Yes Repatha is a PCSK9i, but it also causes similar muscle pain as statins(but the muscle pain is via a different pathway from statins). Just not as frequent as statins-but is listed as the 3rd most common side effect after runny nose and inj site pain. A low dose Rapamycin(2mg) seems to have stopped my Repatha muscle pain. Not sure if it will help statins.

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Did you initially start on a higher dose of Rapa and titrate down? I’m curious why you settled on the 2mg dose. If I do ever go back on it, I was considering a lower dose than the 6mg/wk I was on for a couple months, but stopped due to mouth sores and a cut that had healing issues…

I had a friend who tried rapamycin and had the same experience, it completely wiped him out. I wonder if this issue (or association) is due to some type of genotype issue, or other issue. My friend tends to have higher blood pressure already which he tries to control but may be inconsistent on. He also has more central adipose tissue (ie. a bit of a ā€œgutā€) and probably higher inflammation issues related to this. I wonder if these factors may influence response to rapamycin. I don’t think there is any data yet, but something to consider. Anyone else see any other possible correlations to ā€œpoor respondersā€ to rapamycin?

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I don’t remember if I shared this, but many months ago my husband tried taking it, but he finally threw in the towel.

At night, he would get a fevers and night sweats.

His doctor, who was confident it wasn’t caused by rapa, ran a bunch of labs to rule anything else out.

When he stopped, the fevers went away, and hen he went back on, they came back. He experimented 2 different times. The first time he was on 6mg weekly, and the second attempt was at 4mg.

He’s a super fit guy who makes me look like the Pillsbury Doughboy, so body composition was not a contributing factor in this case.

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I’m one of those people. So is the fatigue a sign that rapamycin is actually repairing the body, or is it simply a side effect?


In mouse studies, fatigue is usually a sign of aging. I really wish I felt energetic after taking rapamycin. Unfortunately, I feel extremely exhausted every time I take it.

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Then there are those who feel nothing as a result of taking rapamycin. I’m now on week 14 of taking 8mg once per week. Same protocol, every Saturday first thing in the morning on an empty stomach and then nothing but matcha for the next 2 hours or so. And I know I absorb rapa, because even at 6mg, 50 hours later my blood levels of sirolimus are like 5.6 ng

Yet I feel absolutely nothing subjectively from taking it. Neither the day of, or on subsequent days. I do see side effects - minor pimple on the nose or chin (I never get pimples otherwise). These come and go, some weeks there, some weeks nothing. Honestly, it feels like I’m taking nothing - good thing I can get blood tests otherwise I’d suspect the pills were duds.

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I guess I’ll chime in also with a bit of more nuanced N=1 based on time I take it. When I take rapa (usually 5mg) before bed I wake up tired but not necessarily in a bad way, It’s like being very relaxed but not motivated I almost like the feeling, kind of hard to explain. When I take it in the morning/during the day, I feel absolutely nothing. I do however always get very mild flu like symptoms for the first two days in the mornings (when I wake up) but symptoms disappear soon after I wake up. BTW, 5mgs is my sweet spot as I have never gotten mouth sores from this dose. I used to do 6mgs and would often get mouth sores (very uncomfortable) so I switched to 5mgs and haven’t had a case in over 4 months now.

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It is odd the range of side effects that people get from taking rapamycin. I wonder why this is and what it means.
Personally I have never felt any side effects except diarrhea the next day after taking massive doses.
It has never affected my sleep or made me tired. In fact, when I first started taking rapamycin, I often felt slightly elated the next day. Now I feel nothing.

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I have often wondered if some side effects might be ameliorated by lengthening the dose interval enough to create a rapamycin free period, especially for older individuals. Other important benefits might also follow.

The study most often cited for ā€œimmune rejuvenationā€ did not test continuous weekly sirolimus exposure. It tested brief mTOR inhibition followed by complete withdrawal.

The 2014 Mannick trial gave adults aged 65 and older six weeks of everolimus, followed by a two-week drug-free interval before administering an influenza vaccination. Vaccine responses improved by approximately 20%, and PD-1–expressing CD4 and CD8 T cells declined. The immune benefit was therefore expressed after treatment had stopped, not merely while the drug was present.

The 2018 trial similarly treated older adults for six weeks with low-dose mTOR inhibitors (different arms using Everolimus and/or dactolisib), followed by withdrawal. Similar to the 2014 study, the most effective regimen enhanced antiviral gene expression, improved influenza-vaccine responses and reduced reported infections during subsequent follow-up.

These trials do not prove that the washout was necessary because they did not randomize participants to vaccination on-drug versus off-drug. They did establish that a transient course can produce immune benefits that survive drug clearance.

Given the other forms of evidence that a strong immune system accounts for much of the variance in surviving intact into old age, a regimen that created drug free intervals might lessen side effects and produce the most useful effects. Even a months on followed by months off regimen is not ruled out by current evidence.

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I also feel nothing and cannot say if I have any side effects.

Unfortunately I just had a horrible experience with a bacterial infection and Rapamycin. 11 days ago, I contracted a bacterial gastrointestinal infection (food poisoning). It coincided with a 7 mg + GFJ dose shortly after. I had bad diarrhea for 10 days and needed to go on antibiotics. In the past my body would clear it up after about 3 days without antibiotics.

So be careful and realize Rapamycin will make any bacterial infection much worse than it normally would be.

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What a coincidence, I went through the exact same thing ten days ago :joy:. Unfortunately, I also threw up two or three times, and I only just got back to normal in the last two days.

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Yes, bacterial infections tend to be exacerbated by rapamycin (whereas viral tend to be milder). Especially high doses can be problematic. Surgery - get off rapamycin - that’s what I did in December '25 when I had my ACDF procedure. And recovery - wound healing and postoperative infections are negatively affected by rapamycin. Rapa is a great drug, but like all drugs it has downsides and limitations. Many also avoid rapa for a couple of weeks before and after vaccinations - I personally don’t, but we all have to be cognizant of potential risks with any drug and rapa is no exception. YMMV.

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The night I took rapamycin, I slept very poorly and kept waking up. Then the next day, if I walked for more than half an hour, I felt extremely tired and experienced muscle weakness.

I took Pfizer Rapamune 2mg/week + grapefruit.

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That sounds like you had real rapamycin.

It seems there’s at least one other protocol for dosing rapamycin (for rheumatoid arthritis), this time 0.5mg taken once every 2 days. Now I’m wondering since seeing user Satchel’s 2mg/wk dosing experience, if there isn’t some room for tuning dosage to the current state of one’s immune system?

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I’ve had the same side effects, like fragmented sleep, and I get extremely exhausted in the afternoon. My fingers also feel like they have tendinitis, but it’s basically back to normal by day three.

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I’m not sure at all if I would keep taking rapamycin if I got 2 days of exhaustion after my doses. Nobody has a standard protocol for responses like this, but if I were getting these types of side effects I would definitely do some significant blood tests (perhaps the day after dosing) to see if I can identify the blood level changes that might be contributing to these side effects. Perhaps a less frequent dosing schedule, or lower dose, is appropriate?

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Maybe the dose is too high. I will try lower dose later.

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If you have a possibility of extending your life 10-20% (we truly don’t know), but you’re spending 25% of that extension in a sleepy stupor and feeling bad, it probably isn’t worth the trade-off, right?

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