Fatigue - Side Effect

Has anyone had to stop taking Rapamycin because of fatigue that didn’t go away even after a period of adjustment?

With each dose I’ve become progressively more tired. The first two doses (0.5mg one day apart) seemed to actually give me energy, although an underlying, low level fatigue was still present. I didn’t have any significant response to the 3rd dose (1mg two days from the previous dose), certainly no “rush” as with the first two. It did seem to make me a bit more tired, although not debilitatingly so. The next day I felt as if I had a virus, extreme joint aches and felt affected by histamines, but the day after these symptoms were mostly gone.

I took the 4th dose (0.5mg two days from the previous dose) this morning and in less than an hour had become extremely sleepy. So far this fatigue hasn’t lifted.

To be clear, I don’t suffer from CFS. I naturally have fairly high energy levels despite the Hashimoto’s, and I can make a direct correlation between these drugs (the Metformin and Rapamycin) and the fatigue.

I’m taking Rapamycin for Hashimoto’s disease on top of T4, T3 and LDN, as well as a number of supplements. My goal is to alleviate a series of debilitating inflammatory symptoms that thyroid hormone replacement and natural supplements aren’t improving. I had previously taken Metformin for this purpose, and while it worked, I had to come off it after 5 months because it gave me really bad fatigue. I spent these 5 months experimenting with different doses and intervals of dosage; in the end I was taking 250mg IR every 4th day but was still exhausted.

The Rapamycin does seem to be alleviating the inflammatory symptoms, but the fatigue concerns me as I’m afraid of a repeat of my Metformin adventure. Does anyone have any experience with this, or know what might be causing it? Would appreciate any help or ideas.

In case this is relevant, I’m taking Pfizer brand Rapamune.


I’m also on Rapamune, following a schedule of 1 mg every day for 3 weeks, then a week-long break. Surprisingly, I haven’t noticed any increase in fatigue. When I was taking a weekly dose of 6 mg, I did experience fatigue, although it felt more like a satisfying exhaustion, similar to post-orgasm fatigue. It’s interesting how different dosing schedules can affect how we feel. I’m not taking Rapamune for any specific condition; rather, it’s to help manage autoimmune symptoms like dermatitis, dyshidrosis, and rhinitis.


Yes, I have fatigue like @scta123 mentioned above on the day of taking Rapamycin and the day after. If you are dosing every other day, then it is possible you could be in a constant state of mild fatigue. I dose every week, so the fatigue only affects the first couple of days, and those are my ‘chill’ days anyways. On those days I can still drive and perform normally although I wouldn’t mind taking an afternoon nap…


This is a pretty unusual dosing strategy, what is your rationale for it? Did someone suggest the daily for Hashimoto’s disease?

Most of us take rapamycin once every week to once every two weeks. Have you seen our dosing thread? What is the Rapamycin Dose / Dosage for Anti-Aging or Longevity?

and our FAQ: Rapamycin Frequently Asked Questions (FAQ)

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How long were you on a weekly dose of 6 mg, and how quickly did the fatigue take to come on? How were your symptoms (dermatitis, dyshidrosis, and rhinitis) when you were taking it once a week? Which protocol best managed your symptoms? Do the symptoms return during your off week? Sorry for the deluge of questions, there’s so little known about how this works for autoimmune conditions.

I’m not taking it for longevity, I’m taking to suppress symptoms of an autoimmune disease so I’m going to be taking it constantly. My approach will have to be closer to that of a transplant patient - I’m trying to take the lowest dose as frequently as necessary to not completely wash out. I won’t have holidays from it. So far, judging from my symptoms, the half life seems to be about 2.5 days for me. I’m taking it every 3 days at the moment.

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The half-life of Rapamycin is usually considered 63 hours. So, about 2.625 days.


We have one transplant patient here taking rapamycin on a schedule similar to yours. @LaraPo has been taking rapamycin for many years on mostly a daily basis (but not every day now I believe) so she’s our local expert on this type of dosing regimen. I don’t recall her getting any significant ongoing fatigue, so it may be an issue that rapamycin is triggering due to some some unique interaction with your biology or some of the other drugs you are taking.


I was on a weekly dose for six months, starting from 1 mg per week and gradually increasing to 6 mg per week. I took rapamycin in the morning, and by the afternoon, I began to feel fatigued. This fatigue persisted throughout the next day, similar to what @DeStrider experienced. After noticing some improvements in my autoimmune issues, I decided to try my current dosing schedule based on research and anecdotal evidence. I’ve seen much better results since then: dishydrosis is in remission, dermatitis has improved by 80%, and rhinitis is probably 60-70% better. Joint pain has also decreased by around 30-40%. Although symptoms don’t return after a week, I recently had surgery and took three weeks off, during which everything came back. It took another three weeks to calm everything back down.


You are right, I don’t experience any fatigue or any bad side effects on my dose (1mg for 3 days of each week). It works well for my kidney (creatinine 0.92, BUN 15).

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I took 6mg + gfc and then 2mg + gfc. No fatigue. It does trigger my gout within 12 hours, so I drink lots of water in the first 24 hours. Also I get bad smelling farts which I use active carbon pills to control.

You might want to consider the possibility of reactivated EBV.

I’m also taking it for autoimmune diseases and started at 1mg every second day. By the two week mark I was in definite flare of ankylosing spondylitis and it felt like my spine was on fire. Same thing happened with a biologic treatment. There was a paradoxical pro-inflammatory response.

Then it was mentioned in a fb group I’m in and a research paper posted on the proinflammatory response that can occur. For some people it subsides as the body adjusts in two weeks or so but I ended up iller and iller and very disappointed because rapa is my last ditch effort havning reacted to so many biologics.

I quit and waited for the flare to die down, which it did, and the pain of medication induced flare is quite particular for me, and then resumed with 1mg weekly and a slow build to 3mg weekly - which seems like it should not work for AI stuff - but it is!

I’m at 3mg weekly and potentiated last dose with half a grapefruit and it’s working. My inflammatory markers are decreasing. I’m not in remission yet but I don’t expect that too quickly on this regime.