Thank you very much. This is indeed the study I was interested in. I have studied the article and copied a few interesting sentences :
" We conducted a decentralized, uncontrolled trial of rapamycin in 86 patients with ME/CFS to evaluate its safety and efficacy………
Of the 40 patients, 29 (72.5%) showed strong recovery in PEM, fatigue, and OI, along with improvements in MFI fatigue domains and SF-36aspects….
These clinical responses were accompanied by the upregulation of BECLIN-1 and suppression of pSer258-ATG13,supporting a mechanistic link between the therapeutic benefit and restoration of autophagy signaling……
ELISA analysis of BECLIN-1: ELISA of BECLIN-1 was performed based on a kit (Cat# ab254511) and by a protocol described in the manufacturer’s protocol……
…. 86 participants were initiated on therapy with low-dose rapamycin. Of these, 70 completed the T1 phase (day 36), 55 completed the T2 phase (day 60), and 46 completed the full 90-day study protocol (T3), as shown in the study flowchart……
Importantly, discontinuation from the study was most commonly attributed to financial barriers as this pilot trial did not cover the cost of the study drug or safety laboratory tests. A secondary reason for discontinuation was a lack of perceived clinical benefit or a clinical decision to initiate a different therapy that may or may not interact with the study protocol. "
Measuring BECLIN-1 seems to be a simple test. This may be of interest noct only for ME/CFS patients using Rapamycin, but also in the case of use for life extension.
There is a discrepancy in the number of patients: 46 completed the study, but only 40 are included in the analysis.
Simmaron is now preparing a second, placebo controlled study with the use also of higher dosis: 20 mg of formulated rapamycin which will mean 10+mg Rapa content.
Interestingly they say also that determination of individual half-lifes will be important :-), a well known topic for us. I will publish some more data on this shortly,
Best, M.
Hi, are you suffering from ME/CFS ?
Your comment leaves me puzzled, to my knowledge Simmaron’s is the first study on this. Have I missed something ? I would very much appreciate your pointing me to further data on the subject.
Simmaron is now preparing a second, placebo controlled study with the use also of higher dosis: 20 mg of formulated rapamycin which will mean 10+mg Rapa content.
Best, M.
Yes it is one of the first clinical trials focused on ME/CFS but what I am saying is that there may be participants that find no benefit in the 6mg weekly dose and determine rapamycin would not help them, but if they tried it at a higher dose then it might have been different. Looking at the many anecdotes of people trying it for themselves (here and on other forums and places like r/cfs) it seems that a dose in the 8-12mg range weekly (some even higher) brings the most benefit.
Maybe. According to the PEARL trial data, compounded rapamycin is approximately 1/3 of the serum value of the coated rapamycin. That would mean 45mg compounded translates to 15mg coated.
There are mixed reports about that, centering on the claim that many commercially available “enteric” coated shells are not in fact enteric in the sense that they pass through the stomach undissolved into the small intestine. But there are ones that supposedly do and are legit - there are threads about it somewhere on this site. In principle, rapamycin in such a legit shell should act just as an enteric coated one. That’s the theory. Who knows what the reality is. For me, I take the rapamycin from Indian pharmacies two major brands Eris/Biocon or Zydus, and I have tested my blood levels of rapamycin 50 hours after a 6mg dose and both showed up robustly, thus telling me that whatever the coating on the two Indian brands, they are absorbed by my body well. Let’s keep in mind that everyone’s absorption is slightly different, so you have to measure to know how it works for you. I take on an empty stomach, because I don’t want any confounders. YMMV.
I have been on 14 mg/week without effect since 3 months. I thought I was at the upper range, I also measured my peak values twice at 1/2/3 hours, I got an avg result of 66 ug/l and my decay values over time (6 measurements) showed an half time of 42 hrs. Another member found 88 hrs . The most quoted value in the literature is 66 hrs. So there is a strong individual variation which is to be expected.
Did you do any measurements of the blood values at 36 mg/week ? That would be very interesting.
What symptoms improved most at 36 mg ?
Hi, I am replying to this question from you here as this is “our” ME/CFS thead
Sorry for the delayed answer, I have not been well. To answer your questions:
-We never really found out what the trigger was
-I started to have symptoms out of the blue and lost 8 kg muscle in 6 months (I was very sporty)
-I have been diagnosed also with IBM
-Yes, my immunology is not normal. I have been treated by immunologist but never with corticosteroid. We tried two monoclonal antibodies without success.
A question to you: what are your blood levels of rapa ?
Sorry you haven’t been feeling well… I know exactly what your going through… and it completely ruined my life.
I still haven’t taken the blood test for rapa levels. I plan to do it towards the end of this month.
There are certain individuals who’s fatigue almost completely vanishes using large, immunosuppressant doses of corticosteroids. I’m one of those individuals; when I take 30mg of prednisone everything disappears. It does however have terrible side effects, and can destroy your bone density, among other issues. But it might be a good predictor of whether or not rapa helps you.
mAbs are different, and are addressing a very specific infection/attack, whereas corticosteroids are system wide, and suppress your entire immune response. I’m not sure what IBM is, did you mean IBS? If so, many who have fatigue have IBS. If you have IBD (crohn’s or Ulceritive colitis) that can definitely point to immune disregulation, and sometimes immune overactivity.
I don’t know the mechanism for why rapa can dramatically help many with CFS/ME. But there is a subset of us who definitely have immune overactivity… and I suspect anything that has strong and system-wide immunosuppressive effects will help. But it could be some other reason.
As a side note… Rapam gets me to about 70% cured… which is amazing… but its not 100%. To get that last 30%, I’m fine-tuning my diet, and re-conditioning myself.
IBM is Inclusion Body Myositis. I started having Dysphagia, one of the symptoms, but fortunately with IVIG I have this under control.
Rapa seems to work by inhibiting mTOR1 and hence improve autophagy (and hence improve in longevity), and in the case of ME/CFS especially mitophagy. There are many articles on this, I used ChatGPT to do the search.
Amazing the progress you made with Rapa ! I started at 7 mg, went to 14 mg for 3 months without any improvement, then I saw your post and titrated up to 30 mg, first time last week. I’ll stay at 30 mg for a few weeks and hope for improvement. Note that I take liquid Rapamune from Pfizer, the most bioavailable form. It is still available in Europe (I am in Switzerland), it was discontinued from Pfizer elsewhere because of too much competition from formulators (!).
How quickly did your improvement set in ?
I have measured my pik at 14 mg twice: Pik 3 Curves 14 mg Feb March 2025.pdf (90.1 KB)
I used a quadratic best fit model using ChatGPT for calculation and graph, My finding are consisteng with others, the pik is between 2-3 hours. Best if you do a few measurements the first time. If you do only one I would do it at 2.5 hrs. I am really interested in what pik value you get, it may be a pointer for me.
To get the 30% maybe also try some supplements ?
Best, M.
Sorry to hear about your situation. I will do the blood measurement shortly after dosing.
The mitophagy is one possible mechanism for improving ME/CFS, but it’s still early in the debate; and its possible it’s more than one mechanism.
For me, the improvement is pretty quick… within 1-3 days. And the symptoms usually come back after about 2 weeks off.
Assuming you are taking the most bioavailable form… 30mg is a lot. I hope it helps, but if its already been a week and you still feel no improvement, It may not give you the benefit that I get from it.
