Trial Report Low Dose Rapamycin Alleviates Clinical Symptoms of Fatigue and PEM in ME/CFS Patients via Improvement of Autophagy, 2025, Ruan et al

[V.R.T.]

The wasf3 paper is probably the best evidence we have but it needs to be followed up.

Anyone got any word on whats going on there? Last I heard Hwang et al were moving ahead with a small drug trial...

 

[Covidivici]

Disclaimer, this is 100% anecdotal:

Interestingly, rapamycin initially restored my energy and mental sharpness to the point where after two full weeks of feeling great, I risked a HIIT workout (spoiler: that was not smart. It led to a PEM crash). The crash lasted two weeks. Another three weeks went by with me resuming some function (not quite as much as before the crash) until, out of literally nowhere (I live in an airtight bubble), I came down with flu-like symptoms, then tested positive for COVID.

That was a major WTF moment.

Other than feeding/hanging out with my neighbours' cat during their trip abroad (with N95 on for the first four days, then without which I assume was my mistake — that cat is a kisser) I can't see how I could have caught it. I never leave home without a fit-tested N95 and even then, it's just to walk to the pharmacy or grocery store. No one else in my household ever tested positive. My spouse was livid: They do everything to keep me safe and here I went and got sick again on my own.

I was so flabbergasted that I actually wondered if rapamycin might not have led to either reactivation of the virus (following the viral persistence theory) or for a mutated version of it to break through. Neither of which I've ever heard of happening to anyone.

So yeah, it was probably the f%@ing cat. Consequently, my baseline ended up halved. I went from functional-but-cautious-not-to-trigger-PEM to basically bed bound. End of anecdote.

Edit: not sure what mitochondrial issues Dr Younger is referring to as there is no clear evidence for a specific mitochondrial problem yet.

I was under the impression that Rob Wüst was onto something:

"Biopsies of Long COVID patients vs controls before they exercised showed little difference. But as soon as they'd done mild exercise, the control group's mitochondria got more efficient whereas those with Long COVID (now suffering from PEM) got worse."

Relevant thread:

Preprint Thread 'Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest, 2025, Charlton, Wust et al'

May 6, 2025

Abstract:
Patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suffer from a reduced exercise capacity, skeletal muscle abnormalities and post-exertional malaise (PEM), where symptoms worsen with cognitive or physical exertion. PEM often results in avoidance of physical activity, resulting in a lower aerobic fitness, which may contribute to skeletal muscle abnormalities.

Here, we compared whole-body exercise responses and skeletal muscle adaptations after strict 60-day bed rest in healthy people with those in patients with long COVID and ME/CFS, and...

• Nightsong
• bed rest deconditioning long covid me/cfs muscle rob wust
• Replies: 58
• Forum: ME/CFS research

• 

 

[wingate]

rapamycin is a f***ing nasty drug

Could you elaborate on this? What makes it so bad?

 

[Utsikt]

Could you elaborate on this? What makes it so bad?

For those forum members who don't know. mTOR is basically the central agent that controls cell metabolism (it has two functional complexes mTORC1 and mTORC2) it has its fingers in every pie that you can imagine. Because of this and because of cancer I would not be surprised if it is the single most researched protein kinase in history (which is an advantage, we know how it fits into a lot of cell biology in detail)

 

[Annavive]

Now published, see post #37
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Low Dose Rapamycin Alleviates Clinical Symptoms of Fatigue and PEM in ME/CFS Patients via Improvement of Autophagy

Brian T. Ruan, Sarojini Bulbule, Amy Reyes, Bela Chheda, Lucinda Bateman, Jennifer Bell, Braydon Yellman, Stephanie Grach, Jon Berner, Daniel L. Peterson, David Kaufman, Avik Roy, C. Gunnar Gottschalk

Background
mTOR activation is associated with chronic inflammation in ME/CFS. Previous studies have shown that sustained mTOR activation can cause chronic muscle fatigue by inhibiting ATG13-mediated autophagy. This highlights the pivotal role of mTOR in the pathogenesis of ME/CFS.

Methods
We conducted a decentralized, uncontrolled trial of rapamycin in 86 patients with ME/CFS to evaluate its safety and efficacy. Low-dose rapamycin (6 mg/kg) was administered, and core ME/CFS symptoms were assessed on days 30 (T1), 60 (T2), and 90 (T3). Plasma levels of autophagy metabolites, such as pSer258-ATG13 and BECLIN-1, were measured and correlated with clinical outcomes, specifically MFI.

Results
Rapamycin (6 mg/week) was tolerated without any SAEs. Of the 40 patients, 29 (72.5%) showed strong recovery in PEM, fatigue, and OI, along with improvements in MFI fatigue domains and SF-36 aspects. High levels of BECLIN-1 were detected in T3. Plasma pSer258-ATG13 levels were strongly downregulated at T1. Spearman’s correlation analysis indicated an association between autophagy impairment and reduced activity.

Conclusions
Low-dose rapamycin effectively reduced PEM and other key symptoms in patients with ME/CFS, as measured by BAS, SSS, MFI, and SF-36. Future studies should encompass dose optimization and develop a diagnostic tool to identify responders with mTOR-mediated autophagy disruption.

Link | PDF (Preprint: ResearchSquare) [Open Access]

My ME specialist in my country wish to put me on low dose rapamycin (brand name he prescribed: rapamune). He wishes me to start at 1mg/week and slowly titrate up to 6mg/week.

As must as I am happy to try it, I am concerned about the possible damage it can cause long term. If there are any long term use studies I would be interested

 

[Jonathan Edwards]

As must as I am happy to try it, I am concerned about the possible damage it can cause long term. If there are any long term use studies I would be interested

My cncern is that there are no studies that provide any meaningful evidence of benefit. The study quoted is useless.

 

[Utsikt]

My ME specialist in my country wish to put me on low dose rapamycin (brand name he prescribed: rapamune). He wishes me to start at 1mg/week and slowly titrate up to 6mg/week.

That sounds like what Storla does here in Norway. I think he cites this study and he doesn’t seem to understand how flawed it is. He also thinks people with perfectionism or childhood trauma are more likely to get ME/CFS..

In case you missed these comments:

rapamycin is a f***ing nasty drug so seeing anecdotes of people losing baseline and reading here that drop-outs were excluded from the results is worrisome given that people are going to see this study on twitter and ask their doctor for a prescription

Need double blinded rct urgently to clear this up because the genie is out of the bottle

In as many uncountable ways as any number of metabolic disturbances if present may interact with processes that we believe may drive the illness. These particular pathways affect pretty much all of the cell. It has to be framed within a specific, start-to-finish signalling process to be evaluated in specific terms.

It turns off the most central and interconnected protein kinase complex in mammalian biology

 

[Annavive]

That sounds like what Storla does here in Norway. I think he cites this study and he doesn’t seem to understand how flawed it is. He also thinks people with perfectionism or childhood trauma are more likely to get ME/CFS..

In case you missed these comments:

Thank you very much for this information alongside highlighting the previous comments, I did miss some of these! I have not yet started rapa and I am indeed concerned about trying it even short term now after seeing the comments here, many thanks again