• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

mTor Inhibitor Rapamune Helps 5 ME/CFS Patients in Dallas

Messages
516
This is purely anecdotal, but I have been taking berberine for about a week now, and Berberine is a mtor inhibitor. link I have worked my way up to 300mg a day and feel a big improvement in my health.

I am taking it for SIBO and I think that's where most of my benefits are coming from. If it is as they say, a mtor inhibitor, it hasn't done me any harm whatsoever, in fact it's been a great help. I have read the metabolomics study saying that mtor is already inhibited in cfs. So it don't really make a lot of sense to me, but it is really helping me a lot!
Berberine is a little alarming, it's used in the diabetes research and its mechanism is this other part that your link happens to mention: "In view of the evidence that BRB localizes in mitochondria, inhibits respiratory electron chain". They know it as a mitochondrial inhibitor.
[No comment on rapamycin, perfectly plausible it helps in one way, not to mention people have gotten symptom relief from mTor inhibitors all the time]
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
I don't want to get too excited, because I just started Famvir (replacing Valtrex) recently and I also felt great right away with the change to Famvir, but it didn't last more than a day and a half. That was dissappointing, and I'm not sure if Rapamune will be similar, although I feel better on the Rapamune than I did on the first day of Famvir. We'll see how it goes on Rapamune in the next few days.

Fair enough! Will be following your progress
 

nandixon

Senior Member
Messages
1,092
Assuming that Rapamune (sirolimus aka rapamycin) does turn out to be beneficial for a number of people, I don't think there's much chance that this means mTORC1 is actually over-activated in ME/CFS. I'm definitely sticking with it being under-activated/inhibited.

A couple of explanations for why rapamycin might be working are:

1. Perhaps under-activation of mTORC1 in ME/CFS is actually a beneficial adaptation of the body in its attempt to deal with the disease and further inhibition of mTORC1 by rapamycin is helping achieve this goal.

2. Perhaps there is some non-mTORC1 related beneficial effect that rapamycin has that outweighs the seemingly negative effect of inhibition of mTORC1.

Regarding #1, a mouse study found that rapamycin was able to protect cardiac function in a sepsis model by further reducing mTORC1 activity that had already been reduced upon pathological exposure to lipopolysacharride (LPS). (Not sure if it's just a coincidence here that ME/CFS has been found to closely resemble SIRS/sepsis at the mRNA gene expression level.)

Regarding #2, even though rapamycin inhibits the mTORC1 enzyme complex it actually increases the activity of the upstream Akt regulator enzyme. (The above mouse study also notes this as well.) This is pretty remarkable because most other substances that might inhibit mTORC1 will usually inhibit Akt too (e.g., metformin). So this might be a key aspect to the beneficial effect of rapamycin, assuming it is actually helping.

Lastly, I notice that both Mary Adelman (in the original post) and also @XenForo previously found that low dose naltrexone (LDN) is helpful for them. So it's possible that rapamycin may only work for that subgroup of patients. LDN is very toxic to me but I'm very curious how I'd respond to rapamycin. (Note that naltrexone inhibits both mTORC1 and Akt.)
 
Last edited:

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
Berberine is a little alarming, it's used in the diabetes research and its mechanism is this other part that your link happens to mention: "In view of the evidence that BRB localizes in mitochondria, inhibits respiratory electron chain". They know it as a mitochondrial inhibitor.

I saw that when I read the paper, and it made my heart skip a beat.;) My experience with Berberine is clearly very positive though. I've been taking it for about 3 weeks now and have worked my way up to 500mg a day. I feel dramatically better!!

My flu like symptoms are greatly reduced, if fact I usually have a few hours a day, almost every day, where my symptoms are 80-90% gone. Just in general, I feel much better, more energy, more clear-headed, better mood, etc.

I really think that it's oxidative stress, caused by immune activation, from LPS in the gut that's causing the mito. dysfunction. So my intention is to treat the source of the mito dysfunction, in hopes that will allow them to function normally again.
 
Messages
516
Regarding #2, even though rapamycin inhibits the mTORC1 enzyme complex it actually increases the activity of the upstream Akt regulator enzyme. (The above mouse study also notes this as well.) This is pretty remarkable because most other substances that might inhibit mTORC1 will usually inhibit Akt too (e.g., metformin). So this might be a key aspect to the beneficial effect of rapamycin, assuming it is actually helping.
That isn't unheard of though, some AMPK activators can activate Akt like https://www.ncbi.nlm.nih.gov/pubmed/20167101, lipoic acid, etc. It does come up. (sometimes related to others such as mTORC2 but not always, which it shouldn't be for rapamycin)

Those are plausible ideas, but to me unless rapamycin affects some critical (immune) cell type uniquely, or some other unique effect, it doesn't scream "take me" compared to others (several-day half-life, so unless you can cycle it for this similar to its other applications, longer-term I'd get worried).

I really think that it's oxidative stress, caused by immune activation, from LPS in the gut that's causing the mito. dysfunction. So my intention is to treat the source of the mito dysfunction, in hopes that will allow them to function normally again.
I believe you (and sure my gut is as much a source of problems), it's just that unless it has a truly unique therapeutic effect, I have to believe there are more efficient ways to do that! (that's my theme here)
 

XenForo

Senior Member
Messages
107
i searched sci-hub for "hydroxychloroquine "b cell" (ablation, depletion)" and couldn't find anything showing plaquenil depleting b cells. But, of course, I might have just missed something or needed to revise my search terms.
 

Jill

Senior Member
Messages
209
Location
Auckland, NZ
I wonder why the Dallas dr gave it to their patients ? Any ideas or what tests would indicate the use of it. We have a Dr that will endeavour to try anything within reason on Al, and this med is available in NZ for transplants
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
Interesting.. 30 percent ish of my t-cells are double positive for CD45RA and CDRO. Rituximab didn`t work, so i would be interested in something touching on t-cells. Might not be related though.
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
I wonder why the Dallas dr gave it to their patients ?

He's a forward thinking oncologist applying his model of the disease with the tools available

Any ideas or what tests would indicate the use of it.

Not sure. Just a stab in the dark but maybe ANA, CellTrend, B-cell count

Interesting.. 30 percent ish of my t-cells are double positive for CD45RA and CDRO. Rituximab didn`t work, so i would be interested in something touching on t-cells. Might not be related though.

Interesting, what tests did you use to determine your T-cell metrics?
 

nandixon

Senior Member
Messages
1,092
I wonder why the Dallas dr gave it to their patients ? Any ideas or what tests would indicate the use of it. We have a Dr that will endeavour to try anything within reason on Al, and this med is available in NZ for transplants
It's not clear to me exactly what the nature is of the other 4 patients that Marcia Adelman refers to. Because in a later post in the cited blog she says:

The others he was seeing for other medical challenges but who also had me/cfs.
This sounds like the other patients are either cancer patients or have autoimmune blood diseases - because the doctor is an oncologist and hematologist.

In either of those cases it might make sense to give the mTORC1 inhibitor Rapamune (rapamycin/sirolimus) since mTORC1 is commonly over-activated in cancers and Rapamune can be very effective in autoimmune cytopenias.

It would be nice to know how their ME/CFS fits in, timewise, with respect to their other illnesses.
 
Last edited:

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
Jesse don`t know what type of test that is, but I had extensive phenotyping of my b- and t-cells under investigations at the immunological ward at one of the main hospitals in Norway. Had a bone marrow test which also had some weird results, but it could also just be random variation. Nonetheless it has made me suspect there must be something immunological.

Rapamune was apparantly just finished undergoing a phase 2 for Lupus. They havent published yet
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
Oh and the test result i referred to above was apparently something they were researching at the hospital. They had seen it in a lot of patients with immunological diseases lately, due to the improvement of testing. Last thing i heard they were gonna do extensive genetic testing to see if something comes up.
 

XenForo

Senior Member
Messages
107
I wonder why the Dallas dr gave it to their patients ? Any ideas or what tests would indicate the use of it. We have a Dr ...
From Marcia Adelman over on HealthRising.org:
"The doctor who prescribed Rapamune is my husband’s hematologist. I was too ill to accompany him on his visits so we used FaceTime so I could listen and ask questions about his condition. One day hubbie explained why I was unable to be there and Dr said I should come see him and mentioned treating others with my symptoms with Rapamune with success.

I knew this relapse was different from others and that for 2 years my immune system was way out of whack and inflammation as result made sense to me given Fluge and Mella research as well as Jarred Younger hypotheses and other researchers writings. Apparently one of this Dr patients came to him with a stack of research asking if willing to work with her with immune suppressant.

The others he was seeing for other medical challenges but who also had me/cfs. All are improved. This is a very highly respected oncologist in the Dallas area and apparently an outside the box thinker."
quoted from here:https://www.healthrising.org/blog/2017/03/08/davis-strategic-approach-chronic-fatigue-syndrome/
 
Last edited:

XenForo

Senior Member
Messages
107

Jill

Senior Member
Messages
209
Location
Auckland, NZ
Weird that it's so being used in lupus as so many of us get that similar lupus rash . One dr was convinced al had lupus based on the red rash across his nose but no positive lupus tests. This guy might be onto something . Please please keep us in touch :)