Key Pathophysiological Role of Skeletal Muscle Disturbance in Post COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Accumulated

[SWAlexander]

ABSTRACT​

Background​

Recent studies provide strong evidence for a key role of skeletal muscle pathophysiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In a 2021 review article on the pathophysiology of ME/CFS, we postulated that hypoperfusion and ischemia can result in excessive sodium and calcium overload in skeletal muscles of ME/CFS patients to cause mitochondrial damage. Since then, experimental evidence has been provided that supports this concept.

Methods​

We collect, summarize and discuss the current state of knowledge for the key role of skeletal muscle pathophysiology. We try to explain which risk factors and mechanisms are responsible for a subgroup of patients with post COVID syndrome (PCS) to develop ME/CFS (PC-ME/CFS).

Results https://onlinelibrary.wiley.com/doi/10.1002/jcsm.13669​

 

[andyguitar]

Looks interesting @SWAlexander For those who cant get through the whole paper Section 6 at the end of it will fill you in. For those who can't manage that... the researchers believe that damage to skeletal muscle mitochondria is the key driving force of symptoms. Treatments they suggest might work are Mestinon sometimes used for POTS, and Vericiguat a vasodilator. They also mention using Immunoadsorption to remove autoantibodies. @Howard and @sunshine44 might find this interesting.

 

[SWAlexander]

remove autoantibodies. @Howard and @sunshine44 might find this interesting.

Thank you for pointing me in the right direction—I’ll look into this further. In the meantime, I’ve written a short preview, keeping in mind my permanent low potassium levels. Your feedback and input would be greatly appreciated! https://swaresearch.blogspot.com/2024/12/the-role-of-skeletal-muscle.html

 

[Howard]

we postulated that hypoperfusion and ischemia can result in excessive sodium and calcium overload in skeletal muscles of ME/CFS patients to cause mitochondrial damage.

I did a basic search online - "Muscle exertion can release sodium and calcium in the bloodstream through a condition called rhabdomyolysis"

I've told several physicians in the past that my condition is most similar to rhabdomyolysis. However, my blood work results never indicate elevated CK levels. And either way, my doctor's are never willing to go there (my son nearly died from rhabdomyolysis when he was 3 years old, perhaps indicating a genetic feature).

But that's been a long standing theory of mine.

My other assumption all along is that I have vitamin D resistance. The higher my vitamin D levels are, the better I feel (overall), and it's less likely that I have severe P.E.M. post muscle exertion.

Vitamin D is known to be anti-inflammatory in the way that it decreases the likelihood of autoimmune sensitivity.

At least, this is my understanding of my current state.

My former medical advocate tried to get me on Mestinon, but I couldn't get any doctors to buy in, much less consider any of my theories, despite providing supporting documentation.

Also, the Coimbra Protocol entails taking massive vitamin D doses, while limiting calcium. I feel confident that if I were able to partake in this protocol I could possibly be healed. But as it stands, I cannot. It's required that I drink at least 2.5 l of water per day, and then also, limit my calcium to less than 400 mg. The problem is that my feeding formula has upwards of 350 mg of calcium per bottle. And I do not have any other feeding formula solution is available to me that I can tolerate.

I think I'm going to redouble my efforts with a particular Coimbra Protocol specialist, a doctor that happens to be a local. Perhaps he can provide alternate solutions, or a workaround, for me.

Thank you for posting this, and also, linking this for me. Perhaps I'll be inspired to once again push my personal agenda! LOL

Howard

 

[sunshine44]

Looks interesting @SWAlexander For those who cant get through the whole paper Section 6 at the end of it will fill you in. For those who can't manage that... the researchers believe that damage to skeletal muscle mitochondria is the key driving force of symptoms. Treatments they suggest might work are Mestinon sometimes used for POTS, and Vericiguat a vasodilator. They also mention using Immunoadsorption to remove autoantibodies. @Howard and @sunshine44 might find this interesting.

Thank you, Andy.
I will look into this.
I really feel like something collapsed in certain muscle groups since mycoplasma in my neck brain and other parts. Intuitively. It’s insane.

Thank you for sharing guys.

 

[andyguitar]

My former medical advocate tried to get me on Mestinon, but I couldn't get any doctors to buy in, much less consider any of my theories, despite providing supporting documentation.

Well if this research is correct it can be confirmed with a clinical trial. If that is a success I cant see any problem with getting Mestinon. Something I forgot to mention is that the researchers call this "Sodium induced Calcium Overload". That also goes by the name of "Hypercalcemia" but that might not be exactly the same thing in this context. However the symptoms of Hypercalcemia are similar to me/cfs.

 

[Howard]

Something I forgot to mention is that the researchers call this "Sodium induced Calcium Overload". That also goes by the name of "Hypercalcemia" but that might not be exactly the same thing in this context. However the symptoms of Hypercalcemia are similar to me/cfs.

Fortunately or unfortunately, my blood work always comes back as being normal, including calcium levels, etc.

I'll reconfirm with my physician next week, see what she has to say. Thank you

 

[sunshine44]

Well if this research is correct it can be confirmed with a clinical trial. If that is a success I cant see any problem with getting Mestinon. Something I forgot to mention is that the researchers call this "Sodium induced Calcium Overload". That also goes by the name of "Hypercalcemia" but that might not be exactly the same thing in this context. However the symptoms of Hypercalcemia are similar to me/cfs.

That’s very interesting as I’ve been told I get bizarre calcium buildups in strange places. Placenta etc. I remember it showed on a catscan once too but no one was very concerned.

Thry did try me on midrodine in hospital which paralyzed me for 12 hours and I had stroke crisis team called in. Absolutely horrific. I’m just not sure how to go about my plight anymore. Apparently midrodine is a very gentle drug and this was not expected.

Will re read what you are saying Andy.

 

[SWAlexander]

rhabdomyolysis

rhabdomyolysis, perhaps indicating a genetic feature. Absolutely possible.
This is part of my ongoing research as I work to determine if factors beyond post-polio syndrome or SMA could be contributing to muscle weakness. So far, I've shared my findings with others with related symptoms: https://swaresearch.blogspot.com/2024/10/the-impact-of-acids-on-muscular-and.html

 

[Wishful]

the researchers believe that damage to skeletal muscle mitochondria is the key driving force of symptoms.

Including the neurological ones? I suppose that to muscle-focused researchers, everything looks like a muscle problem. I expect there's a subgroup of PWME who have only neurological symptoms and no muscle symptoms.

 

[andyguitar]

Fortunately or unfortunately, my blood work always comes back as being normal, including calcium levels, etc.

Testing blood for mineral levels is helpful for some things but it wont always reveal what is going on inside a cell, which is what we need to know.. There are tests for intracellular mineral levels which are used in medical research but I have so far not found any that are available to patients, except for one company in the UK called Epicare Health. Cost is about £200 and they test mineral levels inside red and white blood cells. There must be labs in the USA that do this sort of test.

 

[andyguitar]

Including the neurological ones?

Yes-effects cardiovascular function, leading to among other things hypovolaemia. You might want to have a look at notes 38-39 on the paper.

 

[Wishful]

Hypovolaemia doesn't seem to fit me. My cardiovascular function seems okay. I'm not seeing how muscle mitochondria are causing brainfog, lethargy and pain from non-muscular causes without showing any signs of muscle weakness or other dysfunction.

 

[andyguitar]

I'm not seeing how muscle mitochondria are causing brainfog, lethargy and pain

The breakdown causes the contents of the cell to leak into the blood. Among those released are peptides. Peptides can trigger Mast Cells.

 

[Oliver3]

Would calcium channel blockers work in this case.
Also I believe , but could be wrong, that the OMF was trialling mestinon in the LIFT trial. I so der how that's gone

 

[andyguitar]

Would calcium channel blockers work in this case.

Yeah might help. This certainly gives us something to think about. My thoughts at the moment are that if muscle damage is happening in me/cfs patients almost any time they exert themselves then it could lead to the production of an almost constant flow of inflammatory substances into the blood stream. I mentioned peptides-cant say which ones- and there is also histamine release. Well a good thing in all this is that if this is what is happening it can be tested for and treated.

 

[Oliver3]

Jack Kruse ( I know Insufferable) recommends the use of calcium channel blockers in his protocol for boosting mitochondrial health from light.

 

[Oliver3]

I agree with your analysis. The only thing I'd add is it's going to take smthg strong to stop histamine release and the inflammatory cascade. I use a hell of a lot of anti inflammatory supplements and anti histamines both natural and over the counter.. They help but I still get worse as I age.
I'm pinning my hopes on gene editing in the long run. Once CRISPR really gets underway. If there is a fault in the muscle DNA then surely that could be fixed?

 

[bad1080]

The higher my vitamin D levels are, the better I feel (overall), and it's less likely that I have severe P.E.M. post muscle exertion.

how high are we talking here? (either blood levels or intake amount would be interesting)

 

[bad1080]

rhabdomyolysis

"Once urine output is established, sodium bicarbonate and mannitol are commonly used but they are poorly supported by the evidence." from: https://en.wikipedia.org/wiki/Rhabdomyolysis

the sodium bicarbonate part is interesting because of this:

A daily dose of baking soda may help reduce the destructive inflammation of autoimmune diseases like rheumatoid arthritis, scientists say. They have some of the first evidence of how the cheap, over-the-counter antacid can encourage our spleen to promote instead an anti-inflammatory environment that could be therapeutic in the face of inflammatory disease, scientists report.

from: https://forums.phoenixrising.me/thr...oimmune-and-allergies-and-inflammation.91091/