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

[TracyD]

I asked Dr. Scheibenbogen:
I just read your interesting article on the role of skeletal muscle disturbance in ME/CFS. I appreciate the advances in knowledge about skeletal muscle problems, but I was unclear whether this really is the root of PEM, for two reasons:

• For me and many others, discernible symptoms of PEM take a couple of days to develop, and I believe that exercise studies have shown that cytokine changes track with this. Does the mechanism that you proposed account for this timing?
• I believe that multiple labs have shown that ME/CFS cells can be returned to an apparently healthy state either by filtering an unknown factor out of the blood. I think Fluge and Mella showed that this returned the pyruvate dehydrogenase complex in the mitochondria to healthy function. In fact, I was briefly returned to health after Inuspheresis treatment in Frankfurt. Again, it was unclear to me (as a layperson): does your proposed mechanism account for this?

And she responded:
the mechanism we describe fits well with the delay of PEM symptoms.
We have performed a study filtering immunoglobulins by immunoadsorption and this can result in improvement of all symptoms including PEM. What the mechanism of the INUS apheresis is I dont know.
https://www.sciencedirect.com/scien...4003302?ssrnid=4911576&dgcid=SSRN_redirect_SD

 

[Wishful]

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

You can propose any sort of Rube Goldberg mechanism, involving mast cells and the kidneys and the tooth roots and toenails, which would result in neurological symptoms, but it's harder to come up with a theory that explains the symptoms and explains the lack of other symptoms and responses that the mechanism should show. If I have neurological symptoms while my muscles and cardiovascular function seem normal, a simpler explanation is that muscles are not involved.

 

[Howard]

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

Two months ago I was in the midst of an all-encompassing relapse (severe P.E.M., strained breathing, insomnia, scalp psoriasis, extreme stimuli sensitivity, etc.) with my vitamin D coming in at 30 ng/mL.

I've hadn't realized my levels were so low. I am convinced I suffer from Vitamin D Resistance. When my level reaches 50, I can operate a manual wheelchair, play guitar, and avoid P.E.M. episodes by pacing. I'm also of the mind that I may one day walk again if I can double my vitamin D levels, perhaps approaching 100 ng/mL.

Because I have Celiac Disease, as well as severe gastroparesis (and a feeding tube), I do not readily absorb vitamin D via nutritional intake. I rely exclusively upon direct sunlight exposure, and a newly purchased UVB light (at $600).

 

[andyguitar]

Also I believe , but could be wrong, that the OMF was trialling mestinon in the LIFT trial.

Yes, trial will end in about June 2026.

The only thing I'd add is it's going to take smthg strong to stop histamine release and the inflammatory cascade.

Yes antihistamines could be helpful. Also worth consideration are Branched Chain Amino Acids (BCAA) which can help to repair/rebuild muscles. Affordable and pretty safe.

Once CRISPR really gets underway. If there is a fault in the muscle DNA then surely that could be fixed?

A long way off I suspect. And if there is a genetic predisposition here it might not be muscular in origin. Mast cells perhaps?

 

[bad1080]

When my level reaches 50, I can operate a manual wheelchair, play guitar, and avoid P.E.M. episodes by pacing. I'm also of the mind that I may one day walk again if I can double my vitamin D levels, perhaps approaching 100 ng/mL.

thanks! i usually hover around 50ng/ml since i started supplementing. it says >100ng/ml is potentially toxic on the range here, so keep that in mind.

 

[Oliver3]

Yes a long way off but a possibility say in 15 years..
I've bought some amino acids actually
Thanks for the tip. I'll start retaking them.
Did you see Ron's message? Looking into the role of manganese amongst many other threads. That's a connective tissue area.
I've always felt that was ground zero. Cell wall shape and integrity

 

[Oliver3]

You can propose any sort of Rube Goldberg mechanism, involving mast cells and the kidneys and the tooth roots and toenails, which would result in neurological symptoms, but it's harder to come up with a theory that explains the symptoms and explains the lack of other symptoms and responses that the mechanism should show. If I have neurological symptoms while my muscles and cardiovascular function seem normal, a simpler explanation is that muscles are not involved.

Mast cells can be overactive or degranulate more easily in one part of the body. There may specific abnormal amounts in one part of the body that degranulate easily and set off a cascade

 

[andyguitar]

Did you see Ron's message? Looking into the role of manganese amongst many other threads.

Will check it out.

I've bought some amino acids actually
Thanks for the tip. I'll start retaking them.

Dont expect a quick fix as it can take a few weeks to rebuild muscle, particularly as exercise is not an option to most me/cfs patients. The 2 drugs suggested by the papers authors look like the best option to deal with the cause of the muscle problems. Although in the case of the vasodilator Vericiguat there are other drugs in that class that have a similar effect. Also some herbs. Got something in the back of my mind about all this. Can't quite find it.

 

[Oliver3]

Cheers Andy. Will start taking them.
Just as a side note. A lot of people talk about sympathetic dominance being the reason we are so sick.
There's only a year between me and my brothers he has an anxiety disorder, likely very lite Asperger's, or at least the sensorial elements....I'm the same. The difference is he recovers!. We have similar muscle definition but he has a much better vasculature. You can see it in his hands etc. very healthy.
He works ridiculous hours and still runs 10 km a few days a week, WITH an anxiety disorder.
There's something about both the vascularity and the ability to recover that seems integral.
I feel to some degree it's how the muscles are fed.
But also there's smthg about healing cycles ( ala naviaux) that seems to put me into shutdown and have zero tolerance for exercise or stress.
It's not the stress itself but the ability to recover etc

 

[andyguitar]

There's something about both the vascularity and the ability to recover that seems integral.
I feel to some degree it's how the muscles are fed.
But also there's smthg about healing cycles ( ala naviaux) that seems to put me into shutdown and have zero tolerance for exercise or stress.
It's not the stress itself but the ability to recover etc

Well the main point in this paper, in the sense of the many other papers it's based on, is that there is something wrong with oxygen levels/delivery and that causes damage to muscles. And also causes an imbalance in intracellular minerals. So we could describe it as hypoxia. Hypoxia does effect intacellular mineral levels. Also worth noting that hypoventilation- shallow breathing- can have that effect. Which makes me wonder if those who have me/cfs and have been diagnosed with sleep apnea are also shallow breathing when awake and that is the cause of their "me/cfs".

 

[Oliver3]

Well the main point in this paper, in the sense of the many other papers it's based on, is that there is something wrong with oxygen levels/delivery and that causes damage to muscles. And also causes an imbalance in intracellular minerals. So we could describe it as hypoxia. Hypoxia does effect intacellular mineral levels. Also worth noting that hypoventilation- shallow breathing- can have that effect. Which makes me wonder if those who have me/cfs and have been diagnosed with sleep apnea are also shallow breathing when awake and that is the cause of their "me/cfs".

I agree with everything you say but shallow breathing is common in all people with anxiety disorders.
I trained with the classical buteyko school to learn how to control my breathing. . I got to the point where I could hold my breath for three minutes on a normal breath and I trained myself to not hyperventilate. That's what buteyko is. The call it the Siberian strangle!!!
Funnily enough buteyko taught us to wake at three in the morning to do a pause. We also taped our mouths to get better sleep with no apnea. Again it helps you to feel oxygenated. But it didn't cure my lack of stamina.. there's smthg in the way electricity and mitochondria are not working properly. I know we know all this
I got many benefits from doing it. There's smthg really deep going on in me patients that's related to our very tissue structure. I just feel that so intuitively.. I have no resilience like I say my brother has a severe anxiety disorder, but he doesn't have PEM, . Doesnt have migraines. Can't feel his pulse all over his body etc etc..all that dysautonomia stuff...he just doesn't have. Why?
If there's one thing I know about , it's breath work and I'd recommend buteyko, and to some extent hof, or Simon Olivier borg. They all take different approaches to the same end.
I can breathe two breaths a minute for hours. It helps. It's not the panacea tho.
Maybe there's a subset of people who it does.

What worries me is, my father's side of the family. They all had anxiety disorders but were extremely fit and lived into their nineties.

The males in my mum's side of the family died of heart attacks in their mid forties.
Guess whose frame I've got? Not my dads.

There's smthg shutting down energy production then a cascade goes from there and there's something wrong or not strong with the cardio system. That's in my experience

 

[sb4]

Can't feel his pulse all over his body

would you say you have a chronic bounding pulse? Most with ME / POTS don't have this. It's my worst symptom.

 

[Oliver3]

would you say you have a chronic bounding pulse? Most with ME / POTS don't have this. It's my worst symptom.

It's not chronic in terms of all the time every minute..but it's there most days and in a crash it's worse it's a freaking nightmare isn't it

 

[Oliver3]

would you say you have a chronic bounding pulse? Most with ME / POTS don't have this. It's my worst symptom.

If I didn't take bets blockers maybe it would be chronic

 

[sb4]

It's not chronic in terms of all the time every minute..but it's there most days and in a crash it's worse it's a freaking nightmare isn't it

Absolute nightmare mate. I've had it for 13 years straight day and night. Last few months it's been really strong. It feels like my ANS is constantly being lit up.

I'd describe it as imagine somebody jumped out at you and said boo and it caused you to jump and you can feel your heart pounding in your chest for a couple of seconds. It's like that but 24/7.

I've been talking with a few others on discord who have the same problem. Some have it started from COVID, some from a bad trip on drugs, some from a panic attack.

Makes me think, if the onset was panic attack and drug trip then maybe the fact that my onset was post viral isn't that important. Maybe my brain wiring has just got stuck in this loop somehow.

 

[andyguitar]

I agree with everything you say but shallow breathing is common in all people with anxiety disorders.
I trained with the classical buteyko school to learn how to control my breathing. . I got to the point where I could hold my breath for three minutes on a normal breath and I trained myself to not hyperventilate.

Ah, by shallow breathing I mean hypoventilation which has a different effect than hyperventilation. Neither is good.

The males in my mum's side of the family died of heart attacks in their mid forties.
Guess whose frame I've got? Not my dads.

Then you need to keep an eye on your cholesterol levels.

There's smthg shutting down energy production then a cascade goes from there and there's something wrong or not strong with the cardio system. That's in my experience

Hypoxia leads to reduced mitochondrial ATP production. Cells respond by switching to glycolysis for energy production. Less efficient. Could be the reason for the energy deficit.

 

[Oliver3]

No

Ah, by shallow breathing I mean hypoventilation which has a different effect than hyperventilation. Neither is good.

Then you need to keep an eye on your cholesterol levels.

Hypoxia leads to reduced mitochondrial ATP production. Cells respond by switching to glycolysis for energy production. Less efficient. Could be the reason for the energy deficit.

There's a big misunderstanding about breathing. Have you heard of the bohr effects? The more you breath the less oxygenated the tissue. The Indian yogis knew a long time ago that over breathing is a way of dispelling carbon dioxide. C02 is vital in that its needed to push oxygen into the cells. The higher your tolerance to c02. The better the affinity and therefore efficiency of oxygen delivery.
Hbot would work for all c02 sufferers if this was the root problem.
I had a calcium score of my arteries. They're clean as if four years ago but I was very ill then and now.
It's way more complex than just oxygen delivery.
I hear you about hypoxia. As Ron said, this looks a little like sepsis. But it's not.

The electrons are not working properly .bthe mitos aren't. I've been sick since I was 11. I could still do stuff as a kid. Was in the cross country team. One of the fastest in the year
But I was never well.

It's eds combines with" x "combined will th some kind of mental, physichal biological trauma.

All cardio systems are not made from the same connective tissue. Why are some people inherently strong and resilient, like my brother despite a high stress job and emotional issues and early childhood trauma.?
Tho cholesterol is important, hyperinsulimia is more important. My half sister has PCOS and connective tissue issues. She has blood sugar issues and has to be careful. People with PCOS are predicated towards all the things we see in the RCCCX theory .My brother who is my full blood can do whatever he wants. He's fit as a fiddle.
It's smthg in the connective tissue of the vasculature that's most important.
Like you can have clean arteries and still have angina. Why is that?
Our capillary beds seem different. There's preload failure in many patients and some with smaller hearts etc.
But even all this doesn't account for why we are so ill in my opinion.
I'm certainly not trying to be argumentative. But like I say, there's many people with anxiety disorders that don't have m.e.

 

[Oliver3]

In my experience, anxiety disorders are more common in people with connective tissue problems.
In general even those who don't have connective tissue problems as they get older become less resilient to stress. Why? It's an interesting question to me..

My point is..yes, we are a stress phenotype . We are susceptible. But the stark nature of how Illvww get is not down to breathing. I've trained ten years in breathing techniques.bi know it's not that from my experience.bgetting oxygen into tissues is important. But maybe it's the vasculature that's the problem.
And maybe the hyperventilation is part of the sympathetic response to our bodies trying to compensate for the lack of oxygen at a deep level

 

[Oliver3]

Do you do anything to try and counteract these things.
I'm not sure it's totally about the brain.
For example, there was a time when strong antioxidants would stop that feeling in its tracks..no anxiety....so there's smthg dirty in the blood or smthg autoimmune.
I had the same experience Whitney had and Ron noticed. I got access to diaezepam ( it's a touching subject that one I know).
My veins relaxed straight away. Now most people would say, there you go, that's anxiety. But it didn't feel that way to me. It felt like my vascular system was being aides. I believe it helps release nitric oxide.
I know some people try n.o. donors and have success with them.
Like I've said a few times. My bro has a terrible anxiety disorder...but no m.e. so it's not the brain being switched on that's the problem in my view. It really doesn't help but about blood perfusion independent of anxiety problems.
When I was less ill, I noticed if I kept my circadian rhythms correct, I had no sympathetic issues. My illness has gone past the stage where that helps. But there's something going on at an electrical level in our cells too. I know this was looked at by Ron et Al because I contacted them and they said they were looking into electron transport chains.

I'm really glad they're looking into the muscle thing and blood and oxygen delivery.
To have drugs that give us relief would be great.
If your body can handle it, aspirin also takes the edge off those pulsing feelings.
Excuse my ramblings. The brain fog is pretty heavy.
I believe we're gonna hit on some treatments soon enough but this , as we know is such a complex disease

 

[Oliver3]

Absolute nightmare mate. I've had it for 13 years straight day and night. Last few months it's been really strong. It feels like my ANS is constantly being lit up.

I'd describe it as imagine somebody jumped out at you and said boo and it caused you to jump and you can feel your heart pounding in your chest for a couple of seconds. It's like that but 24/7.

I've been talking with a few others on discord who have the same problem. Some have it started from COVID, some from a bad trip on drugs, some from a panic attack.

Makes me think, if the onset was panic attack and drug trip then maybe the fact that my onset was post viral isn't that important. Maybe my brain wiring has just got stuck in this loop somehow.

I think there's many roads to m.e. including vaccinations, medications, trauma drugs, high stress but a viral trigger is very common. Interestingly, my mum has the same problem Ron Davies had as a child. Myocarditis. There's seems to be a genetic fault in how we process stressors particular viruses.
I wouldn't beat yourself up. It's deffo not your fault. My brother did trips, drugs etc, but he doesn't have m.e.
I know loads of people who did drugs and heavily so and they're fine.
It's some kindve fault that needs treating.
For example there was a time if I wore compression stockings, my sympathetic drive stopped. In my view, the sympathetic drive in m.e. is trying to compensate for this lack of blood delivery.

Of course we're all different. But good to share I guess.
Hang on in there. It's a living nightmare but long COVID is going to bring treatment I'm sure of that