Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

[SWAlexander]

Abstract
Background
Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls.

Conclusion
Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03616-z

Somebody on Twitter believes it could be related to Ischemia-Reperfusion (muscle oxygen deprivation).
Wouldn't a recovery period regulate calcium overload?

 

[Violeta]

@SWAlexander, Did you see this article by @HSoorei on Twitter? Would it make sense that those with ME/CFS have activation of NLRP3 and those who don't have ME/CFS exercise doesn't activate NLRP3?
https://www.frontiersin.org/articles/10.3389/fimmu.2022.926895/full#.Y5GZKMWgTVY.twitter


NLRP3: Role in ischemia/reperfusion injuries


And this is not from that article, but I am wondering if K+ efflux causes Na influx.

Mechanistically, ATP induces inflammasome activation mainly through its action on cell membrane receptor P2X7R (42, 43). After ATP engagement, P2X7R molecules form a non-selective cation channel for efflux of K+ ion.

 

[SWAlexander]

Did you see this article by @HSoorei on Twitter?

No, it was a posting in German from

https://twitter.com/i/web/status/1601581074395512833

.

I must admit while reading daily science papers for years, instead of finding clues, I become more confused than I ever was.
Reperfusion injury (i'r injury)?

efflux of K+ ion

I read this publication a while ago about K+ ion while searching for hypokalaemia, the reason why I have permanent low potassium.
Adrenaline causes potassium influx in skeletal muscle and potassium efflux in cardiac muscle in rats: the role of Na/K ATPase https://pubmed.ncbi.nlm.nih.gov/3025540/

I still can´t make a connection between low potassium, skeletal muscle and adrenaline.
Is there a simple way to explain this? I think I have a neural overload (brain damage)

 

[Violeta]

No, it was a posting in German from https://twitter.com/i/web/status/1601581074395512833.

Translation:

"The resulting calcium overload impairs mitochondrial metabolism and the endothelium, further worsening the energetic situation in a vicious cycle that may explain post-exertional malaise, exercise intolerance, and chronicity."

Oh, it's the calcium!

 

[Violeta]

No, it was a posting in German from

https://twitter.com/i/web/status/1601581074395512833

.

I must admit while reading daily science papers for years, instead of finding clues, I become more confused than I ever was.
Reperfusion injury (i'r injury)?


I read this publication a while ago about K+ ion while searching for hypokalaemia, the reason why I have permanent low potassium.
Adrenaline causes potassium influx in skeletal muscle and potassium efflux in cardiac muscle in rats: the role of Na/K ATPase https://pubmed.ncbi.nlm.nih.gov/3025540/

I still can´t make a connection between low potassium, skeletal muscle and adrenaline.
Is there a simple way to explain this? I think I have a neural overload (brain damage)

Oh, thanks, that's why I couldn't find it.

So sodium influx causes calcium influx.

I cannot figure out, either, why adrenaline causes potassium influx in skeletal muscle and efflux in cardia muscle. I tried to figure it out by looking up alpha and beta adrenergic receptors, but that just messed with my mind.

Do you have low potassium symptoms and low blood levels? Do you take a supplement?

 

[SWAlexander]

Oh, it's the calcium!

Good point. Now how do we approach calcium overload?

 

[SWAlexander]

Do you have low potassium symptoms and low blood levels? Do you take a supplement?

Low potassium blood levels. The first time tested in 2016 and low ever since. The recommendation by UNMH was 2 bananas per day. I followed the protocol for years but potassium blood levels remain low.

here we go again in circles. I mentioned once before that MR/CFS could be related to Addison's disease
According to https://www.mayoclinic.org/diseases-conditions/addisons-disease/symptoms-causes/syc-20350293
Can adrenal insufficiency cause low potassium?

With adrenal insufficiency, the inability to increase cortisol production with stress can lead to an addisonian crisis. An addisonian crisis is a life-threatening situation that results in low blood pressure, low blood levels of sugar and high blood levels of potassium.

 

[SWAlexander]

but that just messed with my mind.

You are not alone. Still trying to get the connection, maybe tomorrow.

 

[Violeta]

Good point. Now how do we approach calcium overload?

I think they forgot to ask the question 'what caused the sodium influx in the first place?'

And I think I found the answer, inflammation.

That's what this article is about.
https://www.frontiersin.org/articles/10.3389/fimmu.2022.926895/full#.Y5GZKMWgTVY.twitter

 

[Consul]

Trying to summarize. In the discussion section they talk about all this. Sounds like a mix of many things that gones wrong and suddenly your caught in a vicious cycle.

Beta adrenergic receptor dysfunction leading to hypostimulation of the sodium-potassion exchanger. So its not made to export sodium properly.

Hypoperfusion causing a poor energy state in the muscles, e.g because of hypoxia leading to cellular acidosis. So with both low energy and acidosis you have poor supply of ATP and lots of H+ protons you have to remove and this cost alot of ATP as well as increased cellular sodium because you have to use the proton-sodium exchanger.

So now you have two different problems thats causing increased cellular sodium so you have to get rid of it through the calcium-sodium exchanger but that runs into the problem where you import alot of calcium into the cell which further can mess up the mitochondrial function and they mention that it causes endothelium function as well - further enhancing the problems you already have.

So if there are autoantibodies messing with Beta- adr receptors then hopefully the ongoing trial with darutumumab will pick it up. Also i would guess that the neurological symptoms are caused by the ANS trying to compensate for this mess.

 

[BrightCandle]

This might be one of the places all that salt went. The main way I solved my dizziness was adding salt, I have now "caught up" but I need a lot more daily than I used to before I got ill. My body leached all the salt from me and I had a lot of trouble early on getting hydrated properly, now I need daily electrolytes.

 

[SWAlexander]

My body leached all the salt from me and I had a lot of trouble early on getting hydrated properly, now I need daily electrolytes.

Very interesting. I also was graving salt. Then I had a TSH test, which turned out normal.
I did not believe the result, so I had my thyroid checked with very bad results. Post #29

 

[SWAlexander]

inflammation

Oh yes, it is always inflammation that goofs up the whole ANS system.
What is the answer? Steroids, Methotrexate that calms your immune system?
But here is the problem. To take Methotrexate you need good liver test results otherwise there will be kidney bleeding problems.
I had very good liver test results before I was put on Methotrexate once a week, for 3 months. Results: kidney bleeding.
I´m on Hydrocortisone, still have plenty of inflammation.
My question for a "cure" would be, what is the trigger and how do we remove what triggers inflammation?
If it is one of the 9 different herpes or any other virus, we are doomed because there is no cure.
Treating symptoms is just a merry go round.

And here is more to the infection / inflammation merry go round.
Impact of pre-existing chronic viral infection and reactivation on the development of long COVID
https://pubmed.ncbi.nlm.nih.gov/36454631/
Results:
We observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen (EBNA) IgG levels, but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52).

 

[SWAlexander]

Science knows that every virus has a nucleus.

Here is my big question.
1. What seam to be the problem with destroying the nucleus of the virus outside the human body?

2. how can the virus nucleus be eliminated when it has already entered the human (or mammalian) body without damaging the organ or human DNA?

This could be a challenge for Crisper cas9 to alter virus DNA to make it ineffective.

 

[Violeta]

Oh yes, it is always inflammation that goofs up the whole ANS system.
What is the answer? Steroids, Methotrexate that calms your immune system?
But here is the problem. To take Methotrexate you need good liver test results otherwise there will be kidney bleeding problems.
I had very good liver test results before I was put on Methotrexate once a week, for 3 months. Results: kidney bleeding.
I´m on Hydrocortisone, still have plenty of inflammation.
My question for a "cure" would be, what is the trigger and how do we remove what triggers inflammation?
If it is one of the 9 different herpes or any other virus, we are doomed because there is no cure.
Treating symptoms is just a merry go round.

And here is more to the infection / inflammation merry go round.
Impact of pre-existing chronic viral infection and reactivation on the development of long COVID
https://pubmed.ncbi.nlm.nih.gov/36454631/
Results:
We observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen (EBNA) IgG levels, but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52).

Inflammation in my knee spreading through my leg muscles is really bothering me right now. I don't know what to do. This is not the first time I've had this. I don't know what made it kick in again, but maybe starch. This time trying starch I avoided gluten, but I guess that isn't good enough.

Manuel Ruiz talks about lymphoid aggregates in the knees containing B cells infected with ebv. Maybe I should think about from that point of view. I just don't know. I'm so tired, too. Just really depressing.

 

[SWAlexander]

I just don't know. I'm so tired, too. Just really depressing.

I have experienced the same for months. It is elevated inflammation. Have you been checked for thrombosis? In my case, it was potassium deficiency in addition.

 

[bertiedog]

Can I put a word in here for the role of the Thyroid in muscle metabolism because from my experience it is MASSIVE. That is if one has an underfunctioning thyroid which is probably almost guaranteed with a long standing, severe illness like ME/CFS, then there is no way one's muscles are going to function correctly.

From my experience as a long time sufferer of hypothyroidism (over 27 years but not always with the blood results to show it) I can experience very different function of the muscles, especially in my legs depending on what thyroid medication I am on. This has become very obvious to me in the past 3 months when I realised my usual medication of natural dessicated thyroid or NDT plus a tiny amount 25 mcg thyroxine wasn't working or enough for me as I had zero energy and could hardly walk more than 10 minutes. I would then experience a lot of pain and lock up of my leg muscles plus I was getting daily migraines. I also realised I could hardly hold a hairdryer for enough time to dry my short hair.

I should say that the adrenal bit is also relavant to me as I have been on between 5-6.5 mg Prednisolone for 21 years as I have adrenal insufficiency but I don't think its quite at Addison's level (its never been tested) but I did have 2 episodes of adrenal crisis in 2007 when I had come off the steroid as I had a short period when it looked as if my adrenal function had picked up and it was ok for 3 months but then I had a minor 1st crisis with diarrhoea and vomitting but then a few months later when I had restarted my steroid but at a very small dose I had a major crisis again with uncontrolled diarrhoea and vomitting but I ended up passing out on the toilet and falling to the ground and was unable to move I just had to lie there until help came as luckily I wasn't alone. I remember everything was black and I couldn't move a muscle and ended up being dragged into my lounge after I was given some h/c (but not enough). There was zero energy and I couldn't ever sit up, I just knew I had to get some steroid in me.

I guess its obvious that my sodium had plummeted but I was in no fit state to realise this!

Anyway after that I knew that I could never come off my steroid but it took some time to be able to tolerate any thyroid medication because I had to bulld up my adrenal function.

I realise I am hijacking this thread so better stop now but if anybody is interested in my experience of how the workings of the thyroid (obviously with support of adrenal meds if necessary) can hugely affect the working of our muscles. It's definitely to do with T3, the active thyroid hormone btw.

Pam

 

[SWAlexander]

hijacking this thread

No Pam, you are NOT hijacking this thread. Thank you for your post.
I welcome your experience very much since I have the same.
Only after my T3 was over the roof, I could convince my doctor that I need a thyroid check in addition to my adrenal insufficiency.
There are people I know personally who have (some of them with milder symptoms), never had a preventive full hormone checkup.
I call this ignorance and medical neglect.

Maybe we should make a list of the most needed tests:
Catecholamines (dopamine, norepinephrine, and epinephrine), cortisol/ACTH, TSH, (and even prostaglandins), etc.

This mineral test would be a beginning that could lead to a preliminary diagnosis:
magnesium, selenium, zinc,
calcium, potassium, sodium,
phosphorus, chromium, copper,
manganese, molybdenum +
aluminum, antimony, arsenic,
barium, beryllium, bismuth,
lead, cadmium, cesium, cerium,
gadolinium, gallium, gold,
indium, iridium, cobalt,
nickel, palladium, platinum,
mercury, silver, strontium,
thallium, titanium, uranium,
vanadium, tin, zirconium

 

[Violeta]

Can I put a word in here for the role of the Thyroid in muscle metabolism because from my experience it is MASSIVE. That is if one has an underfunctioning thyroid which is probably almost guaranteed with a long standing, severe illness like ME/CFS, then there is no way one's muscles are going to function correctly.

From my experience as a long time sufferer of hypothyroidism (over 27 years but not always with the blood results to show it) I can experience very different function of the muscles, especially in my legs depending on what thyroid medication I am on. This has become very obvious to me in the past 3 months when I realised my usual medication of natural dessicated thyroid or NDT plus a tiny amount 25 mcg thyroxine wasn't working or enough for me as I had zero energy and could hardly walk more than 10 minutes. I would then experience a lot of pain and lock up of my leg muscles plus I was getting daily migraines. I also realised I could hardly hold a hairdryer for enough time to dry my short hair.

I should say that the adrenal bit is also relavant to me as I have been on between 5-6.5 mg Prednisolone for 21 years as I have adrenal insufficiency but I don't think its quite at Addison's level (its never been tested) but I did have 2 episodes of adrenal crisis in 2007 when I had come off the steroid as I had a short period when it looked as if my adrenal function had picked up and it was ok for 3 months but then I had a minor 1st crisis with diarrhoea and vomitting but then a few months later when I had restarted my steroid but at a very small dose I had a major crisis again with uncontrolled diarrhoea and vomitting but I ended up passing out on the toilet and falling to the ground and was unable to move I just had to lie there until help came as luckily I wasn't alone. I remember everything was black and I couldn't move a muscle and ended up being dragged into my lounge after I was given some h/c (but not enough). There was zero energy and I couldn't ever sit up, I just knew I had to get some steroid in me.

I guess its obvious that my sodium had plummeted but I was in no fit state to realise this!

Anyway after that I knew that I could never come off my steroid but it took some time to be able to tolerate any thyroid medication because I had to bulld up my adrenal function.

I realise I am hijacking this thread so better stop now but if anybody is interested in my experience of how the workings of the thyroid (obviously with support of adrenal meds if necessary) can hugely affect the working of our muscles. It's definitely to do with T3, the active thyroid hormone btw.

Pam

Pam, this is a good point, and I actually have recently been considering thyroid issue as a cause of my leg issues.

I have had low body temperature for many years, but when I had testing done my TSH was okay, ( I forget what T4 was, and they didn't test T3), they told me there was nothing wrong. I know most are familiar with that story.

My temperature has rarely been above 97.7, and recently has gone down to 96.6. I have tried natural dessicated thyroid and it made things worse.

There are other things that can affect the correct functioning of thyroid, I know everyone here knows that, but it's so difficult to find a doctor that would help figure it out. The doctors in my area that seem to be more in tune with stuff like that charge a horrendous amount of money just to be in their practice.

Anyway, I am working on this problem now, we'll see where it takes me.

There may be something in my thyroid (mercury, etc)?
Difficulty somewhere turning T4 into T3?
Something wrong with liver?

First of all, removing starches, absolutely all goitrogens from diet.
Consistently taking selenium
Consistently taking seaweed that is high in iodine
Tyrosine

And you're right, Pam, to bring up adrenals, too.

Hope you are feeling better

 

[Violeta]

And look at this homeopathic materia medica list of symptoms for thyroidinum. I was born with amblyopia!


Thyroid produces anćmia, emaciation, muscular weakness, sweating, headache, nervous tremor of face and limbs, tingling sensations, paralysis. Heart rate increased, exophthalmus and dilation of pupils. In myxśdema and cretinism its effects are striking. Rheumatoid arthritis. Infantile wasting.

Rickets. Delayed union of fractures. In half grain doses twice a day over a considerable period said to be effective in undescended testicle in boys. Thyroid exercises a general regulating influence over the mechanism of the organs of nutrition, growth and development. Thyroid weakness causes decided craving for large amount of sweets.

Of use in psoriasis; and tachycardia. Arrested development in children. Improves the memory. Goitre. Excessive obesity. Acts better with pale patients, rather than those of high color. Amblyopia. Mammary tumor. Uterine fibroid. Great weakness and hunger, yet loses flesh. Nocturnal enuresis. Agalactea. Begin treatment early in pregnancy. Dose 1 1/2 gr. 2 to 3 times daily. Vomiting of pregnancy (give early in morning before patient gets up). Fibroid tumors of the breast, 2x trit. Dilates arterioles (Adrenaline contacts them). Sensation of faintness and nausea. Marked sensitiveness to cold Hypothyroidism after acute diseases, i.e, weakness. Easy fatigue, weak pulse, tendency to fainting, palpitation, cold hands and feet, low blood pressure, chilliness and sensitive to cold (Thyroid 1x3 times daily). Has a powerful diuretic action in myxodema and various types of edema.

Check the link for more interesting symptoms broken down by part of body.

http://www.homeoint.org/books/boericmm/t/thyr.htm