This study is fascinating. Comes out of nowhere, seemingly. I've never heard of any other me/cfs research covering sodium content in muscles. But because this is Scheinbenbogen i'm paying very serious attention. I think her work on alpha and beta autoantibodies is extremely important; I'm convinced bloodflow and endothelial dysfunction matter a lot to a subset of patients.
What i've found is the sodium study seems to be related to this hypothesis which they published in 2021. I put the key part in bold:
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Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Abstract
Chronic Fatigue Syndrome or Myalgic Encephaloymelitis (ME/CFS) is a frequent debilitating disease with an enigmatic etiology. The finding of autoantibodies against ß2-adrenergic receptors (ß2AdR) prompted us to hypothesize that ß2AdR dysfunction is of critical importance in the pathophysiology of ME/CFS. Our hypothesis published previously considers ME/CFS as a disease caused by a dysfunctional autonomic nervous system (ANS) system: sympathetic overactivity in the presence of vascular dysregulation by ß2AdR dysfunction causes predominance of vasoconstrictor influences in brain and skeletal muscles, which in the latter is opposed by the metabolically stimulated release of endogenous vasodilators (functional sympatholysis).
An enigmatic bioenergetic disturbance in skeletal muscle strongly contributes to this release. Excessive generation of these vasodilators with algesic properties and spillover into the systemic circulation could explain hypovolemia, suppression of renin (paradoxon) and the enigmatic symptoms. In this hypothesis paper the mechanisms underlying the energetic disturbance in muscles will be explained and merged with the first hypothesis.
The key information is that ß2AdR also stimulates the Na+/K+-ATPase in skeletal muscles. Appropriate muscular perfusion as well as function of the Na+/K+-ATPase determine muscle fatigability. We presume that dysfunction of the ß2AdR also leads to an insufficient stimulation of the Na+/K+-ATPase causing sodium overload which reverses the transport direction of the sodium-calcium exchanger (NCX) to import calcium instead of exporting it as is also known from the ischemia–reperfusion paradigm.
The ensuing calcium overload affects the mitochondria, cytoplasmatic metabolism and the endothelium which further worsens the energetic situation (vicious circle) to explain postexertional malaise, exercise intolerance and chronification. Reduced Na+/K+-ATPase activity is not the only cause for cellular sodium loading. In poor energetic situations increased proton production raises intracellular sodium via sodium-proton-exchanger subtype-1 (NHE1), the most important proton-extruder in skeletal muscle. Finally, sodium overload is due to diminished sodium outward transport and enhanced cellular sodium loading. As soon as this disturbance would have occurred in a severe manner the threshold for re-induction would be strongly lowered, mainly due to an upregulated NHE1, so that it could repeat at low levels of exercise, even by activities of everyday life, re-inducing mitochondrial, metabolic and vascular dysfunction to perpetuate the disease.
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SO the basic idea here is during exercise the body is supposed to clear sodium out of the muscle cells using a little pump. That pump isn't working properluy. They seem to have two theories on why, one being a lack of ATP due to unknown energy production problems. The other being problems with alpha-adrenergic receptors.
When sodium builds up too high, the muscle cells start sucking in calcium instead of spitting it out. That's when things go really bad. mitochondria stop making energy properlu and they argue the endothelium gets damaged too (weird flip from subcellular to more macrolevel tissue here?).
My takes:
1. Sounds plausible but I'm definitely nervous about the fact that so many of us with POTS benefit from high sodium diets. How can that possibly be consistent?! Presumably inceasing dietary sodium lifts plasma sodium, which increases the sodium gradient, and makes it even easier for sodium to get into cells? It leaves me wondering if maybe intracellular sodium might be beneficial/compensatory rather than pathological ... but then we do see that chart above saying higher intracellular sodium is correlated with lower strength. is that proof one way or another? idk. Notably they suggest eating more potassium. Bananas all round!
2. theories are cheap. There's enough conflicting data and moving parts in mecfs that a person with an education in biology can assemble a compelling-sounding narrative pretty easily. I'm glad they're getting data to test the theory. Sample size is small though and also, there's probably an infinity of other theories that could make sense to explain the finding, not just the one they are trying to test.
3. this must link up somehow with Australia's Griffith University team and their obsession with the trpm3 calcium channel? (prove it, disprove it, i'm not sure. griffith seems to think the trpm3 isn't working well and not enough calcium is going in the cell. What if the body has shut down trpm3 because there's enough Ca2+ in there already?)
