Only downregulation of the electron transport chain could explain catastrophic loss of ATP and catastrophic downregulation of NAD+/NADH.
False. Categorically. Its not the only possibilility at all, though it is a possibility. There may be nothing wrong with regulation or function of the electron transport chain. It could easily be somewhere else. Such as mitochondrial transporters. Or oxygen supply with tissue hypoxia.
What can be said, which you might be saying but not clearly enough, is that there is insufficient mitochondrial energy production. That does mean the ETC is not producing as much energy as we need, but it does not mean the problem is in the ETC, its regulation or function. Its a possibility, not a certainty.
I have used bicarb in the past and was not impressed, but that does not mean it wont work in combination with things I hadn't tried at the time. Very often we need combinations and single effects don't work as well as combination therapies. What is more interesting is to try bicarb in conjunction with increased activity. I have not tested this yet to see if it alters PEM for me.
Blood oxygen saturation is irrelevant in local tissue hypoxia. Its a deceptive figure. Its also irrelevant if oxygen is not properly dumping where needed, which can induce local tissue hypoxia. It tells you about the potential supply, but not if its used. Its indicative, nothing more. We need some way to measure our local oxygen and carbon dioxide in working muscle. We need some scan to measure small vessel perfusion in working muscle.
Now as to regulation, if its a regulation problem then its probably hormonally mediated, and by that I include immune hormones, at least in muscle. Its less clear about the brain. I would bet its eicosanoid mediated, but that could easily be wrong.
I would not want to rule out viral toxin mediation though, or even mycotoxins, at least at this point.
Detox issues can also do it. It turns out (and I have not investigated the issue in depth) that even salicylates can cause issues leading to poor mitochondrial function. I wonder if this is a direct effect, or secondary due to eicosanoid imbalance. I may have to look into this.
One thing we cannot be sure of though is whether or not the mitochondrial problem is the primary problem. I very much doubt it. I think its secondary, but that its the primary cause of much of our pathophysiology.
Currently it looks like the primary pathophysiology is immune disregulation in the brain,, probably in the microglia. However the driving force could even be pathogens such as enteroviruses.
Its important not to prematurely confuse pathophysiology with causation. Treating pathophysiology treats symptoms, but if the root cause is not treated then even with improved symptoms you cannot achieve a cure. We now know a lot about pathophysiology but there are still a lot of potential theories out there about causation, even without considering the cause may be something we have not investigated yet ... that is if there is a single cause and not many or a combination effect.
The simple analogy is that energy production is a long chain. We know there is a break in the chain, but that could be anywhere in that chain. In reality its more like a complex chain of spaghetti web, with loops, only linear in parts. The ETC is a few links in the chain, not the whole chain. We do know that glycolysis is working though, as we make lactate in abundance.
I do expect that supporting the electron transport chain will help, and the research indicates that both CoQ10 and NADH are helpful. I do wonder if SOD would help, and of ways to boost it.
One thing I don't think is very helpful is ATP. Ribose should be
much more effective as a supplement. An entire bottle of ATP pills would give you enough energy for only a few minutes, though it would boost the substrate pool. Ribose also boosts AMP and ADP synthesis, but much more cheaply.
