Hi, Gerwyn.
Thanks for the response. I welcome disagreement--that's what makes the scientific world go 'round!
-)
I agree that there are symptoms in CFS that are attributable to mito dysfunction, for sure, such as the physical fatigue. But I also think that there are other symptoms that are caused by glutathione depletion that do not involve the mitochondria. When I first realized that glutathione is low in CFS (and there is very good evidence for that now, especially if one looks at the plasma reduced glutathione level, not just the red blood cell total glutathione, which is easier to measure but does not reflect tissue cell glutathione levels as well), I tracked down the whole list of things that glutathione is normally known to do, and it was like a roll call of things that are not being done well in CFS. If you want to see them, I've discussed some of them in my 2004 and 2007 poster papers, which can be found at cfsresearch.org by clicking on CFS/M.E. and then on my name.
As another piece of evidence, I would note that in our clinical study, in which we treated to lift the methylation cycle block, so that glutathione rose, the patients reported significant increases in their energy levels. I take that to mean that their mito function improved from this treatment, and that would be consistent with the methylation cycle block--glutathione depletion combination causing mito dysfunction.
As another piece of evidence, I have seen the urine organic acids test results from quite a few PWCs over the past several years, and quite a few show a partial block in the Krebs cycle after citric acid. It is attributable to low activity of the enzyme aconitase, and that is one of the enzymes that is known to be susceptible to oxidative stress, because of its iron-sulfur complex. Decreased glutathione results in oxidative stress. So that is consistent with low glutathione causing a partial block in the Krebs cycle, which will manifest as mito dysfunction. So again, I think this fits together well with the notion that glutathione depletion causes the mito dysfunction in CFS.
I agree that mitochondrial dysfunction is a major feature in ME/CFS, but what causes it? I don't think that either Dr. Myhill or Dr. McLaren Howard have come up with an explanation for that. The treatments given are partly substances that require methylation for their synthesis (such as Co Q-10 and carnitine), and I think that also points back to a problem with the methylation cycle, which is linked to the glutathione depletion by a vicious circle mechanism, which is what makes this disorder chronic, in my opinion. My point is that I think the pieces fit together well in this hypothesis, and I haven't heard of another comprehensive hypothesis that fits the evidence as well. But I'm certainly open to the possibility.
Best regards,
Rich