Hi, guys.
You have probably read my posts on glutathione, mitochondria and exercise in ME/CFS before, but I just want to reiterate some things here on this thread, in case there are people reading this who haven't.
As you probably all know, the muscles are powered by ATP, and the lion's share of the ATP is normally produced by the mitochondria.
There is considerable evidence for mito dysfunction in ME/CFS, especially the work of Myhill et al. in the UK.
This mito dysfunction means that the rate of production of ATP is limited, as is the utilization of oxygen and the production of carbon dioxide. These have all been documented by lab testing.
The use of both carbs and fats for fuel in ME/CFS is limited to lower rates than normal. Amino acids from protein are more readily burned for ATP production in ME/CFS. This accounts for the lower weight gain and higher energy status that most PWMEs experience if they adopt a high-protein diet.
The initial cause of the mito dysfunction in ME/CFS is a drop in glutathione and a corresponding rise in oxidative stress. This inhibits enzymes in both the Krebs cycle and the electron transfer chain (respiratory chain) in the mitochondrion, and therefore limits the rate of production of ATP. These features have been documented by lab testing.
As time goes on, additional factors exacerbate the mito dysfunction. These include lack of sufficient creatine, carnitine and coenzyme Q10. These all require methylation for their synthesis, but the methylation cycle becomes partially blocked because of a chain of events involving a functional deficiency of vitamin B12, which is caused by the depletion of glutathione. In addition, toxins and pathogens build up over time because of the dysfunction of the immune system and the detox system that result from the vicious circle involving glutathione depletion and the methylation cycle partial block. Furthermore, the cells become unable to properly regulate their essential minerals levels, because there is insufficient ATP to power the membrane ion pumps. All of these aspects have also been documented by lab testing.
It's true that many PWMEs experience some benefit by boosting their glutathione levels by various direct means. However, these gains are only temporary. If the boosting is stopped, the benefits disappear. This is supported by the experiences of many PWMEs over several years.
The way to bring permanent benefits for most PWMEs is to address the partial methylation cycle block with active forms of folate at RDA-level dosages, together with high-dose B12 (hydroxocobalamin, methylcobalamin, and/or adenosylcobalamin, but not cyanocobalamin), taken either sublingually or by injection (some other nutrients will likely be necessary, also, depending on deficiencies). This will correct the partial methylation cycle block and will also cause glutathione to come up automatically and to stay up, in most PWMEs. This has been shown by a clinical study.
Some exercise is beneficial, as noted by others here. However, overexercising likely damages the mitochondria, due to the elevated oxidative stress. If mitochondria become severely damaged, they are destroyed by autophagy, and new mitochondria are normally produced by fission of existing mitochondria. I am concerned that if too much exercise is undertaken in ME/CFS, over time the damage to the mitochondrial DNA by the oxidative stress may be severe enough that it is no longer possible to replace damaged mitochondria with healthy new mitochondria. I think this can result in a chronic deficit in energy availability for cells, including muscle cells, even after the vicious circle mechanism is corrected.
So my message is please don't overdo exercise while you have this vicious circle mechanism in play, and please give a methylation-type treatment a try if you have not already done so, because I believe it is the best hope for fixing this problem.
Best regards,
Rich
Thanks for following up on this. cheers
