(This is a repost of a comment I made on Part III of Jen's series of articles on PEM in CFS.)
Hi, Jen.
I enjoyed your articles on PEM.
I would like to enlarge a little on the cardiovascular/energy system aspect that you mentioned.
The observed low oxygen consumption, high lactate and oxidative stress in CFS all point to problems with the mitochondria. There is abundant evidence for mito dysfunction in CFS. The most direct evidence is the work of Dr. John McLaren Howard of AcumenLab in the UK. Some of this was described in the paper by Myhill, Booth and Howard showing a correlation between lab measures of mito dysfunction and degree of disability in CFS patients.
Mito dysfunction can easily explain the basic physical and mental fatigue, as well as the diastolic dysfunction of the heart in CFS.
To explain PEM on the basis of a mito dysfunction issue requires a mechanism that worsens the mito dysfunction as a result of placing greater demands on the mitochondria. I'm aware of two possible explanations that have been suggested:
The first is the one embodied in the book by Dr. Stephen Sinatra, called The Sinatra Solution. This explanation has been applied to CFS by Dr. Sarah Myhill. The idea is that when high demand is placed on the mitochondria for ATP, and the mitochondria are not able to keep up with this demand, some of the ADP reacts with other ADP, producing ATP plus AMP. This supplies some ATP temporarily, but the AMP breaks down to adenosine and exits from the cell. Thus, the cell has to start from scratch to build new ADP, and this is a slow process, requiring synthesis of D-ribose. This time lag is what gives rise to the PEM under this hypothesis.
The second is one I suggested several years ago, and I think it may still have some viability. The idea is that the mitos are in a state of oxidative stress, as we know. In my hypothesis, this is due to depletion of glutathione. Others have different views as to the cause of the oxidative stress, including Prof. Pall and Dr. Cheney. Nevertheless, I think we agree that there is oxidative stress, as has been shown by many measurements. It is known that the most vulnerable molecules in the mitochondria to oxidative stress are the unsaturated fatty acids in the phospholipid membranes of the mitochondria. These membranes are very important to the production of ATP, because this is carried out by enzymes that are embedded in these membranes. When higher demands for ATP are placed on the mitochondria, the state of oxidative stress worsens, because oxidizing free radicals are a normal product of metabolism, and higher the metabolic rate, the higher the oxidative stress, when glutathione is depleted and thus the antioxidant enzyme system is dysfunctional. I have suggested that this extra demand thus produces more damage to the mito membranes. The cells are able to repair this damage, at least to some extent, but this takes time. I suggest that that delayed repair process could account for PEM, and that this would be consistent with other things we know about the mitochondria in CFS.
Anyway, thank you for writing about a very important aspect of CFS, and I hope your effort attracts more attention to this aspect of CFS, because I think it holds the key to developing a better understanding of this disorder.
Best regards,
Rich Van Konynenburg