Debilitating fatigue is a symptom of many other illnesses, like EDS, and reduced mitochondrial capacity could be the culprit.
a model exploring mitochondrial dynamics – may help explain what’s causing the post-exertional problems
this study extended a well-known metabolic model explaining what happens to the mitochondria in the skeletal muscles during exercise. The authors enhanced it by adding some processes to it (lactate accumulations / purine degradation) known to occur in the mitochondria.
The Study
The model covers two parts of the inner mitochondria – the cytosolic space and the mitochrondrial matrix. It does not cover interactions between the mitochondrial membrane and the rest of the mitochondria
The production of the model was sparked by a number of findings (reduced ATP production and peak oxygen uptake) suggesting problems with aerobic (oxygen related) energy production, were present in chronic fatigue syndrome. Findings of increased acidification, reduced anaerobic threshold and prolonged pH recovery times suggested that anaerobic respiration – a less efficient and more toxic form of energy production – was attempting to compensate for a broken aerobic energy production system.
Results
Several studies suggest that the rates of ATP production/oxidative phosphorylation (mitochondrial capacity) are about 65% of normal in ME/CFS.
This model suggests reduced mitochondrial capacity could be causing the ATP problems and the increased acidosis and lactate accumulations found in several studies. (The increased acidosis is the problem, lactate is not. Lactate is produced to protect the cell from acidification.)
Healthy people are able to maintain an ATP level during exercise that protects their mitochondria. The models suggested, however, that the minimum ATP levels maintained in ME/CFS patients during exercise, may be significantly lower
Acidosis Plays Key Role
Anaerobic respiration greatly increases the rate of acidosis. Acidification is produced by the breakdown (hydrolysis) of ATP and is related, if I have it right, to increased rates of cell damage
Prolonged Recovery Periods
The reduction in the adenine pool means the cell will need time in the post-exercise period to get back to normal
The model predicted it would take 3-5 times longer for the ATP levels in the muscles of ME/CFS patients to return to normal after exercise than for healthy controls. The model predicted that short (30 seconds), intense exercise periods would be easier for “ME/CFS patients” to recover from.
The model predicted it would take 49 hours for ATP levels in the muscles to return to normal after a longer (30 minutes) but more moderate period of exercise.
Recovery Reversal
The model suggested that mitochondrial depletion results in more difficulty with longer bouts of moderate exercise, than with shorter bouts of intense exercise.
This pattern was opposite to that found in the controls.
It should be emphasized that this is a model, and therefore does not necessarily demonstrate what’s happening in ME/CFS.
Study referred to in this article:
In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome | Nicor Lengert, Barbara Drossel Institute for Condensed Matter Physics, Technische Universität. Biophysical Chemistry 202 (2015) 21–31
Highlights
- Metabolite dynamics in skeletal muscles are simulated during high intensity exercise.
- We take into account exercise induced purine nucleotide loss and de novo synthesis.
- A reduced mitochondrial capacity is assumed for CFS patients.
- CFS simulations exhibit critically low levels of ATP and a prolonged recovery time.
- Additionally an increased acidosis and lactate accumulation is observed in CFS.
Abstract
Post-exertional malaise is commonly observed in patients with myalgic encephalomyelitis/chronic fatigue syndrome, but its mechanism is not yet well understood.
A reduced capacity for mitochondrial ATP synthesis is associated with the pathogenesis of CFS and is suspected to be a major contribution to exercise intolerance in CFS patients.
To demonstrate the connection between a reduced mitochondrial capacity and exercise intolerance, we present a model which simulates metabolite dynamics in skeletal muscles during exercise and recovery.
CFS simulations exhibit critically low levels of ATP, where an increased rate of cell death would be expected.
To stabilize the energy supply at low ATP concentrations the total adenine nucleotide pool is reduced substantially causing a prolonged recovery time even without consideration of other factors, such as immunological dysregulations and oxidative stress.
Repeated exercises worsen this situation considerably. Furthermore, CFS simulations exhibited an increased acidosis and lactate accumulation consistent with experimental observations.
For more info on mitochondria, see tag:
https://edsinfo.wordpress.com/tag/mitochondria/
EDS and Chronic Pain News & Info 
This is why I love that your blog feeds into my website. I do believe that CFS, Fibro, etc. are linked somehow to mitochondrial depletion. From the physiological perspective as someone who has all of these distinctly conditions and separate from EDS, I can see how each is different, yet can be affected by one underlying trigger that causes symptoms to flare. Obviously, EDS is how our bodies are built, but what if we find a gene(s) that can both affect the structure and integrity of our connective tissues in utero. Furthermore, this same gene mutation could cause us to be predisposed to a second comorbid condition that triggers CFS, Fibro and autoimmune conditions. Or, maybe the gene mutation causes changes in energy metabolism that affects the function of the mitochondria, thus resulting in CFS, Fibro., etc. when the system is pushed? It does seem that there could be a few genes that do this. What they would be .. Not sure. Maybe something like CBS gene mutations, ones that were previously not thought to cause any physical symptoms and/or lead to a full CBS gene deletion, which leads to homosysteinuria? CBS gene mutations have been associated with a slew of CTD related symptoms and issues, but it’s previously been thought that a person is only symptomatic if he/she has the autosomal recessive disorder, vs. just one mutation or is a carrier. I can’t help but wonder about a gene like the CBS gene, because it’s mutations have been associated with issues processing foods that contain sulfur, the MTHFR mutation, triggering mast cell issues and issues mentioned above that can cause CTD symptoms. If these mutations have already been associated with Marfan’s-like CTD issues, can we really discount the idea that just maybe these genes are not only pathogenic when a the autosomal recessive disorder is present, but maybe when we are also just are carriers? A mutation with a gene such as this, seems to give the idea that there maybe something that causes all issues, as well as links EDS to Mast Cell issues. It would also then make sense that mast cell issues could be the other underlying condition that is triggered, thus resulting in CFS, Fibro and other conditions to flare. Additionally, we now know that the immune system does reach the brain bc lymph vessels have been found in brain tissue, when they previously did not think that the lymph system was above the neck. The question is…what could occur during mast cell reactions that affect the mitochondria of the cells? Or, maybe it was the same trigger that cause mast cells to flare and also caused a change in the energy production in the mitochondria, therefore resulting in CFS. Sorry for the long comment, but I think we are close to finding the link between all of this and maybe then closer to finding the gene(s) for HEDS.
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