The effect of ME/CFS severity on cellular bioenergetic function (Tomas et al. 2020)

Diwi9

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The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function
  • Cara Tomas ,
  • Joanna L. Elson,
  • Victoria Strassheim,
  • Julia L. Newton,
  • Mark Walker

  • Published: April 10, 2020
Abstract
Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts. We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs. Both ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction. Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were calculated by taking into account respiratory acidification. This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function. Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts. This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231136
 

Diwi9

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On classifying level of severity:
There were two cohorts of ME/CFS patients with differing levels of disease severity included in this study. The moderately affected cohort had reduced mobility due to the disease but were able to attend the local fatigue clinic. Most of the moderately affected patients were able to walk into the clinic unaided but a small proportion needed the assistance of crutches or a wheelchair. The severely affected cohort were either housebound or bedbound by the disease and were unable to attend the clinic even with the use of a wheelchair. This is in line with the recognised classifications of disease severity in ME/CFS as outlined in the NICE guidelines and the International Consensus Criteria (ICC) [16, 17]. ME/CFS symptom severity is defined by the reduction in activity compared to pre-illness. Moderately affected patients are mostly housebound by the disease while severely affected patients are mostly bedridden [17].
 

ljimbo423

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We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs. Both ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort.

This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction.

This seems to say that mitochondrial dysfunction does not cause the different levels of disease severity in ME/CFS, (ie- mild, moderate and severe). Am I missing something here or is this what they are saying?
 

ljimbo423

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This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.

I think this is the answer to my last post.:)

Glycolysis takes place in the cytoplasm of the cell. Therefore it's separate from the mitochondria.

So it seems they are saying what separates moderately affected patients from severely affected patients, is that the severely affected patients have impaired glycolysis and mitochondrial dysfunction.

Where the moderately affected patients only have mitochondrial dysfunction.
 

Diwi9

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I think this is the answer to my last post.:)

Glycolysis takes place in the cytoplasm of the cell. Therefore it's separate from the mitochondria.

So it seems they are saying what separates moderately affected patients from severely affected patients, is that the severely affected patients have impaired glycolysis and mitochondrial dysfunction.

Where the moderately affected patients only have mitochondrial dysfunction.
They also make the point because the mitochondrial dysfunction effect is equal in both subsets, we cannot blame it on deconditioning. The authors were unable to determine if the glycolysis issues are the cause of the condition of the severe state or an effect of the condition of the severe state (basically whether glycolysis is impaired and thus caused a severe state, or if the fact that the severe are so limited in their physical function that is causing impaired glycolysis).
 

ebethc

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They also make the point because the mitochondrial dysfunction effect is equal in both subsets

does this mean that ALL CFS patients tested had mitochondrial dysfunction, and a subset also had impaired glycolysis?

we cannot blame it on deconditioning.

what is deconditioning

The authors were unable to determine if the glycolysis issues are the cause of the condition of the severe state or an effect of the condition of the severe state (basically whether glycolysis is impaired and thus caused a severe state, or if the fact that the severe are so limited in their physical function that is causing impaired glycolysis).

interesting..

--
what are the tests used to evaluate mitochondrial function and glycolysis?

what kind of doctor evaluates mitochondrial function?

do glycolytic impairments make it difficult to process carbs?
 
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„This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction.“

That sentence is a bit confiusing. I think they can just tell if there is mito dysfuncion or not. I wonder if prusty is able to quantify the mito function and tell if there is a correlation to the severety.