Cellular bioenergetics is impaired in patients with CFS (2017) Tomas, Strassheim, Newton et al

Full article paywalled
https://www.newscientist.com/article/blood-cells-chronic-fatigue-syndrome-drained-energy/
Thirteen years ago, Cara Tomas was rendered bedbound with chronic fatigue syndrome. It came on suddenly, she says, without warning signs. Even now she has good days and bad days due to the lingering effects of the disease. “A lot of people dismiss it as a psychological disease, which is a big frustration,” she says.

Tomas knows more about CFS than most. A PhD student at Newcastle University in the UK, she has just published a paper demonstrating that white blood cells in people with the disease are as listless as the people themselves often feel. “Now we’ve shown there’s a physiological difference, it could explain the whole-body fatigue shown by patients,” she says.
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If the bulk of the problem is in muscle etc. then the specifics of maximal respiratory capacity will be a little different to just white blood cells.
 
Forgive me if I've missed something stated here or presented in the paper, but to me I don't think the researchers have found what they claim to have found. The title claims they have found a causal relationship between low energy production in immune cells and CFS, but from what I've read I think they've only found a correlation between low energy production in immune cells and people with (chronic) fatigue. It could be that low energy production is a product of fatigue, chronic fatigue or just a lack of long term exercise.
 
Saturnation said:
It could be that low energy production is a product of fatigue, chronic fatigue or just a lack of long term exercise.
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Indeed, correlation does not prove causation, and the authors address this point in the Discussion:
The use of sedentary controls and activity monitors in future studies would prove beneficial to show the effect of activity levels on PBMC bioenergetics.
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But it's pretty well established via 2-day CPET, and listening to any patient, that onset of the disease precedes a lack of exercise. So while it's possible some abnormalities might be more generally applicable in other sedentary groups, it the case of ME patients the disease would still be the ultimate cause by triggering the need for sedentary behavior. And even if the abnormalities are merely a downstream result, and not at all causative, it still helps in understanding and treating the effects of ME/CFS.

Are you aware of any research indicating a similar inability for healthy sedentary subjects to increase respiratory capacity, or to compensate for low-glucose conditions? It's not an area I've read about much, but I haven't heard anything concrete about deconditioning causing these sorts of changes, just the usual vague speculations used to prop up psychosomatic theories of ME/CFS. Such speculations are so flimsy in other regards that it's never been necessary to debunk them by looking into the bioenergetics of deconditioning - though maybe it would be beneficial to do so in the context of actual science like this paper :p
 
Saturnation said:
Forgive me if I've missed something stated here or presented in the paper, but to me I don't think the researchers have found what they claim to have found. The title claims they have found a causal relationship between low energy production in immune cells and CFS, but from what I've read I think they've only found a correlation between low energy production in immune cells and people with (chronic) fatigue. It could be that low energy production is a product of fatigue, chronic fatigue or just a lack of long term exercise.
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From the bits of the paper I read they were careful to to over claim. We can talk about correlation and causation and here I think it is important to understand the findings in the context of what we know about cell biology and hence what the statistics mean in terms of the mechanisms we understand (or a further examination of mechanisms). That would be the correct way to use statistics - correlations as you say are just correlations and when they suggest something that needs to be investigated and not just assumed. I have no knowledge of biology to use to interpret the results.

In reality I think little certainty can be concluded from the paper as the sample sets are small. Too me it is a potentially interesting clue that is worth looking at in more detail. They make this comment in the discussion:

While the primary limitation of this study was sample size which resulted in underpowered analysis, particularly for the freshly isolated control cohort, it should be noted that the data presented here shows only preliminary findings. Higher sample sizes and longitudinal sample collection will be sought in the future to further validate the results obtained here, and potentially the power required to detect differences in other parameters.
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And given the results this further work looks important to do.
 
It is correct to say they have not proven causation, just association, and statistically limited association at that due to the sample size. Like @Valentijn I am interested in this in comparison to repeat CPET findings. There is no question this study needs replication on a larger data set. Muscle and perhaps other tissue also needs to be tested. The 2 day CPET protocol would also be good, however this will mean actual patients need to be recruited, but then they have to do that for skin or muscle biopsy too. Gut biopsy is another possibility. Many diseases are first investigated from blood, even if the disease is active in some other tissue. Most things wind up in blood or spinal fluid, as these both transport waste.

However for a small investigatory study the findings are remarkable. Like many such studies its possible the findings will disappear in a larger or more carefully selected cohort. They used the Fukuda criteria. However this fits with quite a number of other findings.

I just started watching a video interview by a patient with Ron Davis. He commented that they had to scrap a lot of data because they used a biobank, and get fresh samples. Biobanks use storage protocols that were adequate at the time, but with new technology they are not always acceptable. So the samples have value that is limited to those tests for which it is not going to be a problem.

For historical interest, the first indications of this I got interested in were in a paper from 1996 by Wong and others. I forget most of the details, but they concluded that glycolysis was accelerated. I accepted their data but pointed out to some biochemists that the same findings would occur if mitochondrial function was limited. The point is that this Seahorse data might be interpreted differently over time as we understand the mechanisms better.
 
Valentijn said:
Are you aware of any research indicating a similar inability for healthy sedentary subjects to increase respiratory capacity, or to compensate for low-glucose conditions? It's not an area I've read about much, but I haven't heard anything concrete about deconditioning causing these sorts of changes, ...
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I'm no biologist and I lack enough energy to become one. I'm just trying to apply my experience in logical deduction to find how concrete the findings are.

Someone suggested to me that you could make a theoretical argument based on the result from

Impact of Lifelong Sedentary Behavior on Mitochondrial Function of Mice Skeletal Muscle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981452/

I guess it's just the current nature of medical research that the title of the paper infers findings that the research doesn't actually totally support?
 
alex3619 said:
It is correct to say they have not proven causation, just association, and statistically limited association at that due to the sample size.
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I'm wondering if that paper doesn't just show that low mitochondrial function is only a symptom of fatigue and not that fatigue is a symptom of low mitochondrial function? If you take a normal healthy human and run them into the ground over a week, then test them I suspect that you might find low mitochondrial function in them as well. At least that's my theory based on what I've read in that paper.
 
Saturnation said:
I'm wondering if that paper doesn't just show that low mitochondrial function is only a symptom of fatigue and not that fatigue is a symptom of low mitochondrial function? If you take a normal healthy human and run them into the ground over a week, then test them I suspect that you might find low mitochondrial function in them as well. At least that's my theory based on what I've read in that paper.
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You think next time persons with overtraining syndrome must be used as controls?
 
lansbergen said:
You think next time persons with overtraining syndrome must be used as controls?
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If you consider that mitochondrial function could be a result of fatigue, then you need to find some way to disprove that?

Isn't that science. Come up with a theory and do your best to disprove it? Sadly I see little evidence of this approach within and outside of the science realm (though I have little experience from within).
 
Saturnation said:
Isn't that science. Come up with a theory and do your best to disprove it? Sadly I see little evidence of this approach
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Sadly this is often the case, and nearly always the case in psychopsychiatry.

With CPET data for ME or strictly defined CFS the problems are not found in sedentary controls. I do not know if this includes long term bedbound patients. Its why I think comparison of blood findings and exercise findings are essential, and why not throw in miRNA, cytokines and other blood parameters known to be be abnormal after exercise? However a proper formal comparison of repeat CPET data in ME with other diseases has not happened, aside from MS.
 
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