The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function, 2020, Tomas et al

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

 

From the discussion section (all bolding mine).

ETA: Added 2nd and 3rd quotes.

 

I see this study was based at Newcastle with Julia Newton as one of the authors.

 

I thought we hadn't previously seen good evidence of mitochondrial dysfunction in PwME?

What do you think of this, @Jonathan Edwards?

 

I still think that losing at peripheral blood mononiuclearcells is very difficult to interpret. As I have said before, white cells in the blood are more roles by definition not doing anything much - just being transported to somewhere they might do something. If there was a mitochondrial abnormality responsible for ME type symptoms I would expect it to show as shifts in metabolites in tissues like muscle or lever that can be assessed by magnetic resonance spectroscopy.

I find it very hard to assess papers from abstracts these days. For some reason the crucial numerical data are no longer included in abstracts. To me that is bad science, whether it is due to journal fashion or obfuscation by authors.

 

Yes, but I am not motivated to trawl through papers if the abstract indicates I am likely to find nothing very illuminating. I have had to work on that basis for forty years - otherwise I would never have had time to do any science myself.

 

Hopefully me research UK will publish a lay summary. I did t really understand what they were saying about acidification and I think that they Said the severe ME Lowered glycolysis was correlation not necessarily cause. nice to see some decent research coming out of the uk although I assume “larger studies are required”.
I was surprised to see a paper with JLN initials.
It seems respiratory acidification is something to do with carbon dioxide levels?.


Found this, i don’t know relevance https://www.healthline.com/health/respiratory-acidosis

 

Yes, agree, pretty disconcerting that there are exactly zero quantitative data in the abstract.

 

I am uneasy by these researchers using the imo “off key” criteria of nice and icc, to redefine how the severities are classified. These have been at odds with the severity scales and how groups like the 25% define themselves.

I'm not suggesting there's bad intent , it was probable convenience or lack of expertise. The problem with severe ME defined as mostly bedbound, is it decreases the numbers in the severe category (harmful when the general incidence number is often inflated ie the 25% become the 5- 10% and easier to justify the marginalisation)


Afaic it's also inaccurate. Usually severe m.e is divided into upper and lower categories and I think there are thousands of people essentially not mostly, housebound who aren't mostly bedridden.

i also personally understood moderately affected to be not working but able to leave the home most days.
_________________________

This post has been copied and several posts moved to this thread:
ME severity scales - discussion

 

I have yet to read the study, but based on what is earlier on this thread this study is not claiming no mitochondrial dysfunction. Its claiming severity is not associated with mitochondrial dysfunction. This means that the sicker patients have more or less the same mitochondrial function as the moderate patients. Its glycolytic function that makes the difference.

If replicated this could be huge. It implies that multiple energy production pathways are suppressed. It open up new investigatory and treatment targets ... its no longer mitochondria or something else, its mitochondria AND something else.

They really need to do this on cell types other than PBMCs though. That would be an important issue in further studies.

 

I'm sure you recall Karl Morten's study on muscle cells. Karl has been trying to get funding to do more work on this.

Anyone heard anything about the nano-needle?

 

Which to my medically uneducated brain makes me wonder what it might be that could cause damage to more than one aspect of the energy processing? The same cause hitting multiple aspects, but differently for different people? Or maybe it starts with one thing getting hit, and perhaps for some people that then cascading and further damaging other parts of their energy processing system? Possibly due to still-intact aspects being under more strain?

I wonder if there is any understanding if, for those with multiple aspect failures, if all those aspects failed at the same time, or if they went wrong sequentially.

The idea that severity maybe relates to how many different aspects might be impacted is intriguing.

(I know 'aspects' is a poor word choice here, but unsure what the right word is).

 

I went looking and responded on the Nanoneedle paper thread.
https://www.s4me.info/threads/a-nan...dyarpour-davis-et-al.9284/page-22#post-253676

 

meres.uk/CellBioenerg
http://www.meresearch.org.uk/our-research/completed-studies/cellular-bioenergetic-function/

MERUK write up.

They are defining moderate ME as housebound and severe bedridden which I still find problematic as said above.

Unfortunately they don’t expand at all on respiratory acidification. Is it that in severe ME, who they take as bedridden , that the breathing is impaired due to lying on Back, causing an oxygen Co2 issue which explains some of the glycolysis dysfunction but not all?

I note Dr Charles Shepherd has said those longterm bedridden with neurological or rheumatoid conditions, I assume that includes ME, would be at high risk of respiratory complications in covid, someone explained to me that was due to impaired or restricted lung function in bedridden people.

 

Didn't Paul Fisher identify glycolytic problems?

 

Pure speculation, but it looks to me as though its orchestrated, part of an evolutionary response, perhaps in respect to viruses. It hasn't necessarily kicked in all the way with milder patients, but does so when a patient goes severe. There are two questions here ... first, what is the mechanism doing the glycolytic derangement, and secondly what mechanism is orchestrating all this ... what are the details and what triggers it. Again, this is just speculation.

Implications regarding glycolysis are maybe 24 years old now.

What is important here is there is a differential in glycolysis in patient severity stratification. I have other business to attend to so have not read the paper yet.