Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients (2019) Tomas, Brown, Newton, Elson

Thanks, the huge flaw here is that Fukuda is broken, as another Newton paper proved but failed to say. In fact we can say that it has been shown Fukuda eliminates statistical relevance of data for ME and IMHO this is a null result, not worth giving credence.

https://www.s4me.info/threads/impai...re-common-2019-newton-et-al.8040/#post-142247

 

from the paper, and on another thing:

i understand, ophthalmoplegia (there are various forms) may be caused by demyelination of nerves.
this demyelination may be triggered by mitochondrial fails - which may be also a problem in mecfs.

together with the mitochondrial issues, the various forms of opthalmoplegia can show as
- ptosis (eye lids)
- troubles with eye nerves (various vision issues, reading/focussing)
- with face nerves (inability to move eye brows)
- hearing loss
- elevated blood lactate (weakness limbs, neck)
- elevated pyruvate
...

opthalmoplegia diseases are slow progressing and can start anytime, mostly in ppl below 20.
causes are unknown, but can be genetic.

in such a case, copaxone should help with demyelination?
why is this so expensive ?

 

That paper along with this recent paper explicitly show the problem is not within the mitochondria. That is a key part of the mystery.

 

@Snow Leopard

there is
a) true mitochondrial damage
b) fake mitochondrial damage

mecfs is b), i understand.
in what class is the optho-disease, a) or b) ?

these ophto-symptoms are mine.
(sorry for having no clue on whatsoever)

 

In looking upstream, the Tomas et al paper suggests "The lack of differences in PBMCs may suggest that the abnormalities found in whole cells shown previously is not due to abnormalities in the mitochondrial respiratory chain complexes but rather at different points of the respiration pathway such as movement of glucose into cells, AMPK abnormalities, or altered functioning of other mitochondrial enzymes (Tomas et al., 2017)."

I am not a biochemist (or a clinician), so I hesitate to put this out there, but ...
Given that some clinicians recommend ketogenic diets for ME, and I've seen some papers suggesting that AMPK production/functioning may be affected by ketosis:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898565/,
https://www.mdpi.com/2072-6643/10/10/1339
https://link.springer.com/article/10.1007/s11745-016-4156-7
is this something that should be being investigated further? Is anyone already looking in this direction?

 

It depends on the foods in the Keto diet. RBC deformability is improved by high polyunsaturated fat diets, and made worse by high saturated fat diets. Of course this presumes the polyunsaturated fats are not trans fats. Trans fats are even worse than saturated fats.

 

I would imagine that depends on the cause of the RBC abnormalities or deformabilty-disability to begin with.

 

That will modify it, but the flexibility of a membrane is due in a large part to its fat composition. Now in the case of oxidative and nitrosative stress, where those fats get damaged, polyunsaturated fats will have decreased benefit. This is particularly the case if they become trans fats.

Now having lots of poly in the membrane is not always a good thing for other reasons. It might lead to increased series two eicosanoid synthesis, for example. Many of those eicosanoids will be inflammatory.

We are still learning about the factors that induce or inhibit RBC deformation, some of which might be endothelial not due to the RBCs themselves. I can say that in many patients, myself included, a high poly diet did not fix our ME. Its not that simple.

There are at least some drugs that might have an impact as well. I think some might wind up being in clinical trials for ME.

 

My biggest signal is for missing heat shock protein,so I think the protein in the blood will be unfolded protein and the unfolded protein response kicks in

 

The problem is there is some evidence that fatty acid transport is also disturbed, meaning a ketogenic diet on its own may actually make things worse.. .

https://www.ncbi.nlm.nih.gov/pubmed/21205027

 

I think the RBC deformability might need to be considered separately, as the “there’s something in the blood” theory still applies where plasma alone has been added to healthy cells, and found to diminish their ability to utilise oxygen.

 

Really appreciate your knowledge on this. I keep trying to get a local consultant with a background in CPET to read the research. Will let you know if I'm ever successful

 

Could you please explain this more fully for idiots like me?

 

I have discovered the hard way that I cannot live without eating cardohydrates. If I do not have enough I collapse with hypoglycaemia (confirmed by blood test). To defer a collapse a little bit (if I am waiting for food, say) I sit perfectly still.

 

mecfs ppl may show the extreme opposite of BHD breath holding divers ?
perhaps, the problem is not exactly lactate

... and then there was ATIVAN increasing the mitchondrial respiration... faik

 

I think the jury is out on whether a ketogenic diet is useful. I think glucose is still by far the most efficient energy source available to us and what the human body has adopted ..the brain uses about 70% of the glucose we normally consume. Whether our energy production is dysfunctional doesn’t necessarily equate to it being completely broken and so going extreme with a less efficient energy production does seem counterintuitive.

It seems to me that we are talking degrees of dysfunction so it may be that a ketogenic diet may not be that helpful for the milder, but may be more beneficial for the more severe. However that makes some pretty broad assumptions. If a ketogenic diet were a significant improver I think we would know by now.

 

Don’t we have to break down the fats we eat first though to create the membrane phospholipids? I thought circulating fats are no larger than medium chain triglycerides and mostly fatty acids? So whether it’s poly when you eat it ..it mainly becomes fatty acids in the end anyway before it gets near to being part of a membrane. You also need saturated fatty acids for membrane production I think (although I am a bit hazy on that). I always thought the benefit of a diet higher in polyunsaturated fat than saturated fat was to reduce the amount of circulating cholesterol in the bloodstream and provide a source of omega fatty acids rather than anything to do with cell membranes?