Substrate utilisation of cultured skeletal muscle cells in patients with CFS, Tomas et al, 2020

[FMMM1]

Would you not need to do this to avoid being in a catabolic state?

I think Ron Davis has said that there was some evidence that Whitney had been cannibalising his muscle - there's a particular excretion product which is increased in these circumstances.
Not sure if Ron has introduced these amino acids as a means of increasing Whitney's nutrition.

Chris Armstrong (OMF) is returning to Melbourne - he's focusing on nitrogen metabolism; which I assume is all of this protein stuff.

Fluge and Mella published their PDH paper in December 2016 - why does it take so long to move these things along? Money/competing priorities I guess but still frustrating.

 

[FMMM1]

No offence to you @strategist but so tired of hearing of diet remedy for our yet to be explained disease. This is not a diet deficient problem.

If it's yet to be explained, and there seems to be evidence of utilising certain amino acids, then is diet unreasonable? Also I think Ron Davis and Chris Armstrong may have considered diet supplementation.

 

[Kitty]

If it's yet to be explained, and there seems to be evidence of utilising certain amino acids, then is diet unreasonable?

Yes, I don't think what's being researched is the same as a diet deficiency. Some or all of us may be consuming more of a resource than normal; if that's shown to be the case it makes sense to take in a bit more of it, as long as it's not going to cause problems elsewhere.

(Although one of the questions is going to be whether eating more of X can actually increase the body's reserves of it, of course; it's not always that simple.)

 

[Hoopoe]

https://www.nature.com/articles/srep34990

Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711–0.890, P < 0.0001) and 0.750 (95% CI: 0.584–0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma.

This is just one of the studies that found problems in the general area of the TCA and urea cycle.

Data from the UK Biobank also suggested that the gene for the ornithine transporter 1 was associated with ME/CFS (ornithine plays a role in the urea cycle).

 

[FMMM1]

i think that amino acid utilization is interesting and may be providing clues as of what is going on in the muscle cells (albeit in vitro). But i am more interested in knowing
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7) whether there can be less invasive tests that can be performed that can be a surrogate to a muscle biopsy (i had one done, it was not fun afterwards) for instance metabolomics
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Milo "The dysfunction in glucose oxidation [muscle cells] is similar to what has previously been shown in blood cells from CFS patients." This seems to indicate that PBMCs would be a substitute i.e. for muscle cells.

However, @Jonathan Edwards suggestion, re MR Spectroscopy, would be much more interesting i.e. if the sensitivity of MR Spectroscopy is adequate.

 

[FMMM1]

Yes, I don't think what's being researched is the same as a diet deficiency. Some or all of us may be consuming more of a resource than normal; if that's shown to be the case it makes sense to take in a bit more of it, as long as it's not going to cause problems elsewhere.

(Although one of the questions is going to be whether eating more of X can actually increase the body's reserves of it, of course; it's not always that simple.)

I suspect you're correct i.e. if you're consuming more of X (certain amino acids for energy production) then supplementing your diet with X may not lead to an improvement in your health/functioning.

I wonder if a blood test (PMBCs) could identify people who have this problem and then a genetic test could be used to identify genes (gene expression) that are relevant?

 

[Hoopoe]

Amino acids are definitely absorbed in the gut.

 

[FMMM1]

I recall that Ron Tompkins (OMF) was planning to do work on muscle cells i.e. with UK researchers - any news of that?

Anyone with links to OMF on this forum?

@Giada Da Ros

 

[FMMM1]

Amino acids are definitely absorbed in the gut.

Hi @strategist hope you don't mind me pointing out @alicec explanation of how amino acids etc. are utilised for energy, there also info re diet supplementation,

https://www.s4me.info/threads/amino-acids-and-energy-production.1262/#post-21189

perhaps alicec could link it to this thread.

Also, here's a quote from alicec's post
"They [Fluge & Mella] then showed that the pyruvate dehydrogenase complex (PDH), which catalyses the pyruvate to acetylCoA conversion, is inhibited in ME/CFS.

This was a result of upregulation of genes coding for several enzymes which inhibit PDH, viz SIRT4, members of the PDH kinase family of enzymes (PDK) and the transcription factor PPRD."

I was just wondering if the levels of SIRT4 etc. would be a biomarker for ME i.e. inhibition of PDH? Sure someone has thought of that and discounted it.

Fluge and Mella thought the metabolic changes were reversible; however, Cara et al propose that they are not reversible - transferred to next generation of cells.

Someone mentioned the UK Biobank turned up a possible link to Ornithine Transporter?

Quite a bit of interesting information.

 

[Andy]

Someone mentioned the UK Biobank turned up a possible link to Ornithine Transporter?

Significant association of DNA variants with self-reported ME/CFS (Chris Ponting blog)

 

[leokitten]

Have they, or anyone else, examined cells collected from the muscle biopsies and tried to confirm or refute the Prusty hypothesis that the reduced OXPHOS they are seeing is due to mitochondrial fragmentation?

 

[DMissa]

Have they, or anyone else, examined cells collected from the muscle biopsies and tried to confirm or refute the Prusty hypothesis that the reduced OXPHOS they are seeing is due to mitochondrial fragmentation?

Not sure, but if somebody does visually inspect ME/CFS mitochondria specifically in muscle one would hope for a comparison against sedentary controls. Muscle mitochondria from people who can't undertake exercise, or can only undertake reduced exercise (due to disease burden) would probably look different from a more active person's given that muscle mitochondrial biogenesis is stimulated by exercise. This would have to be dismissed as a potential confounding variable.