Discussion in 'BioMedical ME/CFS Research' started by John Mac, Oct 26, 2020.
"Muscle biopsies obtained from the vastus lateralis were collected from 9 CFS patients and 11 age/sex matched controls. On the day of biopsy, CFS patients completed a fatigue impact scale (FIS) questionnaire so that functional limitations due to fatigue could be measured25. Age, gender and body mass index (BMI) of patients were also recorded. For healthy control participants only age and gender information was collected. Participants were recruited via the Newcastle NHS clinic for CFS at the Newcastle Hospitals NHS foundation Trust. All CFS patients fulfilled the Fukuda diagnostic criteria1."
So they didn't take muscle biopsies from patients after exercise?
The first sentence from this study says "Chronic fatigue syndrome (CFS) patients often suffer from severe muscle pain and an inability to exercise due to muscle fatigue".
I don't have the inability to exercise, I can exercise with no problems. I have PEM. Maybe they worded it wrong?
Lots of us can't, though, our muscles will just stop working. I use a wheelie because my legs give way when they run out of oomph!
I wonder what the results would show before and after exercise, and if that would highlight what is occurring with PEM.
Perhaps no difference?
The only downside to ever seeing an increase in biomedical research is that it's all so above my meager understanding of biology that I can't really judge or appreciate much of it. Unlike the high school level logical fallacies out of BPS land, which can usually be summed up in a single paragraph without reducing its information.
This seems to be the main takeaway:
Summarized in the conclusion:
And if my very poor understanding of biology does not mislead me, points to mitochondria as the culprit:
Why you gotta misbehave, mitochondria?
I think the study was more about how well our cells utilise different energy substrates, and whether they retain their energy dysfunction even after being cultured and manipulated in vitro (they do) than about the difference between muscles cell samples that are taken before and after exercise.
The work seems to give us some clues as to where in the process the dysfunction could be happening (i.e., upstream of the TCA cycle), and – importantly – has potentially shown that it can be reversed, since using galactose as a substrate seems to restore OXPHOS.
I'm writing this as if I understand it properly...nothing could be further from the truth!
My try on summarizing below.. Please point out if ive said something wrong, I only have basic knowledge of this stuff from ancient biology uni lectures
In short: Muscle cells from the skeleton of ME patients are unable to use glucose as efficiently as muscle cells from the skeleton of healthy people
The same problem has previously been seen in cells from the blood of ME patients (Tomas, C. et al. Cellular bioenergetics is impaired in patients with chronic fatigue syndrome. PLoS ONE 12, e0186802 (2017).
The authors say this is consistent with the hypothesis that ME is a systemic disease.
The fact that this dysfunction of glucose metabolism continues in cell cultures may indicate that ME involves epigenetic and genetic changes.
The function was normal in the cells when galactose was used as a substrate, as well as various fatty acids. The authors say this, together with the fact that glycolysis is normal, may indicate that the problem lies in a mechanism between pyrovate dehydrogenase (an enzyme complex that breaks down glucose) and the TCA cycle (where pyruvate from glycolysis is oxidized in the mitochondrial matrix)
The authors point out that this is consistent with the findings of Fluge & Mella, which indicated a disease mechanism in which the oxidation of pyruvate in the mitochondria was abnormal (Fluge, O. et al. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy / chronic fatigue syndrome. JCI Insight 1, e89376 (2016).)
Otherwise: Small study, and diagnosis according to the Fukuda criteria. I do not know anything about the specific biochemistry here in general, as it is beyond my competence.
But think this is exciting (y)
According to my understanding, a problem in the step between glycolysis and the citric acid cycle is consistent with a previous Norwegian study proposing that the enzyme pyruvate dehydrogenase (PDH) was impaired.
"Results show that CFS skeletal muscle cells are unable to utilise glucose to the same extent as healthy control cells."
It says in the abstract.
But where are the results?
What they show is for the reader to decide.
This is not how science is written, sorry.
If the findings were due to genetics people would be born with ME.
They might be due to epigenetic, but that might include a shift in fibre ratio in ME muscle as a result of incapacity, which would mean that cultures had different proportions of muscle cell types (for instance).
I still think for any of this to have any plausibility it should be possible to find real-time changes in metabolites in ME patients during exercise using MR spectroscopy. Otherwise we are looking at the equivalent of banana plants growing in the drawing room. They don't tell you much about bananas.
Whats wrong with the results? You dont think they can conclude as they did based on their findings? Asking cause I cant analyze them professionally
I like the spectroscopy idea
Was just complaining that there are NO results in the abstract. If an abstract is this badly written I cannot be bothered to read more.
Ahh right, I remember you saying that at another time too now
Maybe patients could benefit from a diet rich in aminoacids in category 2 and 3 (in the picture in my previous post here).
Does this tie in with the mismatch between complex 1 and complex V in mitochondria reported previously by others ?
Would you not need to do this to avoid being in a catabolic state?
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 deficiency problem.
The paper is open access.
9 CFS patients, 10 controls
Glucose as a substrate for skeletal muscle cells
A. Basal respiration - note significance between healthy controls and CFS - **. Pretty good. OCR is oxygen consumption rate.
E. Maximal respiration -
The cells were stressed somehow and so had to work harder. Look at the y axis for the units of oxygen consumption rate. They are a lot higher than for the basal respiration rate study. The healthy controls and CFS mostly look different (significance *), although some of the CFS samples were as good as the healthy control average and some of the healthy controls were as bad as the CFS average.
G. whole mitochondrial stress test trace in untreated cells.
I think the figure references might be wrong here? Should it be "2A, E" as per the charts in my post above? Chart 2C is actually of ATP production.
Using glucose as a substrate:
Figure 2c is supposed to to be of ATP production. I don't understand the y-axis unit. Is that an error? How is oxygen consumption a measure of ATP production?
Figure 2 C
Protein requirements are higher in many diseases, without it meaning anything else than the body having increased need in illness. I'd very much like to know if our illness is one of those where protein requirements are higher, for whatever reason. (I get tired of people overselling diet as well, but I am also frustrated when my curriculum includes nutritional support of people with many different illnesses with no mention of ME although there are overlapping issues. Like not being able to stand upright and prepare food, or even to get shopping done when you want/need to).
@Mij I wonder if having a biopsy taken is enough stress on the cells to cause some change in them? Maybe not PEM but.. I don't know too much about growing primary cell lines though
@Amw66 Those complexes are downstream of the reaction they propose is problematic.
@Hutan Can they have used oxygen consumption as a proxy for ATP production? I know I've made graphs for an exam with e. Coli oxygen consumption on one axis and ATP production on the other.
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
1) why this is happening.
2) whether the same thing happens in other diseases
3) whether the muscle cells return to a normal state when fed amino acids
4) whether the same thing happens in other kinds of cells (PBMC, smooth muscles, etc)
5) whether it can be reproduced with a larger sample, by a different team
6) whether there is a variation of the results according to severity and number of years sick
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
8) whether they have done the sick plasma experiment on healthy muscle tissue, and healthy plasma on sick muscle tissue.
I think that due to the fact that there are no treatment available and severe shortage of experts in the field, patients in our community feel there is nothing to lose to jump to conclusion and hit the supplement online store. In my view though, jumping to conclusions is premature. Science is not there yet and the authors of the paper would be first in line to agree with this.
Separate names with a comma.