A Thought Experiment on Muscles

[Jonathan Edwards]

I have always been a bit puzzled as to what people think might explain the change in results on the second day CPET in ME/CFS.

It could be a change in lungs, altering oxygen availability maybe.
Or in the power of heart contraction maybe.
Or provision of fuels by the liver maybe.

But my impression is that people think there is a change in muscle with use. Perhaps use induces changes in mitochondria in muscle cells?

If that is the case then presumably the second day effect will apply specifically to muscles used on day 1.

If that is the case there should be no need to exercise lots of muscles if one could use just one muscle group and detect a shift in performance in that muscle. For instance forearm flexors used for gripping. The exercise could be squeezing a blood pressure machine bulb and seeing how long you can go on hitting 200mmHg once every two seconds.

I guess that it is more difficult to detect changes in oxygen usage with just one muscle. But if one muscle does not flag on day 2 then maybe the theory needs changing?

Interested to hear from those who know more about these things.

 

[Sasha]

I have always been a bit puzzled as to what people think might explain the change in results on the second day CPET in ME/CFS.

I thought there was some question about whether the change on the second day was a solid and replicable finding?

 

[richie]

I thought there was some question about whether the change on the second day was a solid and replicable finding?

The good/bad day phenomenon in an individual might be part of that as with e.g. lung function tests and other such. But do you mean inconsistent results in a single person or in those with an ME diagnosis person by person?

 

[richie]

I have always been a bit puzzled as to what people think might explain the change in results on the second day CPET in ME/CFS.


Interested to hear from those who know more about these things.

I know little but I wonder if there is anything in this by Cort Johnson referring to Protons/J Newton and the autonomic system,

A "Fatigue" Disorder No More? - What Multiple Sclerosis Taught Us About Fatigue and Chronic Fatigue Syndrome - Health Rising

 

[Sasha]

The good/bad day phenomenon in an individual might be part of that as with e.g. lung function tests and other such. But do you mean inconsistent results in a single person or in those with an ME diagnosis person by person?

I mean the Snell, Steven, VanNess etc. studies in which they got PwME into the lab, and healthy controls, ran them all through a 2-day CPET and compared the results.

 

[richie]

I mean the etc. studies in which they got PwME into the lab, and healthy controls, ran them all through a 2-day CPET and compared the results.

What particular issues did they find? I had a cursory look on MEpedia and the results seemed OK.

 

[rapidboson]

If that is the case there should be no need to exercise lots of muscles if one could use just one muscle group and detect a shift in performance in that muscle. For instance forearm flexors used for gripping.

I might understand you wrong, but isn't that what they do in diagnosis already? Grip strength, 10 repeats, wait an hour and have another go with 10 repeats. People with ME / PEM(?) will not be able to reach the same grip strength the second time around as they had an hour prior.

 

[rapidboson]

Perhaps use induces changes in mitochondria in muscle cells?

I remember some studies that have shown damage (?) to the mitochondria in specific areas of the muscle, maybe the sarcolemma or sarcomeres (something like that) but not all througout the muscle fibers?
Does that ring a bell?

 

[Jonathan Edwards]

There is no doubt that the drop on day 2 with CPET is not uniform across people with ME/CFS and there are differences between studies. I ma not sure how robust the observation is in general - there might be a number of uninteresting explanations - but I am thought experimenting have assumed that there might be something in it. But only might. A study of a single muscle group might show that we cannot blame mitochondria in muscle and further studies might indicate we cannot blame anything else much of interest.

 

[Jonathan Edwards]

Grip strength, 10 repeats, wait an hour and have another go with 10 repeats. People with ME / PEM(?) will not be able to reach the same grip strength the second time around as they had an hour prior.

Are there any data on that?
And if there are why are people still getting on bicycles?

 

[Evergreen]

Are there any data on that?
And if there are why are people still getting on bicycles?

Have a look at Jones DE, Hollingsworth KG, Jakovljevic DG, Fattakhova G, Pairman J, Blamire AM, Trenell MI, Newton JL. Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study. Eur J Clin Invest. 2012 Feb;42(2):186-94. doi: 10.1111/j.1365-2362.2011.02567.x. Epub 2011 Jul 12. PMID: 21749371.

https://pubmed.ncbi.nlm.nih.gov/21749371/

The CFS patients in the normal PCr depletion group [those who exerted adequately] showed a marked increase in intramuscular acidosis compared to the controls after a similar level of work. This phenomenon was seen after each of the three linked exercise periods with no apparent reduction in acidosis with repeat exercise of the type reported in normal subjects (Fig. 4b–d).

 

[rapidboson]

Are there any data on that?
And if there are why are people still getting on bicycles?

https://www.mdpi.com/2077-0383/13/7/2153

This for example? Sorry, brainfog.
There's been several such studies in the past years iirc

 

[hotblack]

The only studies I’m aware of on repeated hand grip strength are all in one go, not on subsequent days.

They show both lower maximal grip strength but also lower on subsequent tests which is associated with severity. I’d really like some sort of longitudinal study so we can get a better idea of these changes in context with other symptoms and to get an idea of whatever the recovery time to an individuals maximum is.

Edit: the papers on hand grip strength discussed on here https://www.s4me.info/search/38610482/?q=Hand+grip+strength&o=date&c[title_only]=1

 

[OrganicChilli]

Are there any data on that?

I found these papers:

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02774-w

https://www.mdpi.com/2077-0383/13/7/2153

https://www.sciencedirect.com/science/article/pii/S0268003323001869

https://pmc.ncbi.nlm.nih.gov/articles/PMC6277492/

 

[RainbowCloud]

Just wanted to throw in that for me excessive cognitive or emotional exertion can mean that I’m generally less able in my whole body, so it doesn’t even need to be exercise/muscular use in the first place that means I will experience reduced muscle ability as a consequence.

Because of that, I feel there’s an issue in the product of energy use (whether that’s a build up of something that has a knock on effect eg. on autophagy, or oxygen issues, I don’t know) and so it doesn’t matter what you did to use the energy, just having used it is going to have consequences everywhere.

(I hope what I’m trying to get at makes sense - sorry, struggling today!)

 

[Simon M]

Are there any data on that?
And if there are why are people still getting on bicycles?

The problem with the faster drop in grips strength for me/CFS versus healthy controls, is that something similar is seen in a number of illnesses – it’s not specific.

The CPET studies do you see more unusual, but there’s very little comparison data. I believe the one consistent effect is in day-2 ventilatory threshold.

that’s only the group level. For some individuals the effect a large, but often it’s only modest or trivial. That is, in the very few studies where they have published data at the individual level.

What’s frustrating is there hasn’t been a meta analysis. I believe that workwell now have data on over 400 individuals, yet hasn’t published an analysis of all 400.

And the effect is still small whereas the good/bad effect in the illness is absolutely huge. And the effect is also small when you can compare healthy people with people with ME. It just seems on the margins.

If you factor in that what causes postexertional malaise is trivial by comparison with the maximum exercise test – which I doubt many people with this illnesscould even undertake, and I wonder its significance.

Finally, what about post Exertional malaise.

These studies are often Presented
as of studies of PEM. Though researchers frequently failed to publish or measured data on that.

if it is PEM, then maybe exercising a single muscle wouldn’t be enough to trigger it and therefore you get normal day two results.

sorry, that’s a bit of a list of my doubts about the data. I’m not sure how much weight the finding can bear

 

[Sasha]

What particular issues did they find? I had a cursory look on MEpedia and the results seemed OK.

I thought the problem was with replicability but I've just done a bit of a search where I thought I'd seen that and I'm wondering if my impression was imaginary!

 

[Utsikt]

If that is the case there should be no need to exercise lots of muscles if one could use just one muscle group and detect a shift in performance in that muscle. For instance forearm flexors used for gripping. The exercise could be squeezing a blood pressure machine bulb and seeing how long you can go on hitting 200mmHg once every two seconds.

I believe Fluge and Mella are working on something along those lines. They asked for pwME (CCC, probably >=moderate due to in person) and healthy controls last summer. Afaik, they got as many people as they needed.

Although I’m not sure what they will be measuring.

You can see the device here:

 

[Sasha]

What’s frustrating is there hasn’t been a meta analysis. I believe that workwell now have data on over 400 individuals, yet hasn’t published an analysis of all 400.

That's a pity. I wonder if they can be prodded to do so? Or to hand over their data to someone who would?

I wonder if we have people here who could do that.

 

[Jonathan Edwards]

Have a look at Jones DE, Hollingsworth KG, Jakovljevic DG, Fattakhova G, Pairman J, Blamire AM, Trenell MI, Newton JL. Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study.

Was that a single muscle group study? The abstract talks of Vo2 max changes. It also seems different from other CPET studies in that day 1 was low.

This for example? Sorry, brainfog.

I think that was just one off grip strength?

Just wanted to throw in that for me excessive cognitive or emotional exertion can mean that I’m generally less able in my whole body, so it doesn’t even need to be exercise/muscular use in the first place that means I will experience reduced muscle ability as a consequence.

Which I guess is the rabbit loose that sets this line of thought going, yes.

Because of that, I feel there’s an issue in the product of energy use (whether that’s a build up of something that has a knock on effect eg. on autophagy, or oxygen issues, I don’t know) and so it doesn’t matter what you did to use the energy, just having used it is going to have consequences everywhere.

Except that there seems no way that we are talking about using up energy for sever people who get PEM after trivial exertion. There is still plenty of oxygen and glucose around.