Do ME symptoms fit with the faulty energy metabolism hypothesis?

Karl Morten.

As well as the liver, Lladislav was talking about scanning calf muscles with what I now assume to be magnetic resonance spectroscopy (https://en.wikipedia.org/wiki/In_vivo_magnetic_resonance_spectroscopy)
Oxford Centre for Clinical Magnetic Resonance Research website, https://www.rdm.ox.ac.uk/about/our-...ntre-for-clinical-magnetic-resonance-research

 

Could the signalling pathways be disrupted because the cells lack energy ?

 

I find the "anything" very hard to accept, though would readily accept that many things could be physical, but it is a crucial distinction. Bereavements, for example, can significantly alter people's behaviour, especially the more 'unnatural' ones, where people lose loved ones unexpectedly, particularly children, and/or from violence. Or terrifying experiences, even when no physical trauma occurred. Or deeply abusive relationships where there is no physical harm nor even threat of harm, but nonetheless the constant drip, drip, drip of mental gaslighting abuse being inflicted year in year out; people in these conditions end up behaving way different to what they would if in good healthy relationships.

 

Is it possible this blocking of DNA replication might also be happening during certain phases of the ME symptoms fluctuation? Just wondered because I'm guessing that if DNA replication has been held off for a while, then once the body has beaten the virus-or-whatever-other-spurious-trigger itself, and DNA replication can resume again, there must be something of a backlog to catch up on; could something like this account for time-delayed consequences for pwME? Could catching up with such a backlog put someone into an especially grotty state (PEM?) until the system reaches equilibrium again?

 

'Physical' just means causal. As Bertrand Russell pointed out, and many others before and after, we know nothing of the physical world other than patterns of causation. And as far as we know physical covers all causes in that all the causes involved in thoughts seem to be mediated by the same sorts of events in brains as we see elsewhere - electrical forces acting etc.

So bereavement affects behaviour through physical processes in the brain.

There is no doubt that bereavement belongs to a very special sort of physical causation that involves sensory inputs and higher brain function of the sort we associate with emotions and thoughts. And it is perfectly legitimate to separate out those causes. But they are still physical. So the dissection has to be made at a different cut.

 

I wonder if using Ron Davis's technique of adding a salt solution to force cells to perform a workout would it be possible to model PEM in vitro?

Davis adds a salt solution to cells because this forces the cells to generate energy in order to maintain the salt concentrations inside the cell. So the salt solution is like a forced gym workout for cells in vitro.

So it might be possible to add a salt solution to the cells for a few hours, to push these cells through a workout, and then return the cells to normal saline levels.

Then some time later, you could repeat the process, pushing the cells through a second workout, by adding the salt solution again.

If the cells had developed PEM after the first workout, then you might expect ATP energy output performance to deteriorate in the second workout (analogous to the 2-day CPET). But in healthy control cells, the performance presumably would not deteriorate in the second workout.

You should be able to measure ATP energy output performance of the cells with a machine such as the Agilent Seahorse.



It also might be possible to test the Myhill ATP molecule depletion theory of PEM in this in vitro experiment: if PEM is indeed due to ATP molecule depletion, then you may be able to measure reduced ATP molecule levels in cells placed under a long salt solution workout such that the cells develop PEM.

I don't think the Seahorse can measure the ATP molecule count, but there may be other means to do this.

 

@Jonathan Edwards

It looks like Robert Phair agrees with you that there is no compelling evidence for dysfunctional energy production in ME/CFS.

Here

https://forums.phoenixrising.me/threads/the-ido-metabolic-trap-guy.62727/page-15

 

I think am probably banned from that place.

 

Should be OK to look.....Voyeurism is permitted.

 

Not necessarily. The link is to a members only page.

 

I don't experience that pattern at all, makes me wonder if I have a different illness.

For me, physical activity can increase brain fog, but prolonged cognitive activity doesn't make my legs any weaker.

 

Normal muscle strength and fatigability in patients with effort syndromes BMJ, 1988

Their definition of effort syndromes includes ME and Royal Free disease:

 

The "fatiguing" test was conducted on the adductor pollicis (one of the thumb muscles), but this doesn't exactly put much strain on the cardiovascular system (though a blood pressure cuff was used during some of the tests). The result shows that the nerve function itself is probably normal and the stimulation test was insufficient to induce abnormal fatiguability of force generation. A key point may be that anerobic force generation may be normal, but sustained aerobic output could still be a problem.

 

i would think "other" performance tests may be interesting, and get much deeper insight into reduced exercise "tolerance"

- normal under "load" (weights added)
- incline walking

...sure, it then sounds like someone has a lung-heart-prob rather...
but there seems nothing measurable...

but im wondering, if different "types of exercise" show a much bigger difference to HCs (than bike and the peanuts things they use to do in the tests).
participants: HCs + pwmecfs + typically deconditioned ppl

 

Yeah. Of course they dismiss the tachycardia, dyspnea and other cardiovascular symptoms as being due to cardiovascular deconditioning.

 

On hidden rotting food I have no way of knowing. It could be either or both. This is stuff I have not noticed, so I don't know how long its been there or what my level of contact was.

 

I don't think we can say for sure that the mitochondria are damaged, but we can say that energy production is impaired. Its the nature of that impairment where the confusion lies. We literally don't know why, we can only measure it such as through CPET. This means the problem could be at many levels, even extracellular, such as with microcirculation.

The nanoneedle findings do strongly suggest there is at least an important cell based component. We still need to understand what is happening, and why.

 

@Jonathan Edwards

So in case some weren't able or willing to access the above cited PR thread:

Phair says that every time there is a good case for a dysfunction in energy production, there is an offsetting case for there being no dysfunction. He mentions that Paul Fisher's talk in Australia was convincing, but it was followed by a talk by Cara Thomas that was equally convincing to him in showing no dysfunction, but using different cell types. He also mentions that Vermeulen (2014) found no difference in resting oxygen consumption in ME/CFS. Vermeulen did show differences during exercise, but Phair notes that CFS patients are sick at rest.

 

Are we tho?

At rest I mean.

I have metrics, gained via a fitness tracker when crashed, that strongly suggests that even tho I may not be moving I am pretty far from at rest.

I don't know exactly what its picking up but it's picking up something.

 

Re the Karl Morten ATP profiles test replication ( which showed no significant difference on fresh blood) - has anyone looked into why there is such a big difference between controls and pwme after 24 hours ( would that not give a clue as to something awry?)