PEM discussion thread - post-exertional malaise

And we have absolutely no evidence for it being the use of calories that actually causes the reaction. So we would be flying entirely in the dark.
Calories/min, or a model derived from it, as the exertion measure is my hypothesis and I have some evidence though I'm yet to make it public. In any case, the notion of exertion as a subjective concept, at least pertaining to PEM, needs to be dispatched with. We already have fatigue as a subjective psychological idea from BPS via effort preference, and we wouldn't want that extended to PEM. Such idea can be positively dismissed in any event given the typical 12-48 hour delay. If it is not subjective, it has to be objective whether it is cal/min or something else.
 
And mental exertion uses minimal calories – fewer than the type of physical activities which the same patients are able to do without causing PEM. So if PEM can be caused by mental exertion that would be evidence that it’s not caused by the use of calories.
Whatever the damage caused by that calorie expenditure is confined in the brain and they'll need to be cleaned up or repaired by the brain immune system. No reason to think that such repair process won't cause PEM.
 
In any case, the notion of exertion as a subjective concept, at least pertaining to PEM, needs to be dispatched with.

But if it is the basis of a symptom that patients are expected to recognise it has to be subjective. They do not measure calories. If you want to get away from that then presumably exertion should not be used as a term. We should talk of power (calories per time would be power) or of total energy usage. So far I don't think we have established even which of those is relevant - and they are very different in implications.
 
Subjectively it feels that a simple measure like calories per unit of time does not correspond to what ever culminates in triggering PEM. Other things interact like the novelty of the activity, additional sensory stimuli or orthostatic issues. For example walking x metres on level ground alone, might not trigger PEM but walking x metres over uneven ground whilst talking to someone might. A subjective, in a non scientific sense, feeling of effort seems to relate to triggering PEM over and above what theoretically could be measured in joules.

Also units of whatever cumulates to trigger PEM, again subjectively, does not seem to have a simple relationship with time; for example walking a hundred metres in one go might trigger PEM, but walking ten metres ten times over a period of time might not. However doing different things, each alone does not trigger PEM, over a period of time may cumulatively trigger PEM. It is not obvious whether the relevant time period is hours or days, whether interspersing rest impacts the consequences of activity, what the impact of switching between types of activity (physical, cognitive, etc) is.

Also in relation to PEM, either pre triggering or when in ‘recovery’, what are the vital components of rest. Some years ago I experimented with the idea that periods of lying flat on my back in a darkened room with out any distraction, sound, etc and trying to empty my mind of any thoughts might enable me to increase productive activity in any time period. Although this may be a necessary response to PEM once triggered, I found trying to do this preemptively was anything but restful and messed up my psychological state, I found such preemptive rest required some form of distraction to be achievable, that is som low level cognitive activity made the rest more restful.
 
I've mentioned elsewhere that adrenalin (which causes some downstream biochemical effects such as production of interferons) might be a mechanism that can explain why both physical and mental exertion can cause PEM. That would help to explain why 3 hours of mental work done while lying down in bed might not cause PEM, but the same amount of work done while upright and to a deadline might be more likely to.

Adrenalin seems to allow action now, at the cost of function later. A less pronounced version of that than PEM probably is a normal survival benefit for an animal - in an emergency you can perform, but you do need to rest after, to recover.

I've seen lots of people here say that they feel temporarily better when stressed or when there is something novel happening. Perhaps the adrenalin response to a stressor is operating normally, but it is that the release of interferons and whatever else as a result of the adrenalin is causing the problem?
 
I think there are a myriad of ways in which “exertion” could refer to a biological process that is not strictly correlated with “calories” (itself poorly defined in a biological context).

When it comes to energy consumption of the brain, it also bears remembering that the processes of substrate mobilization and utilization are going to be very different from the muscle.

Meaning that if PEM has something to do with the processes which increase utilization of different fuel sources (be that AMPK phosphorylation, increased glucose uptake, fatty acid mobilization, etc), this will look different between tissues.

For example, in the brain, the primary fuel source is lactate supplied dynamically by astrocytes which themselves uptake and process glucose. In the muscle, you have a combination of glucose usage and local fat stores, which release more fatty acids locally in response to activity.

So yes, it would be oversimplistic to talk only of calories for many reasons, least of which because modulation of cellular metabolism in the brain, and what may happen when those various processes operate less efficiently, looks massively different than in muscle (and looks different still than other tissues)
 
I thought calorie was a unit of energy is very precisely defined (as most physics units are)?
and it can be measured at the level of direct chemical interactions very well.

In the biological context, where you have billions of interactions happening on top of each other with different thermogenic properties, along with systemic regulation of body temperature obscuring the ability to measure heat change, you can’t measure anything definitely.

All calorie estimates for food or activity at anything more complicated than a few in-vitro protein interactions are simply a guess based on numbers from some very controlled reactions that may not apply at all in a living organism
 
Could you share the source for this? I’d be interested to read as I’ve only heard of the relationship going in the opposite direction
I talked about it here

Exercise/being upright/heat/ mental exertion >adrenalin > activates t-cells >
activated T cells produce interferon, among other things that might contribute to PEM

There's a study in mice.

I'm happy to have it explained why it can't be a mechanism for PEM.
 
I've mentioned elsewhere that adrenalin (which causes some downstream biochemical effects such as production of interferons) might be a mechanism that can explain why both physical and mental exertion can cause PEM.

Adrenalin really fits my wife's PEM - in addition to physical-effort-triggering (delayed in her early years, when she was unwittingly overdoing things; 25 years later, now moderate/severe, PEM is much more immediate), it also fits the speed/ease with which cognitive or emotional effort induces it now ... required calorific expenditure is very low if any.
 
I talked about it here

Exercise/being upright/heat/ mental exertion >adrenalin > activates t-cells >
activated T cells produce interferon, among other things that might contribute to PEM

There's a study in mice.

I'm happy to have it explained why it can't be a mechanism for PEM.
I feel like cortisol should also be looked in this context as adrenaline and cortisol work together in the stress response. Cortisol lasts a lot longer and has many effects on the body.

I wonder if anyone has measured their cortisol after overexertion and during PEM.
 
I had a 24hr urine cortisol test during delayed PEM and it was normal. The urine test might not be the best test to measure though.
Yeah I guess the measurements don't even need to be abnormal for there do be cascading effects due to ME/CFS. I just always think it fits well with the insomnia many people experience at PEM onset / during PEM.
 
I don't experience insomnia or any sleep issues during PEM onset or during. Sleeping doesn't relieve PEM either. There have been debates on cortisol but nothing concrete has come out of it.

Years ago a friend with ME did the ACTH stimulation test and it came back normal. She didn't have insomnia either.
 
Does @poetinsf have something with the idea of tolerance?

To me, none of it seems like inputs and outputs. It's a substantial, often variable, and sometimes devastating reduction in tolerance to almost everything—perhaps caused by some kind of biological brake being applied.
 
I talked about it here

Exercise/being upright/heat/ mental exertion >adrenalin > activates t-cells >
activated T cells produce interferon, among other things that might contribute to PEM

There's a study in mice.

I'm happy to have it explained why it can't be a mechanism for PEM.
one thing I've been increasingly conscious of, both (I think) in creating PEM and when in PEM, is that there is the orthostatic and there is the just supporting one's own body - and in that the more upright but also if for example you have a supportive chair which supports arms, neck, back. My car seat for example is a pretty good fit, and is a best fit for supporting everything I need it to support if it is pretty upright, and stops doing so once recline and so I'd find I was better off with it being upright evne though orthostatic is sort of a big thing for me too.

I think* that this was a thing when I was less ill as by the end of a day in the office it was that desperate feeling of needing to rest my head on the back of the chair, and when I got home getting head and face supported by a pillow. I mention this because I'm conscious these days so many would assume it is just me 'being ill but having to be out of bed' or of course that ole deconditioning assumptions. But it was there, just slower to catch up with me, when I was having to live a life where noone sensible could have claimed it was a vicious circle of deconditioning because I was having to 'act normal' so claiming other healthy people who did the same as me were somehow free of this because they did more was nonsense (unless you were the type who assumed I was wrong in what I was saying)

I will say though that I definitely used 'momentum' (a term I'm stealing from @Sean because it was spot on) in getting through any day where I wasn't at home. Whether that was adrenaline specifically I don't know but certainly I'd feel better walking that bit fast to get it done, and schzuzz it up vs doing it slowly sometimes, and if I couldn't sit I'd have to move (orthostatic issues) and that probably doesn't help that it was pushing through a sense of exhuastion and maybe sleepiness so keeping a bit focused if I could. On the other hand I'm not sure in creating PEM that did me much good - hence why these trying to be clever 'how to manage fatigue' type documents we've started seeing that are giving out exactly this same advice I know is just making the problem worse/denying it (complete misunderstanding of what the issue is and using that short-term coerce people into performing x and 'see it's better' even though you know in your body what you are doing) longer-term.

So I'm kind of intrigued what kind of measures an app type thing could come up with that can distinguish the change in whatever it is that happens due to orthostatic and how some of us are having to then compensate it and the above (body wanting to slump and lie down) with things that stop us collapsing when we are in situations when we can't. And how if we can control for things and isolate these different scenarios and reactions how they relate to what PEM /later effect someone gets on another day.

And now of course when I'm more ill it is a case of when in PEM I might be able to eventually get a little bit less than flat if I can get pillows supporting my whole body and limbs, and if on a better day then the clock starts when out of bed and it feels it runs down much much faster if I'm sitting and not supported vs maybe just a little reclined (but not enough to really make a difference to orthostatic, just gravity/weight) and very supported in all the areas I need.

As it would be quite likely to be correlated with these situations also happenning on days where I'm having to do more of 'something else' on this list, eg obviously this automatically interacts with orthostatic because I'm also 'more upright' (although slumped by the end of it) but might be having to do it to speak to someone or do an appointment it is hard to unpick.
 
Back
Top Bottom