Do ME symptoms fit with the faulty energy metabolism hypothesis?

Another interesting observation.

It's what's missing in all of those severity scales. They all have something along the lines of "symptoms mild/moderate/severe at rest" to estimate severity of illness. For me that results in nonsense. When I was mild my symptoms were "moderate at rest" (no pacing, so continuous state of PEM). Now that I'm severe symptoms are often "mild at rest" (pacing, but when in PEM symptoms are diabolical).

It makes much more sense to look at what level of activity triggers PEM to estimate severity. When I was mild I could safely manage a 20 minute walk (though stupidly I almost always did more) whereas now 2 minutes will send me into PEM.

This could fit with an energy metabolism problem as hypothesised in my previous post:

increased severity of illness --> bigger (upstream?) 'fault' that causes ATP generation problems --> less ATP --> more 'danger' signal pumped out more quickly --> more susceptible to worse PEM

Does any of this even make sense? I'm in the diabolical symptoms phase of PEM and feeling somewhat disoriented in the foggy maze of my own thoughts... back to bed I think.

 

My experiences are the same as @Trish 's OP. And this thread is fascinating, I always feel so grateful to you @Jonathan Edwards as you have obviously really listened to the experiences of patients - ie trying to understand what it's really like before coming up with theories that cant fit - which seems to be what a lot of researchers do. This illness is extremely nuanced in it's manifestations & istm that it will take the kind of approach you are applying to make any headway at all.

One thing i have always pondered is how on earth too much mental activity can make my muscles weak. When in PEM or even directly after the (purely mental) activity - eg reading/thinking (which i always have to do reclining with legs up or i dont have the energy to think straight) or even after too much sensory input (eg lying still listening to music in bright sunlight for too long), after that my leg muscles will shake when i try to climb the stairs, in the same way they do when i have standing up for too long/walked too far.
This is something that always takes me by surprise, (even 17years in) so it cant even be that i'm expecting it to happen & therefore 'look' for it, - i never expect to be so physically weak after mental activity, but i often struggle to lift the milk bottle after a bit of reading. I really do wonder why that is, as i wasn't using the muscles in my arms at all while listening to music.

Any ideas?

 

I don't think its only impaired energy metabolism, though that is a large component. We are still learning what it is. However this is not just about impaired energy in our muscles, but many tissues in our bodies, and not all identified yet I suspect.

I am not sure about the magnesium, but I wonder if the low omega 3 fats might be linked to high levels of oxidative stress, or a high need for nerve repair. I would expect a high need for magnesium but it is not clear why this would necessarily lead to low levels if diet is adequate.

Right now I am in day three of a very rare symptom for me, severe weakness. I cannot always type a letter (I try and think I do but fail), and cannot grasp things I can normally grasp. Its disturbing to type this text. I wonder if its electrolyte depletion, and have tested calcium to some effect, need to try more but I have limited options. I feel like I am going to collapse but am not super low on energy.

ME is not just energy depletion, but there is no doubt its part of the complex of problems.

We should not dismiss the epigenetic and expressed gene changes, which have as yet not understood consequences, nor should we ignore metabolite depletion.

I have noticed a recent question as to our hyper- versus hypo- metabolism. We have low energy, but high energy metabolism throughput, but also low intermediate metabolites in many pathways. So its a mix of hyper- and hypo-, depending on what is being discussed. Indeed the low oxidative energy production means much more metabolism of glucose, but via glycolysis and lactic acid which does not produce energy as efficiently. Hypo- and hyper- go together. Lactic acid also puts an energy strain on the liver.

 

I recall one occasion where I was in a crash and trying to get home. I moved at a very slow shuffle, rested regularly, and could not pick my feet up at all. At one point I had to use an elevator rather than a few steps. Even one step was too much.

 

This might be too long for some to read. Sorry for this.

Yes, there are similarities to having a flu and overdoing and the flu worsens severely. Except that the ME PEM has many more symptoms, so many and severe.

Now that my ME is more moderate I can do more before stirring up PEM symptoms. When I say stirring up PEM I mean that the symptoms that I do already have at moderate level, become worse with the added PEM. So, there is always a level of ME going on symptom-wise at whatever level you are at, PEM is what is added on top.

When I was in severe ME I would get an instant headache, my sinuses would start aching, difficulty walking, talking and thinking and I would get other symptoms as well straightaway. My breathing would also deteriorate as if I had run a marathon. I would head straight for bed and be very unwell. The next day I would worsen and it would take a few days or more to ease a bit.

The problem with very severe and severe ME is that you can do very little without triggering PEM and so you are on a rollercoaster of PEM on top of PEM. This level of ME is not a comfortable one, there's a lot of desperation and trying to hang in there. You are mostly suffering day in and day out with symptoms that are very loud and never-ending and from hour to hour you don't know what you are going to experience next symptom-wise because there are so many coming and going and some stay longer than others, symptoms added on top of other ones.

I agree with others about the 3 different PEMs. I experience the instant, delayed and the accumulation PEM.

 

I have had one more. If there is any rotting or moldy food about, like fallen down behind something, then I can get something very like PEM.

 

I wonder if your blood pressure is dropping too low @alex3619 you probably have checked for this though? I'm thinking of you.

 

Ok I’m confused here.

Is the suggestion here that

A) Paul Fisher’s data https://www.s4me.info/threads/video...nsatory-changes-in-me-cfs-patient-cells.9177/ are incorrect

OR

B) These data are correct but that they are not relevant to the symptoms of CFS—rather Fisher’s observations are a by-product or a downstream effect of the real cause of ME/CFS. If this scenario is true, then any interventions that “fix” the mitochondria would not treat or cure CFS.

Thanks for any clarification.

 

Me too. Although I would describe it more as mental activity makes my legs ache as if I had been running around on them all day (at least that is my memory of how it used to feel back when I was well).

 

I think B but they are relevant to the symptoms.

 

I have severe OI but also worsening high blood pressure. Its much more likely to be too high unless I accidentally took a double dose of blood pressure meds.

 

@Jaybee00 Has Dr Fisher published anything or are these preliminary findings reported at a conference?

 

It's the latter - it's his presentation at the recent Emerge conference.

 

When I am exerting there comes a point, soon or later, when it feels as if I run out of something and I can't go on till I have it back (like visual purple). Signalling problems are just not fast enough to account for the few seconds that make movement possible again.

The theory that seems to match my symptoms best is that we have trouble producing enough ATP or something biochemical. Healthy people have plenty but we are limited. At rest it may be adequate but when we need more to move an arm, say, it does not leave enough for other processes which are less important at that moment. Like blood been taken from the extremities to the core when it is cold.

If that diversion is for a few minutes, no problem but if it goes on or is extreme then there will be down stream effects that will magnify leading to further problems like digestion or OI

Also the processes that clean up the byproducts of anaerobic respiration use energy as well so there is less available causing delayed PEM eventually.

Writing is a good example of the problems we have. One ME doctor would get his patients to write out their symptoms in the waiting room to look for deterioration.

 

My experiences particularly concur with @Rosie’s of accumulation PEM. That is just how I experience it.
Instant PEM is very variable. Sometimes I seem to evade it for up to 36 hours then it hits and it takes 2-4 days for it to recede. The length of time to initiation of PEM and recovery from it ( still with ME) seems to depend on what has triggered it. Some things take longer to pass through. Am currently PEMed from family visit on Sunday. Interaction with more than 1 person provokes heavier PEM, as does trying to understand how something works. I have to think hard and I can feel the battery running out.

Apologies for not reading all posts: not taking in enough.

 

Is it immediate or delayed symptoms?

I experience immediate PEM like symptoms during allergy season without cognitive issues when I over exert just a little, the energy overexertion is always delayed PEM.

 

Exactly the same for me. I can be sitting calculating formulas for 15 minutes and when I get up my calves and legs feel as though I have climbed a mountain at high speed. My equilibrium is also affected.

 

I’ve also wondered about this one. I’m always amazed that cognitive activity can seemingly cause pain and aches in my muscles.

I’ve always assumed that whatever causes PEM is triggered when I use too much energy and it doesn’t matter if that’s physical or cognitive activity. It’s a hard one to get your head around though.

 

Yes, it is not a purely central process and nor is it purely delayed... The immediate effects are in the muscles used and these muscles are affected more in the subsequent days.

I don't experience that at all (muscle weakness post-exam for example). I can experience stiffness, pain etc. if I am in the same position for a long period of time (e.g. reading), but it is not muscle weakness as a result.