• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

What causes PEM symptoms?

daisybell

Senior Member
Messages
1,613
Location
New Zealand
I am just coming out of a 'crash' and have been thinking about what could explain PEM...
This last bout was I think brought on by socialising, possibly on the back of too much physical activity preparing for Xmas...
But what is it that can cause all systems to slide so quickly? I feel not only the physical fatigue, but also huge cognitive fatigue, and also what I can only describe as a hormonal wave... Sinking down.

It's like watching the waves on a beach, and suddenly realising that the sea has retreated too far and a tsunami is coming.

Is energy production so similar throughout the brain and body that a problem with this can cause all the symptoms? And so quickly?

Is there really the fluctuation in hormones/neurotransmitters that I feel?

Sorry if these are daft questions, but I see PEM discussed lots in terms of what we do to bring it on, and what it feels like, but not why it happens at a biochemical level.
 

Mij

Messages
2,353
@daisybell

have you seen this video by Mark VanNess? He states that lactic acid is not what produces muscle soreness contrary to what most think. It's the byproduct CO2 (potent acid), if it's not rid by the body it can cause toxicity.

PEM can affect each of us differently depending which system is affected, metabolic, pulomary etc

 

halcyon

Senior Member
Messages
2,482
Sorry if these are daft questions, but I see PEM discussed lots in terms of what we do to bring it on, and what it feels like, but not why it happens at a biochemical level.
It's quite the opposite of a daft question. In fact if we could answer this question we'd likely be that much closer to understanding the cause of this disease.

The only thing that's clear is that we have an exaggerated physiological response to exertion. For example, this study by Light et al. that found greater expression of metabolite sensing, adrenergic, and immune function genes in ME patients versus controls after exertion.

Also, as Mij mentioned, there is an abnormal lactate response to exertion found in ME patients. This study by Lane et al. confirmed this occurs in patients with chronic enterovirus infection.

These are just two examples, but I think you get the point. Exertion can cause an increase of substances that can have a powerful effect on our physiology and cause myriad of symptoms.
 

daisybell

Senior Member
Messages
1,613
Location
New Zealand
It's quite the opposite of a daft question. In fact if we could answer this question we'd likely be that much closer to understanding the cause of this disease.

The only thing that's clear is that we have an exaggerated physiological response to exertion. For example, this study by Light et al. that found greater expression of metabolite sensing, adrenergic, and immune function genes in ME patients versus controls after exertion.

Also, as Mij mentioned, there is an abnormal lactate response to exertion found in ME patients. This study by Lane et al. confirmed this occurs in patients with chronic enterovirus infection.

Do those responses explain the rapid onset of symptoms though? That's what I can't get my head around... How can so many systems 'meltdown' so quickly? Surely the expression of genes can't account for it? And does lactate explain the neurological stuff?
 

halcyon

Senior Member
Messages
2,482
Do those responses explain the rapid onset of symptoms though? That's what I can't get my head around... How can so many systems 'meltdown' so quickly? Surely the expression of genes can't account for it? And does lactate explain the neurological stuff?
I believe they can. For example, increased expression of immune system genes can mean increased release of inflammatory cytokines. These cytokines can cause immediate changes to occur in organs all throughout the body.

I'm not sure about your last question, but excess lactate is definitely not a good thing and can cause a variety of symptoms, as in lactic acidosis.
 

daisybell

Senior Member
Messages
1,613
Location
New Zealand
Thanks @halcyon
Can cytokines result in the feeling of excess lactate?
How can PEM brought on by cognitive overload have as a symptom the aching heavy muscles?
I guess I just can't see how it all ties together. There are lots of explanations for each bit of the issue, but the big picture seems so elusive!
 

Scarecrow

Revolting Peasant
Messages
1,904
Location
Scotland
@daisybell You're link on the P2P thread was just fine.

The other thing that might be going on with PEM (in addition to metabolic and immunological stuff) is OI issues. For example, do you have a typical reaction to shopping (standing a lot) as opposed to walking at a steady pace?
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Nobody knows what PEM is. There are lots of theories. What we do know is our lactate goes nuts, some hormones go nuts, and some cytokines go nuts. To top this off there is a crash in energy production and efficiency. You can find out a lot about this by looking at the Light's and Workwell's research.

To top this all off our brains have reduced blood flow after exercise, and lower metabolic rate.

We know a fair bit about the physiology, but what is causing it comes down to unproven hypotheses.

Its been known for at least a decade and a half that lactic acid does not cause muscle problems. It helps muscle problems. Lactic acid is only an issue if its severe and prolonged (e.g. constantly for 3 days), as it can trigger acidosis. However lactic acid is a marker for metabolic issues. Its not the cause, but id demonstrates an issue is present. Overworked muscle produces lactate. Ours produces (in in vitro testing) twenty times as much as controls.
 

daisybell

Senior Member
Messages
1,613
Location
New Zealand
@alex3619
Has anyone in your mind come close to a good theory? We seem to be so far downstream, and nothing I have read gives causation clearly. Endothelial dysfunction can only be part of the picture.... The same with endocrine issues... I can't believe that there are a whole load of monsters upstream, surely there must be one driving all the others, and it has to be deep in the brain?
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Nobody has a complete theory. They all look at their little bits. Its like, they put five pieces together of 1000 piece jigsaw puzzle, and guess at the big picture. They then go looking for more pieces, and slowly add them. Someone else started on a different set of pieces, and are slowly putting them together. Both have different ideas of what the whole puzzle is. Both think their ideas are the most important.

In time the pieces will merge, and instead of the puzzle being mostly things that don't fit, it will be the holes that are the exception not the pieces that do fit.
 

daisybell

Senior Member
Messages
1,613
Location
New Zealand
Nobody has a complete theory. They all look at their little bits. Its like, they put five pieces together of 1000 piece jigsaw puzzle, and guess at the big picture. They then go looking for more pieces, and slowly add them. Someone else started on a different set of pieces, and are slowly putting them together. Both have different ideas of what the whole puzzle is. Both think their ideas are the most important.

In time the pieces will merge, and instead of the puzzle being mostly things that don't fit, it will be the holes that are the exception not the pieces that do fit.
I hope you're right! I do worry that we are still at the stage of people making up the puzzle, based on only their few pieces, and that the world of research is so competitive, even in ME which most won't touch, that the necessary sharing is being so slow to get going. And we know that hoof prints don't mean horses for us!
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
For me standing still is the worst. It is much better to walk. Why is this?

This is usually caused by some kind of dysautonomia (autonomic system dysfunction). Anyone with that symptom needs a tilt table test to find out what kind of dysautonomia they have so they can be put on the right treatment.

Walking is better then standing with some of the dysautonomias eg POTS.. usually due to low blood volume. When you walk you are helping keep the blood getting to your brain easier, where as when you stand.. its pooling in your body in areas eg in the abdomen and legs.

Anyway, you a need tilt table test done (or a standing poor mans test for POTS at the very least).
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
One CFS study found huge amounts of lactic acid is being built up in us, I think it was something like up to 300 times normal amounts. No wonder our bodies can hurt!
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I'm not sure about your last question, but excess lactate is definitely not a good thing and can cause a variety of symptoms, as in lactic acidosis.
To a point and for reasonable time frames, lactate IS a good thing. The more, the better. It increases oxygen dumping and alters enzyme activity to ramp up metabolism. What it is though is indicator of something bad going on. It is a sign of insufficient mitochondrial metabolism, where demand exceeds capacity.

Lactic acidosis takes days to manifest. This is because the high lactate alters enzyme activity, which increases lactate, setting up a positive feedback loop that ends in death. Substantive alterations of the key enzyme 2,3 bpg takes a day or several. Short term lactate in us is during exercise and for some hours later. It might lead to lactic acidosis if we keep pushing and pushing for days though.
 

beaker

ME/cfs 1986
Messages
773
Location
USA
For me standing still is the worst. It is much better to walk. Why is this?
Julian Stewart, and colleagues have recently ( and in the past) published studies using intra cranial doppler to measure blood flow to the brain during tilts ( sorry too flared to look up links for you) . I have been told others have been using this device as well. It gives hard proof to show that when standing your blood flow to brain drastically declines.

I would think that losing blood to the brain would trigger all sorts of things that the brain controls to react and/or to have those things not function well.
That to me seems like a good reason for a part of PEM as well as immediate reaction, of course, of how awful one feels standing still. your body is going into a faint, which in a way is a protective mechanism. a faint gets you down flat to get that blood back to your brain.
 

heapsreal

iherb 10% discount code OPA989,
Messages
10,089
Location
australia (brisbane)
It's a good question that started this thread, the next would be how to recover from it or prevent it.

I have tried supplying the different energy substrates that make atp ie creatine, ribose, glutamine and bcaa as well as the mito supps like q10 and carnitine. They help some but don't appear to be the answer fully.

I have thought of general recovery like anabolism and try to optimize sleep which helps growth hormone and other anabolic hormones for growth and repair as well as ttestosterone and dhea replacement. Again it helps some but there is just a missing piece in the energy production and recovery.

I find if I'm rested enough I can produce the energy but the bigger issue for me is the recovery process. This process I find myself thinking about abit to try and increase my function a little more. Makes my head spin thinking about it.