Does existing science sufficiently demonstrate that exertion is the correct focus concept?

[Samuel]

now seems like a good time to post this. had it for a while but
seid etc. are popping up.

has the following idea been ruled out?

===

pem, pene (meicc) and exertion intolerance (iom) seem to
refer to exertion causing crashes.

sometimes it is claimed that if you do not have it, then you
do not have the disease. sometimes it is claimed that if
you do have it, then you do have the disease.

question: is this concept slightly but significantly wrong?

===

consider what i will roughly call intolerances (or
exposures):

1) exertion
2) stimulation
3) food or medicine reactions
4) social presence (think of whitney dafoe)
5) orthostatic -- being vertical
6) noise -- total and percussive
7) mold exposures
8) pesticide and chemical exposures like vinyl or gasoline
fumes
9) motion
10) flashing
11) looming
12) light (think of darkened rooms)
13) social reasoning
14) eye contact
15) interpersonal conflict
16) pain
17) nausea
18) low blood sugar
19) too hot
20) too cold
21) emergency room doctors thinking you are not sick
22) having no support
23) medical procedures

these cause crashes in many pwme.

===

why do we emphasize exertion more than intoleranaces?

are we sure only m.e. has pem? are we sure only people with
pem have m.e.? are we sure neither is the case for
intolerances above thresholds? is that why?

are crashes not relevant in m.e.?

===

some try to FIT INTOLERANCES INTO AN EXERTION FRAMEWORK:

"stimulation makes your neurons exert which causes crashes".

this is a non-insane hypothesis, but most interlocutors
don't think about cells, so it is misleading at best. do we
know whether it is biologically true?

could this be premature? could it be theory shoehorning?

===

yet there seems to be an almost contradictory idea.

some speak of intolerances as SEPARATE FROM EXERTION,
WITHOUT INCLUDING THEM AS CRASH CAUSERS.

for example, they call them symptoms, perhaps the ones that
get worse from exertion. thus, pem is a META-symptom.

is there science giving us confidence that EXERTION crashes
and STIMULATION crashes are biologically distinct? should
we draw a circle around exertion as the only META-symptom?

===

putting all this together:

what if exertion/activity is not the only cause of worsening
that scientists should focus on?

could the emphasis on pem be misleading new good scientists?

===

exert is defined by wordnet: '3: make a great effort at a
mental or physical task'. PHYSICAL and COGNITIVE is what
most people think of as exertion.

people DON'T think of "people standing there while you lie
horizontal" causing a crash!

but it can.

could physical and cognitive exertion be MERELY the most
CONSPICUOUS exposures in the most AVAILABLE subpopulations?

===

===

ok, please be gentle with me. maybe i have the wrong end of
the stick. but imo basic questions are worth asking.

is this idea ruled out? i want to focus on the biological
science. NOT QUESTIONNAIRES.

especially measurements that are done on diverse
presentations (severity, symptom profile, exposure history,
etc.), courses (relapsing/remitting, progressive,
exposure-worsened progressive, etc.), onset types (gradual,
sudden, staged, etc.).

 

[Wonko]

Probably all very good questions that should be asked, I am currently unable to answer them, I am currently unable to hold on to enough of them to understand your underlying hypothesis, assuming you have one, it's a lot of words if you don't

Things like this probably need to be asked, but I have no idea what the answer/answers are right now.

ETA - although this one has an easy answer

is there science giving us confidence that EXERTION crashes
and STIMULATION crashes are biologically distinct?

which is - probably not, I would doubt it - there is only science to back things up if someone has done it - and I would seriously doubt the people in charge of the purse strings would consider such things 'relevant', what with them not fitting the currently 'accepted' model of what ME is.

 

[Peter T]

@Samuel, I am struggling to read your post. This is partly my cognitive problems, but also I think when you copied and pasted it here the original formatting was lost. I hope you don't mind me trying to reformat it in order to try to understand it. Here is my attempt:

Now seems like a good time to post this. Had it for a while, but SEID etc. are popping up.

Has the following idea been ruled out?

PEM, PENE (MEICC) and exertion intolerance (IOM) seem to refer to exertion causing crashes. Sometimes it is claimed that if you do not have it, then you do not have the disease. Sometimes it is claimed that if you do have it, then you do have the disease.

Question: Is this concept slightly but significantly wrong?

Consider what I will roughly call intolerances (or exposures):
1) exertion
2) stimulation
3) food or medicine reactions
4) social presence (think of Whitney Dafoe)
5) orthostatic - being vertical
6) noise - total and percussive
7) mold exposures
8) pesticide and chemical exposures like vinyl or gasoline fumes
9) motion
10) flashing
11) looming
12) light (think of darkened rooms)
13) social reasoning
14) eye contact
15) interpersonal conflict
16) pain
17) nausea
18) low blood sugar
19) too hot
20) too cold
21) emergency room doctors thinking you are not sick
22) having no support
23) medical procedures

These cause crashes in many pwme.

Why do we emphasize exertion more than intolerances? Are we sure only ME has PEM? Are we sure only people with PEM have ME? Are we sure neither is the case for intolerances above thresholds? Is that why? Are crashes not relevant in ME?

Some try to FIT INTOLERANCES INTO AN EXERTION FRAMEWORK:

"Stimulation makes your neurons exert which causes crashes".

This is a non-insane hypothesis, but most interlocutors don't think about cells, so it is misleading at best. Do we know whether it is biologically true? Could this be premature? Could it be theory shoehorning?

Yet there seems to be an almost contradictory idea.

Some speak of intolerances as SEPARATE FROM EXERTION, WITHOUT INCLUDING THEM AS CRASH CAUSERS. For example, they call them symptoms, perhaps the ones that get worse from exertion. Thus, PEM is a META-symptom.

Is there science giving us confidence that EXERTION crashes and STIMULATION crashes are biologically distinct? Should we draw a circle around exertion as the only META-symptom?

Putting all this together:

What if exertion/activity is not the only cause of worsening that scientists should focus on? Could the emphasis on PEM be misleading new good scientists? Exert is defined by wordnet: 'make a great effort at a mental or physical task'. PHYSICAL and COGNITIVE is what most people think of as exertion.

People DON'T think of "people standing there while you lie horizontal" causing a crash, but it can. Could physical and cognitive exertion be MERELY the most CONSPICUOUS exposures in the most AVAILABLE subpopulations?

OK, please be gentle with me. Maybe I have the wrong end of the stick. But imo basic questions are worth asking.

Is this idea ruled out? I want to focus on the biological science. NOT QUESTIONNAIRES. Especially measurements that are done on diverse presentations (severity, symptom profile, exposure history, etc.), courses (relapsing/remitting, progressive, exposure-worsened progressive, etc.), onset types (gradual, sudden, staged, etc.).

My apologies if this has misrepresented what you are saying. If I understand correctly you are asking:

What is the relationship between the ideas of 'post exertional malaise' and 'exercise intolerance'?

How does the idea that 'exertion' triggers a crash relate to the reality of the many other common 'intolerances' triggering our symptoms? Are we looking at different mechanisms with PEM being a distinguishing feature of ME, or are we looking at a single mechanism underlying our many intolerances with PEM being only one example?

Is the assertion that PEM is necessary and sufficient for ME and unique to ME the best way of looking at the situation, or is it even correct? Should we rather be looking the full range of the intolerances and asking questions about trigger thresholds?

Personally I also wonder if we should be looking at what we mean by 'crashes'. I have my ME symptoms which vary in intensity, but can persist at severely disabliling levels for months and years, is this then an ongoing crash? I personally distinguish between ongoing symptoms and a sudden worsening or even appearance of symptoms following exertion which I would call a crash. Sometimes intolerances including exertion can trigger a crash, but also sometimes the appearance of intolerances seem to be best described as a symptom of the crash.

[edited for clarity]

 

[Peter T]

could the emphasis on pem be misleading new good scientists?

The emphasis on PEM as a defining characteristic of ME is used in the selection of research subjects, but it is not generally the object of most biomedical research. So though it is used to direct researchers as to who to look at, I don't think it is restricting what they look at. Even when researchers are specifically investigating physiological reactions to exercise they are not necessarily investigating PEM.

So though we are using a diagnostic criteria that is not fully understood and is inadequately defined, I don't believe it is necessarily limiting research which by necessity is 'trying to pull ourselves up by our own boot straps' until we have established reliable biomarkers.

That is not to say that understanding PEM and refining our descriptive language for ME is not of major importance in understanding/describing our experience and in finding ways to manage our symptoms. For me the greatest value of the idea of PEM at our present level of understanding is that it gives us a concept that can be used to help ourselves and others, both lay and professional, understand that ME is qualitively different to 'being tired', to help understand there is a unique and abnormal biological process involved even though we do not fully understand that process.

[edited for clarity]

 

[Trish]

The 2 day CPET is an example of a test that shows there is something different in the response to exercise in pwME compared to healthy people and people with apparently similar conditions like MS. Both ME and MS cause fatigue, but only pwME have reduced aerobic capacity as shown on the 2 day CPET the day after exertion.

I think most pwme who do the 2day CPET report PEM after the test, which is why we are warned against doing the test unless we have to for good reason. So perhaps this is biomedical evidence that PEM is a thing worth studying, and it can be induced reliably by doing a 2day CPET and other biological things can be measured and tested to see if they change after this exercise. I think several current studies are doing just that - testing before and after an exercise challenge.


It might be interesting to test whether, for example, cognitive exertion, noise overstimulation, provocation with other things that individuals report triggering their PEM have the same effects as exercise on these biochemical tests. In other words, is the reaction of pwme to sensory stimuli that can set off PEM the same as the reaction to physical activity?

 

[Sly Saint]

ME is qualitively different to 'being tired', to help understand there is a unique and abnormal biological process involved even though we do not fully understand that process.

thank you for this; I was just trying to come up with something along those lines for this thread:
https://www.s4me.info/threads/is-the-fatigue-tiredness-experienced-by-pwme-a-form-of-dynapenia.6022/

I was toying with cause and effect descriptors but although I can 'see' what I want to say in my head, cannot find a succinct way to put it into words.

 

[JaimeS]

some speak of intolerances as SEPARATE FROM EXERTION,
WITHOUT INCLUDING THEM AS CRASH CAUSERS.

This was one of the changes that someone asked for re: the CDC's new recs for ME. It was a really interesting idea to me, because I hadn't thought of it that way, before. But both intolerances and sensitivities have sent me crashing -- beyond the shadow of a doubt.

Rob (Phair) once asked me if the crashes were different in character when they were from different stimuli and my knee-jerk response was 'no'.

But then I had a sensory-stimulus crash and had to acknowledge that the symptoms, while they had overlap, were not the same.

It's not something I've examined this closely before Rob brought it up. The basic feeling is feeling sick/poisoned, weighted down, and with burning or tingling in the muscles, sometimes with twitching. But the other symptoms vary depending on the stimulus: orthostatic issues, mental/cognitive effort, physical effort. So.

Yes, it probably matters. And it's probably part of why PEM is so hard to define. I felt I understood it well until I started asking other patients to describe PEM to me and they all had different answers that were all different from mine.

Moreover, there are 'mini crashes' where I feel much worse but for only a few hours. Finally, I have "PEM-lite" where I'm just dragging for multiple days in a row, but it's hard to call it 'crashed' when I know what a full-on crash feels like. I've started to call these 'a slump'!

 

[Inara]

In other words, is the reaction of pwme to sensory stimuli that can set off PEM the same as the reaction to physical activity?

Wasn't there a researcher at the Stanford conference saying he causes PEM by massaging?

What is the relationship between the ideas of 'post exertional malaise' and 'exercise intolerance'?

How does the idea that 'exertion' triggers a crash relate to the reality of the many other common 'intolerances' triggering our symptoms? Are we looking at different mechanisms with PEM being a distinguishing feature of ME, or are we looking at a single mechanism underlying our many intolerances with PEM being only one example?

Is the assertion that PEM is necessary and sufficient for ME and unique to ME the best way of looking at the situation, or is it even correct? Should we rather be looking the full range of the intolerances and asking questions about trigger thresholds?

Your post, @Samuel, made me understand something. It also comes in the right time for me, having a discussion about SEID, CFS, ME in ICD in mind.

It was my husband pointing it out during an appointment with a doctor, that my sole problem isn't that I can't train anymore and that my muscles burn instantly, but that the disease affects my entire life. This includes all of what you listed (No. 1-23). I think you're right that it has to be made clear that it's not only "exercise" that can make it worse, but also any activity (in the severe cases, "activity" could be the body functions). I am also unsure about the word "exertion" in the sense that most people link to "exertion" a marathon or a 24h-shift in a hospital. In case of ME, "exertion" can be noise or just music or making food, buying food, going for a walk, having an infection etc. But that's not the meaning of "exertion" itself.

I don't know why, but I can't get warm with "intolerance", although it's not false.

Regarding PEM: No, it doesn't seem to be ME exclusive alone. I think about @TrixieStix' story, or mine (ME isn't ruled out, but it seems the mutation I have wasn't found in other ME patients, but I confess I don't know if it was looked for. In that case I have ME symptoms, but I wouldn't have ME.) I know of someone with a hypophosphatasia diagnosis that has ME symptoms, including PEM. I therefore think it's important to look at diseases that share a certain amount of symptoms with ME. Also, it's sometimes hard to put into words what one experiences. I think it possible that person1 PEM is not the same as person2 PEM; and if it's PEM at all? Some will mean "swiftly exhausted but after a day's rest, it's ok" (that's already disabling), some will mean "I feel worse for days" etc.

Still, PEM is a central feature in ME. It seems other diseases focus on another symptom.

Coming back to SEID, and reflecting upon your post a bit, it seems to be too narrow in the sense that it focuses on the exertion intolerance alone and leaves out all the other intolerances. It suggests the problem in ME is exercise/activity alone, which is not entirely correct, because (many?) people with ME also have symptoms when lying in bed.

I hope I understood you correctly.

Edit: @JaimeS, your post is quite interesting. That's what I mean with "person1 PEM" and "person2 PEM". It's worth observing my PEMs for the future a bit to see if there are a quality differences...

 

[Sly Saint]

Something else, that was briefly discussed on another thread, that doesn't seem to be being considered with regards activity and any other stimuli and PEM is the possibility that it is cumulative.

For me, this makes much more sense and might help to explain the different 'delay' times and fits in with the energy envelope theory.

 

[NelliePledge]

Is exertion used as a shorthand for ‘use of energy’ intolerance. And depending on your type and severity of ME this can mean literally anything that requires your body to expend energy which may or not be something you can actively control. So the milder people it will be taking any brisk exercise, it can also be something cognitively demanding like working. It can also be related to digestion of food which takes a lot of energy. And if your body has a reaction against a chemical it uses more energy for that reaction?? And noise and light are causing cognitive energy demands. Talking uses cognitive energy. The more severe you are the more underlying energy demands that people don’t even normally register as requiring any physical or cognitive energy cause ‘Overexertion’ such as the presence of someone in the room with you.

Someone highlighted enervating as a possible description maybe on another thread ? and it would seem that’s what Dr Hanson calls her centre at Cornell. But even then I’m not sure this would include the energy use that is involved in a reaction rather than an action.

ETA I went looking for a link to definition of enervate and it refers to heat causing enervation so it does cover off a reaction. https://dictionary.cambridge.org/dictionary/english/enervating

 

[Wonko]

My understanding is that, of total calories used, actual exercise/work/movement accounts for only a fairly small proportion, for most people i.e. most of the energy used is for background tasks.

This is why weight is generally lost in the kitchen, through dietary changes/restriction, rather than the gym.

e.g. assuming (and this is just a made up figure) that only 40% of calories used/energy expenditure is 'voluntary' - as a result of working, exercise, general stuff. This leaves 60% used by the organic processes of keeping you alive.

If you have a condition which impairs energy production/utilisation by 25% this would result in you having only 15% available for voluntary activity, as opposed to a normal persons, scaleable, 40%.

If you have a condition which impairs energy production/utilisation by 50% then there isn't enough energy to meet your basal metabolic rates demands, and your body can't even manage basic 'housekeeping' to keep you alive and healthy.

Obviously it's a lot more complicated than that, you body doesn't simply switch off bits it doesn't have the energy to run properly, so what seems to happen in practice is that various bits of you get downgraded.

As the brain is a particularly high energy user, cutting back on it's available resources, may lead to cognitive issues,whilst other systems may also be running less optimally due to energy restrictions,we tend to live in our heads, so a energy deficit there, is noticeable, more noticeable.

Or, some words.

 

[Keela Too]

@Wonko What you are saying is similar to my thoughts in this post.

http://sallyjustme.blogspot.com/2016/05/disposable-energy.html

 

[Jonathan Edwards]

I think you may be spot on, @Samuel.

 

[Hoopoe]

I would say that different triggers produce (somewhat) different kinds of symptom exacerbations.

 

[JaimeS]

Wasn't there a researcher at the Stanford conference saying he causes PEM by massaging?

Yes, Moreau.

 

[Samuel]

Coming back to SEID, and reflecting upon your post a bit, it seems to be too narrow in the sense that it focuses on the exertion intolerance alone and leaves out all the other intolerances. It suggests the problem in ME is exercise/activity alone, which is not entirely correct, because (many?) people with ME also have symptoms when lying in bed.

I hope I understood you correctly.

yes.

a major question in the op is whether we are focusing too much on activity, perhaps merely because that, out of all of the intolerances, is the most conspicuous and available and commonly described.

as an example hypothesis: subjects who enter studies are almost always able to travel to the lab. if there is a correlation between that ability and the /prominence/ of activity as a crash causer, then this might bias scientists into thinking that crashes from activity are more significant than crashes from the rest of the intolerances. take a look at those in darkened rooms. maybe the relative prominence of activity as a crash causer is smaller.

so we could be biased by sampling into thinking it is an activity-related disease, when it is an intolerance-related disease (see list in op).

ETA: 1) that was just an example hypothesis and 2) we're only talking about "core symptoms"; it is quite clear that a lot have e.g. gastroparesis and that a lot have e.g. reversed phase sleep despite it being rare and so on.

 

[Samuel]

... For me the greatest value of the idea of PEM at our present level of understanding is that it gives us a concept that can be used to help ourselves and others, both lay and professional, understand that ME is qualitively different to 'being tired', to help understand there is a unique and abnormal biological process involved even though we do not fully understand that process.

my opinion is possibly opposite to your opinion as expressed here. assuming i understand yours.

i agree that in principle activity intolerance as opposed to popular understandings of the disease could be a limited win in understanding. we keep trying to make it a win.

but i am going to (try to in fog) argue that that debate is possibly conceding practically everything to the wrong understanding. and it will be a battle fought forever until activism or science changes really really significantly.

we can't operate on hope. it fails.

the reason is that it is still in the domain of activity. it's too subtle a distinction. not to us on this forum, but to those who need to understand.

it is too subtle to say "not fatigue or tiredness but this other thing that sounds a lot like fatigue or tiredness." which gets an "ok, whatever".

practically nobody cares. you can't force them to care. there is global propaganda pushing int he other direction. as part of a systematic and widespread attack on a civilian population.

and it might well be ignoring stuff about the disease that is relevant! that is what op is saying.

i don't think we should ever have been in the debate over whether the disease is being tired. i don't think the value of saying it isn't being tired is useful except as a kind of attempt to hold back a gale with an umbrella.

for some it is being tired. and that is ok. but the fact that there exist those who progressed from that to a comletely different looking disease should nix that debate. they did not switch diseases! ergo: the debate about tiredness or fatigue is misplaced.

please see myth 1 including any footnotes in http://thekafkapandemic.blogspot.com/2013/03/three-damaging-myths-about-severity.html . which says the same thing but possibly more clearly.

there exists a dirty lawyer trick. focus on one (preferably trivial seeming) part of plaintiff argument. make plaintiff talk about that.

this distracts from big picture.

i think that's what we end up doing unintentionally when we stay in the activity domain.

getting back to understanding:

emphasizing activity is contributing to the perception that the whole thing is activity related. or fatigue. or tiredness. whateverrrrrrrrrrrrrz.

look at abstracts from practically ANY biology paper. the disease in those abstracts looks like mild altitude sickness. the disease is characterized by .....

it has improved recently to "highly debilitating" or something.

you frequently get something like "and similar". this makes no sense. perhaps in being nonspecific? aha. ok. whateverzzzzz. let's watch cat videos on youtube.

or perhaps in being in the activity domain. aha. i get it now. i'm tired too. check email.

reinforcing the activity domain stuff is reinforcing the same thing everybody thinks anyway.

a lot of audiences have rational ignorance. we need to hit them with stuff they do not know.

there is stuff about characterization in http://thekafkapandemic.blogspot.com/2012/03/characterization-and-unaware-mild.html

===

and i don't think we should ever have been in the debate over whether there is pathophysiology. if you look at the entire disease, it is A PRIORI bollocks.

at best, witchcraft and alien abduction are no less possible. i have expressed this more carefully in future posts.

===

please don't hold me to my wording in any of this post. or anything posted today.

idk if i have clarified.

thank you for reading.

 

[Creekside]

Late to the discussion, but I think there's confusion between PEM and crashes or other worsening of symptoms. We don't have a proper, verifiable clinical definition of PEM but it does seem to be separate from crashes and other worsening. Some of the triggers you listed might apply to those 'non-PEM' responses.

For myself, I get definite PEM from both physical exertion and from cerebral exertion. I seem to get the same symptoms from both (hard to tell differences) but my physically-induced PEM has a consistent 24 hr delay, while cerebrally-induced PEM can take place within an hour (inconsistent delay). Also, I can block my physically-induced PEM by taking cumin (Cuminum cyminum), but it doesn't work against my cerebrally-induced PEM. So, the two types are different, but have some commonalities.

"stimulation makes your neurons exert which causes crashes".

I had this theory just last evening. I wondered whether physical exertion has a significant cerebral exertion component, and apparently this is true. The harder a physical task is, the more cerebral effort is required. Thus it is at least possible that physical exertion triggers PEM due to the extra cerebral activity. Some of the other things in your list of exposures also require significant extra cerebral effort. My conclusion is that all PEM might be caused by cerebral activity. It's up to someone more capable to prove or disprove that theory.

 

[Mithriel]

If the Workwell results are correct, and what they have found matches my ME very well, we have broken aerobic energy production systems in our cells.

When a cell is set to work it uses an anaerobic respiration pathway which produces pyruvate and 2-5 ATP. After a few minutes the accumulated pyruvate is fed into the citric acid cycle which basically metabolises oxygen to produce about 32 molecules of ATP (which is the battery of the body)

In healthy people, these 32 molecules of ATP from each cycle run the metabolism. When they exert themselves, physically or cognitively there is plenty of energy available to run things. If they do need more energy than is available the body uses the anaerobic system (which carries on in the background all the time) as an emergency system for a while. This is when you get out of breath (and is called aerobic exercise just to confuse things!)

(This is a very simplistic explanation of the science but it gives the main points.)

What happens with us is we are forced to rely too much on the anaerobic system. We hit that point much sooner than healthy controls. The shortage of ATP can affect every system but especially those that need a lot of energy such as the muscles and the brain. In people who have this defect both physical and cognitive systems will crash because of the same problem.

In MS, the symptoms you have depend on which nerves are affected by demyelination. I believe that ME is the same; the symptoms you experience will depend on which type of organ has the most cells affected by damaged aerobic respiration.

These problems with exertion are the only ones unique to ME. Even if we share symptoms with other diseases it is necessary to concentrate the science on the one that is different and then work outwards from that to shared things.

 

[Samuel]

Late to the discussion, but I think there's confusion between PEM and crashes or other worsening of symptoms. We don't have a proper, verifiable clinical definition of PEM but it does seem to be separate from crashes and other worsening.

Hi @Creekside, can you elaborate on the differences among pem, crashes, and other worsening of symptoms?