Rapid fatigability or a lower amount of available energy - the same thing or different?

[Andy]

So to state from the start, I don't have the answer to the question in the thread title, but that's why I've started the thread.

I've been mulling over how I might present ME on a basic level to people who don't understand it and rather than launch into PEM from the start, I thought emphasising the reduced level of available energy would be an easier concept for people to grasp (and that could then lead more naturally on to the consequences of overexertion). But do people here feel that the best explanation is simply that we have a reduced store of energy, or that our ability to replenish the store is diminished, or both?

While I would love to have scientific proof for any of this then that would be great but I'm as interested in whether this matches the experiences of people here.

 

[Jonathan Edwards]

What are you meaning by energy, Andy?
Strictly speaking the store of energy, chemically, in someone with ME is going to be the same as a normal person.

You talk of availability of energy. I see that as meaning two different things. One is the sense of energy not being available - which is very much part of my own experience now that I am over 70. The other is a biochemical explanation in terms of pathways that might make energy less available. I think the question is whether the first meaning is followed by the second or whether in fact the sense of energy not being available is nothing to do with biochemical pathways making energy available. Unfortunately, I don't think we know.

So I guess the question is what concept you want people to grasp and are we in a position to present ME in those terms? My intuition is that my own sense of limited available energy has nothing to do with a store of energy in the chemical sense. It seems more likely to be due to neural signals telling me to stop doing things.

 

[Andy]

Strictly speaking the store of energy, chemically, in someone with ME is going to be the same as a normal person.

Do we have proof of this, or is this based on the assumption that there doesn't seem to be a reason to think otherwise?

So I guess the question is what concept you want people to grasp and are we in a position to present ME in those terms? My intuition is that my own sense of limited available energy has nothing to do with a store of energy in the chemical sense. It seems more likely to be due to neural signals telling me to stop doing things.

Well the concept that I want to put across is "how does this disease affects those who have it" in a way that an 'average person' might be able to grasp, and if I can base that on science then all the better. Ideally I would also avoid anything that might be interpreted, by that same 'average person', as meaning that ME is 'in the head'.

 

[Invisible Woman]

I feel like I experience both reduced available energy and rapid fatigability. It seems the lower the available energy the less efficient my body is at using it and so the more rapid my fatigability is.

or to look at it the other way around - he same task can feel like it requires significantly different amounts of energy on different days. The more energy it seems to require the more rapid my fatigability.

When healthy I had plenty of energy reserves so I'm not sure how well I would have related to that.

It's a double whammy. Like running very low in petrol/diesel but the nearest petrol station is up at the top of a very steep hill.

 

[cassava7]

Strictly speaking, those are different but correlated. Someone with the sensation of lower available energy from a fatiguing condition (e.g. anemia) will feel that they run out of energy quicker than their healthy self would.

However, they would not a priori suffer from the same consequences of exertion as in ME/CFS (e.g. increased acidosis and orthostatic intolerance). For a same task, those probably result in increased energy consumption compared to people who do not experience these symptoms, i.e. they cause more rapid fatigability in ME/CFS.

So the feeling of reduced energy is either compounded by symptoms that increase energy expenditure compared to healthy people and quicken fatigability, or not. In ME/CFS, I would say there is both the feeling of reduced energy and rapid fatigability, and that the latter is due to the former as well as exertion-induced symptoms.

(This is also true of organ damage or limiting respiratory, metabolic, cardiovascular, autoimmune diseases, e.g. BPCO, tachycardia, lupus, RA, glycogen storage diseases, or neurological diseases that impair information processing. All cause exertion to require more energy, but not necessarily for the same activities as ME/CFS — e.g. only when exercising vs. essential daily tasks — or to the same level.)

 

[Wonko]

A bad analogy;

If normal is like riding a bike down a hill then reduced energy is like riding uphill, and with PEM the wheels are wonky.

So the effort required to travel a set distance is much more, as is the exertion, and total effort (a wonky wheel makes coordination etc much more difficult as well as increasing the simple energy expense)

 

[Andy]

It seems to me that there are multiple possible explanations (in the broadest sense of 'explanation', I'm not claiming that there are established facts to support any of these);

1. We start with less energy.
2. We start with the same amount of energy as other people but our body is less efficient at accessing and/or using it.
3. We start with the same energy, have no problem accessing it or using it, but our ability to replenish it is less efficient.

At the moment any other explanation seems to me a variation on these.

PEM might be a consequence of these but could also be an additional mechanism that kicks in after a certain level of overexertion.

 

[Art Vandelay]

But do people here feel that the best explanation is simply that we have a reduced store of energy, or that our ability to replenish the store is diminished, or both?

Neither. I feel sick, not tired. When I over-exert myself, I feel even more horrendously ill. Not tired.

As I've said elsewhere on this forum, I describe ME/CFS as the worst flu of your life combined with a nasty hangover or feeling poisoned. On a bad day, it also feels like I've been beaten from head to toe with a baseball bat.

It is nothing like the 'tiredness' one would experience after going to the gym or even running a marathon for example.

Edit: this is my attempt to explain what a crash feels like for me. I don't mention 'tiredness' or 'fatigue' at all because I don't feel either word is appropriate or accurate to describe my experience.

 

[Wonko]

the way I used to think of it is that 'something' inside my cells is damaged.

Meaning that energy production is reduced, and that cleanup is less efficient. Eventually this leads to a situation where the cells are drowning in toxic byproducts unable to clear it at anything like a sufficient rate, and this 'interferes with everything.

Meaning everything that requires energy, including 'cleanup' is much less efficient, requires more effort, and makes the situation worse.

It is possible under this thought model that the amount of energy required to clean up/get rid of byproducts is at or just above that which is available - and I end up bedbound, unable to do anything.

There's more but you probably get the gist, and why this particular model is wrong - but for many years, even before I knew anything about ME, it formed the basis of my understanding and helped me 'balance' things - a primitive form of pacing when I didn;t understand why, or tha that was what I was doing.

 

[Jonathan Edwards]

Do we have proof of this, or is this based on the assumption that there doesn't seem to be a reason to think otherwise?

I think we have reasonable proof of it in that energy stores basically boil down to combustible organic matter and PWME weigh about the same as normal people. If you have a few millimetres of subcutaneous fat you have some energy stores. I don't think that is what we are interested in though. But if it isn't we need a definition of energy that actually means something. I worry that explanations like this end up sounding as if they mean something but don't so give a false impression of understanding.

Well the concept that I want to put across is "how does this disease affects those who have it" in a way that an 'average person' might be able to grasp, and if I can base that on science then all the better. Ideally I would also avoid anything that might be interpreted, by that same 'average person', as meaning that ME is 'in the head'.

You seem to want an explanation in terms of a process and I don't think we have that. Isn't it tricky to suggest that ME isn't in the head because we know it is so-and-so when we don't know that? I personally don't see any evidence for disturbed energy utilisation in ME that would explain the symptoms. I can see that there is a sense of reduced access to 'energy' but that is energy in a sense that does not have anything to do with 'stores'. It would be a bit like saying that people with insomnia do not have access to their sleep stores. We don't think there are sleep stores in any relevant sense.

 

[Andy]

Neither. When I over-exert myself, I feel horrendously ill. Not tired.

But my initial posts aren't talking about overexertion. I apologise if my post wasn't clear, but I'm talking about attempting to describe the limited capacities of pwME.

 

[Art Vandelay]

But my initial posts aren't talking about overexertion. I apologise if my post wasn't clear, but I'm talking about attempting to describe the limited capacities of pwME.

Sorry, that was my fault for not explaining myself properly. I edited my post a few minutes ago to clarify (and probably still didn't do a good job of it).

I feel like my capacity is limited because I am sick much in the same way that someone with a severe flu is limited in what they can do. It is not primarily due to 'tiredness' or a lack of energy.

 

[Milo]

I did not read everyone’s response, but here is my short answer:

Rapid fatiguability suggests that the person is doing something leading to ‘fatigue’ or a lower state of functioning.

Lower amount of available energy does not require one to have done a task- you can wake up with lower amount of available energy.

So to me they are different things.

 

[Andy]

You seem to want an explanation in terms of a process and I don't think we have that.

Possibly my use of the word explanation has confused things; I'm wanting a description of the experiences of people with ME that is as universal as it can be, and is as easily understandable as possible to lay people.

Isn't it tricky to suggest that ME isn't in the head because we know it is so-and-so when we don't know that?

I would have no intention to make such a claim, just attempt to avoid any opportunity for the 'it's psychological/in the head' argument to come up. I personally have no issue with ME involving biological processes in the brain, either as a cause or as a consequence, but for the general lay person that can be easily converted into an 'understanding' that ME is a consequence of faulty thinking, so if I can avoid it then I'd like to.

 

[MEMarge]

From a parent/friend view.

Daughter and friend feel ill all the time. They never feel well, even on a good day. They are at opposite ends of "moderate".

They both definitely have less available energy than healthy people. So Z can manage maybe an hour for coffee and chat, at the right time of day. There is obvious dropping off towards the end of the hour, cognitively and physically. This was especially noticeable when we were doing the PIP process! She would not be able to do this everyday.

My daughter can, some weeks, manage an outing of a couple of hours, or having a friend round. This is preceded and followed by a few days of doing very little physically, other than getting up/dressed/eating etc. Her cognitive processing is always significantly impaired. There is no way she can understand the AS level Maths that she passed with an A grade, nearly a decade ago.

I do like the battery analogy. Most people understand this from phones/laptops etc in that they run down and then neeed recharging. But with age or an Apple product, in time it cannot fully recharge. My daughter manages a tiny percentage of the activity that she used to be able to do, pre ME.

To me that fits with the issue that pyruvate dehydrogenase activity is impaired, resulting in anaerobic glycolysis, which yields a much smaller number of ATP molecules per molecule of glucose. This occurs, rather than the aerobic metabolism, including the Krebs cycle, which produces roughly 10 times more ATP.

I know you are not asking re the biochemical explanation, but at least 2, if not 3 research groups have results showing this. Sure those results need larger samples to confirm the results. Also investigations into what is causing the reduced activity of the enzyme, such as auto antibodies on membrane receptors etc., to understand the pathology better and move towards potential treatments.

 

[cassava7]

1. We start with less energy.
2. We start with the same amount of energy as other people but our body is less efficient at accessing and/or using it.
3. We start with the same energy, have no problem accessing it or using it, but our ability to replenish it is less efficient.

At the moment any other explanation seems to me a variation on these.

A variation on @Wonko's proposal, which would account for tentative evidence from 2 day CPET studies such as increased acidosis:

3bis. We start with the same energy, have no problem accessing it and using it, but using it causes abnormal consequences that prevent us from replenishing it efficiently.
3ter. We start with the same energy, have no problem accessing it, but it is used differently and in a way that prevents us from replenishing it efficiently.

Although there is no evidence that ME/CFS is the result of an ongoing infection, since the symptoms feel very similar to a flu, it would be interesting as a comparison to know whether available cellular energy is reduced during an infection.

 

[JemPD]

Neither. I feel sick, not tired. When I over-exert myself, I feel even more horrendously ill. Not tired.

As I've said elsewhere on this forum, I describe ME/CFS as the worst flu of your life combined with a nasty hangover or feeling poisoned. On a bad day, it also feels like I've been beaten from head to toe with a baseball bat.

It is nothing like the 'tiredness' one would experience after going to the gym or even running a marathon for example.

Edit: this is my attempt to explain what a crash feels like for me. I don't mention 'tiredness' or 'fatigue' at all because I don't feel either word is appropriate or accurate to describe my experience.

This.


I understand what you're trying to do @Andy & this isnt a critisism of it, it's just that personally I always steer well clear of the word 'energy' when talking to people about ME. Because people (when trying to understand another's experience) always try to relate whats being said to what they already know, & when i was healthy i used to sometimes say "goodness me i am so tired i've got no energy at all today".

What i meant was that i felt flat & sluggish, like it was a big effort to peel my arse off the settee & do things, but i was still entirely capable of doing whatever i needed/wanted to, i just felt lethargic....
So my sense of how much energy i had was that i didnt have much, but i was still pretty much unlimited in what i was actually able to do.

So if i mention 'lack of energy' or 'running out of energy' to people, they mostly say "oh yes i know what that's like", but they are relating it to their own experiences of feeling as i described.

And that is NOTHING like what i'm experiencing! and i dont want people to think that is how i feel. I'd be thrilled to only feel like that! When i say i feel too ill/weak to stand up, it's because when i try to, because i need to, i cant. And while that may be technically an issue with energy production/baseline/replenishment, in my experience people always think it means "feeling knackered but still totally capable if you push yourself". And thats not what i want them to think, because it's grossly inaccurate, so i dont use the word.

So I'm not sure i can usefully conrtibute to the distinction you're trying to make Andy

ETA not suggesting that energy is the 'wrong' word... i dont know what the 'right' word is, just saying what i use/prefer & why

 

[NelliePledge]

In my opinion whatever you say healthies will say me too whether the word is fatigue, energy or ill.

i think there is definitely something about energy but it is so closely tied up to levels of symptoms pain, fluish feeling headache sore throat or whatever it is. I don’t get up until I have taken painkillers and when they kick in I feel like I have more energy. I weigh a lot more than average person so clearly I have stores of energy in terms of fat but others especially some with very severe ME have very low BMI.

i think the fatiguability aspect for me is probably down to orthostatic intolerance so is that really to do with energy at all?

 

[FMMM1]

But my initial posts aren't talking about overexertion. I apologise if my post wasn't clear, but I'm talking about attempting to describe the limited capacities of pwME.

Not directly relevant but Fluge and Mella published a paper suggesting impaired PDH - basically anything that needed to go through pyruvate was impaired (2015). Fluge and Mella suggested a signalling problem led to this outcome.

Chris Armstrong's work also suggested that certain amino acids (those that enter the citric acid cycle after pyruvate) were preferentially used (2014) for energy production. So there's been some suggestion of a change in metabolism re energy production - don't know how that research is going.

Chris Armstrong's work also suggested higher levels of blood glucose - i.e. amino acids being used in preference to available glucose.

Japanese study?

Maybe you could weave a little about studies showing changes in energy production and then go from there.

 

[Mij]

I have experienced, ME loss of available energy (for lack of a better explanation) and need to lie down, very low ferritin fatigue (weepy type of tired fatigue), and now menopause full stop unable to walk another step fatigue. They ALL feel different.

My healthy (now 60 yr old) sister told me a few years ago that she felt less power in her legs when she was running since starting menopause. I asked her how she felt the next day, she said she felt fine.