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

[rvallee]

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.

I mostly ignored it for years, but I had mild chronic fatigue since my teens. I could still do most normal things and was active, but I was tired all the time. Never stopped me from being relentless when playing sports or doing hard work. I did see my GP at the time and all he did is a blood panel and never talked about it again. I had a really bad GP...

Absolutely nothing to do with the ME exhaustion, which is more similar to the kind that comes from the flu with a fever, when it's more apt to talk of weakness, of struggling with minimal exertion. It's a much more complex concept than normal fatigue, way more layers and depth.

To an external observer it's impossible to see the difference, but they are nothing alike. Fatigue was never the right word for it. It's used only because this is what people know it as and it's very hard to add new vocabulary, especially against motivated denial.

I know what being tired all the time is. It's absolutely nothing like ME. This is completely above and beyond it and is better described as sick. Except medicine does not accept sick as a description. Which is amazingly foolish and has choked all progress, all because we can't use the right word even though it is obviously the right one.

It reminds me of how there didn't used to be a name for... what was it blue? Blue and green were basically called shades of the same color? And if you ask people in a culture that doesn't differentiate they will basically call it the same color, though probably not with fully saturated colors, but still.

Words matter. This isn't a problem of description, it's a problem of which words apply and how different words describe different things, all because a bunch of people don't want there to be a difference because it would otherwise invalidate their belief system and throw their career into well-deserved disarray.

And as for an early question over what is meant by energy, same as in physics: the ability to do work, which for the most part means moving energy (and ultimately mostly means chemical processes). We don't know what the micro level is, just the macro level.

But it's work in the broader sense, of moving a limb, walking, pushing something, or just thinking, which ultimately works through electrochemical processes so in the end it's just a matter of scale, the same way as the mechanics of a single object ultimately comes down to molecular interactions pushing against one another in one direction or another.

 

[Barry]

When people speak of having available energy, be it in the context of ME/CFS or not, they are also speaking about energy available at the rate it is needed (which is actually power) and not just availability of energy per se.

If you do a particular task, then by and large it takes the same amount of energy no matter if you do it quickly or slowly. But typically the "less energy" you have, the more slowly you are able to do a task - because your body cannot provide the energy at the required rate. People speak of energy in a general sense when in reality it is often more akin to power they are talking about.

So for instance, lets say we are talking about the energy needed to walk distance x. All other things being equal it will take the same amount of energy to walk that distance, slow or fast. (Yes, I do appreciate there will be efficiency differences, but that is secondary, and why I say all other things being equal). If energy itself was the only limitation, and delivery rate was not an issue, then a person with ME/CFS would be able to walk at full tilt until their energy ran out, and then just stop. So if they had enough energy to walk half x then they would be able to go halfway as a fast as a normal healthy person, but then come to an abrupt halt.

But taking my wife as an example, who I would say is mild these days, she cannot walk at normal pace, it is slower than normal. So the rate at which her body is able to process energy is restricted compared to how she once was. And when it starts to fade it typically fades much faster. Basically her power output is much lower than it should be, and drops off much quicker than it used to.

 

[Barry]

Also, as noted earlier on, my wife's energy input is pretty much normal - she eats a normal diet. But that energy does not get to where it is needed at the rate it is needed. From that I deduce that her body is failing to process the energy properly. Energy in is pretty much at the normal rate; energy out is much slower than the normal rate.

 

[Jonathan Edwards]

I still think people are muddling up the sense of 'energy' with energy sources as defined in biochemistry. I think these are two completely different meanings of the word. They might have a link but it may be very indirect.

If the idea is to explain to healthy pool what ME feels like then the sense of energy is relevant. But analogies with batteries and fuel tanks seem to me just to confuse things.

 

[Creekside]

A good topic. As with several other posters, I do not feel any reduction in available energy or the rate at which I can use it. I believe I have a neurological disorder which impairs my ability to make the effort required to do things. My legs might feel like going for a 40 km ride (and would be able to do it without problem), but my head wants to flop onto a pillow and not do anything. If I absolutely had to do the exertion, I could, but I think it's the same thing as if I had a serious flu infection: yes I can push myself, but I really don't feel like it.

With the CPET experiments, and various experiments measuring mitochondrial function, I think that such ATP production impairments may be a common downstream effect of ME (and experimenters select subjects that fit that criteria), but isn't a core part of ME. Maybe it's common--but not essential--for ME to alter some hormone or cytokine levels, or hinder some RNA transcription or some such mechanism that impairs mitochondria. In my case, I think there's some subtle alteration of some brain cells in some part of my brain. I think it's part of or related to 'sickness behaviour'.

I just skimmed through "Metabolic features of chronic fatigue syndrome" (Naviaux +). The paper points out that it's not as simple as one function in the mitochondria being hampered; there are a lot external functions responsible for proper functioning of ATP production. Mitochondria offloaded a lot of those mechanisms to the cell to focus on the few mechanisms that couldn't be done elsewhere. That means there are a lot of cellular functions and even extra-cellular factors that affect ATP production. Alter the rate of production of one protein in the cell, and that could mess up ATP production, whether in the mitochondria or how they interact. In some PWME, that slight change might be limited to some brain cells, perhaps only in a small (but important!) part of the brain. In others, it might also affect cells and mitochondria elsewhere in the body. Since mitochodrial problems seem common in ME, it might be a rare genetic variant (or epigenetic factor?) that protects the cells outside of the brain but doesn't exist in the brain cells. I remember coming across a paper (can't find it now) that said that mtDNA in the brain is slightly different from that elsewhere in the body, so that might explain it.

Here's a thought for you: what if there are a lot more people who do have part of the mechanism for ME activated (and might test positive on an ME test when they actually develop one), but they have some other mechanism that prevents some of the downstream effects from showing up? There might be variability in people's responses to ME's core dysfunction.

 

[ME/CFS Skeptic]

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.

Perhaps there is nothing wrong with our energy system but there is something else, a bodily signal that gives us terribly symptoms whenever we try to do something.

As an analogy, take someone with severe back pain. He might not have an energy problem to take out the weed in his garden, but the back pain prevents him from doing so.

 

[Creekside]

If the idea is to explain to healthy pool what ME feels like then the sense of energy is relevant. But analogies with batteries and fuel tanks seem to me just to confuse things.

I agree; it can confuse perceptions, and it doesn't apply to all PWME. My preferred explanation for how it feels is how we feel when we have a flu: we feel lousy, achey and lethargic/brainfogged overall and just want to hide under a blanket until it goes away. ... and after 20 years of this, I'm still waiting for it to go away.

Does "It feels like the flu (or mono?) that doesn't go away." work as a simple explanation for how ME feels? That leaves out many extra symptoms (OI/POTS, gut issues, etc) that some PWME develop, and doesn't include PEM, but for the fatigue-like symptoms, I think most people without ME would at least be able to relate to the unpleasantness of 'flu-like'.

 

[DokaGirl]

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.

Excellent description @Invisible Woman - that is exactly how I feel. Like a more under powered engine than needed for many ordinary tasks. With extraordinary demands I can start the task, but my power doesn't endure, and I am forced to stop because my power runs out.

Thank you @ Andy for posing this question. I think lower amount of available energy and rapid fatigability are linked in ME, at least for me. Let's say on an energy scale of one to 10 a pwME goes along everyday at a level of 1 to 5; we know there is variability in our functioning. Add in an extraordinary demand for that person already functioning at a 1 to 5, and you will have someone who very rapidly experiences an increase in various symptoms, including fatigue.

I don't know if there are diseases where just extraordinary demands cause rapid fatigabity: a person goes along just fine, and they only become quickly fatigued with an extraordinary demand. That isn't to say there aren't any disease like this.

Very obviously, this is a difficult concept to get across to healthy people. I have known people who are healthy for all intents and purposes , who are also quite sedentary. They don't see any difference between themselves and someone with ME who needs to rest a lot. Even though very sedentary, taking on tasks above their usual activity level will not tire them out. More extraordinary tasks might but not run of the mill things like shopping and cleaning the house.

 

[lunarainbows]

A good topic. As with several other posters, I do not feel any reduction in available energy or the rate at which I can use it. I believe I have a neurological disorder which impairs my ability to make the effort required to do things. My legs might feel like going for a 40 km ride (and would be able to do it without problem), but my head wants to flop onto a pillow and not do anything. If I absolutely had to do the exertion, I could, but I think it's the same thing as if I had a serious flu infection: yes I can push myself, but I really don't feel like it.

Hmm. This is exactly the opposite of what I experience. My head does not want to flop onto a pillow or do nothing. That sounds more like a problem with motivation to me. I don’t have any problems with motivation or with my head like that - if anything, my head wants to do far more than I know I should, and I end up doing those things and becoming more ill.

I also don’t agree with what someone else said earlier too about the perception / feeling of not having the energy to do things. It’s not a perception. I actually do not have the energy to do things. If I do push myself, I became extremely unwell, and it’s not because I perceive im unwell, I actually am unwell. I became unable to eat, swallow, move my limbs - I do not have the energy to move or to do those things.

I have rapid fatiguability and I also think I’m starting from a much lower energy point than healthy people. I feel very ill, and very fatigued, even before I start doing things. This happens even if Im very well rested. I know fatigue isn’t the right word but right now it’s the only word I can think of - this feeling of having absolutely no energy, of losing energy quickly just by being upright for a few seconds and then not being able to be upright or talk etc, and so little resources to pull from. And that energy fading so quickly. So in my experience, I would describe it as both things.

 

[Barry]

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

I think this has to be true, given that food is the energy source and my wife consumes a normal amount of food. It's something between there and it getting to where it is needed that is the problem. And yes, I do appreciate that that must involve an awful lot of very complex biological processing - at least when it comes to trying to pinpoint where it is going wrong.

 

[Jonathan Edwards]

I actually do not have the energy to do things.

I can understand what you mean here but this is not having what in common talk we call 'energy' which is not energy in any sense like a battery or a fuel tank. As you say it seems that you could push yourself - so the energy is available, but using it makes you feel unwell. In a way I am completely agreeing with you - the problem is feeling unwell and that is not a matter of running out of energy. When a middle distance runner runs out of energy availability for muscles they do not feel unwell. The legs just feel as if they have got frozen at a certain speed that will not increase - it is like turning the throttle up on an engine beyond the point where there is maximum feed - nothing more happens.

When we have flu I actually think there is a block to access to energy usage in muscles in that if you were asked to lift something very heavy when in the middle of flu your arms simply would not work. But again I think that is a neural inhibition probably due to gamma interferon in the muscles.

 

[Barry]

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.

I don't know if this is any help, but I once heard that when a pwME "runs out of energy" it is much akin to what a marathon runner experiences when they "hit the wall" ... except of course for a pwME it is an endless succession of such experiences. Totally and utterly f****d, nothing left inside, and feeling truly ghastly. When the science of ME/CFS is properly understood, it would not surprise me if that analogy doesn't have an element of truth to it.

 

[Jonathan Edwards]

what a marathon runner experiences when they "hit the wall" ... Totally and utterly f****d, nothing left inside, and feeling truly ghastly.

That sounds plausible from what PWME describe. If you hit a barrier in a 800 metre race it is just a freezing up. If you hit a barrier in a 5000 metre race it is more likely to be this ghastliness. You could probably sprint for 50 metres but the pain of another 1000 metres is the problem.

 

[Hoopoe]

One I think remarkable aspect of my fatigueability is that mental exertion can cause widespread weakness and fatigue in the rest of the body so that it visible affects my gait and walking speed.

And similarly, after a walk I'm not very talkative because my brain is affected as well. Presumably by the orthostatic stress.

Another observation is that the exhaustion caused by walking manifests itself fully only after slowing down considerably or stopping. I'm not sure to what degree this is normal. It seems similar to what is described in periodic paralysis where upon stopping exercise, the potassium balance in muscles changes and paralysis can occur.

I suspect this could be a factor (for the milder patients) that makes people overexert because it can promote a behaviour where one tries to keep going to avoid the sudden drop in energy that might make it difficult to get anything more done for the next hours or the rest of the day.

 

[ME/CFS Skeptic]

One I think remarkable aspect of my fatigueability is that mental exertion can cause widespread weakness and fatigue in the rest of the body so that it visible affects my gait and walking speed.

I think I have this as well. After overextending cognitively (for example talking during a family gather) I can have muscle soreness in y legs the next day (even though I didn't use my legs for most of the day).

I think this would be something rather easy to put to the test.

 

[Hoopoe]

Potassium regulation during exercise and recovery

The concentrations of extracellular and intracellular potassium (K+) in skeletal muscle influence muscle cell function and are also important determinants of cardiovascular and respiratory function. Several studies over the years have shown that exercise results in a release of K+ ions from contracting muscles which produces a decrease in intracellular K+ concentrations and an increase in plasma K+ concentrations. Following exercise there is a recovery of intracellular K+ concentrations in previously contracting muscle and plasma K+ concentrations rapidly return to resting values.

https://pubmed.ncbi.nlm.nih.gov/1656509/

So the fatigue appears to hit fully when the potassium in blood returns to muscle cells.

 

[Snow Leopard]

The legs just feel as if they have got frozen at a certain speed that will not increase - it is like turning the throttle up on an engine beyond the point where there is maximum feed - nothing more happens.

That is my experience of the rapid fatigability when exercising. The power we expect to be there is not there at all and any effort to push harder is also associated with a rapid increase in pain (which diminishes quickly if I back off).

One I think remarkable aspect of my fatigueability is that mental exertion can cause widespread weakness and fatigue in the rest of the body so that it visible affects my gait and walking speed.

The remarkable part is not all of us have that experience. (this has been discussed several times recently)

https://www.s4me.info/threads/poll-physical-vs-cognitive-pem-same-or-different.16948/

For me, physical exertion can lead to cognitive symptoms, but cognitive exertion does not lead to increased fatigability or weakness of my muscles.

My legs might feel like going for a 40 km ride (and would be able to do it without problem), but my head wants to flop onto a pillow and not do anything. If I absolutely had to do the exertion, I could, but I think it's the same thing as if I had a serious flu infection: yes I can push myself, but I really don't feel like it.

That is not my experience at all. I like exercising. For me, riding up a steep hill is fun, but this is something I can no longer do without an electric bike. On the 2 day CPET, my heart rate peaked at 202BPM on the first day and 194BPM the second day - my problem is not a lack of pre-motor cortex drive! Overall I had above average VO2Max for my age, though by no means athletic. (Absolute VO2 of around 3.5L/min)

 

[alex3619]

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?

Not sure that is right either. The simple answer is we don't know yet, but if the purpose is a simple analogy to explain to people we don't need to be 100% on the mechanisms.

My way of thinking is we have low mitochondrial respiratory reserve. That is the capacity to ramp up mitochondrial energy production is tiny, and how tiny reflects on the severity. A very severe patient is, I suspect, already in emergency energy mode, both in conserving energy and producing it. A mild patient has some modest reserve but its quickly reached, after which they are in emergency mode just like the rest of us, and the lactate shunt and other mechanisms are engaged.

So in a modern analogy I guess we are like a laptop or tablet with barely enough battery power to get out of standby mode. Its not a great analogy though, maybe someone could come up with better. The very severe are indeed in standby mode, standing by until there is enough energy for a life. Or maybe a better analogy is a computer with a damaged power supply installed, it cannot draw enough juice to enable full function, and if your graphics card kicks in watch out! Again, not a great analogy. Perhaps a vehicle analogy where someone stole your engine and you had to put a tiny engine in to replace it, one that barely gets the vehicle moving.

To go back to the original idea I think we have a decreased energy store if we have diminished it and not had the chance to replace it. Its a trickle charger problem, the one we have is inadequate for the device. So the store of energy is low as it never got fully charged up. In nearly all cases this means that the energy store will be low, as we need to do stuff again long before its fully charged.

The problem with all these is we have so many biochemical interactions and things that limit or decrease energy that all simple analogies are weak. We also still do not understand the problem. In regular analogies what is the equivalent to feedback that diminishes energy production after activity? At the moment I am blank on a simple explanation for that, especially since we desperately need even more research so we can understand it better ourselves.

The spoon analogy was to explain just this problem, but did not explain the low recharge very well, or what happens if we overuse our limited energy.

Maybe a power grid analogy?

 

[Milo]

For me, physical exertion can lead to cognitive symptoms, but cognitive exertion does not lead to increased fatigability or weakness of my muscles

The opposite is true for me. Funny we are all a bit different but also very similar in the symptomatology, which begs in my view to explore this further in research.

 

[alex3619]

Let me tackle this a different way, but first let me say this is partly hypothetical, not factual.

Going back to low mitochondrial respiratory reserve, if you start to exceed that reserve the body will try to conserve energy production, including signals to tell you to slow down or stop. In other words, you feel terrible. Acid sensors in the body are going off. All sorts of signals and feedback loops are probably operating, though we don't really understand them yet. If we knew what the something in the blood that appears to be decreasing energy production actually was, and what regulates it, we might have a better idea.

When mitochondria are taxed beyond their capacity they have emergency pathways. This includes catabolic paths that effectively eat mitochdondrial substrates and take time to replace. Glycolysis ramps up but the mitochondria does not. Acid is produced that can accumulate and lead to fatigue sensations. Other mechanisms might exist that these things signal, mechanisms that lead someone to want to lie down, or stop, or just not attempt anything. I am talking biochemistry, not psychology, but if the brain gets a bunch of "oh darn I am knackered" signals then the psychology will go with that. I am also talking, potentially, immunology.

We are not going to get to the bottom of this without more science. We just don't know enough.