Open (Palmerston North, New Zealand) Effects of exercise at anaerobic threshold on post exertional malaise in individuals with ME/CFS

see mark vinks paper:
https://www.researchgate.net/public...gic_EncephalomyelitisChronic_Fatigue_Syndrome

 

I think there are different ways to define the anaerobic threshold like measuring lactate levels and see if they rise above normal levels (like Mark Vink did in his study) or by looking at differences in respiration, like most CPET-studies do (using the ventilatory threshold).

I was sort of speculating that there might be a disconnect between the two in ME patients causing the the ventilatory threshold to overestimate the anaerobic threshold. The idea behind it, is that in ME patients the problem is not so much the supply of oxygen but the capacity to use it.

This is mere speculating though.

 

This seems to me the crux of the issue. If the problem is with 'preload' in terms of blood feed to the heart it would be the other way around I guess.

 

I am trying to think how this fits when we have high venous oxygen. I do think this is not a normal exercise response, but due to a block at, for example, pyruvate dehydrogenase.

I wonder if blood oxygen is kind of high but so is lactate due to, effectively, a metabolic shunt. As I have said, we need better studies. Nobody can reconcile the findings with all the data we have generally.

On the other hand, if microcirculation is compromised then circulating oxygen will be higher than otherwise, lots of tissues will not be getting oxygen, and energy can start being made via a divergence to lactate due to that local oxygen supply, rather than general supply.

I am sure there are other options, but we need studies to test these ideas and show which are wrong.

 

It's quite easy, just do some kind of rapid high power activity. This easily exceeds the power available through aerobic metabolism.

I'd also like to point out once again, that the anaerobic threshold is well below maximum ventilation, in fact my VO2 consumption at the ventilatory threshold was around 50% of VO2peak.

A key aspect of the CPET is that it is graded - the power requirement of the participant typically increases at a linear rate (as defined by the test parameters), this is how the thresholds can be easily observed.

It is not merely about supply of oxygen, but rather shifts in metabolism as muscle fibres are recruited to deliver a particular power output. This occurs to either to respond to high demands, or increased fatigue, though obviously once all fibres are active, no further power increase is possible. Changes in heart rate (and heart rate variability, suggesting increased sympathetic neural drive), breathing rate etc. seem to lag slightly behind these changes.

There is a notable fatigue effect, submaximal exercise can become VO2 max under certain circumstances, this is due to the "Slow component" of VO2 kinetics. https://www.ncbi.nlm.nih.gov/pubmed/21552162

Which brings us back to a central question, what does the sensation of fatigue actually predict? (I've been trying to hint this strongly throughout my posts in this thread, though I guess I haven't been doing a very good job).

 

Do you mean that O2 uptake via the lungs and blood is normal, but the oxygen doesn't reach the cell where it is needed?

(By the way, here https://www.ncbi.nlm.nih.gov/pubmed/3551513 the anaerobic threshold is defined as

I would be interested if muscle burning - like the one from exercise - only can occurr with lactate production.)

Edit: I know it may bore some, but what I found interesting: If calcium signaling to the mitochondria is in a certain way disrupted, the oxygen uptake by the mitochondria decreases. I.e. aerobic ATP production doesn't work properly anymore. That would be an example where oxygen uptake via the lungs is normal, the problem is on the cell level.

 

That's possible. I remember the authors of 2 day CPET studies speculating about this. See for example Vermeulen et al. 2014. I was thinking more about the O2 correctly reaching the cell but some metabolic abnormality blocking it's normal use in aerobic energy production.

Again, this is all speculation...
Would be interesting if we could ask our questions to an exercise physiologist with experience in ME/CFS.

 

I agree with you. This is the biggest problem. Otherwise I would just be sad that I couldn't do sports anymore, but I would be able to work in an office and have a social life as a couch potato.
The problem is that sitting/walking for long hours is suddenly enormous "activity" and I HAVE to lie down during the day (don't have OI!), otherwise tomorrow is even worse.

I also can't do sports or raise my heart rate in any significant way, but that is a different problem. Maybe they have to start testing mild ME-patients to find this out, when I was more severe it was all muddled and I couldn't do anything. Now I'm a bit better, it's a lot more clear what causes me PEM.

 

The answer is that just lactate is insufficient to trigger sensations and is also insufficient to provide a perception of effort. You might remember this study from Light/Pollack that has been discussed here and elsewhere (Phoenix Rising, Health Rising)?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946674/

The followup commentaries on this are fascinating too.

 

My understanding is that lactate does not, at least in normal physiology, cause muscle burning. Its not sufficient. Carbonic acid, from failure to remove carbon dioxide, is the primary acid.

PS I mean primary acid in exercising.

 

I have heard similarly. The authors I read, however, emphasized that it was still not entirely clear what the precise mechanism of ‘muscle burning’ is. There may be slightly different mechanisms behind immediate-onset muscle soreness and delayed-onset muscle soreness, in the context of healthy anaerobic exercise.

The authors I read felt that the ‘muscle burning’ sensation was probably mediated by a combination of localized acidity and extracellular ATP. They felt that the main culprit in localized acidity was likely H+ ions expelled by stressed mitochondria.

As @Snow Leopard mentioned, the Light/Pollack study is illuminating here.

 

Many patients I have talked to or read about use being out of breath, breathing heavily etc., as an early warning sign of impending PEM. Its not infallible, but it is a good sign we have done too much. Now this does not mean that damage is not being done even before that, or that damage is not being done without breathing heavily, for example after high cognitive demand. However the brain does need a lot of energy, and various brain studies have found we activate more of the brain for the tasks we do. This might well increase brain energy demand.

Travelling in a train or bus uses much more energy than it used to. Again, while not a big deal for healthy people, it can be a major issue for us ... I get PEM on buses for example, though not all the time, and not if its a nice sedate ride. Due to other issues on top of this I no longer uses public buses.

 

Thank you @Snow Leopard! I'll read it. I don't remember the discussion because I wasn't sick in 2013, but maybe I'll return to have a look.

Edit: Do you have a link at hand? Didn't find a thread on PR.

 

@Michiel Tack , could you say whether stiffness or pain were predominant in your feeling of muscle soreness?

I have no clue of muscle and exercise physiology, just got the impression that many words we use (and are used by researchers) to describe our exercise related impaiments are indefinite in a manner that makes it hard to be sure what is meant.

So I just throw in my personal experience and am curious how others experience muscle soreness or stiffness (and how this could relate to the CEPT results.)

In my case, the muscle problems in the current form developed not from the start of having ME, only after a decade or so. In the first years I had no muscle pain at all, and muscle stiffness other than normal muscle soreness after exercising only rarely occured.

Regarding movement impairments, for me, pain still plays hardly a role now. The stiffness is always predominant. Only when I try too hard to move my stiff limbs (or more rarely my neck or torso) it will hurt, and when this induces spasms, it will become extremely painful. But when I stop moving, the spasms and pain mostly will entirely remit within some minutes, whereas the stiffness will remain longer.

I can distinguish diverse types of stiffness, though.

The most impairing stiffness occurs when I make quick movements (e.g. try to walk fast) or while or immediately after I repeatedly stretch my muscles or use much strength ("much" for me means e.g. vacuum-cleaning or stirring pastry). It also occured when my muscles repeatedly were being stretched passively by a physiotherapist (he won't do that again!).

Sometimes it also occurs suddenly, without an obvious trigger.

The result is not only feeling a bit stiff, but I am only able to move the affected limbs or torso extremely slowly, with difficulty or sometimes not at all. E.g. I hardly can walk, grip things or sit up. Usually, this extreme stiffness will remit slowly over 0,5 - 2 hours, only a mild stiffness remains. (Only sometimes it will return frequently over some days or even weeks, e.g. after a viral or urinary tract infection)

On the other hand, there is the enduring mild stiffness that will increase with delayed PEM. This gets stronger with mild exertion (e.g. brushing teeth, walking short distances), is mostly not painful, but still debilitating regarding daily activities.

When a doctor said my temporary strange gait was due to "motor fatigue" I first thought all those movement challenges could be just due to motor fatigue. But I'm not sure if motor fatigue can be induced also by passive muscle stretching or can occur suddenly, without previous exertion?

And how could motor fatigue affect the 2-day-CPET test? (Haven't done one myself, though).

Perhaps motor and muscles (or microcirculation related stuff in both brain and muscles?) are involved at different stages?

Also, I am much easier getting both a high heart rate and related heavy breathing when having delayed PEM (eta: when severely PEM-ed: heavy breathing just for altering my position, but climbing a flight of stairs with moderate PEM, when I am able to do so at all, will surely get me out of breath. So, I agree with others, that getting out of breath is not needed to induce PEM, but with PEM I will get out of breath sooner, e.g. when I push myself very hard despite PEM, which I have to do when my partner isn't around to support me in daily tasks.)

S, to me the 2-day CPET seems useful for me to show that mildly affected pwME aren't deconditioned, but some strange physiological things happen after exertion compared to healthy people. This may correlate with getting sooner out of breath when having PEM. However, I don't recall whether the 2-day CPET studies actually assessed PEM on the second day, or if the altered results on the second day occured independent from subjective/ objective PEM?

(And isn't the heart also a muscle that has to be supplied by all stuff that other muscles need to work, too, only the signals to get them work being generated differently)?

Have others also developed enduring/ repeated muscle stiffness only some years after getting ill with ME? And do you experience your muscle related impairments always as painful?

Also tagging you, @Jonathan Edwards, in case this might be of interest for you.

(I'm late to the discussion and was only able to skim the thread. Please alert me in case my ramblings are too muddled or off-topic. In any case, apologies for the long text.).

(Edited for clarity.)

 

It's not really pain and stiffness sounds to benign. It's actualy very similar to a normal person going beyond his/her limits when exercising, for example a cyclist after a race, not being able to walk straight for a moment. Don't know the correct word for this in English, probably muscle soreness, but in a severe form.

My experience is quite different from yours. I can do short movements rather normally but my muscle tire abnormally fast. So I get the feeling of having finished a marathon or bike race, while I'm actually just making a short walk.

I contrast to you, I had this since the very beginning of my ME - before other symptoms, except for exhaustion, became apparent or severe. At the time I was very fit, played a lot of sports etc. so it certainly wasn't related to deconditioning.

 

Thanks, @Michiel Tack , and apologies for my former versions of this reply (a combination of brain-fog and limited English).

I'll try again:
It's interesting how you describe your feeling of lactic acid filled muscles. I first associated this with an unsual, early onset of muscle soreness. which I always associated with pain, from mild to intensive, accompanied by stiffness. For me, when muscle soreness is strong enough to limit my movements, usually the pain is the limiting factor.

The most typical form of muscle soreness for me is pain accompanied by stiffness, a normal, not illness-related reaction 12-24h after unusual or increased exercise. This muscle soreness can range from mild to intensive, while I experience (as I experienced in pre-ME-times) only the intensive form as partially and temporarily debilitating (lasting < 48h), and again the pain is the most debilitating part, not the stiffness.

Since having moderate ME, I rarely experience intensive muscle soreness as I understand it. For me now the limiting factors in doing physical activities are muscle stiffness, coordination problems, weakness, and vertigo.

This description seems to me also to resemble one of the types of my, now illnes-related, reactions to exercise.

I understand that this impairment is severe enough to stop you continuing an activity with a presumably low power-output (walk) after an inadequate amount of time (short).

I think it's interesting how long this impairment (inability to walk strait) lasts after you interrupt the activity? How long have you to pause before you are able to walk the same distance again?

In my case, the duration varies from some minutes or hours to up to several days depending on the sort of activity but also on the state of the illness I'm currently in.

Edited for clarity.

 

Your wish must have had an effect. Saw on FB yesterday that they're still looking for more participants.

 

Well, I could say that I wish my wishes could be different. I have become so jaded with regard to any sort of belief in either competence or in the case of some subset of research a will to suspend a prior bias.

I try not to dwell on it.

Let's hope that the whole of medical scientific inquiry births a renaissance of actually valid research findings very soon.