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

Yes, if the study is well-intentioned then that is a great start. But it's crucial they understand that any normal monitoring for harms may not be adequate for PwME, given how many reports there are of PwME going from mild/moderate to severe from graded exercise programmes that supposedly 'ensure' no harm comes to people. I think it very important researchers try hard to really understand the issues that patients and advocates report, so they can understand much better the sort of things they must watch out for ... which may well be additional to what they otherwise realised. Especially if the trial is going to push people to their limits - one of the big uncertainties with ME is knowing what those limits are actually defined by, so how can you recognise them. And especially the fact that the consequences can be delayed until some time after the cause, which is always a very tricky condition to adequately manage, especially where safety is concerned.

 

Do not think this is mentioned allready but hodges et al. allready did a study of the 2 day CPET procedure in which they compared MECFS patients to MS patients.

The current study seems to investigate pacing by using heart rate at aerobic threshold as a limit. So it seems like they are independently trying to replicate or investigate the work of the Workwell Foundation.

The focus on exercise is probably because that's what their area of expertise is (they work at the School of Sport and Exercise at Massey university). So I very much welcome their interest in ME/CFS and hope they will study PEM into more detail.

 

Dear study authors (if you happen to read this). It seems clear to me that the current emphasis on exercise as treatment for ME/CFS was an error. It's a confusion of cause and effect. The poor fitness in patients is not the cause of the illness, it's the consequence. You should be looking into finding ways to increase the exertion tolerance of patients. I think you will find that patients, once they are less ill, will naturally resume higher activity levels. It has been 30 years that people say they can treat ME/CFS with exercise therapy, and we still do not have reliable evidence that exercise therapy is effective. By reliable I mean unambiguously better than placebo, results that are replicated, and apply to a population that meets most ME/CFS criteria. I don't think there are any studies that meet these reasonable criteria. That's because lack of exercise has nothing to do with why patients are ill, so it's hard to demonstrate a meaningful benefit.

 

They also need to understand that physical energy expenditure can also have a negative impact on our cognitive deficit.

I don't want to talk or process information after 'exercise'.

 

Because it is the most interesting phenomena if we wish to understand the altered effort perception in CFS patients. I agree that this might not be so useful in terms of management...

Amongst healthy people and patients with various conditions (other than breathing restricted conditions such as COPD), the ventilatory threshold/anaerobic threshold directly matches the increase in effort perception on the Borg scale during a CPET. In CFS patients who have a reduction in their anaerobic threshold due to PEM, guess what, a change in effort perception directly mirrors this reduction.

There is a however myth that it is pushing past the anaerobic threshold that causes PEM and that keeping your heart rate down below this level will somehow prevent PEM. I have had severe PEM after doing prolonged low intensity activity (fixing my electric bike), but avoided severe PEM after exercising briefly past my anaerobic threshold while pedaling on said bike (heart rate 160+) and then resting. Occasional brief spurts above the anaerobic threshold is how you can maintain or even increase VO2max without doing much exercise overall - you only need to do less than 10 minutes of exercise one day a week to maintain an above average VO2max for one's age and bodyweight.

If you want to be fast in the 1500m, you will be regularly exceeding the anaerobic threshold during training ("speed training"), so that you can improve your performance at the threshold...

I don't believe there is any serious evidence that the effort perception you are speaking of is due to cytokine signals. However there have been a few interesting studies which have tried to investigate what could influence such signals, eg does infusion of adrenaline alter VO2Max or effort perception? (answer: no)
https://www.ncbi.nlm.nih.gov/pubmed/16215769

Yes, it is quite different. Hitting the wall is due to glycogen depletion, not merely exceeding the anaerobic threshold.

This does beg an interesting question though...

"The effect of exercise induced glycogen depletion on the lactate, ventilatory and electromyographic thresholds."
https://www.ncbi.nlm.nih.gov/pubmed/9190123
"Effects of glycogen depletion and work load on postexercise O2 consumption and blood lactate."
https://www.ncbi.nlm.nih.gov/pubmed/533743
"Effects of glycogen depletion and pedaling speed on "anaerobic threshold"."
https://www.ncbi.nlm.nih.gov/pubmed/6809718

 

See my cooking and baking adventure yesterday. That was prolonged low intensity activity and triggered noticable changes to heart rate plus a symptom increase on the next day. Unless mixing the dough counts as high intensity exercise .

 

Many thanks.

 

I'm speculating due to insufficient information but it looks like they're intending to do test 1 up to threshold to establish where the threshold is.

Then later do a 2-day test below threshold to see if patients can replicate their VO2max or whatever on day 2.

There are lots of confounding factors already mentioned in this thread related to effects of pre-test exertion and duration of effort.

Even ignoring those, there's another potential confounding factor. The anaerobic threshold in ME may simply not be stable. In healthy people it is supposed to be quite stable day to day and only change slowly in response to consistent training. Is that also the case in ME? I suspect not. Why? One, I track heart rate variability that is also supposed to be stable day to day and only change slowly in response to consistent training, again in healthy people. In ME it can swing significantly from day to day, mirroring daily fluctuations in ME severity. It is not unreasonable to assume that VO2max and HRV would move - fluctuate - in tandem. Two, the HR I can operate at on a good day without causing PEM is higher than the safe HR on a not so good day. If HR is an approximation of VO2max this indicates that VO2max could fluctuate.

If I'm right then a single test to establish anaerobic threshold in an ME patient would not give a reliable, meaningful result. Unfortunately there's no easy solution to this as it's not really possible to exercise an ME patient to threshold every day to measure fluctuations.

 

I am not sure. I don't pretend to understand exactly what they have shown.

My understanding is that when you start exercising it looks 'anaerobic' in the sense that it is before breathing rate increases and oxygen uptake increases. However, I am not sure it is actually anaerobic at the muscle level. My understanding s that since there is plenty of oxygen around normally (red cells are fully oxygenated) the muscle can use aerobic respiration at the start. It is only after it has used up oxygen that it has to shift to anaerobic. And if you start out jogging and keep the pace gentle then you never hit anaerobic at all because your lungs keep the oxygen up by shifting more air.

I don't think PWME can hit anaerobic very early because their anaerobic threshold is not that different from sedentary controls if I remember rightly. I think they must hit anaerobic threshold somewhere around 100-200 Watts. So I don't think the 'early anaerobic phase' is an issue here.

Maybe someone here is an expert?

 

I think they are different. Anaerobic threshold is the point at which you can no longer transport enough oxygen to muscle to keep it working on aerobic glucose breakdown. It switches to anaerobic glycolysis. But that produces lactate and after a while of producing lactate you build up lactate and hit the wall. So Mo Farah runs below anaerobic threshold for 9,600 metres and then suddenly sprints ahead, exceeding his anaerobic threshold. Because he is so fit he can keep that up for 400 metres, whereas most people can only do it for 100. He aims to hit the wall exactly 1 metre before the tape and falls to the ground, passing the tape in the process.

Or put another way. Chris Hoy's anaerobic threshold may have been 500 Watts but when sprinting he could produce 2400 Watts for a short period. These are very different levels.

 

Actually, if I was less severe and if I happened to live near Massey I would register for the study out of curiosity, to get more detailed information. Having knowledgeable patients engage could even help improve study design, if not for this study (protocols may already be fixed) then for future studies.

Whether I then would actually participate or not would very much depend on the information received.

 

Do we know if PwME can safely exercise to their anaerobic threshold. Or might there be some other disease-specific threshold they may reach before that, with potential risk of harm if pushed further?

 

I don't think we know much about this at all.

I doubt that getting symptoms at a lower threshold would be anything unusual. Most illnesses that make one feel weak prevent activity way below anaerobic threshold. An acute viral infection can reduce one to stumbling to the loo and back and no more.

I don't actually think anaerobic threshold is likely to be that important. If it was we would expect our bodies to signal we had reached it but they don't. We don't know if we are exceeding the threshold. We just know that if we exceed it for long enough we hit a wall.

 

Personal note: for me the experience that characterized ME/CFS during exercise (I had a gradual onset and so for a while had mild ME) is extreme muscle soreness (like I had just run half a marathon) after mild physical activity.

The weird thing is that I wasn't out of breath. In fact sometimes I felt I could do more but my muscles were saying they had run half a marathon. It felt like the muscle soreness you have after going anaerobic, like my legs were full of lactic acid. I was quite athletic at the time so it definitly wasn't related to deconditioning.

According to Jonathan's reasoning this is strange because I wasn't out of breath, but it makes me wonder: perhaps the problem isn't so much the supply of oxygen (the task of red blood cells) but the capacity to use it (the task of mitochondria)?

 

@JaimeS I think this came up before somewhere and you responded to it. There is more to PEM than heart rate monitoring during exercise. I don't believe in the heart rate monitoring for ME/CFS as there are abnormal biological changes taking place which have already been proven out in research with exercise and various blood tests. Also, cognition cannot be monitored. This also leads to PEM; balancing a checkbook after monitoring heart rate during exercise spells C-R-A-S-H.

 

When a PwME hits this completely done in stage, it is presumably possible to test if there is any unused oxygen still available?

 

I used to think that the 2 day CPET results and deficiencies in aerobic capacity made sense because exercising with ME often feels like your muscles instantaneously fill up with lactic acid (not only I but also Anil Van Der Zee and Marc Vink have described it like that). But now I'm not so sure anymore. The 2 day CPET results are only evident after a heavy exercise on the first day and the aerobic threshold seems too high to explain the lactic acid feeling some of us experience after exercises that are far less taxing...

Can anyone help explain this paradox?

You could argue that the patients in the trials have a milder form of ME and thus an anaerobic threshhold that is not as low as in patients with severe ME. Yet I personally remember having the lactic acid feeling after minor physical activity back when I had mild ME.

Is there some way to experience a lactic acid feeling without reaching the anaerobic or is possible that ME patients do reach the anaerobic threshold and produce lactic acid at an early stage, but without the exercise test picking this up? I think CPET uses the ventilatory treshold which is related to breathing rate and oxygen uptake and doesn't measure lactic acid directly (could be wrong though).

 

I agree with @Jonathan Edwards, the anaerobic threshold is not a magic threshold.

The most interesting exercise finding in ME patients is that the ventilatory threshold is reduced on the 2nd CPET. Now the ventilatory threshold is associated with, but not caused by the anaerobic threshold, in fact under certain physiological conditions the ventilatory threshold and anaerobic threshold can become decoupled somewhat. The key to the ventilatory threshold is it indicates the switch from slow twitch to fast twitch muscle fibres. The problem is not a build up of lactic acid.
Now my hypothesis relates to the following - fatigue sensation is about predicting future performance, namely how long you will be able to keep up a particular activity. The idea is that there is a persistent *peripheral* signal that suggests fatigability, but is not necessarily strong enough to have an effect on performance until a certain threshold is met - during the 2 day CPET, that signal is increased and as such, the signal(s) relating to the ventilatory threshold in this case is reduced.

 

It would be interesting to get some expert advice here.

Myss is that the lactic acid feeling is not necessarily due to lactate. My memory is that when one reaches 'the wall' muscles are painful to use but if one sit son the ground there is no pain. So the lactate is not producing the pain directly. Maybe the pain actually arises from a conflict in the spinal reflex - the brain tells the nerves to tell the muscle to contract but the muscle cannot do so. The stretch receptors get unexpected signals, the servo efferents respond with wrong signals and you end up fighting yourself. It might be that lactate feeds in to this signalling chemically but maybe people just talk of it as a lactate problem because lactate correlates with the inability of the muscle to contract any more.

My own experience is that when I have flu I get a very similar 'wall' when trying to go upstairs or put out the garbage bins at very low levels of effort. This presumably has nothing to do with lactate but may be a similar conflict in the reflex because of cytokine induced muscle inhibition.