New paper: Aerobic Energy production and lactic acid excretion inhibited in severe ME

[Gingergrrl]

That's just as likely given that recovery is relatively quick (12 hrs) compared to much longer recovery more typical of PEM.

So if a person walks a few feet from their bed to their toilet and this triggers a 12 hour recovery period which includes shortness of breath, chest pain, muscle fatigue and pain, etc, this would be considered "relatively quick" for you?

I'm just saying taking 12 hours to recover from walking across a room is not definitive evidence of ME.

Um... Okay.

 

[MeSci]

SOC said: ↑
That's just as likely given that recovery is relatively quick (12 hrs) compared to much longer recovery more typical of PEM.

So if a person walks a few feet from their bed to their toilet and this triggers a 12 hour recovery period which includes shortness of breath, chest pain, muscle fatigue and pain, etc, this would be considered "relatively quick" for you?

SOC said: ↑
I'm just saying taking 12 hours to recover from walking across a room is not definitive evidence of ME.

Um... Okay.

I'm inclined to agree with SOC. PEM is almost always delayed, usually lasts longer than 12 hours, and those particular symptoms could be due to other c0nditions. PwME commonly also have an immediate type of fatigue, which may take a few minutes to a number of hours to recover from, but so do other conditions.

 

[Rick Sanchez]

The experiment was done by the researcher on only one person (himself). So you have to take the ''study'' with a grain of salt. (There are countless reasons for this, won't even start listing them here)

That being said, I really commend the author for having done this. I have always wanted to try and take before, during and after blood samples of my self when exercising. Since exercising is probably where our body will reveal most about the horrible condition we suffer from, since it is the time it is stressed out the most.

Another thing of importance is that the author is suffering from a severe case. This is also important, since people suffering from extreme CFS / ME will most likely reveal the most about the disease.

Really wish that more of these experiments could be conducted on a larger scale. Especially because they are not that expensive to carry out (compared to alternative tests), and very quick to carry out.

Simply find 100 people with severe CFS / ME, who are willing to do whatever constitues ''exercise'' for them. And then messure all sorts of different things (and mix it up with food like the author did).

The point about food is actually especially interesting. Because it is something I can relate to. I am someone with mild / CFS / ME who had been trying in the past to exercise to get better (I didn't understand I had CFS / ME). And food had an impact on how everything from exercise to simply studying would affect my CFS / ME. I was a lot more prone to brainfog and thus a flare / crash, if I worked out or studied after a ''large'' meal.

 

[Bob]

If someone has an immediate reaction to exertion and then takes 12 hours of rest to improve, then that's perhaps not enough in itself to define ME, but the full context needs to be considered. To define ME, I would say that PEM can be delayed and has the potential to last for an extended time period. However, if someone is so incredibly ill, and bed-bound, then they're in a constant state of exhaustion, and things are not straightforward. I expect if this patient did more than a brief walk to the toilet then the consequences would be catastrophic; the post-exertional reaction would be dire and long lasting.

I have roughly three different types of 'recovery' periods. If I slightly over-do things during a single period of exertion, then I get tired and I can rest afterwards and get back to baseline energy after a day of resting. Or, if I over-extend myself slightly more, then it may take me a week of resting to return to baseline. Or, if I massively over-do things then my baseline plummets and it can take me months or years to return to a better state of health. I think all three situations involve PEM, but I'd only refer to the latter situation as a relapse, whereby my baseline crashes for an extended period. If I experience a set-back for a day or week then I tend to think of it as part of the day-to-day unavoidable fluctuations, rather than a relapse, but it still involves PEM.

Sometimes my set-backs are clearly delayed for 24 hours, but other times the consequences of over-exertion can be immediately obvious; Sometimes relapses are disastrous, with an obvious sudden downwards shift in the illness, but relapses take various shapes and forms.

So I think the full context needs to be considered when considering PEM in relation to ME.

Edit: And that's just my experience - other people may experience other patterns.

 

[jimells]

While reading this thread I wondered, "What do we actually know about severe ME?", as opposed to anecdotes and theories, of which there seem to be an infinite number. The answer appears to be, "Nothing." I could not find a single study on severe "CFS". The closest I could find on Pubmed is a Jason 2009 paper that analyzes a pediatric case definition.

It's astounding that we don't have any answer at all to basic critical questions such as, "Are severe patients always in "PEM"? Are they constantly exceeding their anaerobic threshold?"

This paper suggests the patient is *not* constantly exceeding AT, since he lists the lactate as 1.6, but immediately exceeds it by getting out of bed.

The aerobic threshold (AeT) is sometimes defined as the exercise intensity at which anaerobic energy pathways start to operate and where blood lactate reaches a concentration of 2 mmol/litre (at rest it is around 1).

But of course that tells us little about other severe patients, especially those who can't get out of bed at all.

 

[Seven7]

FYI, I came to the same conclusion as of this guy just by observing my overdo / pain patterns. And I have learn to feel the tiredness/ heaviness feeling as too much latic acid in the body. By drinking baking soda and massage I learn to control it. Sometimes is fast, sometimes the heaviness takes days to settled in,

All depends on the trigger and the level of exertion how fast the PEM will hit.

 

[jimells]

Another way to measure lactate levels non-invasively is using Near-infrared spectroscopy. There are wearable NIRS sensors for professionals, so they can monitor their lactate levels real-time.
Although the lactate threshold is defined as the point when lactic acid starts to accumulate, some testers approximate this by using the point at which lactate reaches a concentration of 4 mM (at rest it is around 1 mM).

Anybody know anything about wearable lactate monitors? I wonder if this could be a useful way for patients to determine their own anaerobic threshold, without all the pinpricks and waiting and expense of the method used in this thread's discussion paper.

 

[Gingergrrl]

It's astounding that we don't have any answer at all to basic critical questions such as, "Are severe patients always in "PEM"? Are they constantly exceeding their anaerobic threshold?"

Thank you @jimells for saying this and as patients transition to the very severe state, such as Whitney Dafoe and countless others, I believe this to be the case. I used to be able to walk an hour and then get what I now know to be PEM. Now on good days, I can walk from bed to bathroom unassisted and on bad days, I am pushed in wheelchair.

I have never had my lactic acid levels tested so cannot comment on that aspect or the role it plays (or does not play.) but I suspect very ill patients can trigger PEM by rolling over in bed. I now get shortness of breath and angina if I attempt to walk one stair and it is immediate.

I thank God for doctors like Vink who are taking matters into their own hands to try to get some answers to help this community. I hope he is not reading this to see that others have determined he does not have the "real" ME/CFS like they do.

I have stayed quiet on these types of threads for six months and plan to continue as they are way too stressful for me but I had to speak up for the severely ill and give this man props for the study he carried out.

 

[Rick Sanchez]

While reading this thread I wondered, "What do we actually know about severe ME?", as opposed to anecdotes and theories, of which there seem to be an infinite number. The answer appears to be, "Nothing." I could not find a single study on severe "CFS". The closest I could find on Pubmed is a Jason 2009 paper that analyzes a pediatric case definition.

It's astounding that we don't have any answer at all to basic critical questions such as, "Are severe patients always in "PEM"? Are they constantly exceeding their anaerobic threshold?"

Completely agree. It is absolutely insane if you think about it. The irony is that the reason for this is due to the nature of the disease

1) People who suffer from it are simply too fatigued to actually carry out anything of note, or even able to take initiative to do something. I really wish I could do more. But when every week of your life is a challenge of not getting worse, than you simply do not have the energy. I mean jesus, we don't even have the energy to complain properly! Also dying of ''fatigue'' simply isn't as sexy as dying from some other horrible disease.

2) Other people won't do it for us, since it is still so ingrained in our society, that we suffer from a psychological problem, since there are absolutely no visible signs of the disease.

 

[Rick Sanchez]

Thank you @jimells for saying this and as patients transition to the very severe state, such as Whitney Dafoe and countless others, I believe this to be the case. I used to be able to walk an hour and then get what I now know to be PEM. Now on good days, I can walk from bed to bathroom unassisted and on bad days, I am pushed in wheelchair.

I have never had my lactic acid levels tested so cannot comment on that aspect or the role it plays (or does not play.) but I suspect very ill patients can trigger PEM by rolling over in bed. I now get shortness of breath and angina if I attempt to walk one stair and it is immediate.

I thank God for doctors like Vink who are taking matters into their own hands to try to get some answers to help this community. I hope he is not reading this to see that others have determined he does not have the "real" ME/CFS like they do.

I have stayed quiet on these types of threads for six months and plan to continue as they are way too stressful for me but I had to speak up for the severely ill and give this man props for the study he carried out.

This is honestly the worst part about this forum. It's a sort of pissing contest about who has it worst, as if our lives aren't shit enough now we have to compete about who is worst off?

Really well said though. Glad you sacrificed some of your energy to contribute to the discussion. Hope you get better

 

[Gingergrrl]

Really well said though. Glad you sacrificed some of your energy to contribute to the discussion. Hope you get better

@Rick Sanchez Thank you and I appreciate the kind words and support. I do not plan to participate further in this discussion but felt I needed to say what I said as I felt strongly about it.

 

[Bob]

This is honestly the worst part about this forum. It's a sort of pissing contest about who has it worst, as if our lives aren't shit enough now we have to compete about who is worst off?

Perhaps I've missed something but I haven't seen any of that going on in this thread, and I think you may have misinterpreted some of the comments made. Apart from a single thoughtless and dismissive post, unless I've missed something, the comments in this thread have questioned whether an immediate reaction to exertion and a twelve hour recovery time are typical of ME, and are adequate to diagnose ME. If we can't explore that issue between ourselves, to try to better understand ME, then where is that discussion going to happen?

Other comments have expressed an interest in the paper while questioning its scientific rigour. Questioning the rigour of a scientific publication is part of the scientific process; If a person publishes a scientific paper then they expect it to be discussed and critiqued; praised and criticised; There's no point in publishing if you don't want it discussed. If we don't agree with the criticisms of the paper, then we can challenge them, as has been done in this thread in a respectful way.

It's an interesting paper that has stimulated discussion, as demonstrated by all the comments in this thread. And I think the bulk of the discussion in this thread has been helpful and interesting.

 

[Valentijn]

This is honestly the worst part about this forum. It's a sort of pissing contest about who has it worst, as if our lives aren't shit enough now we have to compete about who is worst off?

The discussion was about the absence or presence of a symptom (PEM), not about severity. The author/subject of the study is obviously severely disabled. And I do disagree with your characterization about pissing contests on the forum. It isn't a matter of "who's sickest" - it's a matter of "who has the symptoms required to be diagnosed with ME."

In the severe cases, there does not seem to be an easy way to determine discrete episodes of PEM, or even the capability for the patient to engage in a discrete triggering event. So I don't think there's an easy "yes" or "no" regarding PEM in those cases. However I would expect that they were in a milder state of ME at some point in the past, where PEM could be clearly experienced and observed.

But I do find it a little bizarre that some people are so closely questioning the diagnosis of someone severely disabled. It's not like he felt a bit down for a while before pulling himself out of it with burlesque dancing, and went to the Daily Mail to spread the news The description of his case isn't harming anyone, and it's actually somewhat helpful. And quite inspirational.

 

[lansbergen]

This is honestly the worst part about this forum. It's a sort of pissing contest about who has it worst, as if our lives aren't shit enough now we have to compete about who is worst off?

I went from mild to moderate to severe to very severe and after starting taking the immune modulator very slowly from very severe to severe to moderate and somtimes I think it is only mild now. What is the pissing contest in that?

 

[Gijs]

This 'Medical center' and person of the study doesn't exist on the address in the Netherlands.

 

[Sidereal]

I wonder if perhaps the people who are questioning his ME diagnosis have never experienced ME of extreme severity where even walking to the toilet (or, in some cases, rolling over in bed or moving your limbs) depletes your muscle power - immediately. In a very severe patient like the author, I don't think the body ever has enough energy generation capacity to be able to get through exertion without immediate problems. It may be that delayed PEM simply indicates a higher level of health/functionality of those who are still able to participate in research studies and go to doctors' offices. It's interesting that the ICC says PENE is the cardinal symptom while Ramsay said

Muscle fatiguability, whereby, even after a minor degree of physical effort, three, four or five days, or longer, elapse before full muscle power is restored and constitutes the sheet anchor of diagnosis. Without it I would be unwilling to diagnose a patient as suffering from ME, but it is most important to stress the fact that cases of ME or mild or even moderate severity may have normal muscle power in a remission. In such cases, tests for muscle power should be repeated after exercise.

Notice how he doesn't say anything about delayed onset of symptoms. He obviously saw a lot of severe hospitalised cases during the Royal Free outbreak. I wonder if the ICC is more geared toward the mild patient who can do stuff like 2-day CPET or the moderate patient who can still potter around a bit without collapsing to the ground from minor muscle work or go to a doctor's office but then crash for days afterwards.

These days I'm moderate and the ICC describes me well (though Ramsay's definition describes me better) but there was a time when I was severe, bordering on very severe, and the PENE description was no longer relevant to me. To give you an example, a couple of years ago I was bedridden and only left the bed to go to the toilet and eat meals. Living in an apartment at the time meant that these trips only required a few steps each way. I was very depleted by each trip and it took me hours to "recover" from them. Then one day I went to answer the door and the cat ran out, ended up two floors up and refused to come down. Like a moron instead of getting the elevator I decided for some inexplicable reason (severe patient with POTS standing upright = brain hypoperfusion = reasoning skills and judgment in the toilet) to walk up the two flights of stairs to get him. What could possibly go wrong? Anyway, I made it back to bed somehow but man, I thought I was going to die for sure. Angina, severe shortness of breath, pain in muscles, tachycardia worse than usual, extreme muscle weakness, sore throat etc. etc. This went on for several days where I couldn't catch my breath etc. So yeah, it was immediate and it lasted for days. The trips to the toilet and the dining table caused immediate symptoms but simply weren't depleting enough to cause symptoms lasting days.

It may be that the author's trip to the toilet isn't strenuous enough to trigger the true post-exertional amplification lasting days or weeks or months for him though he might have real PEM too but simply isn't in a position to trigger it because he collapses long before he's able to damage himself with a more significant overexertion. It could be the same underlying process though.

I wonder if the folks with delayed PEM who think immediate symptoms from exertion indicate "exercise intolerance" would experience immediate PEM too if they challenged their bodies with something more substantial like trying to run. Not that I would recommend doing this in a million years; I'm just making a comparison between this patient (who might be hitting the anaerobic wall from walking to the toilet since to him that is the equivalent or running a marathon) and a moderate patient who might need to run on a treadmill for a few minutes before they hit the wall and collapse with acidosis.

Re: exercise intolerance, I often compare my situation of prolonged recovery from exercise, autonomic symptoms, weird flu-like inflammatory symptoms etc. during PEM to someone like my father who has heart disease, mild COPD, is on like a dozen meds and has classic exercise intolerance with breathlessness and fatigue on exertion but after a good nap or a night's sleep he's as good as new. I don't think there anything more than a superficial similarity between ME/CFS reaction to exercise and and exercise intolerance in other diseases. I think if this guy had another disease that was causing such severe exertional intolerance that leaves him bedridden for years it would have declared itself by now on conventional medical tests.

 

[Mij]

In the severe cases, there does not seem to be an easy way to determine discrete episodes of PEM, or even the capability for the patient to engage in a discrete triggering event. So I don't think there's an easy "yes" or "no" regarding PEM in those cases. However I would expect that they were in a milder state of ME at some point in the past, where PEM could be clearly experienced and observed.

Very true. I've been ill for 24yrs and diagnosed with atypical M.E by a specialist who co-authored the Canadian def. and yet I still questioned MY own diagnosis for the first 6.5 years. Many factors play a role and this illness morphs over the years. Vink's experiment is interesting but he's only been ill for a short time and I don't see anyone questioning the fact that he's ill. I don't see anything he wrote regarding his experiment as being indicative that he has M.E. .

Perhaps those of us who have OI, severe autonomic dysfunction or constant viral reactivation etc experience PEM differently.

 

[Valentijn]

I wonder if the folks with delayed PEM who think immediate symptoms from exertion indicate "exercise intolerance" would experience immediate PEM too if they challenged their bodies with something more substantial like trying to run.

I agree with most of what you say. I think the "running" example is a good one. But I still don't think those pretty immediate effects are the same as PEM.

I did the equivalent of going for a run when my condition was moderate. Due to inability to find a wheelchair near the parking areas, and a lack of sufficient assistance from the airport personnel, I ended up walking 1-2 kilometers through an airport with way too much standing. By the time I got to my seat, I was in very bad shape ... I was exhausted, I couldn't catch my breath, I couldn't think straight, and my heart rate was probably very elevated.

And after take-off, I realized I couldn't stand up because my right thigh muscle had literally stopped responding when I tried to move it, and it stayed that way for over an hour. Somehow my gross over-exertion in the past 2 hours had resulted in a bit of temporary paralysis, and some other symptoms as well. But those symptoms were definitely not PEM. The PEM clearly started the following day and lasted two weeks.

So my contention is that we usually have a few things going on, which might or might not be part of the same process or otherwise interacting with each other:

1. Delayed PEM, resulting in the onset or exacerbation of immune, neurological, and muscular symptoms
2. Orthostatic Intolerance, with immediate or moderately delayed onset (in the same day) potentially resulting in breathlessness, elevated heart rate, low blood pressure, etc
3. Exercise Intolerance, maybe triggered by OI, but perhaps triggered by other things instead of, or in addition to OI, hitting during or shortly after (within a couple hours of) exertion.

My personal impression is that with severe patients they are either in a constant state of PEM, or their trigger for immediate exercise intolerance is so low that their body will not let even let them exert enough to trigger PEM. It might arise due to damage done by the disease, or as a measure for the body to protect itself from more damage. Alternatively, the PEM and the exercise intolerance could both be parts of the same process.

So my interpretation would be that the elevated lactate found in the patient, which he has associated with his 12 hour muscle recovery time, would be due to the exercise intolerance aspect of his disease, rather than the PEM aspect which should show up later.

But it's also possible that all three things (Lactate, exercise intolerance, and PEM) are part of the same process. For example, perhaps the exertion triggers the excessive rise in lactate, which triggers the exercise intolerance symptoms, and triggers the process which results in PEM the next day.

Regardless of the precise mechanism, I don't see any good reason to question his diagnosis. It seems perfectly consistent with severe ME.

 

[Hip]

On the suggestion of @justy, I am reposting the following here:

I think it's worth trying to reproduce Mark Vink's results.

Possibly his prolonged elevations in lactate level will not be found in all ME/CFS patients; but it would be interesting to know how many other patients have these prolonged lactate elevations, and whether the manifestation of such prolonged elevations might correlate to ME/CFS severity, or correlate to some specific ME/CFS subtype.

I am wondering is whether this very simple blood lactate after exercise test might have any diagnostic implications. Might a relatively cheap blood lactate meter be a useful diagnostic tool for ME/CFS?

For those interested in participating in an informal PR forum study on blood lactate levels after exercise, see this thread.