Loss Of Capacity To Recover From Acidosis On Repeat Exercise In CFS (Jones et al,'11)

[Dolphin]

Secondly, what is the 'Fatigue Impact Scale' referred to?

Short answer:

Assessment of Severity of Fatigue

In order to quantify fatigue all participants completed the generic fatigue measure, the
Fatigue Impact scale (FIS). This tool has been validated for self-completion in both normal
populations and CFS patients [31]. The range of potential scores is 0-160 with higher scores
indicating increased fatigue.

31.Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional
impact of fatigue: initial validation of the fatigue impact scale. Clinical Infectious Diseases
1994;18:S79-83.

 

[Dolphin]

I should say that this wasn't the authors first paper on acidosis. The other paper(s) probably talked about the biology more which may be which this paper concentrated a bit more on the novel finding that some hadn't done the exercise test hard enough.

 

[justinreilly]

It's nothing too deep.

Basically their theory is that some people are so phobic about exercise that they won't do an exercise program; and the ones that do exercise have excess acidosis which they claim has a logical treatment, exercise.

As well as the reasons given above, I think part of their reasoning is that the patients get the acid from exercise in the anaerobic phase - if one can get people fitter so they don't hit the anaerobic phase, they won't experience the acid as much (I think that is what they are saying/hinting at) as well as (what I said previously that) they're extrapolating from other groups, where doing exercise may reduce excessive acidosis (but they haven't shown it works in CFS and indeed, their results suggests the opposite happens in CFS to other groups).

That makes sense. (of course they don't know anything about ME or they wouldn't come to these conclusions)

 

[Dolphin]

Regarding their theory that this might explain the mixed results for programs designed to involve exercise and that some people might need some sort of therapy to persuad them to exercise first: somebody pointed out to me today that that's basically what GET-based CBT and GET are.

 

[Holmsey]

Repeat Exercise Study -

This was posted today on the ME Associations web site -

Research: difficulties with repeating exercise, how muscle function responds to exercise, European Journal of Clinical Investigation, February 2012
by Tony Britton on January 9, 2012
Eur J Clin Invest. 2012 Feb;42(2):186-94. doi: 10.1111/j.1365-2362.2011.02567.x. Epub 2011 Jul 12.

Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study.

Jones DE, Hollingsworth KG, Jakovljevic DG, Fattakhova G, Pairman J, Blamire AM, Trenell MI, Newton JL.
Institute of Cellular Medicine Newcastle Magnetic Resonance Centre Institute for Ageing and Health The UK NIHR Biomedical Research Centre in Ageing and Age Related Diseases Newcastle Centre for Brain Ageing and Vitality, Newcastle University, Newcastle, UK.

Abstract

BACKGROUND? Chronic fatigue syndrome (CFS) patients frequently describe difficulties with repeat exercise. Here, we explore muscle bioenergetic function in response to three bouts of exercise.

METHODS? A total of 18 CFS (CDC 1994) patients and 12 sedentary controls underwent assessment of maximal voluntary contraction (MVC), repeat exercise with magnetic resonance spectroscopy and cardio-respiratory fitness test to determine anaerobic threshold.

RESULTS? Chronic fatigue syndrome patients undertaking MVC fell into two distinct groups: 8 (45%) showed normal PCr depletion in response to exercise at 35% of MVC (PCr depletion >33%; lower 95% CI for controls); 10 CFS patients had low PCr depletion (generating abnormally low MVC values). The CFS whole group exhibited significantly reduced anaerobic threshold, heart rate, VO(2), VO(2) peak and peak work compared to controls. Resting muscle pH was similar in controls and both CFS patient groups. However, the CFS group achieving normal PCr depletion values showed increased intramuscular acidosis compared to controls after similar work after each of the three exercise periods with no apparent reduction in acidosis with repeat exercise of the type reported in normal subjects. This CFS group also exhibited significant prolongation (almost 4-fold) of the time taken for pH to recover to baseline.

CONCLUSION? When exercising to comparable levels to normal controls, CFS patients exhibit profound abnormality in bioenergetic function and response to it. Although exercise intervention is the logical treatment for patients showing acidosis, any trial must exclude subjects who do not initiate exercise as they will not benefit. This potentially explains previous mixed results in CFS exercise trials.

2011 The Authors. European Journal of Clinical Investigation 2011 Stichting European Society for Clinical Investigation Journal Foundation.

PMID: 21749371 [PubMed - in process]


--------------------------------------------------------------------------------

 

[Nielk]

This is great! Thanks Holmsey for posting.
Eventhough it's a small study, it seems to show a definite difference in excersise results between CFS patients vs normals.
Coming especially from the UK, this is huge. I was really glad to read this!

 

[Holmsey]

UK

Yep, I notice there's a piece by Cort on the home page suggesting there's perhaps been a shift in the UK. There certainly seems to have been a number of papers over the last few months involving the UK, then there's the recomendations to the Scottish Parliament to seperate definitions of ME from CFS by using the CDC to establish ME and only upon failure moving to Oxford for a diagnosis of CFS.

This study, although via an English University, also indicates the CDC was used for selection, a major step forward in itself. Added to that we've news that Liverpool Uni will be conducting an advanced Mito study. Just a pity we're still getting garbage like the City of Bath Schools study thrown in, while that's still happening the politicians have an excuse for inaction.

Still, every bio study I'm reading about is identifying abnormalities, meaning their researchers are most likely at odds with NICE, researchers speak and I doubt they're going to rubish their own work so the alternative is to rubish the status quo. Here's hoping this is the year where the myths are well and truly busted.

 

[Sallysblooms]

I thought there were studies out already. At least UK is figuring it out. That is fantastic.

 

[Dolphin]

A thread on this paper already exists - please use that.

There is already a thread on this: http://forums.phoenixrising.me/show...-CFS-(Jones-et-al-11)&highlight=Hollingsworth

It would be good if future posts went there (so people like me don't feel we have to make the same points twice).

I will see if I can get somebody to merge the two threads.

In future, please do a search of the forum for papers to see if a thread already exists on a paper. Thanks.

 

[Esther12]

Funny it was posted by MEA so long after it came out. Thanks for your analysis in the other thread D.

 

[Marco]

Thanks for wading through this Dolphin.

I'm a little surprised that this has been well received.

It appears to highlight quite a significant sub-group with a motivational problem/exercise phobia who may have skewed the effectiveness of previous graded exercise trials downwards and who might require additional prior cogntive therapy.

The slightly larger (appropriately motivated) group show a massive increase in acidosis without the compensatory mechanisms found in PBC and mitochondrial disease for which graded exercise is beneficial. Ergo they conclude that this group is deconditioned and graded exercise would raise their anaerobic threshold.

Presumably they are reasoning that if there was an actual pathology then this group would have the same mechanism to deal with acidoisis when there has been a switch to largely anaerobic functioning.

This is very much at odds with the findings of Lane and Fulle et al amongst others plus the fact that many of us went from very active to unable to tolerate any aerobic exercise pretty much overnight (and with absolutely no lack of motivation to do so). It also plays very much into the hands of the motivation/deconditioned theorists.

Perhaps I have misinterpreted? I hope so as this is presumably the same Julia Newton in receipt of the latest MRC grants?

Understanding the pathogenesis of autonomic dysfunction in chronic fatigue syndrome and its relationship with cognitive impairment. Principal investigator: Professor Julia Newton

 

[Valentijn]

The slightly larger (appropriately motivated) group show a massive increase in acidosis without the compensatory mechanisms found in PBC and mitochondrial disease for which graded exercise is beneficial. Ergo they conclude that this group is deconditioned and graded exercise would raise their anaerobic threshold.

Doesn't using sedentary controls account for results that might otherwise be attributed to deconditioning?

 

[Holmsey]

Appologies

There is already a thread on this: http://forums.phoenixrising.me/show...-CFS-(Jones-et-al-11)&highlight=Hollingsworth

It would be good if future posts went there (so people like me don't feel we have to make the same points twice).

I will see if I can get somebody to merge the two threads.

In future, please do a search of the forum for papers to see if a thread already exists on a paper. Thanks.

It was not my intention to put anyone to any extra effort, the paper posted on the ME Associations website states:

Eur J Clin Invest. 2012 Feb;42(2):186-94. doi: 10.1111/j.1365-2362.2011.02567.x. Epub 2011 Jul 12.

As it's not February yet I figured it had been released ahead of publication, I then did a quick check on both the Research and Lattest news forums before posting. As Esther points out, strange that it has just been posted on the ME Association's site, in fact even today it is still their 'latest' article.

Anyway, as I said, appologies and thanks for bringing your critique to my attention.

Was happy, now depressed...probably need some exersize

 

[Esther12]

Was happy, now depressed...probably need some exersize

Dolphin is the guardian of the research forum. You should see what happens when someone posts non-CFS latest research in here!

 

[Marco]

Doesn't using sedentary controls account for results that might otherwise be attributed to deconditioning?

I'm not sure it does. Physiological changes due to inactivity are usually associated with prolonged and pronounced inactivity as might be associated with being bed bound or otherwise off your feet for whatever reason. The sedentary controls in this case were selected because they did a small amount of aerobic exercise per week and presumably this is in addition to normal daily activities. An appropriate control for a chronically ill group would surely be a similar group but one that does not necessarily share the same underlying pathology.

But I do agree that it seems strange that they should demonstrate a clearly disproportionate level of lacate acidosis that isn't followed by the compensatory mechanisms seen in PBC and mito disease but then conclude that graded exercise should be effective with ME/CFS as it is with both the former diseases. Surely an alternative (and possibly more likely) explanation is that lack of a compensatory mechanism may actually be an important contributor to PEM and worth investigating further?

It appears this is what was planned and was one of the three research projects pitched to the MRC :

This is a very exciting time for research in CFS/ME and we are eagerly awaiting the outcome from the recent MRC specific funding call for CFS/ME projects. The group in Newcastle submitted 3 applications; one to look in more detail at what causes autonomic dysfunction (problems with blood pressure regulation) and how it relates to cognitive function ( in diseases other than CFS/ME this relationship is well established and we want to see whether the same is true in CFS/ME), the second one was to explore the mechanisms that lead to the acid accumulation that we have found in those with CFS/ME and whether we can treat it, and finally a third project looking at the immunological profile in those with CFS/ME. So our fingers (and toes) are tightly crossed.

http://niceguidelines.blogspot.com/2011/09/professor-julia-newton-has-made-3.html

Not that I have any problem with investigating autonomic dysfunction and how it affects cognition as I could live productively without being able to exercise aerobically but it does seem a rather bizarrre decision to 'go off at a tangent' rather than fund a follow up to a study which showed a clear adverse reaction to exercise - which is the key symptom that differentiates ME/CFS from other 'fatigue states'. Particularly when GET is one of only two NICE recommended treatments and one which is particularly controversial.

 

[Dolphin]

It was not my intention to put anyone to any extra effort, the paper posted on the ME Associations website states:

As it's not February yet I figured it had been released ahead of publication, I then did a quick check on both the Research and Lattest news forums before posting. As Esther points out, strange that it has just been posted on the ME Association's site, in fact even today it is still their 'latest' article.

Anyway, as I said, appologies and thanks for bringing your critique to my attention.

Was happy, now depressed...probably need some exersize

It's no major problem, Holmsey. I was just taking the opportunity to making a general point. I certainly wouldn't want to make anyone depressed.

The memory of a lot of people with the illness is not great. The MEA actually highlighted the study on their site on June 30: http://www.meassociation.org.uk/?p=6842 .

 

[Dolphin]

But I do agree that it seems strange that they should demonstrate a clearly disproportionate level of lacate acidosis that isn't followed by the compensatory mechanisms seen in PBC and mito disease but then conclude that graded exercise should be effective with ME/CFS as it is with both the former diseases. Surely an alternative (and possibly more likely) explanation is that lack of a compensatory mechanism may actually be an important contributor to PEM and worth investigating further?

I agree and find it frustrating.

I think the problem is that they (to some extent) have been convinced that CBT and GET works for some people. If I remember correctly from this study, they don't think the other group of patients would benefit from GET programs as they wouldn't do the exercise but somebody has benefited so it must be the group with abnormal acidosis by a process of elimination.

I think it might have been welcomed because few people read the full paper and this group has produced other good work.

They might have lost out in the MRC grants because of the Liverpool muscle/mitochondria study - the MRC might have wanted a variety of studies so chose one of their other ones instead.

 

[Dolphin]

@mrkipping on Twitter found this which I find somewhat frustrating (although not totally):

Professor Newton then presented a whistle-stop tour of Chronic Fatigue Syndrome (CFS) – CFS has a prevalence of 0.2-0.4% and subsequently clinicians are typically underexposed to this syndrome and lack confidence managing it. The Graded Exercise Therapy (GET) by NICE was presented as a possible treatment algorithm but with varied results. Her research has shown at least 2 different muscle phenotypes exist in people with CFS, which may explain why some people responded better to GET. How long then until pharmacogenetics becomes everyday practice?

http://blogs.bmj.com/bjsm/2014/04/2...nference-imwideawake-basem-spring-conference/

 

[peggy-sue]

Good controls do seem to be a major problem.

I was once prescribed contraceptives, (early on in my illness) which came with the usual warning leaflet, which said;

"Not to be taken by women of a sedentary nature, eg. with a broken leg."

I did wonder, as somebody with a broken leg could probably do a lot more than I can.
I did not take the pills.
I did get very angry at the stupid gp.

Perhaps folk with broken legs would make for better controls than folk who just naturally prefer inactivity or have jobs that enforce it?