Is there any evidence that deconditioning alone causes pain and fatigue?

[oceanblue]

PS: I think that often more can be learnt about CFS by reading non-CFS papers than those by 'CFS specialists'. A lot of similar issues can be found, but tend to be discussed more seriously, and with greater concern for the interests of patients.

Normally I find it refreshing to read stuff from another field, away from the suffocating biases of many CFS researchers (and maybe my own too). But just read a 2007 review paper Physiological Basis of Fatigue that manages to say a lot about how deconditioning can cause fatigue - without backing it up with a single reference, which is odd given that other types of fatigue are well-referenced (180+ in total, zero on deconditioning). E.gs

Increased rest paradoxically can result in further deconditioning and exacerbate cancer-related fatigue syndrome [no ref].

Summary ... Fatigue from exertion may be related to deconditioning [no ref]

It's almost as if it's a consensus view that is excepted as self-evident without the need for any validation. A bit weird really. And a bit like CFS research too.

 

[Don Quichotte]

you may find those interesting:

http://well.blogs.nytimes.com/2012/05/30/can-exercise-be-bad-for-you/

http://well.blogs.nytimes.com/2012/05/31/afraid-to-speak-up-at-the-doctors-office/

 

[Don Quichotte]

The Hippocratic message concerning the foundation on which rest the relations between physician and patient may be summed up in a famous maxim: "as to disease, make a habit of two things- to help, or at least do no harm." Here Hippocrates clearly asserts that the purpose of medicine is to protect the interests of the patient. But the physician's unique point of view serves to lend nuance to what was to become a more dogmatic position with the philosophers. Because the injunction to "do good" represents an ideal that the physician cannot always attain, he adds "or at least do no harm" failing to be useful, the physician must not worsen a patient's condition through an untimely intervention.

to know how to question a patient was indispensable, but it was also necessary to know how to listen…the patient's response served as a guide for the physician in the course of treatment-but only on the condition that the physician knew how to interpret it. Where he did, an attentive dialogue came to be established that marked the beginning of authentic partnership between physician and patient in fighting illness. The art had three factors, the disease, the patient and the physician.

( From: Hippocrates, Jacques Jouanna)

 

[oceanblue]

you may find those interesting:
NYT: For Some, Exercise May Increase Heart Risk

Thanks, that was interesting.

Just to summarise the key points: a new study found that in rigorously done trials of exercise, for around 1 in 10 of participants at least one measure of 'success' e.g. lower blood pressure or choloesterol levesl, got worse, not better. The authors looked for lots of possible explanations of this such gender, age or fitness level at the start of the trial butcouldn't find anything that predicted the negative responses.

Also, the article points out that claims for the efficacy of exercise are based on improvements in measurable factors eg blood pressure, not long term-follow up showing that unfit people who take up exercise are actually healthier as a result.

The evidence still suggests that exercise is good for most people, but it appears this isn't a universal truth.

 

[oceanblue]

I remember starting this thread, linking to a review from 2008 that says:

"However, research findings about the precise role of physical deconditioning in CFS/FM are equivocal. Taken together, findings converge to suggest that the degree of physical deconditioning varies significantly among patients and that in contrast with previous theories this factor does not seem to play a specific pathophysiological role in the illness.27"

Van Houdenhove B, Verheyen L, Pardaens K, et al: Decreased motor performance in patients with chronic fatigue syndrome: should we treat low effort capacity or reduced effort tolerance? Clin Rehabil 2007; 21:1121–1142[Abstract/Free Full Text]

Really, the piss-poor results from GET alone should indicate that de-conditioning is not the primary problem.

I agree re PACE/GET, but I am interested in how deconditioned CFS patients are as a secondary consequence. That review reference [27] above is - in a big surprise - not necessarily robust. Amongst the 'evidence against deconditioning' studies it lists the monster (n>400) De Becker study which actually seems to provide evidence FOR deconditioning. Stil working my way through all this.

 

[oceanblue]

I'm still looking at deconditioning research but this Fulcher & White study from 2000 deservesspecial mention as it claims to make the case for both deconditioning as a perpetuating factor in and GET as the answer to CFS.

Strength and physiological response to exercise in patients with chronic fatigue syndrome
Kathy Y Fulcher, Peter D White

Abstract

OBJECTIVE To measure strength, aerobic exercise capacity and efficiency, and functional incapacity in patients with chronic fatigue syndrome (CFS) who do not have a current psychiatric disorder.

METHODS Sixty six patients with CFS without a current psychiatric disorder, 30 healthy but sedentary controls, and 15 patients with a current major depressive disorder were recruited into the study. Exercise capacity and efficiency were assessed by monitoring peak and submaximal oxygen uptake, heart rate, blood lactate, duration of exercise, and perceived exertion during a treadmill walking test. Strength was measured using twitch interpolated voluntary isometric quadriceps contractions. Symptomatic measures included physical and mental fatigue, mood, sleep, somatic amplification, and functional incapacity.

RESULTS Compared with sedentary controls, patients with CFS were physically weaker, had a significantly reduced exercise capacity, and perceived greater effort during exercise, but were equally unfit. Compared with depressed controls, patients with CFS had significantly higher submaximal oxygen uptakes during exercise, were weaker, and perceived greater physical fatigue and incapacity. Multiple regression models suggested that exercise incapacity in CFS was related to quadriceps muscle weakness, increased cardiovascular response to exercise, and body mass index. The best model of the increased exercise capacity found after graded exercise therapy consisted of a reduction in submaximal heart rate response to exercise.

CONCLUSIONS Patients with CFS were weaker than sedentary and depressed controls and as unfit as sedentary controls. Low exercise capacity in patients with CFS was related to quadriceps muscle weakness, low physical fitness, and a high body mass ratio. Improved physical fitness after treatment was associated with increased exercise capacity. These data imply that physical deconditioning helps to maintain physical disability in CFS and that a treatment designed to reverse deconditioning helps to improve physical function.

 

[oceanblue]

Commentary on Fulcher & White deconditioning paper

First, full credit to the authors for using objective measures of improvment alongside the self-reported ones. That said, there's some sleight of hand in this study, particularly when it comes to the interpretation and I'll pick out some key points:

1. The sedentary controls may not be very sedentary

2. In any case the patients in this sample don't appear particularly deconditioned

3. GET improvements in fitness don't relate correlate with self-rated overall improvements

4. The authors themselves caution against generalising from the study findings

Other than that, this study is definitive.

True levels of deconditioning in patients
As I said before, the overall evidence isn't clear cut, but this particular study suggests low levels of patient deconditioning, so it is unlikely to be clinically important.

Controls may not have beenthat sedentary: "Only those subjects who took part in no strenuous activity and exercised moderately less than once a week were accepted for entry into the study". Other studies specified that controls must have jobs where they are sitting down most of the time. As controls were recurited via Bart's hospital (in central London), it's likely they included staff who will spend a lot of time walking given the size of hospitals. And many commuters have to walk quite a way as part of their daily journey to and from work, and if this was the case the controls would be even further from sedentary.

The treadmill results also suggest that controls were in decent physical shape with a VO2 max of 34.1 ml/kg/min, higher, but not statistically different from the patients figure of 30.6 ml/kg/min. Compared with population norms (see next post) the Control mean would count as average (making the 'sendentary' claim uncertain) while the mean for CFS patients would be the top-end of 'Fair', ahead of a good chunk of the population - and therefore unlikely to be the cause of CFS.

Questionable model assumptions & interpretation
The authors used multiple regression modelling to 'explain' their findings among CFS patients. Unsurprisingly, BMI, quadriceps muscle strength and submaximal heart rate were predictors of exercise tolerance, as you would expect in any population. Anything specific to CFS patients? Not if you ignore it:

The regression models of exercise tolerance (time spent on the treadmill) showed a close association with RPE [Rated Perceived Exertion], but we excluded this in our final models as, like others, we found that exercise intolerance was at least partially dependent on RPE.11

Now a lot of people with CFS/ME, and probably even quite a few researchers studying it might not be surprised to see a strong association between RPE and exercise intorlerance. They and might even think it was a hallmark of the illness and that unusually high levels of fatigue characteristic of the illness explained the exercise intolerance.

So deliberately excluding this factor from their model is a little 'careless' and might explain why the modelcould only explain around 50% of the variance - it would be interesting to know what %age of variance would be explained with RPE included.

The regression model for increased exercise tolerance supports the importance of reversing deconditioning in CFS. Although we found no significant association between feeling better after graded exercise treatment and becoming stronger or fitter,14 ...

Er, I think that might rather contradict the deconditioning model.

Even the authors urge caution in interpreting and generalising their results

This work supports a hypothesis that disability in CFS is maintained by both physical deconditioning6 and a low threshold for certain somatic perceptions.40 Both of these factors may themselves be secondary to inactivity and causal attributions.10 [however] The alternative interpretation is that these changes are secondary to whatever else might be causing inactivity in CFS.4

We would in any case advise caution in interpreting and generalising from these data because of the bias inherent in a case-control study, the need for replication of these data, the lack of blindness in some of the measures, and the few comparison patients with a major depressive illness.

If this study were a used car, would you buy it?

Those author caveats hardly squares with the Peter White's subsequent citing of this study as evidence for the importance of GET and treating 'deconditioning'.

 

[oceanblue]

VO2 max as a measure of fitness
They most widely used measure of fitness is VO2 max, the amount of oxygen consumed at peak exertion, which is usually measured using an incremental treadmill or cycle ergometer test. It's standardised by expressing as millilitres of O2 conumed per minute, per Kg of body mass. VO2 max decreases with age and is generally a bit higher for men, but should be comparable in age and sex matched samples.

VO2 max norms (ml O2/min/kg)
There are also published population norms, e.g: for age 30-39
Women: Good: 34-38; Average=30-33; Fair=26-29; Poor=22-25;
Men:Good: 41-46; Average=36-40; Fair=31-35; Poor=27-30;

For a 75% female sample (ml O2/min/kg):
most CFS samples are 70%-80% female, so for a 75% female sample aged 30-39 (as for the Fulcher & White study), the weighted norm ranges would be:
Average 32- 35
Fair 27- 31
Poor 23- 26

Population distribution of VO2 max fitness levels:
Above average: 33%
Average: 34%
Fair: 22%
Poor: 8%
Very Poor: 3%

 

[Sean]

These data imply that...

Torture data enough, and it will imply almost anything you want it to.

 

[WillowJ]

@OB "@!# another paper to read! I mean, thanks, that looks highly relevant."
lol

 

[oceanblue]

While the data from most VO2 max studies strongly supports a lack of deconditioning in CFS patients, the largest study of all (n=427) provides strong evidence for deconditioning. I'm puzzled by the difference in results and would appreciate any comments. Here's the monster study:

Exercise Capacity in Chronic Fatigue Syndrome, 2000
Pascale De Becker, PhD; Johan Roeykens, PT; Masha Reynders, PT; Neil McGregor, MD, PhD; Kenny De Meirleir, MD, PhD

Background Patients with chronic fatigue syndrome (CFS) suffer from various symptoms, including debilitating fatigue, muscle pain, and muscle weakness. Patients with CFS can experience marked functional impairment. In this study, we evaluated the exercise capacity in a large cohort of female patients with CFS.

Methods Patients with CFS and matched sedentary control subjects performed a maximal test with graded increase on a bicycle ergometer. Gas exchange ratio was continuously measured. In a second stage, we examined only those persons who achieved a maximal effort as defined by 2 end points: a respiratory quotient of at least 1.0 and an age-predicted target heart rate of at least 85%. Data were assessed using univariate and multivariate statistical methods.

Results The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects. The maximal workload and maximal oxygen uptake attained by the patients with CFS were almost half those achieved by the control subjects. Analyzing only those persons who performed a maximal exercise test, similar findings were observed.

Conclusions When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances.

To put this into context, most studies find aVO2 max around 28-30 ml/kg/min (not much below average) while this study finds a VO2 max of 20.5, rising for 22.7 ml/kg/minfor the 40% of patients who were deemed to have reached maximal exertion - which is poor or very poor.

I'm not entirely sure why the results from this large study are so different from the other studies. The fact that all the subjects are female rather than 75% would only account for a 1 point difference. This study used a cycle ergometer rather than a treadmill, but the consensus seems to be that this makes very little difference in VO2max levels, at least in healthy individuals.

The authors say:

We believe that the failure to assess the more severely affected patients appears to have led to a disparity in study conclusions about the exercise capacity in patients with CFS

This may well be a factor, but subjects still had to make it to the hospital and be willing to attempt the VO2max test and I don't if it it's enough to account for all the difference on its own.

Unfortunately they give no other data (e.g. SF36 PF scores) to help assess the functional impairment of their patients. For comparison, the Fulcher paper that found a CFS VO2 max of around 30 reported a meanSF36 PF score of 48 (PACE was around 39 at baseline). Perhaps this De Becker study might have had a meanSF36 PF score as low as 30, but I suspect that it would be hard to make it to hospital for assessment withanything under 25 - andthey would need a lot of patients with a score of 25 to bring the mean down to 30.

'What if' comparison
For a 'what if', let's assume the De Becker study patients had a mean SF36 PF score of 33 to go with the known VO2 max of 20.7. This compares with a mean SF36 score of 48 and VO2 max of 30 in the Fulcher study based on 75% female, so let's say an equivalent VO2 max score of 28 ml/kg/min for female patients:
De Becker: VO2max = 21 (SF36 PF = 33)
Fulcher: VO2max =28 (SF36 PF= 48)

To but compare the relative scores, we need to factor in that VO2max has a smaller range of possible scores than the SF36. SF36 PF goes from zero (all but immobilised but still alive) to 100 for a moderately fit person (range = 100), while VO2max probably ranges from, lets say, 7 to 40 (range 33) for the same groups. So the SF36 range is roughly 3x that of VO2 max. Looking at the difference between the De Becker (low performance) and Fulcher (average performance):

Fulcher vs De Becker: VO2max +7; SF36 +15
Even allowing for the greater range of SF36, the difference between the two studies could be largely be accounted for by the De Becker study using more severely affected patients. Though as there was no SF36 data in the De Becker study this remains speculation.

Comments very welcome

Edit: one final observation - higher resting heart rates might be a factor in the lower VO2max of CFS patients relative to controls. Looking only at those who achieved "Maximal" effort, mean heart rates were:

CFS: At rest=93 bpm, Maximal=167, difference=74bpm
Controls: Rest=83.5 bpm, Maximal=174, difference=92bpm

So controls' heart rates increased by an average of 92 bpm while controls only managed 74 bpm. Fewer bpm means less blood pumped and less O2 consumed. Though it's possible the higher resting heart rate is a general feature of deconditioning.

 

[biophile]

Some quick comments from a brief glance of the De Becker et al 2000 paper.

Fulcher study = Oxford criteria. De Becker study = CDC 1988 and/or CDC 1994 criteria.

As you already pointed out, the CFS patients in this study may be more severely affected. The study can only, at most, support the (unsurprising) existence of deconditioning in more severely affected patients when compared to asymptomatic healthy sedentary controls "who did sitting work and performed a maximum of 1 hour of sports per week". This is different than supporting the claims for a major role for deconditioning in perpetuating CFS symptoms and disability.

Also, the problem seems more complex than simple deconditioning anyway, the authors themselves seem to suspect (additional) autonomic nervous system disturbance judging from other data they collected.

Similarly, VO2 scores may be misleading because these could be significantly affected by pathophysiology, for example, haven't some CFS studies shown VO2 can drop as much as 20-50% on serial testing? People don't just become 20-50% "deconditioned" in 24 hours due to inactivity, something else is going on. In my own experience, post-exertional relapse can make me feel suddenly much less fit than compared to 24 hours before.

 

[oceanblue]

Some quick comments from a brief glance of the De Becker et al 2000 paper.

Fulcher study = Oxford criteria. De Becker study = CDC 1988 and/or CDC 1994 criteria.

Thanks for all the comments, Biophile, that's really helpful. Good point about Oxford vs CDC criteria, don't know how I forgot about that (having made notes on the paper!)

The study can only, at most, support the (unsurprising) existence of deconditioning in more severely affected patients when compared to asymptomatic healthy sedentary controls "who did sitting work and performed a maximum of 1 hour of sports per week". This is different than supporting the claims for a major role for deconditioning in perpetuating CFS symptoms and disability.

Also, the problem seems more complex than simple deconditioning anyway, the authors themselves seem to suspect (additional) autonomic nervous system disturbance judging from other data they collected.

Completely agree with you that this only relates to the existence of deconditioing, not it playing a causal role. I hope to address this in future posts.

The authors did suggest there could be ANS disturbance, but I found their speculation pretty unconvincing. They also speculated, equally unconvincingly, that CFS patients might have a primary cardiac defect.

Similarly, VO2 scores may be misleading because these could be significantly affected by pathophysiology, for example, haven't some CFS studies shown VO2 can drop as much as 20-50% on serial testing?

Sure, it could in some, that's why the VO2 max data is interesting for patients who achieved >85% of age-predicted heart rate and with a respiratory quotient > 1 (ie well into anaerobic activity) - which is widely used to determine if patients have been able to achieve a 'true' maximum. The data for the 40% of patients deemed to reach a true max (vs 80% of controls) also showed very low VO2max; in other CFS studies that wasn't the case.

People don't just become 20-50% "deconditioned" in 24 hours due to inactivity, something else is going on. In my own experience, post-exertional relapse can make me feel suddenly much less fit than compared to 24 hours before.

Agreed, but I think this is a separate issue, since the first test would still show deconditioning (and there was just the one test in this study). Also, Pacific labs seemed to have failed to replicate that intriguing result, and in any case had a dodgy sample where 1 in 4 "CFS" patients reported no ill-effects from 2 maximal work outs in 24 hours. I've posted on this somewhere if you are interested.

 

[Esther12]

This is the sort of research I know little about but...

who were deemed to have reached maximal exertion - which is poor or very poor.

Is it possible that one group of researchers were less willing to push their patients than another? Or that one group of patients were less willing to be pushed?

I've no idea how these sorts of tests are run though, so this could be a silly point.

 

[oceanblue]

This is the sort of research I know little about but...

Is it possible that one group of researchers were less willing to push their patients than another? Or that one group of patients were less willing to be pushed?

I've no idea how these sorts of tests are run though, so this could be a silly point.

Good point. Because it isn't easy to reach maximal exertion, it's normal practice to verbally encourage participants during the final stages of the test. This happened in the Fulcher study but the De Becker study doesn't say either way.

However, the issue of 'truly' achieving maximal exertion is always an issue to some extent, which is why the De Becker study looked separately at those who reached the more objective measures of an RQ>1 and >85% of age-predicted heart rate (other studies have used a slightly higher threshold of RQ>1.1 and HR>90% predicted).

Fulcher used blood lactate rather than RQ to measure levels of anaerobic activity (ie measure of how hard patients pushed) so they can't be compared. However, both gave peak Heart Rates and it looks like the 'maximum' De Becker patients were pushing almost as hard as the Fulcher patients:

De Becker ('max'): 91.5% age-predicted heart rate,VO2max=22.7
Fulcher (all): 93.4% age-predicted heart rate, VO2 max=30.6

So the Fulcher patients may have been pushing fractionally more than the De Becker 'max' ones, but it wouldn't account for the large difference in VO2max.

 

[Esther12]

I have no idea what most of that means, and now is not the time to learn!

Thanks for your notes on this OB, I've been keeping up with this thread and found it interesting, even if I can't contribute much.

 

[oceanblue]

I have no idea what most of that means, and now is not the time to learn!

You're not the first person to respond like that to one of my posts. Glad you are interestedin the thread.

 

[floydguy]

FWIW...I don't think "de-conditioning" causes fatigue and pain. Despite the fact that my ability to exercise is severely limited I don't consider myself "deconditioned" (until proven otherwise anyway). I am able to walk, ride a bike casually, etc. However, I do have significant issues with breathing, heart rate, etc. My personal experience suggests an ANS issue with exercise. And despite being somewhat active I am in complete physical misery, which doesn't seem to change with activity - unless I really "push" it, then I'll crash.

 

[PhoenixDown]

Just to add my 2 cents, I was still looking relatively muscular (for my body mass) when my "fibromyalgia" pain stopped me from getting on with my already fatigue riddled life. It was that pain that put an end to years of accomplishment in the gym, talk about circular argument.

So it was rather insulting to read what doctors really thought of fibromyalgia after I'd put in so much dedication. Just like doctors ignoring consequent PEM in other patients, they ignored the consequent pain/injury worsening I reported, and basically told me to exercise even if it made me worse. Disrespectful would be an understatement.

So how are they objectively defining deconditioning?

 

[oceanblue]

Just like doctors ignoring consequent PEM in other patients, they ignored the consequent pain/injury worsening I reported, and basically told me to exercise even if it made me worse. Disrespectful would be an understatement.

So how are they objectively defining deconditioning?

There are no absolute definitions Usually the controls in CFS studies on not appropriate, but there are VO2max norms which are useful.http://forums.phoenixrising.me/index.php?posts/273546/

http://forums.phoenixrising.me/index.php?posts/273546/