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

[oceanblue]

"CFS patients have low normal level of fitness"
I think this 1996 study by Sisto is fairly typical of research on VO2max levels of CFS patients, with exception of the large De Becker study.

The controls weren't really sedentary, but the VO2max levels of theCFS patientsare interesting. They were divided into the 40% that acheived maximal exertion ("Max",within 10bpm of age-predicted heart rate and RQ>1), and 60% that did not. Nb no verbal encouragement was given during the testing as the testers didn't want to overstress patients.

VO2 'max' ml/min/kg
"Max" patients: 28.1 (for women, 26-29 is 'fair', 30-33 is average)
no-Max patients: 23.9
All: 25.9

We do know something about the patients: 22 women with a mean age of 34 and none had been ill for more than 4 years; 50% were unable to work, 29% could only work part-time and presumably the remaining 21% could work full-time. I'm not sure, but I think this is a fairly typical work pattern for patients in CBT/GET trials, and, as the authors point out, they are not very fit, but not deconditioned either. Which is interesting as deconditioning is a key assumptions of both CBT and GET. If anyone has data on typical work status of trial participants, please do post details.

 

[oceanblue]

Weak link between (self-reported) activity and fitness levels in the general population

I don't know how important this finding is, but the deconditioning model of CFS implies a strong relationship between activity and fitness (conditioning) levels. In the general population this doesn't seem to be true.

A 1998 study on the general population in Northern Ireland (n=1,600) found very little correlation at all between activity levels and fitness measured by a sub-maximal treadmill:

There was no statistically significant relationship between current or past activity and fitness after adjustment for possible confounding factors, with the exception of a relationship between fitness and activity in males so that the difference between no activity and habitual vigorous activity in predicted VO2max was 4.4mls/kg/min (10.1%).

A new study from Brazil of employees (n=2,300) in particular a employer health-screeningprogramme found a moderate correlation between activity and fitness:

Self-reported physical activity level and treadmill fitness were moderately correlated (r=0.383).

It's all a lot less conclusive than I'd expected. Of course, these studies look at the correlation across large populations, it doesn't look at the correlations for individuals between increasing of decreasing fitness levels and changes in activity levels.

 

[Esther12]

Hi OB - there was that recent BBC documentary about this. Something like: some of the population get fitness benefits from exercise, some don't, and there some sort of test to see which group one falls in to. The documentary was discussed here because they used some 'techno trousers' (that's why I call them) to measure activity levels.

I've got no idea how solid the science behind all this is, and have no papers to reference, but it sounded like an area where there'd been changes in understanding over the last few years.

 

[oceanblue]

Hi OB - there was that recent BBC documentary about this. Something like: some of the population get fitness benefits from exercise, some don't, and there some sort of test to see which group one falls in to. The documentary was discussed here because they used some 'techno trousers' (that's why I call them) to measure activity levels.

I've got no idea how solid the science behind all this is, and have no papers to reference, but it sounded like an area where there'd been changes in understanding over the last few years.

Thanks, e12, that's really interesting. And particularly helpful as I think that study was looking the level of how individuals respond to exercise, rather than the studies I mentioned which looked at activity vs fitness across a population (i.e.they were cross-sectional rather than longitudinallike the one you mentioned). If any one has any links I'd be grateful.

 

[Esther12]

Hi OB. Here's a link to a review of the programme I mentioned:

http://suite101.com/article/a-personal-review-of-the-bbc-programme-3-minute-fitness-a404094

 

[Esther12]

~Here's another non-academic article that could be related to the 'brain limiting activity levels' theme:

http://walrusmagazine.com/articles/2012.07-sports-the-race-against-time/

It might give you leads to other studies in this area.

 

[oceanblue]

Hi OB. Here's a link to a review of the programme I mentioned:

http://suite101.com/article/a-personal-review-of-the-bbc-programme-3-minute-fitness-a404094

Thanks: I thought this was very interesting:

1. Super Responders – those people who can seriously improve on their cardio performance. This was tested by measuring their VO2Max levels. Super Responders can easily double their cardiovascular performance. They account for 15% of people.
2. Non-Responders – these are people who show minimal or no changes in their VO2Max levels. They account for 20% of people. At the end of the trial Michael Morley discovered that he fell into this group and although his VO2Max level did not increase over the trial period of 3 minutes of exercise per week, he could exercise for longer. That in itself is an improvement.
3. [ so by my reckoning, 65% are somewhere inbetween - 'normal' responders]

 

[oceanblue]

~Here's another non-academic article that could be related to the 'brain limiting activity levels' theme:
The Race against time/
It might give you leads to other studies in this area.

Thanks, very interesting. I'd come across Tim Noakes and his 'Brain is theCentral Governor of Fatigue' model before, which is intriguing totally aside from CFS, and even more so as it provides a possible mechanism that could go wrong in our illness. I was always amazed when doctors told me 'we can assure you there is nothing wrong with you physically' when they, along with everyones else, were unable to explain how fatigue works in healthy individuals. How could they possibly tell if my fatigue system was working normallywhen they didn't evenknow where to look?

 

[oceanblue]

Cardiac Deconditioning? Lack of clear evidence
Another approach to measuring deconditioning is to look at the working of the heart at rest - heart function is an important part of fitness so deconditioning could show up in reduced cardiac function, or change structure. Unfortunately 2 studies that do look at heart function, and find evidence of deconditioning, have weaknesses that mean the findings need confirmation.

These are really notes for my benefit, no need to read on unless you are really interested.


A large study (n=273, De Lorenzo 1998) found evidence of cardiac deconditioning relative to controls, but the controls were otherwise healthy individuals who reported no fatigue in the previous 6 months and were not matched for activity levels. Consequently, the findings can't be seen as definitive.

A smaller, more recent paper (n=56, Hurwitz 2010, commentary by Stewart) found that more severely affected CFS patients had reduced cardiac stroke volume, i.e. pumped less blood with each heartbeat compared with controls. Intriguingly, the the reduced stroke volume was almost entirely accounted for by reduced blood volume, and reduced blood volume is common in healthy people deconditioned (in experimental studies, mainly linked to the Space programme) by bed rest. However, the less severely affected CFS patients were not significantly different from controls and there were no measures of CFS activity levels to ensure they were matched by the 'sedentary' controls.

 

[oceanblue]

Evidence of higher rates of exertion, but not of deconditioning, in CFS patients vs well-matched controls

I like this 2004 study by Karen Wallman which went to considerable lengths to find controls that are matched in activity levels to patients, as well as using a submaximal test that is less likely to deter CFS patients from participating. As usual, some of the Discussion section requires a strong stomach, as the authors close one eye and squint with the other to conclude that the problem with CFS patients is lack of effort, excessive symptom focusing or whatever suits their cause. But there is plenty of good data too, which actually fits a more straightforward conclusion that CFS is characterised by easy fatigability and likely post-exertional malaise.

Physiological Responses during a Submaximal Cycle Test in Chronic

Results: Comparison of absolute physiological results recorded at the end of each incremental work level of the exercise test showed that ratings of perceived effort (RPE) was the only variable that was significantly different between the two groups

ie measures of fitness such as VO2 and lactate production were the same between CFS patients and matched sedentary controlsat each workload, but CFS patients perceived more effort for the same work, and also stopped the exercise earlier than controls.

This is some of the best evidence I've seen for a lack of deconditioning in CFS patients relative to well-matched controls, particularly as it's at submaximal levels of exertion that are more relevant to the real world than maximal tests. It's also good evidence that CFS patients find exercise more taxing than sedentary people with similar day-to-day levels of activity.

Edit: almost all the exercise studies I've seen seem to find that RPE is higher in CFS patients than in (sedentary) controls; this study adds weight to that finding because the controls are so well matched for activity levels.

 

[oceanblue]

More detailed analysis of Wallman paper​

They used a relative measure of exertion vs work, defined as RPE at maximum/workload at maximum, in RPE per watts. It's easier to understand as RPE per 100 watts, which gives whole number

CFS=0.16 [16 per 100 watts]
Controls=0.10 [10]

ie CFS patients are more fatigued than controls after adjusting for the amount of workload. Most patients (25/31) made it to 100 Watts, though the RPE of those that did was just over 14 (75% effort, somewhat hard to hard), which is about the same as those sedentary controls that made it to 175 watts

Selection of appropriate patients and matched controls
Lots of very sensible points here:

Criteria noted above to define “sedentary” control subjects ignores the possibility that although a subject may not participate in regular exercise, they might still be physically very active. For example, an individual who reads or watches television all day is classified under the same heading of “sedentary” as another individual who may care for active toddlers, shop, mow the lawns, and participate in gardening on a regular basis. This particular matching process promotes the possibility that the control subjects who participated in these studies, may on average, have been fitter than their CFS counterparts, consequently biasing results...

Consequently, it is proposed that in order to accurately assess physiological function in CFS, control subjects should be matched to CFS subjects according to gender, age, height, body mass, as well as current activity levels.

Another area of concern with studies that assessed physical function in CFS sufferers is the common use of exercise tests that require subjects to provide a maximal effort (4,9,22,24). Although maximal oxygen consumption testing is recognized as the gold standard measurement of cardiorespiratory function, its use in a population that is characterized by severe fatigue and whose symptoms are typically reported to be exacerbated by exercise (29) may be detrimental, as well as deter potential subjects from participating in trials. This would suggest that submaximal exercise tests may be a more appropriate means to assess physical function in CFS subjects. Use of a submaximal exercise test may encourage more symptomatic CFS subjects to participate in research studies, which may result in the assessment of a greater range of physical capabilities and consequently provide results that are more representative of the CFS population.

Patients and controls were assesed for activity:

Weekly kilojoules for specific activities (that did not include any
sitting or lying down activities) were determined using
the Older Adult Exercise Status Inventory (OA-ESI; 21).
Reliability and validity have been established for this questionnaire (21).

21. O’BRIEN COUSINS, S. An older adult exercise status inventory:
reliability and validity. J. Sport Behav. 19:288–302, 1996.

I haven't been able to access this article to see how they validated the questionnaire.


One weakness in this study is that though they used Fukuda criteria it was merely 'confirmed by each subject's medical doctor' rather than independently assessed by the study.

Also:

Additionally, in order to address the commonly reported cyclical nature of symptoms in CFS (11), all variables assessed were measured weekly over a 4-wk period and then averaged

Which means that patients can adjust their exertion levels based on their previous experience of the test ie can reduce exertion levels to minimise PEM, as in real life. I think this should make the findings more robust.

 

[Esther12]

Thanks OB. Interesting that this paper has only been cited by one other. Looks like Wallman did some other stuff that was helpful in promoting GET.

 

[oceanblue]

Thanks OB. Interesting that this paper has only been cited by one other. Looks like Wallman did some other stuff that was helpful in promoting GET.

Cited by 30 according to my google search but that is very low, maybe no one liked the findings. Wallman is very pro GET and concluded GET would be a good idea from this paper, even though the data didn't support that conclusion. But that's true generally in this area eg Fulcher & White claiming they had shown deconditioning when their CFS patients were well within population norms ('normal', even).

 

[oceanblue]

I think I might be about to give up on this: just like it appeared there was overall evidence of no deconditioning in CFS patients, I've come across a fairly large study (n=85)with seemingly sedentary sedentary patientsthat does indicate deconditioning. This sits alongside the large De Becker study that also supports deconditioning:

Edit: this doesn't really show any evidence of deconditioning as the CFS patients failed to get anywhere near their age-predicted max heart rates, which is essential for meaningful VO2max comparisons. CFS patients only achieved 68.5% of age-predicted max heart rate compared with 87.5% for controls.

Physiological responses to arm and leg exercise in women patients with chronic fatigue syndrome
Javierre... De Meirleir, 2007, Journal of CFS

The strongest part of this study is the criteria for sedentary which look pretty strict, even though there were only 15 controls:

Selection for our control group required more than one year of extremely sedentary lifestyle, that is, very sedentary work, not walking to work, no hobby/leisure activities requiring any physical effort, no physical activity, and no obligations that would increase physical activity, such as owning a pet that needed walking. These requirements are different from the term "sedentary" as it is used to define normal, healthy individuals who are not engaged in regular, structured physical activity, which describes most individuals

It's hard to compare VO2max from this study with other studies as patients completed an arm ergometer test to exhaustion only 10 minutes before starting the cycle ergometer would be poor for women but looks a bit better considering they've just completed a maximal arm ergometer. CFS patients scored just 14.3.

Caveats:

1. There was no direct comparison of activity levels between CFS patients and controls, as in the Wallman study. It is possible that the study used particularly severely affected cases.The cycle ergometer test was unusually gentle (2 mins at 0W increasing by only 12.5W every 2 minutes) and most patients still only managed 10 minutes.
2. The CFS case definition cited was one I'd never heard of before: [13. Holmes GP, Kaplan JE, Schonberger B, Straus SE, Zegaus LS, Gantz NM. Definition of the chronic fatigue syndrome. Ann Intern Med 1993; 109: 993-998.] Presumably this is an update of the Holmes criteria pre-Fukuda, though I hadn't realised such a definiton existed.
3. The number of controls, 15, was very small.

So, maybe this isn't the best study in the world

 

[Esther12]

I think I might be about to give up on this

So after an exhaustive search of the literature, you've been able to reach the conclusion that... the evidence is contradictory and no-one can sensibly claim anything. Ah well, I'm sure the researchers had fun!

 

[oceanblue]

So after an exhaustive search of the literature, you've been able to reach the conclusion that... the evidence is contradictory and no-one can sensibly claim anything. Ah well, I'm sure the researchers had fun!

Indeed! While that's the norm in CFS it looked for a while as if this one area would come up trumps. And actually...

Just noticed that Javierre paper doesn't really show any evidence of deconditioning as the CFS patients failed to get anywhere near their age-predicted max heart rates, which is essential for meaningful VO2max comparisons. Post edited above.

So in fact, most of the evidence does overall point to no significant decondtioning in CFS patients compared with properly sedentary controls who go about their lives quite happily without CFS-like symptoms. The rather large fly in the ointment is the very big De Becker study that does find evidence of deconditioning, which oddly isn't cited much by those arguing for deconditioning.

 

[Esther12]

While that's the norm in CFS

It's a bit of a distressing norm. CFS research is (semi-)interesting as a study of medical culture, prejudices and assumptions, but rarely seems to tell us anything about why those with CFS are ill. I completely understand why most people have no interest in looking at the evidence around CFS, and instead just want to be able to assume that they can trust those who claim to be experts - there are so many more interesting and revealing areas of research to read instead!

 

[oceanblue]

there are so many more interesting and revealing areas of research to read instead!

Someone gave me a subscription to Nature and I fully agree with that. Though CFS research is hardly alone in its mediocrity (though it's zealtory is unusual). As a scientist I know once said to me "the problem with a lot of clinical science is that it isn't science". Ouch.

 

[oceanblue]

Deconditioning: The Space Age Studies

Perhaps the best way to understand the impact of deconditioning alone on the human body is to measure its impact on healthy people who voluntarily decondtion through long-term bed rest. Luckily, such studies were conducted as part of both US and Russian space programmes as they tried to understand the long-term effects of zero gravity on astronauts - bed rest was seen as the rather low-tech best available approximation on Earth to zero gravity effects.

Unsurprisingly, such studies are generally quite small (e.g. n=5) as it isn't easy to persuade healthy people to be confined to bed for months on end. Nonetheless, the studies were thorough and if deconditioning is a powerful and universal effect - as claimed by those who argue it is a primary perpetuating factor in CFS - then the small sample size is less important.

edit: Many of these Space Age studies are from an era when abstracts weren't mandatory (ie all you get is the title) so I haven't been able to explore quite a few of the references. This means I might have missed some important material, though I did manage to track down at least and abstract for all of the frequently cited papers.

Reports on specfic bed rest studies will follow

 

[oceanblue]

Extended bed rest may not have such a big impact on fitness (and function)

I can't remember the exact figures quoted (Dolphin?) but I'm pretty sure proponents of the deconditioning model for CFS have stated that something like 30% of muscle mass is lost after 10 days in bed. The implication is that resting too much quickly leads to a spiral of lost function, more tiredness, more rest and so on.

However, when researchers have measured the effect of bed rest on healthy volunteers, using VO2max which is generally excepted as the best measure of fitness, they found it isn't that dramatic. A 2006 paper (see below) reviewed evidence for VO2max decline after 14, 42 and 90 days. These are the results:

Change in VO2max from baseline after bed rest of:
14 days: -13% (average -1% per day)
42 days: -16.6% (-0.4%/day)
90 days: - 27% (-0.3%/day)

Effectively, as bed rest increases, the effect on VO2max declines i.e. fitness is lost more slowly as time goes on. A 27% loss of fitness after 3 months of complete round-the-clock bed rest is hardly spectacular, and the kind of CFS patients who make it to CFS outpatient clinics and studies won't be resting anything like as much as this.

That said, so much bed rest is inevitably unhealthy and does lead to unwelcome changes including decline in immune function and muscle loss, but on its own this seems unlikely to cause or even perpetuate CFS.


Factors determining the time course of VO2(max) decay during bedrest: implications for VO2(max) limitation (Capelli 2006)

The aim of this study was to characterize the time course of maximal oxygen consumption VO2(max) changes during bedrests longer than 30 days, on the hypothesis that the decrease in VO2(max) tends to asymptote.

On a total of 26 subjects who participated in one of three bedrest campaigns without countermeasures, lasting 14, 42 and 90 days, respectively, VO2(max) maximal cardiac output (Qmax) and maximal systemic O2 delivery (QaO2max) were measured.

After all periods of [bedrest], VO2max, Qmax, and QaO2max were significantly lower than before...

The asymptotic VO2max decay demonstrates the possibility that humans could keep working effectively even after an extremely long time in microgravity...