Finally, a summary of the main evidence from this thread:
Deconditioning and its role in CFS
The idea that inactivity will lead to a vicious cycle of deconditioning, increased fatigue and further reduced activity is widespread in medicine. In the case of CFS, some have argued that whatever triggers the initial illness, CFS is primarily perpetuated by such a cycle of inactivity and deconditioning. The 2011 PACE trial explicitly used this theory as the rationale for Graded Exercise Therapy, GET.
Perhaps the sheer plausibility of the Deconditioning hypothesis explains its popularity, but the idea falls when tested against the evidence - such as the effect of deconditioning on healthy people, the actual level of deconditioning among CFS patients and the (in)ability of of exercise programmes to restore fitness and health to patients.
What is Deconditioning anyway?
In medical research, deconditioning is usually interpreted as having become so unfit that normal activities of life become fatiguing. Deconditioning in almost always measured in the same way as fitness, by measuring maximal oxygen uptake, VO2 max. This is the volume of oxygen consumed by a person at maximal exertion, and the higher the VO2 max, the fitter person, while very low VO2 max scores indicate deconditioning.
Normally VO2 max is given relative to body weight, and a woman of average fitness in her thirties will consume around 35 mls Oxygen per minute, per kilo of body mass, or 35ml O2/min/Kg. The very best elite female endurance athletes can achieve a VO2 max of over 70 ml/min/kg. There are no definitive levels for 'deconditioned', but 15-20 ml/min/kg would probably be seen as deconditioned. At rest, the average person will consume around 5-6 ml/min/kg. [Relevant
population norms]
Measuring VO2 max
VO2 max is measured on a treadmill or cycle ergometer which is made progressively harder so that maximum exertion is achieved within 10 to 15 minutes. Oxygen consumption is measured as the intake (and exhalation) of oxygen through specially adapted face mask. For more information about how this is measured, read
Lannie's article about VO2 max testing she underwent at Pacific Labs.
How could Deconditioning lead to fatigue?
Deconditioning is widely thought to lead to a vicious cycle of fatigue, inactivity and more deconditioning. James Rimmer recently proposed there may even be a
Disability-Associated Deconditioning Syndrome, Rimmer illustrated the presumed vicious cycle in an
earlier paper:
However, Rimmer makes clear this is an unproven hypothesis, and, as evidence that disabled patients are deconditioned, he includes a graph of as yet unpublished VO2 max data for disabled patients showing levels around 15ml/O2/kg, which is undoubtedly deconditioned.
Other researchers make bold claims for the deconditioning without any such evidence to back them up. For instance, a
recent review of the link between fatigue and deconditioning in stroke found that there was no association between fatigue and any measure of fitness or activity, yet still managed to conclude that "it still remains highly
plausible that exercise can have a positive influence on fatigue". And a review looking at the many possible causes of fatigue
concluded that deconditioning leads to fatigue, yet didn't cite a single paper to support this - while running up over 180 references in support of other causes of fatigue.
Are CFS patients really deconditioned?
If the deconditioning theory is correct then CFS patients must be deconditioned, otherwise it can't be the cause of their fatigue or other symptoms. There have been at least fourteen studies looking at fitness levels and the
largest study, with over 400 patients, did find evidence of deconditioning, but most other studies did not. Authors of the large study suggested their findings were due to assessing more severely affected patients than other studies - though the patients in other studies are probably more typical of the patients targeted in outpatient Graded Exercise programmes.
Actually, quite a few of these other studies did conclude that CFS patients were deconditioned, but this is because they didn't use properly matched sedentary controls, a point illustrated by
Sisto, who noted her patients had lower fitness than controls, but were still within population norms.
One study that did match controls for activity levels found no difference between these sedentary but healthy controls and CFS patients. But the
most impressive study, for me, was by Wallman who very carefully matched controls, and used a sub-maximal rather than maximal test as it was a better test of real-world capability and would be less likely to deter CFS patients from taking part. She found no difference in fitness levels between CFS patients and healthy but sedentary controls. Such is the nature of this field that despite this finding of a lack of deconditioning Wallman nonetheless concluded that GET was the appropriate treatment.
One
important study by Kathy Fulcher (and Peter White, who ran the PACE Trial) found patients had a VO2 max of 31 ml/kg/min, comfortably within population fitness norms and no different from their controls. The authors then suggested that the patients were 'deconditioned' as they had less
muscle tone than controls, but firstly the controls were not properly matched sedentary controls, and secondly this seems to be arguing that reduced muscle tone is responsible for CFS - surely not? What makes this study so interesting is that these figures are for patients recruited into a trial of Graded Exercise, which specifically aimed to address deconditioning that appears not to exist in these patients.
A later study from Peter White concluded that "fatigue was not caused by current levels of inactivity" in the CFS patients studied.
So it appears that while some patients are deconditioned - and those that are bedbound must surely be - many patients are not deconditioned yet still have CFS. This does rather rule out a primary role for deconditioning in perpetuating the illness.
Space Age studies: the effect of deconditioning on healthy people
The ideal way to measure the negative effects of deconditioning is to take a bunch of healthy people and get them to become almost completely inactive, then see what deconditioning does to their health. Fortunately a number of such studies have been done thanks to NASA and the Soviet Space Agency (and their volunteers), who wanted to see what the long-term effects of weightlessness (or microgravity) would be on their astronauts. It turns out that the best proxy for weightlessness on Earth is long-term Bed Rest, a rather low-tech solution, but a very informative one for understanding the effects of inactivity separate from any possible illness.
Unsurprisingly, long-term bed rest is not good for the human body. Amongst other problems, blood volume reduces rapidly, calcium is lost from the bones and the immune system suffers. Deconditioning takes place too, but at a relatively slow rate. A
2006 study found that while VO2 max (fitness) reduced by 13% in 14 days (1% a day), it only declines by twice that over 3 months, an average 0.3% loss a day. Contrast this with the statement in the PACE GET Manual given as a reason not to rest after a setback: "we can lose 10 % of our muscle strength in just one week of bed-rest, or even 1% per day". The implication is that after 30 days you would lose 30%, maybe even 365% in a full year...
The only studies I could find* that noted fatigue as a problem were
very long-term: a 6-month study noted: "Mild fatigue was noted for several months and then disappeared". Another,
even longer term study, (n=3, 7-8.5 months) commented: "During reambulation [recovery after bed rest] ... easy fatigability was subjectively noted for 4-6 months."
Which suggests that deconditioning might at best cause mild fatigue (presumably at rest), and that when
highly deconditioned activity can cause easy fatigability similar to the situation with CFS. But the people in these studies had just spent around 8 months confined to bed and would have been way, way more deconditioned that CFS patients in outpatient clinics.
So deconditioning, even from months of enforced bed rest, only seems to cause minor problems with fatigue at rest or fatigability, and this was at levels of deconditioning far greater than apply to CFS patients attending GET clinics.
*health warnings
Many of these studies were carried out in the 1960s and 1970s when research abstracts were not routinely made available, so tracking down some studies in the literature has proved impossible for me. However, I read most of the frequently-cited ones. The studies also rarely set out to specifically measure fatigue, but as they were carried out to see if deconditioning would reduce astronauts ability to function, there would surely have been unambiguous reports of fatigue or fatigability if this really had been a problem.
Also, most of these studies were small, presumably because it's not easy to persuade healthy people to take to their beds for many months. However, the deconditioning argument is universal in that everyone is expected to decondition as a result of inactivity, not just a minority.
Does Graded Exercise work for CFS?
The ultimate test of the theory that deconditioning plays the
primary role in perpetuating CFS is to use exercise to reverse the deconditioning and so produce recovery. This is exactly the approach tested in the PACE trial, as the therapists manual explains:
Physical deconditioning, exercise intolerance and avoidance caused by relative inactivity are reversed by gradually and carefully re-introducing regular physical exercise, aiming to return a patient to normal health and ability.
The Lancet trial paper itself merely talks of 'improvements' fatigue and function, but if deconditioning is the primary cause then dramatic results should follow from reversing it.
The effects of exercise on CFS
Compared with the control group, Graded Exercise (GET) led to rather modest improvements in fatigue and physical function. Fatigue improved by an average of 2 points on what is effectively a 22 point scale, while function improved by 9.4 points (0-100 scale). However, both of these measures rely on patient reports and so are liable to self-report bias, especially in an unblinded trial. The one more objective measure included in the Trial was the 6-Minute Walking Test. GET patients improved their walking distance by an average of just 35 metres (compared with controls) after a year of exercise training. This left them completing an average distance of 379 metres, spectacularly short of the expected 575m for healthy adults - even though the most common choice of exercise for GET patients was walking. There is a wonderful animation that shows the walking distance progress made in PACE compared with healthy controls:
To really put these results into context, the GET Therapists manual expects most CFS participants will be able to start aerobic exercise by week 4 [page 46], and riding an exercise bike for 20 minutes every day is given as an example of a long term goal by the end of the programme [page 41] It also states that,
Apart from improvements in CFS/ME and function, a major objective for GET is to undertake.. the amount of exercise recommended by the Chief Medical Officer of 30-45 minute sessions of moderate intensity physical activity at least five times a week.[p24]
The Trial also found that there was no improvement in working hours lost in the GET group relative to controls.
Big trials, small results
PACE was the largest clinical trial of CFS treatment ever carried out, with 160 patients in the GET group.
FINE, the second largest CFS clinical trial (n=95) tested 'Pragmatic Rehabilitation', a therapy that also aims to reverse the presumed deconditioning responsible for perpetuating CFS. This study found no improvement, relative to controls, in either fatigue or function one year after treatment. The authors went on to re-analyse their data using a different scoring method and found a small improvement in fatigue, similar to PACE, but still no improvement in function. These results are not consistent with the idea that deconditioning is the primary force perpetuating CFS.
One final point on effectiveness, from that
Fulcher & White study again. This found that fitness (VO2 max) improved by 13% in the GET group compared with baseline indicating a modest gain from exercise. It also found a modest improvement in this group relative to controls. However, the two were unrelated:
we found no significant association between feeling better after graded exercise treatment and becoming stronger or fitter
So they took patients who, on average, were not deconditioned and found that they could improve their fitness by a modest amount, but that fitness improvement did not correlate at all with overall improvement.
Conclusion
To sum up, the bulk of the evidence weighs strongly against deconditioning playing a
primary role in perpetuating CFS. Firstly, most CFS patients - at least those well enough to get to secondary clinics for measurement and treatment - are not deconditioned compared with sedentary but healthy controls. Secondly, studies of long-term bed rest in healthy adults indicates that deconditioning can, at best, play only a minor role in fatigue amongst outpatients, either at rest or in response to exercise. And finally, the largest studies carried out to date on CFS patients show that exercise or rehabilitation programmes do not lead to substantial gains of the kind that would be expected from reversing the underlying cause of the illness.
Each of these individually is a serious obstacle to the deconditioning theory of CFS. Taken together, it's hard to see how anyone can still argue that deconditioning plays a primary role in perpetuating CFS.
Feedback welcome
Please let me know if you see any errors or think I've missed out any important evidence.