What does deconditioning look like?

Deconditioning has long been one of the most popular theories in explaining the illness myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). An excessive amount of bed rest was thought to cause a self-perpetuating cycling of fatigue, pain, and other disabling symptoms. This blog post examines what deconditioning looks like and how it differs from ME/CFS.

The theory

Deconditioning refers to physiological changes following inactivity. Because ME/CFS patients are unable to maintain normal activity levels, it is often assumed that deconditioning contributes to their symptoms.

In the hyperbole version of this theory, the syndrome itself is believed to result from inactivity and deconditioning. The PACE study, for example, the biggest treatment trial in the field, tested exercise therapy based on the assumption that ME/CFS “is perpetuated by reversible physiological changes of deconditioning and avoidance of activity.” Anton Wagenmakers, a professor of exercise metabolism at Maastricht University, speculated that CFS represents “the physiology of people on the low end of the spectrum of physical activity”. In a 1999 editorial, he wrote:

“I also suspect that the prevalence of CFS may well be reduced substantially if society in general becomes more active and follows the advice of experienced exercise physiologists, which is that man is a machine which is supposed to work, run, cycle and play in order to maintain a healthy functioning body and mind. However, the gradual decrease in daily physical activity seen in modern society may have the opposite effect and make CFS a serious health threat for the twenty first century.”

A more nuanced version assumes that deconditioning is but one of many factors that contribute to ME/CFS disability although one that is hard to exclude. Physical abnormalities reported in the literature are often said to reflect deconditioning rather than ME/CFS pathology.

NASA bed rest studies

Unfortunately, it is rather difficult to get a clear view of what pure deconditioning looks like. In the chronically ill, for example, it is nearly impossible to separate the effects of inactivity from the disease process itself. The most reliable evidence comes from experiments in which healthy people voluntarily undergo extreme inactivity to measure the effects on their health and bodies.

Since the 1960s, NASA has conducted multiple of these so-called bed rest studies. For the space agency, head-down bed rest is a convenient method to mimic the physiological effects of microgravity that astronauts endure in space (full water immersion was tried first but was not practically feasible). Russian researchers discovered that a horizontal bed tilted to a negative 6-degree angle formed a reasonable proxy for weightlessness during space flight.

These NASA bed rest studies have important limitations. They are usually performed on a small group of young, healthy male participants and focus on severe deconditioning in a relatively short period (up to 120 days). But because bed rest was strictly enforced, and these studies have been repeated multiple times, they provide the strongest evidence on what deconditioning looks like.

Physiological changes

“Beneath the comfort of the blanket, there lurks a host of formidable dangers.” With these words, British endocrinologist Richard Asher challenged the idea of (mandatory) bed rest as a therapy for tuberculosis, peptic ulcer, heart attack, and many other health conditions. Writing mid-20^th century, Asher warned that the effects of bed rest were underappreciated and often did more harm than good.

The NASA studies support this view, demonstrating that bed rest affects almost every bodily system. Some of the changes are quite dramatic. One study found that 3 weeks of bedrest in 20-year-olds had a more profound impact on physical work capacity than 3 decades of aging.

• One of the first noticeable changes is a drop in blood volume by approximately 10-20%. Most of the decline occurs within the first 1-3 days with only slow changes thereafter. There is also a decline in red blood cell mass.

• Maximal oxygen consumption (VO2 max) decreases by approximately 0.4% per day. VO2 max is an important measure that indicates how much oxygen your body can absorb during exercise. It reflects the effectiveness of your lungs and cardiovascular system and is often used as a measure of general fitness or deconditioning. At the end of some bed rest studies, VO2 max had dropped by a quarter.

• Another consistent finding is insulin resistance. In numerous bed rest studies, insulin sensitivity in the muscle decreased suggesting that inactivity may be an important risk factor for type II diabetes.

• Muscle loss also occurs. Stabilizer, the group of muscles that work to maintain posture, and balance, are affected the most. Astronauts returning from space were sometimes said to have ‘chicken legs’ because their leg muscles had atrophied. One review reported that knee extensor muscles such as the quadriceps decreased by approximately 10% after one month of bed rest, increasing to 18% after 4 months.

• Bone density decreases by approximately 0.5-1% per month. Calcium leaves the bones because there is a lack of physical forces working on the bone. Increased mineral excretion by bed rest may explain why many bedridden patients suffer from kidney stones.

Blood clots are frequently observed in the chronically ill and believed to be a consequence of lying still in bed. The NASA studies, however, suggest that (short-term) bed rest by itself is not associated with hypercoagulable states in healthy subjects.

Because of the detrimental bodily changes listed above, space flights now include on average 2 hours of exercise to keep astronauts fit during their missions.

Few mentions of symptoms

If the ME/CFS literature can be summarized as a lot of severe symptoms with few consistent physiological abnormalities, the bed rest studies show almost the complete opposite picture. The changes in the body are spectacular, fast, and measurable but there is hardly any mention of debilitating symptoms.

In part, this may be because many studies were written in the mid to late 20^th century when there was less attention to what participants were experiencing. Symptoms may have been present but not recorded. However, if deconditioning leads to a debilitating clinical syndrome such as ME/CFS, then one might assume that NASA researchers would have highlighted this as an important finding. After all, they were examining how deconditioning would impact astronauts’ performance in space missions.

Based on published testimonies, participants in bed rest studies struggled with boredom, immobility, and lack of social interaction more than symptoms caused by deconditioning. One participant wrote: “I found myself at the end of the ten weeks in good spirits and feeling healthy—until the last day of the study.”  Another participant described how her body adapted to being inactive: “All of a sudden my body just said: ‘OK, this is our new reality and we’ll deal with it.’ Within a couple of weeks I felt normal and actually getting up was the hard part. You get used to lying down and it actually starts to feel normal.”

Does inactivity cause fatigue?

Some subjective complaints were noted such as back pain, headache, or constipation with participants sometimes needing a mild laxative. Sleeping problems and tiredness were also mentioned but in a severity that is more like jetlag than ME/CFS. Studies mention “easy fatigability”, “only moderate signs of fatigue”, or that “mild fatigue was noted for several months and then disappeared.” An older study, however, noted “generalized weakness with ease of fatigue on the slightest exertion”.

Fatigue is a vague description that covers a lot of ground (hence why most ME/CFS patients feel it is not a good description of their disability). To get a better picture we need some measure of intensity. Unfortunately, we found only a couple of (short-term) bed rest studies that measured fatigue using a questionnaire. One used the popular multidimensional fatigue inventory (MFI). Over 21 days of mandatory bed rest, participants’ fatigue showed no significant increase. Scores on the MFI general fatigue and physical fatigue subscales were approximately 10 on a scale from 4 to 20. In comparison ME/CFS patients usually have scores around 18.

Another study used a subjective fatigue scale after 14 days of head-down bed rest. The items ‘feel fatigue in entire body’  and ‘no energy ‘, did not significantly change as the trial progressed. At the end of the 14 days of bed rest, 22% said they felt fatigued in the entire body and 26% said they had no energy. A third study tested 8 subjects before and after 17 days of bed rest using a fatigue scale. The authors report that “fatigue scores showed little change across all periods.”

It is also valuable to look at patients who are severely deconditioning for example because of spinal cord injury (SCI). If deconditioning causes debilitating fatigue, then one would expect to see it clearly in this patient population but that is not the case. A large study of persons who had lived with SCI for more than 20 years found that “surprisingly, the prevalence of fatigue (total fatigue (TF)) did not differ between the study population and the norm.” The authors used the Likert version of the Chalder Fatigue Scale (0-33) and persons with spinal cord injury had a mean score of 12. ME/CFS patients, however, usually score around 28, close to the maximum of the scale. Another study used the binary version of the Chalder Fatigue Scale (0-11). SCI patients had a mean score of 3.2, below the threshold of 4 points which indicates excessive fatigue. In comparison, ME/CFS patients usually score around 9 points.

In conclusion, it seems very unlikely that deconditioning causes the debilitating fatigue and lack of energy seen in ME/CFS.

Cognitive dysfunction

Cognitive difficulties are sometimes mentioned in bed rest studies but rarely so. Reviews concluded that “cognitive functioning does not appear to be adversely affected by long-duration head-down bed rest” and that “any cognitive effects of bed rest thus remain to be established.”

Common ME/CFS symptoms such as post-exertional malaise, widespread pain, and light and noise sensitivity are not mentioned in bed rest studies at all. This is curious because researchers have repeatedly claimed that deconditioning can account for these symptoms. The patient manual for exercise therapy used in the PACE trial, for example, stated that “prolonged rest results in a change in the way the brain perceives external sensations, like noise and light, with consequent sensitivity. This may result in visual problems and sensitivity to noise.” An editorial on the role of physical inactivity in ME/CFS claimed that deconditioning caused “not only fatigue, exercise avoidance, and intolerance, but also sensitivity to noise, reduced visual acuity, orthostatic intolerance, and heat and cold intolerance, amongst others.”

There seems to be little to no evidence for such statements even though they have been repeated multiple times. We have tried to track their references and sources but were unable to find bed rest or other studies that demonstrate that these symptoms result from deconditioning.

Orthostatic intolerance

There is one notable exception, however. Orthostatic intolerance is reported in most bed rest studies. Symptoms such as dizziness and (nearly) fainting when changing to an upright position are mentioned repeatedly in the literature.

NASA researchers found that most astronauts could not complete a 10-minute tilt table test after a space flight and some even had to be carried off their spaceships. Similar (but less pronounced) problems were noted in head-down bed rest studies, even after a short duration. Participants often struggle with balance, coordination, and maintaining an upright position. Several studies (examples here, here, and here) have reported heart rate increases upon standing of more than 30 beats per minute, the threshold used in diagnostic criteria for postural orthostatic tachycardia syndrome (POTS).

Even though orthostatic intolerance is likely more the result of a horizontal position than inactivity, it is nonetheless relevant to ME/CFS as many are bedbound or need to lie down most of the day because of their illness. Interestingly, research by space agencies suggests that exercising horizontally is insufficient to counter all of the negative effects mentioned above and that frequently standing upright is equally important.

Speedy recovery

Another interesting difference between ME/CFS and deconditioning is exercise and recovery. As one review noted, “most of the deconditioning is rapidly reversible except for bone loss in long-term space or bed rest studies.”  Others report that the rate of recovery is roughly proportional to the extent of the deterioration in bed rest. Muscle mass is restored, insulin sensitivity increases, and blood volume returns to normal levels. The human body is remarkably adaptable.

The Dallas bed rest study forms an illustrative example. This study took place in the 1960s and, although it wasn’t led by NASA researchers, it is considered a classic in the field. Five young and healthy men voluntarily underwent 20 days of strict bed rest. Their VO2 max started at 3.3 L/min and dropped by 27% to 2.4 L/min during the resting period. But afterward, they started a strenuous exercise program by which they were able to increase their VO2 max to 3.9 L/min. So not only were the effects of bed rest completely reversed, but participants could also increase their cardiovascular fitness to 118%  of the baseline value.

The fast improvements are also noted in testimonies. One participant in a 70-day bed rest study explained that “within a few days of casual strolling and formal reconditioning exercise, my balance returned and my endurance began to recover. By the end of the two-week post-bed-rest period, I felt 95 percent physically normal. I was ready to go.”

Contrast this with the experience of ME/CFS patients who have been unable to increase their VO2 max, fitness, or activity levels despite participating in graded exercise therapy for several weeks. Rather than feeling ‘ready to go’ ME/CFS patients often report feeling significantly worse after exercise.

Anecdotally, some patients who experienced severe deconditioning earlier in their lives, for example after surgery or accident, reported that the experience is very different from ME/CFS. On the Phoenix Rising forum, one person wrote: “‘I broke my pelvis several years before I got CFS. I had to stay in bed for a few weeks, so I became deconditioned, but as soon as I recovered enough I started swimming as I had before my accident, gradually working up to a mile. The experience of being injured and deconditioned was not like the experience of illness with CFS.’”

Deconditioning in ME/CFS

Another finding that does not fit the theory is that ME/CFS patients are not extremely deconditioned. The most used measure for fitness is VO2 max which is influenced by age (it decreases when you get older) and sex (women tend to have lower values than men). For ME/CFS we need to look at a reference population that is approximately 75% female and has a mean age of around 40 years.

Most studies have found that ME/CFS patients have VO2 max values between 20 and 30 ml/kg/min. Comparing this to US reference values would put them somewhere between the lowest 25th and 10th percentile. The median of the general population is around 30 ml/kg/min. These data suggest that many patients have normal VO2 max values and that approximately 10% of the US population scores lower than the ME/CFS mean fitness. In comparison, estimates of VO2 max in patients with tetraplegia and paraplegia indicate values around 10-14 ml/kg/min. These data contradict Wagenmaker’s speculation that ME/CFS represents “the physiology of people on the low end of the spectrum of physical activity.”  

Several researchers have highlighted this inconsistency in the deconditioning hypothesis. One group wrote that “because there was no significant difference in fitness between CFS and controls, it is not likely that physical fitness should be considered a perpetuating factor in CFS .” Another research team noted that exercise “programs could well be based on a false premise if the intention is to improve patient management and well-being by correcting the effects of deconditioning.”

Unfortunately, this seems to be exactly what has happened. The VO2 max measured in exercise trials (examples here and here) for ME/CFS is around 30 ml/kg/min, values that are normal and close to the population mean for participants’ age and sex. These trials were treating deconditioning that wasn’t there in the first place.

Unsurprisingly, these studies also found few correlations between improvements in fitness and symptoms such as fatigue. The first exercise trial for ME/CFS for example, reported: “We found no significant association between feeling better after graded exercise treatment and becoming stronger or fitter.” Others noted that “Changes in exercise capacity measures were rather modest and did not correlate or only weakly correlated with HRQoL[health-related quality of life]/psychosocial variables.” Similarly, in the PACE trial, “fitness measures do not appear to mediate the effects of either treatment”.

Longitudinal studies

Lastly, we looked at longitudinal studies that follow up on healthy persons before they develop (self-reported) ME/CFS to see if fitness and exercise form a risk factor for the syndrome.

One study that used the data from the 1970 British birth cohort reported that higher levels of exercise in childhood were associated with a lower risk of ME/CFS. However, a closer look shows that this study only found a trend (p=0.04) and that other exercise measures such as hours of sports played at school were not associated with ME/CFS.

Data from the 1958 birth cohort indicated that “there was no evidence that performing sporting activity at age 11 was associated with reduced odds of CFS/ME, or that persistent physical activity in early- to mid-adulthood increased the risk of CFS/ME”. The 1946 birth cohort found the opposite effect, namely that increased levels of exercise throughout childhood and early adult life increased the risk of ME/CFS. Lastly, the Lifelines cohort from the Netherlands provided the largest sample size and found that physical activity was not associated with ME/CFS (with an odds ratio of exactly 1).

Summary

In conclusion, there is no evidence to suggest that low activity levels predispose people to developing ME/CFS. Deconditioning does not cause extreme fatigue, widespread pain, or sensitivity to light and sound. Patients who are more deconditioned than ME/CFS patients do not experience these symptoms. While exercise is a fast and effective cure for deconditioning, it fails to help ME/CFS patients get fitter or less ill. And although deconditioning may contribute to some ME/CFS symptoms such as orthostatic intolerance, it is unlikely to be the main explanation for these patients’ disability.

Notes

* Many thanks to Simon Mcgrath (oceanblue on the Phoenix Rising forum) for analyzing the literature more than 10 years before me. Your commentary was very helpful in writing this updated overview.