Why Exercise May Make Some CFS Sufferers Feel Worse

Anyone who suffers from chronic fatigue has been told to exercise, as if exercise is the silver bullet for a condition that involves chronic inflammation, oxidative stress, multiple allergies and, for many people, genetics. 

Alas, while many people with CFS benefit from exercise, a few become significantly worse. There are two possible reasons why exercise makes some CFS patients feel worse: 

• An increase in cytokines--proteins that serve as chemical messengers to regulate the immune system--that have been linked to CFS.
• Low levels of the adrenal hormone DHEA or its variant, DHEA-S

An old study from 2010 may explain the effect of exercise on CFS patients. Researchers tested the level of cytokines in both healthy controls and CFS patients. The CFS patients differed in their response to exericise: some felt that exercise improved their symptoms while others reported feeling fatigued for days afterwards. Researchers found that healthy controls and people with CFS who benefited from exercise experienced an elevation of only one cytokine after exercise. In contrast, those CFS patients who felt more exhausted after exercise experienced a rise in six cytokines and failed to show post-exercise decreases in other cytokines that the normal controls did.

A statement from the abstract (summary) of the research:

Those CFS patients experiencing a greater SF lasting through 48 h post-exercise showed increases in six cytokines at 8 h post-exercise (pro-inflammatory IL-1β, IL-8, and IL-12, anti-inflammatory IL-10 and IL-13, and in IL-6). The high SF group also failed to show post-exercise decreases in CD40L, TNFα, or IL-13 as shown by controls or by the less symptomatic CFS patients. Higher baseline IL-6 was associated with higher baseline fatigue, and greater IL-6 and CD40L increases at 8 h post-exercise (when white cell counts increased significantly) were related to greater fatigue and pain increases at 48 h, although the IL-6 effect was strongly influenced by one patient.

Why Do Higher Cytokine Levels after Exercise Matter?

A variety of studies, summarized in this review paper, have found altered cytokine levels in chronic fatigue patients compared to healthy controls. Some of the cytokines released by those CFS patients who feel worse after exercise are the same one like IL-1B that are found in CFS patients even before exercise. If exercise causes IL-1B levels to rise, no wonder so many CFS patients feel worse after a workout. 

What do DHEA Levels Have to Do with CFS and Response to Exercise

While a few studies have found higher DHEA levels in CFS patients, most have found lower levels of this hormone.  Furthermore, low DHEA levels correlate with immune system alterations and inflammation associated with with disorder. 

While I know of no studies of DHEA and exercise in CFS patients, an exercise study of older adults found an interesting link. Older women in their 80s and 90s were divided into two groups based on DHEA level and then given an exercise program. Those women in the group with the highest DHEA levels showed decreased blood pressure and lower levels of blood glucose and cholesterol. However, women in the group with the lowest DHEA showed no improvement on any of the measures.

The take-home message: response to exercise depends, at least for older women, on having adequate DHEA levels. With inadequate amounts of this hormone, exercise is much less beneficial.

A Third Factor in Evaluating Exercise as a Treatment for Chronic Fatigue

Yes, exercise does help many people with CFS but its effectivness is overrated.  Why?

Two factors: performance bias and detection bias. 

In an ideal experiment, there are two groups, one receiving the treatment and a second group that is not receiving the treatment. In this case, one group is exercising. The other is not. Other than this one difference, the exercise group and the non-exercise group should be as close to identical as possible. The average age of one group should be almost the same as the average age of the other group. There should be roughly the same number of men and women in both groups. Average levels of education and income should be the same, too. Obviously, no one can achieve perfect equality on all measures but by testing a lot of people, these factors tend to cancel each other out and approach equality. . 

The two groups should also be treated identically in every respect except that one group is not receiving the treatment. This is known as blinding because the people in the experiment are "blind" to whether they are getting a treatment or a placebo of some kind. When the person collecting the information about the results also doesn't know who is in what group, that condition is called "double blinding." 

What is performance bias? Performance bias occurs when either the people being tested or the researchers collecting the information know whether those being tested are receiving the treatment or not receiving it. In other words, when an experiment is not double-blinded, a risk of bias exists. 

People who know they are receiving the treatment may experience a placebo effect or may want to "fake good" to please the researchers. On the other hand, those evaluating response to treatment may give the test group extra attention, even if they don't do it consciously. 

 Does performance bias affect outcomes? Yes, it does. A website on research biases managed by the University of Oxford indicates that this lack of double-blinding can alter outcomes by 13% for reasons that have nothing to do with the effectiveness of the treatment. 

In exercise studies, it is almost impossible to avoid performance bias: people know whether they are exercising or not. 

Detection bias results from differences in the way information about the treatment's effectiveness is collected or verified." The catalog of biases gives an interesting example: Some researchers found that smokers were less likely to develop certain kinds of skin cancers. However, later research found that smokers were less likely to have regular skin cancer screenings than non-smokers. This difference in preventive health care between the two groups led to a difference in the way data was collected, leading to an undercount of skin cancer cases among smokers and hence to detection bias.

One can speculate on whether detection bias exists in studies of CFS and exercise. The possibility, I believe is non-trivial. After all, if a person knows she feels worse after exercise,why would she volunteer for a study to test the effectiveness of it?

The take-home message: If exercise does't work for you, there are clear physical reasons why it doesn't. That failure is not in your head. It is real. Listen to your body. Work on healing other factors associated with the disease first. Then, add exercise to your healing regimen gradually.