Post-Exertional Malaise in Chronic Fatigue Syndrome

Part 2 of 3

woman looking tired and stressed
 JGI/Jamie Grill

As we learned in part one, What is Post-Exertional Malaise, people with chronic fatigue syndrome (ME/CFS) see an often dramatic upswing in symptoms following exertion. This is a hallmark symptom of the disease and one that researchers have been trying to figure out for years. We still have much to learn about this symptom, but we do know that multiple physiological abnormalities are linked to post-exertional malaise (PEM).

Physiological Abnormalities

Researchers have identified exercise-related abnormalities in multiple systems, including the immune system, the central nervous system, and the cardiovascular system. So far, however, they have not been able to conclude that these abnormalities are the cause(s) of PEM. A 2014 review of the medical literature identified several altered immune system responses in ME/CFS, many of which were tied to exercise and PEM. These included:

  • A more pronounced response in the complement system (a part of the immune system that helps clear pathogens from your body),
  • An increase in oxidative stress (a type of cellular damage) combined with a poor antioxidant response,
  • An alteration in the immune cells' gene expression profile.

Other research (Morris 2014) has examined abnormalities relating to a substance called adenosine triphosphate (ATP), which is a form of cellular energy. ME/CFS is believed to be associated with an impaired ability to create ATP at the mitochondrial level. (Mitochondria are structures in your cells that convert nutrients into ATP.)

A 2015 study using a computer model of the disease (Lengert) looked at critically low levels of ATP, which typically would lead to an increased rate of cell death. A chain reaction beginning with low ATP led to immunological dysregulations and oxidative stress, according to the model. Researchers say that repeated exertion made the situation considerably worse. In 2012, a paper examining mitochondrial function and ME/CFS (Morris) discussed multiple abnormalities, including:

  • Activated immuno-inflammatory pathways,
  • Increased levels of pro-inflammatory cytokines,
  • Increased levels of nuclear factor-kB,
  • Aberrations in mitochondrial functions, including a low production of ATP.

The researchers theorized that these factors may, at least in part, lead to mitochondrial exhaustion, which means that when the body demands energy (in the form of ATP), the energy simply is not there.

Another 2015 study used a type of scan called near-infrared spectroscopy to measure oxygen use during mild exercise. Compared to healthy people in the control group, participants with ME/CFS were found to have abnormal changes in oxygenation of hemoglobin (a protein in red blood cells that transports oxygen t­o your cells) after exertion.

Any combination of these factors could logically contribute to PEM. Still, researchers have a lot of work ahead of them. Some researchers have suggested that certain abnormalities could be used as an objective diagnostic marker for ME/CFS while others believe PEM could be a useful way for doctors to measure the severity of the illness.

More importantly, the more we learn about what's going on in the body during PEM, the closer we are to understanding how to treat it.

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