The Role of Muscle Metabolites in Chronic Fatigue Syndrome

For healthy people, a strenuous workout may exhaust them – but in a good way that leaves them feeling challenged and healthy. For people who suffer with Chronic Fatigue Syndrome (CFS), or Systemic Exertion Intolerance Disease (SEID), as it was recently renamed, simply walking across a room can leave them as wiped out as the over-enthusiastic athlete.

Finding the origin of fatigue

How do we know when we have become exhausted or wiped out? The neural pathways in our bodies transmit the sensation of fatigue to the brain. In some sensitive individuals, such as those with CFS/SEID, they may be overperforming in that area.

Research suggests that muscles and other peripheral tissues may be contributing to feelings of fatigue, as well. By confirming the origin of fatigue, researchers hope to be able to create therapies to help people deal more effectively with their disease.

CFS/SEID has proven to be a difficult disease to diagnose, because its chief symptom of fatigue is also associated with so many other conditions. To date, approximately more than one million people suffer from it, but they are currently undiagnosed.

Muscle metabolites

A study from the University of Florida College of Medicine focused on trying to define the role of muscle metabolites in this disease. Muscle metabolites, specifically lactic acid and adenosine triphosphate (ATP), were believed to contribute to the development of feelings of fatigue.

They found that these substances were released during exercise and were shown to activate neural pathways. These very same pathways appear to be highly sensitive in patients with CFS/SEID, compared to patients without it. This is a new aspect that had not been previously researched.

“For most of us, at the end of strenuous exertion we feel exhausted and need to stop – but we will recover rapidly,” said lead author Roland Staud, professor of rheumatology and clinical immunology at University of Florida College of Medicine. “However, these individuals tire much more rapidly and sometimes just after moving across a room, they are fully exhausted. This takes a toll on their lives.”

Sending fatigue messages to the brain

Researchers explain that exercise causes muscles to produce metabolites, such as ATP, which are detected by metaboreceptors that activate an information transfer along fatigue pathways to the brain. In patients with CFS/SEID, their neural pathways become highly sensitive to these metabolites, and this causes a trigger of excessive fatigue messages to the brain.

For their study, researchers recruited a group of 68 participants; 39 were patients with CFS/SEID, and 29 were patients without it. All participants were asked to wear a blood pressure cuff above the elbows on their dominant arm while they squeezed a spring-loaded device at the absolute maximum capacity of 100 percent. They were then asked to squeeze it again to 50 percent of their capacity for as long as they were able to maintain it.

Immediately following the hand exercises, the blood pressure cuff was inflated to trap the muscle metabolites in the forearm muscles. This caused them to collect rather than being cleared by the circulatory system as they normally would be. Because of their captivity, the metabolites continued activating fatigue pathways to the brain. This gave researchers an opportunity to measure the amount of fatigue and pain that could occur from trapped metabolites.

fatigueThe findings of the study showed that both participants with CFS/SEID and those without reported increases in their levels of fatigue. However, patients with the disease reported severely higher levels of pain and fatigue compared to those without the disease. Patients with SEID rated their levels of fatigue at 5.5 on a scale of 0 to 10, compared to patients without SEID, who only rated their fatigue at 1.5 using the same scale.

The exercises were repeated a half hour later on the opposite arm. However, this time the blood pressure cuff was not used to trap the metabolites in the forearm. When participants rated their fatigue, both those with and without the disease were fatigued, but much less without the trapped metabolites.

“The take-home message here is, like many of the pain studies we have conducted, there are both peripheral and central nervous system factors at play in these complex syndromes,” said coauthor Michael E. Robinson, professor in the department of clinical and health psychology at University of Florida College of Medicine. “Our study seems to highlight the important role of these peripheral tissues.”

We will keep you posted on any developments in this fascinating research.

-The Alternative Daily


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