The more serious type of fatigue is the one resulting from excessive build-up of ROS in the muscle and depletion of ATP. This type of “fatigue” is extreme prostration that occurs 8 or more hours after exercise (or what passes for “exercise” in CFS/ME patients and would be considered normal activity by healthy people.) Patients feel a deep, whole-body weariness and feel the necessity to lie still and not move due to extreme fatigue. Trying to even turn over in bed requires a great deal of painful effort of will. In addition, patients feel very sore all over their bodies. CFS/ME patients often describe this as feeling being beaten up and run over by a Mack truck or bus. The term post-exertional “malaise” seems pathetically inadequate as a descriptor of this feeling.
Mitochondrial specialist Dr. Donald Johns has warned that when a patient feels this way, it is very important to listen to his/her body. The extreme fatigue feeling is from depletion of ATP and the beaten-up/run-over feeling is from excessive ROS that not only did permanent damage to muscle cells, but also is still doing damage. Thus, it is essential to stay in bed and move as little as possible until the condition improves—even if that takes days. The best thing to do is for the patient to try to avoid getting into this condition in the first place by pacing and staying inside his/her “energy envelope.” This is not so easy to do at times, however.
ROS produced in the mitochondria damage mitochondrial DNA, for instance.3 This leads to alterations to the polypeptides encoded by the DNA. A decrease in electron transfer then ensues, but electron transfer is needed for generation of ATP. Thus, more ROS are produced in a vicious circle of oxidative distress and energetic decline.52 Mitochondrial DNA damage also results in daughter cells that are mutated and in cellular apoptosis.4, 5, 6, 7, 28
Muscle inflammation and oxidative stress are now known to play an important role in muscle atrophy.53 In addition, many CFS/ME patients have a low-grade fever, which means they have high levels of interleukin-1 (IL-1).54, 55 IL-1 is known to cause muscle catabolism (muscle destruction).54, 55 So CFS/ME patients with high levels of ROS and low-grade fevers can expect noticeable destruction of skeletal muscle with difficulty in replacing it.
ROS generated from mitochondria also damages proteins and lipid in membrane components for mitochondria membranes and cellular membranes. This results in more mitochondrial dysfunction and cellular apoptosis.4, 5, 6, 7, 28