Mitochondrial Dysfunction and Post-Exertional Malaise

Mitochondrial Dysfunction, Post-Exertional Malaise and CFS/ME

Though this article refers to Chronic Fatigue Syndrome, these symptoms often overlap with other chronic conditions, like Fibromyalgia.  Also, people with EDS are often suspected of having mitochondrial issues.

It has been well documented that there is an abnormal increase in cytokines (chemicals released by the immune system) in CFS/ME patients following mild exercise. This causes another type of fatigue on top of the mitochondrial dysfunction fatigue discussed below. Cytokines in general, without the exercise trigger, can cause fatigue.  There are probably additional causes of fatigue (such as orthostatic intolerance) as well.

Role of mitochondria in cellular function

Except for red blood cells, every cell of the human body contains mitochondria—which are cellular bodies that manufacture the energy needed by the cell in order to function.

The Krebs cycle involves vitamin B-1 (thiamine), vitamin B-2 (riboflavin), magnesium, and malate (from malic acid), which has implications for treatment of mitochondrial disorders.

A more technical description of how this works:

“When the energy in ATP is utilized during cell work (ATP hydrolysis), protons are produced. The mitochondria normally incorporate these protons back into ATP, thus preventing buildup of protons and maintaining neutral pH. If oxygen supply is inadequate (hypoxia), the mitochondria are unable to continue ATP synthesis at a rate sufficient to supply the cell with the required ATP.

In this situation, glycolysis is increased to provide additional ATP, and the excess pyruvate produced is converted into lactate and released from the cell into the bloodstream, where it accumulates over time. While increased glycolysis helps compensate for less ATP from oxidative phosphorylation, it cannot bind the protons resulting from ATP hydrolysis. Therefore, proton concentration rises and causes acidosis.

Generally speaking, cells prefer to use glucose as a fuel, under oxygenation. During fasting, fatty acids and ketone bodies are more important energy sources for most cells, with the idea that the glucose available is saved for brain cells

The situation in skeletal muscle cells is more complicated. The choice of fuel source is largely determined by exercise intensity and duration. As exercise intensity increases, the use of glucose/glycogen intensifies. However, at low intensity or moderate exercise, fatty acid is the preferred fuel.

It is now known that dysfunctional mitochondria play an important role in diseases of the brain such as Alzheimer’s, and Parkinson’s.

Type-2 diabetes mellitus is also known to be an acquired mitochondrial dysfunction disease of the mitochondria in skeletal muscle and the pancreas

normally 67% of the volume of skeletal muscle cells is occupied by mitochondria, compared to 20-30% of cardiac muscle cells

The evidence that CFS/ME is at least in part an acquired mitochondrial dysfunction disease of skeletal muscle is now quite strong

Characteristics and consequences of mitochondrial dysfunction fatigue in skeletal muscle

Those who have mitochondrial dysfunction of the skeletal muscle can experience two main types of fatigue.

  1. One is the result of increased acidosis inside the muscle cells and has as a marker increased lactate in the blood. This is a result of muscle cells trying to create ATP when there is insufficient oxygen. Endurance athletes (such as marathoners) can experience this type of fatigue. They refer to it as “hitting the wall.”8, 9 It is also referred to as “metabolic fatigue.”
  2. The second type of fatigue is the result of a large build-up of Reactive Oxygen Species (ROS) and depletion of ATP in the muscle cells. As far as we can determine from a careful search of the medical literature, this second type of fatigue is unique to patients with known inherited genetic mitochondrial diseases of skeletal muscle, AIDS patients undergoing treatment with antiretroviral drugs (who have severe mitochondrial dysfunction),47and CFS/ME patients experiencing post-exertional “malaise.” It is this second type of fatigue that has the most permanent serious consequences for patients.

The first type of fatigue, metabolic fatigue, feels like a burning, dull aching weariness in muscles. The affected muscles feel stiff and affected limbs feel heavier and heavier, as the ability of the muscles to contract declines. The increased acidity in the muscle cell lowers the sensitivity of the contractile apparatus to calcium Ca2+. It is unclear what exact role lactic acid has in this process, but increased lactate in the blood is a marker for this type of fatigue

As mentioned in the preceding section, a subgroup of CFS/ME patients have an abnormal rise in lactate with minor exercise and a very slow recovery from this condition

It should be noted that excess lactic acid is now known to be neurotoxic, so continual problems with this could lead to the death or damage of motor neurons in skeletal muscle

the patient needs to make constant cost/benefit judgments about doing activities that use energy. There will be times that a patient decides that the psychological and emotional benefit of an activity outweighs the physical cost.

It is psychologically important for a patient to have some daily activity that creates a vestige of joy and psychological well-being, and not put everything “on hold” awaiting a recovery that might not come.

there are no known pharmaceuticals for mitochondrial dysfunction

Supplements to treat mitochondrial dysfunction

  • Magnesium  (up to 600 mg a day ) (Blood levels must be monitored periodically for patient safety)
  • Co-enzyme Q-10 (100-200 mg three times a day
  • Acetyl-l-carnitine (500-1000 mg three times a day)  (The acetyl-l form of acetyl-carnitine crosses the blood/brain barrier and helps brain mitochondria as well)
  • Creatine
  • Folic acid
  • Malic acid (600-1200 mg twice a day)

Recovery from prostration fatigue

  • Vitamin B-1 (thiamine)  (100 mg twice a day)
  • Vitamin B-2 (riboflavin) (100 mg)70, 50, 55, 79, 80
  • Biotin (5 mg twice a day)

Postponing build-up of lactic acidosis

  • Time-release guaifenesin (600-800 mg)

Precisely why guaifenesin works is unknown, but it definitely does work for some patients. Guaifenesin is a uricosuric—a drug that increases the excretion of uric acid from the blood into urine.

It seems to help the excretion of excess phosphate from the cells of the body, which might have a bearing on mitochondrial dysfunction, since excess intracellular phosphate builds up with the hydrogen ion H+. Thus it might just act as a chemical buffer in the blood, slowing the build-up of acidity.

This was originally posted on April 30, 2014, but in light of the recently documented association of CFS and EDS I believe it’s even more important.

Since the time of orignal posting, I have explored the role of guaifenesin and found more evidence of its effectiveness:

I had wrongly credited the article to @CortJohnson, but I now realize he had sourced it from The Massachusetts CFIDS/ME & FM Association so I’ve corrected that.

Other thoughts?

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.