ME/CFS Oxidative Stress and Mitochondrial Dysfunction

In “All Arrows Point Inwards” we discussed the effects of a reduction or elimination, of the gluten protein found in some grains and lactose sugar found in cow’s milk. The positive effects for the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) sufferer may well include the reduction or elimination of symptoms including brain fog, IBS, a decline in the negative immune response, while also reducing the chance of acquiring auto immune diseases.

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Unfortunately a reduction in these symptoms is not the entire solution to the problems faced by a ME/CFS affected individual. We need to look a little deeper for further explanations of crushing exhaustion and slow recovery time. To do this we will look down to the cellular level and the function of an organelle (cell compartment) called the mitochondria.

B0007276 Eukaryotic cellMitochondria are responsible for transforming the food we consume into use able energy at the cellular level. It is theorised that the mitochondria, which has its own DNA (different from that of our own cells) may have been a separate organism very early in the evolutionary process. These organelles could have entered early cell forms, resulting in a symbiotic relationship to benefit both the cell and organelle.

The mitochondria’s role in animal cells is immensely important and a typical animal cell will have a range of 1000 to 2000 of these organelles. The cells in most need of energy have the most concentrations of mitochondria. For example half the weight of the heart can be related to concentrations of mitochondria. High concentrations are found in skeletal muscle cells, the brain and liver cells.   

The mitochondrial metabolic process is reliant upon oxygen (aerobic) as a respiratory agent and glucose (simple sugar) as the fuel. The end stage of cellular respiration produces the chemical adenosine triphosphate commonly known as ATP. This chemical is the predominant cellular fuel and cellular energy is created by breaking a chemical bond reducing ATP to ADP (Adenosine Diphosphate).

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This process is then recycled building ADP back to ATP (Please see the diagram below). The recycling process requires energy, however the energy used to rebuild ADP to ATP is less than the energy created when an ATP bond is broken.

ATP Cycle

Glucose + Oxygen + ATP + Mitochondria = Energy & ADP

 ADP + Glucose + Oxygen = ATP

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When oxygen is used in a respiratory cycle like the ATP cycle it is very efficient for energy production. However, it is also potentially harmful. A substance known as Reactive Oxygen Species (ROS) is created, more commonly known as a free radical. These molecules are harmful because they react with other cell molecules stripping them of electrons (electrons like to be in pairs).

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This process is known as oxidation and has a negative cascading effect on other molecules and cells resulting in tissue damage.  The body’s natural defence against free radicals is through the use of antioxidant molecules.

If we imagine a metal foundry in which a worker is hammering a heated piece of metal. We can see that energy is used and created when the hammer contacts the metal.

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However, we can also see hot sparks flying from this kinetic process and the foundry worker is sensibly clothed in protective gear. Wearing protective equipment is akin to the role of an antioxidant. Cells have adapted to protect themselves from this process and use antioxidant molecules as a safeguard against free radical damage. These antioxidants help to absorb the harmful sparks or radicals. Antioxidants are able to do this by donating an electron, restoring balance to molecules and the cellular system, thus preventing a negative cascading effect.

Free radicals can also damage the mitochondria in the circulatory system causing red blood cells to lose elasticity and change shape. This prevents easy movement through the very small capillaries. This has obvious connotations, as the cell needs a good supply of oxygen to produce the highest energy output as described in the ATP Cycle. 

The processes described above are known as aerobic respiration (with oxygen) when we demand higher levels of energy, for example when exercising, the body has an additional energy backup system this is called anaerobic respiration (without oxygen).

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Anaerobic respiration does not require oxygen but is less efficient than aerobic respiration producing only 2 molecules of ATP per glucose molecule compared with aerobic respiration which produces 38 ATP molecules per glucose molecule. The process of switching from aerobic to anaerobic respiration is essential to supply energy to cells (mainly skeletal muscle cells) when we cannot obtain sufficient oxygen to the cells. For example long distance running will switch between the two respiration processes and running on a sprint will switch to anaerobic respiration when oxygen demand cannot be met.

As aerobic respiration produces consequential free radicals; Anaerobic respiration produces lactic acid, as a by product of oxygen free energy. We all remember our muscles aching or burning the morning after returning to the gym for the first time or when we used those muscles we didn’t know existed. This pain is the result of lactic acid production these painful sensations will reduce as our muscles increase cell growth (increasing mitochondria) through training and fitness.

The combination of mitochondrial compromised cells and poor red blood cell circulation may result in respiration switching; aerobic respiration (with oxygen) to anaerobic respiration (without oxygen). This switching process may result in an unusual increase in lactic acid production. Due to mitochondrial compromised cells and poor detoxification potential the lactic acid may not be removed adequately resulting in lactic acid remaining in the cells for longer periods, causing prolonged periods of pain.

Using these hypothesis ME/CFS patients would not have to perform any significant exercise for lactic acid production, highlighting the importance for activity management and an effective use of pacing.

Mitochondrial DNA can become easily damaged due to the nature of cellular energy creation (producing free radicals) and the Mitochondria’s location within the cell. Studies have shown that DNA injury can occur in some patients with ME/CFS, resulting in altered gene expression. When the mitochondria’s DNA mechanism becomes impaired errors are produced by the damaged DNA leading those damaged cells to produce more genetic variations. Poor gene expression can also lead to an increase in oxidative stress and free radical damage, resulting in a severely compromised cell; a cell that can eventually die.

When a cell dies the dead cell matter enters the blood stream to be filtered by the liver. This process adds to the burden of the liver by increasing the potential for liver toxicity. Comparable studies have shown that individuals with ME/CFS have the same levels of cell free DNA (dead cell matter) in their blood as those having chemotherapy for cancer. This illustrates the importance of immediate action to reduce cell damage and extra burden on the liver.

Well that’s the science bit over with. In Part Two of “ME/CFS Oxidative Stress and Mitochondrial Dysfunction” we look at some preventative measures the ME/CFS affected individual can take.

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