What is Chronic Fatigue? Part 3: The Role of Mitochondria and ATP

Mitochondria2Within the Chronic Fatigue Picture it helps to know WHERE and HOW we create energy.

Mitochondria are rod-shaped organelles that can be considered the power generators of the cell, converting oxygen and nutrients into a substance known as Adenosine Tri-Phosphate (ATP).

ATP is the chemical energy “currency” of the cell that powers the cell’s metabolic activities. This process is called aerobic respiration and is the reason we breathe oxygen.

Without mitochondria humans and  animals would likely not exist because we need large amounts of energy in order to survive. In fact, mitochondria enable cells to produce 15 times more ATP (energy currency) than they could otherwise.

Chronic Fatigue Syndrome as we have discussed is a multi-factorial health condition, with a number of imbalances contributing to the over-all experience of CFS.  However mitochondrial imbalance can explain more than any other contributory factor Post Exertional Fatigue, which is a key player within differential diagnosis.

Mitochondria’s key function is the Recycling of ATP to ADP and back to ATP.

This cycle relies upon various nutrient substrates such as D Ribose, Carnitine, B3, Co-enzyme A, Co-enzyme Q10.  The role of these substrates is to move into the cell in the process of completing the important recycling metabolic process.

As the nutrients are harnessed, Adenosine Tri-Phosphate becomes Adenosine Di-Phosphate (ATP > ADP). This process actually releases energy, whilst becoming carbon dioxide and water.

Rate Limiting Factors:

Firstly a deficiency in any of the substrates mentioned above create a BLOCK within the cycle.  Therefore nutrient deficiency plays into mitochondrial insufficiency.

And because Carnitine, Co-enzyme Q10 and other substrates result from a process called methylation (a biological process that will be expanded on in subsequent Blog posts), when a person under-methylates there is automatically a material deficiency regarding these substrates.

However others things also BLOCK this cycle, like heavy metals, hair dyes and excessive oxidative stress. Excessive oxidative stress destroys both the fatty membrane of the cells and the mitochondria itself.

Further to, there is a protein called trans locator protein responsible for moving ATP and ADP from the mitochondria cell to the cytosol of the cell.  When mitochondria senses that ADP/ATP have been depleted, used up for cells function etc, then this triggers mitochondria to produce more ATP. So this constant re-cycling occurs.

The key thing about those individuals who struggle with a rate limiting factor is when they push through, meaning that they carry on doing exercise when or even in some cases just daily chores and tasks throughout their day, and they are not capable recycling the ADP to ATP then the body goes into emergency mode.  What this means is that the body then targets ADP to be broken down instead because there is not ample ATP because boundaries have been crossed.

ADP is then broken down to AMP, which is a purine, and is lost to the system since it is then urinated out of the body.  Understood by leaders in the field of CFS to be a metabolic disaster.  This is where Post Exertional Fatigue comes from.  Usually the person pushes through and can feel fine, and even feel fine the following day. But the day after that could be when they crash!!!

AMP cannot be recycled.  ADP then has to be built from scratch before it is then recycled to ATP.

However Mitochondrial function is not enough to create CFS on it’s own.  Rather understood a down-steam consequence of other factors. 

A key factor in how the disease is managed as well as forged is the personality type of the person.  If you are a perfectionist for instance who finds it hard to pace, then typically as soon as the person has some energy they use it up again.  




What is Chronic Fatigue? Part 2: Multiple systems under-functioning

Chronic Fatigue Syndrome is a notoriously tricky illness to pin-down.  Since CFS related health-issues tend to be serious to the degree that it can be life altering, but they are usually not so serious that they become a classified disease like heart disease.  This is not only confusing to the sufferer, but immensely frustrating too since many of the symptoms are not taken seriously by mainstream medicine.

1.  The first condition to be common among CFS sufferers is Adrenal Fatigue.

Unrecognised by most General Practitioners, Adrenal Fatigue affects our energy performance.  It influences how we regulate energy via our adrenal glands, but it is not Addison’s Disease – which is a recognised disease. Adrenal Fatigue is a serious life altering condition – but it is not adrenal failure.

So what tends to happen is the adrenal glands are tested with a blood test.  But because a blood test is not a sensitive enough test to pick up on adrenal dysregyulation, results come back suggesting they are functioning normally.

This presents false understanding and confusion when the sufferer is experiencing low energy due to sub-optimal adrenal function, but the tests being used are not sensitive enough to pick up on the true performance.

A four-point saliva test should be provided, obtainable by private labs through the UK and over-seas.  The four-point saliva test picks up on steroid hormone excretions throughout the day, tracking adaptogenic responses.  And therefore provides clear understanding of how the adrenal glands are ‘responding’ and adapting to daily stressors.

2.  The second condition is Left Ventricular Disease.

Studies release that a shocking 35% of us is said to have this condition, however the CFS / ME sufferer will experience the downstream effects of this condition as a chronic and debilitating element of the whole CFS picture.

They may be aware that their heart feels unstable, but unable to identify this through medical means since it is not classic heart disease and easily missed.

3.  The third piece to the Chronic Fatigue conundrum is the role of gut Dysbiosis.

Often present in those with Chronic Fatigue.  Gut Dysbiosis fits in to the picture of both Adrenal Fatigue and Chronic Fatigue Syndrome due to the role the adrenal glands play in providing an anti-inflammatory cortico-steroid (cortisol) to the body to buffer inflammation in the gut.

Causative factors for inflammation in the gut: 

Food Intolerances / Virus / Toxins such as methyl-mercury / Stress

Gut Dysbiosis has a number of potential causative factors with stress, food intolerances as well as toxins such as methyl mercury trumping possible causes for. Gut Dysbiosis is chronic low grade inflammation, however it is not inflammatory bowel disease (IBD) and therefore unrecognised by medical communities once again.

4.  The fourth mechanical issue to arise within CFS, and ties in with performance of the heart, liver and adrenal glands is Mitochondrial dysfunction.

This is not an inborn error of the mitochondria, however it is an inherited epigenetic malfunction.  What that means is that due to the environment the mitochondria has been presented within, functionality of mitochondria is reduced.  The trouble is, when there is poor mitochondrial function, then everything else in the body is affected.  But in particular the function of the heart and liver since this is where mot mitochondria resides.

Nutrients which positively support Mitochondria Function / Krebs Cycle:

D-Ribose / L-Carnitine / B3 (NAD) / Co-enzyme A / Co-enzyme Q10

What causes mitochondrial breakdown:

Crisps, rancid fats, hydrogenated oils, poor nutrient profile, toxic metals blocking biochemical pathways and oxidative stress.

5.  The fifth area of health which has more studies relating to CFS then any other area, is Nitric Oxide and Oxidative Stress.

Within the central nervous system and under normal conditions, Nitric Oxide (NO) is an important physiological signaling molecule, however when produced in large excess Nitric Oxide also displays neurotoxicity and is a risk to heart health.

Nitric Oxide has been found to be excessively high in Chronic Fatigue Sufferers and is seen in conjunction with risk factors for cardiovascular disease.

6.  The sixth element of Chronic Fatigue Syndrome is the observable Inflammation.

Inflammation is present but it is not a classifiable Auto-immune Disease.

7.  The seventh component to this complex condition is the presence of low grade infections.

Infections and co-infections are often present in CFS sufferers:

Ususal infections:

Epstein Bar / HHV6 / Enteroviruses / Cytomegalo viruses / Parovirus B19 / Retrovirus


Mycoplasma / Chlamydia / Chronic Borrelia / Bucella / Rickettsia / Babesia 

Altogether we can view this complex condition as a disease of compromised milieu. Triggered by increased cellular stresses such as toxic heavy metals, infections and emotional stressors.

Strengthening the milieu / biological terrain interior will help to de-activate the viruses present.

8.  Finally the eighth piece in this Chronic Fatigue quandary, is emotional status of the CFS sufferer.

It is interesting to note that Chronic Fatigue patients tend to fall in three main personality categories known as energy depleting psychology types.

The Acheiver Perfectionis Type

Anxiety Type

The Helper Type

There can also be a genetic or epigenetic predisposition element to our stress responses to emotional trauma. Meaning that this can be either genetically inherited or genetically learned behaviour.  And then the condition / illness itself perpetuates further trauma in the sufferer as there is constant fear of becoming ill.  Other behaviours feed in to this cycle such as avoidance of certain foods and situations that they believe will make their condition worse.

Each category will be expanded upon within subsequent posts in the coming weeks.







What is Chronic Fatigue? Part 1: Definition and complex adaptive systems.

Chronic Fatigue, otherwise known as ME (Myalgic Encephalomyelitis), is a harrowing and debilitating condition, with no differential diagnosis in medical terms.  Diagnosis is exclusion based only, therefore other conditions similar by experience and presentation of symptoms, must first be eliminated. To receive the diagnosis of CFS/ME other possibilities such as cancer, liver disease, heart disease, auto immune condition must be eliminated.  When nothing else comes up after 6 months of unrelenting fatigue then the diagnosis is given.  This is the FUKUDA criteria.

Low grade chronic inflammation has been found consistently in those with Chronic Fatigue.  Inflammation of the brain and spinal chord as well as muscle pain and tenderness.  According to official guidelines in the realms of psychology 1990’s CFS was understood to be and unrelenting and debilitating condition, more functionally impaired that congestive heart failure, Multiple Sclerosis, Type 2 Diabetes, and even End stage renal disease!


The realms of psychology also cleverly defines CFS from depression by differentiating underlying motivations.

Ask the question ‘ What would you want to do with your life?’

The depressed person will tell you that they do not know.  While the CFS person will give you an in exhaustive list, but if it wasn’t for their energy!!

Do personality types then factor in to Chronic Fatigue Syndrome?

There is also a clinical definition of neuro chemistry which ties into psychological predisposition.  High serotonin is often found in those with Chronic Fatigue Syndrome rather than low serotonin.  Depression is LOW serotonin.

Chronic Fatigue has not gained much traction within medical communities, and this is largely down to the linear medical model and approach typically adopted by allopathic medicine.

Ultimately Chronic Fatigue Syndrome is a thresh-hold illness, with a range of imbalances resulting in a perfect storm ending up with post exertional fatigue and CFS.

This does not serve those with CFS/ME, since there are multiple biological adaptive systems which will be under-functioning.  And when you seek to support one system alone, within the Chronic Fatigue Model, you can very easily upset other systems which are also functioning to the brink of chaos and tip them over.

This is an extremely important point when understanding the nature of this condition and its healing pathway.  Since it feels as though we have lost control our bodies.  We are no longer in control of how much energy we have, there may be pain throughout the body and we seek to regain control.

And so, when multiple systems have collapsed and reorganised to a new level.  Meaning that the way we produce energy is no longer happening as it should, and we have limited energy, then this is the new norm, and the system is stable.  True, we don’t have energy, and we have lost control.  But, the system is still stable.

By attempting to heal CFS / ME without an understanding of how biological-systems lean in to each other.  Therefore looking at ‘communication between systems’, it becomes easy collapse currently stable systems into temporary chaos and to feel sicker than ever!

For this reason a wholistic approach, Otherwise known as a systems biology approach, which values multiple systems, is the only model which can successfully support the CFS sufferer toward health.  This is why the medical model cannot help the CFS / ME sufferer.  And we end up feeling sicker, more terrified, more out of control and more at sea with our symptoms than ever before.