Mitochondrial Diseases and Adrenal Fatigue Syndrome

By: Michael Lam, MD, MPH; Dorine Lam, RDN, MS, MPH

a photo of mitochondriaThe mitochondria in all our cells are the energy power plants or the engine block for our bodies. They produce a chemical called ATP, the body’s currency for energy. Mitochondria provide over 90 percent of the body’s energy. When someone is diagnosed with mitochondrial disease, it means that they are not functioning properly in the area of energy production.

Medically, mitochondrial disease is a category of different diseases grouped together. These different diseases present in different forms and vary widely with no two patients presenting with the same symptoms.

The symptoms appear similar to quite a few diseases, including Alzheimer’s disease, autism, chronic fatigue, Lou Gehrig’s disease, muscular dystrophy, and Parkinson’s disease. Mitochondrial weakness at the sub-clinical state also mimics conditions such as liver sluggishness, extracellular matrix congestion, and Adrenal Fatigue Syndrome (AFS).

When the mitochondrial system is malfunctioning then it can be fatal, such as Leigh’s disease. This affects one in 25,000. Most mitochondrial dysfunction is not fatal, but living a normal and vibrant lifestyle can be severely compromised. One in 2,500-3,000 people are affected in some way by mitochondrial disease.

Symptoms of Mitochondrial Disease

Each mitochondrion is an energy factory within the cell. Sugars and fats are imported, broken down, converted and exported as ATP. This highly complex process requires various special protein complexes at different stages for fruition. Mitochondrial diseases are caused by genetic mutations, resulting in deficiencies in one or more of the protein complexes required to make ATP. When a cell is filled with defective mitochondria, not only does it become deprived of ATP, it also can accumulate a backlog of unused fuel molecules and oxygen. Potentially harmful byproducts such as lactic acid can accumulate. A state of lactic acidosis can result, and symptoms can be mild to severe. They include muscle fatigue, aches, and cramps. Meanwhile, unused oxygen in the cells can be converted into highly destructive compounds called reactive oxygen species, including free radicals that cause oxidative stress.

ATP made from mitochondria provides the predominant source of power for muscle cells to contract and supports proper nerve cell firing. The combination of reduced energy availability with mitochondria disease and resulting free radical accumulation in these cells can also give rise to subtle signs and symptoms such as brain fog, joint pain of unknown origin, psoriasis, and fatigue.

When the mitochondrion fails, energy production slows down inside the cell, which is injurious and can even cause the cell to die off. Symptoms all depend on which cells in the body have the malfunctioning mitochondria. Diseases of the mitochondria appear to cause the most damage to cells of the brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems.

Symptoms include:

  • Low energy state and fatigue, with low exercise tolerance level and fatigue on exertion.
  • Low cardiac output, leading to congestive heart failure.
  • Developmental delays below the normal growth curve
  • Gastrointestinal disorders, such as leaky gut, irritable bowl, and constipation
  • Lactic acidosis, with symptoms such as muscle soreness, pain and cramps.
  • Liver disease and congestion, with symptoms such as brain fog, and an inability to tolerate medications or supplements
  • Loss of motor control, coordination
  • Neurological problems
  • Seizures
  • Susceptibility to infection
  • Swallowing difficulties
  • Thyroid dysfunction

Mitochondrial disease can make its appearance at any age, though childhood onset is most common. In many people, this disease is not even diagnosed, as there is a lack of awareness in the medical community and in the public at large.

Mitochondria—Much More Than Energy Factories

There are as many as 3,000 genes that make up one single mitochondrion. In addition to energy production, mitochondria are what contain the rate-controlling enzymes for the biosynthesis of pyrimidine (dihydroorotate dehydrogenase) and the synthesis of heme (D-aminolevulinic acid synthase). In the liver, mitochondria work in a specialized manner to detoxify ammonia, which forms in the urea cycle. Mitochondria are also needed to metabolize cholesterol, for the synthesis of testosterone and estrogen, to metabolize neurotransmitters and for the production and detoxification of free radicals. They perform all of these functions as well as metabolizing or oxidizing the fat, carbohydrates and protein we consume.

Diagnosing Mitochondrial Disease

A scientist searching for mitochondrial diseaseWhen considering a diagnosis of mitochondrial disease, patients must be evaluated very carefully for other diseases as well. Anytime anyone presents with fatigue and low energy state, a complete cardiac, hormonal, hematological, oncological and metabolic workup is needed. When the investigation result is normal, an out of the box differential diagnosis needs to be considered. They include Adrenal Fatigue Syndrome and mitochondrial disease.

Unfortunately, there isn’t a single test developed yet to diagnose mitochondrial disease in the majority of patients. In today’s medical environment oxidative phosphorylation (OXPHOS) enzymology alone is not sufficient for an accurate diagnosis.

Mitochondrial disease is diagnosed by using an integrated approach with multiple means and a detailed history, which would include:

  • Brain imaging
  • Clinical observations
  • Evaluating laboratory results
  • Muscle biopsies

An alert physician with experience in orthomolecular medicine is usually required for a proper diagnosis as it is rare that genetic testing would be adequate for an accurate diagnosis of the disease.

Tests Used for Diagnostic Purposes

There are three different categories of diagnostic criteria:

  • Genetic testing of mitochondrial DNA (mtDNA) and nuclear DNA
  • Metabolic markers of blood, urine and cerebral spinal fluid
  • Muscle testing assessing liver respirometry, CoQ levels, and muscle pathology

Diagnosis is considered positive if two or more tests from two categories show abnormal results.

Defective mitochondria produce large quantities of oxygen free radicals. Comparing patients who have a mitochondrial disorder with healthy people, researchers have found that their blood glutathione level was significantly reduced in white blood cells from mitochondrial diseased patients. This indicates a low level of antioxidant defenses. Measuring blood glutathione levels can be used as a biomarker to monitor the mitochondrial disorders.

Mitochondrial Disorders and Adrenal Fatigue Syndrome

Adrenal Fatigue Syndrome is a stress induced neuro-endocrine dysfunction of the body. The hallmark symptom is fatigue of unknown origin despite normal medical investigation. There are four clinical stages of clinical progression, from mild to severe. In advanced stages, one can be incapacitated and housebound, unable to work or lead a normal social life.

Most people with AFS carry on normal lives and are thus unaware of the potential negative natural progression of this condition until quite late. Allopathic physicians are ignorant of this condition and thus reject its notion. Do not be surprised if your doctor tells you AFS does not exist.

Many symptoms of mitochondria disease and AFS are similar. Fatigue caused by a purposeful down regulation of bodily function to conserve energy in the case of AFS ultimately results in reduced formation of ATP from the mitochondria to achieve its effect. Diseases of mitochondrial dysfunction will result in a body that is unable to produce the necessary amount of ATP. The common clinical pathway for both AFS and mitochondrial disease is fatigue.

Mitochondria Cocktail

Now there are no effective treatments for mitochondrial disease from a prescription medication perspective.

We know that many vitamins are required for synthesis of mitochondrial respiratory chain components. Biosynthesis of the key components of mitochondrial respiratory chain, coenzyme Q, for example, is dependent on vitamins B2, B6, B12, folic acid, pantethine, pantothenic acid, niacinamide and vitamin C.

As well, vitamins B1, B2, B6, niacin, biotin, folic acid, pantethine, and pantothenic acid are important for metabolic pathways in mitochondrial respiration and energy production. Vitamins C, E, niacin and folic acid are excellent scavengers of free radicals once formed. They help prevent mitochondrial oxidative damage and mitochondrial aging.

Many mitochondrial diseases are linked to vitamin deficiencies and can be improved by vitamin supplementation. Proper nutritional supplements targeted to enhance the mitochondria require a nutritional cocktail for best results.

Substrates to be considered for the mito-cocktail include coenzyme Q10, L-carnitine, vitamin C, glutathione, B complex, trace minerals, marine phytoplanktons, pantethine and pantothenic acid, vitamin D, and magnesium.

Subclinical Mitochondrial Disease

You do not have to be diagnosed with Mitochondrial Disease in order to have its weaknesses such as adrenal fatigue/One does not need to have documented and diagnosable mitochondrial disease to suffer symptoms of mitochondrial weakness. Be on the look out for fatigue, a low energy state, insomnia, water retention, low body temperature, reduced thyroid function, reduced gastric assimilation, a weak urine stream, menstrual irregularity, constipation, dry skin, and an unstable mood. Signs and symptoms may be subtle, but they are clearly visible if you are on the alert. They point to a body that has reduced energy output from the mitochondria. These symptoms are similar to those experiencing hypothyroid or Adrenal Fatigue Syndrome. Viewed objectively, it is clear that the body is unable to go into overdrive when called upon. There is not enough fuel. It is like a car that moves slowly despite the gasoline pedal in full open throttle.

As AFS progresses from mild to severe, peripheral organ resistance frequently develops. Thyroid replacement becomes less effective, and organ resistance to cortisol surfaces. In order to achieve the same therapeutic effect, hormonal dosages must be increased. Not everyone can tolerate higher doses, which has many undesirable side effects, including anxiety, heart palpitations, and insomnia.

With organ resistance, fewer hormones are able to reach the mitochondria to facilitate its function. Less energy will be produced as a result. A state of subclinical mitochondrial disease is therefore an inescapable reality for many. Practically speaking, almost everyone in advanced stages of AFS will have certain degrees of mitochondrial weakness and lowered energy output, even if there is an absence of clinical diagnosable mitochondrial disease.

Without fortifying the mitochondria as the adrenals are healing, overall recovery from AFS is often slow and retarded. That is why mitochondrial fortification should be part of every comprehensive adrenal fatigue recovery program. The key is to know when to support the mitochondria, as bad timing can make AFS worse, especially in advanced stages.

Strategies for those with Adrenal Fatigue Syndrome

If you have mitochondrial disease and AFS concurrently with fatigue as the primary symptom, helping mitochondrial function should reduce fatigue in principal. This is true if AFS is in the early stages where fatigue is mild to moderate.

There are caveats, however. A significantly positive energy response with mitochondrial support may mask underlying unresolved adrenal problems. Energy levels can quickly reduce as mitochondrial support is withheld. It is important therefore that mitochondrial and adrenal support be concurrent but balanced. That way, when mitochondrial support is stopped, the adrenals are strong and well healed in order to continue unassisted and avoid any adrenal crashes. Failure to consider this two-pronged balanced approach is a common recovery mistake.

If you are in advanced stages of AFS when fatigue is moderate to severe, or if you are house bound and have little energy to do but basic chores of normal living, embarking on mitochondria supplementation should begin only after the adrenals are stable, internal toxin levels reduced, the liver decongested, and the extracellular matrix cleansed. Dosage should start at a very low dose and titrate upwards to reach therapeutic goals.

Due to the prevalence of paradoxical reactions in advanced AFS, do not be surprised if the body rejects any of these good nutrients, even at low dosages. The more advanced the AFS, the higher the risk. It is not unusual for paradoxical reactions to surface, where fatigue is worsening. Exaggerated positive responses may also surface, resulting in a sense of anxiety, irritability, insomnia, and heart palpitations. Both are undesirable and indicate dosage and delivery system adjustments are needed. Both occur when the mitochondria are overstressed or receptor site sensitivity increased. It is a sign that the body is not quite ready for mitochondrial support.

Catabolic State and Mitochondrial Support

Those who are in a catabolic state where the body is loosing muscle mass and protein and thus weight need to be extremely careful when it comes to mitochondrial support. Examples are those in very advanced stages of AFS, in post-surgery, with large open wounds. They are already in a fragile state within. Many have concurrent low body fluid volume, low blood pressure, temperature intolerance, electrolyte imbalance, delayed food sensitivity and intolerance, receptor sight disorders, liver congestion, extracellular matrix pollution, and severe fatigue.

The body is in a slow-down mode, with all nonessential functions, such as reproduction, shut off in order to conserve energy for survival. That is why most at this stage have low libido and irregular or absent menses. At the same time, the autonomic nervous system is activated and on full alert. As a result, the body is flooded in a sea of norepinephrine and adrenaline. The body is entrenched in a fight or flight mode at this time. The mitochondria is one of the last soldiers standing and working hard to put out the necessary ATP to keep the vital organs functioning, especially the heart, liver and kidneys. Already overworked mitochondrial cannot be stressed further. What the mitochondria needs is rest. It should not be driven to work harder by any nutrients even though they are supportive of mitochondrial function in normal situations.

Nutrients, no matter how good, administered at the wrong time will worsen the overall condition. Recognizing the proper timing is an art requiring extensive clinical experience correlating the state of the body with its ability to tolerate different kinds of nutrients. Failure to consider these factors is a common reason for AFS recovery failure.

Further ramping up mitochondrial function when the mitochondria is already at or close to peak output may lead to reduced marginal return over time at best. Energy output may go up for a short time and then plateau, while anxiety escalates quickly, leading to a state of wired anxiety. Those with AFS may experience adrenal crashes, with extreme fatigue and physical incapacitation. Many are bedridden for days and sometimes weeks.

The glands responsible for Adrenal FatigueTo avoid this, a better strategy is to reduce internal sympathetic tone and its hormones norepinephrine and adrenaline load first through stabilizing and healing the adrenals. This is best accomplished by a comprehensive recovery program using gentle and nurturing natural compounds. Herbs, glandular, and hormone should be avoided. The focus is on building and providing an alternative nutritional safety net for the body to dip into at times when it needs energy in order to stabilize and turn off the sympathetic alarm response. As the body regains its calm with this strategy, symptoms such as anxiety, fatigue, hypoglycemia, and insomnia reduces. Symptoms suggestive of sympathetic overtone commonly seen in advanced AFS such as heart pounding, postural hypotension, lightheadedness on arising, reactive hypoglycemia, and heart palpitations will resolve spontaneously. Once this is achieved, the next step is to make sure the extracellular matrix is cleansed and the liver is not congested. Only after these conditions are met should one proceed on mitochondrial support, which will yield results without the risk of decompensating adrenal crashes.


Mitochondrial disease is a category of different diseases grouped together. The common characteristic is the same—fatigue and low energy state from reduced mitochondrial ATP formulation. Fortunately, there are natural compounds with proven mitochondrial support. Because the cell wall protects the mitochondria, a proper delivery system is of vital importance to ensure bioavailability for this key to any successful mitochondrial recovery program. Sufferers of Adrenal Fatigue Syndrome, especially in advanced stages, invariably have some level of mitochondrial weakness. Recovery faces special challenges with timing, dosage, and delivery system needed for mitochondrial support. Extensive clinical experience is required to avoid adrenal crashes and retarded recovery.

If you are suffering from mitochondrial diseases and have Adrenal Fatigue Syndrome, recovery needs to be personalized. An improper approach to recovery can complicate, deter, or even exacerbate your current state.

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© Copyright 2014 Michael Lam, M.D. All Rights Reserved.