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Chronic Fatigue Syndrome
by June Butlin, MBANT, M.Sc., Ph.D
"This is serious" our news anchor told me privately." You're starting to repeat yourself all the time. People are noticing. I'm worried about you".

"I'm just so busy that I'm forgetting stuff," I told her. I didn't bring up the swollen glands, the unbearable headaches that no medicine could help, and the pain in my joints, which was so intense that I'd often wrap bandages around my wrists and ankles at night to keep them from moving. I was trying to look and act like the old Tim. Everything was just fine. That was what I wanted everyone, especially myself to believe". (1)

The worst was to come. Tim was yet to realise that he would suffer interminably from exhaustion, loosing his intellectual capacity, career as a news director, social life, friends, self-esteem and his favourite recreational activity of flying.

He is suffering from an insidiously, debilitating and bewildering disease called Chronic Fatigue Syndrome, which is beyond the comprehension of many people. The disease varies itself in intensity and duration, and is characterised by fatigue, muscular aches and pains, headaches, myalgias, weakness, sore throats, swelling, depression, fever, sleep disturbances and tenderness in the lymph nodes. Also cognitive impairment, poor concentration, loss of memory function, depression, anxiety, irritability, panic, sensitivities to foods, drugs, alcohol and chemicals and balance problems. (2-4)

Chronic Fatigue Syndrome is not a new disease and references to similar conditions go back to the 1860's under the names of "Neuromyasthemia", "Yuppie Flu", "Post Viral Fatigue Syndrome", "Chronic Immune Deficiency Syndrome", and "Myalgic Encephalomyelitis". Others such as "Iceland Disease", "Royal Free Disease", "Tapanui flu" and "Akureyri Disease" are named after locations where large-scale outbreaks of the disease occurred. All of these conditions are symptoms of underlying causes, which have not yet been fully identified, and the preferred name is Chronic Fatigue Syndrome because it characterises the major symptom of the illness without referring to aetiology.

Just as Tim was initially in denial of his illness many doctors suffer from the same problem. They refuse to recognise the condition as they can't find anything physically wrong, and the diagnosis usually given is psychological in nature. Many doctors and other people consider those suffering from chronic fatigue syndrome as malingerers, hypochondriacs or hysterical. However, the facts are that 200,000-500,000 people in America and 150,000 people in Great Britain suffer from CFS including an estimated 24,000 children and young adults with many more cases going undiagnosed. Younger patients suffer greatly because of the impact the illness has on school attendance, lack of understanding amongst teachers and educational psychologists, and social workers who seem to attribute the problem to family dysfunction. The incidence of CFS is three times higher in females than males, but can affect people of all ages, races and socio-economic background. The highest cases seem to occur in Caucasian women aged 25-45 years of age.(5a,5b)

The average patient suffering from chronic fatigue syndrome has been ill for a duration of four years or more and is significantly disabled ie. unable to work or perform normal tasks of daily living. The insurance industry has earmarked this condition as one to be disputed strongly for benefits. Social security benefits frequently require three applications and a hearing over a period of two to three years in order to obtain benefits. Those suffering from CFS have often employed numerous traditional and alternative medical therapies without benefit before being diagnosed. Several studies have suggested that less than 10% of subjects with chronic fatigue improve with standard clinical approaches over time with the majority remaining significantly impaired over long term follow up.(5c)

The increasing numbers of people suffering from chronic fatigue, pressure groups, and the mass amount of research data have forced the "Centre for Disease Control" to produce an operational definition for chronic fatigue syndrome. The Centre for Disease Control came up with two criterion. The first criteria is " New onset of persistent or relapsing, debilitating fatigue or easy fatigability in a person who has no previous history of similar symptoms that does not resolve with bed rest, and that is severe enough to reduce or impair average daily activity below 50% of the patient's premorbid activity level for a period of at least six months". The second major criteria is "not meeting the criteria for other medical or psychiatric disorders and is characteristically worse following levels of physical exertion that has been easily tolerated in the past and absence of around thirty conditions including chronic psychiatric disorders, post exertion malaise, sore throats, headaches, joint pain, sleep disturbances or swelling and tenderness of lymph nodes.(6a) The medical and psychiatric disorders also include:

Endocrine malfunctions: hyperparathyroidism, diabetes millitus, adrenal disorder, thyroid disorder and panhypopituitarism.

Neurological: anxiety disorder, post traumatic stress disorder, somatoform disorder, multiple sclerosis, amyotrophic lateral sclerosis, depression, myasthenia gravis, atypical narcolepsy.

Infectious: HIV, coccidiomyycosis, post-polio syndrome, subacute bacterial endocarditis.

Metabolic: toxic exposure, anaemia, hypercalcemia, hypomagnesemia.

Immune: inflammatory bowel disease, autoimmune disorders, severe allergies, sarcoidosis. 6b

CFS is therefore a clinically defined condition, but there is still little scientific proof due to the lack of definitive laboratory tests. One laboratory test however is worthy of recognition and this is Dr Costa's study in 1995 investigating brain perfusion abnormalities in patients with CFS. An initial pilot study revealed widespread reduction of regional brain perfusion in 24 CFS patients compared with 24 normal volunteers. Hypoperfusion of the brain stem was marked and constant (0.72+/-0.05 vs 0.80+/- 0.04, p<0.0001). The follow up study tested whether perfusion of the brain stem in CFS differed from that in normal patients with major depression and others with epilepsy. 146 subjects took part of which 40 were normal volunteers, 67 patients with CFS including the 24 in the pilot study, 16 patients with no psychiatric disorders, 13 with CFS and depression, 14 with CFS and other psychiatric disorders, 10 epileptics, 20 young depressed patients and 9 elderley individuals.

Brain perfusion ratios were calculated using 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) and single photon emossion tomography (SPET) with a dedicated three-detector gamma camera computer system (GE Neurocam). The results confirmed that there was brain stem hyppoperfusion in all CFS patients. Also the 16 CFS patients with no psychiatric disorders and the initial 24 patients in the pilot study showed significantly lower brain perfusion (0.71+/-0.03) than did depressed patients (0.77+/-0.03 ANOVA,p<0.0001). Thus patients with CFS have a generalised reduction of brain perfusion with a particular pattern of hypofusion of the brainstem. This method of diagnosing is expensive and not readily available, however it may eventually be used as a scientific proven diagnostic test. Measures taken to improve blood circulation may improve blood perfusion as well as the mental confusion and exhaustion prevalent in all those suffering. (7)

Diagnosis therefore usually occurs by the process of elimination and a patient may see specialists in several fields including neurology, immunology and psychiatry before getting a diagnosis of chronic fatigue syndrome.

The research on individual and multifactorial causes of chronic fatigue syndrome seems endless, as any underlying factors impacting energy levels need to be considered.


The main areas of research focus on the major factors of viruses, low immunity, stress, depression, impaired liver function, environmental illness, iatragenic
co-factors, mitochondrial abnormalities and hypothalamus pituitary adrenal axis. Other factors to consider are candida albicans, leaky gut, hypothyroid, hypoglycaemia, anaemia, nutritional deficiencies, food allergies, sleep disturbances, emotional problems, breathing, posture and lack of exercise.


Focussing on the main areas of research, underlying viral aetiology of the condition is well established although there are different views as to the viruses responsible. Britains favour enteroviruses such as coxackievirus, ECHO virus, and polio virus, and the Americans favour the Epstein Barr virus, including herpes simplex cytomegalovirus and varicella zoster.8-10 There is also a retrovirus connection, which was discovered by researchers at the Wistar Institute in 1990 who found a possible link between CFS and Human T Cell Lymphotropic Virus 2 (HTLV). Retroviruses are associated with certain leukaemias, lymphomas and chronic diseases of the central nervous system.11-12 All these viruses have the ability to remain dormant in the body, after the initial infection, ready to proliferate when the immune system is compromised.

Immune system abnormalities are therefore associated with CFS ( Table 1(Ed: not available yet)(13)

Elevated levels of antibodies to viral proteins
Decreased natural killer cell activity
Low or elevated antibody levels
Increased or decreased levels of circulating immune complexes
Increased Interleukin 2 levels
Increased or decreased interferon levels
Altered helper/ suppressor T cell ratio



Researchers hypothesise that certain components of the immune system in patients with chronic fatigue syndrome may be overactive, underactive or both.
The most consistent abnormality is a decreased number or activity of natural killer cells, which can destroy cancer and viral cells. (14) Also a reduced ability of the lymphocytes to function, possibly resulting from altered production of interferon levels, which help the differentiation and proliferation of the lymphocytes. When interferon levels are low, viral infection is likely and when interferon levels are high, the symptoms are the same as CFS and include memory deficits, muscle aches and lethargy. Similar affects can occur with increased amounts of Interleukin (2). Low levels of specific immunoglobulins are also reported, which are closely associated with allergies, and the presence of elevated antibodies to viral proteins.(15-22)

An interesting area of research is the impaired activation of the hypothalamic- pituitary- adrenal axis (HPA), which is the hormonal centre of stress control. Demitrack reached this conclusion when he found that CFS sufferers had a reduced production of the adrenal hormone cortisol. Many sufferers do recall a critical period of stress such as emotional, physical and spiritual stress, overwork, sleep disruption and severe tension before they developed the symptoms of chronic fatigue. This chronic stress leads to impaired communication between the regulatory hormones that affect the adrenal glands. This in turn leads to low cortisol production which causes debilitating fatigue, especially after exercise, joint and muscle pain, enlarged lymph nodes, exacerbation of allergic responses, and disturbances of mood and sleep. Nutrients to support adrenal function include vitamin C, vitamin B6, zinc, magnesium and pantothenic acid. All of these nutrients play a critical role in the health of the adrenal gland as well as the manufacture of adrenal hormones. During stress the levels of these nutrients decrease. For example during chemical, emotional, psychological or physiological stress, the urinary excretion of vitamin C is increased. Extra vitamin C in the form of supplementation and an increased intake of vitamin C rich foods such as oranges, broccoli and kiwi are recommended to keep the immune and adrenal glands strong. Pantothenic acid is needed in high levels during stress and a deficiency will result in adrenal atrophy characterised by fatigue, headache, sleep disturbances, nausea, and abdominal discomfort. Pantothenic acid is found in whole grains legumes, cauliflower, broccoli, salmon, liver, sweet potatoes, and tomatoes. Extra vitamin B6, zinc and magnesium can be taken in supplement form in the appropriate dosage of B6 50-100mg, zinc 20-30mg, and magnesium 250-500mg. The research on the hypothalamic- pituitary-adrenal axis connects well with Dr. Costa's study and the immune system studies. Linked with stress is depression, which is said to be the commonest cause of chronic fatigue in the absence of any pre-existing physical condition.(23)

Energy is produced in the mitochondria of each cell and therefore changes in mitochondrial function will also contribute to chronic fatigue. These changes can be due to deficiencies in amino acids, enzymes, minerals and vitamins, particularly B vitamins. In one study CFS patients showed increased 2'-5' A synthetase and R. Nase L activity leading to a depletion of cellular ATP, the energy molecule.(24)

Also indicated in CFS are iatrogenic co-factors including prescription drugs: antihypertensives, anti-inflammatories, birth control pills, antihistamines, corticosteroids, tranquillisers, steroids and antibiotics in particular. Antibiotics may be lethal as they can last in the body up to eighteen months, and are capable of affecting DNA if given for longer than two weeks. They also have a role to play in candida albicans, leaky gut and allergies causing weaknesses in the body.

There are close connections between CFS, fibromyalgia and multiple chemical sensitivities. (25-27) The only difference in diagnostic criteria between CFS and fibromyalgia is the requirement of musculoskeletal pain in fibromyalgia, and chronic fatigue in CFS. A person suffering from multiple chemical sensitivity can also display all the symptoms of CFS and fibromyalgia. Multiple chemical sensitivity (MCS) is defined as an acquired disorder characterised by recurrent symptoms referable to multiple organ systems, occurring in response to demonstrable exposure to many chemically unrelated compounds at doses far below those established in the general population to cause harmful effects. There are approximately 70,000 chemical compounds (zenobiotics) in current commercial production occurring in food, air, water, and pharmaceuticals. Single, multiple, or combinations of these chemicals play havoc in the body and can react with chromosomes in our cells to cause damage to DNA. One example is the chemical used in sheep dips causing organophosphorous pesticide poisoning resulting in similar symptoms to CFS and fibromyalgia. (28) Other examples are inorganic pollutants including ozone, carbon monoxide, nitrous oxide, sulphur dioxides, heavy metals and other metals. Organic pollutants include all pesticides, formaldehydes, solvents such as toluene and xylene, drugs, terpenes, cleaning chemicals, cigarette smoke, combustible products, consumer products such as clothing, building materials and hygiene products and biological compounds. The most toxic organic pollutants are those classified as halogenated aromatic and aliphatic hydrocarbons. Most of these chemicals are fat-soluble and the enzymes for the Phase 1 and Phase 2 liver detoxification pathways are responsible for breaking these toxins down for easier elimination to the digestive tract, via the gall bladder. However if the liver enzymes are not functioning the toxins will be stored in the body's cells, particularly in the adipose tissue. Fevers or fasting may result in the release of large quantities of these fat-soluble pollutants from the storage sites into the systemic system causing toxic poisoning. This could account for the high incidence of chronic fatigue onset after fevers.(29) If a person is affected by chemicals it may be wise to give the liver support through foods, supplements and cleansing diets.

Successful treatment of CFS requires comprehensive diagnosis taking into account medical history and study of the body's systems. The procedure involves eliminating the elements causing fatigue, and will include the major factors we have discussed as well as checking for other factors such as candida albicans, leaky gut, hypothyroid, hypoglycaemia, anaemia, nutritional deficiencies, food allergies, sleep disturbances, emotional problems, breathing, posture and lack of exercise. Appropriate treatment can then be given for the person with CFS based on their biochemical individuality.

A good starting point for any CFS sufferer would be to look at their diet as energy levels are directly related to nutrient intake. Foods to avoid are those containing hormones, antibiotics, pesticides, fertilisers, artificial preservatives, colours, irradiation and those that are genetically modified as they are toxic to the body. Also foods that are tinned, frozen or cooked with microwaves should not be used as they are depleted in nutrients and leach vital life force energy out of the person which is the energy needed for healing. Alcohol, coffee and tea should be avoided as they contain toxins and deplete the liver of beneficial nutrients and can cause damage during their detoxification process.

It is recommended that the patient follows a well balanced, organic, wholefood, nutrition programme which is high in fresh foods. The diet should be rich in vegetables, wholegrains and pulses containing soluble and insoluble fibres, fish nuts, seeds, herbs, seaweed and natural seasonings. It should also be low in saturated fat and salt. Lots of filtered water should also be taken. This will help to cleanse the body of its toxic overload and avoid further damage from the chemicals found in processed foods and drink.

Useful foods to include are the Omega 3 and Omega 6 fatty acids found in flaxseed and fish oils, which enhance the immune system.30 The active ingredient gamma linolenic acid has been shown to help patients overcome severe fatigue, muscle pain, depression and confusion. Detoxifying foods are also important, examples of which are organic vegetable juices, pears, blueberries, strawberries, papaya and apples. Also sprouts, asparagus, mustard greens, radishes and cruciferous vegetables such as brocolli, Brussels sprouts, cauliflower and cabbage. There is an immune enhancing soup from China that can help someone suffering from chronic fatigue. The recipe contains whole astragalus root with onions, garlic, ginger, brown rice and fresh vegetables with miso to boost nutrient content and flavour. Sea vegetables including wakame, kombu, hijiki, arame and dulse are beneficial for the maintenance of bone marrow, thyroid gland and thymus. Also garlic containing allicin, which has potent antibacterial, antifungal, anti-inflammatory, antiviral, anti tumour and antiparasitic properties (31)

Supplementation is also important, as almost any nutritional deficiency will result in chronic fatigue. Amongst the important ones that enhance the immune system are beta carotene, retinol, pantothenic acid, pyridoxine, riboflavin, D-alpha tocopherol and ascorbic acid. Cyanocobalamin, vitamin B12 is also of vital importance as it is associated with optimal functioning of the immune system by helping with the production of red blood cells and transporting oxygen to the tissues . Adaptogenic plants are especially good at stimulating the body's immune system by increasing CD4 counts, interferon production, macrophage activity and natural killer cell action. Examples of adaptogens are Astragalus Membranaceus (Astragalus), and Eleutherococcus Senticosus (Siberian Ginseng). (32)

Glycyrrhiza Glabra has anti viral properties and a role to play in the HPA axis as it increases cortisol levels by blocking the enzyme that breaks it down. The whole root must be used as deglycyrrhizinated acid (DGL) has had the glucocorticoid potentiating glycyrrhizic and glycyrrhetinic acids removed (33-34)

Supplements specifically involved in fatigue are iron, folic acid B vitamins and magnesium. Magnesium is needed to produce ATP (energy) and it does this in two ways. In the aspartate form it feeds into the Krebbs cycle to provide ATP and in the citrate form it is a component of the Krebbs cycle. It also helps to calm the body aids relaxation and sleep, improves memory and reduces irritability 35. Co Q 10 (Ubiquuinone) is a co-factor in the electron transport chain in the mitochondria involved in the synthesis of ATP (energy), and is essential for the health of the tissues and organs.

Research continues to help those suffering from this clinically perplexing disorder and a new supplement called NADH offers new hope for CFS. Stabilised, oral NADH has been developed by Professor Georg D. Birkmayer, M.D PhD. and was patented in 1993. NADH is the biological substance nicotinamide adenine dinucleotide, which is a metabolyte of niacinamide, the active co-enzyme form of vitamin B3. (36)

It is an important molecule for producing energy in the body as it is the main carrier of electrons during the oxidation of macronutrients, which produce energy in the mitochondria of each cell. Each molecule of NADH can produce 3 molecules of adenosine triphosphate (ATP), the energy compound.


Simplified Diagram of the stages of Metabolism that lead from food to NADH (37)
 


Food


Protein Carbohydrates Fat


Amino Acids Glucose Fatty Acids


Pyruvate


Acetyl CoA


Krebbs Cycle


NADH


Oxygen ATP


Water


All cells contain NADH and the quantity is dependent on the amount of energy that the cell requires. For example the heart muscle which has to contract 86,400 x a day needs 90 milligrams and the brain and muscle tissue 50 milligrams. The more NADH the cell has available the more energy it can produce, and therefore an invaluable supplement for CFS. However as NADH is a co-enzyme (helper enzyme) it is also able to amplify other enzymes to be catalysts in many different biochemical reactions within the body to help other factors involved in CFS. It aids immunity by being involved in the formation of reduced glutathione, the cell's major antioxidant, to prevent free radical attack. Reduced glutathione, in turn, provides further support for the immune system by regenerating the vitamin antioxidants C and E. 38 NADH also helps to repair DNA damage preventing detrimental changes on a cellular level, and aids in the production of dopamine, adrenalin and seratonin to lift depression, aidsco-ordination and improves mental function. (39-41)

An approved FDA ongoing study, which started in 1996, is being conducted by George-Town University to evaluate the efficacy of NADH, administered orally to a group of patients with CFS, in a double- blind, placebo controlled, crossover study. 26 patients who fulfilled the Centre for Disease Control's criteria for CFS completed the study. Medical history, physical examination, laboratory studies and questionnaire were obtained at weeks 4, 8 and12. The subjects received either 10mg of NADH or a placebo for 4 weeks and then had a break for four weeks before taking the alternate regimen for four weeks.

The results showed that 31% of the patients responded favourably to NADH and that there were no side effects. A further open label follow up study revealed a 72% improvement. The main response of the patients was characterised by improvement in fatigue, decrease in symptoms and improvement in quality of life.(42)

In the follow up study Dr. Bellanti at the American College of Allergy, Asthma and Immunology found that 75% of the patients showed elevated levels of 5-HIAA the major breakdown product of seratonin, which is involved in brain chemistry. When treated with NADH 70% of the patients returned to a normal range. These results suggest that the measurements of urinary 5-HIAA may be a useful predictive marker of disease activity in CFS patients, and could also provide an objective measure of improvement following therapy with NADH .44 The results of these studies clearly indicate that NADH may be a valuable adjunctive therapy in the management of CFS.

Of interest NADH is also effective in people suffering from Alzheimer disease, Parkinson's Disease, depression, protection against the side effects of the drug Azidothymidine used for sufferers of Aids, immune stimulation and DNA (deoxyribonucleic acid) repair.

NADH will not work for all those suffering from chronic fatigue syndrome as the disease vary in intensity and frequent relapses or worsening of symptoms are common. Also the duration of symptoms vary in individual cases. It is important to realise that every person is different biochemically and anyone suffering from chronic fatigue syndrome should be treated as a person with a diagnosis of chronic fatigue syndrome and not treated as the diagnosis. I have included a case study of my client Mark, who suffered from CFS along with the recommendations that he followed to achieve health and fitness. NADH was a very useful supplement that Mark took in the later stages of his recovery, which without a doubt helped him to regain his full vital energy back.

Mark's Case Study on Chronic Fatigue Syndrome:
The clients I love to work with are those who are dedicated to improving their own health and are prepared to do what is necessary to achieve this. These clients see health as their own responsibility and are usually brilliant at giving constructive feedback between consultations. This feedback is vitally important and acts as a diagnostic tool, to help me guide my clients to recover their health.

Mark is one such client, who came to me in sheer despair. He was suffering from severe tiredness, a racing heartbeat and continuous noises in his head. The doctors and specialists had treated him for tinnitus, labarynthitis, hyperventilation syndrome, depression and menieres disease. There had been very little success with any of these approaches.

Taking Mark's history into account I found that he had a genetic background of poor immunity and had been a very weak child. In his twenties he worked extremely hard to achieve a successful computer consulting business. He also played hard, going out most evenings, drinking alcohol, and staying up late. He swam competitively, raced his mountain bike at the weekends and camped regularly in extreme conditions. On the camping trips he drank water from flowing streams, which as Mark says, was not very clean, and often contaminated. His diet consisted of high meat and dairy, and lots of fast and processed foods of a very unbalanced, nutritional nature.

By the age of thirty Mark's health was in decline and he suffered from frequent infections and colds, and felt under par most of the time. Finally, his energy seemed to seep out of his body and he began to sleep for 18 hours a day. This lasted many weeks, and when the worst was over, it left him feeling exhausted, depleted, shaky and suffering anxiety and panic attacks. He was unable to relax, became sensitive to the cold weather, developed tinnitus and an inability to judge distances.

Physiologically the case study revealed major problems in digestion and elimination, hypoglycaemia, adrenal exhaustion, hypothyroidism and macro-mineral imbalance. Psychologically Mark felt depressed and yearned to be in optimum health in order to follow his sporting activities and work full time in his business. He was unable to do any sport except for walking, as exercise left him feeling totally depleted for days afterwards. These repercussions eventually made him fearful of any exertion.

There were seven phases to Mark's treatment strategy each building upon the preceding phase and supporting the proceeding phase. The first phase was to make sure that Mark had adequate nutrients in the diet from protein, carbohydrate, fat, vitamins, minerals, oxygen and water This was achieved by placing Mark on a good quality, organic, food regime, and walking in the fresh air each day. A general anti-oxidant supplement, vitamin C, a multi vitamin and mineral without iron and copper, and a multi B complex were also taken.

The second phase was to target the hypoglycaemia by eating a protein breakfast and five small meals each day, four of which were to contain vegetables. This high vegetable diet would also help to counteract the macromineral imbalance. Once these two phases were established the body was able to start its own healing process and the specific problem areas could then be identified and supported.

Mark's immune system was clearly depleted and the kinesiology test indicated that he was in a post "Epstein Barr" viral state. The Epstein Barr virus is often associated with chronic fatigue and reduced immunity. So the third phase was to activate the body's immune system to mobilise its natural defence mechanisms, and to clear the body's detoxification pathways. The areas targeted were the skin, colon and liver. Skin brushing was used to remove the dead skin cells, which allowed the toxins to be eliminated from the skin more easily. The colon and liver were cleansed with herbs and a special drink taken each morning made from olive oil, citrus juice, garlic, ginger, milk thistle and dandelion.

This article first appeared in Positive Health Magazine

© Copyright Positive Health Magazine 2001
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