Explaining the Root Causes of the Chronic Fatigue Type Syndrome and their Reversal

A. What is the difference between Chronic Fatigue Immune Dysfunction Syndrome and simply chronic fatigue as a symptom?

The former is a complex and serious illness that affects many body organ systems. The exact cause has not been elucidated and I think that is because there are multiple causes and most traditional researchers think in a very linear fashion, looking for that "one x factor" that is the cause of an illness. It has a lot to do with the way our minds were trained to think and analyze things during our formative training period.

The CFIDS syndrome is characterized by incapacitating fatigue that manifests itself as very severe exhaustion, leaving the individual without the physical abilities to carry out the normal functions of every day life. This is the type of illness that can last for many years. There is a great deal of confusion about the diagnosis of this disease because it can look like so many other illnesses that have overwhelming fatigue as part of their complex. Illnesses like Multiple Sclerosis can start out looking like it, as well as Fibromyalgia, Lupus, Lyme Disease and certain post-viral syndromes. In Europe this illness goes under the name of myalgic encephalomyelitis.

The simple term "chronic fatigue" can be a symptom and not a specific illness with specific characteristics. There is no doubt that, in my practice, for every patient that fits the CDC criteria of CFIDS, there are 100 that suffer with a significant degree of exhaustion and fatigue but without all the other criteria that are needed to make the CFIDS diagnosis. The real bottom line here is not the name given to what a patient is suffering with, but determining the cause of it.

B. How is CFIDS diagnosed in a clinical way?

In order to clinically diagnose this entity, one must do a thorough history and physical examination, a mental status examination and laboratory tests to identify any underlying conditions or other specific diseases. Diagnosis can be made if the patient meets the following criteria:

A clinically evaluated and unexplained chronic fatigue that has the characteristics of being relapsing and quite persistent and is of new onset rather than lifelong. It is not the result of any specific ongoing exertion in the patient's life, is not relieved by rest, and definitely results in a substantial reduction in previous levels of occupational, educational, social or personal activities.
There also must be four or more of the following symptoms present:
a. short-term memory problems

b. concentration problems

c. sore throat

d. tender lymph nodes

e. muscle pain

f. multi-joint pain without swelling or redness

g. headaches that are of a new type, pattern or severity

h. unrefreshing sleep

i. post exertional malaise lasting more than 24 hours

All of these symptoms must have persisted or recurred for a period of six months or more and must not have pre-dated the fatigue.

On the other hand, the patient with a complaint of chronically being fatigued can be just as sick or sicker and not have all of these specific symptoms that make up the criteria for making the diagnosis of CFIDS. These patients can have only some of the symptoms and a series of others like: indigestion, eczema, flatulence, abdominal pain, visual problems, lost libido, vulvadynia, chronic yeast infections, hair loss, postnasal drainage, irritable bowel syndrome, constipation, chronic cough, profuse sweating, tinnitus, parasthesias, tremors, depression, anxiety, PMS, fibrocystic breast disease, chills, fever and many more. Such an illness is still very devastating, although it is not called CFIDS. It is necessary to identify the root causes of the illness and begin a healing process to remove the impediments that are preventing the body from its natural ability to heal.

C. Who gets this type of illness?

Both the CFIDS and the 'CFS' illness can affect individuals from all age groups and socio-economic strata. The majority of the individuals that suffer with this illness are women between the ages of 25 and 45. Some estimates have approximated that there are between 200,000 and 500,000 people in the US who have this illness we call CFIDS and an enormous number suffer with the other problems of chronic fatigue.

D. How are the root causes unravelled?

It is proposed by several investigators that CFIDS is an illness secondary to damage to the 2'5'a-synthetase system of cellular enzymes. At first it was thought that only a viral insult could activate the immune system, thereby causing an increase in alpha interferon and an upregulation of that enzyme system, followed by an increase in the RNAase. This would then lead to a decrease in the efficient operation of the messenger RNA and therefore an inefficiency in the process of the production of cellular protein. This then leads to a decrease in cellular metabolism, followed by a diminution in the production of ATP.

Since every cell in the body can be involved in this process, one will see the following things happening:

muscle effect: weakness and fatigue
kidney effect: abnormal function
colon effect: obstructive characteristics
liver effect: abnormal liver function
heart effect: arrhythmias and heart failure
ear effect: hearing loss
eye effect: muscle weakness and retinal problems
In addition to the above, one might see ataxia and seizures due to either neurotoxicity or a secondary effect of alpha interferon on the brain. There can also be secondary effects on the production of TSH and CRH, which are hypothalamic hormones that are suppressed in the process. The effects of this might be a decrease in the output of thyroid hormones and their sequelae, and the symptoms of dysautonomia from depression of CRH.

Because of immune activation there is also the development of sensitivities to varied environmental factors such as foods, chemicals and inhalant allergens. This we call allergy and chemical sensitivity.

Since the original theory of the viral etiology for this process, we have begun to study the possibilities that toxins such as heavy metals and chemicals can play a role in the activation of this 2'5a-synthetase system. This allows us to evaluate the patient to find not only the root causes of these illnesses but the areas of dysfunction that lead to the primary symptoms the patient suffers with.

The following is a list of the comprehensive evaluation that is done at our center to fill in the puzzle pieces of these "syndromes."

Toxic Chemical Evaluation
Toxic Heavy Metal Evaluation using a "challenge" technique.
Viral Studies using PCR technology
Mycoplasma PCR Evaluation
2'5A Synthetase System Evaluation
RNAase Evaluation
Free Radical Cytokine Evaluation
Various Immune Studies
Apoptosis Index
Cell Cycle Analysis
Sensitivity and Allergic Evaluation
Gastrointestinal Evaluations
Nutritional Biochemical Evaluations
Oxygenation and Carbon Monoxide Characteristics
Oxidative Stress Studies
Hormonal Evaluation
Detoxification
Intestinal Permeability Characteristics
Peripheral Nervous System Evaluation (if needed by history)
Central Nervous System Evaluation (if indicated)
Summary of the Origins of this Illness

This illness probably begins with a genetic predisposition. This can present a problem with the ability to detoxify as it relates to the liver or to some HLA type. There may be problems with the antioxidant enzyme systems. We know there is a combination of both genetic and environmental influences that lead to this type of illness. I think the toxins, subclinically at a molecular level, either through oxidative stress mechanisms or through direct damage to the cellular structures themselves, lead to the downhill spiral we call chronic fatigue.

Whether there are infectious agents like viruses or cell-wall deficient organisms like mycoplasma that play a role in this illness varies from patient to patient. The question is whether the infection came first or became a problem secondary to the lack of quality immune function. It probably can happen both ways. The bottom line is that the mitochondria are injured and there is a downregulation of cellular functioning in all the organ systems leading to these illnesses.

E. How does the healing process begin?

This is a very complicated part of this discussion because the healing of the human body in this very complex disease process is multifaceted. It is almost impossible to offer a comprehensive therapeutic protocol to help any patient with these illnesses because protocols must be very individualized. In general, therapy characteristics are: a) removal of toxic impediments to healing that are found during the evaluation, b) provision of the nutritional fuel the body needs to have the cells working in an efficient manner, c) implementation of a program that will heal damaged organs, d) correction of oxidative (free radical) overload, e) correction of hormonal imbalances, f) destruction of living, multiplying pathogens, g) correction of oxygenation pathology, h) correction of any maldigestion or malabsorption, i) identification of any allergic triggers, j) improvement of detoxication, etc.

In general, some types of therapy we use are:

a. Intravenous Nutritional Therapies (various types)

b. Ozone Therapy

c. Ultraviolet Blood Irradiation Therapy

d. Antimicrobial Therapy (herbal and drug)

e. Transfer Factor

f. Thymus Therapy

g. Oxygen Therapy

h. Chelation Therapy

i. Sauna Depuration Therapy

j. Allergy Desensitization Therapy

k. Environmental Controls

l. Mitochondrial Upregulation Therapy

m. Upregulation of the liver detoxication system

n. Therapy for cerebral dysfunction

o. Antioxidant Therapy

F. An Innovative Theory Concerning Low Level Carbon Monoxide Toxicity In Patients With CFS, Etc.

We are not talking here about acute toxic exposure to carbon monoxide. There are many sources of carbon monoxide both outside and inside the body. The burning of any fuel produces it. The primary sources are inside buildings where it causes much more concern than outside exposure to this compound. The three most important areas of concern are tobacco smoke, automobile exhaust and gas ranges. Other items are oil and gas furnaces, water and space heaters, ovens, wood and coal stoves, wood and coal fireplaces, gas log inserts and explosives.

Internally, the body produces carbon monoxide from chemicals that get into our bodies: formaldehyde and dichloromethane. It is difficult to monitor CO because it is a colorless, odorless and tasteless gas.

The endogenous form of CO (from inside the body) is also a major problem. Any sort of stress increases the production of the enzyme hemeoxygenase. This enzyme breaks down into iron, biliverdin and CO. The different stresses that have been shown to stimulate this enzyme are heat, light, sound, odors, electromagnetic fields, infection, toxins, physical stress and psychological stressors. These stressors lead to chronic low level CO exposure. This enzyme is responsible for about 75% of the body's production of CO. The other internal sources of the production of CO are the auto-oxidation of phenols, flavonoids and halomethanes, and the photo-oxidation of organic compounds and the lipid peroxidation of lipid membranes.

The measurement of endogenously produced CO is done by measuring it in exhaled breath or indirectly using HO-1 measurements in different organs. The old standby of measuring carboxyhemoglobin only measures the percent of hemoglobin. that is bound to CO. This is commonly normal in individuals with low level toxicity.

G. What are the symptoms of low level CO poisoning?

The CO in the body can be stored until it has left the body. CO binds much more tightly to heme than oxygen does. In so doing it reduces the number of binding sites that are available for oxygen to bind to. Because of this, the oxygen binds more tightly. In the muscle tissue, the CO binds more tightly to myoglobin than the oxygen does, thereby interfering with the utilization of oxygen during exercise. This is especially true when it comes to cardiac muscle.

CO can interfere with the function of the cytochrome systems which are needed for oxidative metabolism and detoxication. Because CO interferes with the oxygenation of all tissues, any organ can be affected, but the brain, heart and lungs are the most commonly affected. The most common symptoms of acute CO poisoning are the same as those of chronic CO poisoning, the difference being that they can vary over time and can wax and wane in response to the external environment.

The most common symptoms:

headache
fatigue and weakness
muscle pain and cramps
nausea and vomiting
diarrhea
confusion and memory loss
lack of coordination and dizziness
chest pain and tachycardia
difficult or shallow breathing
changes in sensitivity of hearing, vision, smell, taste and touch
Because these symptoms are common to so many disorders, there is no single one of the them that is diagnostic. It is important for the physician to be alert to these symptoms and think about the possibility of low level CO toxicity in patients who present some of these complaints.

H. Biomarkers of Chronic Low Level CO Toxicity

The most sensitive study of the process of low level toxicity is the triple-headed SPECT scan of the brain. This study will reveal decreased blood flow to areas of the brain that improve with special forms of oxygen therapy. Another method of showing this pathology is to look at the blood gases in the patient. One has to look at both the arterial and venous blood gases to be accurate; the venous (pVO-2) is a measurement of the amount of oxygen found in the blood at the vein in the elbow area without the use of a tourniquet. This is not the same as mixed venous oxygen which is done at a central line. The normal value for this is in the neighborhood of 25mm of rig. Some of the patients with CFIDS and MCS, as well as Fibromyalgia, have levels that can be as high as 50. Therefore, this is another simple marker for the measurement of the syndrome of low level CO toxicity. It also allows for easy follow-up of the therapy.

I. Treatment for CO Toxicity

There have only been anecdotal reports of amazing improvements in patients with either CFS, MCS or Fibromyalgia using the process called Extended Normobaric Oxygen Therapy (ENOT). It is the use of 100% oxygen over prolonged periods of time, using special equipment so that only pure oxygen gets to the patient. It does take many weeks of daily therapy to see the results, but they can be dramatic. Keep in mind that this is not a cure for these conditions - it is only a temporary solution to the patient's symptoms while the physician works on the "healing of the body" using the evaluation and therapeutic techniques that have been previously outlined.

J. The Correlation Between CFS, MCS and Fibromyalgia

There appears to be a very close relationship between these three conditions. Quite often, the same patient can suffer with all three of these syndromes and other times not. The most important aspect of this relationship is that these patients almost always suffer with a fatigue-like illness. A very important paper was written in 1994 that correlated these three syndromes (Buchwald and Garrity).

The results showed that the three patient groups were quite similar in demographic characteristics and in the presence of similar symptoms.

It may be that the same root causes are at play in all three of these illnesses. It has been my clinical experience over the last ten years that this is in fact, the case. Case histories of patients with all three of these syndromes all have similar root causes to their illnesses. Even more important, these illnesses can be reversed by dealing with their multifaceted nature and their root causes.

K. Case histories

This patient was a 39-year-old caucasian female who presented to our center with a history of more than 20 years of multiple organ system complaints. The following are a list of those complaints that also fit the CDC criteria for the CFIDS:
chronic fatigue
Fibromyalgia pain
eczema
itching and watery eyes
chronic post nasal drainage
chronic sore throats
chronic bad taste and breath
wheezing
chronic dry cough and mucus production
night sweats
abdominal cramping, flatulence and diarrhea
muscle pain
morning muscle stiffness
leg cramps
restless legs
hypersomnia
difficulty in concentration
sensitivity to chemicals
sensitivity to dust, pollens, molds and foods
headache
During the physical exam it was found that the patient had multiple trigger points in various areas on the back, but not the criteria for fibromyalgia. The only other significant finding was that of obesity.

The laboratory studies revealed the following:

a. hyperinsulinemia

b. Type 2 Diabetes Mellitus

c. elevated blood levels of DDE (a metabolite of DDT)

d. autoimmunity with a positive SS-A antibody

e. Syndrome X

f. deficiencies of calcium, magnesium, potassium, selenium and phosphorous on the red blood cell mineral analysis

g. elevated mercury level in a 24-hour urine challenge study

h. abnormal liver detoxication: low phase 1/2 ratios, elevated phase 2 glycine and glucuronidation conjugation indicating chemical toxicity, signs of oxidative stress with increased hydroxyl radical characteristics.

i. comprehensive digestive stool analysis: there was an overgrowth of candida glabrata and a deficiency of SIG-A

j. allergy skin tests: these showed positive responses to many foods, trees, weeds, grasses, mites, dust and salicylates

The therapeutic modalities that were started on this patient included:

An avoidance diet - removing all the foods from her diet that she was found to be sensitive to.
Environmental controls - this is a program that removes from the individual's environment all the things that the person is sensitive to that are in the air, water and food. The use of air and water purification and organic foods will accomplish these modalities.
Immunotherapy - to develop a program that will build resistance in the immune system to all of the things the individual is reactive to. In this case, the patient received 18 months of a vaccine called EPD.
The patient received therapy with DMPS, which is a chelator for metals. In this particular case it was for removal of mercury.
Nutritional therapy - the patient received various therapies that included antioxidants, nutrients to improve the function of the liver, and therapies to build up the levels of cellular nutrients that would aid in the efficient operation of the mitochondria and other organelles. Chromium, vanadium, and niacin are also used to aid the processing of both carbohydrates and lipids.
Anticandida therapy - because of yeast overgrowth in the colon, we used an anticandida program and a yeast-free diet.
This patient began to show signs of improvement within the first few months. It was a steady uphill climb. At the conclusion of 18 months of the EPD therapy, the patient no longer felt she needed to travel 500 miles to come to the Center, and she was feeling 90% better than when she began the program at our Center.

2. This patient was a 35-year-old caucasian female with a childhood history of chronic allergies and chronic headaches. At age 15 she developed Irritable Bowel Syndrome. Three years prior to coming to our Center she began to develop a slowly progressive form of chronic fatigue. She visited many physicians, including several who were supposedly specialists in the field of chronic fatigue types of illnesses.

She continued to progress to the point of a vegetative state. I saw her in this condition in 1997. She had severe fatigue and exhaustion along with severe diffuse muscle weakness. There were also a multitude of tic-like muscle spasms that almost resembled fasiculations. As it turns out, they were not, and the tics and tremulousness later disappeared as part of her overall therapy. She also suffered with significant neurocognitive processing problems.

Her history revealed that she had been exposed to a variety of toxic chemicals over the last few years. She lived on a golf course with the many herbicides, pesticides and solvents that are part of that environment. Her husband was a builder, so the house they lived in was new, and there were many different solvents there. The couple also renovated houses and had moved often.

During the history-taking session in my office, the patient was so weak that the entire 90 minutes of history taking was done with her lying down. The following are a list of her complaints at the time of that first interview:

severe fatigue
muscle weakness
muscle twitches
eczema
urticaria (hives)
multiple chemical sensitivity
constant headaches
premenstrual migraines
hearing loss
tinnitus
nasal and eye itch
dry mouth
hoarseness
swollen lymph gland in the neck
post nasal drainage
abdominal bloating
flatulence
cramping of abdomen
nausea
diarrhea
chronic belching
retastes food
anal itch
muscle pain
morning stiffness
numbness, and pins and needles of hands
tremors
lack of coordination
tics
dizzy and spacey
chronic insomnia
excessive sweating
depression
anxiety
forgetful
hypersomnia in the daytime
irritability
Previous laboratory studies revealed the following:

a. low uric acid

b. deficient Vitamin B-3 and B-12

c. borderline low testosterone levels

d. low plasma amino acids

The physical exam revealed the following findings:

a. fibrocystic breast changes

b. diffusely weak muscles

c. tender finger and wrist joints

d. twitching of various muscles including the tongue

e. bilateral hyper-reflexia

We began a very comprehensive laboratory investigation, which had never been done. The following are the compilation of results of that "discovery."

immunoglobulins, sed rate, C-Reactive, lymphocyte mitogen stimulation test
C-3 complement - low
immune complexes - normal
ANA- normal
low total lymphocytes
past EBV infection
thyroid function including free T-3 - normal
borderline MAG autoantibody level
positive neuronal nuclear autoantibody
abnormal amino acid metabolism: maldigestion, sarcosine elevation indicating toxicity and taurine deficiency
mineral deficiency: magnesium, phosphorous and boron with elevation of cellular mercury levels
DNA damage - as seen by the DNA adduct test, 8H2DG
low choline levels
low normal levels: A, B2, B3, Inositol and carnitine
leaky gut syndrome as seen on the lactulose mannitol challenge
liver detoxication study: abnormal phase I or the so called pathological detoxifier, abnormal sulfate metabolism, elevated phase 2 levels indicating active xenobiotic toxicity
Renal Mineral Leak Syndrome: this was discovered after a great deal of investigation and trial and error. It revealed that she was losing large amounts of magnesium, potassium, selenium and zinc.
low IGF-1 levels
The diagnoses based on the above evaluation were:

a. Chronic Fatigue Immune Dysfunction Syndrome

b. Chemical Toxicity

c. Pathological Liver Detoxication and Sulfate Metabolism Abnormalities

d. Leaky Gut Syndrome

e. Severe Nutritional Deficiencies

f. Maldigestion Syndrome

g. Renal Leak Syndrome

h. Taurine Wasting Syndrome

i. Multiple Chemical Sensitivity

j. Allergies: food, inhalant and preservatives, etc.

k. Autoimmune Encephalopathy

l. Autoimmune Thyroid Binding Autoantibody Production

m. Complement Deficiency

n. Mercury Toxicity

o. Estrogen Dominance Syndrome

Our therapies consisted of the following:

1. oral and intravenous nutritional therapy

antioxidants

mineral therapy

amino acid therapy

nutritional liver upregulation

miscellaneous items: Calcium D Glucanate, Acetyl L Carnitine, Amrit Kalash, Beta Glucan, IP-6, Ginkgo Biloba, Essential Fatty Acids, Phosphatidylcholine and serine, Glutathione, N-Acetyl Cysteine, Lipoic Acid, Naringinin, Magnesium Sulfate, Thymus Extracts, S- Adenosylmethionine, Methylcobalamine,etc.

2. Ultraviolet Blood Irradiation
3. Growth Hormone Therapy
4. Chelation with DMPS and DMSA
5. Sauna Depuration Therapy
6. Food Avoidance Diet
7. Environmental controls
8. Progesterone Therapy
9. Gastrointestinal Healing Therapy (probiotics, glutamine, aloe vera, antifungal and antibacterial)
After about one and a half years of continuous therapy, this patient was approximately 90% improved. She almost felt like she did before all of this happened to her. She never moved off the golf course, however.

I think this is a classic story of one of the sickest young women I have ever come across who could not find help in the orthodox world of medicine, including all of the specialists that would have dealt with these symptoms. The reason is that this type of illness cannot be solved by thinking in a linear fashion. One must investigate these illnesses by looking at the origins of the molecular bases of the illness and investigating all of the organ systems to determine those that require healing processes. The only thing that keeps the human body from healing and repairing are certain impediments - the toxins of our world that have accumulated in our bodies and the occult infections that have gained entrance as a result of the compromised immune systems the toxins have created. Remove those impediments, heal the damaged organs, give the patient the fuel they have lost (nutrients), destroy the invading organisms, and the body will slowly return to a state of balance (homeostasis) and total health.

I think the point has been made clear that it is necessary for the medical establishment to change its paradigm and stop looking for the "X" factor that is responsible for causing an illness. That way of thinking, which is the way the medical school curriculum still teaches, will never be able to solve the illnesses of the new millennium.

We must start thinking about the origins of the illness as they relate to the environment we have created over the last 200 years. We must change the course and direct our creativity to more multifaceted thought processes that allow us to get to the level of the molecule, where these illnesses begin. We must think of the "molecular" basis of illness, which deals with toxins and free radicals.

It is not going to be an easy task because the basic teaching to the "healers" of our day does not deal with any of this innovative, new paradigm. They are still learning what drugs they should use to treat the symptoms of these illnesses - an approach that has little to do with healing of the damaged human body. Let us try to work together to stop this insanity. It will not change unless the public wants it to change by refusing to accept drugs to treat symptoms, and refusing to allow their physicians to tell them, "We just don't know why this happens - all we can do is treat your symptoms and you will have to learn to live with it."

[*]I want to thank Dr. Paul Cheney and Mr. Albert Donnay for information I gathered from their writings.

Correspondence: Stephen B. Edelson, MD, FAAFP, FAAEM Clinical Molecular Medicine 3833 Roswell Road, Suite 110 Atlanta, Georgia 30342-4432 USA Fax 404-841-6416 Email: sbedelson@pol.net Website: www.edelsoncenter.com

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By Stephen Edelson

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