Book Notes: From Fatigued to Fantastic

Chapter 9: Other Rx

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Treating Food and Other Allergies and Sensitivities

NAET - A Powerful Way to Diagnose and Eliminate Allergies and Sensitivities

A Breakthrough Treatment for Allergies
By K. Nambudripad, L.Ac., Ph. D

STAY FREE OF ALLERGIES FOR LIFE! I couldn't believe my eyes when I read those words. They were my introduction to NAET, Nambudripad's Allergy Elimination Techniques. A dramatic new treatment for the cure of allergies [and sensitivities].

I am one of the thirty-five million Americans who know they have allergies and who want and pray for relief. The discovery of NAET treatment came as incredible, welcomed news. For the fifty percent of Americans (128 million people) suffering from various health problems caused by allergies not yet known to them, NAET will come as an astonishing surprise.

For we, the allergic [and sensitive], there is the possibility of an attack any time we introduce anything into our body or environment. I define an allergy to be an unusual or exaggerated response of sensitive individuals to certain substances. This type of biological hypersensitivity occurs in sensitive individuals, while remaining innocuous in similar amounts and circumstances in others. [Editors Note: Be aware that this definition of ‘allergy’ is quite different than the medical definition. I prefer to use the term ‘sensitivities’. I have seen NAET effectively treat both allergies and sensitivities.]

Undiagnosed allergies can produce symptoms, illnesses, even chronic diseases like migraine headache, backache, asthma etc. These can affect every system and organ in the body. Chronic Fatigue Syndrome, Fibromyalgia, immune disorders, hyperactivity, arthritis, anxiety, depression, addictions and many other conditions can be allergy-based. Until the mystery of allergies was revealed to me, I continued to spend years and many dollars, fruitlessly visiting medical specialists, never getting better. Simply passing an open door of a nail salon immediately affected my lungs and soon after, my eyes began tearing with no end in sight. Within twenty minuets in a meeting at someone's home, where hours earlier the pets had been put out side or out of sight, I would feel a tingling in my throat. This would be followed by extensive sneezing and wheezing for hours, interfering with my sleep. These events left me exhausted for the next two to three days.

What is NAET?

The treatment known as Nambudripad's Allergy Elimination Techniques, NAET, is a blending of the non-invasive procedures from Western and Eastern healing practices that help to eliminate allergies of all kinds, permanently. It is a specific treatment procedure formulated by combining chiropractic and Chinese Medicine principles applied through spinal manipulation, acupuncture, kinesiology, acupressure and nutrition. This powerful process was discovered quite accidentally in November of 1983 by Dr. Devi S. Nambudripad, who is a Doctor of Oriental Medical, Doctor of the Chiropractic Arts, Licensed Acupuncturist, R.N., and Ph.D. Through the years she has ceaselessly perfected her technique while studying the effect of this technique on thousands of patients.

NAET uses Muscle Response Testing (MRT) to confirm the presence of allergic reactivity. Once identified, Dr. Nambudripad uses spinal manipulation, acupressure and / or acupuncture procedures to eliminate the allergy. The treatment is geared to re-program the brain's negative responses towards the allergen(s) to a positive response whenever these substances are contacted in the future. NAET is based on the Chinese Medicine principle, that "no disease is possible when your body is in perfect balance". Through NAET, my health is being brought back into a "homeostasis" or a perfect energy balance throughout my entire body. NAET offers an Energy Medicine solution to allergic conditions by balancing the body and mind through three pathways:

* The mind-body energy pathway (Psycho-somatic pathway),

* The body-mind energy pathway( Somato- visceral pathway) and

* The mind-body-organ pathway (Psycho-somato-visceral pathway)

All of this is accomplished through the stimulation of the spinal nerves using a specific acupuncture/acupressure and spinal manipulation protocol without drugs, allergy shots, or any forms of invasive entry into the body.

For the last fifteen years, Dr. Nambudripad has been using her own discovery, the Nambudripad's Allergy Elimination Technique (NAET), at her clinic in Buena Park, California, to relieve between 80-90% of her patients' hidden allergies. People come to her from all over America and other countries for this unprecedented degree of relief. She has taught NAET to over 1,300 licensed doctors of chiropractic, acupuncture and traditional medicine. That means, this innovative allergy treatment is now available in many parts of the U.S. and other countries as well. Based on the principle that all matter is associated with energy fields, NAET makes use of the central and autonomic nervous systems ability to recognize and respond to these energy fields. The human brain is intelligent beyond belief. It constantly gathers information from all around us, minute to minute, second to second, and stores it in its memory bank to recall it at a later time as needed. The brain remembers and/or registers everything that has happened during a lifetime. As a result, we have a tremendous ability to interact with the energy fields of all things: people, animals, matters, objects, electrical and Electro-magnetic forces, liquids, gases, polluted dust, pollens, chemicals, etc. as we encounter them in daily life. We are may not be consciously aware of the encounters with these energy fields. This is the silent job of our autonomic nervous system as it maintains our body functions, manages our breathing, keeps the heart beating, falling asleep, waking up, thinking, etc.

All neurons or cells in the body are connected by an interlinking network of nerve fibers. These produce the fastest, most proficient communication system in the body. This communication is powered by our vital energy known as "Chi" in Chinese vocabulary.

When our bodies no longer respond to the signals from this communication system, we are pronounced dead. Communication between brain cells, body cells, body organs or different body parts takes place within a fraction of a second. Any blockage in this communication network causes disruption in the circulation of vital energy. This in turn will cause imbalance in the energy pathways, body cells, organs and functions of the cells and organs. Imbalances in the energy channels over a long period of time will result in illness or disease.

Located throughout the body, these energy pathways contain many Electro-magnetic cells called Bonham corpuscles. These cellular structures are very sensitive. They filter all the energetic movements through the energy pathways. They can let the energy pass through them easily or they can selectively block the energy transmission through them. They can also be blocked in both their chemical and electrical charges so that the energy pathway in which they exist is effected in a negative manner. Allergic and sensitivity response comes into play when a perceived allergen (or the source of energy disruption) blocks a pathway on either the physical, biochemical, or emotional (cellular) level.

Beginning with infancy and childhood, we encounter many adverse energies. Exposure to various hostile things such as radiation, chemical toxins from external sources (bacterial infection), toxins from internal sources (lactic acid buildup), physical trauma causing damage to the tissue, long term illness causing a weakened immune system, severe malnutrition causing obstruction in the nerve conductivity, emotional traumas, etc. All these can disrupt the energy circulation and leave blockages in the energy meridians, in the DNA, or cell memory. Each of these traumas imprints a certain frequency in the energy meridians and in the genes.

Events or thoughts taking place in or around the body are captured into the memory and stored in the memory bank (of the brain, for the duration of a lifetime) to be recalled as the need arises. This is a defense mechanism to protect the organism from possible similar future dangers. Then, at a future contact, any substance or event that falls within the similar frequency of conductivity, be it physical, chemical or emotional, can activate the same template creating similar responses that the organism experienced upon first exposure.

If the first imprint produced an unpleasant reaction, the following ones with similar frequencies will cause similar unpleasant reactions. This unpleasant reaction of the organism is called an allergic or sensitivity reaction. If it is not removed or repaired similar energies with similar frequencies will not be able to conduct energy (travel) through the area due to the blockage(s). Until they are removed, these blockages can stay forever on the energy pathways causing varying degrees of strain on the target organs, tissues and nerve tracts. Such continuous stress will cause acute and chronic symptoms and illnesses due to a lack of energy supply to the related functions of the vital organs such as the circulatory, digestive, respiratory, excretory and immune systems, etc.

How Does NAET Work?

The first step was to discover each of my blockages. I wondered if there was an easy way to locate them without going through extensive laboratory tests and radiological examinations, etc.? The answer came back, "Yes!" Dr. Nambudripad explained that these blockages can be tested using a simple procedure called muscle response testing (MRT). In this procedure, the doctor compared the strength of a specific muscle in my arm, in the absence and in the presence of a suspected allergen. The particular muscle tested remained very strong in the absence of the allergen. The same muscle becomes weak in the presence of the allergen (or anything the body is sensitive to).

The blockages of the energy channels (meridians) are released through manual manipulation (acupressure) of specific meridian points located along the spine thus allowing the energy to flow freely for the few moments that it takes the brain to reprogram in a new memory.

After she determined what my allergies were, in the presence of the particular allergen, Dr. Nambudripad instructed me to lie on my stomach. She then used a pressure device and occasionally used her thumbs to stimulate the energy flow along the ascending and descending nerve tracts of my spine through a series of specific acupressure points.

In the presence of the allergen, my body was brought into perfect balance with the creation of a new memory about the allergen. This new memory now over-writes my previous one and becomes my most recent and permanent one.

I was then asked to lie face up while Dr. Devi re-tested my muscle strength in the presence and in the absence of the allergen. My muscle was now strong in the presence of the allergen. Following this step, I was taken into another room for acupucture. Acupuncture was applied to the energy-balancing points on my hands and legs.

My entire body remained in a state of perfect balance for approximately twenty minutes.

When the needles were removed I was again re-checked for the integrity of the same muscle that was used initially. A strong muscle test indicated that the particular allergen, being held in my hand, was not going to produce any adverse reaction for me in the future.

As the final step, I was instructed to avoid all contact and proximity with the allergen (no touching, no eating, no smelling, etc.) for 24 hours (this can be decreased to 4 hours by doing the treatment on a special magnetic mat). The twelve major energy meridians "reset" themselves at two hours per pathway.

This discovery could not have come at a better time. According to Dr. Nambudripad, "the modern world we live in is getting so over-loaded with new chemicals. Allergic people are being driven away into a separate new world...a world of isolation. Far more people have allergies, than doctors, or the patients themselves, have ever suspected. The shocking fact is that there is hardly any human disease or condition in which allergic factors are not involved. Actually, any substance under the sun, including sunlight itself, can cause an allergic reaction in any sensitive individual." To my great relief, we now have NAET! I can have my nails done, enjoy the experience, and rest that night. I am free!

Dr. Nambudripad has personally certified over 1,371 licensed health professionals from all over the world. The number of NAET specialists steadily increases as she conducts monthly training seminars at her educational facility in Buena Park, California. NAET practitioners are now able to eliminate allergies of all kinds, in people (and animals) everywhere. In her studies, Dr. Nambudripad has found "people can be allergic to anything. There are some people who are literally allergic to everything. Foods, clothing, plants, chemicals, air-borne dust and pollutants, vitamins, tap water, vaccines, furniture, plastic, metals, wedding rings, piano keys, water, heat, acrylic fingernails, clothing labels, saliva, sweat, even their own adrenaline. The list is staggering."

In her bold new book, "Say Goodbye to Illness", Dr. Nambudripad promises to and will absolutely "revolutionize the practice of medicine." It may sound like an exaggeration, but for Dr. Nambudripad and her extensive, on-going research, it is the simple truth. Dozens of dramatic case studies presented in the book support her strong claim.

Diagnosing hidden allergies in itself is not revolutionary. Environmental medicine has been doing that for several decades. Usually the allergenic substance is removed from the patient's life. They go on a rotation diet, and they can manage. Suddenly, with Nambudripad's techniques applied, people are allowed to continue using the very substance that has made them sick, without any further adverse results. The allergy is simply gone.

The secret to NAET is to re-train the brain and nervous system to no longer react to the offending substance. We can see how this works by way of a few stories from her research case histories.
Tina was a 29 year old woman, who came to Dr. Nambudripad complaining of severe daily migraine headaches for the past nine years. Upon her arrival that particular day she did not have one. When ever she had gotten a headache, she would suffer for days, and was now having severe headaches.

The only unusual thing she had done during the nine years was to become a strict vegetarian. When she was tested through MRT, she was found to be very allergic to Vitamin C. She was given a Vitamin C pill to chew. Within ten minutes she had an intense reaction: she instantly got a headache. It intensified along with nausea, chills, muscular stiffness, and an elevated body temperature (fever).

Dr. Nambudripad treated her at once for an allergy to Vitamin C. Within 30 minutes, she felt better. On the following visit, she shared the good news that she had not had another headache, what so ever, after her first visit to our office five days prior.

Nina, 35 year old female, suffered from severe ragweed allergy all her life. During the allergy season, she had to hide indoors for days and weeks at a time. After she got treated with NAET with Dr. Devi, she is absolutely free of symptoms during the allergy season for the last two years now.

Six-year-old Dominic suffered from severe autism and his parents were very sad to watch him suffer, until his mother was given the book "Say Goodbye To Illness" by Dr. Devi by her psychologist. She immediately took him to Dr. Devi. After 20-25 NAET treatments with Dr. Devi, Dominic is a normal boy who attends regular school now.

Five-year-old Daniel suffered from repeated ear infection, frequent bronchitis, and asthma. Whenever he took the prescription medication "amoxicillin", or any other antibiotics including erythrocine, he broke out in rashes and hives, sometimes along with fever for days. His pediatrician suggested his mother to try NAET and gave her the book to read. She took Jason immediately to Dr. Devi. Now he can use amoxicillin or any other usual prescription medication without any reaction if needed. He also reacted to grasses, pollens, pesticides, and dust. He was treated for all these substances with NAET. He does not have any adverse reactions to the environmental substances anymore. Now he is a healthy 11 years old. He does not get any asthma anymore. He can virtually eat anything, go anywhere, and play in the grass in the school in the little league team.

Nancy had severe allergy to latex. She could not use any product with latex in it. She would get hives, weeping skin blisters, fever, and many other systemic symptoms with any contact with latex. Few times, she almost went into an anaphylactic shocks whenever she used latex derivatives for a short period of time. Because of this she could not even see any Dentist or get her teeth cleaned. After NAET treatments with Dr. Devi, she got her teeth cleaned for the first time in her life. Now she is working full time with various latex products without any adverse reaction.

Thomas was a computer programmer, age 28, who started experiencing extreme fatigue only a year after taking a new job. He was so tired he hated going to work. His job performance dropped, he could barely walk without someone's help. He was diagnosed as having chronic fatigue syndrome. He took time off from work, seemingly facing a grim future. Yet he started to feel better, just by being home. But when he returned to work, he got worse again.

This cycle continued for four years until he had the good fortune to visit Dr. Nambudripad. She tested Thomas for allergies and found he was allergic to the plastic material of his computer keyboard and to computer screen radiation. She used NAET on Thomas and he was able to resume full time work with no further allergic reactions.

How is this possible? Normally, the patient would remove the allergenic substance and stay away from it forevermore, yet here are Tina and Thomas able to resume living while in contact with a substance that had made them terribly sick. The secret of NAET lies in the energy pathways, the energy blockages and the NAET treatments described above.

Here's what happens, according to Dr. Nambudripad's theory. Our energy systems and brain interpret a particular substance as potentially harmful to our body. For other people these items, a diamond ring, a carob-coated cherry, a peanut or hot water are harmless, everyday trivialities. Let's say for my system, one or more of these is toxic. My energy pathways freeze up as a way of defending the body against this unsuitable substance. This in turn blocks my energy meridians and if the condition never changes, the overall functioning of my body suffers.

"With the first bite of most allergic foods, the brain begins to block the energy channels to prevent the entrance of the adverse energy of the food into the body," Nambudripad explains. This is what produces allergies. In Tina's case, it was her stomach meridian that got blocked and kept generating the allergic symptoms of migraine headaches. The sudden blocking of the meridians is one of the quickest defense mechanisms of the brain to stop the allergen from entering deeper into the body.

Imagine you are washing your face with soap and water, and a drop of soapy water goes into your eye. Your immediate response is to shut your eyes tight to prevent any more soap entering your eye. You keep your eyes closed until you wash your eyes with clean water or dry it off, until you are sure it is safe to open your eyes again. The same principle is applied here when an irritant's energy tries to enter our energy meridians. Just like the soapy water caused energy disturbance in the eye, the irritant (an allergen) causes an energy disturbance in a meridian. This blocks the energy flow, the body becomes unbalanced, symptoms show up, and eventually, you get sick.

Using Dr. Nambudripad's Allergy Elimination Techniques, the re-interpretation undoes the body's conditioned response and allows it to co-exist again with everyday items. "Is a permanent cure for allergies possible?" At last the answer is a definite "yes"! Dr. Nambudripad learned the principles of NAET via the most organic personal process- being sick since childhood with multiple illnesses; eczema, arthritis, joint aches, bronchitis, insomnia, clinical depression, sinusitis, migraine headaches, chronic exhaustion, plus having suffered three miscarriages. These events were her best possible teachers.

By the time she arrived in Los Angeles nearly twenty years ago from India, she was taking thirty aspirins a day to survive. She tried a wide variety of doctors, techniques, medicines, herbs, vitamins, and nutritional programs. Everything just made her worse. The only things she was not allergic to were white rice and broccoli. "Every inch of my body ached," said the young Nambudripad.

Finally, she stumbled upon an acupuncturist who tested her for allergies. He was the first physician Dr. Nambudripad encountered who made the link between her rather stunning list of problems and undiagnosed allergies. "I followed my doctor/teacher's advice and ate white rice and broccoli exclusively." All of her symptoms started to lift, but as soon as she started to add more items to her food list, the allergic reactions returned. "I was simply allergic to everything under the sun," she said. Was she to live on rice and broccoli the rest of her life? That is what she did for the next forty-two months.

Then one day she ate a piece of carrot and made a discovery that led to NAET. After eating only a few bites of carrot, Dr. Nambudripad instantly felt tired and lethargic, as if she were going to faint. She used muscle testing on herself and learned she was highly allergic to carrots. Was this to be just another item added to her unending list of untouchable substances? No. This time Dr. Nambudripad had an idea.

She and her husband Kris, a licensed Acupuncturist, gave her acupuncture, working with the points they knew would keep her awake or prevent her from going into shock. After the treatment she slept for forty-five minutes. When she awoke she felt completely different. Assessing how she was now feeling as to how she felt just prior to inserting the needles, and comparing to how she had felt for years, this was a new state of "supreme well-being." No longer feeling sick and tired, she jumped off of the treatment table with the acupuncture needles still in tact. She found a few pieces of carrots stuck to the bare skin on her back. These must have dropped on the table in the panic while her husband was treating her with the needles.

That's when she saw the link between holding the allergenic substance within the body's electromagnetic field while receiving a treatment for adverse food reaction. Somehow the combination of the two took the allergenic charge out of the carrots. Her body was no longer repulsed by the energy of the carrots. To prove it, she ate the remainder of the carrot and had no allergic reaction what so ever. She tested her muscles for carrots and the response was strong. Carrots had lost their allergic effect.

The result is NAET. In the last fifteen years of clinical use it has entirely relieved allergy symptoms or produced satisfactory improvements in 80-90% of her patients, which number in the thousands. "In every case, allergies were cleared out, never to return," reports Dr. Nambudripad, from her "profound" research files. And all this without any strict rotation or elimination diets to avoid the allergy-producing substance.

Recognition of Allergy in Medical Practice

The experience opened Dr. Nambudripad's eyes to a new world of cause and effect in understanding allergies. "I discovered that although allergy awareness has been gaining acceptance as a separate area of medical study in the last few years, allergy certainly has not been given the recognition it deserves as a primary cause of many types of disorders and illnesses."

Both physicians and patients have attested to the high degree of success with NAET treatments. Many people have said goodbye to illnesses they thought were permanent afflictions. I have included a few brief testimonials.

"Dr. Nambudripad's Allergy Elimination Technique is the most incredible practice tool I have seen in health care in my forty years of practice," states chiropractor John Kassler, from North Carolina.

"I have seen NAET put my extremely sick patients back in control of their lives once again. After completion of a NAET treatment program, they are free of symptoms, free of excessive medication, and free once again to enjoy good food and good health." comments acupuncturist Jan K. Steele, L.Ac., O.M.D.

Even the allergy specialists, such as Environmental Medicine physician Sandra Denton, M.D., of the Alaska Alternative Medicine Center in Anchorage, admit that NAET has shown them something new about treating allergies.

Dr. Denton herself had endured chronic fatigue syndrome and serious asthma for years until Dr. Nambudripad revealed the host of substances she was allergic to and freed her body of its need to react against them. "Dr. Nambudripad pointed out to me that many health problems in people all over the world are undiagnosed allergic reactions. The immune system is compromised by multiple allergic reactions that allow diseases to attack the weakened host," Denton says.

"I felt as if I was let out of jail, that I escaped from allergy hell!" A comment from a case history recorded by an acupuncturist using NAET treatments.

This happy patient, like many others, has experienced a way to transform the allergic body into a healthy, balanced, and livable body.

To find a NAET practitioner – see http://www.naet.com/.

BIBLIOGRAPHY

Nambudripad, Devi S., D.C., L.Ac., R.N., Ph.D.,OMD., You Can Reprogram Your Brain to Perfect Health. 1989, Singer Publishing, Rancho Mirage, CA

Nambudripad, Devi S., Say Goodbye to Illness. 1993, Delta Publishing Co., Buena Park, CA

Nambudripad, Devi S., The NAET Guide Book - Companion to Say Goodbye to Illness. 1994, Delta Publishing Co., Buena Park, CA

MacConaill, M. A., Muscles Send Movements. 1977, Robert E. Krieger Publishing Co. Huntington, N.Y.

Goodheart, George, J., Applied Kinesiology, 1974 Research Manual. N.P., 1974

Elimination Diets - by Doris Rapp

How Do You Do the First Part of the Diet?

During the first week, most meats, fruits and vegetables can be eaten. (The “allowed” and “forbidden” foods are listed in Table1.) Keep detailed records in a food diary of exactly what is eaten. Most individuals who are going to respond favorably to this diet do so about the 6th or 7th day; others respond as early as the 2nd or, rarely, as late as the 14th day.

If your child or you are better in a week or less, begin Part 2 of the diet on the 8th day. Improvement noted on day 2 may greatly increase by day 7. The object is to see the maximum amount of improvement which can be noted during the first 7 days.

If you want to help your entire family, urge everyone to try the diet at the same time. Typically, several family members will note improvement in how they feel or act when this is done.

If you or your child are not better within a week, re-check the diet records for the initial week of the diet. Were only the allowed foods eaten? If your child repeatedly forgot and ate the wrong foods or drank the wrong beverages at school or at home, the item which was not deleted or omitted from the diet may be the culprit. Try Part 1 of the diet again, but this time try much harder to adhere strictly to the diet. It’s best to do the diet only one time, but do it right. This fast, inexpensive method of food allergy detection can sometimes provide rapid, safe relief of many chronic medical and behavioral complaints. [Editors Note: It is not uncommon to undergo some moderate withdrawal and worsening of symptoms and cravings when offending foods are first eliminated. These usually pass after the first 7-8 days on the elimination diet].

Occasionally, a person is severely worse during Part1 of the diet. If this happens, immediately stop the diet. A frequent cause is that the patient has begun to ingest an excessive amount of an unsuspected offending food or beverage. A child who substitutes apple or grape juice for milk, for example, may act or behave much worse if apple or grape juice, is the cause of this child’s symptoms. Retry Part 1 of the diet, but stop the suspect food or beverage which you think made you or your child worse.

Rarely, someone who was not helped during the first week will dramatically improve with a more prolonged diet. Continue Part 1 for two weeks, not one week. If Part 1 of the diet is tried and has not helped by the fourteenth day, this particular diet is probably not the answer. The medical problems are not related to foods or are possibly due to other frequently eaten or craved items, i.e., mushrooms, cinnamon, coffee, tea, tobacco, etc., which were not removed from the diet.

If an infection occurs during the diet, stop the diet until you are well. It is too difficult to interpret the results if it is continued.

During Part 1 of the diet, the following foods are omitted in all forms: milk and dairy products (yogurt, cheese, ice cream, casein, sodium caseinate, whey), wheat (bread, cake, cookies, baked gods), eggs, corn, sugar, chocolate (cocoa or cola), peas (peanut butter), citrus (orange, lemon, lime, grapefruit), food colorings, food additives and preservatives. No luncheon meats, sausage, ham or bacon are allowed. If there is some question about a specific food, do not eat it. Also, exclude any other food or beverage that is craved in excess because such items are frequently unsuspected causes of various medical or emotional problems.

Table 1

Allowed

Forbidden

Cereals – Rice (rice puffs only), Oats – Oatmeal made with honey barley

Cereals – Foods containing wheat flour, (most cakes, cookies, bread, baked goods), corn, popcorn, cereal mixtures (Granola).

Fruits – Any fresh fruit, except citrus. Canned if in their own juice & without artificial color, sugar or preservatives.

Fruits – Citrus (orange, lemon, lime, grapefruit)

Vegetables – Any fresh vegetables, except corn and peas. Potatoes & homemade French Fries.

Vegetables – Any frozen or canned vegetables, corn, peas or mixed vegetables.

Meats – Chicken & turkey (non-basted), Louis Rich ground turkey, veal, beef, pork, lamb, fish, tuna.

Meats – Luncheon meats, wieners, bacon, artificially dyed hamburger/meat, ham, dyed salmon, lobster, breaded meats, meats with stuffing.

Beverages – Water, single herb or plain tea with honey, grape juice (bottled – Welch’s), frozen apple juice (Lincoln or pure apple), pure pineapple juice (no corn or dextrose).

Beverages – Milk or dairy drinks with casein or whey, fruit beverages except those so specified, kool-aid, Coffee Rich (yellow dye), 7-Up, Squirt, Teem, cola, Dr. Pepper, Ginger ale.

Snacks – Potato chips (no additives), RyKrisp crackers & pure honey, raisins (unsulfured).

Snacks – Corn chips (Fritos), Chocolate/cocoa, hard candy, ice cream or sherbet.

Miscellaneous – Pure honey, homemade vinegar/oil dressing, sea salt, pepper, pure maple syrup, homemade soup.

Miscellaneous – Sugar, bread, cake, cookies, (except special recipes), eggs, dyed (colored) - vitamins, pills, mouthwash, toothpaste, medicines, cough syrups, etc., jelly or jam, Jello, Margarine/diet spreads (dyes & corn), peanut butter/peanuts, Sorbitol (corn), cheese.

Multiple Food Elimination Diet, Part 2

How Do You Do The Second Part of The Diet?

Day 8 – Add milk

Day 9 – Add wheat

Day 10 – Add sugar

Day 11 – Add egg

Day 12 – Add cocoa

Day 13 – Add food coloring

Day 14 – Add corn

Day 15 – Add preservatives

Day 16 – Add citrus

Day 17 – Add peanut butter

During Part 2 of the diet, one food is reintroduced into the diet, in excess, each day. Keep detailed records of how you or your child feels at the beginning and the end of each day, and observe carefully for one hour after a food is tried or eaten again. Start with a teaspoon or ½ cup of the test food item and double the amount eaten every few hours, so that by the end of the day at least a “normal” amount has been ingested. Do any symptoms suddenly reappear? If there are no symptoms during the day, during the night or the next morning before breakfast, the food tested the day before is probably all right and may be eaten whenever desired. If the test food causes symptoms, stop eating it in all forms until you can secure the advice of your physician. Do not try another test food until the symptoms from the previous food test have subsided. Usually you will notice that symptoms caused by a food occur within one hour. Symptoms such as canker sores, bed-wetting, tight joints, ear fluid, and bowel problems can be caused by a food and tend to cause delayed reactions several hours later.

If symptoms persist, Alka-Seltzer Antacid Formula without aspirin (gold foil) or Alka-Aid can be purchased from the health food store. (Dose is 1 tablet for a 6 year-old, 2 tablets for a 12 year-old.) Don’t use if liver or kidney disease are present. The usual allergy medications can be taken, so your symptoms subside quickly. If concerned, check with the doctor. Remember: If one of the listed foods causes a reaction which is not helped by Alka-Seltzer in gold foil and which lasts over 24 hours, DO NOT TRY to check the response to another possible problem food until the reaction has entirely subsided.

Watch closely to see what happens each day. One food might cause a stuffy nose, the next, no reaction at all, the next a bellyache. Some reactions occur immediately, others in several hours. Once again, if a food obviously causes serious symptoms, it should not be tried. NEVER TEST ANY FOOD WITHOUT YOUR DOCTOR’S ADVICE IF IT CAUSED SERIOUS MEDICAL PROBLEMS IN THE PAST. FOR EXAMPLE: IF EGG OR PEANUT CAUSED IMMEDIATE THROAT SWELLING OR FISH CAUSED SEVERE ASTHMA, IT IS UNSAFE TO TRY EVEN A SPECK OF THESE FOODS.

If you are uncertain whether a food causes symptoms or not, discontinue it until the other foods have been checked. Then try the suspect food again at a five day interval, i.e.: Tuesday and Saturday. See if symptoms recur each time.

If you want to learn even more about what each food does when it is eaten again, do the following:

For children, have them write and draw. Does either change or deteriorate before and 20 minutes after a food is eaten? If it does, the items ingested could affect your child’s school work.

Take the pulse. If it increases by 20 to 40 points after eating a particular food, once again your body could be warning about some food sensitivity.

Use a pocket peak flow meter if you have asthma. Use this before and 20 minutes after each food. If the reading on the gauge falls 15%, or over 50 or so points, that food or beverage could be the cause of wheezing.

Specific Details of Part 2 of Diet

Day 8: The day you add milk. Add lots of milk and cottage cheese. No butter, margarine or yellow cheese unless you are absolutely certain they contain NO yellow dyes.

Day 9: The day you add wheat, add Triscuits or pure wheat cereal. If you had trouble from milk, be sure NOT to give milk products. Use Italian bread or kosher bread because these should not contain milk (casein or whey), but always read labels to be sure. You can bake if you like, but you must not use eggs or sugar. Remember, eat no dairy products and do not drink any milk if these seemed to cause medical problems. If milk caused no problem, milk products can be eaten.

Day 10: The day you add sugar. Eat sugar cubes to eat and ad granulated sugar to the allowed foods. If milk or wheat caused trouble, they must be avoided or you can’t tell if the sugar is tolerated. Many react within one hour after 4-8 sugar cubes. Yeast overgrowth can cause sugar reactions as well.

Day 11: The day you add egg, eat them in usual forms, cooked or as eggnog. Remember, again, no wheat, milk or sugar can be consumed if any of these caused problems. Be sure to skip this food challenge if you already know egg is a problem.

Day 12: The day you add cocoa, use dark chocolate with water, cocoa (pure Hershey’s cocoa powder) and honey or pure maple syrup. No candy bars are allowed because they contain milk or corn. Remember no milk, wheat, sugar, dyes or eggs are allowed if any of these caused symptoms.

Day 13: The day you add food coloring, try Jello, jelly or artificially colored fruit beverages ( soda pop, Kool-aid), popsicles or cereal. Try to give lots of yellow, purple and red items because the patient might react to only one of these colors. Remember to avoid milk, wheat, cola or sugar in all forms if any of these were a problem. If sugar caused symptoms, use honey or pure maple syrup as a sweetener or add food coloring to plain pure gelatin. If milk, wheat or sugar were tolerated, they may be eaten.

Day 14: The day you add corn, try corn, corn meal, corn flakes and plain popcorn. The latter can be made with salt. If milk, wheat, sugar, dyes, eggs or chocolate cause trouble, you can’t give them on the same day you give corn. If you do, you won’t be able to tell which is at fault. Do not use butter on popcorn if there is a milk sensitivity.

Day 15: The day you add preservative, eat foods which contain any preservatives or food additives. Read every label. In particular, eat luncheon meat, bologna, hot dogs, bread, baked goods or soups which contain many preservatives and additives.

Day 16: The day you add citrus, eat a large amount of lemon, lime, grapefruit and orange as fresh fruit or in juice. Avoid artificial dyes if food colors were a problem.

Day 17: The day you add peanut butter, eat lots of peanut butter or peanuts. Test for this only if it’s a favorite food. Use Rykrisp if no wheat is allowed. Use pure peanut butter without additives (Smuckers).

Special Tips For The Food Elimination Diet

The “allowed” foods can be selected, combined and eaten in any quantity. If you are a bit suspicious, start with a tiny amount and increase during the day if no symptoms are revealed.

For beverage, you can mix the allowed fruits in the blender with spring water and honey (or pure maple syrup). Use these on cereal to replace milk. Use carbonated water to create pop.

Your usual medications can be taken during the diet. If you improve, you may find that certain antihistamines are needed less often by the end of the first week. Try to use only white pills (crushed for small children and placed in applesauce or mashed potatoes) or colorless liquids. Most liquid medications contain corn, sugar, artificial flavors and artificial dyes which can cause symptoms. Check with your pharmacist or physician about any questions you may have regarding this.

Once you determine which foods cause specific symptoms, you must discuss the problem with your physician. Some foods cannot be omitted for indefinite periods of time if proper nutrition is to be maintained. Call The Allergy Research Foundation at 716-875-5578 for the phone number of a dietician/nutritionist if you have any diet questions.

Do not try the diet when you have an infection or are receiving an antibiotic which contains dye, sugar, flavoring or corn.

Although symptoms from a single food vary, food sensitivities are often evident in several family members. For this reason, urge the entire family to do the diet. One person might develop headaches, another a stuffy nose and a third, hyperactivity, and another might wet the bed. The same food allergy, i.e., milk, can be a problem for several generations of a family. For this reason, make cooking easier by placing the entire family on a diet. A fringe benefit may be that you relieve some “emotional or learn-to-live-with-it” type health problems caused by certain foods or beverages in several family members.

If your child refuses the diet, try offering a reward. Promise a gala party if there is no cheating and if it is obvious that the child is truly trying very hard to cooperate in every way. The party should take place AFTER both parts of the diet are completed. At that time give your child the foods that caused the symptoms providing they were not severe or incapacitating. This will be a double check confirming the effect of these foods on your child. Alka-Aid (available at health food stores) will prevent or stop reactions in many children in 10-15 minutes depending upon whether it is given before or after a problem food is eaten.

If you or your child have asthma, add the test food back into the diet with extreme care. It is possible that an unsuspected food could precipitate a sudden severe asthma attack. Have asthma medications on hand during Part 2 of the diet and use the Pocket Peak Flow Meter to help find out exactly what is causing you or your child to wheeze. If you are concerned or your asthma has ever been severe or frightening, check carefully with you doctor before trying the diet.

If you or your child are worse during the first 2 to 3 days after the diet, this could just be “normal” withdrawal symptoms (i.e., nausea, headache, irritability). These usually subside by the fourth day. If you or your child are worse by the 5th or 6th day, suspect whatever you substituted for milk or whatever you are eating in excess while you are on the diet (i.e., potatoes).

If you are routinely worse (impatient, angry, tired, irritable, headachy, hyperactive) before meals, think about hypoglycemia or low blood sugar. If this is your problem, merely eating a small protein snack every hour or two all day might make you stay on a more even keel and feel much better.

What Else Is Inexpensive and Possibly Effective?

Stop all scented items, aerosols and chemical-smelling personal or cleaning preparations in your home (particularly in the bedroom and bathroom).

Compare to how you feel, act, behave, your pulse, your breathing, your writing, and your drawing before and 10 to 40 minutes after you eat or drink, go into every room at home/school/work, go outside versus inside, smell an unavoidable chemical or engage in your hobby. If you feel, act, or behave worse in some way, your pulse increases by 20, your breathing (Peak Flow Meter) drops 20%, or your writing or drawing is worse, find out what you ate, touched, or smelled that is a problem.

Additional details are available in: Doris Rapp’s books: “Is This Your Child?” – available from 800-787-8780. “The Impossible Child” and “Allergies and Your Family”.

Neurotoxins

For more information, see www.chronicneurotoxins.com

Guaifenesin

I rarely use this approach because I find others to be more effective and one can not use most natural products or herbs while on it. I have not found it to be worth the loss of the rest of the natural armamentarium to use Guaifenisin, but a snmall subset of FMS sufferers have obtained dramatic relief from it. For an interview with Dr. Paul st Amand who developed this treatment approach see http://www.immunesupport.com/library/showarticle.cfm/ID/6023

Methylation Defect Therapies

This treatment approach (and theory) developed by Rich Van Konynenburg is VERY promising. I will start with a 1 page information sheet we give patients, followed by a complex article written by him. Rich is wonderful, and I have great respect for him.

SIMPLIFIED METHYLATION PROTOCOL

Developed by Rich Van Konynenburg

As proposed by Amy Yasko

BASIC MATERIALS

* Folapro: ¼ tablet (200mcg) daily

* Intrinsic B12/folate: ¼ tablet daily

* Complete Vitamin and Ultra-Antioxidant Neurological Health Formula: start with ¼ tablet and work up dosage as tolerated to 2 tablets daily

* Phosphatidyl Serine Complex: 1 softgel capsule daily

* Perque B12: 1 sublingual lozenge daily

The first two supplement tablets are difficult to break into quarters. They can, alternatively, be crushed into powders, then separated on a flat surface, and the powders can be mixed together. They can be taken orally with water, with or without food.

Occasionally these can make patients sleepy, so some take them at bedtime. They can be taken any time of day, with or without food.

GO SLOWLY. Occasionally, as the methylation cycle blockages are released, toxins are released and processed by the body, and this can lead to an exacerbation of symptoms. IF THIS HAPPENS (most often in the first 4 days), try smaller doses, every other day. SLOWLY work up to the full dosages. It usually takes ~ 3-8 weeks to see the benefit. (You should know by the time you finish the bottles above. If you have questions, please call our office to discuss them.)

To give an idea of its effectiveness, this has been the experience of Dr. Neil Nathan, an excellent CFS/FMS expert:

“I now have responses (meaning, I've seen the patients back after 30-60 days of use) from 30 of them. 25 report significant improvement, 6, marked improvement. 5 note no change at all. 8 had significant reactions, and all but one have been slowly weaned into the protocol with good results. Since these are all treated patients who have incomplete
healing, I believe these are really exciting results.”

Other Potentially Useful Supplements

After 4 months, and if these first five are well tolerated, we can consider adding

* SAMe 400mg daily

* Methylation Support RNA Formula

* Glutathione support

* Molybdenum as a trace mineral

Below is the experience of Dr Karen Vrchota, another excellent CFS expert, with the methylation protocol:

I've received an update from Dr. Karen Vrchota in Winona, MN on her experience so far with the simplified treatment approach for lifting the methylation cycle block. I think you will find this interesting, as she is finding that components of your protocol seem to be helpful when used together with the methylation cycle block treatment. She started using this treatment in July, 2007. She has given me permission to share her comments with other clinicians and with researchers. It's important to note that her comments represent impressions from clinical experience, not a controlled clinical trial. Here are her comments. The notes added in brackets are mine.

"We have about 90 people taking the methylation protocol. [She's using what I've called the "simplified treatment approach."]

About 20% report "Wow! This is really making a big difference."

About 20% go down hill quickly on it and want to get back on Teitelbaum's Protocol.

An additional 5% do not tolerate any of the protocol and can not take it long enough to give it a try.

About 2/3 seem generally satisfied with slow steady improvement.

No one has been able to get off anti-viral or anti-bacterial or anti-yeast therapy due to increased immune function.

One 71-year-old female had been doing well 2 months off antibiotics for Lyme, was switched from Teitelbaum protocol to methylation protocol and had a flare of Lyme with heart block, fevers, anxiety, joint swelling. Her TSH soared to 12.6 after being stable for years on Synthroid 112 mcg. Going off the methylation protocol did not help, we had to restart her on antibiotics.

I would say I feel I need some additional way of telling who will do well.

I know it is not:

* Those with chemical sensitivities

* Magnesium sterate sensitive patients

* Soy sensitive patients

* Lyme and Babesia combo patients

No one feels as well on Perque B12 as they did on Methylcobalamin shots 25 mg/ml 0.2 ml SQ daily.

Almost every one feels better with magnesium product added back in, such as magnesium potassium aspartate or magnesium malic acid.

Most fatigued patients feel better with mitochondrial support [added to simplified treatment approach] such as:

* NAC and ALA

* Acetyl L Carnitine 1500 mg on empty stomach in AM

* CoQ 10 100-400 mg bid-tid with food

Those with cold hands and feet feel better with nattokinase [added to the simplified treatment approach].

ESR does not go from 0-4 back into the 5-20 range, and symptoms of immune system activated hypofibrinolysis go unchecked [on simplified treatment approach alone].

Sleep seems better on and off with very little connection to circumstances."

Glutathione Depletion – Methylation Cycle Block: A Hypothesis for the Pathogenesis of Chronic Fatigue Syndrome

By Richard A Van Konynenburg, Ph.D. (Independent Researcher and Consultant)
richvank@aol.com
8th International IACFS Conference on Chronic Fatigue Syndrome, Fibromyalgia and other Related Illnesses
Ft. Lauderdale, Florida, U.S.A.
January 10-14, 2007

INTRODUCTION AND HYPOTHESIS

At the Seventh International Conference of the AACFS in 2004, the author proposed and defended the hypothesis that glutathione depletion is an important part of the pathogenesis of CFS (1).

In the conclusions of that paper it was noted that it seemed likely that there are vicious circle mechanisms involved in CFS that prevent glutathione repletion from being the complete answer for treating this disorder.

Recent autism research (2,3) suggests that in that disorder a vicious circle involving the methylation cycle apparently chronically holds down the level of glutathione.

The present author has recently proposed (4) that this same mechanism is active in many cases of CFS. This model for CFS will be referred to as the Glutathione Depletion—Methylation Cycle Block (GD-MCB) Hypothesis.

This mechanism appears to be capable of explaining and drawing together numerous features of CFS that have been reported in the peer-reviewed literature.

What is the methylation cycle, and what does it do?

(See diagram)

The methylation cycle (also called the methionine cycle) (5) is a major part of the biochemistry of sulfur and of methyl (CH3) groups in the body. It is also tightly linked to folate metabolism and is one of the two biochemical processes in the human body that require vitamin B12 (the other being the methylmalonate pathway, which enables use of certain amino acids to provide energy to the cells).

This cycle supplies methyl groups for a large number of methylation reactions, including those that methylate (and thus silence) DNA (6), and those involved in the synthesis of a wide variety of substances, including creatine (7), choline (7), carnitine (8), coenzyme Q-10 (9), melatonin (10), and myelin basic protein (11). Methylation is also used to metabolize the catecholamines dopamine, norepinephrine and epinephrine (12), to inactivate histamine (13), and to methylate phospholipids (14), promoting transmission of signals through membranes.

The role of the methylation cycle in the sulfur metabolism is to supply sulfur-containing metabolites to form a variety of important substances, including cysteine, glutathione, taurine and sulfate, via its connection with the transsulfuration pathway (5).

This cycle balances the demands for methylation and for control of oxidative stress (15).

How is the methylation cycle dysfunctional in autism, and how is this related to glutathione depletion?

In autism the methylation cycle was found by James et al. (2,3) to be blocked at methionine synthase, which is the step involving methylation of homocysteine to form methionine (see diagram).

Two effects of this block that they measured are a significant decrease in the level of plasma methionine and lowering of the ratio of S-adenosylmethionine to S-adenosylhomocysteine. The latter causes a decreased capacity for promoting methylation reactions (16).

In addition, they found (2,3) that the flow through the transsulfuration pathway (see diagram) was also decreased, resulting in lower plasma levels of cysteine and glutathione and a lowered ratio of reduced to oxidized glutathione, all of which they measured. This lowered ratio reflects a state of oxidative stress (17).

The block in the methylation cycle and the glutathione problem were found to be linked, since supplements used to restore the methylation cycle to normal operation (methylcobalamin, folinic acid and trimethylglycine) also restored the levels of reduced and oxidized glutathione (2).

Do genetic factors contribute to producing this methylation cycle dysfunction in autism?

It is known from studies of twins that genetics plays an important predisposing role in autism (18). The fact that the rate of incidence of autism has increased dramatically in recent years is evidence that there is also an important environmental component in the development of cases of autism (3), since the population’s genetic inheritance is relatively constant over much longer periods.

James et al. (3) found that there are measurable genetic differences between children with autism and healthy controls. The differences they measured are associated with genes that encode enzymes and other proteins impacting the methylation cycle, the folate metabolism and the glutathione system.

In particular they found differences in allele frequency and/or significant gene-gene interactions for genes encoding the reduced folate carrier (RFC), transcobalamin II (TCN2), catechol-O-methyltransferase (COMT), methylenetetrahydrofolate reductase (MTHFR), and one of the glutathione transferases (GST M1).

These genetic results, combined with the biochemical observations of dysfunction in the methylation cycle, strongly suggest that variations in genes associated with this cycle and its related biochemistry are involved in the genetic predisposition to developing autism.

What evidence suggests that this same dysfunction and similar genetic factors are also present in chronic fatigue syndrome?

1. Methionine concentrations are reported to be below normal in both plasma (19) and urine (20) in CFS patients. Low methionine can be caused by a methylation cycle block.

2. Four magnetic resonance spectroscopy studies in CFS (21-24) have found elevated choline-to-creatine ratios in various parts of the brain. Both choline and creatine arise partly from the diet and partly from synthesis in the body. Since the syntheses of these two substances are the main users of methylation (7), a methylation deficit would be expected to decrease the rate of synthesis of both of them, and hence to decrease their levels in the cells. When this occurred, it would be unlikely that their ratio would remain the same, since the fractions of each supplied by synthesis would not likely be the same, nor would the decrease in rates of synthesis of these two substances likely to be proportional to their levels in the cells. Since creatine synthesis is the greater user of methylation (7), it might be expected that the choline-to-creatine ratio would increase, as is observed. It therefore appears that a methylation cycle block could explain this well-replicated observation in CFS.

What evidence suggests that this same dysfunction is also present in chronic fatigue syndrome?

3. Some substances that require methylation for their biosynthesis have been found to be at below-normal levels in CFS patients, and/or patients have been found to benefit by supplementing them. This has been reported in eleven of the studies in CFS of carnitine, beginning with the work of Kuratsune et al. (25-34), both the studies of coenzyme Q10 (35, 36), a study that included choline as phosphatidylcholine in a combination supplement (37), and one recent study of melatonin (38) (though it should be mentioned that earlier studies of melatonin in CFS found normal or elevated levels, and/or did not find benefit from supplementation (see review in ref. 39), suggesting that other issues in addition to the methylation deficit might be involved in the case of melatonin. See “Magnesium depletion” later in this paper).

4. Vitamin B12, which plays a key role in the methylation cycle and was one of the supplements used to restore this cycle in the autism work (2), has a long history (39,40) as one of the most helpful of the essential nutrients in CFS when given in high-dosage injections. Lapp and Cheney (41, 42) found that in urine organic acids testing of 100 CFS patients, 33% had elevated homocysteine, 38% had elevated methylmalonate, and 13% had both (29,30). The elevated homocysteine implicates the methylation cycle, while the elevated methylmalonate indicates that the other pathway that requires vitamin B12 showed deficiency as well. Lapp and Cheney (42) found that 50 to 80% of over 2,000 patients reported benefit from high-dose vitamin B12 injections. Evengard et al. (43) reported that vitamin B12 levels in the cerebrospinal fluid of 10 of 16 CFS patients were below their detection limit of 3.7 pmol/L. Regland et al. (44) found both low vitamin B12 (in 10 out of 12 patients) and high homocysteine (in all 12 patients studied) in the cerebrospinal fluid of CFS patients. There were significant correlations between these parameters and symptoms.

Regland et al. (45) performed an open trial in which they gave 1,000 microgram weekly injections of hydroxocobalamin for at least 3 months to the 10 female patients from this study who had both low B12 and elevated homocysteine. They found that the treatment was significantly more beneficial if the patient did not have the thermolabile allele of the polymorphic gene for MTHFR. They concluded that vitamin B12 deficiency was probably contributing to the increased homocysteine levels. They also found that the effect of vitamin B12 supplementation was dependent on whether the available methyl groups were further deprived by the existence of thermolabile MTHFR. This work implicated the methylation cycle in the pathogenesis of CFS, and it also pointed to the importance of a genetic component, involving one of the same genes that have been implicated in autism (3).

5. Folinic acid was recently found to produce subjective improvement in symptoms in 81% of 58 CFS patients tested (46). This was also one of the supplements used to restore the methylation cycle in the autism research (2).

6. Many studies have reported evidence for oxidative stress in CFS (47-61).

7. There have been several reports of depletion of reduced glutathione in at least a substantial subset of CFS patients (49-51, 53,54,59,62). Reduced glutathione augmentation is now widely used by CFS clinicians, who have found that augmenting glutathione by various means has been helpful to many of their patients (49,50,63-65).

8. Polymorphisms in the gene coding for the COMT enzyme were found by Goertzel et al. (66) to be some of the most important of those examined for distinguishing CFS cases from controls. As noted earlier, COMT is a methyltransferase, associated with the methylation cycle. In autism, the COMT 472G>A polymorphism showed significant difference between cases and controls (3).

If this same dysfunction is present in both autism and CFS, how can the obvious differences between these two disorders be explained?

Major differences are seen in the gender ratio and in the symptoms of these two disorders.

Autism is found primarily in boys, at a ratio of about 4 to1 (boys to girls) (67), while CFS occurs mainly in adult women at a ratio measured at 1.8 to 1 (women to men) by Jason et al. (68) in one large epidemiological study and 4.5 to 1 (women to men) by Reyes et al. (69) in another.

The most striking symptoms in autism involve the brain and are very characteristic of this disorder. They are described as follows by the Diagnostic and Statistical Manual of Mental Disorders (70):

1. Qualitative impairment in social interaction, as manifested by at least two of the following:

a. Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction.
b. Failure to develop peer relationships appropriate to developmental level.
c. A lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest).
d. Lack of social or emotional reciprocity.

2. Qualitative impairments in communication as manifested by at least one of the following:

a. Delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gestures or mime).
b. In individuals with adequate speech, marked impairments in the ability to initiate or sustain a conversation with others.
c. Stereotyped and repetitive use of language or idiosyncratic language.
d. Lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level.

3. Restricted repetitive and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:

a. Encompassing preoccupation with one or more stereotypic and restricted patterns of interest that is abnormal either in intensity or focus.
b. Apparently inflexible adherence to specific, nonfunctional routines or rituals.
c. Stereotypic and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements).
d. Persistent preoccupation with parts of objects.

CFS involves a large variety of symptoms (71,72), the chief ones being extreme fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, muscle pain, and symptoms involving the brain that are significant but less profound than in autism (e.g. cognitive and memory difficulties).

The author proposes that these differences result at least in part from the different ages at onset. Autism develops early in life, before the brain is completely developed and before puberty, while the onset of CFS occurs after brain development is completed and (for the most part) after puberty.

Pangborn (73) has discussed five hypotheses that have been suggested to explain the higher prevalence of autism in boys. Of these, the one that appears to be most consistent with the present author’s hypothesis of a common pathogenesis between CFS and autism is the one put forward by Geier and Geier (74). Their hypothesis proposes that the higher prevalence of autism in boys results from the potentiation of mercury toxicity by testosterone, while estrogen is protective. There is increasing evidence that mercury was a significant factor in the etiology of many cases of autism, because mercury-containing thimerosol was used as a preservative in vaccines given to them. Since thimerosol was removed from childhood vaccines, the number of new cases of neurodevelopmental disorders, including autism, has been found to be dropping (75).

The present author has proposed a hypothesis (76) to explain the higher prevalence of CFS in women, involving an additional bias toward oxidative stress due to redox cycling in the metabolism of estradiol when certain polymorphisms are present.

With regard to symptoms, it seems likely that the role of methylation in the formation of myelin basic protein (77) is at least part of the explanation for the major problems in brain development in autism and the symptoms that result from them.

Fatigue is not recognized to be a major feature of autism. However, it should be noted that the evaluation of fatigue is usually based on self-report, which is not possible in children who are unable to speak. Also, it seems possible that fatigue may be manifested differently in very young children as compared with adults. Features such as hyperactivity and irritability may reflect fatigue in these patients.

Chronic pain may also be difficult to identify and characterize in children who do not have speech. A recent paper suggests that chronic pain may be the initial presenting symptom in cases of undiagnosed autism (78).

Many of the other phenomena found in CFS are also found in autism, but historically they have not received as much attention in autism as the brain-related symptoms, perhaps because the latter are so striking and profound. Some of the other phenomena that autism has in common with CFS in addition to those already mentioned are elevated proinflammatory cytokines (79), Th2 shift in the immune response (80), low natural killer cell activity (81), mitochondrial dysfunction (82, 83), carnitine deficiency (83), hypothalamus-pituitary-adrenal (HPA) axis dysfunction (84), gut problems (85), and sleep problems (86).

How does the Glutathione Depletion—Methylation Cycle Block (GD-MCB) Hypothesis explain other aspects of chronic fatigue syndrome?

Etiology: According to the GD-MCB Hypothesis, CFS is caused by a combination of two factors:

(1) a genetic predisposition (87), which is currently only partly known, and

(2) some combination of a variety of physical, chemical, biological and/or psychological/emotional stressors, the particular combination differing from one case to another (See Ref. 1 for a review.).

So far, polymorphisms in genes coding for the following proteins have been found to be associated with CFS in general or with a subset:

(1) Serotonin transporter (5-HTT) gene promoter (88)

(2) Corticosteroid binding globulin (CBG) (89)

(3) Tumor necrosis factor (TNF) (90)

(4) Interferon gamma (IFN-gamma) (90)

(4) Proopiomelanocortin (POMC) (91)

(5) Nuclear receptor subfamily 3, group C, member 1, glucocorticoid receptor (66,91)

(6) Monoamine oxidase A (MAO A) (91)

(7) Monoamine oxidase B (MAO B) (91)

(8) Tryptophan hydroxylase 2 (TPH2) (66,91)

(9) Catechol-O-methyltransferase (COMT) (66)

In addition, a COMT polymorphism has reported to be associated with fibromyalgia (92, 93), and polymorphisms in the genes for the detoxication enzymes CYP2D6 (cytochrome P450 2D6) and NAT2 (N-acetyl transferase 2) have been found to be associated with multiple chemical sensitivities (94). These may be relevant to CFS because of its high comorbidities with these two disorders.

All these proteins touch on the pathogenesis mechanism described in this paper, which is what would be expected if this Hypothesis is valid.

With regard to the stressors found to precede onset of CFS, they are known to raise cortisol secretion (prior to onset and early in the course of the illness), to raise epinephrine secretion and to place demands on glutathione, leading to oxidative stress (1).

According to this Hypothesis, when reduced glutathione is sufficiently depleted and the oxidative stress therefore becomes sufficiently severe in a person having the appropriate genetic predisposition, a block is established at methionine synthase in the methylation cycle (95,2,3). Because the methylation cycle is located upstream of cysteine and glutathione in the sulfur metabolism, these are further depleted, and a vicious circle is formed.

Note that infectious pathogens are included among the possible biological stressors that can contribute to the onset of CFS. In particular, Borrelia burgdorferi, the bacterium responsible for Lyme disease, has been found to deplete glutathione in its host (96). This may explain the very similar pathophysiologies of chronic Lyme disease and CFS. This may also explain the epidemic clusters of CFS, which seem to have been produced by a virulent infectious pathogen (or pathogens). Perhaps the genetic factors are less important in producing the onset if a very virulent pathogen is present.

Epidemiology: According to the GD-MCB Hypothesis, the prevalence of CFS is determined by the frequency in the population of the combined presence of certain genetic polymorphisms (yet to be completely identified) and of the above described stressors occurring coincidentally in those having the polymorphisms. As noted earlier, the author has proposed that the higher prevalence in women is a result of increased bias toward oxidative stress, resulting from redox cycling in the metabolism of estradiol when certain polymorphisms in detoxication enzymes are present (76).

Suppression of parts of the immune response: Elevation of cortisol due to long-term stressors causes a suppression of the cell-mediated immune response and a shift to Th2 (97).

Depletion of reduced glutathione likewise causes a shift to Th2 (98, 99).

The elevation of cortisol prior to onset and in the early course of the illness also (temporarily) suppresses inflammation (100).

The cytotoxicity of natural killer (NK) cells and CD8 T cells in CFS has been found to be low, and Maher et al. found this to be associated with a deficiency of perforin secretion (101). According to the GD-MCB Hypothesis, in CFS perforin secretion is inhibited by depletion of reduced glutathione because glutathione is needed to form the disulfide bonds in their proper configurations in secretory proteins (102). Depletion of glutathione therefore causes misfolding and recycle of perforin molecules, which have twenty cysteine residues and thus ten disulfide bonds (103). This misfolding mechanism would affect other secretory proteins in CFS that are synthesized in cells having glutathione depletion as well, which may account for the observation of misfolded proteins in the spinal fluid of CFS patients by Baraniuk et al. (104).

Proliferation of T lymphocytes is inhibited by the block in the folate cycle, which inhibits production of new RNA and DNA (105).

Viral and intracellular bacterial reactivation: According to the GD-MCB Hypothesis, depletion of reduced glutathione is the trigger for the reactivation of latent viral and intracellular bacteria in CFS. The infections found initially in a case of CFS are usually due to those pathogens that are capable of residing in the body in the latent state, suggesting that these infections arise by reactivation (106). In general, intracellular glutathione depletion is associated with the activation of several types of viruses (1, 107-111) as well as Chlamydia (112), and it may account for reactivation of other latent intracellular bacteria as well. In herpes simplex type 1 viral infection, raising the glutathione concentration inhibits viral replication by blocking the formation of disulfide bonds in glycoprotein B (111). Since glycoprotein B appears to be present in all herpes virus types (113), it is likely that glutathione depletion is responsible for reactivation of Epstein-Barr virus, cytomegalovirus and HHV-6 in CFS.

The Coxsackie B3 virus genome is known to code for glutathione peroxidase, a selenium-containing enzyme (114). Taylor has suggested (115) that such viruses suppress the immune system of the host by depleting its selenium, thus inhibiting the host’s use of glutathione peroxidase. Since glutathione peroxidase makes use of Glutathione, depletion of reduced glutathione itself would therefore assist this virus in its mechanism of infection.

Populations more deficient in selenium would be expected to be more vulnerable to Coxsackie B3 infection. It is interesting to note that nearly all the studies of Coxsackie virus in CFS have come from the UK. The population there has become more deficient in selenium since the 1970s, when major sources of grain in the diet were changed to areas with selenium-deficient soils (116).

Immune activation: This occurs when the immune system detects the reactivation of pathogens (117).

Activation of 2-5A, RNase-L pathway (118): This pathway is activated by interferon and double stranded RNA as part of the cellular response to viral reactivation. According to the GD-MCB Hypothesis, RNase-L remains activated in CFS because of the suppression of the cell-mediated immune response and the consequent failure to defeat the viral infection (See Suppression of parts of the immune response, above.)

Mitochondrial dysfunction and the onset of physical fatigue: As hypothesized by Bounous and Molson (119), competition between the oxidative skeletal muscle cells and

The immune system for the decreased supply of glutathione and cysteine causes depletion of reduced glutathione in the skeletal muscles. According to the GD-MCB Hypothesis, this inhibits the glutathione peroxidase reaction and allows hydrogen peroxide to build up. This in turn probably exerts product inhibition on the superoxide dismutase reaction, which allows superoxide, produced as part of normal oxidative metabolism, to rise in the mitochondria of the oxidative skeletal muscle cells. Superoxide reacts with nitric oxide to produce peroxynitrite, as Pall (120) has pointed out. Superoxide also interacts with aconitase in the Krebs cycle to inhibit it (121), and peroxynitrite can cause partial blockades in the Krebs cycle and also the respiratory chain (120, 122). These reactions lower the rate of production of ATP, and this constitutes mitochondrial dysfunction. Since ATP is needed to power muscle contraction, lack of it produces physical fatigue.

RNase-L cleavage, leading to formation of the low molecular weight version (123): Depletion of reduced glutathione removes inhibition of the activity of calpain (124), which is located in the cytosol with RNase-L, and calpain cleaves RNase-L (125). (Elastase, the other enzyme found by Englebienne et al. (125) to be able to cleave RNase-L in the laboratory, is confined to granules and vesicles inside living cells (126), and thus is not in contact with RNase-L.)

Failure to defeat viral and intracellular bacterial infections and continuing immune activation: According to the GD-MCB Hypothesis, these occur because of depletion of reduced glutathione (127) and also because the folate metabolism block prevents production of new DNA and RNA for proliferation of T lymphocytes (105).

Depletion of magnesium: There is a long history showing depletion of magnesium in CFS and benefits of supplementation, both orally and by injection (See review in Ref. 39). Magnesium depletion may be responsible for a variety of symptoms that are found in CFS (128), including mitochondrial dysfunction, muscle twitching, muscle pain, sleep problems and cardiac arrhythmia. In connection with sleep problems, Durlach et al. have found that magnesium depletion is associated with abnormalities in the level of melatonin and dysregulation of biorhythms (129). Manuel y Keenoy et al. (54) found that the subset of CFS patients that was resistant to repletion of magnesium in their clinical study also showed glutathione depletion. It has also been found that glutathione depletion causes magnesium depletion in red blood cells (130). According to the GD-MCB Hypothesis, the depletion of intracellular magnesium in CFS is another result of depletion of reduced glutathione.

Buildup of toxins: Glutathione depletion allows toxins, including heavy metals, to build up, because there is not enough glutathione to conjugate these toxins as rapidly as they enter the body. Mercury is of particular concern, because the population in general has considerable exposure to it from dental amalgams, fish consumption, and environmental sources such as nearby coal-fired power plants. There is considerable clinical experience of mercury buildup in CFS patients (1). Immune testing has also shown evidence that the immune system has responded to elevated mercury in CFS patients (131-133).

Solidification of the vicious circle: After the vicious circle has developed involving the methylation cycle block and the depletion of glutathione, another factor must come into play to lock in this situation chronically. It seems likely that buildup of toxins is the factor responsible for this, by blocking the formation of methylcobalamin and thus the activity of methionine synthase. It has been shown that one of the important roles of glutathione normally is to protect the very much smaller (by six orders of magnitude) concentrations of cobalamins from reaction with toxins by forming glutathionylcobalamin (134). Without this protection, cobalamins are vulnerable to reaction with a variety of toxins. An example is mercury. It has been found that very small concentrations of mercury are required to block the methionine synthase reaction (135). Because of this additional factor, attempts simply to correct the glutathione depletion and the oxidative stress after the Cobalamins have reacted with toxins in most cases will not restore normal function of the methylation cycle (1).

Neurotransmitter dysfunction: The production of melatonin from serotonin as well as the metabolism of the catecholamines require methylation, as noted earlier, and according to the GD-MCB Hypothesis, they are inhibited because of the decreased methylation capacity. Also, genetic polymorphisms involving enzymes in the neurotransmitter system have been found to be more frequent in at least some subsets of CFS patients, as noted earlier. These factors cause dysfunction of the neurotransmitters.

Further development of mitochondrial dysfunction: As the course of the illness progresses, it is likely that other factors that result from glutathione depletion and the methylation cycle block come into play and further suppress the operation of the mitochondria. These include the buildup of toxins and infections, depletion of magnesium, and damage to the phospholipid membranes of the mitochondria by oxidizing free radicals (136). Because the essential fatty acids in these membranes are polyunsaturated, they are the most vulnerable to oxidation (137), and they become depleted, at least in some CFS patients (See review in Ref. 39).

HPA axis blunting (138): According to this Hypothesis, glutathione depletion in the pituitary gland inhibits production of proopiomelanocortin (POMC) (which has two disulfide bonds in its N-terminal fragment (139)), and hence secretion of ACTH (which is part of POMC), by the same mechanism as inhibition of perforin synthesis (102) (See Suppression of parts of the immune response, above.). This results in the lowering of cortisol secretion by the adrenal glands, which is a late finding in the course of the illness (140). As noted earlier, genetic polymorphisms in POMC may also be involved in a subset of CFS patients (91).

Diabetes insipidus (excessive urination, thirst, decrease in blood volume): According to this Hypothesis, glutathione depletion inhibits production of arginine vasopressin (141), which has one disulfide bond (142), by the same biochemical mechanism by which it inhibits perforin and ACTH synthesis (102). It is likely that the secretion of oxytocin, which also has one disulfide bond and is also synthesized in the hypothalamus, is also inhibited. Measurements of oxytocin in CFS have not been reported, but there is evidence that it is low in some fibromyalgia patients (143), which may be relevant because of the high comorbidity of CFS and fibromyalgia. A clinician has reported benefit from oxytocin injections in fibromyalgia patients (144).

Low cardiac output (145): According to this Hypothesis, this occurs because depletion of reduced glutathione in the heart muscle cells lowers the rate of production of ATP, as in the skeletal muscle cells. This produces diastolic dysfunction as observed by Cheney (146, 147). Both low blood volume (see Diabetes insipidus, above), which produces low venous return, and diastolic dysfunction, which decreases filling of the left ventricle, produce low cardiac output. In addition, in some cases, as observed by Lerner et al., viral infections produce cardiomyopathy (148). According to the GD-MCB Hypothesis, this is a result of depletion of reduced glutathione and suppression of cell-mediated immunity. This is another factor that can decrease cardiac output in CFS.

Orthostatic hypotension and orthostatic tachycardia (149): According to this Hypothesis, these occur because of low blood volume, low cardiac output and HPA axis blunting (See Diabetes insipidus, Low cardiac output, and HPA axis blunting, above.).

Loss of temperature regulation: As pointed out by Cheney (146), this occurs because of low cardiac output (see Low cardiac output, above), which causes the autonomic nervous system to decrease blood flow to the skin. This removes the ability to regulate the rate of heat loss from the skin.

Hashimoto’s thyroiditis (150) and elevated incidence of thyroid cancer (151): According to this Hypothesis, Hashimoto’s thyroiditis occurs in CFS because depletion of reduced glutathione in the thyroid gland allows damage to thyroglobulin by hydrogen peroxide, as proposed by Duthoit et al. (152). In addition, hydrogen peroxide damage to DNA in the thyroid gland may be responsible for the elevated incidence of cancer there. Hydrogen peroxide is produced normally by the thyroid to oxidize iodide in the process of making thyroid hormones (153).

Increasing variety of infections (154) and inflammation (155): According to this Hypothesis, viral, intracellular bacterial and fungal infections accumulate over time because the cell-mediated immune response is dysfunctional (See Suppression of parts of the immune response, above.). Inflammation becomes more severe because of the decreased secretion of cortisol later in the course of the illness (See HPA axis blunting, above), and because of the rise in histamine as a result of lack of sufficient methylation capacity to deactivate it (156).

Slow gastric emptying (157) and gastroesophageal reflux: According to this Hypothesis, in CFS these result from mitochondrial dysfunction in the parietal cells of the stomach, due to depletion of reduced glutathione, which results in low production of stomach acid. (Anecdotally, many CFS patients have reported absence of eructation after ingestion of sodium bicarbonate solution on an empty stomach, suggesting low stomach acid status.) A slower rate of gastric emptying was found to be associated with higher pH, i.e. lower acid status (158).

Gut problems: According to this Hypothesis, several of the above factors converge to produce problems in the gut in CFS, often referred to as irritable bowel syndrome (IBS). These factors include glutathione depletion, low cardiac output, immune suppression, low stomach acid production, neurotransmitter dysfunction (note that serotonin plays a major role in gut motility), and increasing variety of infections and inflammation.

The degree of abnormality of a lactulose breath test (indicating small intestinal bacterial overgrowth) in fibromyalgia patients was found by Pimentel et al. to be greater than in IBS patients without fibromyalgia (159). In addition, they found that the abnormality was correlated with somatic pain (159). (This may be relevant because of the high comorbidity of CFS with fibromyalgia.)

Brain-related problems: According to this Hypothesis, several of the above factors also converge to produce problems in the brain. These include glutathione (and cysteine) depletion, low cardiac output, failure to defeat infections and continued immune activation, neurotransmitter dysfunction, decreased methylation capacity to maintain myelin, and increasing variety of infections and inflammation.

Relapsing (Crashing) (160): Many CFS patients have chronically low glutathione levels. According to this Hypothesis, when the level of stressors is temporarily increased, the levels of reduced glutathione become more severely depleted, and this produces the so-called crashing phenomenon. After a period of rest, reduced glutathione levels are increased to the chronically low levels that existed prior to the increased stressors.

Alcohol intolerance (161): According to this Hypothesis, because of mitochondrial dysfunction, the skeletal muscles of CFS patients depend more than normal on glycolysis for ATP production. Increased use of glycolysis requires increased use of gluconeogenesis by the liver to convert lactate and pyruvate back to glucose (Cori cycle). In CFS, this is hampered by low cortisol levels. The metabolism of ethanol by the liver further inhibits gluconeogenesis,

Producing hypoglycemia and lactic acidosis. This accounts for the alcohol intolerance reported by many CFS patients.

Weight gain: According to this Hypothesis, the weight gain often seen in CFS results from the inability to metabolize carbohydrates and fats at normal rates, because of partial blockades in the Krebs cycle produced by depletion of reduced glutathione. Excess carbohydrates are cycled back to glucose by gluconeogenesis, and ultimately are converted to stored fat.

Low serum amino acid levels (19): According to this Hypothesis, these result from the burning of amino acids as fuel at higher rates than normal. Amino acids are able to enter the Krebs cycle by anaplerosis, downstream of the partial blockades, so they can be used as fuel in place of carbohydrates and fats.

The pathogenesis of CFS becomes increasingly complex as it proceeds, because of the interactions and feedback loops that develop. For this reason, determining the cause-effect relationships for all the aspects of the resulting pathophysiology is a problem that is exceedingly difficult. Nevertheless, understanding the etiology and early pathogenesis provides a basis for developing a more effective treatment approach.

CONCLUSIONS

There is abundant and compelling evidence that the glutathione depletion—methylation cycle block mechanism is an important part of the pathogenesis for at least a substantial subset of chronic fatigue syndrome patients.

A pathogenesis hypothesis based on this mechanism is capable of explaining and unifying many of the published observations regarding chronic fatigue syndrome, and it provides a basis for developing a more effective treatment approach.

KEY TO DIAGRAM

The diagram shows the methylation cycle at the top right, the folate cycle at the top left, and the transsulfuration pathway at the bottom right.

The enzymes that catalyze the reactions are shown in boxes:

BHMT - Betaine homocysteine methyltransferase
CBS - Cystathionine beta synthase
CDO - Cysteine dioxygenase
CGL - Cystathionine gamma lyase
GCL - Glutamate cysteine ligase
GS - Glutathione synthase
MAT - Methionine adenosyltransferase
MS - Methionine synthase
MSR - Methionine synthase reductase
MTase - Methyltransferase (a class of enzymes)
MTHFR - Methylene tetrahydrofolate reductase
SHT - Serine hydroxymethyltransferase
TS - Thymidylate synthase

Most of the metabolites are spelled out. The ones that are abbreviated are as follows:

DMG - Dimethylglycine
SAH - S-Adenosylhomocysteine
SAM - S-Adenosylmethionine
THF - Tetrahydrofolate
TMG - Trimethylglycine (betaine)

The cofactor and coenzyme are as follows:

P5P - Pyridoxal phosphate, the active form of Vitamin B6
B12 - Methylcobalamin, one of the active forms of Vitamin B12

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Here's an update I just completed. Note that some adverse effects have shown up in a few people on the simplified treatment approach based on the methylation cycle block. They are described toward the end of this article.

Rich

July 18, 2007

Simplified Treatment Approach Based on the Glutathione Depletion-Methylation Cycle Block Pathogenesis Hypothesis for Chronic Fatigue Syndrome (CFS) by Rich Van Konynenburg, Ph.D.

I first want to note that I am a researcher, not a clinician, and that what I have to say here should not be interpreted as medical advice.

In January, 2007, in an effort to shed light on the validity of the Glutathione Depletion-Methylation Cycle Block (GD-MCB) Pathogenesis Hypothesis for Chronic Fatigue Syndrome (CFS), and to help clinicians to develop a practical treatment based on this Hypothesis, I suggested a simplified treatment approach. This approach is designed to lift the hypothesized methylation cycle block and to restore glutathione levels to normal. It was derived from a complete treatment program developed by Dr. Amy Yasko, N.D., Ph.D., for autism and other disorders that are also thought to involve methylation cycle block and glutathione depletion.

A fairly large number of people with chronic fatigue syndrome (PWCs) have since voluntarily chosen to try this treatment approach, many with the help of their physicians. It now appears to be working well for many of these PWCs, but some serious adverse effects have also been reported in a few cases. Controlled testing of this treatment approach has not yet been done, but early results from these volunteers suggest that this would not only be worthwhile in view of indications of the efficacy of this approach, but also necessary to ensure its safe application.

I would like to describe the history of the Glutathione Depletion-Methylation Cycle Block (GD-MCB) Hypothesis and the simplified treatment approach that is based upon it, and point out what I think the early treatment results mean with regard to this Hypothesis. But before I do so, I want to emphasize the following cautionary statements:

While in the past I have stated that PWCs should cooperate with their physicians in trying the simplified treatment approach, as a result of experiences with this treatment approach that have been reported to me recently, I have concluded that it must be entered upon only under the supervision of a licensed physician, to make sure that if there are individual issues that arise, they can be taken care of immediately. The treatment approach itself consists only of nonprescription nutritional supplements that are normally found naturally in the body and are necessary for normal biochemistry to take place. It would thus appear to be fairly benign on its surface. However, it is now clear to me that restarting the methylation cycle after it has been blocked for extended periods, particularly in those PWCs whose general health has become quite debilitated, or those who have certain respiratory, cardiac, endocrine or autoimmune conditions, can present some serious challenges and hazards. I suspect that there is still much more to be learned about possible adverse effects of applying this treatment approach among the very heterogeneous CFS population, and this work properly lies in the province of clinicians. I believe that I have now carried this work as far as a nonclinical researcher can appropriately carry it. I am hopeful that clinicians will apply and test this treatment approach in order to learn how it may be safely, effectively, and practically utilized to treat PWCs, and it appears that this is now beginning to occur.

As some readers will probably be aware, I presented a poster paper describing the above-mentioned Hypothesis at the most recent IACFS conference in Florida last January. It can be found on the internet on Cort Johnson’s website: http://phoenix-cfs.org/GSH%20Methylation%20Van%20Konynenburg.htm

This Hypothesis has not yet been published in the peer-reviewed literature. My emphasis up to now has instead been upon addressing questions that remained to be answered before this Hypothesis could be considered for clinical testing and application in the form of a practical treatment approach.

The history of the development of this Hypothesis is as follows:

In 1999, I first learned from two public talks presented by Dr. Paul Cheney that many PWCs are depleted in glutathione, and that taking steps to build glutathione can be helpful to many. Dr. Derek Enlander has since reported to me that he began injecting glutathione as part of a complex into CFS patients as early as 1991. I also found that Dr. Patricia Salvato had reported in early 1998 on her use of intramuscular injection of glutathione in 276 patients. Over the years, quite a few CFS doctors have incorporated means of building glutathione into their protocols, either by administration of glutathione itself by various routes, or by oral supplementation with glutathione precursors, such as whey protein products.

What is glutathione, and what does it do?

Glutathione is technically a tripeptide, which can be thought of as being like a very small protein, as it is made up of only three amino acids (while proteins are made up of many more). It is present naturally in every cell of the body, as well as in the blood, the bile and the fluid lining the lungs. The liver is normally the main producer of glutathione in the body. Glutathione plays many important roles in the body. Probably the best known are its protection against oxidative stress produced by oxidizing free radicals and other reactive oxygen species, its support for the immune system, and its role in removing a variety of toxic substances from the body.

When glutathione becomes somewhat depleted, as it does in many cases of CFS, its normal functions are simply not performed well. Many of the symptoms of CFS as well as observed abnormal results on specialized lab tests can be traced directly to glutathione depletion, as I described in an earlier AACFS poster paper in 2004. It can be found on Cort Johnson’s website: http://phoenix-cfs.org/GluAACFS04.htm.

As I noted in that paper, while direct efforts to build glutathione are helpful to many PWCs, for most they provide only temporary improvement and do not result in permanent restoration of glutathione levels or a cure for CFS. I suspected that a vicious circle mechanism must be involved in holding down the glutathione levels in CFS.

Then, later in 2004, an important paper was published involving research into autism by S. Jill James and her coworkers: “Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism”(Am J Clin Nutr. 2004 Dec;80(6):1611-7). The study they reported showed that glutathione is depleted also in autism, and that this depletion is associated with a block in what is known as the methylation cycle (or methionine cycle).

Before discussing this further, I want to address the question “What is the methylation cycle, and what does it do?”

The methylation cycle is part of the basic biochemistry of the body, and is believed to operate in every cell. This cycle includes the amino acid methionine as well as S-adenosylmethionine (SAMe, used as a supplement by some PWCs), S-adenosylhomocysteine, and homocysteine. Some homocysteine is converted back to methionine, thus completing the cycle. There are two parallel pathways from homocysteine to methionine. They are the methionine synthase pathway and the BHMT (betaine homocysteine methionine transferase) pathway. The methylation cycle is directly linked to the folate metabolism and to the transsulfuration pathway.

The methylation cycle performs many vital roles in the body. First, by means of SAMe, it supplies methyl (CH3) groups to many different biochemical reactions. Some of them produce substances such as coenzyme Q-10 and carnitine, which have been found to be depleted in many PWCs. Methylation also plays an important role in “silencing” certain DNA to prevent its expression, and in producing myelin for the brain and nervous system.

The methylation cycle also controls the body’s response to oxidative stress, by governing how much homocysteine is diverted into the transsulfuration pathway, which contributes to determining the rate of synthesis of glutathione.

A third important role of the methylation cycle is to control the overall sulfur metabolism of the body. In this role, besides controlling glutathione synthesis, it exerts control over synthesis of several other important substances, including cysteine, taurine and sulfate.

When the methylation cycle is blocked at the enzyme methionine synthase, these important roles are not carried out properly. In addition, a methylation cycle block necessarily causes a block in the folate metabolism, to which it is intimately linked, and this interferes with synthesis of new DNA and RNA, among other important effects.

Two of the most significant effects of a methylation cycle block are that neither the immune system nor the detox system can operate properly. If the methylation cycle remains blocked for an extended period of time, infections and toxins can be expected to build up in the body.

After I read the paper by S. Jill James and her coworkers (referred to above), I began to suspect that the genetic factors and biochemical mechanism they had found in autism are the same or similar to those important in CFS. A block earlier than glutathione in the sulfur metabolism, at the methylation cycle, could explain the persistent glutathione depletion in CFS. It began to dawn on me that other aspects of CFS that did not appear to be explained by glutathione depletion per se could be explained by a methylation cycle block.

It was difficult for me initially to believe that there was a connection between autism and CFS, given the profoundly different symptoms and different affected population groups (primarily boys in autism, compared to primarily adult women in CFS). However, I knew of others who had publicly suggested such a connection in the past (Dr. Michael Goldberg in the U.S. and Prof. Malcolm Hooper in the UK), and this new study seemed to provide more detailed evidence of this connection at the genetic and biochemical levels.

I began to look into autism in more detail, and I attended the Long Beach conference of the Defeat Autism Now! (DAN!) project in October of 2005. The more I learned about autism, the more I became convinced that are dealing in CFS with many of the same issues at the genetic and biochemical levels. The book by Drs. Jon Pangborn and Sidney Baker entitled “Autism: Effective Biomedical Treatments” (Autism Research Institute, September, 2005) provides excellent explanations of the biochemistry of autism, and the parallels with CFS can be seen there.

I want to emphasize that I did not develop the Glutathione Depletion--Methylation Cycle Block Hypothesis out of thin air. The autism researchers had already provided a convincing basis for this model in that disorder. S. Jill James and coworkers did much of the clinical work that underlies it. Richard Deth and his coworkers had worked out much of the theory of the methylation cycle block and had applied it to autism. Professors James and Deth had been presenting talks on their work at autism conferences. The physicians in the DAN! project (as well as Dr. Amy Yasko, though I had not yet learned of her work when I began to understand the importance of the methylation cycle block) had already been treating autism cases by measures intended to lift the methylation cycle block. What I did was to apply the results of their work to CFS, and to present a detailed biochemical and symptomological case to support the proposition that this model also applies to CFS.

What is the essence of the Glutathione Depletion-Methylation Cycle Block Hypothesis for the Pathogenesis of CFS?

This hypothesis proposes first that in order to develop CFS, a person must have inherited genetic variations (also called SNPs or single-nucleotide polymorphisms) in a combination of certain genes that code for enzymes and other proteins associated with the methylation cycle and related pathways.

The hypothesis further proposes that the person must also be subjected to some combination of a variety of long-term physical, chemical, biological or psychological/emotional stressors that lowers glutathione levels to the point that a block occurs in the enzyme methionine synthase in the methylation cycle, in response to the oxidative stress that is inherent in glutathione depletion. The formation of this block is aided by the presence of the inherited genetic polymorphisms. This lowering of glutathione levels also simultaneously removes the normal protection that glutathione provides to vitamin B12 and allows the accumulation in the body of toxins that can interfere with the utilization of vitamin B12, mercury perhaps being the dominant one.

This hypothesis further proposes that the result of the above is that the level of methylcobalamin is held too low to support the methionine synthase reaction, and it therefore becomes chronically blocked. This produces a vicious circle mechanism that causes CFS to become a chronic condition.

Finally, this hypothesis proposes that all the features of CFS can be shown to originate from this root cause. While I have not yet demonstrated this for every feature of CFS, the first paper cited in this article explains a large number of them in detail on this basis. Previous treatments for CFS have dealt with downstream issues in the pathogenesis, but they have not completely addressed this root cause, and, in my opinion, that is we have not seen many completely cured CFS cases up to now. Note that when I refer to cured cases, I do not mean that the genetic predisposition has been removed, but that that the PWCs are healthy from the symptomatic point of view.

As I became more convinced of the parallels between autism and CFS, I began to point out this connection to some clinicians directly and to others via the internet, as well as to PWCs in internet groups, and I began encouraging them to consider the treatments that were being used by the Defeat Autism Now! project to treat autism, focusing on unblocking the methylation cycle. A small number of PWCs tried this approach, and while some initial benefits were observed from this, it did not seem to be an effective approach over the long term, at least in the way I was suggesting that it be applied. I then learned of the work of Dr. Amy Yasko, N.D., Ph.D. in autism. I studied her materials, including the book written by her and Dr. Garry Gordon entitled “The Puzzle of Autism,” joined her discussion forum at http://www.ch3nutrigenomics.com/ and eventually attended her teaching seminar in Boston in October of 2006. After considering all of this, I concluded that it was likely that her treatment approach could help many PWCs, so I decided to emphasize it. An important feature of her work is her effort to tie the genetics of individuals to the biochemistry and to do tailored treatment based on genetics, again directed toward correcting the methylation cycle block, but also incorporating support for a variety of body systems and organs. I also learned that Dr. Yasko had had some experience in using her approach in cases of CFS as well as a variety of adult neurological disorders, but that she was currently focusing primarily on autism.

I wrote a short article pointing out the connection I was seeing between autism and CFS and pointing to these treatments, and it was published in the October 2006 issue of the Townsend Letter. This can be found at the following url: http://findarticles.com/p/articles/mi_m0ISW/is_279/ai_n16865315

Quite a few PWCs acted on my suggestion to try Dr. Yasko’s full treatment approach, and they are currently continuing with it. Many of them participate in the Yahoo cfs_yasko internet group, a group that was specifically formed for them, which can be found at http://health.groups.yahoo.com/group/CFS_Yasko/.

Most of them are currently in the first step of this treatment approach, and they are generally reporting that this treatment is producing considerable detoxification of their bodies, as monitored by urine testing. The full Yasko treatment approach involves detailed genetic and biochemical testing, and is rather expensive and complex. While some PWCs are in a position to pursue this treatment and appear to be doing so successfully, it seemed to me that there are many others for whom this approach is beyond reach, either for economic or cognitive reasons or both. Practicing physicians have generally also found this treatment to be somewhat cumbersome to incorporate into their practices because of the complexity and the considerable time and expense required to tailor the treatment to each individual patient.

In response to these issues and to requests from clinicians for a written description of practical CFS treatment based on this hypothesis, I wrote an article that outlined the full Yasko treatment approach, but also described a simplified treatment approach that incorporated nutritional supplements that form the core of Dr. Yasko's so-called "step 2." This is the step in her treatment program that involves actually lifting the block in the methylation cycle. This article can be found on Cort Johnson’s website: http://phoenix-cfs.org/GSH%20Methylation%20Treatment%20Konynenburg.htm

When I proposed this approach, I did not know what fraction of the PWC population would be able to tolerate the resulting die-off of pathogens and mobilization of toxins that would result from the consequent ramp-up of the immune system and the detox system after they had been dysfunctional for such long times during the long illness duration of many PWCs. As can be seen in the above-cited article, I was not very optimistic. However, I still thought it was worth a try, since the existing full Yasko approach did not seem to have the characteristics necessary for wide use in the CFS community, and it appeared that lifting the methylation cycle block was the key to recovery for many PWCs. With the help of a woman (name omitted to protect her privacy) who is currently receiving the full Yasko treatment herself, I selected a basic set of seven supplements from Dr. Yasko's step 2, as discussed in the above-mentioned article.

After this article was presented on the internet, another woman (name omitted to protect privacy) decided to try this simplified treatment approach. As a result of benefits that occurred almost immediately, she reported her experience on the ImmuneSupport.com CFS discussion board. In response to her reports, others began to try this approach. This began in February of 2007, and the number of people on this treatment has continued to grow, the longest duration of treatment now being somewhat more than four months, ranging down to some as short as a few days.

As experience has been gained, I have shortened the initial list of seven supplements in the suggested simplified treatment approach to five, as described below. The cost of the basic five supplements is somewhat more that two dollars per day.

After suggesting this treatment approach, I initially attempted to maintain a list of those who were trying it, based on reports I received from physicians and individual PWCs. However, when the number of people I was aware of grew past 60, I no longer felt that I could maintain a complete count. Many have been reporting their progress periodically to the ImmuneSupport board, and a new Yahoo group also has been established recently for PWCs trying this approach, at the following url: http://health.groups.yahoo.com/group/simplified_protocol_support/.

I will now describe the current version of the simplified treatment approach based on the Glutathione Depletion--Methylation Cycle Block Hypothesis.

All the supplements used in this approach can be obtained from the http://www.holisticheal.com site, or all but the Complete Vitamin and Neurological Health Formula can be obtained elsewhere. Please note that I have no financial interest in any of the supplements that I have suggested in the simplified treatment approach.

As I mentioned above, these supplements and dosages have been selected by Dr. Amy Yasko as part of her complete treatment approach, as described in her book "The Puzzle of Autism." Substitutions or changes in dosages may not have the same effect as the combination of supplements and dosages suggested, although it is wise to start with smaller dosages than those given below, and it is also wise to start with one supplement at a time and work up to the total of five supplements, to test carefully for adverse effects. It will take somewhat longer to reach the suggested combination and dosages by this route, but early experience has shown that this is prudent.

As I also mentioned above, this treatment approach should be attempted only under the supervision of a licensed physician, so that any individual issues that arise can be properly dealt with. It's important to "listen to one’s body" when doing this treatment. If the detox becomes too intense to tolerate, or if significant adverse effects appear, as described below, the supplements should be discontinued, and the situation should be evaluated immediately by a licensed physician. This treatment will produce die-off and detox symptoms as the immune system and detox system come back to normal operation and begin ridding the body of accumulated infections and toxins. This appears to be inevitable, if health is to be restored. It may require considerable judgment and clinical experience on the part of the physician to distinguish between inevitable die-off and detox symptoms and possible adverse effects.

While die-off and detox symptoms are occurring, there will also likely be improvement in CFS symptoms over time. The intensity of the expected die-off and detox symptoms can be decreased by lowering the dosages of the supplements. These symptoms probably result from the body’s limited rates of excretion of toxins. If toxins are mobilized more rapidly than they can be excreted, their levels will rise in the blood, and it is likely that this will produce more severe die-off and detox symptoms. By lowering the dosages, and thus slowing the rate of mobilization of toxins, their levels in the blood can be lowered, thus ameliorating the symptoms.

The temptation to try to get better faster by increasing the dosages suggested by Dr. Yasko must be resisted. In particular, the suggested dosages for the FolaPro and the Intrinsi/B12/folate supplements should not be exceeded. Some who have done this have experienced very unpleasant levels of detox symptoms that had momentum and did not decrease rapidly when the supplements were stopped.

As improvements in energy level and cognition occur, it is tempting for PWCs to overdo activities, which, early in the treatment, can still result in “crashing.” It is wise to resist this temptation as well, because complete recovery will not occur overnight with this treatment approach.

I am not aware of negative interactions between the five basic supplements and prescription medications used by physicians in treating CFS. However, this treatment approach should not be attempted without considering together with a licensed physician possible interactions between the supplements included in it and any prescription medications that are being taken. This is particularly important if addition of SAMe to the basic five supplements is contemplated.

When this treatment approach is used together with prescription medications, a licensed physician must be consulted before discontinuing any prescription medications. Some of them can cause very serious withdrawal symptoms if stopped too abruptly.

If this treatment approach is begun by a PWC who is taking a thyroid hormone supplement for a hypothyroid condition, the PWC and the supervising physician should be alert to the possibility that HYPERthyroid symptoms, such as palpitations and sweats, can occur, even very soon after starting this treatment. The physician should be consulted about possibly adjusting or eliminating the thyroid hormone supplementation if this occurs.

Here are the five supplements, as found in Dr. Yasko’s book “The Puzzle of Autism,” (p. 49) and as described in detail on her website http://www.holisticheal.com :

Konynenburg

1. One-quarter tablet (200 micrograms) Folapro (Folapro is 5-methyl tetrahydrofolate, an active form of folate, which is sold by Metagenics with a license from Merck, which holds the patent on synthesis).

2. One-quarter tablet Intrinsic B12/folate (This includes 200 micrograms of folate as a combination of folic acid, 5-methyl tetrahydrofolate, and 5-formyl tetrahydrofolate, also known as folinic acid or leucovorin (another active form of folate), 125 micrograms of vitamin B12 as cyanocobalamin, 22.5 milligrams of calcium, 17.25 milligrams of phosphorus, and 5 milligrams of intrinsic factor)

3. Up to two tablets (It’s best to start with one-quarter tablet and work up as tolerated) Complete Vitamin and Ultra-Antioxidant Neurological Health Formula from Holistic Health Consultants (This is a multivitamin, multimineral supplement with some additional ingredients. It does not contain iron or copper, and it has a high ratio of magnesium to calcium. It contains antioxidants, some trimethylglycine, some nucleotides, and several supplements to support the sulfur metabolism.)

4. One softgel capsule Phosphatidyl Serine Complex (This includes the phospholipids and some fatty acids)

5. One sublingual lozenge Perque B12 (2,000 micrograms hydroxocobalamin with some mannitol, sucanat, magnesium and cherry extract)

The first two supplement tablets are difficult to break into quarters. One of the PWCs who is following the simplified treatment approach has suggested that an alternative approach is to crush them into powders, mix the powders together, and divide the powders into quarters using a knife or single-edged razor blade and a flat surface. The powders can be taken orally with water, with or without food, and do not taste bad.

Some people have asked what time of the day to take the supplements. A few have reported that the supplements make them sleepy, so they take them at bedtime. If this is not an issue, they can be taken at any time of the day, with or without food.

Since some questions have been asked about which components of this treatment approach are essential, and since some PWCs appear to be taking augmented versions of the simplified GD-MCB treatment approach that I wrote about in my January treatment paper (cited above), I want to offer some comments to help PWCs and their physicians to evaluate which supplements to include in treatment.

FolaPro--This is included because many PWCs have a genetic polymorphism in their MTHFR (methylene tetrahydrofolate reductase) enzyme that affects the production of 5-methyltetrahydrofolate (which is identical to the product FolaPro). This form of folate is the one used by the methionine synthase enzyme, which is the enzyme that appears to be blocked in many cases of CFS. If PWCs were to have their genetics characterized, as in the full Yasko approach, they would know for sure whether they needed this supplement, but in the simplified approach I suggest simply giving it to everyone. This should not present problems, because the total folate dose, including the FolaPro and the folates in the Intrinsi/B12/folate supplement, amounts to 400 micrograms per day, which is within the upper limit for folate supplementation for adults and for children four years of age and older, as recommended by the Institute for Medicine of the U.S. National Academy of Sciences.

Intrinsi/B12/folate--This supplement contains three forms of folate--FolaPro, folinic acid (identical to the drug leucovorin) and folic acid (the most common commercial folate supplement). It also has some cyanocobalamin (the most common commercial vitamin B12 supplement) and some intrinsic factor (identical to that normally secreted by the stomach to enable vitamin B12 absorption by the gut) as well as some other things. The folinic acid is helpful because some people can't use ordinary folic acid well, as a result of genetic issues. Also, this helps to supply forms of folate that will make up for the low tetrahydrofolate resulting from the block in methionine synthase, until this is corrected. This enzyme normally converts 5-methytetrahydrofolate to tetrahydrofolate, which is needed in other reactions. This supplement also has some intrinsic factor and some cyano-B12 to help those who have a type of pernicious anemia that results from low production of intrinsic factor in the stomach and which prevents them from absorbing B12 in the gut. Vitamin B12 is needed by the enzyme methionine synthase, in the form of methylcobalamin, but this supplement has cyanocobalamin, which must be converted in the body by glutathione and SAMe to form methylcobalamin. As glutathione and SAMe come up, this should become more effective.

Complete Vitamin and Ultra-Antioxidant Neurological Health Formula--This is Dr. Amy Yasko's basic high-potency general nutritional supplement. This is a general foundation for the biochemistry of the body. I suspect that this supplement is better for PWCs trying the simplified treatment approach than other high-potency general nutritional supplements, because it has particular things needed for dealing with a methylation cycle block, including some TMG and sulfur metabolism supplements as well as nucleotides. It is also high in magnesium and low in calcium, and has no iron or copper. As far as I know, there are no other supplements with all these characteristics. I therefore believe that this supplement is important for use in the treatment approach. The TMG helps to stimulate the BHMT pathway in the methylation cycle, and that helps to build SAMe, which is needed by the parallel methionine synthase pathway. The nucleotides will help to supply RNA and DNA for making new cells until the folate cycle is operating normally again.

Phosphatidylserine complex—This contains various phosphatidyls and fatty acids, which will help to repair damaged membranes, including those in cells of the brain and nervous system. It should help with the cortisol response. It also has some choline, which can be converted to TMG (betaine) in the body, to help stimulate the BHMT pathway.

Perque B12--This is sublingual hydroxocobalamin. The dosage is fairly large, in order to overcome the blocking of B12 by toxins such as mercury in CFS. As I mentioned above, B12 is needed to stimulate the activity of methionine synthase. Methylcobalamin is actually the form needed, but some people cannot tolerate supplementing it for genetic reasons, and I'm also concerned that people with high body burdens of mercuric mercury could move mercury into the brain if they take too much methylcobalamin. Methylcobalamin is the only substance in biological systems that is known to be able to methylate mercury. (Note that methylcobalamin is the substance used by bacteria to perform methylation on environmental mercury, and the resulting methylmercury is concentrated in the food chain up to the large predatory fish and enters the human diet.) Methylmercury can readily cross the blood-brain barrier. Methylation of mercury by methylcobalamin has been reported in the literature to occur within the bodies of guinea pigs in laboratory experiments. Perque B12 is sublingual to compensate for poor B12 absorption in the gut of many people.

There are also two other supplements that were included in the earlier version of the simplified approach:

SAMe--This is normally part of the methylation cycle. Depending on genetic variations (SNPs or polymorphisms) some PWCs can't tolerate much of this, and some need more. If PWCs can't tolerate this, they should leave it out, because stimulating the BHMT pathway, using TMG and choline in the other supplements, will probably make enough SAMe for them naturally. For people who can tolerate SAMe, a dosage of 400 mg per day is suggested.

Methylation Support RNA Formula--This is a mixture of RNAs that is designed to help the methylation cycle. It is somewhat expensive, and is not essential, but is helpful if people can afford it. Dr. Amy Yasko has since advised me that if a PWC desires to take only one of her RNA Products, she would suggest choosing either the Health Foundation RNA Formula or the Stress Foundation RNA Formula, rather than the Methylation Support RNA Formula, as being most helpful to take the edge off the detox.

The above suggested list of supplements may not be optimum, and future clinical studies may produce an improved protocol. I think that the forms of folate and B12 are probably essential, because they target what I believe is the root issue in the abnormal biochemistry of CFS. I think the Complete supplement is important to support the general biochemistry and to correct deficiencies that might be present in essential nutrients, as well as to support the methylation cycle and the rest of the sulfur metabolism. I think that some way of stimulating the BHMT pathway is important, also, to bring up SAMe, and the phosphatidyl serine complex provides this, as does the TMG included in the Complete supplement.

With regard to possible interactions between the supplements in the simplified treatment approach and other supplements that PWCs may be taking, I am aware of two: (1) I would not recommend taking additional folate beyond what is suggested above, since the various forms of folate compete with each other for absorption, and it is important to get enough of the active forms into the body. Also, it is important not to take too much folate, as mentioned above, because this can cause the detox to develop a momentum, so that it will take some time to slow it down if you want to do that. (2) I would also not recommend taking additional trimethylglycine (TMG, also called betaine) or additional forms of choline, such as phosphatidylcholine or lecithin, since that may stimulate the BHMT pathway too much at the expense of the methionine synthase pathway. The betaine-HCl used to augment stomach acid is something that may have to be omitted while doing this treatment, too, since it will contribute to this stimulation.

Adding glutathione support will help some people, as will adding molybdenum.
As more things are added, though, one is moving toward the full Yasko approach, which is more complicated and expensive. If this is done, I recommend that it be done with the guidance of Dr. Yasko and under the supervision of a personal physician. The simplified treatment approach appears to work well by itself for many PWCs, but others may find that the die-off and detox (or even adverse effects) from this approach used by itself are too severe. In those cases, the PWCs could consult “The Puzzle of Autism,” sold on Amazon.com, to consider together with their doctors what else discussed there might help them. If the simplified approach seems to help to some degree, and it captures one’s attention for that reason, but it still either does not accomplish all that is desired, or it is not tolerated, then perhaps the next step would be to consider the full Yasko treatment. At least then there would be stronger motivation to look into it. Otherwise, it can appear very daunting to many PWCs.

The reported responses to this treatment approach have mainly involved a combination of two categories of effects: (1) improvements in some of the common CFS symptoms (some of them quite rapid and profound), and (2) intensification or initial appearance of a variety of symptoms that appear to result from increased detoxification and immune system attack on infections. The former are most welcome, and they are what continue to motivate the people on this treatment, in the face of the detox and die-off symptoms, which are unpleasant but appear to be inevitable, given the large body burdens of toxins and infections that many PWCs have accumulated during their illness, lacking adequate detox capability and cell-mediated immune response during that time.

In addition to these main responses, a few PWCs have reported adverse effects, some of them quite serious. These are discussed below. A few of those who have started the treatment have stopped it for various reasons, including adverse effects. Some have taken breaks from the treatment and have then returned to it or are planning to do so.

While this informal testing of the simplified treatment approach currently is not being carried out in a controlled fashion, and while not all the PWCs trying it are using the complete suggested complement of supplements, it is nevertheless possible to state that the treatment appears to be working for quite a few PWCs, though not all.

The following symptoms of CFS have been reported to have been corrected by various PWCs on this treatment. Note that these are gathered from reports from many PWCs, so that not all have been reported by a single person.

1. Improvement in sleep (though a few have reported increased difficulty in sleeping initially).
2. Ending of the need for and intolerance of continued thyroid hormone supplementation.
3. Termination of excessive urination and night-time urination.
4. Restoration of normal body temperature from lower values.
5. Restoration of normal blood pressure from lower values.
6. Initiation of attack by immune system on longstanding infections.
7. Increased energy and ability to carry on higher levels of activity without post-exertional fatigue or malaise. Termination of “crashing.”
8. Lifting of brain fog, increase in cognitive ability, return of memory.
9. Relief from hypoglycemia symptoms
10. Improvement in alcohol tolerance
11. Decrease in pain (though some have experienced increases in pain temporarily, as well as increased headaches, presumably as a result of detoxing).
12. Notice of and remarking by friends and therapists on improvements in the PWC's condition.
13. Necessity to adjust relationship with spouse, because not as much caregiving is needed. Need to work out more balanced responsibilities in relationship in view of improved health and improved desire and ability to be assertive.
14. Return of ability to read and retain what has been read.
15. Return of ability to take a shower standing up.
16. Return of ability to sit up for long times.
17. Return of ability to drive for long distances.
18. Improved tolerance for heat.
18. Feeling unusually calm.
19. Feeling "more normal and part of the world."
20. Ability to stop steroid hormone support without experiencing problems from doing it.
21. Lowered sensation of being under stress.
22. Loss of excess weight.

The following reported symptoms, also gathered from various PWCs trying this simplified treatment approach, are those that I suspect result from die-off and detox:

1. Headaches, “heavy head,” “heavy-feeling headaches”
2. Alternated periods of mental “fuzziness” and greater mental clarity
3. Feeling “muggy-headed” or “blah” or sick in the morning
4. Transient malaise, flu-like symptoms
5. Transiently increased fatigue, waxing and waning fatigue, feeling more tired and sluggish, weakness
6. Dizziness
7. Irritability
8. Sensation of “brain firing: bing, bong, bing, bong,” “brain moving very fast”
9. Depression, feeling overwhelmed, strong emotions
10. Greater need for “healing naps.”
11. Swollen or painful lymph nodes
12. Mild fevers
13. Runny nose, low grade “sniffles,” sneezing, coughing
14. Sore throat
15. Rashes
16. Itching
17. Increased perspiration, unusual smelling perspiration
18. “Metallic” taste in mouth
19. Transient nausea, “sick to stomach”
20. Abdominal cramping/pain
21. Increased bowel movements
22. Diarrhea, loose stools, urgency
23. Unusual color of stools, e.g. green
24. Temporarily increased urination
25. Transiently increased thirst
26. Clear urine
27. Unusual smelling urine
28. Transient increased muscle pain

Finally, the responses reported below are more serious, and I would classify them as adverse effects of the treatment. This list includes all the adverse effects of which I am aware at the time of writing this article, but I suspect that as more PWCs try this treatment with the assistance of their physicians, this list will grow. I am describing these as they have been reported on the ImmuneSupport CFS discussion board by the PWCs who experienced them. Though this information may be incomplete, and cause—effect relationships are difficult to determine exactly from the available information, I’m hopeful that it will be helpful to clinicians and other PWCs:

1. One person had had a history of severe pesticide exposure and also autonomous multi-nodular goiter, which she described as follows: “Gradually the right lobe grew to over 4 cm x 4cm, and [I] had to have right lobe out. . . This same surgeon made the decision to leave the left lobe in, as I had always had trouble with thyroid med back then too. So, they restarted my Synthroid and I stayed on that for [a] few more years. I ALWAYS had shortness of breath and became VERY tachycardic upon ANY activity. . .” This person started the simplified treatment approach on March 21, 2007 (actually using higher dosages than suggested for FolaPro and Intrinsi/B12/folate). On May 19, she went to an emergency room with tachycardia, chest pain, trouble breathing, trouble sleeping, elevated blood pressure and fever of 100.7 F. She was admitted to the hospital and released the next day. No evidence was found for heart attack. This person later reported the following: “I followed up with my PCP and had CT scan of neck and chest and my goiter is causing tracheal compression, again, and breathing is VERY hard. . . My area hospitals can't do this surgery because my goiter grows substernal, deep in my chest.” This person has expressed a desire to continue the simplified treatment approach, but is currently exploring the possibility of first having additional surgery on the multinodular goiter.

2. A second person had a history of lung problems due to both carbon monoxide exposure and exposure to molds, as well as heart-related symptoms. She started part of the simplified treatment approach on May 27, 2007. After having been nearly homebound for ten years, she was able to begin riding a bicycle. However, in early July, 2007, she went to an emergency room twice with severe breathing problems (shortness of breath), a fever of 99.8 to 100.1 F. that eventually lasted for sixteen days, and severe chest and left arm pain. No evidence was found for heart attack. She was diagnosed with an enlarged left atrium and diastolic dysfunction. She has currently discontinued the simplified treatment approach and is under the care of cardiologists.

3. A third person had a history of autoimmune disease, including Sjogren’s syndrome. After her fourth dosage of combined FolaPro and Intrinsi/B12/folate, she experienced “a moderately severe autoimmune flare, with numerous joint and soft tissue issues, fatigue, pain, etc.” She also experienced a severe flare of Sjogren’s syndrome, with “very dry mouth, dry eyes, and severe eye pain.” Six days after discontinuing the supplements, she had a thorough ophthalmology workup and was diagnosed with autoimmune scleritis. She has been given topical steroids and has reported that her eyes are greatly improved.

4. At least two persons experienced a temporary termination of peristalsis of the gut and consequent constipation after beginning the simplified treatment approach. In these two cases, induction of diarrhea cleared material from the gut, but did not restore the peristalsis. In both cases, peristalsis restarted twelve days after terminating the folate-containing supplements. One of these persons had a history of treatment with psychotropic drugs, including Klonopin. About 18 hours after starting to get relief from the constipation, she became very sick, with “vomiting, vise-like headache, and shaking.” She had many bowel movements over a ten-hour period, and then began to feel better. The other had a history of autoimmune diseases, including Sjogren’s syndrome and Autoimmune Ovaritis, as well as diastolic dysfunction.

There are many questions remaining to be answered about this treatment
approach, including the following:

1. For which PWCs would this be an appropriate treatment approach?
2. For what fraction of the entire PWC population will this treatment approach be beneficial?
3. How can PWCs who are likely to experience adverse effects from this treatment approach be identified beforehand, so that these effects can be avoided?
4. Are there PWCs who are too debilitated to be able to tolerate the detoxing and die-off processes that result from this treatment approach, and if so, will the full Yasko treatment approach be suitable for them?
5. Will the simplified treatment approach actually lead to continuing improvements over longer times for those who find it beneficial, all the way to cured cases?
6. Will the simplified treatment approach be effective in cases of "pure fibromyalgia" as it appears to be in many cases of CFS?
7. How can this treatment approach be further improved?

And many more.

However, the results to date seem encouraging. I suspect that many PWCs can be helped by this treatment approach or something similar to it. I also believe that the appearance of improvement in such a wide range of CFS symptoms when this treatment approach is used provides evidence that a block in the methylation cycle does in fact lie at the root of the biochemical and physiological derangements found in many PWCs, or very near to it. The wide range of symptoms that appear to be associated with die-off and detox appear to give evidence that this treatment is in fact stimulating more normal operation of the immune and detox systems.

I want to reiterate what I wrote near the beginning of this article: This treatment approach must be entered upon only under the supervision of a licensed physician, to make sure that if there are individual issues that arise, they can be taken care of immediately. The treatment approach itself consists only of nonprescription supplements that are normally found naturally in the body and are necessary for normal biochemistry to take place. It would thus appear to be fairly benign on its surface. However, it must be pointed out that restarting the methylation cycle after it has been blocked for extended periods, particularly in those PWCs whose general health has become quite debilitated, or those who have certain respiratory, cardiac, endocrine or autoimmune conditions, can present some serious challenges. I believe that there is still much more to be learned about the possible hazards of applying this treatment approach to the very heterogeneous CFS population, and this work properly lies in the province of clinicians. I am not a licensed physician, but a researcher. I believe that I have carried this work as far as a researcher can appropriately carry it. I am hopeful that clinicians will further test this treatment approach in order to learn how it may be safely, effectively, and practically utilized to treat PWCs, and it appears that this is now beginning to occur.

I also hope that physicians or their patients who decide to try this treatment approach will let me know how it works for them, though I may not be able to answer all the emails I receive, as their volume is growing.

Rich Van Konynenburg, Ph.D.
Independent Researcher and Consultant
richvank@aol.com

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