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Posted Dec 02 2008 3:06am 1 Comment
Remember that this is juat a post of my blog, and it evolves, so to see the full story go to: (English) or (Spanish)
My current doc: Josepa Rigau Av Catalunya, 12, 3º, 1ª 43002 Tarragona Spain +34977220358 (I do recommend! hoeopathy and biological medicine, significant improvement)

Note: You can see the original version of this post with all kind of links to sources cliquing in the title of this post.

CFS-CFIDS-ME, etc, are multi systemic illnesses which have, in most cases, a strong viral and/or toxic component. Several systems are deregulated, or perhaps permanently damaged, including the immune system, the endocrine system and the neurological system.

When we revise all the research trends published they converge in the following theory for CFS
An external stressor such as toxics, heavy metals, viral infection, trauma, surgery... forces the adrenals, and under this oxidative stress status, glutathione is consumed and exhausted. When this stressor continues and becomes chronic, leads to a blockage of the methylation cycle, which also blocks the Krebs cycle, the immune system, urea cycle, etc... Under this situation, a mitochondrial failure is developed that brings fatigue as a result among many other alterations, like cardiac implications demonstrated by Cheney and Lener... Once the illness has become chronic, with the detox system blocked, a debilitated immune system due to the mitochondrial failure and the lack of genetic material to function properly, opportunistic infections arise and toxics accumulate in the body, aggravating more the condition of patients.

A)Diagnostic Valuable Test Although not generally accepted as a diagnostic test, they have been claimed by researchers to be useful markers for the disease and tend to be present in most of the patients. Nevertheless the value of these is more for diagnosis than for treatment of the condition.In order of importance: RNASe-L, PKR and Elastase levels, Nitric Oxide in serum and oxidation levels, SPECT and xenon SPECT scans of the brain, MRI scans of the brain, PET scans of the brain, Neuropsychological testing, EEG brain maps and QEEG brain maps, Erythrocyte sedimentation rate (ESR), Insulin levels and glucose tolerance tests, 24-Hour Holter monitor, Tilt table examination, Exercise testing and chemical stress tests, Neurological examination and the Romberg or tandem Romberg test.

B)Aditional abnormalities test found in CFS patients should be checked at least once, and based on the criteria of the physician that is treating you, it might be necessary to repeat them periodically to evaluate the evolution of the protocol followed in your case.

-Tests of the immune system: The Th1-Th2 relationship of the immune system, Low NK activity (as opposed to levels), T-Activated Linfocites Count, % Linfocites, Cellular Inversion at CHMI and/or CHMII level, Elevations of circulating cytokines, Immunoglobulin deficiencies
-Serology Test: IgG for viruses such as Epstein-Barr, CMV, HHV6. Additionally we need to get tested for all possible infections that could have caused a reaction in our hormonal stress, and therefore in the serology we should include: mononucleosis, Hepatitis B & C, LES markers, Toxoplasma, antibodies of candida albicans, Babesia, Erchilia, Bartonella, Borrelia etc...
-Levels of amino acids in blood and urine 24h or spot.
-Liver function
-Candida levels, in order to detect subclinical fungi infections like candida albicans, there are special urine test that measure the metabolites that will help us to rule it out it also can be observed the metabolites through an Organic Acids Test.

According to the results, patients should seek be treated for each one of the abnormalities which show up. There are allopathic treatments (can be problematic for some, as CFS-MEers tend to have also Chemical Sensitivities) or homeopathic treatments (in Germany, they are very commonly used).
Diet is also important regarding dealing with chemical sensitivities, amino acid levels, candida levels.

C) Advance testing on CFS: Besides theses regular, although not standard test mentioned above, there are additional test that can be run, and will deliver relevant input for CFS patients. There is a protocol to regulate these different abnormalities, which might be causing part of the symptoms in CFS, as a few of the latest research published postulates. We will discuss below some of them in here

-Mitochondrial Profile This is in the latest research the main responsible for CFS. There is a test run in UK by Dr. Myhill. This test measures the enzyme SODase (Superoxide Dismutasa) This enzyme is necessary in the detox process of free radicals of the mitochondria, as well as the CoQ10 levels, Niacinamide and Intracellular Magnesium. And most of all the efficiency of the mitochondria in converting ADP into ATP. It also measures the free ADN which is a nice marker to observe the cellular damage and apoptosis or PKR which is the programmed cellular death due to oxidative stress.

-Adrenal Hormones in Saliva: This test is useful to treat the adrenal failure, because there is a treatment for it. The test is run during a whole day (8:00, 12:00, 16:00, 20:00) Cortisol and DHEA levels are tested. Also is necessary to test for a potential subclinical Thyroids problem (TSH, T3 and T4). Preferably in urine 24h, because subclinical thyroids is not always detectable in serum. Additionally a hair mineral test can be done to observe the unbalance existing in terms of minerals caused by suprarenal malfunction and correct it accordingly. Last but not least,

-HPU Test: This test measures a metabolic disorder, often occuring as a biochemical-enzymatic familiarly during the chemical reaction of formation of the red blood pigment. (Hemosynthesis).
It can be said that Kryptopyrrolurea is not a symptom, but rather the primal cause for different symptoms and disease states, among others hipoglucemia.
In the German-speaking countries, is abbreviated as KPU. In the Netherlands HPU. In England the abbreviation is HPL.

-Hypercoagulation Testing?: As a part of Hemex's research, they have developed a test to determine if a patient has this hypercoagulation disorder. The Immune System Activation of Coagulation (ISAC) tests five substances; abnormal results on any two of the five is considered to be a positive indicator of hypercoagulation. Their results thus far have found 79-92 percent of the CFS and/or FM patients they tested have hypercoagulation. As with many of the more detailed blood tests developed in the past decade, the defects causing hypercoagulation are rarely or not at all detectable by the standard laboratory tests performed at general labs, such as Unilab, Quest Diagnostics, etc. The standard coagulation workup done by these labs assess only the risk of actual clotting, whereas the ISAC panel is 10-20 times more sensitive.

-Metilation Panel (methionine cycle): This blood test is meant to observe the potential blockage of the methylation cycle, and therefore the potential detox treatment and follow up through urine. If after this analysis, you observe a blocked Methylation Cycle, then is wise to do a metal in urine test to have a starting point for the detox treatment. This test will be useful to follow up the metal excretion in the detox protocol or / and adapt the mineral doses intake.

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.

In autism the methylation cycle was found to be blocked at methionine synthase, which is the step involving methylation of homocysteine to form methionine, resulting in lower plasma levels of cysteine and glutathione and a lowered ratio of reduced to oxidized glutathione. This lowered ratio reflects a state of oxidative stress.

It is known from studies of twins that genetics plays an important predisposing role in autism.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, since the population’s genetic inheritance is relatively constant over much longer periods.

Evidence suggests that this same dysfunction is also present in chronic fatigue syndrome: Low methionine levels in serum and urine, below-normal levels of carnitine, coenzyme Q10 and melatonin. All these substances require methylation for their biosynthesis.

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

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.

-Glutathione and Selenium Test: The best complement to Methylation Panel, would be to check Reduced Glutathione RBC GSH, Oxidated Glutathione (RBC GSSG) and Total Glutathione (RBC). The important one is RBC GSH, and also the ratio of this one versus RBC GSSG. This is relevant given that the low levels of glutathione due to the blocked methylation cycle, is the main responsible for the symptoms of CFS. In the initial states of oxidative stress in this illness Total Glutathione could be miss leading and be normal or even high, that is why we test for the other two as well. Besides, even if Glutathione comes normal, if Selenium level is low, the enzymes could not work properly.

Depletion of reduced glutathione likewise causes a shift to Th2. Depletion of reduced glutathione is the trigger for the reactivation of latent viral and intracellular bacteria in CFS. In general, intracellular glutathione depletion is associated with the activation of several types of viruses. It is likely that glutathione depletion is responsible for reactivation of Epstein-Barr virus, cytomegalovirus and HHV-6 in CFS. Populations more deficient in selenium would be expected to be more vulnerable to Coxsackie B3 infection.

-LITOCROMO P450 (Genetic Profile of the Urine Cycle) This is a genetic study that can be done later, and it reflects the pharma genetic of the liver taking into account 15 genes and 92 polyforms. This study will give us information of what foods or medications are not assimilated by our liver and therefore should be skipped. The problem again is that insurance only covers you this study when you have cancer or aids… This test is particularly useful in the case that Glutathione and Selenium comes out normal, but what is not working are the enzymes that regulate it due to their genetic polyforms.

-DETOXIFICATION TEST: Our bodies must be able to detoxify, or neutralize, toxins from the external environment as well as those produced within our own bodies. This process takes place mostly in the liver, and consists of two phases. In Phase I toxins are activated, which means that they are altered in such a way that carrier molecules (Phase II) are able to transport them out of the body. A handy analogy is the bagging of our trash (Phase I), so that the garbage man can pick it up and cart it away (Phase II). Phase I is accomplished by a family of enzymes called "cytochrome P450", and Phase II takes place via a number of important mechanisms, four of which we measure in this test, with the help of the challenge substances, caffeine, acetaminophen and aspirin. Both Phase I and Phase II of detoxification must function adequately so that toxins are able to be neutralized, and the two phases must be in balance with each other so that the activated compounds from Phase I cannot accumulate in the body and cause damage. Laboratory: Genova Diagnostics

-Porphyrine Test is different of methylation panel, in the sense that is useful to corroborate that toxicity comes from mercury or lead. Metals would not normally show up in the urine unless you are following a detox protocol, the reason for this is that they are accumulated in the organs. Elevations of the individual porphyrin species can have a number of causes, including heredity and environmental contact. Chronic exposure to toxic metals, including lead, mercury, arsenic, aluminum, and cadmium often results in organ-specific accumulation that compromises target organ physiological function. Heavy metals impair many aspects of metabolism, while chronic exposure to organic chemicals, such as pesticides, can have deleterious effects on the body’s biochemistry and adversely affect cellular function.

-Complete Stool Analysis including parasites: Stools are teeming with bacteria, some beneficial, some neutral, and some that can be harmful. It is important to know what you have, especially if you have health problems. Health-enhancing intestinal bacteria serve to prevent the overgrowth of potentially harmful bacteria in the gut. Stool testing can also assess your body’s ability to digest food, the pH, and the amount of mucus present. A Triple Faeces Test is recommended for parasite testing, given that specificity drops when a single sample is taken. Three days in a row is recommended and scraped in the external annus is also necessary, given that is where parasites eggs are normally displayed.

-Metabolic Analysis Profile or Organic Acids Test: This profile measures 39 organic acids that play a role in four critical areas: gastrointestinal function and dysbiosis, cellular and mitochondrial energy metabolism, neurotransmitter metabolism, and nutritional assessment of vitamins and minerals that serve as critical enzyme cofactors. Test results allow practitioners to design comprehensive, customized therapies to restore optimal metabolic health. This test can be done at Genova Diagnostics USA

Urinary organic acid analysis for metabolic profiling has traditionally been used for detection of neonatal inborn errors of metabolism. Since the reporting of isovaleric acidemia in 1966, there has been a rapidly growing list of disorders resulting in elevated excretion of metabolic intermediates. The application of the testing to assess special nutrient requirements of individuals is discussed in a variety of sources. Organic acid profiling has also been useful in identification of the source of toxicants from the environment and the gut.

When you do the Organic Acids Test plus Figlue (Formiminoglutamic acid), then is not necessary a MAP.
MAP is a variation of organic acids test, but besides looks at FIGLU, which is necessary to know the state of methylation cycle. FIGLU will be high if there is a deficiency of Tetrahidrofolate (THF), a type of B9, and this occurs when there is a blocked methylation cycle. If you run a Methylation Panel, they already look at THF level, and therefore FIGLU is not necessary. In conclusion, when you run a methylation panel plus an organic Acids Test, a MAP won’t be necessary, neither the FIGLU.

For further interpretation of additional test results, visit:

D) Ruling out test: Numerous CFS specialists have reported that a subgroup of those diagnosed with CFS, especially those whose CFS was gradual-onset as opposed to sudden-onset, have been misdiagnosed and actually have another chronic medical condition. The following medical conditions should be ruled out before a diagnosis of CFS can be made
•Multiple Sclerosis (MS). ~5% of cases are missed MS according to Dr. Byron Hyde.
•Systemic Lupus Erythematosus (SLE). ~5% of cases are missed SLE according to Dr. Chris Reading.
•Myocardial infarcts. At least 5-10% of cases according to Dr. Byron Hyde. (1)
•Cerebral-Arterial Obstructions.
•Primary adrenal insufficiency (Addison's Disease). (2)
•Primary hypothyroidism (3)
•Liver disease.
•Renal (kidney) disease.
•Rheumatoid arthritis.
•Reiter's disease.
•Sjogren's syndrome.
•Diabetes mellitus.
•Inflammatory bowel disease.
•Hepatitis B/C & HIV.
•Cancer Screening test Ca 125 (Ovarian Cancer)
•Espirometry and full functional study including effort test (Neumologyst)
•Ross River Vius (Australian mosquito, in case you have travelled in the area)
•Colonoscopy for Celiac Disease
•Lyme Test: This is something that need to be ruled out, and the Elisa test that checks for IgG and IgM for Borrelia has a very low specificity, and therefore is not enough. Also need to test for potential coinfections: Babesia, Erchilia, Bartonella... Preferably a Western Blot test and CD57 count should be run to rule out this disease. Igenex and Labcorp in the US are the best labs to get tested. In Europe you can try Melisa labs in Germany. Lyme disease is as controversial as CFS. Some say that is simply part of SCF, because normally Lyme should be cure with a short time set of antibiotics, and some other say is a different illness with an specific long term antibiotic protocol. Either case, it will help you to know if you have an active tick bite toxicity in your body. 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. 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.
•Notes(1)Electrocardiogram & Ecocardiogram - Doppler (Cardiologyst)
(2)Not to be confused with sub-clinical adrenal insufficiency secondary to pituitary dysfunction, which is a common feature of CFS.
(3)Not to be confused with sub-clinical thyroid dysfunction, which is a common feature of CFS.

Note: Obviously the vast majority o these tests are not covered by the insurance companies, given the unfair status that this medical condition has at the moment. All this testing can contribute to a significant improvement on the quality of life of patients. It could also help researchers to find better protocols and treatment if the size of the CFS patients sample was bigger, while being covered by insurers. This eventually could lead to a cure.

Also you can check this laboratory in europe for many of the test described in C) Advance Testing

Dr E. F. Vogelaar (This laboratory is the only one in Europe that they do the methylation panel)
Prof Clinitian Nutrition
Benadir University, Mogadishu
Tel: +31 30 287 14 92
Fax: +31 30 280 26 88
Work Mail:

Besides there is also another good choice in The Netherlands which is a subsidiary of Genova Diagnostics (
Biltstraat 152
3572 BN Utrecht
Tel.: +31 (0) 24 3572545
Fax: +31 (0) 24 6452899

In the US, this is the laboratory that runs the methylation panel
Vitamin Diagnostics
Industrial Drive & Route 35
Cliffwood Beach, N.J. 07735 USA
(732) 583-7773
Phone: 1 (732) 583-7773
Fax: 1 (732) 583-7774)
Comments (1)
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Here is some additional information about the "genetics" of this condition that was written by our Genetic Counselor and other genetic professionals: I hope it helps. Thanks, AccessDNA
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