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Übersetzungsvorlage Nummer 1

Original veröffentlicht von Rich van Konynenburg

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

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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)

How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome?

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.

1.2How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome?

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).

1.3How does the GD-MCB hypothesis explain other aspects of chronic fatigue syndrome?

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).

1.4How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome?

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

1.5How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome?

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

1.6How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome?

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.)

1.7How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome?

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

1.8How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome? (continued)

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

1.9How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome? (continued)

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).

1.10How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome? (continued)

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).

1.11How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome? (continued)

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.

1.12How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome? (continued)

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

1.13How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome? (continued)

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.)

1.14How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome? (continued)

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,

1.15How does the GD-MCB Hypothesis explain other aspects of chronic fatigue syndrome? (continued)

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.


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.

(A Yahoo discussion group is now devoted to these topics. You can find it at
CFS_Yasko : Dr. Amy Yasko CFS Treatment

Quelle: Glutathione and Methylation in and chronic fatigue syndrome (ME/CFS)

Geändert von alibiorangerl (02.03.12 um 21:52 Uhr)

Der Methylierungszyklus - eine zentrale Ursache? ENGLISH ORIG

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Ich habe mich im stillen Kämmerlein zunächst an eine andere Übersetzung gewagt:

A Simpler Explanation of the Glutathione/Methylation Blockade Theory (12/08)- Rich provides a step by step simpler explanation of his theoryA Simple Explanation of the Glutathione/Methylation Depletion Theory of ME/CFS by Rich Von Konynenburg (12/08)
To get an isolated case of CFS (I'm not talking here about the epidemics or clusters), you have to have inherited some genetic variations from your parents. These are called polymorphisms or single-nucleotide polymorphisms. We know what some of the important ones are, but we don't know all of them yet. This is a topic that needs more research.

2. You also have to have some things happen in your life that place demands on your supply of glutathione. Glutathione is like a very small protein, and there is some in every cell of your body, and in your blood. It protects your body from quite a few things that can cause problems, including chemicals that are toxic, and oxidizing free radicals. It also helps the immune system to fight bugs (bacteria, viruses, fungi) so that you are protected from infections by them.*

3. Oxidizing free radicals are molecules that have an odd number of electrons, and are very chemically reactive. They are normally formed as part of the metabolism in the body, but if they rise to high levels and are not eliminated by glutathione and the rest of the antioxidant system, they will react with things they shouldn't, and cause problems. This situation is called oxidative stress, and it is probably the best-proven biochemical aspect of chronic fatigue syndrome.

4. There are a variety of things in your life that can place demands on your glutathione. These include physical injuries or surgery to your body, exposure to toxic chemicals such as pesticides, solvents, or heavy metals like mercury, arsenic or lead, exposure to infectious agents or vaccinations, or emotional stress that causes secretion of a lot of cortisol and adrenaline, especially if it continues over a long time. Just about anything that "stresses" your body or your mind will place a demand on glutathione. All people experience a variety of stressors all the time, and a healthy person's body is able to keep up with the demands for glutathione by recycling used glutathione molecules and by making new ones as needed. However, if a person's body cannot keep up, either because of extra-high demands or inherited genetic polymorphisms that interfere with recycling or making glutathione, or both, the levels of glutathione in the cells can go too low. When glutathione is properly measured in most people with CFS (such as in the Vitamin Diagnostics methylation pathways panel), it is found to be below normal.

5. One of the jobs that glutathione normally does is to protect your supply of vitamin B12 from reacting with toxins. If left unprotected, vitamin B12 is very reactive chemically. If it reacts with toxins, it can't be used for its important jobs in your body. A routine blood test for vitamin B12 will not reveal this problem. In fact, many people with CFS appear to have elevated levels of B12 in their blood, while their bodies are not able to use it properly. The best test to reveal this is a urine organic acids test that includes methylmalonic acid. It will be high if the B12 is being sidetracked, and this is commonly seen in people with CFS.

6. When your glutathione level goes too low, your B12 becomes naked and vulnerable, and is hijacked by toxins. Also, the levels of toxins rise in the body when there isn't enough glutathione to take them out, so there are two unfortunate things that work together to sabotage your B12 when glutathione goes too low.

7. The most important job that B12 has in the body is to form methylcobalamin, which is one of the two active forms of B12. This form is needed by the enzyme methionine synthase, to do its job. An enzyme is a substance that catalyzes, or encourages, a certain biochemical reaction.*

8. When there isn't enough methylcobalamin, methionine synthase has to slow down its reaction. Its reaction lies at the junction of the methylation cycle and the folate cycle, so when this reaction slows down, it affects both these cycles.

9. The methylation cycle is found in all the cells of the body (not counting the red blood cells, which are unusual in a lot of ways). The methylation cycle has some important jobs to do. First, it acts as a little factory to supply methyl (CH3) groups to a large number of reactions in the body. Some of these reactions make things like creatine, carnitine, coenzyme Q10, phosphatidylcholine, melatonin, and lots of other important substances for the body. It is not a coincidence that these substances are found to be low in CFS, so that people try taking them as supplements. Not enough of them is being made because of the partial block in the methylation cycle. The methylation cycle also supplies methyl groups to be attached to DNA molecules, and this helps to determine whether the blueprints in the DNA will be used to make certain proteins according to their patterns. The "reading" of DNA is referred to as "gene expression." Methyl groups prevent or "silence" gene expression. Overexpression of genes has been observed in CFS patients, and I suspect this is at least partly due prevent to lack of sufficient methylation to silence gene expression.

10. Another thing that the methylation cycle does is to regulate the overall use of sulfur in the body. Sulfur comes in from the diet in the form of amino acids in protein (methionine and cysteine) and as taurine and some as sulfate. The methylation cycle regulates the production of the various substances that contain sulfur that are needed by the body. The levels of various sulfur metabolites are often found to be abnormal in people with CFS.*

11. One of the most important sulfur-containing substances in the body is glutathione, so now you can see how this is starting to look like a dog chasing its tail! The thing that causes chronic fatigue syndrome to be chronic, and keeps people ill for years and years, is this interaction between glutathione, vitamin B12, and the methylation cycle. When glutathione goes too low, the effect on vitamin B12 slows down the methylation cycle too much. The sulfur metabolites are then dumped into the transsulfuration pathwayn (which is connected to the methylation cycle) too much, are oxidized to form cystine, pass through hydrogen sulfide, and are eventually converted to thiosulfate and sulfate and are excreted in the urine. This lowers the production of glutathione, which requires cysteine rather than cystine, and now there is a vicious circle mechanism that preserves this malfunction and keeps you sick.

12. That's the basic biochemical mechanism of CFS. I believe that everything else flows from this. As you know, there are many symptoms in CFS. I won't discuss all of them in detail here, but here's how I believe the fatigue occurs: The cells have little powerplants in them, called mitochondria. Their job is to use food as fuel to produce ATP (adenosine triphosphate). ATP acts as a source of energy to drive a very large number of reactions in the cells. For examples, it drives the contraction of the muscle fibers, and it provides the energy to send nerve impulses. It also supplies the energy to make stomach acid and digestive enzymes to digest our food, and many, many other things.*

When glutathione goes too low in the muscle cells, the levels of oxidizing free radicals rise, and these react with parts of the "machinery" in the little powerplants, lowering their output of ATP. So the muscle cells then experience an energy crisis, and that's what causes the fatigue. Over time, because of the lack of enough glutathione, more problems accumulate in the mitochondria, including toxins, viral DNA, and mineral imbalances. These have been observed in the ATP Profiles and Translocator Protein test panels offered by Acumen Lab in the*UK.

13. There are explanations that flow from this basic mechanism for other aspects of CFS. I haven't figured out explanations for all of the aspects of CFS, but I do think I understand a large number of them in some detail, and I've been able to explain enough of them that I believe this mechanism will account for the rest as well, if we can figure out the underlying biochemistry. My 2007 IACFS conference poster paper presented outlines of many of these explanations.

14. The involvement of infections by bacteria, viruses and fungi appears to have two aspects in CFS. First, as mentioned above, infectious agents can act as one of the stressors that initially bring down the level of glutathione and produce the onset of isolated cases of CFS in people who are genetically susceptible. I suspect that the clusters or epidemic occurrences of CFS (such as at*Incline*Village*in the mid-80s) were caused by particularly virulent infectious agents, such as powerful viruses, and the genetic factor is less important in these cases.

15. Second, when a person's glutathione, methylation cycle, and folate cycle are not operating normally because of the vicious circle described above, the immune system does not function properly. In this case, viruses and bacteria that reside inside our cells and that are always in the body in their dormant, resting states are able to reactivate and produce infections, which the immune system is not able to totally put down. This accounts for the observation that most of the viral and intracellular bacterial infections seen in CFS patients are caused by pathogens that most of the population is carrying around in their dormant states.

16. Third, when the immune system's defenses are down, a person can catch new infections from others or from the environment, and the immune system is not able to defeat them, so they accumulate over time. Dr. Garth Nicolson has found that the longer a person has been ill, the more infections they have, on the average.

17. Other things that accumulate over time are various types of toxins, because the detox system depends to a large extent on the sulfur metabolism, and it will not be operating properly as long as the person has CFS. The body stores much of these toxins in fat, but as the levels get higher, they begin cause problems throughout the biochemistry of the cells. Many people with CFS have been tested for toxins (most commonly the heavy metal toxins, which are the most easily tested) and they are commonly found to be elevated.*

18. The longer a person is chronically ill with CFS, the more toxins and infections accumulate in their body, and the more symptoms they experience. This explains why the disorder changes over time, and why some people become extremely debilitated after being ill for many years.

19. The main key to turning this process around is to help the methionine synthase enzyme to operate more normally, so that the partial block in the methylation cycle and the folate cycle are lifted, and glutathione is brought back up to normal. That is what the simplified treatment approach is designed to do, and so far, the evidence is that it does do these things in most people who have CFS. I recommend that people with CFS have the Vitamin Diagnostics methylation pathways panel run to find out if they do in fact have a partial methylation cycle block and glutathione depletion before deciding, with their doctors, whether to try this treatment. This also provides a baseline so that progress can be judged later on by repeating it every few months during the treatment. Symptoms may not be a good guide to judge progress during treatment, because detoxing and die-off can make the symptoms worse, while in fact they are exactly what is needed to move the person toward recovery.

20. The main question I'm working on now is what else needs to be done to bring people to recovery? I don't have complete answers to this question yet. Many people may recover from this treatment alone, but it is proving to be a slow process, and we will need more time to see how this will work out. It does appear that people who suffer from illness due to toxic molds do need to remove themselves from environments where these are present. The small amount of evidence I have so far suggests that people who have Lyme disease will need to have that treated in addition. I'm not sure about certain viral infections. They may also need to be treated. We still have a lot to learn, but I'm convinced that the mechanism I have described above is the core of the abnormal biochemistry in CFS, and correcting it needs to be cornerstone of the treatment.

Quelle: Glutathione/Methylation Theory of ME/CFS: the Simple Explanation

Übersetzung: Ich habe hier ein paar Stolpersteine. Bin für Hilfe dankbar


Rich van Konynenburg gibt eine schrittweise Erläuterung

Um im Einzelfall CFS zu betrachten (ich spreche hier nicht von Epidemien, oder Cluster Ausbrüchen), benötigt man Informationen über die genetischen Varianten über die Patienten. Diese nennt man Polymorphismen, oder einzelne Gen-Polymorphismen (Anmerkung: Oder genetische Disposition).
Uns ist bekannt, welche davon wichtig sind, aber wir kennen noch nicht alle.
Dies ist ein Thema, das mehr Forschung bedarf.

Zudem müssen einige Dinge im Leben passiert sein, die eine Glutathionzufuhr benötigen.
Glutathion ist wie ein kleiner Eiweißbaustein. Es kommt in jeder Körperzelle und im Blut vor.
Es schützt den Körper vor einer Menge von Dingen, die Probleme verursachen können – einschließlich giftigen Chemikalien, oder freien Radikalen die oxidieren.
Es unterstützt ebenso das Immunsystem beim Kampf gegen Eindringlinge (Bakterien, Viren, Pilze), so dass man vor Infektionen durch diese geschützt ist.

3. Oxidierende freie Radikale sind Moleküle, die eine ungewöhnliche (Frage:? passend übersetzt?)
Elektronenzahl besitzen und chemisch sehr reaktionsfreudig sind. Ursprünglich sind sie ein Teil des Stoffwechselgeschehens, aber wenn sie in großen Mengen entstehen und nicht durch Glutathion und dem weiteren Entgiftungssystem abgebaut werden, reagieren sie mit Stoffen, mit denen sie nicht reagieren sollten und verursachen Probleme.
Dies nennt man oxidativen Stress und dies ist der vermutlich bestens bewiesene Aspekt des CFS.

4. Es gibt diverse Varianten von Dingen, die Glutathion beanspruchen können.
Diese beinhalten körperliche Verletzungen, Operationen, Expositionen gegenüber giftigen Chemikalien wie Pestiziden, Lösungsmitteln, Schwermetalle wie Quecksilber, Arsen oder Blei, Exposition gegenüber Infektionserregern, oder Impfungen, oder emotionaler Stress, der zu hoher Ausschüttung von Cortisol und Adrenalin führt – insbesondere, wenn dies über lange Zeit anhält.

Eigentlich alles, was den Körper oder den Geist stresst, benötigt Glutathion.
Jeder Mensch erfährt jederzeit eine Summe von Stressoren – und der Organismus gesunder Personen ist in der Lage dem Glutathionverbrauch nachzukommen, indem verbrauchte Glutathionmoleküle recycled werden und neues Glutathion nach Bedarf hergestellt wird.

Wie dem auch sei – wenn ein Körper nicht mehr mithalten kann, entweder weil ein extra hoher Bedarf an Glutathion besteht, oder genetische Veranlagungen / genetische Dispositionen / Polymorphismen die das Recyclen des Glutathions stören, oder beides zutrifft, können die Glutathionmengen in den Zellen zu gering werden.
Die Glutathionwerte die genau untersucht wurden (z.B. durch Vitamin Diagnostics methylation pathways panel) , sind bei den meisten Personen mit CFS geringer als normal ausgefallen .

5. Eine Aufgabe, die Glutathion normalerweise übernimmt, ist das vorhandene B12 zu schützen, damit es nicht mit Giften reagiert.
Wenn B12 nicht geschützt wird, ist es chemisch sehr reaktionsfreudig.
Wenn B12 mit Giften reagiert, kann es nicht für die wichtigen Aufgaben im Körper genutzt werden.
Ein einfacher Bluttest auf B12 wird diese Problematik nicht anzeigen.
Fakt ist, dass viele CFSler erhöhte B12-Werte im Blut aufweisen, während der Körper nicht in der Lage ist, es ausreichend zu nutzen.
Der beste Test, um das offenzulegen ist eine Urinuntersuchung auf organische Säuren, die den Wert der Methylmalonsäure beinhaltet. Dieser Wert wird hoch ausfallen, wenn B12 „umgeleitet“ wurde – was man bei CFS häufig vorfindet.

6. Wenn der Glutathin-Level zu niedrig wird, verbleibt das B12 ungeschützt und angreifbar und wird von Giften attackiert. Zudem nehmen die Gifte im Körper zu, wenn nicht genügend Glutathion zur Verfügung steht, um sie abzubauen. So arbeiten also unglücklicherweise 2 Dinge zusammen, um das B12 zu sabotieren / verändern, während der Glutathiongehalt sinkt.

7. Die allerwichtigste Aufgabe von B12 im Körper ist es Methylcobalamin herzustellen, welche eine von zwei aktiven Formen des B12 ist.
Diese B12 Form wird von den Enzymen der Methionin Synthese benötigt um arbeiten zu können.
Ein Enzym ist ein Stoff, der verschiedenste biochemische Reaktionen unterstützt und katalysiert.

8. Wenn nicht genügend Methylcobalamin vorhanden ist, muss die Methioninsynthase ihre Reaktionen herunter fahren. Diese Reaktion ist der Knotenpunkt des Methylierungszyklus und des Folsäurezyklus. Wenn also diese Reaktion herunter gerfahren wird, werden beide Zyklen davon betroffen.

9. Der Methylierungszyklus findet in jeder Zelle des Körpers statt (mit Ausnahme der roten Blutkörperchen / Erythrozyten, bei denen vieles ungewöhnlich läuft).
Der Methylierungszyklus hat einige wichtige Aufgaben zu erfüllen.
Erstens arbeitet er wie eine kleine Fabrik um Methylgruppen (CH3 Gruppen) für eine Großzahl von Körperreaktionen bereit zu stellen. Einige der Reaktionen stellen Dinge wie Creatin, Carnitin, Q 10, Phosphatidylcholine, Melatonin, sowie eine Menge anderer für den Körper wichtige Stoffe her.

Es ist kein Zufall, dass ausgerechnet diese Substanzen bei CFS-Patienen in zu geringen Mengen gefunden wurden, so dass die Betroffenen versuchen sie über Nahrungsergänzungsmittel zuzuführen.
Es werden nur unzureichende Mengen von diesen Stoffen hergestellt, weil es eine partielle Blockade im Methylierungszyklus gibt.
Der Methylierungszyklus liefert auch Methylgruppen, um diese den DNA-Molekülen zuzuführen, was wiederum unterstützend festlegt, inwiefern DNA-Kopien genutzt werden um verschiedene Proteine entsprechend ihrer Muster zu nutzen.
Das „lesen“ der DNA bezeichnet man als Genexpression (Anmerkung: Genexpression, der Vorgang, bei dem die genetische Information umgesetzt und für die Zelle nutzbar gemacht wird Quelle: )
Methylgruppen beugen der Genexpression vor, oder „beruhigen“ diese.
Bei CFS-Patienten wurde eine Genetische Überexpression beobachtet, und ich vermute, dass dies letztlich nötig ist um dem Mangel an ausreichender Methylierung zur „stillegenden“ Genexpression vortzbeugen. (Anmerkung: Vom Link bis hier hakt es. Hat jemand eine Idee???)

10. Eine andere Sache, die der Methylierungszyklus übernimmt, ist die Regulation des gesamten Schwefelgebrauchs im Körper. Schwefel wird über die Nahrung in Form von Aminosäuren aus Protein aufgenommen (Methionin und Cystein), sowie als Taurin und etwas Sulfat.
Der Methylierungszyklus reguliert die Produktion diverser Substanzen die Schwefel enthalten und vom Körper benötigt werden. Bei CFS-Patienten sind die Level der Schwefel-Metaboliten häufig nicht normal.

11. Eine der wichtigsten Substanzen im Körper die Schwefel enthält ist Glutathion. Nun wird offensichtlich, wieso es so aussieht wie ein Hund, der seinen Schwanz jagt (Anmerkung: Wir würden sagen, wie sich die Katze in den Schwanz beißt, oder der Schwanz mit dem Hund wedelt ;-) )
Die Sache, die dazu führt, dass CFS chronisch ist und Menschen über Jahre und Jahre krank hält ist diese Interaktion zwischen Glutathion, B12 und dem Methylierungszyklus.
Wenn Glutathion zu weit absinkt, verlangsamt dieser Effekt auf das Vitamin B12 den Methylierungszyklus zu stark.
Die Schwefelmetaboliten werden dann zu viel in den „Transsulfuration“ Nebenweg ausgeworfen / umgeleietet (Anmerkung: Hat jemand eine bessere Übersetzung???) (welcher wiederum mit dem Methylierungyzyklus verknüpft ist), werden oxidiert um Cystin herzustellen, durchlaufen Hydrogensulfid und werden gegebenenfalls in Thiosulfat und Sulfat umgewandelt und über den Urin ausgeschieden (Anmerkung: Wäre dankbar für eine bessere Übersetzung. Hier hänge ich fest).

Dies fährt die Glutathionproduktion herunter, welches eher Cystein als Cystin benötigt – und nun ist der Teufelskreis-Mechanismus da, der diese Fehlfunktion schützt und den Menschen krank hält.

12. Das ist die Basis des biochemischen Mechanismus bei CFS.
Ich glaube, dass alles weitere daraus entsteht. Wie bekannt ist, gibt es viele Symptome bei CFS.
Ich möchte hier nicht alle im Detail diskutieren, aber hier ist die Erläuterung, was ich glaube woher die „Müdigkeit“ / Erschöpfung kommt:
Die Zellen haben kleine Energiekraftwerke genannt Mitochondrien. Ihre Aufgabe ist es Nahrung als
Kraftstoff für die Produktion von ATP zu nutzen (Adenosin Triphosphat).
ATP stellt eine Energiequelle dar, um einen sehr großen Teil von Reaktionen in den Zellen anzutreiben.
Beispielsweise treibt es die Muskelkontraktion an und unterstützt die „Energie“ um Nervenimpulse zu senden. Zudem liefert es die Energie um Magensäure und Verdauungsenzyme zur Verdauung von Nahrung herzustellen, und viele, viele andere Dinge.

Wenn Glutathion in den Muskelzellen zu stark abnimmt, steigen die Mengen von freien Radikalen an – und diese reagieren mit Teilen der Maschinerie der Energiekraftwerke (Mitochondrien), was deren Output / Ausschüttung von ATP vermindert.
Hierdurch erfahren die Muskelzellen eine Energiekrise – und das ist, was zur Erschöpfung führt.
Aufgrund des Mangels von ausreichend Glutathion kommt es im Laufe der Zeit zu zunehmenden Problemen in den Mitochondrien, einschließlich Giften, virulenter DNA und Dysbalancen im Mineralienhaushalt.
Diese wurden in den „ATP-Profiles und Transalocator-Protein Test-Panels die von Acumen Lab in den UK angeboten werden“ beobachtet. (Anmerkung: Ich habe diesen letzten Teil so übersetzt, damit Interessierte diese Tests finden können).

13. Es gibt Erklärungen dafür, die von diesen wesentlichen Mechanismen zu anderen Aspekten des CFS führen. Ich habe noch nicht alle Erklärungen für alle Aspekte des CFS ergründet, aber ich denke schon, dass ich eine große Summe der Aspekte in einigen Details verstanden habe, un dich bin Fähig genügende zu Erörtern, so dass ich glaube, dass dieser Mechanismus für die restlichen ebenso gilt, wenn wir die zugrundeliegende Biochemie herausfinden.
Meine Poster-Paper Präsentation der IACFS Konferenz 2007 präsentiert die Rahmenbedingungen von vielen dieser Erklärungen. (Anmerkung: Hier ist die Posterpräsentation zu finden:Introduction to Glutathione in Chronic Fatigue Syndrome (ME/CFS) Treatment und dann unter *Glutathione/Methylation Powerpoint Presentation herunterladen).

14. Die Beteiligung von Bakterien, Viren und Pilzen scheint zwei Aspekte bei CFS zu haben.
Erstens, wie oben erwähnt, können Infektionserreger als einer der Stressoren agieren die initial den Glutathionspiegel abfallen lassen und den Beginn des einzelnen Falls von CFS bei Personen bilden, die genetisch dafür anfällig sind.
Ich vermute, dass die epidemischen oder Cluster Vorfälle von CFS (solche wie in Incline Village Mitte der 80er) insbesondere durch Erreger von Infektionsviren, also starke Viren verursacht wurden und in diesen Fällen die genetischen Faktoren eine weniger wichtige Rolle spielen.

15. Zweistens – wenn bei einer Person der Glutathionzyklus, Methylierungszyklus und Folsäurezyklus aufgrund der oben genannten Teufelskreise nicht normal abläuft, funktioniert auch das Immunsystem nicht vernünftig. In diesem Fall können Viren und Bakterien die sich in den Zellen befinden und im Körper im Schlummerzustand verharren aus ihrem „Pausenmodus“ reaktiviert werden und Infektionen hervorrufen, die das Immunsystem nicht mehr vollständig herunter fahren kann. Dies zählt zu den Beobachtungen, dass die meisten der viralen und intrazellulären bakteriellen Infektionen die bei CFS-Patienten gefunden werden von Pathogenen Erregern verursacht werden, die der Großteil der Bevölkerung schlummernd in sich trägt.

16. Drittens – Wenn die Abwehrkräfte des Immunsystems unten sind, kann sich die Person neue Infektionen von anderen, oder von der Umwelt zuziehen – und das Immunsystem ist dann nicht in der Lage diese zu bekämpfen, so dass diese sich im Laufe der Zeit ansammeln.
Dr. Garth Nicolsen hat herausgefunden, dass eine Person im Durchschnitt umso mehr Infektionen hat, je länger sie krank ist.

17. Weitere Dinge, die sich im Laufe der zeit ansammeln sind verschiedene Arten von Giften weil das Entgiftungssystem zu einem sehr großen Teil vom Schwefelstoffwechsel abhängig ist – und dieser wird nicht ausreichend funktionieren, solange eine Person CFS hat.
Der Körper speichert viele dieser Toxine im Fett, aber wenn die Giftmengen zunehmen, beginnen sie Schwierigkeiten in der Biochemie der Zellen zu verursachen.
Viele CFS-Patienten wurden auf Toxine hin untersucht (die meisten üblicherweise auf Schwermetallgifte, die am einfachsten zu testen sind) und diese sind üblicherweise erhöht.

18. Je länger eine Person mit CFS chronisch erkrankt ist, desto mehr Toxine und Gifte sammeln sich im Körper an und desto mehr Symptome werden erlebt.
Dies erklärt, warum sich die Krankheit im Laufe der Zeit verändert und warum einige Personen nachdem sie viele Jahre krank waren extrem geschwächt werden.

Der Hauptschlüssel um diesen Prozess umzukehren ist dem Enzym der Methioninsynthese zu helfen wieder besser zu funktionieren, so dass der Methylierungszyklus und der Folsäurezyklus angehoben werden und Glutathion wieder auf ein normales Maß hochgefahren wird.
Das ist, wozu das vereinfachte Behandlungsprotokoll kreiert wurde, und bisher ist die Evidenz so, dass es genau diese Dinge bei den meisten Menschen mit CFS tut.
Ich empfehle, dass Personen mit CFS das „Vitamin Diagnostics methylation pathways panel“
durchführen, um herauszufinden ob sie tatsächlich eine partielle Blockade im Methylierungszyklus und eine Verringerung von Glutathion haben, bevor sie sich mit ihren Behandlern entscheiden, ob sie diese Behandlung durchführen. Es liefert auch eine Grundlage, so dass Fortschritte später beurteilt werden können, wenn die Untersuchung im Verlauf der behandlung alle paar Monate durchgeführt wird.
Symptome sind nicht unbedingt eine gute Orientierung um den Fortschritt während der Behandlung durchzuführen, da die Entgiftung und das Absterben (Anmerkung:Z.B. Von Viren) die Symptome verschlimmern kann, während diese faktisch genau das sind, was nötig ist um den Betroffene in die Besserung zu führen.
(Anmerkung: Bisher hat Jimmy88 ein Labor in den Niederlanden entdeckt, das diese Untersuchung offenbar durchführt: siehe #87, #89 bzw:
The European Laboratory of Nutrients - welcome )

20. Die Hauptfrage an der ich nun arbeite ist, was noch getan werden muss, um die Leute in die Genesung zu bringen?
Ich habe bisher noch keine vollständigen Antworten auf diese Frage. Viele Leute werden allein durch diese Behandlung eine Besserung (oder Genesung) erfahren, aber es ist nachweislich ein langsamer Prozess und wir benötigen mehr Zeit um zu sehen wie es sich entwickelt.
Es scheint, dass Personen die wegen Schimmelpilzen an Krankheit leiden, sich selbst von Umgebungen fern halten müssen wo diese giftigen Pilze präsent sind.
Die wenigen Belege die ich bisher habe suggerieren, dass Personen die Lyme-Borreliose haben diese noch zusätzlich behandeln müssen.
Ich bin bezüglich verschiedener Virusinfektionen nicht sicher. Möglicherweise müssen diese auch behandelt werden.
Wir müssen noch viel lernen, aber ich bin überzeugt, dass die Mechanismen, die ich oben beschrieben habe das Kernstück der gestörten Biochemie bei CFS ist und die Korrektur ein Eckpfeiler der Behandlung sein muss.

Der Methylierungszyklus - eine zentrale Ursache? ENGLISH ORIG

tiga ist offline
Themenstarter Beiträge: 1.283
Seit: 16.03.10

Da gegen Ende der vorigen Übersetzung die Lyme-Borreliose angesprochen wird, hier erstmal der Hinweis, dass RichvanK dazu auch etwas veröffentlicht hat.
Ist lang und per Pdf, daher hier erstmal der Link, sowie die Frage, inwiefern Interesse besteht:

Gruß - tiga

Der Methylierungszyklus - eine zentrale Ursache? ENGLISH ORIG

tiga ist offline
Themenstarter Beiträge: 1.283
Seit: 16.03.10
Salut !

Es gibt eine super tolle Powerpoint Präsentation, die ganz übersichtlich die Zusammenhänge zur Methylierungsstörung ausgehend von Dr. Amy Yasko`s Forschungen darstellt:

AWESOME PRESENTATION - Genetic Bypass Simplified

Gruß - tiga

Der Methylierungszyklus - eine zentrale Ursache? ENGLISH ORIG
Zitat von tiga Beitrag anzeigen
Der Link funktioniert nicht.


Der Methylierungszyklus - eine zentrale Ursache? ENGLISH ORIG

KarlG ist offline
Beiträge: 2.387
Seit: 22.01.11
Der vielleicht?


Der Methylierungszyklus - eine zentrale Ursache? ENGLISH ORIG

alibiorangerl ist offline
Beiträge: 8.955
Seit: 09.09.08
wie ich sehe, ist diese PPT Präsentation kostenpflichtig?!
» Optimismus ist nur ein Mangel an Information. « – Heiner Müller

Der Methylierungszyklus - eine zentrale Ursache? ENGLISH ORIG

kari ist offline
Beiträge: 3.107
Seit: 16.05.07
Hallo AO,

ich kann die Präsentation abrufen, ohne einen Cent zu zahlen.
Danke, fürs Einstellen, Tiga.

Zitat von KarlG Beitrag anzeigen
Der vielleicht?
Oho! Wenn man das zugrunde legt, kann die Borre-Rubrik ja mit der CFIDS-Rubrik zusammengelegt werden
Ich hatte schon öfter mal den Verdacht, dass es so sein könnte:

"Is There a Link between Lyme Disease and Chronic Fatigue Syndrome?"
by Richard A. Van Konynenburg, Ph.D.
LG - kari

Der Methylierungszyklus - eine zentrale Ursache? ENGLISH ORIG

Kullerkugel ist offline
Beiträge: 6.671
Seit: 01.06.10
Hallo ,

Oho! Wenn man das zugrunde legt, kann die Borre-Rubrik ja mit der CFIDS-Rubrik zusammengelegt werden
Die "chronische Form Histaminintoleranz" könntet Ihr getrost dazu packen und einiges andere auch....


Der Methylierungszyklus - eine zentrale Ursache? ENGLISH ORIG

alibiorangerl ist offline
Beiträge: 8.955
Seit: 09.09.08
Wuhu kari,
Zitat von kari Beitrag anzeigen
... ich kann die Präsentation abrufen, ohne einen Cent zu zahlen.
Danke, fürs Einstellen, Tiga.
find ich merkwürdig; Ich seh nur das Titelbild (in orange gehalten) mit Titel-Text samt Autorenname und email, mehr nicht; Es gibt keine Links/Buttons, wo man "weiter" gehen könnte, auch nicht durch einfachs ins Bild klicken; Aber es gibt Buttons, um die PPT-Datei "downzuloaden" oder "auszudrucken" - klick ich darauf, kommt ein pop-up, um mich per facebook-id oder nur email zu identifizieren bzw registrieren, gebe ich (m)eine email ein, gelange ich zu dieser Seite:

Oho! Wenn man das zugrunde legt, kann die Borre-Rubrik ja mit der CFIDS-Rubrik zusammengelegt werden
Ich hatte schon öfter mal den Verdacht, dass es so sein könnte:

"Is There a Link between Lyme Disease and Chronic Fatigue Syndrome?"
by Richard A. Van Konynenburg, Ph.D.
ist ja schon lange kein Geheimnis mehr, dass man (auch) Mikroorganismen (vgl Zoonose ) als (eine) Ursache für CFidS/ME in Betracht zieht
» Optimismus ist nur ein Mangel an Information. « – Heiner Müller

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