Talk:Myalgic encephalomyelitis/chronic fatigue syndrome/Archive 4

message: Have researchers missed a vital clue in CFS? “The Cause of Chronic Fatigue Syndrome; Light at the End of the Tunnel” Author David Eather.  David is a CFS sufferer who ‘discovered’ a treatment for his form of CFS. He interested academics and they worked out the biochemical processes involved. He then self published the book himself in 2000 but is now out of print? As several have expressed a passing interest I have prepared this summary only.
Essentially the book is an hypothesis, that blames CFS symptoms on build up of acetylaldehyde in tissues. He begins by comparing the symptoms of CFS in the book by Dr Anne McIntyre “ME  Post-Viral Syndrome and how to live with it” ISBN: 0044403186; Paperback; 1989-04) with the symptoms of an ‘aldehyde reaction’ had by people born without the enzyme to break down aldehyde (after consuming alcohol) and points out the remarkable similarities, with CFS. Ref for Reaction is a Pharmaceutical Product Guide for product Antabuse
First some biochemistry, in the mitochondria alcohol is broken down to acetyl-aldehyde by the enzyme ‘alcohol dehydrogenase’ then into acetic acid (vinegar) by “aldehyde dehydrogenase” 90% of alcohol is converted in liver mitochondria but in muscles also. Now during aerobic glycolysis also in the mitochondria, during pyruvate conversion to Acetyl CoA, amounts of acetyl alderhyde escape from the ‘pyruvate dehydrogenase’ enzyme. In the healthy the ‘alderhyde dehydrogenase’ enzyme cleans this up. But his hypothesis for CFS is that the mitochondrial ‘alderhyde dehydrogenase’ enzyme is faulty.  
The book goes on to explain how acetylaldehyde  a very toxic substance damages cellular membranes and causes various symptoms of CFS. Muscles, brain, liver, crosses the blood / brain barrier, affects neurotransmitters and causes tinnitus.  Explains why patients have chemical sensitivity to substances that give off acetelalderhyde or formalderhyde. Explains how acetylaldehyde combines with NAD and reduces anaerobic energy, thus compromising two energy processes. When NAD is tied up alternative pathway cytochrome P 450 is activated to clear chemicals and this produces more toxic by-products in much the same way as seen in chronic alcoholics.  L-Methionine is supposedly a standard treatment for acetylalderhyde poisoning, and for alcohol liver damage. Nicotinamide replaces tied up NAD and eases some symptoms, but he suggests should be used with caution, lest exuberance produces more acetylalderhyde.  I think it may be the same subset who benefit from NADH treatment.    if so this hypothesis provides an explanation for these trial results.                                                                   Reference for alcohol intolerance in CFS is Dr Clive Sheperd “Living With M.E.” ; Paperback; 1999-02-01) Who apparently says ‘if there is no alcohol intolerance there is not CFS”.  Note this theory also explains vinegar sensitivity/intolerance in CFS.  Jagra 11:11, 1 October 2007 (UTC)
replies: text: A request for accuracy, please.  It is Dr Anne Macintyre; it is Dr Charles Shepherd - not Dr Clive Sheperd! MEagenda 16:44, 9 October 2007 (UTC)

text: So those two trials (26 and 31 patients) show some benefit for NADH, but were they conducted to test Dr Sheperd's hypothesis? "Have researchers missed a vital clue in CFS?" - if the hypothesis has not been adequately tested then they may have. Is this mirrored by increased incidence of CFS in populations with known reduced acetaldehyde dehydrogenase levels, such as the Japanese? And your comment on vinegar makes no sense at all - vinegar is acetic acid, which is what acetaldehyde is converted to by ALDH! Are you suggesting the enzyme works backwards (which is not in itself impossible).  is a useful read. JFW | T@lk 12:09, 1 October 2007 (UTC)
replies: text: JFW, the OMIM data you linked says the mitochondrial form is ALDH 2 and that has high affinity for NAD, and is deficient in 50% of Orientals, I agree it would be interesting to compare. Do we have statistics for incidence of CFS in Japan? By coincidence it seems the first NADH trial was published about the same time as Dr Sheperd’s book, but predated David Eather’s hypothesis by about a year, so I doubt the hypothesis has been fully tested, certainly they did not include all elements such as the L-methionine in either trial. Indeed the biochemical pathways show the aldehyde dehydrogenase enzyme as two way, but in addition David explains the sequesting of NAD partly shuts down the KREB cycle so any dietary vinegar has no where else to go? The supplementary NADH replacing that produced normally by the KREB cycle. Where as David's approach was to increase NAD and kick start the KREB cycle to produce NADH. Testing both approaches on the same responders would further test the hypothesis? Jagra 11:38, 2 October 2007 (UTC)

text: I don't think this is the forum to set up trials, but I wish you luck in getting this looked at. JFW | T@lk 22:28, 6 October 2007 (UTC)
thread_title: Alcohol Intolerance; a vital clue !

message: A new name was added to the names list so I checked it out; the reference doesn't describe any illness, and a search on the person (news articles, her own blog and biography) mentions nothing about CFS, it only mentions anorexia and even mild stroke. Therefore I removed it. The name list has gone wild and unchecked. Due to the "internet copy and paste effect" many other websites have been citing Wikipedia for these names, and people are assuming in good faith that it is accurate. Going through this list requires checking out related Wikipedia entries for references or finding new references; but I'm sure we all have more important things to do than solely dedicating ourselves to this one task, so perhaps we all need to help out with a few names each. - Tekaphor 04:11, 2 October 2007 (UTC)
thread_title:  Notable cases 

message: Just thought i'd bring up something i found on the bbc website that i think is relevant:    —Preceding unsigned comment added by 84.68.64.84 (talk) 18:40, 2 October 2007 (UTC)
replies: text: Well, we know chocolate is addictive and gives a mood lift especially it seems to the ladies!, this is done thru increased Serotonin. Now it may be that there is a subgroup of CFS patients with high cortisol, but these have not been isolated in studies to date! Increased serotonin a neurotransmitter, means further reduced cortisol. After all that is how Tricyclic antidepressants work (increase serotonin reduce cortisol). 'Can't hurt', I would not be too sure about that! Jagra 11:00, 4 October 2007 (UTC)

text: Dark chocolate contains flavonoids that are good for the bloodstream and work slightly anti-inflammatory. Combined with sugar, however, the total effect of chocolate quickly turns bad. Guido den Broeder 11:10, 4 October 2007 (UTC)
thread_title:  Chocolate Cure 

message: At first glance, an excellent new section i think! although could you explain what this "Beta-endorphin a natural pain killer is considered low" means for me please? Thedreamdied 12:19, 3 October 2007 (UTC)
replies: text: Beta-endorphin is a natural opioid, the reason morphine acts in humans is because it targets cell receptors in the peripheral and central nervous system, meant for our own opioid. CFS is considered a pro-inflammatory condition, cortisol suppresses inflammation, in CFS cortisol is low. Certain immune system changes such as cytokines are pro-inflammatory, essential fatty acid metabolite ratio changes in CFS such as increased LTB4 are pro-inflammatory and so on. With increased inflammation goes increased pain, lower circulating opioid means the pain is felt more, whether this translates to more central sensitization I cannot say. Beta-endorphin also has immune system and neurotransmitter function, the authors of the paper cited say “This finding may reflect the condition of chronic immune activation in CFS” and “Therefore, we would postulate that the fatigue and weakness typical of CFS could be related to low beta-endorphin concentrations at the central nervous system level.” It is found in neurons of the hypothalamus, as well as the pituatary gland, in this regard the latest findings of the CDC in classes of unexplained chronic fatigue, found alterations in gene expression of POMC a precursor polypeptide synthesised in the hypothalamus and pituatary glands that can be cleaved to form products including beta endorphin a natural opiod and pain killer, as well as ACTH which stimulates the adrenal glands to produce cortisol and other hormones. . So I think it is a consequence rather than the cause! Jagra 10:43, 4 October 2007 (UTC)
replies: text: Pain in CFS is, however, primarily caused by the build-up of lactic acid, not by inflammation. Guido den Broeder 10:53, 4 October 2007 (UTC)
replies: text: Yes it seems lactic acid increase is normally associated with increased beta-endorphin  presumably to reduce pain, so less b-endorphin in CFS also goes to more exercise induced muscle pain as well as more inflammatory pain, viz. in joint pain and probably spasm induced pain, trigger points etc. The beta-endorhin findings in CFS and Fibromyalgia also differentiate from  findings in Depression  I probably should add this ref to the article as well.Jagra 11:52, 4 October 2007 (UTC)
replies: text: IIRC there is research that shows that abnormal pain perception in CFS only occurs if there is comorbid Fibromyalgia. Regards, Guido den Broeder 12:56, 4 October 2007 (UTC)
replies: text: b-endorphin is released along with acth in the pituitary as part of the hpa axis, so this again could be related to the hpa axis. Also, there is research showing that fibromyalgia patients tend to have hpa axis overactivation (which could explain the pain) and cfs tend to have underactivation. However I don't know if this research has been replicated or applies to all patients, and it confuses things when you consider that there is a large overlap between cfs and fibromyalgia anyway. The dysfunction is likely to be in the brain, so I don't think we're going to get any real answers until we can look at individual neurons inside the brain in patients to see what is happening. Possibly the hpa axis is normal most of the time, but goes out of whack only during (or after) periods of physical or mental stress. So the only way you're ever going to see what is going on is to somehow look inside the brains of patients 24 hours a  day and see what is going on and how it corresponds with symptoms. And I don't see this happening any time soon. --Sciencewatcher 21:40, 5 October 2007 (UTC)
replies: text:  Sciencewatcher, I am unable to find any studies showing high circadian cortisol, acth, or high beta-endorphin in fibromyalgia, can you provide ref? Jagra 09:48, 9 October 2007 (UTC)

text: This particular dysfunction is situated in and at the mitochondria, although lactic acid will build up in the brain as well. Guido den Broeder 00:36, 6 October 2007 (UTC)
replies: text: At the 8th International Association for CFS/ME conference, Dr Nestadt discussed his findings of ventricular lactate levels: about 3 times higher in ME/CFS patients than in generalized anxiety disorder patients and about 3.5 times higher than healthy controls, plus this increase correlated with self reported levels of fatigue. Nestadt believes there is a shift to anaerobic metabolism, mitochondrial compromise and increased oxidative stress. The study is now in a larger more comprehensive second phase. - Tekaphor 02:20, 6 October 2007 (UTC)
replies: text:  Tekaphor, that fits with David Eather's acetaldehyde hypothesis, mitochondrial compromise and less aerobic puts more reliance on anaerobic energy. Do you have any ref's for Nestadt's work other than conference? Jagra 09:48, 9 October 2007 (UTC)

text: Jagra, unfortunately I was unable to locate a proper citation, perhaps it hasn't been published. If they publish the larger more comprehensive study, it will be a good reference for the neurological section. - Tekaphor 02:54, 10 October 2007 (UTC)
thread_title:  Jagra 

message: From the "treatment" section I removed a piece that belongs in the "crystal ball-gazing" category. It seems to have only indirect bearing on CFS/ME and is quite POV:
:Due to the multi-systemic nature of the illness, and others like it, an emerging branch of medical science called psychoneuroimmunology is exploring how all the various theories fit together.''
It's here for consideration, and because I've managed to trace the references. JFW | T@lk 21:53, 8 October 2007 (UTC)
thread_title: Removed stuff

message: The role of essential fatty acid metabolites in the pathogenesis of CFS is poorly understood even by immunologists, here is the likely scenario. Reduced cortisol reduces lipocortin, increases PLA2, increases lipid peroxidation hence oxidative stress, increases essential fatty acid metabolites, reduces anti oxidants including GSH. Reduced GSH increases LTB4 and reduces PGE2, increases nitric oxide, increase cytokines, reduces CRH. A vicious circle, what stops it, reduced cellular substrates, as found in CFS,  Many immune responses are intended for relatively short term effect but sustained extracellular signalling and intracellular amplification leads to exhaustion of substrate and inactivated enzymes (including the D6D). Other feedback loops exist but can become disordered as hyper response causes increased down regulation of receptors leading to chronic hypo responsiveness. As EFAM’s are potent immuno-modulators we see chronic stimulation leading to both hyper responses and paradoxically hypo responsiveness of the immune system, varying depending upon individual diathesis. Once established the chronic state is maintained by minor stressors. 
For the Article I propose as a rider to the immune dysfunction section a statement that; ‘Sustained hyper responses of the immune system can variably lead to substrate depletion, down regulation of receptors and enzymes leading to hypo responsiveness, that may account for variable immune system findings in CFS. Some of the more common findings include;' (reduce some of the current leading para). Jagra 08:04, 17 October 2007 (UTC)
replies: text: I think the substrate depletion is WP:NOR. If immunologists don't understand this, how can we possibly claim that they do, especially in an inherently un-understood disease like CFS? JFW | T@lk 11:06, 19 October 2007 (UTC)

text: Unless I am mistaken, and precedence would not seem to indicate otherwise, NOR does not apply to this talk page unless pretence is involved. As to what we can include in the Article I think you will find I have not suggested other than what is already in the literature. Jagra 08:45, 22 October 2007 (UTC)

text: Guido, my understanding is that carnitine is needed to transport long chain fatty acids into the mitochondria where B-oxidation produces energy and shortens fatty acid chain length. Specific enzymes are needed in the lipid membranes to enable this, whilst carnitne shortage (produced only in the liver) is found in CFS and said to be the cause of excessive ammonia given off (in sweat) by CFS patients.  There are contradictory reports, meaning it may only apply to subgroups.  Down regulation of these transport enzymes does not seem to be involved?  Although you will note from above references that B-oxidation is affected in (some) CFS. The immune dysgegulation arises from substrate depletion in lipid membranes and presumably these changes could effect other membrane functions, such as the carnitine transport. Do you have any references showing why this may be occuring? Certainly mitochondrial energy disruption would add to other fatigue, although it has been suggested that resulting low acetyl-carnitine, a neuro-transmitter in the brain may be responsible for fatigue sensation  so may be we come full circle for substrate depletion and fatigue sensation??  and it seems also to immune system dysfunction.  What is the distorted protein folding attributed to? Jagra 05:46, 30 October 2007 (UTC)
replies: text: I think not. The fatigue in ME/CFS is not a matter of erroneous sensation; it is real, caused by rapid ATP depletion (where carnitine is also involved), i.e. the neurotransmitters do this job right. Guido den Broeder 10:21, 30 October 2007 (UTC)

text: JFW, I know you are aware of the fact that the selection criteria used in the majority of trials with thumbs up for CBT/GET are a source of controversy themselves. So as for the patients who get better: Who guarantees they had the same disease as those who got worse? The Oxford research definition perhaps, being one of the least restrictive?JayEffage 22:31, 30 October 2007 (UTC)
replies: text: I could level exactly the same accusations at the studies on which these pronouncements are based ("ATP depletion", "carnitine is involved"). What are their inclusion criteria? Is their methology transparent? Have the results been duplicated? JFW | T@lk 16:41, 31 October 2007 (UTC)
replies: text: By all means yes, you could do that, and correctly so. Finally there is some common ground(Playing Griegs "Morning Mood"). I personally think that  - given the background of sky high prevalence figures we have been hearing lately - these anmbiguities could ultimately explain a large part of the controversy. 82.135.91.194 02:26, 1 November 2007 (UTC)

text: By itself, the term CGT is not very informative. What matters is which cognitions are learned or unlearned. If CGT aims to teach the patient to rest in time, i.e. before the ATP cycle fails, and to vary which muscles are used, he will experience significantly less fatigue. This type of CGT combines well with pacing and envelope techniques. If, on the other hand, the therapist thinks he can cure the patient and tries to teach the patient to ignore all signals of fatigue, and exercise is graded up, then there is the risk that not only ATP, but even ADP runs out, and the muscles are damaged. This is why so many patients get worse after this kind of therapy and have to stop halfway through. Guido den Broeder 23:36, 30 October 2007 (UTC)
thread_title: Hyper-response and Immune Dysfunction in CFS

message: :I think the substrate depletion is WP:NOR. If immunologists don't understand this, how can we possibly claim that they do, especially in an inherently un-understood disease like CFS? JFW | T@lk 11:06, 19 October 2007 (UTC)
replies: text: Unless I am mistaken, and precedence would not seem to indicate otherwise, NOR does not apply to this talk page unless pretence is involved. As to what we can include in the Article I think you will find I have not suggested other than what is already in the literature. Jagra 08:45, 22 October 2007 (UTC)
thread_title: Substrate Depletion

message: Essential fatty acid deficiency, ( quite apart from oxidative changes to RBC deformability, the likely result of hyper-response  in CFS, depriving muscle and tissue of oxygen and energy (see above)), causes a reduction of about one third in how soon fatigue occurs,  As Bricker has pointed out this ref  shows why substrate depletion may not be the direct cause of (normal) fatigue, but instead it is the need to prevent substrate depletion further, that triggers the CNS to produce a fatigue state and slow or stop the patient's level of activity. The often extreme fatigue state CFS patients experience could well be protective, although highly distressing, but not inherently pathological. The possibilities tie in with the CDC comments Guido reported below in the (ME section). Main factors; “Cognition loss/sleep loss, Musculoskeletal problems, Inflammation and infection. As a result of these findings, investigators are beginning to consider fatigue as an end product rather than a causal factor of CFS.”  EFAD certainly contributes to cognition, pain sensitivity, body temperature irregularity, altered inflammatory responses and less slow wave sleep.     Jagra 03:00, 29 October 2007 (UTC)
replies: text: Guido, my understanding is that carnitine is needed to transport long chain fatty acids into the mitochondria where B-oxidation produces energy and shortens fatty acid chain length. Specific enzymes are needed in the lipid membranes to enable this, whilst carnitne shortage (produced only in the liver) is found in CFS and said to be the cause of excessive ammonia given off (in sweat) by CFS patients.  There are contradictory reports, meaning it may only apply to subgroups.  Down regulation of these transport enzymes does not seem to be involved?  Although you will note from above references that B-oxidation is affected in (some) CFS. The immune dysgegulation arises from substrate depletion in lipid membranes and presumably these changes could effect other membrane functions, such as the carnitine transport. Do you have any references showing why this may be occuring? Certainly mitochondrial energy disruption would add to other fatigue, although it has been suggested that resulting low acetyl-carnitine, a neuro-transmitter in the brain may be responsible for fatigue sensation  so may be we come full circle for substrate depletion and fatigue sensation??  and it seems also to immune system dysfunction.  What is the distorted protein folding attributed to? Jagra 05:46, 30 October 2007 (UTC)
replies: text: I think not. The fatigue in ME/CFS is not a matter of erroneous sensation; it is real, caused by rapid ATP depletion (where carnitine is also involved), i.e. the neurotransmitters do this job right. Guido den Broeder 10:21, 30 October 2007 (UTC)

text: JFW, I know you are aware of the fact that the selection criteria used in the majority of trials with thumbs up for CBT/GET are a source of controversy themselves. So as for the patients who get better: Who guarantees they had the same disease as those who got worse? The Oxford research definition perhaps, being one of the least restrictive?JayEffage 22:31, 30 October 2007 (UTC)
replies: text: I could level exactly the same accusations at the studies on which these pronouncements are based ("ATP depletion", "carnitine is involved"). What are their inclusion criteria? Is their methology transparent? Have the results been duplicated? JFW | T@lk 16:41, 31 October 2007 (UTC)
replies: text: By all means yes, you could do that, and correctly so. Finally there is some common ground(Playing Griegs "Morning Mood"). I personally think that  - given the background of sky high prevalence figures we have been hearing lately - these anmbiguities could ultimately explain a large part of the controversy. 82.135.91.194 02:26, 1 November 2007 (UTC)

text: By itself, the term CGT is not very informative. What matters is which cognitions are learned or unlearned. If CGT aims to teach the patient to rest in time, i.e. before the ATP cycle fails, and to vary which muscles are used, he will experience significantly less fatigue. This type of CGT combines well with pacing and envelope techniques. If, on the other hand, the therapist thinks he can cure the patient and tries to teach the patient to ignore all signals of fatigue, and exercise is graded up, then there is the risk that not only ATP, but even ADP runs out, and the muscles are damaged. This is why so many patients get worse after this kind of therapy and have to stop halfway through. Guido den Broeder 23:36, 30 October 2007 (UTC)
thread_title: Fatigue and Energy

message: There is gold standard evidence of oxidative stress in CFS indicative of a free radical attack on lipids    Cell membrane fluidity and fatty acid composition is altered in CFS associated with oxidative stress  There is evidence of reduced levels of anti-oxidants, including ubiquinone (CoQ10), glutathione (GSH), and free-radical scavenging enzymes, , low levels of GSH is found associated with low magnesium levels in CFS.   
Glutathione (GSH) an antioxidant is essential for proper lymphocyte responses. Impaired lymphocyte responses to mitogens are one of the more common immune findings in CFS, and may arise as a consequence of sustained hyper-response of the immune system. GSH is also essential for aerobic muscular contraction. An undesirable competition for GSH precursors between the immune and muscular systems may develop.  Thus immune hyper-responsiveness may explain several symptoms and findings in CFS.
Zinc (an anti-oxidant) levels are found low in CFS, and the low findings are found related to low mitogen T-cell responses  Among the altered lipids in CFS are findings of  low n-3 essential fatty acids, related to low zinc findings and lowered mitogen stimulated responses.   This can be explained as zinc activates the production of glutathione (GSH)   
Zinc is also involved in the regulation of aldehyde dehydrogenase. Low levels of zinc inhibit the enzyme, but increased levels of zinc rapidly disinhibit and increase production of acetaldehyde dehydrogenase, likely via increased GSH. Zinc inhibits some enzymes that are not necessarily zinc enzymes, e.g. glyceraldehyde and glycerol phosphate dehydrogenases, and aldehyde dehydrogenase.  (GSH)  glutathione mediates zinc transfer from enzymes to thionein  Thionine removes the metal from an inhibitory zinc-specific enzymatic site with a resultant marked increase of enzyme activity  This increase in aldehyde dehydrogenase has effects on cellular energy and also since glycerol phosphate dehydrogenase is a key enzyme in energy metabolism, the effect of zinc is expected to elicit significant physiological responses, including immune responses. 
In CFS plasma transferrin (lipid protective) levels are found lowered  and MDA levels (a sign of oxidative stress and lipid peroxidation) are found raised.   Metallothionein synthesis can be stimulated in many organs by various metals such as dietary zinc. When zinc-metallothionein was given experimentally in animal studies, it raised transferrin and lowered MDA and reduced lipid peroxidation  Showing the potential for GSH increase via zinc in treatment of hyper-responsive immune systems. Large scale trials that involved injected glutathione in CFIDS/CFS have shown high incidence of improvements. Also suggested was use of selenium supplementation to increase GSH  In mammals, a major function of selenium (Se) and Se-dependent GSH-Peroxidase is to protect cells from oxidative stress. Zinc supplements are recommended for CFS   
Alpha lipoic acid supplementation has also been suggested for CFS  It has recently been found that mitochondrial oxidative stress may inactivate aldehyde dehydrogenase and that the mitochondrial reduced form of A-lipois acid, restores mitochondrial aldehyde dehydrogenase activity by a different means than zinc  Alpha lipoic acid also blocks cytokine formation of one of the likely products of a hyper-response, the essential fatty acid metabolite PGE2  and assists the benefit of n-3 fatty acids in reducing lipid peroxidation.  Cysteine levels have been found low in CFS   N-acetyl cysteine (NAC)and Alpha-lipoic acid can increase GSH concentration indirectly. NAC provides cysteine for GSH synthesis, and alpha lipoic acid is believed to increase intracellular GSH levels by reducing extracellular cystine to cysteine, bypassing the cystine transporter . 
CoQ10 has been found low in CFS.  It is considered valuable as an anti-oxidant and an aid to energy production in neurological and neuromuscular conditions, and is used in association with alpha lipoic acid.  , Alpha-lipoic acid maintains CoQ10 in its anti-oxidant form and experiments demonstrate a superadditive effect with such combination of ubiquinone (CoQ10) in preventing peroxidation of biomembranes.  CoQ10 supplementation was reported of benefit in CFS   In CFS increased ascorbic acid (vitamin C) demand is found  and low vitamin E    
Vitamin C and vitamin E help maintain glutathione in its reduced form GSH . Magnesium supplementation increased serum Vitamin E and reduced lipid peroxidation in CFS    
In view of the many findings of lipid peroxidation and high level evidence for associated oxidative stress in CFS, I propose that the Oxidative stress section of the Article should include the lipid peroxidation findings and that the Treatment section should contain an item on anti-oxidants, where evidence is available and/or where deficiency is found in CFS. Jagra 03:01, 5 November 2007 (UTC)
thread_title: Oxidative stress and Antioxidants

message: LTB4 this essential fatty acid metabolite and its derivatives LTC4, D4, E4, are considered proinflammatory and involved in a number of CFS symptoms and associated conditions including IBS, broncho hypertension, leaky gut syndrome, food intolerance, allergies, also implicated in other conditions such as asthma, atherogenesis, peripheral vascular disease, arteriosclerosis, coeliac disease, and IBD. There is little doubt that this family of metabolites are pro-inflammatory in their own right.
LTB4 is also vasoconstrictive and is produced in the brain, does this explain reduced cerebral and arterial blood perfusion findings in CFS?   
PGE2 a prostaglandin is basically vasodilative and down regulation of PGE2 adds to up regulation effects of LTB4. Both PGE2 and PGD2 are produced in the brain by astrocytes due to numerous stimuli including cytokines. In the hypothalamus they control sleep / wake and hot / cold regulation and disordered essential fatty acid metabolites can explain numerous symptoms in CFS both neurological and in other body systems. Also of relevance is that circulating EFAM’s such as PGE2 can cross the blood brain barrier and LTB4 weakens the BBB.    as can arachodonic acid excess  due to hyper response and increased phospholipase ie reduced cortisol. Jagra 23:39, 12 October 2007 (UTC)
thread_title: Effects of some essential fatty acid metabolites

message: Whilst some have proposed a virus for increasing the permeability of the BBB in CFS. It does not need a virus for a weakened BBB to be implicated, for instance others have shown    that the weakening can occur from; increased serotonin, depleted glutathione (GSH), essential fatty acid deficiency, cytokines, nitric oxide, and peroxynitrite, and stress, all implicated in CFS symptoms. A weakened BBB can allow a virus access to the CNS as a perpetuating factor! I propose adding to the neurological section the consequences of increased serotonin; reduced HPA axis function including reduced cortisol and beta-endorphin also weakening of the blood brain barrier. Jagra 23:39, 12 October 2007 (UTC)
replies: text: It seems a bit speculative, unless you have research showing weakened BBB in CFS patients and evidence of CNS infection in patients. --Sciencewatcher 00:03, 13 October 2007 (UTC)
replies: text: No, under Neurological Abnormalities, at this time I am interested in the serotonin findings in CFS and the known affect on BBB permiability. but for discussion I will add later some thing on virus and CNS Jagra 10:02, 13 October 2007 (UTC)
thread_title: Blood Brain Barrier in CFS

message: @Sciencewatcher, you claim that the publication 
Hyde B. "A New and Simple Definition of Myalgic Encephalomyelitis and a New Simple Definition of Chronic Fatigue Syndrome & A Brief History of Myalgic Encephalomyelitis & An Irreverent History of Chronic Fatigue Syndrome" 
does not exist. Why would you say that, in view of ? Guido den Broeder 20:27, 11 October 2007 (UTC)
replies: text: I had a look on the nightingale site and I couldn't find it anywhere. --Sciencewatcher 21:18, 11 October 2007 (UTC)
replies: text: So? There is no list of publications on that site, so it's hard to tell if one is missing. Guido den Broeder 21:39, 11 October 2007 (UTC)

text: That is a very strange proposition. Are we here to improve an article or to play a game? There is nothing wrong with mentioning a controversy or with the reference to Wessely, but your text does not cover the tale. And if it appears that Hyde's booklet indeed does not exist, it should not be in.Guido den Broeder 08:59, 12 October 2007 (UTC)

text: The letter can be found here: . Regards, Guido den Broeder 17:52, 12 October 2007 (UTC)
thread_title:  Hyde: new and simple definition 

message: First off, I'd like to apologize for placing the POV tag without prior discussion.  After reading the article through a few times late last night, I had some vague concerns about the tone of the article, though didn't know how to fix them.  I see that alternate (negative) viewpoints on the classification and impact of CFS are mentioned in the article, I just believe that they are first stated, and then argued against extensively.  An example of this would be the entire "Social Issues" section, where it begins with:
Many patients find that a chronic fatigue syndrome diagnosis carries a considerable stigma, and has frequently been viewed as malingering, hypochondriac, phobic, "wanting attention" or "yuppie flu".
And follows this statement with many others that seem to argue as to why this is not the case.  Other statements just seem to have an odd tone, for example:
Many CFS sufferers are confined to their house and/or bed. They are unable to take part in normal social activity. They are also excluded from workplace and school socialising.
It's entirely possible that I am incorrect, but these type of phrases seem unencyclopedic to me, as they seem more "personal" and situational rather than objectively factual - even if true.  I have intermittent internet access and may not be able to fully participate in a discussion, but I wanted to explain my placing of the tag.  I fully support that it has been removed; if regular or more knowledgeable editors deem that there are no tone issues with the article, I have no issues with it whatsoever.  I also apologize for having trouble expressing my thoughts on the subject, though hopefully someone knows what I'm getting at. *Vendetta* (whois talk edits) 17:29, 18 November 2007 (UTC)
replies: text: Thanks for explaining, Vendettax. First of all, both statements that you quote are in accordance with the facts as I know them. That said, this is a difficult topic with many emotions involved, and it is quite possible and even likely that some sections carry an undertone that regular contributors do not notice. Feel free to suggest any textual improvements! Regards, Guido den Broeder (talk) 17:42, 18 November 2007 (UTC)
replies: text:  I agree that some of the tone could be improved or better referenced, although the basis of the content is usually warranted. Some of this wording is probably remanents from much earlier versions of the article. - Tekaphor (talk) 02:40, 21 November 2007 (UTC)
replies: text: What if any significance are the brain right sided asymmetry findings in CFS. In Spect scans   , with MRI finding more right sided activation,  and in ME an association with right hemispheric biochemical dominance . Is this connected with the symptom of emotional lability in ME/CFS?  that might go to the emotiveness? Jagra (talk) 08:16, 21 November 2007 (UTC)
thread_title:  POV? 

message: I'm thinking perhaps underneath "Course", it could be changed just list the names of symptoms, rather than detailed descriptions?  —Preceding unsigned comment added by Jobers (talk • contribs) 12:08, 22 November 2007 (UTC)
replies: text: I agree that symptom information without sources should be slashed. JFW | T@lk 23:52, 22 November 2007 (UTC)
replies: text:  Would you intend to list all symptoms? which criteria will be reference base? At last count i was aware of over 100, do you intend an exhaustive listing, at present it is rather arbitrary ? If we use just symptom names (medical) then some plain english explanation will also be neededJagra (talk) 08:24, 23 November 2007 (UTC)
thread_title: Making the article shorter

message: First off, I'd like to apologize for placing the POV tag without prior discussion.  After reading the article through a few times late last night, I had some vague concerns about the tone of the article, though didn't know how to fix them.  I see that alternate (negative) viewpoints on the classification and impact of CFS are mentioned in the article, I just believe that they are first stated, and then argued against extensively.  An example of this would be the entire "Social Issues" section, where it begins with:
Many patients find that a chronic fatigue syndrome diagnosis carries a considerable stigma, and has frequently been viewed as malingering, hypochondriac, phobic, "wanting attention" or "yuppie flu".
And follows this statement with many others that seem to argue as to why this is not the case.  Other statements just seem to have an odd tone, for example:
Many CFS sufferers are confined to their house and/or bed. They are unable to take part in normal social activity. They are also excluded from workplace and school socialising.
It's entirely possible that I am incorrect, but these type of phrases seem unencyclopedic to me, as they seem more "personal" and situational rather than objectively factual - even if true.  I have intermittent internet access and may not be able to fully participate in a discussion, but I wanted to explain my placing of the tag.  I fully support that it has been removed; if regular or more knowledgeable editors deem that there are no tone issues with the article, I have no issues with it whatsoever.  I also apologize for having trouble expressing my thoughts on the subject, though hopefully someone knows what I'm getting at. *Vendetta* (whois talk edits) 17:29, 18 November 2007 (UTC)
replies: text: Thanks for explaining, Vendettax. First of all, both statements that you quote are in accordance with the facts as I know them. That said, this is a difficult topic with many emotions involved, and it is quite possible and even likely that some sections carry an undertone that regular contributors do not notice. Feel free to suggest any textual improvements! Regards, Guido den Broeder (talk) 17:42, 18 November 2007 (UTC)
replies: text:  I agree that some of the tone could be improved or better referenced, although the basis of the content is usually warranted. Some of this wording is probably remanents from much earlier versions of the article. - Tekaphor (talk) 02:40, 21 November 2007 (UTC)
replies: text: What if any significance are the brain right sided asymmetry findings in CFS. In Spect scans   , with MRI finding more right sided activation,  and in ME an association with right hemispheric biochemical dominance . Is this connected with the symptom of emotional lability in ME/CFS?  that might go to the emotiveness? Jagra (talk) 08:16, 21 November 2007 (UTC)
thread_title:  POV? 

message: I'm thinking perhaps underneath "Course", it could be changed just list the names of symptoms, rather than detailed descriptions?  —Preceding unsigned comment added by Jobers (talk • contribs) 12:08, 22 November 2007 (UTC)
replies: text: I agree that symptom information without sources should be slashed. JFW | T@lk 23:52, 22 November 2007 (UTC)
replies: text:  Would you intend to list all symptoms? which criteria will be reference base? At last count i was aware of over 100, do you intend an exhaustive listing, at present it is rather arbitrary ? If we use just symptom names (medical) then some plain english explanation will also be neededJagra (talk) 08:24, 23 November 2007 (UTC)
thread_title: Making the article shorter