Talk:Myalgic encephalomyelitis/chronic fatigue syndrome

Have researchers missed a vital clue in CFS? “The Cause of Chronic Fatigue Syndrome; Light at the End of the Tunnel” Author David Eather. ISBN 0646389025 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. PMID 10071523 PMID 15377055 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.” ISBN 0091816793; 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)Reply

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)Reply

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). Online Mendelian Inheritance in Man (OMIM): 100640 is a useful read. JFW | T@lk 12:09, 1 October 2007 (UTC)Reply

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)Reply

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)Reply

Ronline (talk · contribs) unilaterally split off the "treatment" section into a new article. I have reverted on several grounds; futher explanation is here on Ronline's talkpage. JFW | T@lk 12:09, 1 October 2007 (UTC)Reply

I think the article could be slimmed down some, before any talk of splitting. Although I'm sure even that will not be an easy task. Certainly discussion is needed before any significant action is taken. (This is the only article I have ever come across in Wikipedia which doesn't like to load properly on any browser I've tried.) Cheers. --- Taroaldo 19:58, 1 October 2007 (UTC)Reply

I'm not so sure to be honest. I think its a very, very complex subject, surely it needs a very long article? Just a thought Thedreamdied 20:15, 1 October 2007 (UTC)Reply

Agree with Taroaldo that the article should be slimmed down, not forked to bits. As I told Ronline, the "treatment" section depends on other parts of the article for clarification (e.g. immune boosting for immune deficiencies, fludrocortisone for orthostatic intolerance).

There are large swathes of the article that haven't been reviewed properly by anyone for months. I'm referring to the bit where the references have no PMID/DOI codes. Perhaps that is the content that should be examined closely for redundancies. JFW | T@lk 20:40, 1 October 2007 (UTC)Reply

How about two pages....page one.....summary of article sections for those casual searchers....page two....detailed article like we have now. Page one can be protected ......page two unprotected....that would serve both purposes....page one quick read...page two for what is thought/known and for changes....have fun....sno —Preceding unsigned comment added by Sno2 (talk • contribs) 20:52, 1 October 2007 (UTC)Reply

The bulk of the article is contained within two sections ("proposed causes and pathophysiology" and "treatment") and these sections are related (as JFW pointed out). Much of the treatment is also "proposed" as well and not universally accepted. Considering that these two sections take up a lot of space and are related, perhaps they can be forked together onto a page titled "proposed pathology of and treatments for CFS". Some areas could use a trim, but other areas could be expanded on. A single page would be ideal, but is this practical or likely to become much better any time soon? Other medical articles have separate pages for different aspects of the illness (e.g. diabetes and schizophrenia). I've never had trouble loading this article, but several other editors have expressed issues with it, which could mean that many other people who visit here also have trouble with it. - Tekaphor 03:12, 2 October 2007 (UTC)Reply

I think the problem is editing the article. I have never had problems loading the article, but sometimes if I edit the whole article (rather than individual sections) it takes a very long time or hangs when submitting changes. I think we should seriously trim the "proposed" bits and only have summaries of things that are speculative. --Sciencewatcher 21:44, 5 October 2007 (UTC)Reply

I firmly support the removal of outlandish theories, but I don't think it will happen without a fight. JFW | T@lk 22:29, 6 October 2007 (UTC)Reply

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)Reply

Just thought i'd bring up something i found on the bbc website that i think is relevant: [1] —Preceding unsigned comment added by 84.68.64.84 (talk) 18:40, 2 October 2007 (UTC)Reply

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)Reply

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)Reply

Interesting. So are we saying that the above link has at least some merit? I am interested in this as i myself suffer from CFS, and would be glad to make the switch to dark chocolate if there is a good chance it would help at all, even in the slightest bit.

Being a full time student really puts a strain on my energy levels, and any help or additional info would be welcome! - original link submitter

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)Reply

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. PMID 16610949. So I think it is a consequence rather than the cause! Jagra 10:43, 4 October 2007 (UTC)Reply

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)Reply

Yes it seems lactic acid increase is normally associated with increased beta-endorphin PMID 7836218 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 PMID 12131069 I probably should add this ref to the article as well.Jagra 11:52, 4 October 2007 (UTC)Reply

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)Reply

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)Reply

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)Reply

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)Reply

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)Reply

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)Reply

Jklsc (talk · contribs) is an infrequent contributor who has on numerous occasions made rather sweeping moves. I just noticed that on 1 September he changed the page myalgic encephalomyelitis into a redirect to the improperly (capitals) named page, and on the same day turned Myalgic Encephalomyelitis into a separate page that had previously redirected here. Angus Lepper (talk · contribs) subsequently removed large swathes of information directly lifted from certain websites.

I find it really unhelpful to have multiple articles. I am completely aware of certain voices that insist that ME is a distinct entity from CFS, but these voices happen to be in the minority even in the CFS/ME research community. I am fully supportive of mentioning these voices here, but I think having a separate article very much clouds the issue and just adds to fragmentation. Can we please settle the matter once and for all? JFW | T@lk 06:42, 7 October 2007 (UTC)Reply

On a separate note, thanks to Guido for boldly removing several kibibytes of unsourced cruft. JFW | T@lk 06:42, 7 October 2007 (UTC)Reply

My pleasure. ;-)

No matter can be settled 'once and for all' on Wikipedia. But I still prefer a separate article on Myalgic encephalomyelitis. CFS, is after all, only a working diagnosis. The CFS article could then focus on criteria, symptoms and management, while the ME article could focus on causes, risks and treatment. Guido den Broeder 09:18, 7 October 2007 (UTC)Reply

Are you suggesting ME is not a working diagnosis? Surely, unless MRI or EEG/EMG show changes suggestive of an inflammatory process, or a biopsy is performed (quod non), it is sheer conjencture to suggest an ME patient has -itis of his encephalon and his myelum?

The problem with a separate ME page is that it will immediately become a POV fork, free from the constraints of our present carefully-established editors' panel? A large majority of scientists seems to regard itself as "lumpers" (putting CFS/ME/PVFS in one melting pot) as opposed to a handful of "splitters". Why otherwise would the journal have been called Journal of Chronic Fatigue Syndrome (as opposed to J Myalg Encephalomyelitis)? And I think we can count large names like Leonard Jason, who uses the term without apology in an Arch Intern Med article of which he is the first author. JFW | T@lk 20:30, 7 October 2007 (UTC)Reply

That is correct. ME is not a working diagnosis but a disease entity. Guido den Broeder 21:48, 7 October 2007 (UTC)Reply

So how am I expected to differentiate ME from CFS? Do a brain biopsy looking for an inflammatory process? JFW | T@lk 16:54, 8 October 2007 (UTC)Reply

You can't. It's the same patient (unless you're counting GWS as CFS, too), just a different type of diagnosis. The ones without ME will, once found out, lose the CFS label. Guido den Broeder 18:30, 8 October 2007 (UTC)Reply

"C.F.S." vs "M.E."

Regardless of the issue of central inflammation, or whether they are the essentially same illness, or about the accuracy of ME-itis; the last 20 years has been vastly dominated by CFS research that didn't require several key ME symptoms in the study participants. By comparison there isn't much ME research in existence and most of that is decades old, so while people can point out that evidence for many claims about ME/CFS is lacking, we are faced with the fact that a lot of needed research simply hasn't been done. Unless such research is conducted that uses strict criteria and looks for all currently known possible signs of CNS inflammation, merely saying "the evidence is lacking" is unlikely to discourage ME proponents from referring to the older research and the CNS inflammation found more recently in some patients who died. Perhaps there could also be a larger "CFS vs ME" subsection in the article (as well as a subsection for "CFS vs chronic fatigue").

Leonard Jason may be a "lumper" as JFW implies, but his work and comments highlight the existence of subtypes, problems with the name, and the weaknesses of currently used criteria. We can't expect all ME/CFS patients to have the same pathology or response to treatments, in a similar way this isn't done for all tumour or all depression or all cerebral palsy. He also found the Canadian 2003 definition distinguishes patients with less psychiatric comorbidity and more physical impairment with more neurological symptoms, which questions previous assumptions from other researchers that increasing the requirement of somatic symptoms in CFS criteria necessarily increases the association with psychiatric disorders. Most of all this is essentially already mentioned in a section of the article but could be better reflected through the rest of the article as Bricker previously stated.

Tekaphor 03:43, 9 October 2007 (UTC)Reply

Sources offered for consideration:

• Shepherd C (2007), "ME guideline is unworkable", British Medical Journal 335 (7619): 528-528
• Den Broeder G (2007), "NICE guideline", Lees ME #3, ME/CVS Vereniging, 32-35 (in Dutch)

Guido den Broeder 22:01, 7 October 2007 (UTC)Reply

Hmm. WP:COI applies to the second source, which is in Dutch, for a public not affected by the Guideline in any form or description. Nice. And really suitable for the article, Guido.

Dr Sheperd's reaction in the BMJ (PMID 17855294 ) is predictable. Does he honestly suggest that the trials with GET and CBT were falsified by the trialists? Then why would patients' organisations get such radically different results from the groups that performed the trials?

The letter does not indicate whether Dr Shepherd has written this latter on behalf of the ME Association or a titre personnel. If it was the official response from this large ME charity then perhaps it would be a useful source. JFW | T@lk 16:54, 8 October 2007 (UTC)Reply

Not sure if I'm allowed to put the Dutch reference in. On nl:Wikipedia, I am presently hanging from the highest tree for being so bold with another publication, even though relevance had been established.

The ME Association's position seems equal to Shepherd's, from their press release[2]. Guido den Broeder 18:26, 8 October 2007 (UTC)Reply

But you haven't quoted the ME Association website, you have quoted Suzy Chapman's blog. No attempts have been made in that blog post to provide a URL to the ME Association's statement. Blogs are not generally regarded as WP:RS. JFW | T@lk 21:53, 8 October 2007 (UTC)Reply

At the time at which the ME Association's statement was posted on ME agenda blog the MEA's webmaster had not updated the MEA's website, although the MEA's press release on NICE had been published on various sites, elsewhere. The MEA's press release can be read on the MEA's site here. I have now added a rider to the ME agenda blog entry, redirecting readers to the MEA's site. The MEA's press release is supported by two additional national ME registered charities/patient organisations: The 25% Group for severe ME sufferers and The Young ME Sufferers Trust. MEagenda 14:41, 9 October 2007 (UTC)Reply

The response of Dr Charles Shepherd, Medical Adviser to the MEA, via eBMJ Rapid Responses to the NICE guideline Editorial and Review was also published a week or two later, in the print edition of the BMJ. MEagenda 14:53, 9 October 2007 (UTC)Reply

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.^[1][2][3]

It's here for consideration, and because I've managed to trace the references. JFW | T@lk 21:53, 8 October 2007 (UTC)Reply