# Another determined difference between ME/CFIDS and FMS



## M&M (Jan 20, 2002)

We've spoken on this topic before. About what the differences are between ME/CFIDS and FMS, and why knowing those differences is important. Well, this piece (posted to the Co-Cure list) outlines yet another VERY important difference to know, recognize, and apply in a personal way. It shows how a person with ME/CFIDS responds to exercise therapy as opposed to the way a person with FMS responds to exercise therapy. This is VERY important for us patients to understand, as we can either help our bodies to heal, or exacerbate our own symptoms by either chosing to apply or chosing to ignore this vital information. Hopefully you'll all enjoy it as much as I did!


> quote: "Recent research --- Physiology of Muscles in CFS - an explanation for exercise intolerance ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ A new and exciting development in our understanding of the biological basis of CFS comes from a team in Italy who have demonstrated significant changes to the physiology of muscle. Read the summary, and a comment from MERGE. http://www.meresearch.org.uk/archive/membranes.html Recent research --- Physiology of muscle Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome Fulle S, Beliab S, Vecchieta J, Morabitoa C, Vecchieta L, and Fano G Laboratorio Interuniversitario di Miologia, Universita "G. d'Annunzio", Nuovo Polo Didattico, Via dei Vestini, 31, 66013 Chieti Scalo, Italy; and Universita degli Studi, Perugia, Italy In chronic fatigue syndrome, several reported alterations may be related to specific oxidative modifications in muscle. Since sarcoplasmic reticulum membranes are the basic structures involved in excitationï¿½contraction coupling and the thiol groups of Ca2+ channels of SR terminal cisternae are specific targets for reactive oxygen species, it is possible that excitationï¿½contraction coupling is involved in this pathology. We investigated the possibility that abnormalities in this compartment are involved in the pathogenesis of chronic fatigue syndrome and consequently responsible for characteristic fatigue. The data presented here support this hypothesis and indicate that the sarcolemmal conduction system and some aspects of Ca2+ transport are negatively influenced in chronic fatigue syndrome. In fact, both deregulation of pump activities (Na+/K+ and Ca2+-ATPase) and alteration in the opening status of ryanodine channels may result from increased membrane fluidity involving sarcoplasmic reticulum membranes. Published in: Neuromuscular Disorders 2003; 13: 479ï¿½484. Published by Elsevier Science. Comment from MERGE ~~~~~~~~~~~~~~~~~~ A new and exciting development in the biological basis of CFS comesfrom a team in Italy who have demonstrated significant changes to the physiology of muscle. This is the same team who, in 2000, published evidence of oxidative damage within the vastus lateralis muscles of CFS patients, probably as a consequence of oxygen free radical damage stemming from dysfunctional muscle cell mitochondria. In this most recent study, they suggest that the post-exertional fatigue that is so characteristic of CFS is linked to the basic structures involved in excitation and contraction (E-C) coupling of muscles. Specifically, they hypothesised that the rapid onset of fatigue and accompanying muscle pain are due to modifications of the fluidity of membranes associated with the sarcoplasmic reticulum of the muscle cell. These membranes are central to the spread of action potentials towards the interior of the cell and to the transport of calcium (Ca2+) that initiates contraction of the muscle. The data reported by the Italian group provides novel evidence of disruption to Ca2+ transport in the muscle of ME/CFS patients. This disruption may be a consequence of the energy status of the cell or to gates in the cell membrane, known as ryanodine channels. The study was carried out on a small number of CFS patients who were selected on precise clinical criteria along with a similar number of fibromyalgia patients and controls. It is interesting to note that the abnormalities were found only in the CFS group and not the FMS patients, despite the apparent similarity in some symptoms." Comments from Rich ~~~~~~~~~~~~~~~~ I'd like to comment on why I think this work is significant. By way of background information, the sarcoplasmic reticulum is an organelle found in muscle cells. When a nerve impulse is sent to a muscle cell to tell it to contract, this signal causes the sarcoplasmic reticulum to release calcium ions into the sarcoplasm. These calcium ions then interact with the muscle fiber molecules in such a way to cause them to contract. When it is time for the muscle fiber to relax, the calcium ions are pumped back into the sarcoplasmic reticulum by calcium ion pumps. Both the ion pumps and the muscle fiber molecules themselves are powered by ATP, which is produced by the intermediary metabolism in the cell (glycolysis, Krebs cycle, and respiratory chain). As I reviewed in a chapter on nutrition that I wrote for the recently published Handbook of Chronic Fatigue Syndrome, there is now considerable published evidence showing that there is a condition of oxidative stress in CFS, and this has been shown particularly in skeletal muscle cells, by the same group that published this new work. Prof. Marty Pall has just added to this literature by publishing measurements of increased protein carbonyls in CFS, another indicator of oxidative stress. It was hypothesized some time ago by Prof. Pall (in his published work) and by myself in internet posts over the past few years, that peroxynitrite levels in the cells are elevated, consistent with this condition of oxidative stress. It is known that peroxynitrite will block certain enzymes in the Krebs cycle and in the respiratory chain, and the effect of this can be expected to be a decrease in the rate of production of ATP in these cells. From what I can tell by reading the abstract and comments, it looks as though this new work is consistent with this picture. I have hypothesized that the basic cause of the state of oxidative stress in CFS is the depletion of glutathione. Such a depletion was first pointed out by Dr. Paul Cheney in early 1999, and has recently been confirmed by Vance Spence's group in Dundee, Scotland (Gwen Kennedy et al, talk presented at AACFS meeting in early 2003). Many PWCs (People With CFIDS) on the internet lists have also reported finding low levels of glutathione in their comprehensive detox tests. One of the several important known functions of glutathione is to keep thiol groups in proteins in the reduced state. The abstract above notes the presence of thiol groups in the calcium channels of the sarcoplasmic reticulum. At first glance, it seems to me that the inability to keep these thiols reduced in the presence of glutathione depletion is another possible pathogenetic mechanism in CFS skeletal muscle dysfunction. Perhaps the complete paper sheds some light on whether ATP shortage or lack of thiol reduction by glutathione is the most likely mechanism. In any case, it seems clear that this paper presents evidence that metabolic problems in the skeletal muscles are clearly involved in CFS. I think this is further support for the proposition that emphasis in CFS research needs to be focused on the metabolic aspects. Another important point is that this sarcoplasmic reticulum problem was not observed in patients with fibromyalgia alone, with no CFS. I think this is highly significant, because it is a piece of evidence that helps to separate the pathogeneses of these two similar but still different disorders. It has been known for some time that aerobic exercise is actually beneficial to many who have "pure" fibromyalgia, while it can be disastrous to those with "pure" CFS. I think this paper sheds some light on why that is true.In my opinion, in "pure" CFS, there appears to be a metabolic problem in the skeletal muscle cells such that exercise produces more oxidizing free radicals, and since there is a depletion of glutathione and resulting oxidative stress, these oxidizing free radicals damage molecules in the cells. I think this is the reason for the long recovery time required after aerobic exercise in CFS. In "pure" fibromyalgia, while there is evidence for oxidative stress, it may not be present or may not be as severe in the skeletal muscles. I think this work can help to clarify in what cases exercise therapy can be helpful, and in what cases it probably should be avoided. I think this is a very exciting bit of research, and I hope it attracts the attention of the CFS research community. Rich Van Konynenburg


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## Susan Purry (Nov 6, 2001)

Gosh, that was educational - thanks for posting MrsM!


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## SusanLawton (Dec 23, 2003)

Wow - very heady, but fascinating. Since we are speaking hypothetically, what happens to those of us who have firm diagnoses of *both* FM and CFS?Susan


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