Mitochondria and ME

Discussion in 'Fibromyalgia Main Forum' started by Rafiki, Oct 11, 2008.

  1. Rafiki

    Rafiki New Member

    The Committee for Justice and Recognition of Myalgic Encephalomyelitis

    Mitochondria and Myalgic Encephalomyelitis

    Laboratory studies have confirmed an enormous array of metabolic abnormalities in the blood, breath, urine, stool, and from advanced in vivo assessments of ME patients. However, from the infectious disease specialist and world authority on Myalgic Encephalomyelitis, Dr. Melvin Ramsay, to the distinguished Drs; Behan, Richardson, Cheney, Martin, and Nicolson, the concern of mitochondrial damage as an essential area of pathogenesis has been an important consideration.

    Patients readily appreciate the lack of energy, or “life force”, within their muscles, organs and brain can be a central factor and explain much of their disease. The brain, muscles and immune system are highly energy dependant systems. Clearly damage to the primary energy system will produce widespread abnormalities and consequences.


    There is so much injury to the mitochondria that CFS could be called a mitochondrial disease. A Mitochondrial Encephalomyopathy.

    Paul Cheney

    The significance of Mitochondria in Neurologic Disease,
    is the subject of this major review and reveals the devastating neurologic diseases that can result from mitochondrial dysfunctions.

    ABSTRACT. There is mounting evidence for mitochondrial involvement in neurodegenerative diseases including Alzheimer's, Parkinson's, and Lou Gehrig's Disease (ALS). Mitochondrial DNA mutations, whether inherited or acquired, lead to impaired electron transport chain (ETC) functioning. Impaired electron transport, in turn, leads to decreased ATP (energy) production, formation of damaging free-radicals, and altered calcium handling. These toxic consequences of ETC dysfunction lead to further mitochondrial damage including oxidation of mitochondrial DNA, proteins, and lipids, and opening of the mitochondrial permeability transition pore, an event linked to cell death. Although protective nuclear responses such as antioxidant enzymes may be induced to combat these pathological changes, such a vicious cycle of increasing oxidative damage may insidiously damage neurons over a period of years, eventually leading to neuronal cell death. This article's hypothesis, a synthesis of the mitochondrial mutations and oxidative stress hypotheses of neurodegeneration, is readily tested experimentally, and points out many potential therapeutic targets for preventing or ameliorating these diseases.
    Role of mitochondria in neurodegenerative diseases

    Cassarino DS, Bennett JP Jr.

    University of Virginia Health Sciences Center,

    Brain Research Reviews, 1999, 29;1:1-25 PMID: 9974149


    Dr. Melvin Ramsay Pioneer and World Expert on Myalgic Encephalomyelitis

    ABSTRACT. A record of fifty-three patients admitted to the Infectious Diseases Department of the Royal Free Hospital between April 1955 and September 1957 suffering from 'epidemic neuromyasthenia' establishes the fact that the condition was endemic in the general population before, during and after the outbreak among the staff of the hospital. A further outbreak occurred in North Finchley between 1964 and 1967 and sporadic new cases are still being encountered. The majority of these patients show evidence of involvement of the central and sympathetic nervous systems and the reticulo-endothelial system. Abnormal muscular fatigability is the dominant clinical feature and it is suggested that mitochondrial damage may provide an explanation for this phenomenon. Enzyme tests carried out in seven cases show pathologically high levels of lactic dehydrogenase, and glutamic oxalo-acetic transaminase. A follow-up study suggests that there is one group of patients that recovers completely or nearly completely, a second that recovers but is subject to relapses and a third that shows little or no recovery, these patients remaining incapacitated.

    'Epidemic neuromyasthenia' 1955-1978.

    A. Melvin Ramsay
    Postgrad Med J, 1978 Nov; 54(637) PMID: 746017


    Dr. Behan, Professor of Neurology and long an outstanding investigator of Myalgic Encephalomyelitis. Leading the team of medical scientists at Glasgow have produced a series of remarkable laboratory discoveries, from studies of brain scans, cardiac scans, exercise/oxygen, water metabolism, lipid metabolism and changes in cellular ion channels.

    Evidence of ME infection and Mitochondria damage in muscle biopsy

    ABSTRACT. We have examined the muscle biopsies of 50 patients who had postviral fatigue syndrome (PFS) for from 1 to 17 years. We found mild to severe atrophy of type II fibres in 39 biopsies, with a mild to moderate excess of lipid. On ultrastructural examination, 35 of these specimens showed branching and fusion of mitochondrial cristae. Mitochondrial degeneration was obvious in 40 of the biopsies with swelling, vacuolation, myelin figures and secondary lysosomes. These abnormalities were in obvious contrast to control biopsies, where even mild changes were rarely detected. The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection.

    Behan WM, More IA, Behan PO.

    Acta Neuropathol 1991;83(1):61-5. PMID: 1792865


    Dr Richardson –

    Internationally recognized ME expert physician with five decades of clinical experience.

    From Neurology to Mitochondia

    Initial considerations suggested that in the SPECT scans, the fields of hypoperfusion which were shown to be significant demonstrated localised areas with diminished metabolic requirements. This could be related to diminished cell function which occurred as a result of mitochondrial dysfunction, possibly due to viral infection. This has been well demonstrated by Behan and coworkers.

    It should be noted that mitochondria, as the name implies, are the "nuclear power house" of the cell, from "mitosis" to "apoptosis." During cell life, this mitochondrial "power" results in the generation of energy in the form of ion gradients and ATP synthesis. Mitochondria mediate energy generation through the oxidation of food material which has passed through the blood-brain-barrier (BBB). To this end, mitochondria also contain the enzymes for the Krebs and other fatty acid cycles, and thus govern the respiratory cell pathway of oxygen. Therefore, mitochondrial dysfunction results in a decrease in cell respiration. For instance, abnormal carnitine metabolism in ME/CFS patients is one of the energy metabolic dysfunctions in mitochondria. Carnitine itself is an amino acid used for the transport of fatty acids across the cell membrane to the matrix, a process which is catalysed by the co-enzyme carnitine palmitoxyl transferase. The resulting decrease in oxidation is no doubt the reason for the lack of perfusion requirements demonstrated in the SPECT scans.

    Mitochondria contain DNA and RNA by means of which they replicate. This relates to the development of cells with the formation of deutoplasm and a large increase in protoplasm and mitochondria, which leads to the formation and future function of specialised cells. Other physiological aspects that may underlie the SPECT abnormalities seen in ME/CFS should be considered, such as the anatomical divisions of the brain with enormous variations in function. The latter variations are seen in both the neuroneural and neurohormonal control of the whole body. Consideration should be given to the BBB, as this possibly has some effect on the means of access to the higher centres of viruses or toxins as well as normal nourishment, with the areas above the BBB being possibly more protected than those beneath. However, viruses and other material, e.g., toxins and certain drugs which are fat soluble, may pass this BBB.

    Richardson J, Costa DC.

    J CFS 1998, 4(3)

    See Dr Richardson’s stimulating article;


    John Martin, MD, PhD, Professor of Pathology, long a noted contributor to the science of Immunology, has been pursing the viral causes of neurologic diseases; here reports the evidence of infection.

    Damaged Mitochondria and Intracellular Inclusions in Brain Biopsy

    (from a victim of the recent Arizona ME outbreak)

    ABSTRACT. Unusual pigmented intracellular inclusions are commonly seen in cultures obtained from patients infected with stealth viruses. Some of these structures may potentially provide a source of chemical energy for the infected cells to help compensate for the apparent damage to the cells' mitochondria. They have accordingly been termed alternative cellular energy pigments (ACE pigments). In keeping with this suggestion, the present paper illustrates the diversity of extraneous materials present in vacuolated, mitochondria-damaged cells seen in the brain biopsy of a child with a stealth-virus-associated encephalopathy. (article includes many micrographs of virus damaged mitochondria )

    W. John Martin

    Exp Mol Path 2003, 74;(3):197

    See, Electron microscopy study of damaged mitochondria


    Paul Cheney, MD, PhD, became an expert on ME following the epidemic explosion of this disease in the Lake Tahoe area, which spread worldwide in the 1980s. He has examined thousands of patients, conducted leading edge research and educated doctors, including the recent superb Dallas lecture on Pathophysiology.

    Cheney on the Mitochondrial Damage

    Dr Cheney confirmed: that in CFS there is so much injury to the mitochondria that CFS could be called a mitochondrial disease. A Mitochondrial Encephalomyopathy.

    The main problem in CFIDS is cellular metabolic dysfunction. The body's cells have been damaged and are not able to function normally. Every cell in the body is affected.

    The center of gravity of this disease is a disturbance of cell function that is best described as a mitochondrial dysfunction or energy production dysfunction, with an associated intracellular acidosis.

    Cheney describes some specialized brain scans “It means mitochondrial encephalopathy [brain cell dysfunction caused by mitochondrial dysfunction]. It means the brain isn't working because there isn't enough mitochondrial function to provide energy for it to work.”

    Except of interview with Paul Cheney, MD, PhD

    Carol Sieverling Reports

    DFW CFIDS - 2001

    Cheney comments on Pathophysiology, see;


    Prof. Nicolson - Pioneering scientist in Cell Membrane Dynamics and acclaimed researcher of Tumor Biology, investigated the illness among Gulf veterans and uncovered infections and government efforts to cover-up the military ME epidemic. Here an excerpt on mitochondrial function.

    Chronic Fatigue, Mitochondrial Function and Degenerative Disease

    When mitochondrial function is impaired, the net energy available to cells is limited to the Krebs Cycle and anaerobic metabolism. There are a number of conditions and substances that can impair mitochondrial function,* but oxidation and damage of mitochondrial lipids in membranes are thought to be among the most important causes.* Oxidation of membrane lipids results in modification of membrane fluidity and the electrical potential barrier across mitochondrial membranes, essential elements in the proper functioning of the electron transport chain.* Mitochondrial function appears to be directly related to fatigue, and when patients experience fatigue their mitochondrial function is inevitably impaired. Fatigue is a complex phenomenon determined by several factors, including psychological health. At the biochemical level fatigue is related to the metabolic energy available to tissues and cells. Thus the integrity of cellular and intracellular membranes, especially in the mitochondria, is critical to cell function and energy metabolism. When mitochondrial membrane glycophospholipids, phospholipids, fatty acids, and other essential lipids are damaged by oxidation, they must be repaired or replaced in order to maintain the production of cellular energy to alleviate fatigue.

    The decline of cellular energy production with aging appears to be due, in part, to mitochondrial lipid peroxidation by ROS and the failure to repair or replace damaged molecules at a rate that exceeds their damage. Membrane damage and subsequent mitochondrial dysfunction by ROS can also lead to modifications (especially mutations and deletions) in mitochondrial DNA (mtDNA). The mitochondrial theory of aging proposes that the development of chronic degenerative diseases is the result, in part, of accumulated mtDNA mutations and deletions and oxidative damage to mitochondrial membranes over time.* Indeed, these studies have linked the development of certain chronic diseases with the degree of mitochondrial membrane lipid peroxidation and mtDNA damage. Thus the damage to mtDNA and mitochondrial membranes seems to be involved in the etiology of age-associated degenerative diseases leading to changes in the expression of genes important for cell survival as well as those that control aging.* Restoration of mitochondrial membrane integrity, fluidity and other properties are essential for the optimal functioning of the electron transport chain and oxidative generation of ATP and NADH. Declines in energy production with aging and disease coupled with increases in oxidative stress can change gene expression programs and activate cellular apoptosis programs.* Apoptosis can also be attenuated with the administration of n-3 polyunsaturated fatty acids.*

    The ability to control membrane lipid peroxidation and DNA damage likely play a major role in the aging process and the development of age-related degenerative diseases.*

    Garth L. Nicolson, PhD

    JANA, 2003 6(3): 22-28
  2. simonedb

    simonedb Member

    hey thanks for all that!
    so what has worked best for you rafiki?
  3. Rafiki

    Rafiki New Member

    What has worked best for me? Nothing. Literally :~)

    I just don't move very much. I have become very economical with all movement and I rest after doing anything at all.

    Well, nothing and long rounds of doxycycline because I can't seem to cope with bacterial infections.

    Banya has some experience in this area (see Rocco Baldelli sp? thread) and I'm waiting for her to illuminate things further.

    I'm very interested in what I've read about managing known Mito diseases and may try CoQ10 and, perhaps even med. chain fatty acids.

    It seems that everything they suggest to manage mito disease are things that we have also found we must do -- enough sleep, no infections, avoid stress, avoid over exertion... I posted about this in the other thread, too.


    [This Message was Edited on 10/11/2008]
  4. Rafiki

    Rafiki New Member

    David Bell on ME/CFS as a Mitochondrial Disease 10/09/08 05:21 PM

    by Dr. David S. Bell, MD, FAAP


    Reproduced with generous permission from the April 2008 issue of Dr. Bell’s e-newsletter, Lyndonville News.

    ME/CFS is a disorder involving the cells’ energy-producing mitochondria – but it’s a mitochondrial disease like no other, Dr. Bell believes. He explains why it hasn’t been diagnosed, classified, and studied like other kinds of mitochondrial diseases - and why a change may be “just around the corner.”


    In the past week I have seen two patients who had an exercise lactate test which showed an elevation of blood lactate after mild exercise [considered a sign of mitochondrial damage]. They were told by their physician that they had “mitochondrial disease.” They were advised to take some vitamins, maybe some CoQ-10, and have a nice day. Like nearly everything else, the term mitochondrial disease left these patients feeling bewildered and somewhat lost.

    While I agree that ME/CFS is a mitochondrial disease, this term needs clarification because ME/CFS is a mitochondrial disease like no other.

    Until recently, when a child was diagnosed as having a mitochondrial disease, it was a disaster, even a death sentence, for it meant that there were major abnormalities in the mitochondrial or nuclear DNA that regulated energy production. Without energy (ATP) it is impossible to survive. These diseases are called MELAS, Kearns-Sayre, Leber hereditary optic neuropathy, and so on. Nearly three hundred mitochondrial illnesses have been identified from genetic mutations. It is a specialized area of pediatrics, where it is possible to measure severe abnormalities in the mitochondria on muscle biopsy testing.

    This is what most clinicians think of when the words "mitochondrial disease" are mentioned, but these illnesses do not, in general, apply to ME/CFS. Many patients with ME/CFS have had muscle biopsies, and most of the mitochondrial tests on these biopsies are relatively normal. We will return to why this is in a bit.

    What are Mitochondria?

    Think of mitochondria as the power factories of the cell.

    * Nearly every cell in the body has them, usually around 500 or so in every cell.

    * They take in oxygen and glucose (blood sugar) and put out carbon dioxide and energy (ATP).

    There are two hundred different steps in this process, and we will quiz you after this article. Actually, all you need to know is that:

    * ATP is the prime energy storage chemical (battery) of the body, and

    * Oxidative phosphorylation (ox-phos) is the complex of electron transport chains that do the major work of conversion.

    Because the mechanism of energy production is essential to nearly every cell, a defect will have symptoms in every organ system. Sound familiar? Oxidative metabolism, the ability to utilize oxygen to produce energy, is quite efficient, and it is fascinating to look at the theories of how it came to be part of our cells.

    However, when the energy demand is excessive, the cells revert to a more primitive, and less efficient, form of energy production - anaerobic metabolism (metabolism without oxygen). For an interesting study on the anaerobic threshold [point of reversion] in ME/CFS, see the literature review that follows.

    When to Suspect Mitochondrial Disease

    In a recent review article (Haas et al., 2007) there is a list of symptoms that suggest looking for mitochondrial disease. Among these symptoms are neurologic symptoms such as ataxia (coordination problems), myoclonus (twitching), and encephalopathy (brain injury), exercise intolerance, sensitivity to general anesthesia, and constipation.

    A score sheet has been developed to help in when to suspect mitochondrial disease - and most ME/CFS patients would fall into the positive range. For lots of information on mitochondria please go to But remember that they are talking about “conventional” mitochondrial disorders, not ME/CFS.

    A Mitochondrial Problem Can Be
    Secondary to Some Other Problem

    There is another form of mitochondrial disease, or “secondary mitochondrial disease.” In secondary mitochondrial disease the primary problem is not with the mitochondria, but some other problem that messes up mitochondrial function. There are many illnesses where the primary defect ends up causing problems with the generation of energy in mitochondria.

    For example, thyroid hormone is needed for successful oxidative phosphorylation. With hypothyroidism (low thyroid) energy production is impaired, and fatigue, weakness, temperature regulatory problems, and difficulty concentrating result. This is one of the reasons that when you start to describe fatigue to your primary care physician, he or she begins to write out a script to test for thyroid hormone.

    So What Is the Problem?

    Why has ME/CFS not been diagnosed, studied and classified like other mitochondrial diseases? There are several reasons:

    a. Mitochondrial disease is thought of by clinicians as a fatal disease of infancy, not one that occurs later in life.

    b. Mitochondrial disease is usually thought of as a fixed, structural disease, and ME/CFS is a relapsing, remitting illness with some persons even becoming entirely well.

    c. Mitochondrial diseases are hard to diagnose, requiring muscle biopsies and detailed ox-phos testing.

    d. Ox-phos testing is often normal in ME/CFS, and this has been the critical piece that has diverted attention from mitochondria.

    e. Physicians are used to thinking of organ-specific diseases (liver, kidney, etc), and mitochondria are in all cells.

    f. Few physicians have taken ME/CFS seriously until recently, and research in this area has been scant.

    Of the above reasons, only reason “d” is important to us here (ox-phos testing is often normal in ME/CFS). In 1990 I did a muscle biopsy study on 10 ME/CFS patients with Dr. June Aprille, PhD, an expert in cellular metabolism. All ten persons had relatively normal ox-phos studies. Although we did not publish this finding, it is consistent with the few published studies that have been done.

    How can you have mitochondrial disease when the mechanism tests normal? I think that the answer to this paradox is just around the corner.


    If you have a patient with emphysema who is sitting in an armchair, he or she is not out of breath. You can measure the damage in tests, but to make symptoms, you have to “stress” the system – make the patient run up and down stairs. If a person with G-6-PD deficiency [linked to fava bean allergy] is sitting quietly, the blood looks normal. But feed this person fava beans and abnormalities quickly become obvious.

    Persons with ME/CFS keep themselves at a balance point. They rest for two hours, then do a half hour of activity, then rest, then do more and so on. The worse the illness, the less overall activity is possible. If a ME/CFS patient does absolutely nothing for a few days, they usually feel pretty good. But go to the shopping mall for eight hours and the crash occurs.

    Here is the problem: In the patients studied for mitochondrial disease, they have been resting up (staying above the balance point), and a muscle biopsy done at that moment will probably not show much. But have a ME/CFS patient exercise, and then study mitochondrial function. My hunch is that the ox-phos reactions will be seriously impaired, but this has not been systematically and methodically done. For me, this hypothesis is generated by the VanNess, Snell, and Stevens “Two-day Exercise Test” study described in the next section.

    There are lots of studies that implicate mitochondrial problems; Dr. Hirohiko Kuratsune and carnitine; Dr. Suzanne Vernon and genomics; Dr. Kenny DeMeirleir, Dr. Martin Pall, Dr. Paul Cheney, and many others. But this problem cannot be studied in tiny fragments. It is time for a good study to look at the different steps of the body’s ability to generate energy. Let’s hope we get to see it within our lifetimes.

    Literature Review - the “Two-day Exercise Test”

    In the most recent Journal of Chronic Fatigue Syndrome (Vol 14, Number 2, 2007) there are two articles which may be the first to offer an objective proof of disability in ME/CFS. More importantly, if shown to be correct, they may give us an avenue to test and measure the biochemical abnormality which causes the symptom pattern. I would like to briefly review these two papers and present a case of pediatric ME/CFS which demonstrates the same abnormalities.

    In the first of these papers, Margaret Ciccolella, a lawyer, teams up with Staci Stevens, Chris Snell, and Mark Van Ness of the University of the Pacific to review the legal issues surrounding exercise testing and disability(1). As everyone familiar with ME/CFS well knows, insurance companies require proof of disability, which a standard exercise test may or may not demonstrate. However, even if disability is present, insurance companies have been quick to say that the patient was not trying hard enough, or that the patient is de-conditioned.

    The second paper of this series by VanNess, Snell and Stevens explains the two-day exercise test and presents results for six patients with ME/CFS(2).

    As clinicians have observed, the symptom of “post-exertional malaise” is one of the most distinguishing features of CFS. This symptom is listed as one of the eight in the criteria of the Centers for Disease Control(3), and is central to the diagnosis in the recent Canadian Case Definition(4) and the proposed pediatric case definition(5). It is beginning to look like the symptom of post-exertional malaise is at the root of disability, and may be central to the pathophysiology of this complex illness spectrum.

    A person with ME/CFS may be at home for several days doing little except basic activities of daily living. When this patient decides to go shopping, he or she will drive to the mall and shop for one or two hours. During this time, observers would say that the person looks entirely well, not appearing disabled. However, following this activity the patient will experience an exacerbation of pain and other symptoms of ME/CFS. This exacerbation may last one, two or three days, and, in my opinion, the more severe the illness, the longer and more severe the exacerbation.

    This phenomenon is known as post-exertional malaise. The symptoms of the illness (malaise) are exacerbated by mental, physical or emotional activities (post-exertional). In an employment environment, the patient may be able to do a job well for one or even several days. However, disability lies in the inability to sustain this normal level of activity. The two-day exercise test is the first to begin to explain this phenomenon.

    The exercise test is no different from what has been used for years. The patient exercises on a stationary bicycle (bicycle ergometry) and breathes through plastic tubing to measure the concentration of oxygen and carbon dioxide as well as the total amount of air. The six female patients and six sedentary matched control subjects of the study were all able to achieve maximal exertion. The ME/CFS patients had a slightly lower V02max (maximal oxygen utilization) than controls (28.4 ml/kg/min vs. 26.2 ml/kg/min) and lower VO2 at anaerobic threshold (15.01 ml/kg/min vs. 17.55 mg/kg/min) on the first day of exercise testing.

    These values are not dramatic, nor are they statistically significant.

    It is on the second day that interesting results are seen. The same test was repeated the following day for all 12 subjects. As is often the case, sedentary controls improved slightly in their ability to utilize oxygen, going from 28.4 to 28.9 ml/kg/min for VO2max and from 17.55 to 18.00 ml/kg/min for oxygen utilization at anaerobic threshold. The CFS patients however worsened in both categories: VO2max fell 22% from 26.23 to 20.47 ml/kg/min, and oxygen utilization at anaerobic threshold fell 27%, from 15.01 to 11.01 ml/kg/min.

    To put this into perspective, these values are in the “severe disability” range on the AMA guidelines, and the decline in function from day one to day two cannot be explained by inactivity.

    Sedentary or de-conditioned persons do not change their oxygen utilization because of an exercise test. Even patients with heart disease, cystic fibrosis or other diseases do not vary more than 7% from one day to the next. However, the patients with ME/CFS in this study had a significant drop; something occurred because of the test on the first day that interfered with their ability to utilize oxygen on the next day. And this is exactly what patients with ME/CFS have been describing with the symptom of post-exertional malaise.

    As the authors state, “The fall in oxygen consumption among the CFS patients on the second test appears to suggest metabolic dysfunction rather than a sedentary lifestyle as the cause of diminished exercise capacity in CFS.”


    The results of the two-day exercise testing are objective and not dependent upon subjective symptoms. Moreover, hypochondriasis, intentional falsification, and/or poor effort can be detected by the physiologic parameters. Therefore:

    * The two-day exercise test, if confirmed in a larger trial, could become a clinical trial end point.

    * More importantly, evaluations could be designed which would demonstrate the specific metabolic abnormality generated by the exercise of day one and demonstrated on the second day exercise test.

    It would be my hope that these findings be explored without delay.


    1. Ciccolella M, Stevens S, Snell C, VanNess J: "Legal and Scientific Considerations of the Exercise Stress Test". JCFS 2008, 14(2):61-75.
    2. VanNess JM, Snell CR, Stevens S: "Diminished Cardiopulmonary Capacity During Post-Exertional Malaise". JCFS 2008, 14(2):77-85.
    3. Fukuda K, Straus S, Hickie I, Sharpe M, Dobbins J, Komaroff A, Group ICS: "The chronic fatigue syndrome: a comprehensive approach to its definition and study." Ann Intern Med 1994, 121:953-959.
    4. Carruthers B, Jain A, DeMeirlier K, Peterson D, Klimas N, Lerner A, Bested A, Flor-Henry P, Joshi P, Powles ACP et al: "Myalgic encephalomyelitis/chronic fatigue syndrome: Clinical working case definition, diagnostic and treatment protocols." J Chronic Fatigue Syndrome 2003, 11(1):1-12.
    5. Jason L, Bell D, Rowe K, Van Hoof E, Jordan K, Lapp C, A G, Miike T, Torres-Harding S, DeMeirleir K. "A Pediatric Case Definition for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome." J CFS 2006, 13:1-44

    Dr. Bell's Disclaimer: Any medical advice that is presented in the Lyndonville News is generic and for general informational purposes only. ME/CFS/FM is an extremely complex illness and specific advice may not be appropriate for an individual with this illness. Therefore, should you be interested or wish to pursue any of the ideas presented here, please discuss them with your personal physician.

    Note: This information has not been evaluated by the FDA. It is not meant to prevent, diagnose, treat or cure any illness, condition or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.
  5. mezombie

    mezombie Member

    Rafiki, thanks for putting this information on one thread.

    As you can see, there has been a lot of interest in mitochondrial damage in ME (as well as energy-deficient problems encompassed by "CFS") for some time.

    There are a number of treatment ideas put forth by Cheney and no doubt available on this site as well as CoQ10, as you mentioned, is one. NAC (mentioned below) is another. I have been on many supps meant to help with mito damage, but my brain is blanking them out at the moment (zombie that I am).

    Some ME-specific suggestions are in the treatment section on

    Coconut oil (a source of medium chained fatty acids) is an option and available through a number of supplement companies who have recognized its potential.

    Here's another article that may be of interest:


    Mol Nutr Food Res. 2008 Jul;52(7):780-8.

    Medication-induced mitochondrial damage and disease.

    Neustadt J, Pieczenik SR.
    Montana Integrative Medicine, Bozeman, MT 59718,

    Since the first mitochondrial dysfunction was
    described in the 1960s, the medicine has advanced
    in its understanding the role mitochondria play in
    health and disease.

    Damage to mitochondria is now understood to play a
    role in the pathogenesis of a wide range of
    seemingly unrelated disorders such as schizophrenia,
    bipolar disease, dementia, Alzheimer's disease,
    epilepsy, migraine headaches, strokes, neuropathic
    pain, Parkinson's disease, ataxia, transient ischemic
    attack, cardiomyopathy, coronary artery disease,
    chronic fatigue syndrome, fibromyalgia, retinitis
    pigmentosa, diabetes, hepatitis C, and primary
    biliary cirrhosis.

    Medications have now emerged as a major cause of
    mitochondrial damage, which may explain many
    adverse effects. All classes of psychotropic drugs
    have been documented to damage mitochondria, as
    have stain medications, analgesics such as
    acetaminophen, and many others.

    While targeted nutrient therapies using antioxidants
    or their precursors (e. g., N-acetylcysteine) hold
    promise for improving mitochondrial function, there
    are large gaps in our knowledge.

    The most rational approach is to understand the
    mechanisms underlying mitochondrial damage for
    specific medications and attempt to counteract their
    deleterious effects with nutritional therapies.

    This article reviews our basic understanding of how
    mitochondria function and how medications damage
    mitochondria to create their occasionally fatal
    adverse effects.

    PMID: 18626887 [PubMed - indexed for MEDLINE]

    Reference: *Medication and ME/CFS?*
    By Margaret Williams
    Help ME Circle, 29 August 2008; Co-Cure:

    [This Message was Edited on 10/15/2008]
  6. banya

    banya New Member
  7. banya

    banya New Member

  8. Jayna

    Jayna New Member

    In watching that first video, I note their first study patient was kept in hospital for the first 8 weeks of her exercise/training program. So presumably there was a lot of help for post-exertional pain and malaise symptoms, which are simply not available to many people still living in thier own homes and trying to manage their own lives.

    Also, there is not yet a clear research picture on the mitochondrial malfunctions in ME/CFS, so we don't know if any of her research applies to our patient populations.

    Also, she glossed over the CNS symptoms of mitochondrial myopathies, so we don't know if their study patients were as ill as many of us are from things like low blood volume, orthostatic intolerance and so on.

    She didn't say if or how they supported subsequent patients during bad post-exertional malaise early in their training. We would have to look up the studies themselves to see what the dropout rate was, which might also give clues as to whether post-exertional malaise was a problem for their patients.

    Apparently there were dozens of mutant possibilities and only a couple chosen for an exercise trial.

    However, her several years of studies did demonstrate that a person with a single mitochondrial myopathy can change the balance between their mutated mitochondrial DNA and their healthy mitochondrial DNA through carefully graded resistance training or endurance training.

    Now if only we knew that the mitochondrial portion of ME/CFS was in any way related to the small number of mitochondrial myopathies looked at in these studies, we could say with some assurance that exercise would be beneficial to ME/CFS patients.

    We don't know if there's any connection or not, so we can't say either way whether exercise will help some, all or none of us, or whether - because we weren't the population being studied in teh first place - exercise will make us much sicker for much longer. No way to know... yet.

    [This Message was Edited on 10/15/2008]
  9. simonedb

    simonedb Member

    I wasnt able to view first video. It said exercise a way to shift self into health?
    The second video emphasized how important it is to figure out your individual level of tolerated excercise, too much or too little both bad. Made sense.
    I was very impressed with that 2nd link of mito docs in Indiana, I just wish we were 20 years down the road with knowledge! It was cool too that they acknowledged that health ins companies not in business of "health care" but making profits for their shareholders on the stockmarket! And the doc who said that encouraged activism to get your testing etc paid for by insurance.
  10. Rafiki

    Rafiki New Member

  11. Rafiki

    Rafiki New Member

    DALLAS - Aug. 25, 2005 - A newly discovered protein not only is vital to the immune system's ability to fight off viral infections but also has been found in an unexpected location within the cell, causing researchers to rethink previous notions about the workings of the human immune system.

    Researchers at UT Southwestern Medical Center said their findings may lead to new therapies aimed at preventing and treating viral diseases such as the flu, hepatitis, West Nile virus and SARS. The study is available online and will appear in the Sept. 9 issue of the journal Cell.

    Working with cultured cells, researchers found that the protein, made by a gene they discovered and named MAVS, is located in an unexpected place within the cell - in the membrane of an organelle called the mitochondrion, which until now was best known for generating energy required for daily life.

    "This is the first mitochondrial protein known to be involved in immune defense against any microbial infection," said Dr. Zhijian "James" Chen, associate professor of molecular biology at UT Southwestern and the study's senior author. "This discovery puts mitochondria on the map in terms of immunity, and it opens up a new avenue of research in immunology."

    The researchers modified normal cells so that the cells could not produce the MAVS protein, which is short for Mitochondrial Anti-Viral Signaling protein. Without MAVS, the cells were highly vulnerable to infection with two common viruses in a class called RNA viruses Other RNA viruses include hepatitis C, West Nile, SARS and the flu viruses.

    Cells altered to produce an overabundance of MAVS were protected from dying from viral infection.

    "These results raise the possibility that variations in the expression levels of MAVS may endow different individuals with varying ability to fight off viral diseases," said Dr. Chen, who also is an investigator with the Howard Hughes Medical Institute. "Viruses have evolved along with humans and have developed strategies to evade the host's immunity. It's quite possible that some viruses may target MAVS in order to achieve successful infection. In those cases, therapies that enhance MAVS expression or activity may be a viable option for boosting immune responses against viral diseases."

    The fact that MAVS is located within the membrane of the mitochondrion makes sense for a couple of reasons, Dr. Chen said.

    First, proteins housed within the mitochondria have been shown by researchers, such as UT Southwestern biochemist Dr. Xiaodong Wang and others, to play a role in apoptosis, or programmed cell death. The fact that MAVS is located in the membrane of mitochondria suggests it may play a role in coordinating cell death and immune response, Dr. Chen said.

    Secondly, many scientists believe that mitochondria originally evolved from bacteria that lived within a host organism's cells, eventually developing a symbiotic relationship with host cells. Now that mitochondria are an integral part of our cells, Dr. Chen speculated that mitochondria may have acquired new functions by serving as a sentinel to detect invading pathogens and other stressful signals, ensuring that the host cells survive and thrive even in adverse environments.

    Dr. Chen and his research group are currently working to determine how the MAVS protein functions within the complex series of biochemical reactions that takes place when the body is infected with a virus.

    Researchers at UT Southwestern, led by microbiologist Dr. Michael Gale, and elsewhere have previously found that when an RNA virus invades a cell, a protein called RIG-I first intercepts the virus and binds to viral genetic material. That interaction starts a cascade of biochemical reactions that eventually triggers the cell to make a protein called interferon, which in turn fights off the virus.

    But the chain of events between RIG-I's encounter with the virus and the interferon response is not known. Researchers have been trying to identify and characterize the proteins involved in an effort to better understand the nature of viral infection and how to combat it.

    Dr. Chen said he and his group believe MAVS is among a group of molecules that play a role in activating other proteins - including IRF-3 and NF-kappaB - that prod the cell into making interferon. He also said there is evidence that MAVS binds with RIG-I, but more experiments are needed to determine just how MAVS functions within the cell.

    Other UT Southwestern researchers involved in the studies were lead authors Rashu Seth, a graduate student research assistant, and Dr. Lijun Sun, a postdoctoral researcher in molecular biology, and Chee-Kwee Ea, a graduate student research assistant.

    The research was supported by the National Institutes of Health, the Robert A. Welch Foundation, the Burroughs Wellcome Fund, the Leukemia and Lymphoma Society, the American Cancer Society, and the Howard Hughes Medical Institute.
  12. kallsup

    kallsup New Member

    The protocol I have posted is based on the idea that damage to the mitochondria has interfered with the Krebs cycle in every cell in the body.

    I think it is possible to get into self perpetuating cycle here.

    1.the mitochondria are injured by any of a number of things (fluoride, electromagnetic radiation, medications)
    2. the krebs cycle is impacted and acids accumulate and are not transformed into blood sugar
    3. It becomes almost impossible to move into a fasting state due to the lack of cellular digestion and so deep sleep and growth hormone is limited
    4. The body cannot repair itself without growth hormone and so mitochondria do not get properly repaired (this is a hunch on my part that GH helps with repair of mitochondria)
    5) cellular function becomes even worse due to the fact that at this point they are injuring themselves and so there is another round of the cycle at an even deeper level

    The way out is to fast before sleeping. This allows the slow cellular digestion to complete so that deep sleep can occur and GH, which repairs the body, can be released. Do this every night and take b1 (and the rest of the vitamins in the protocol) and over time you can clear out the toxic build up within your cells and begin to get better.

    The longer you have been sick the longer it will take.
    check out
  13. Rafiki

    Rafiki New Member

    I haven't checked the link out yet. Thanks for posting!

    I'm curious about fasting in the evening. That seems most prudent but on mito sites, for people with known mito disorders, they suggest eating complex carbs late in the evening.

    Of course, I do really, really like my late night carb fix!
  14. kallsup

    kallsup New Member

    yes, GH will fix mitochondria in muscles according to this research

    Enhancement of Muscle Mitochondrial Function by Growth Hormone
    Kevin R. Short, Niels Moller, Maureen L. Bigelow, Jill Coenen-Schimke and K. Sreekumaran Nair

    Endocrinology Research Unit, Mayo Clinic School of Medicine, Rochester, Minnesota 55905

    Address all correspondence and requests for reprints to: K. S. Nair, M.D., Ph.D., Mayo Clinic School of Medicine, Endocrinology Research Unit, 5-194 Joseph, 200 First Street SW, Rochester, Minnesota 55905. E-mail:

    Context: Although GH promotes growth and protein anabolism, which are ATP-dependent processes, the GH effect on mitochondrial regulation remains to be determined.

    Objective: Our objective was to determine the acute effect of GH on mitochondrial oxidative capacity in skeletal muscle of healthy subjects.

    Design and Setting: The study was a randomized crossover design at an academic medical center.

    Participants: Nine healthy men and women completed the study.

    Intervention: GH (150 µg/h) or saline was infused for 14 h on separate days, and muscle biopsies were obtained.

    Main Outcome Measures: Outcome measures included mitochondrial function, gene expression, and protein metabolism.

    Results: The 4-fold increase in plasma GH caused elevations in plasma IGF-I, insulin, glucose, and free fatty acids and a shift in fuel selection, with less carbohydrate (–69%) and leucine (–43%) oxidation and 29% more fat oxidation. Muscle mitochondrial ATP production rate and citrate synthase activity were increased 16–35% in response to GH. GH also resulted in higher abundance of muscle mRNAs encoding IGF-I, mitochondrial proteins from the nuclear (cytochrome c oxidase subunit 4) and mitochondrial (cytochrome c oxidase subunit 3) genomes, the nuclear-derived mitochondrial transcription factor A, and glucose transporter 4. Although GH increased whole-body protein synthesis (nonoxidative disposal of leucine), no effect on synthesis rate of muscle mitochondrial proteins was observed.

    Conclusions: These results demonstrate that acute GH action promotes an increase in mitochondrial oxidative capacity and abundance of several mitochondrial genes. These events may occur through direct or indirect effects of GH on intracellular signaling pathways but do not appear to involve a change in mitochondrial protein synthesis rate.
  15. kallsup

    kallsup New Member

    this is from Wikipedia

    Stimulators of GH secretion include:

    * growth hormone releasing hormone (GHRH) from the arcuate nucleus
    * ghrelin
    * sleep
    * exercise
    * low levels of blood sugar (hypoglycemia)
    * dietary protein
    * increased androgen secretion during puberty (in males from testis and in females from adrenal cortex)
    * arginine[3]

    Inhibitors of GH secretion include:

    * somatostatin from the periventricular nucleus
    * circulating concentrations of GH and IGF-1 (negative feedback)
    * hyperglycemia
    * glucocorticoids
    * estradiol or any estrogen
  16. simonedb

    simonedb Member

    so what do u think of people taking course of antivirals and abx?
  17. kallsup

    kallsup New Member

    Hi Simonedb,
    I am not familar with this approach. However I think there are probably many different ways we can burn out mitochondria and develop FM or CFS including viruses. My only concern would be to make sure the medications chosen did not have side effects that make symptoms worse.
  18. banya

    banya New Member

    These articles are all very interesting. I still feel that there haven't been enough subjects studied to draw any conclusions. For instance, they talk about how much damage is or isn't done to the brain. But I think we need to look at what group of patients are being studied. In a true mitochondrial disease, the affected organs vary. Some mito diseases affect the brain and others don't.

    Again, I'm not saying that we're actually seeing a true mitochondrial disease in most of these patients. But some number* of these patients - CFS, FMS, ME, Lupus, MS, etc have gone on to be studied and were found to actually have a genetic defect and rediagnosed as a mitochondrial disease. If we haven't sorted out all those patients from those who are still going under the CFS, etc diagnosis, how do we do valid studies?

    *I changed "many" to "some number" as I don't wish to imply that the number may be large. No one knows what number or percent. I only know that almost all of the adult mito patients I personally know were previously misdiagnosed with one of the above.
    [This Message was Edited on 10/19/2008]
  19. kallsup

    kallsup New Member

    I think we have to differentiate between mitochondrial damage and mitochondrial disease. This is like the difference between a broken arm (damage) and an arthritic arm (disease).

    My hope is that the mitochondrial involvement in the conditions we have is proven by research to be damage rather than disease, something we get due to exposures rather than a genetic disease.

    I guess we will not know until more research is done.
  20. mezombie

    mezombie Member

    (plus another article)

    OK, I'm back.

    I take CoQ10, Acetyl L-Carnitine, and Magnesium (Lactate, but Glycinate is fine, too). All of these are recommended in the article below. D-Ribose is also suggested. I don't take it because it's a sugar and I'm hypoglycemic.

    I would suggest starting slowly, adding one supplement at a time, but that's me.

    Those are the main supps.

    The article below (by Dr. Sarah Myhill) explains the role of mitochondria in ME (as well as CFS) pretty well.

    For those who haven't tried this protocol, it's well worth considering, IMHO.

    [This Message was Edited on 10/19/2008]

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