I posted this in another section but it was suggested I post it separately: The following study by Julian Ambrus et al is an interesting case study. http://www.jmedicalcasereports.com/content/6/1/55 While the study treated fibromyalgia as mitochondrial myopathy, both ME and fibromyalgia have long since been thought of as having significant mitochondrial dysfunction, which can explain many of the varied symptoms. Eg. see also the work of Brad Chazotte, http://www.ncf-net.org/library/ChazotteCFSandMitochondria.pdf who found that the mitochondrial outer membrane is depolarized in people with ME, which means the permeability functions are impaired. Other work by Sarah Myhill and by David Bell have shown this dysfunction to be ubiquitous in ME. For those unfamiliar with the terminology , mitochondria are both the battery of cells as well as the organelle for toxin clearance from inside cells. What causes the dysfunction (myopathy) is not known. Of course there are several culprits which induce mitochondrial dysfunction. Viruses, which elevate IFNalpha and IFNgamma, various drugs and various Xenobiotic metabolites/toxins such as phthalates and the pesticide rotenone among many other pesticides and the endogenous toxins resulting mainly from oxidative metabolism (ROS or reactive oxygen species). In addition chronic vitamin D and magnesium deficiency cause mitochondrial dysfunction. (Hence the relationahip between vitamin D deficiency and MS, Autism and Schizophrenia) There is some evidence that continual psycho-social stress and sleep deprivation will also cause temporary mitochondrial dysfunction. The fMRI studies showing loss of brain shrinkage are better explained by a more general mitochondrial dysfunction. If the cause is a virus or external (xenobiotic) toxins then it will also be a ROS problem because once the mitochondria are dysfunctional the ROS cannot be cleared properly. In addition, once mitochondria are dysfunctional in highly dependent tissue such as neurons (which often require many mitochondria per cell) the required number of mitochondria are reduced. Ros are not helped by a glutathione deficiency, another deficiency shown almost universally in people with ME and Fibromyalgia. Glutathione is the main substance which clears ROS. Glutathione synthesis is highly impaired when mitochondria are dysfunctional: http://www.ncbi.nlm.nih.gov/pubmed/17936517 There are some researchers who have demonstrated the glutathione dysfunction extensively, eg. Rich van Konynenberg (see his notes on Phoenix rising; http://forums.phoenixrising.me/index.php). I believe the glutathione depletion is due to mitochondrial dysfunction, at least it is an explanation for it. The consequence of mitochondrial dysfunction depends on the tissue/cells affected. Muscle cells will become shorter and fail to contract properly, lactic acid is not cleared properly and fatigue and pain build up. Cells of the spinal chord will no longer have their inhibitory function and pain is amplified without appropriate suppression. Cells of the immune system are mostly activated by signalling which is also faulty and pro-inflammatory cytokines are elevated and natural killer cells are not functional and fail to express their signalling receptors. In addition to all of this the vitamin D system is dysfunctional, possibly because the VDR (vitamin D receptor), a protein which allows vitamin D to communicate with genes is not being made in the required amounts. (The vitamin D system is already impaired in most people because of lack of sun exposure). When the vitamin D system is dysfunctional and the person has vitamin D deficiency. ie less than 35 ng/ml this contributes to muscle fatigue and pain. And as I stated above chronic vitamin D deficiency may be a cause of the mitochondrial dysfunction in the first place especially when combined with toxins and/or elevated viruses. The vitamin D system also controls/activates the "xenobiotic toxin removal system". When this is dysfunctional people have worse MCS (Multiple Chemical Sensitivity), the most perplexing set of symptoms of ME and those which invoke considerable medical skepticism - sadly! After discussing the case study with Julian Ambrus I tried a modified version of the treatment, which I have been on for six months. After three months my wife and daughter went onto the treatment. We are all responding very well. Dr. Ambrus is now following 400 patients in treatment. I have ME with fibromyalgia, my wife has ME with MCS and severe intermittent ataxia, my daughter has ME with severe MCS. We have all been diagnosed with ME by different specialists and our daughter is part of the research at Bond University in Queensland and this research has confirmed her dysfunction and immunological problems eg. low NKCbright cell function. I began the treatment in January 2012, a total of 6 months: I am functioning at about 85-90% of pre-morbidity, Working every day. The first thing I noted after about four weeks was the tremendous lift in energy. It took four months for most of the FM pain to subside and I am now walking about 3 Km daily. I believe the exercise is important but only after the treatment has reduced pain and fatigue. This treatment is a first step for those with severe fatigue. The following symptoms have also ceased for several months now: tremor, diarrhea, poor hearing, inability to find words, sleep improved from 3 hours to 6-7 hours and my morning stiffness has gone, I can type endlessly. Also my fingerprints are returning and the ridging of the fingernails is going. I still have some wrist pain and hot hands first thing in the morning although this is much less and possibly diminishing slowly. The treatment is unusually long and may have to go on for longer. I don't know yet. Becuase of my lifestyle I will be on the vitamin D for the rst of my life. My rationale for the improvement is that improved/normalised mitochondrial function increases cellular function to enable recovery of tissue, modulation of intra-cellular and immunological signalling in all affected systems, in addition the gut imbalances are reduced and the bacterial leakage through the digestive tract wall is reduced. Glutathione synthesis will be normalised. I am hoping/predicting that even if the cause is viral the re-establishement of proper homeostasis will bring the viral infection/activation under control. That it will also improve ROS/toxin clearance more permanently. That I will reach a state where normality of functions will continue. The basic treatment is as follows: a * indicates obligatory, *acetyl carnitine 500mg TD (For mitochondrial function) *CoQ10 200mg TD (For mitochondrial function) *B12, (methyl cobalamine or hydroxy cobalamine) 1mg TD (For mitochondrial function and glutathione increase) vitamin B6 30mg TD (For mitochondrial function and glutathione increase) *folinic acid 800mcg (or folic acid) TD (For mitochondrial function and glutathione increase) * magnesium citrate or magnesium malate 200mg TD (To support vitamin D and to reduce muscular cramps and pain) *vitamin D3 (cholecalciferol, not ergocalciferol and not calcitriol 120 mcg TD, also limit calcium to no more than 500 mg daily) After one month reduce vitamin D to 120 mcg once daily, smae with vitamin K *vitamin K2 (K4+_K7) 100mcg TD (To support vitamin D) vitamin P (PQQ) 10mg BD (For mitochondrial function, actually to increase mitochondrial biogenesis) niacinamide 50mg TD (For mitochondrial function) Optionally include NAC (N-acetyl-cysteine and curcumin 1mg TD and a multivite) TD = three times per day BD = twice daily note: If you take vitamin D you MUST take vitamin K2 and magnesium. This may seem to some a very high dose of vitamin D but recent evidence verifies it is safe. If you want to be sure then have your calcium levels tested during the treatment (1 month, then 6 months should suffice). It is a lot of supplements, so must be taken with meals. As soon as the wrist pain subsides completely I will go off the treatment to see if any symptoms return. So I have no idea how long I will need to be on this regime.