Professor & patients' paper on the solvable biological challenge of ME/CFS: reader-friendly version
Simon McGrath provides a patient-friendly version of a peer-reviewed paper which highlights some of the most promising biomedical research on ME/CFS ...
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translocator protein studies. Help please

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by justy, Nov 26, 2011.

  1. justy

    justy Senior Member

    Hi, i originally posted this as a blog, but it didnt attract many comments. I had my test results back but i dont understand what they mean or what the implications are. There is a lot of stuff about fats which has me really puzzled, i dont think it is mainly from ingesting therm -apparently my body could be doing this to itself. but why? and what to do about it?
    I also had a test result that Dr Myhill had never seen before and she doesnt know what to suggest i do about it. At the moment i feel like it was a waste of money as i dont know what to do with the info.
    For ease i have cut and pasted from the report by Dr Myhill:

    "Translocator Protein Test abnormalities initial examination:
    Damage to the mitochondrial membrane structure the mitochondrial membrane is a phospholipid bi-layer, which requires the right fats in order to make it, freedom from toxic stress and good antioxidant status to maintain it. However mitochondrial membranes differ from normal cell membranes because they contain the phospholipid cardiolipin. This has come to medical interest because of the anti-cardiolipin syndrome first described by Graham Hughes in which he describes a group of patients who have a pro-thrombotic tendency as a result of possessing this antibody. Clinically these patients present with thrombosis and need anti-coagulants for life. This is not the problem here! Cardiolipin is what makes mitochondrial membranes different from normal cell membranes and cardiolipin is an essential part of energy production. Without cardiolipin the inner mitochondrial membrane cannot fold properly and this may account for some of the membrane abnormality described in this test.

    Mitochondrial membrane binding of:
    Lipid damage the mitochondrial membrane is a phospholipid bi-layer and the structure of these lipids is critical towards normal mitochondrial membrane function. There are two major sources of toxic lipids in our environment. The first are lipids that have become oxidised as a result of poor antioxidant status, a second possibility is that lipids have been hydrogenated as a result of eating fats which have been heated or hydrogenated in the margarine making process. A further possibility is the presence of transfatty acids. In nature most fats are present as the cis, or left-handed isomer and fit biological enzyme systems so that they can be excreted. Transfatty acid represent the right-handed version, do not fit biological enzyme systems and literally clog the system up. This is akin to throwing a handful of sand into a finely tuned engine. The problem with these abnormal lipids is that the immune system then has to try to clear them out of the way and this it does in the only way it knows how to which is to fire superoxides at them to try to break them down. The result of this is excessive free radical activity which causes damage in its own right and again attention to antioxidant status is required as a damage limitation exercise.

    Presence of diolein - This is a markedly pro-inflammatory fatty acid probably produced as a result of poor antioxidant status. This means that correcting antioxidant status is likely to be a very important part of recovery. The chemical formulation of diolein is C18:1, cis-9. The base molecule consists of two C18 units that results in two main isomeric forms namely 1,2- and 1,3- diolein. Unfortunately the fluorescent probe doesnt tell us which is present. However the 1,3- form seems to be the most directly toxic while the 1,2- form is the more chemo-attractant (that is to say it attracts white cells which then try to destroy it with superoxides). They probably cause as much damage as each other but by slightly different mechanisms. The 1,2- form has the greater potential to leading to an autoimmune situation. Diolein can be produced directly in cell plasma membranes due to an, as yet, not fully described defect in essential fatty acid metabolism.

    So finding diolein associated with mitochondria could also indicate one of three other main causes. There could be a defect in the production of energy from lipids within the mitochondria, there might be a defect in the production of the mitochondrial membrane itself or the diolein might be an import from any fat source in the body. In the latter case we would have to assume that the intra-mitochondrial chemistry rejects diolein as unsuitable for use as a fuel source.

    The trans-isomers have been found in a few very toxic samples of vegetable oils. If ingested, they cause rapid and generalised toxic effects. If the patient survived the first few hours they generally do well, but some have developed a profound fatigue syndrome one to two months later.

    High levels of aldehydes Justines poor antioxidant status has created other related problems. With poor antioxidant status one cannot detoxify lipid peroxides and aldehydes and so these get stuck onto mitochondrial membranes and possibly onto DNA. Aldehydes are the intermediate product between alcohol and acids. They are toxic to the body and therefore require detoxification by aldehyde dehydrogenase enzymes which are dependant on co-factors such as zinc and B vitamins. They get into our bodies from the outside world as formaldehydes and glutaraldehydes, both of which can be used as solvents (e.g. in the building industry) or as disinfectants (farming industry, hospital disinfectants). They are also produced in the body in for example, metabolism of alcohol. Another possible source of aldehydes are artificial sweeteners. Aspartame is metabolised into formaldehyde -this makes it potentially toxic in susceptible people!

    Aldehydes can be detoxed by oxidation or conjugation and so zinc and glutathione are essential to get rid of them. They can also be got rid of through doing sweating regimes.

    Chemical on translocator sites:
    Moderate levels of cyclopentasiloxane this is a silicone fluid commonly used in cosmetics such as deodorants, sunblocks, hair sprays and skin care products. It is becoming more common in hair conditioners, as it makes the hair easier to brush without breakage

    Moderate levels of a sulphate/hormone complex this is a finding that I have not seen before and I am not quite sure what the implications are for management. John McLaren Howard makes the comment that steroid hormones are detoxified by sulphates and some of these products of metabolism are stuck onto translocator protein. It is certainly the case that when people start to detoxify and mobilise chemicals from the body, the intermediate products from metabolism (typically the offending chemical stuck onto glutathione) can appear on translocator protein. I can only think that this is a parallel situation steroids in the body need to be detoxified just like many other endogenous toxins so perhaps this represents an intermediate step. No specific management it is a case of more of the same.

    Trace of p-dichlorobenzene - p-DCB is used to control moths, moulds and mildew. It is used as a disinfectant in waste containers and restrooms.

    Sorry if this seems a bit long, ive tried to cut it back a bit.
    Big thanks to Alex who already had a good go at explaining this to me on the blog post.
    Thanks, Justy.
  2. richvank

    richvank Senior Member

    Hi, Justy.

    In my hypothesis (the GD-MCB hypothesis), the source of all the problems with the mitochondria in ME/CFS is the combination of glutathione depletion and the partial block in the methylation cycle.

    These have several unfortunate effects on the mitochondria: a rise in oxidative stress, which inhibits enzymes in both the Krebs cycle and the respiratory chain and lowers the rate of production of ATP and causes an energy crisis for the membrane ion pumps, disrupting the concentrations of essential minerals; a rise in toxins, which are not taken out by the detox system and hence bind to enzymes, the translocator protein and DNA; a rise in pathogens, because of dysfunction of the immune system; and depletion of substances needed by the mitochondria that require methylation for their synthesis, including phosphatidylcholine, creatine, carnitine and coenzyme Q10. All of these can be traced back to the chronic vicious circle mechanism involving glutathione depletion and the partial methylation cycle block.

    The treatment of these problems comes back to lifting the partial methylation cycle block with one of the methylation treatments. More information on this can be found in the video and/or slides at$%7Bweburl%7D

    I hope this helps.

    Best regards.

  3. justy

    justy Senior Member

    Thanks Rich, every time i hear you explain the theory it gets easier to understand and sounds more and more convincing.
    Take care, Justy.

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