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mitochondrial test results. need help to understand them

Discussion in 'Diagnostic Guidelines and Laboratory Testing' started by carol, Jan 20, 2011.

  1. carol

    carol

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    I've just had my mitochondrial function test results back and I'm all at sea. Is there a molecular biologist out there who can explain in baby language!!! Or someone who understands these things. My Dr only gave me the briefest of explanations and I've forgotton it !!!! Any help would be gratefully received!
    Low whole cell ATP
    Low ATP-related magnesium
    26% blocking of active sites leading to : Poor ADP to ATP re-conversion
    Low mt-ATP and poor provision of new mt-ATP
    Restricted access, 26% blocked translocator function
    ADP to ATP efficiency 49.5%

    DNA adduct cetrimide(moderate) on gene 21- hydroxylase gene#2
    DNA associated zinc 18ng/ml
    mitochondrial membrane K low-norm
    mitochondrial membrane Mg low
    Mitochondrial membrane Zn Low-norm
    Gene study. Zn/Cu-SOD coded on chromasome 21 Low-normal enzyme activity
  2. ggingues

    ggingues $10 gift code at iHerb GAS343 of $40

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    I would be interested in the analysis of such a thing, thanks for a reminder, I want to have this looked at, another appt to make!
  3. August59

    August59 Daughters High School Graduation

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    You might want to sent richvank a PM or he will probably drop in here pretty soon.
  4. richvank

    richvank Senior Member

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    Hi, Carol.

    As you may know, the mitochondria are the little "power plants" in our cells. They operate by oxidizing fuel from our foods and producing ATP (adenosine triphosphate) which is a substance that is able to contain and pass on energy to power many biochemical reactions in the cells. Among many other things, ATP powers our muscles, our nervous system, and the processes in our digestive system.

    The ATP Profile test you have had at AcumenLab analyzes several aspects of the function of the mitochondria in your neutrophils. The neutrophils are the most abundant type of white cells in the blood. These cells are analyzed because they can be obtained from a blood sample, which is more convenient and less invasive than, say, taking a biopsy of your muscle! So far, it appears that the status of the mitochondria in the neutrophils reflects the status of mitochondria in other types of cells in the body, based on the correlation published by Myhill et al. between ATP Profile test results and the degree of disability in PWMEs/PWCs.

    In the first parts of the profile, Dr. Howard works with the whole neutrophils. Later on, he studies the mitochondria separately.

    The first parameter you listed is the "whole cell ATP." This is a measure of the average amount of ATP in a neutrophil. Yours came out low, indicating that your cells do not have enough ATP. This suggests that the mitochondria are dysfunctional, and are not able to produce ATP as rapidly as they should.

    The second parameter is "magnesium-related ATP." In this measurement, magnesium is added to the cells and then the ATP level is measured again. The idea here is that in order for ATP to be used for most biochemical reactions, it has to be combined with magnesium. If the cells are low in magnesium, this will lower the amount of usable ATP. In your case, the magnesium-related ATP came out low, also, which means that your cells were low in magnesium. (In my view, this is usuallycaused by the cell not having enough ATP to power its ion pumps, so it can't bring in as much magnesium as it needs, though a diet low in magnesium can also be a factor. See at the end for my view of the root causes of mito dysfunction.)

    Next is the "blocking of active sites." This is looking at the process by which the mitochondria convert ADP (adenosine diphosphate) back to ATP. When biochemical reactions use ATP for energy in the cell, one of the phosphate groups is removed, and it becomes ADP. This goes back to the mitochondria and gets "pumped back up" to be ATP, to be used again. There are certain enzymes in the inner membrane of the mitochondria that do this, and they have what are called "active sites" on them. These active sites can be blocked by having toxins bound to them. When this happens, they are not able to do the conversion from ADP to ATP as fast as they should. Your active sites were 26% blocked. I've seen worse, but they should not be blocked at all. (See at end for my view of why toxins are present.)

    The next items are "mt-ATP" and "provision of new mt-ATP." This stands for mitochondrial ATP. In this part of the test, Dr. Howard separates the mitochondria out of the neutrophils, and tests them apart from the rest of the cell. Again, the ATP level came out low, showing that the mitochondria are responsible for the low cellular
    ATP.

    Next is the "translocator function." This part examines the function of the translocator protein, which is the protein that moves the "exhausted" ADP back into the mitochondria, and moves the "pumped up" ATP back out, to be used in the cells. This protein was 26% blocked in your mitochondria. Again, I've seen worse, but this protein should not be blocked. Again, there are toxins acting as "monkey wrenches in the works."

    The next item is the conversion efficiency of ADP to ATP, which came out a little less than half of what it should be (49.5%). Your "engine" is running on only about half its cylinders! This is further evidence that something is "gumming up the works."

    The next item notes that on a gene that codes for making a hydroxylase enzyme, there is a DNA adduct. A DNA adduct is a molecule that is bound to the normal DNA, and doesn't belong there. DNA adducts can interfere with expression of the DNA, i.e. use of its code to make proteins, such as this enzyme. In this case, the adduct has been identified as cetrimide, which is only moderately present. Cetrimide is a disinfectant to which you must have been exposed, and which was not properly removed from your body by your detoxication system. (Are you the person who posted that they were a nurse and used this disinfectant a lot?)

    "DNA asociated zinc" is next. I don't have in front of me what the zinc level should be, associated with the DNA, so I can't say whether it is too low or not. Perhaps that is shown on your lab report. Zinc is generally beneficial and is needed in "zinc fingers" that are involved with expression of DNA.

    The potassium, magnesium, and zinc levels associated with your mitochondrial membrane were low-normal or low. These are essential minerals for enzymes in the mito membrane, so low is not what they should be. (Again, I think the reason they are low is that there is not enough ATP to power the cells' ion pumps, so not enough of these is being imported into the cells.)

    The last item notes that the zinc-copper superoxide dismutase enzyme, which is coded on chromosome 21 (note that humans have 23 pairs of chromosomes in the nucleus of the cell), exhibits low-normal enzyme activity. The superoxide dismutases convert superoxide ions into hydrogen peroxide. Superoxide is an oxidizing free radical that is produced in the normal operation of the mitochondria. It is (O2)- The SODs are part of the body's antioxidant enzyme system, which normally controls oxidative stress, which is damaging to the cells. Zn/Cu superoxide dismutase is the form of superoxide dismutase that operates in the cytosol of the cells (that's the "juice" in the main part of the cells, not inside the mitochondria or the other little orgnanelles or the nucleus of the cell. Apparently there was not an adduct on its gene, but the enzyme activity was still low. This could be due to deficiency in zinc or copper or both, or to an inherited genetic polymorphism in this enzyme.

    That's basically what your ATP-profile test results show. I think Dr. Howard has done brilliant work in developing this test panel. I think it has given us good evidence of mito dysfunction in ME/CFS. Recently, Dr. Vermeulen et al. published a paper questioning whether neutrophil results are truly representative of the situation in other cell types. In response, Dr. Howard is now working on looking at the lymphocytes as well.

    I've seen many results of this panel from PWMEs/PWCs. Your report has a lot in common with others I've seen, though your mitochondria are not as severely dysfunctional as some. Your results are the first I've seen that have shown cetrimide. I've seen several that have shown high nickel, and some that have shown a chemical from permanent hair dye. Occasionally, a variety of other toxins show up as well, such as pesticides or organic solvents, and sometimes viral DNA.

    You are probably wondering what can be done to improve the operation of your mitochondria :)-). Dr. Sarah Myhill has put together a mitochondrial "package" that I understand has been helpful to many people. I think it includes carnitine, coenzyme Q10, B vitamins, magnesium and D-ribose. You can probably find it on her website, which I think is still available, though she has been receiving a lot of flak from the GMC about her website lately. She also recommends supplementing minerals that are found to be low.

    At a more fundamental level, for what it's worth, I have proposed the Glutathione Depletion--Methylation Cycle Block hypothesis (more information available at www.cfsresearch.org by clicking on CFS/M.E. and then on my name). Among other things, this hypothesis seeks to explain the basic reasons for the problems in the mitochondria in ME/CFS, as have shown up on your test panel. Essentially, according to this hypothesis, glutathione becomes depleted, this allows toxins and oxidative stress to build up, and this leads directly to some of the problems seen in the mitochondria, and indirectly to others. It also leads to a partial block in the methylation cycle, which in turn causes depletion of carnitine, coenzyme Q-10, and other metabolites that impact the operation of the mitochondria. In this hypothesis, it is necessary to lift the partial block in the methylation cycle in order to bring about a correction of the fundamental issues that are causing the mitochondrial dysfunction. A protocol for doing this can be found at the above-cited website. Though the mito package described above can help to some degree, I think that the longer-term solution is to address the partial methylation cycle block, which will restore the glutathione levels, and this should clean up the mitochondria and help them to operate more normally.

    I need to say that this must be considered as an unproven hypothesis, though it appears to be consistent with the available evidence. Also, please note that I am a researcher, not a physician, and anyone undergoing methylation treatment needs to be under the care of a licensed physician, since a small number of people have reported serious adverse effects while on this treatment, even though it consists only of targeted nutritional supplements. More information on the adverse effects can be found in the article dated July 18, 2007, at the above-cited website.

    Best regards,

    Rich
  5. carol

    carol

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    Thank you so much for your explanation Yes I was a nurse until I had to retire 18yrs ago. I've been ill for 50yrs, had to do 6 mths extra training to cover all my sick leave! We used cetrimide to scrub up at least 20 times a day. The brain refuses to remember most of my theory, it is so frustrating. Added to the mix is a 100mcgs Fentanyl patch I have for pain = doesn't help the thinking. Thank you again for your help. really appreciated.
  6. globalpilot

    globalpilot Senior Member

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    Hi Rich,
    I have a couple of questions about your excellent analysis:

    a. you said "The next items are "mt-ATP" and "provision of new mt-ATP." This stands for mitochondrial ATP. In this part of the test, Dr. Howard separates the mitochondria out of the neutrophils, and tests them apart from the rest of the cell. Again, the ATP level came out low, showing that the mitochondria are responsible for the low cellular "

    Is it true that low mitrochondria ATP means the mitochondria is responsible for the low cellular energy ? couldn't problems with the krebs cycle which is outside of hte mitochondria cause low mitochondria ATP due to low input of electrons ?

    What part of the test measures "provision of new mt-aTP" ? Is this related to the TL in and the TL out test results ?

    b. Is the 26% blocking of the active sites on the mitochondria membrane the same as the 26% blocking of the translocator protein ? ie. are they assuming all sites are blocked by the same amount ?

    Regards,
    GP
  7. richvank

    richvank Senior Member

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    Hi, GP.

    The Krebs cycle is actually located inside the mitochondria. The mitochondria are normally responsible for producing by far the major part of the ATP in nearly all the cells. Red blood cells are an exception. They do not have mitochondria, and their ATP is produced by glycolysis. One of the subtypes of the skeletal muscle cells (the "fast-twitch" cells) also rely on glycolysis for their ATP. I think there might be one or two others. Can't remember. But yes, the low ATP production in the neutrophils is due to mito dysfunction.

    The details of the test procedure are described in Appendix B of the Myhill et al. paper:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680051/pdf/ijcem0001-0001.pdf

    There is a separate measure of mitochondrial ATP, and then the translocator function is evaluated by two more steps in the procedure.

    It is just a coincidence that the two types of blocking both came out to be 26%. They are measured separately, and usually the numbers come out to be different for the two.

    Best regards,

    Rich
  8. August59

    August59 Daughters High School Graduation

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    I'm not sure how this will play into your problems, but chronic pain meds will almost always abnormally affect some of your sex (estrogen, testosterone and progesterone), steroid (cortisol, dhea and acth) hormones and thyroid hormones. Pain management doctors are starting to pick up on having these tested, but finding an endocrinologist that knows how to balance hormones is just about impossible. Most (not all) endo's think thyroid meds fix everything and will not properly address adrenal issues.

    I speculate that having hormones in balance would in some way help with mitochondrial function and help with detoxification.
  9. carol

    carol

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    Hi August59. I'm ahead of you---after getting my results and then the explanation from Richvank I decided to reduce my fentanyl by half. Horrible withdrawal symptoms and bad pain!! ( going to try acupunture) Then I told my GP. Not the right way to do it!!! I am now out of bed, voice returned, no dizziness, chest pain or breathing problems. All of which I was told were due to thinking myself ill, but I thought were ME symptoms, but were actually Fentanyl!! complicated. I am going to do the methylation protocol but first I think I have to get my vit and minerals corrected. My son is getting married in June, most women would just be worried how fat they look, me, I'm just worried how I'll get there. I need to be better. Richvank's methylation protocol is an opportunity to do something positive, get back in control.
  10. August59

    August59 Daughters High School Graduation

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    I was able to reduce my pain meds but only after I got my hormones some what balanced, reduced constipation, stretching and started methylation protocol. I reduced my pain meds slowly, but consistently and I'm down about 60% from largest dose. All of this has taken place over the last 9 months or so. I was on Fentanyl 100 mcg, but now I am on Exalgo and I'm getting pretty close to making another reduction.

    My only suggestion is to not get to impatient, but I would encourage you to consult PM physician while reducing. I wouldn't be comfortable with just a GP while going through pain med reduction process. I believe you will see some good benefits in reducing your meds and hope you start feeling better soon.
  11. ggingues

    ggingues $10 gift code at iHerb GAS343 of $40

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    Ouch, yes Fentanyl is for dying Cancer patients! That is what I was told by my Dr. I was on it for a month or so, I was waking every hour with major pain of the shoulder I was sleeping on. Glad I got of that drug, my Neurologist was rather useless, 2 years of meds with nothing to really show for it!!

    GG
  12. carol

    carol

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    I've been on Fentanyl for 10 years, morphine for 8 yrs before that. I've just been given more and more as the pain broke through. I totally agree that reduction should be under the care of the pain clinic but I have to wait for an appt, and I've been waiting since Nov and suspect it will be at least another 8 weeks (NHS). I had to do something as my husband was being persuaded by my Docs that I was in need of a psych referral!!!!!(so called imaginary chest pain, difficulties breathing etc). I could not have got to the hospital clinic the state I was in, now I can. Dr's feel powerless in the face of someone in so much pain and want to do something, the trouble is that something sometimes does more harm than good. Crappy situation.
  13. August59

    August59 Daughters High School Graduation

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    I certainly understand your situation and sincerely wish you the best. Please keep us updated if possible.
  14. carol

    carol

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    Will do, and thank you all for your interest, it helps a lot.
  15. Kate_UK

    Kate_UK Senior Member

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    Rich - do you know why reconversion would be poor if the active site is not blocked?
    thanks
  16. richvank

    richvank Senior Member

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    Hi, Kate.

    Oxidative stress downregulates both the Krebs cycle and the repiratory chain. This would be an effect of glutathione depletion on the mitochondria, apart from the buildup of toxins, which usually occurs over time when glutathione is down. My view is that all of the mitochondrial problems stem originally from depletion of glutathione and a partial block of the methylation cycle, which follows, forming a chronic vicious circle. The former allows a rise in oxidative stress and toxin levels, and the latter lowers the production of substances needed by the mitochondria, including carnitine, Co Q-10, phosphatidyl choline and creatine. The blocking of the various enzymes and proteins and the development of DNA adducts in my view are later developments that result from these earlier events. Whether these blocks and adducts show up will depend on how long a person's glutathione has been depleted, and what their exposure levels to toxins are, in my view.

    Best regards,

    Rich

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