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
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