The 12th Invest in ME Research Conference June, 2017, Part 2
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Vitamin Diagnostics Methylation Test

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by jeffrez, Apr 10, 2010.

  1. jeffrez

    jeffrez Senior Member

    This is a question for richvank, but also anyone else who has had this test. I'm wondering if there is a sample results printout anywhere so we can see exactly what is measured and reported by this test, how well it then tailors or guides treatment, etc.

    If it's $300 basically just to say, "yes, you have a methylation block," I'm not sure it's really worth the cost if the treatment is then going to be the same anyway. In that case, just do the protocol. On the other hand, if it specifically identifies where the problem is, tailors treatment to those problems or specific blockages, etc. then I suppose it might be useful. I'd just like to take a look and see what it's about. Or, if the report is simply in the form of a series of values ("X is 34 in a range of 0-50," etc.), knowing what those are would be helpful. Thanks for any info.
  2. richvank

    richvank Senior Member

    Hi, Mr. Kite.

    If you join the Yahoo cfs_yasko group at you can look in the Files section of the website in the file named "VD methylation panel files (add yours!)" and find several results of this panel.

    The value of running this panel, in my opinion, is not only that it does show the condition of the methylation cycle, the folate metabolism, and glutathione, and it makes it possible to determine to some degree what is causing a partial block, if present, but it also gives baseline values so that after a period of treatment, a comparison can be made to see the progress of the treatment. This has been found to be helpful, because improvement can extend over months to years, depending on the status of the person and their body burdens of toxins. Because of detox and die-off symptoms, it is not always possible to gauge the improvement based on symptoms alone. It's true that many people have gone ahead and tried the treatment without running this panel first. Some have later expressed the view that they wish they had run the panel, because later on they have decided to run it when they find that the treatment seems to be helping, but then they have had no initial values with which to compare, which they have wished they had.

    I will go even farther and say that in my opinion, this test panel has a good chance of being the best biomarker panel for CFS diagnosis that we have. I realize that most of the "official" CFS community is not even aware of this panel, so I don't expect early adoption of my point of view! :)-) Nevertheless, that gives you an idea of how significant I believe it is.

    Here is a discussion of this panel and my suggestions for interpreting it:

    Interpretation of the Vitamin Diagnostics
    Methylation Pathways Panel

    Rich Van Konynenburg, Ph.D.

    Several people have asked for help in interpreting the results of
    their Vitamin Diagnostics, Inc., methylation pathway panels. Here are my
    suggestions for doing so. They are based on my study of the
    biochemistry involved, on my own experience with interpreting more
    than 120 of these panel results to date, and on discussion of some of
    the issues with Tapan Audhya, Ph.D., who is the director of the
    Vitamin Diagnostics lab.

    The panel consists of measurement of two forms of glutathione
    (reduced and oxidized), adenosine, S-adenosylmethionine (SAM) , S-
    adenosylhomocysteine (SAH), and seven folic acid derivatives or

    According to Dr. Audhya, the reference ranges for each of these
    metabolites was derived from measurements on at least 120 healthy
    male and female volunteer medical students from ages 20 to 40, non-
    smoking, and with no known chronic diseases. The reference ranges
    extend to plus and minus two standard deviations from the mean of
    these measurements.

    Glutathione: This is a measurement of the concentration of the
    reduced (active) form of glutathione (abbreviated GSH) in the blood
    plasma. From what I've seen, most people with chronic fatigue
    syndrome (PWCs) have values below the reference range. This means
    that they are suffering from glutathione depletion. As they undergo
    the simplified treatment approach to lift the methylation cycle
    block, this value usually rises into the normal range over a period
    of months. I believe that this is very important, because if
    glutathione is low, vitamin B12 is likely unprotected and reacts with toxins
    that build up in the absence of sufficient glutathione to take them
    out. Vitamin B12 is thus “hijacked,” and not enough of it is able to
    convert to methylcobalamin, which is what the methylation cycle needs
    in order to function normally. Also, many of the abnormalities and
    symptoms in CFS can be traced to glutathione depletion.

    Glutathione (oxidized): This is a measurement of the concentration
    of the oxidized form of glutathione (abbreviated GSSG) in the blood
    plasma. In many (but not all) PWCs, it is elevated above the normal
    range, and this represents oxidative stress.

    Adenosine: This is a measure of the concentration of adenosine in the
    blood plasma. Adenosine is a product of the reaction that converts
    SAH to homocysteine. In some PWCs it is high, in some it is low, and
    in some it is in the reference range. I don't yet understand what
    controls the adenosine level, and I suspect there is more than one
    factor involved. In most PWCs who started with abnormal values, the
    adenosine level appears to be moving into the reference range with
    methylation cycle treatment, but more data are needed.

    S-adenosymethionine (RBC) (SAM): This is a measure of the
    concentration of SAM in the red blood cells. Most PWCs have values
    below the reference range, and treatment raises the value. S-
    adenosylmethionine is the main supplier of methyl groups in the body,
    and many biochemical reactions depend on it for their methyl
    groups. A low value for SAM represents low methylation capacity, and
    in CFS, it appears to result from a partial block at the enzyme methionine
    synthase. Many of the abnormalities in CFS can be tied to lack of
    sufficient methyation capacity.

    S-adenosylhomocysteine (RBC) (SAH): This is a measure of the
    concentration of SAH in the red blood cells. In CFS, its value
    ranges from below the reference range, to within the reference range,
    to above the reference range. Values appear to be converging toward
    the reference range with treatment. SAH is the product of reactions
    in which SAM donates methyl groups to other molecules.

    Sum of SAM and SAH: When the sum of SAM and SAH is below 268
    micromoles per deciliter, it appears to suggest the presence of
    upregulating polymorphisms in the cystathione beta synthase (CBS)
    enzyme, though this may not be true in every case.

    Ratio of SAM to SAH: A ratio less than about 4.5 also represents low
    methylation capacity. Both the concentration of SAM and the ratio of
    concentrations of SAM to SAH are important in determining the
    methylation capacity.

    5-CH3-THF: This is a measure of the concentration of 5-methyl
    tetrahydrofolate in the blood plasma. It is normally the most
    abundant form of folate in the blood plasma. It is the form that
    serves as a reactant for the enzyme methionine synthase, and is thus
    the most important form for the methylation cycle. Many PWCs have a
    low value, consistent with a partial block in the methylation cycle.
    The simplified treatment approach includes FolaPro, which is
    commercially produced 5-CH3-THF, so that when this treatment is used,
    this value rises in nearly every PWC. If the concentration of 5-CH3-
    THF is within the reference range, but either SAM or the ratio of SAM
    to SAH is below the reference values, it suggests that there is a
    partial methylation cycle block and that it is caused by
    unavailability of sufficient bioactive B12, rather than
    unavailability of sufficient folate. I have seen this frequently,
    and I think it demonstrates that the “hijacking” of B12 is the root
    cause of most cases of partial methylation cycle block. Usually
    glutathione is low in these cases, which is consistent with lack of
    protection for B12, as well as with toxin buildup.

    10-Formyl-THF: This is a measure of the concentration of 10-formyl
    tetrahydrofolate in the blood plasma. It is usually on the low side in PWCs.
    This form of folate is involved in reactions to form purines, which
    form part of RNA and DNA as well as ATP.

    5-Formyl-THF: This is a measure of the concentration of 5-formyl
    tetrahydrofolate (also called folinic acid) in the blood plasma.
    Most but not all PWCs have a value on the low side. This form is not used
    directly as a substrate in one-carbon transfer reactions, but it can
    be converted into other forms of folate. It is one of the
    supplements in the simplified treatment approach, which helps to
    build up various other forms of folate.

    THF: This is a measure of the concentration of tetrahydrofolate in
    the blood plasma. In PWCs it is lower than the mean normal value of 3.7
    nanomoles per liter in most but not all PWCs. This is the
    fundamental chemically reduced form of folate from which several
    other reduced folate forms are made. The supplement folic acid is
    converted into THF by two sequential reactions catalyzed by
    dihydrofolate reductase (DHFR). THF is also a product of the
    reaction of the methionine synthase enzyme, and it is a reactant in
    the reaction that converts formiminoglutamate (figlu) into
    glutamate. If figlu is high in the Genova Diagnostics Metabolic
    Analysis Profile, it indicates that THF is low.

    Folic acid: This is a measure of the concentration of folic acid in
    the blood plasma. Low values suggest folic acid deficiency in the
    current diet. High values are sometimes associated with inability to
    convert folic acid into other forms of folate, such as because of
    polymorphisms in the DHFR enzyme. They may also be due to high
    supplementation of folic acid.

    Folinic acid (WB): This is a measure of the concentration of folinic
    acid in the whole blood. See comments on 5-formyl-THF above. It
    usually tracks with the plasma 5-formyl-THF concentration.

    Folic acid (RBC): This is a measure of the concentration of folic
    acid in the red blood cells. The red blood cells import folic acid
    when they are initially being formed, but during most of their
    approximately four-month life, they do not normally import, export, or use
    it. They simply serve as reservoirs for it, giving it up when they
    are broken down. Many PWCs have low values. This can be
    caused by a low folic acid status in the diet over the previous few
    months, since the population of RBCs at any time has ages ranging
    from zero to about four months. However, in CFS it can also be
    caused by damage to the cell membranes, which allows folic acid to
    leak out of the cells. Dr. Audhya reports that treatment with omega-
    3 fatty acids can raise this value over time.

  3. kerrilyn

    kerrilyn Senior Member

    Rich, I'd like to ask you the same question about the Genova MAP test. Not about the validity because I was thinking it would be good to have baseline info to start. But if the same above information applies, I was wondering if there is supplied reference info or where to find what the results will mean? Thanks.
  4. richvank

    richvank Senior Member

    Hi, kerrilyn.

    The MAP test is also an excellent panel, and it gives "a lot of bang for the buck," because it analyzes many different organic acids, representing several parts of the overall metabolism, from a single urine sample.
    I use it a lot when I consult on cases. It's best run along with some other tests, because they complement each other, and the whole is thus "greater than the sum of its parts." Urine or plasma amino acids testing, as well as urine or red blood cell or whole blood elements analysis are two of the others that help a lot if done together with the MAP test. Of course, they all cost money!

    Unfortunately, it isn't easy to explain how to interpret the MAP test. It does come with sort of a general interpretation, which is mostly based on looking for nutritional deficiencies, and is put together by a computer program that selects sections based on which things come out very high or very low, and that is somewhat helpful, but the subtleties of chronic fatigue syndrome aren't included in this program, and it really takes some study of the biochemistry and some experience to sort out what all the results mean. Some help can be gotten from the book by Lord and Bralley, which is sold on the site, but there are still things that aren't included in that book. I continue to learn about more aspects of this test as I analyze different cases.

    If I could give straightforward guidance about interpretation of the MAP test, I would. As far as the partial methylation cycle block is concerned, if both methylmalonic and formiminoglutamic acids are elevated on the MAP test, it's very likely that this partial block is present. If pyroglutamic acid is low or high, that's an indication of glutathione depletion. Another indication of glutathione depletion is if there is a fairly big drop between citric acid and the ones that follow it in the Krebs cycle. This last one doesn't always work, though, because some PWCs have sort of a general collapse of the Krebs cycle, so that citric acid is low, too. I guess those are the general clues I can give, but it's really best to look at this set of tests together to try to sort out what's going on.

    Best regards,


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