Discussion in 'Fibromyalgia Main Forum' started by winsomme, Nov 5, 2008.

  1. winsomme

    winsomme New Member

    I saw in another post you explaining how depressed hypothalamic functioning can be explained by a methylation block.

    I was wondering - as mentioned that one of the hormones involved is ACTH - if someone has for instance low GH, but high Cortisol...could that be an indicator that methylation is not the problem?

    also, is that methylation test from Vitamin Diagnostics a blood test and is there a web link?

  2. richvank

    richvank New Member

    Hi, Bill.

    I'm not sure. The best way to determine whether there is a partial methylation cycle block is to run the Vitamin Diagnostics methylation panel. The next best way is to run a urine organic acids test that includes both methylmalonate and figlu, such as the Genova Diagnostics Metabolic Analysis Profile. The latter is less direct, but still gives a good indication that there is a block if both methylmalonate and figlu are elevated.

    One thing I have observed is that during the time course of a case of CFS, cortisol is usually high at the beginning, but over time it develops an abnormal diurnal variation, then drops and is then low. It could be that the cells in the pituitary that produce growth hormone go low in glutathione before those that produce the ACTH, or it could be that the first thing that happens to ACTH is that it is no longer routed to the regulated secretion pathway (because the "hook" in the POMC molecule, which is the precursor for ACTH has improper formation of its disulfide bonds as a result of glutathione depletion), but goes to the unregulated pathway. This is discussed in the medical literature. I think that accounts for the disturbance in the normal diurnal variation of cortisol output that is often seen before the cortisol production overall collapses. I suspect that the latter is due to more severe glutathione depletion as time goes on, so that the POMC molecules are not properly formed initially, and are continuously recycled, so that they total production of ACTH drops.

    Yes, the Vitamin Diagnostics methylation panel requires a blood draw, with a special kit that has preservatives to make sure that the glutathione does not become oxidized during shipping of samples to the lab. Here's the contact information:

    Vitamin Diagnostics, Inc.
    Rt. 35 & Industrial Drive
    Cliffwood Beach, NJ 07735
    Phone:+1 (732) 583-7773
    Fax: +1 (732) 583-7774)

    Lab Director: Tapan Audhya, Ph.D.
    (usually at the lab on Tues. and Wed. from 1 to 3 p.m., Eastern time)

  3. winsomme

    winsomme New Member

    I had this test done about a year ago. would you be willing to look a the results?

    i can send you the .pdf of the whole test result if that would help.

    the things you mentioned:

    methylmalonic acid (MMA) - 14.6

    Formiminoglutamic acid - 2.0

    currently i am doing the Marshall Protocol.

  4. winsomme

    winsomme New Member

    i also had a Urine Amino Acid at the same time which i could also send.

    I don't remember all the results meanings, but i remember that it was not totally what you would expect with methyl prob's...

    for instance

    1-methylhistidine was very high, but 3-methylhistidine was on the low side.
  5. deliarose

    deliarose New Member

    Bill, my latest UAA shows high 1 methyhistidine, low 3-methylhistidine. VD methylation panel (from September) shows my cycle is still blocked although it's not as bad as a year ago.

  6. winsomme

    winsomme New Member


    thanks for the info. yeah, i'm trying to figure out which of my Docs would run it for me.

    the good thing about MAP and UAA is that you can have them done on your own.

    i'm trying to remember which other results applied to methyl block, but i remember that it wasn't really what was expected on either test for a methyl block...

    not one of the genetic kind anyway. i seem to remember that you can have methyl block that isn't do to the a chronic infection could interfere in the krebs and methylation cycles...

    i dug into this a while ago, but i can't remember what all the tests referred to.

    for instance, i remember the 1-methyl can be high if you eat a lot of poultry and meat in general..

    how was your ammonia....I know that was a big reason to get that UAA done and mine was low which also didn't necessarily fit with methyl block...

    also, what exactly does the VD panel show.....what are the test results?

  7. richvank

    richvank New Member

    Hi, Bill.

    Yes, you can send me a .pdf of your MAP results at richvank at aol dot com.

    Below is something I wrote about interpreting the VD methylation panel.


    Several people have asked for help in interpreting the results of
    their Vitamin Diagnostics, Inc., methylation 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. Audha, 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 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 directly 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 are 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 hundreds of biochemical reactions depend on it for their methyl
    groups. A low value for SAM represents low methylation capacity, and
    it usually results from a partial block at the enzyme methionine
    synthase. Many of the abnormalities in CFS result from 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. Most 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 toxin buildup.

    10-Formyl-THF: This is a measure of the concentration of 10-formyl
    tetrahydrofolate in the blood plasma. It is usually low 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 low value. 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. 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 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 normally 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.