Help Interpreting Methylation Panel Results

Discussion in 'Fibromyalgia Main Forum' started by equanimous, Oct 16, 2010.

  1. equanimous

    equanimous New Member

    Just got my methylation panel results back from Health Diagnostics and Research Institute, but I really have no idea how to interpret them or what to do with the information in terms of future treatment and supplementation.

    Amino Acids in Plasma: Unit Ref. Range
    Glutathione (oxidised) 0.51µmol/L 0.16-0.50
    Glutathione (reduced) 3.6 µmol/L 3.8-5.5

    S-Adenosylmethionine (RBC) 210 µmol/dl 221-256
    S-Adenosylhomocysteine (RBC) 50.0 µmol/dl 38.0-49.0
    5-CH3-THF 9.3 nmol/l 8.4-72.6
    10-Formyl-THF 1.2 nmol/l 1.5-8.2
    5-Formyl-THF 1.40 nmol/l 1.20-11.70
    THF 0.73 nmol/l 0.60-6.80
    Folic Acid 17.6 nmol/l 8.9-24.6
    Folinic Acid (WB) 10.2 nmol/l 9.0-35.5
    Folic Acid (RBC) 315 nmol/l 400-1500

    Adensosine 14.5 10^-8 M 16.8-21.4
  2. equanimous

    equanimous New Member

    I'm sorry, I forgot to mention that I've been doing the simplified methylation protocol for over a year, so I'm already on all of those supplements. Thanks!

  3. richvank

    richvank New Member

    Hi, equanimous.

    These results indicate that you still have glutathione depletion and a partial methylation cycle block. The elevated oxidized glutathione and the low RBC folic acid indicate that your body is still in a state of oxidative stress. Sorry about that.

    You are not alone. About one-third of the PWCs who try this treatment initially either do not experience a response (or a sufficient response), or find that they are not able to tolerate it.

    Given that you have been on the methyation cycle treatment for a year, this suggests that something is preventing the lifting of the partial block. There are several possibilities, based on other cases in this one-third:

    1. You may be low in plasma amino acids levels. The most important ones for this part of the metabolism are methionine, serine, cysteine, glutamine and glycine. A Doctor's Data Lab plasma amino acids test will tell you whether any of these are low. This is a common problem in CFS. In many cases the digestive system is not digesting protein very well, and amino acids are not being absorbed well. Also, PWCs tend to burn amino acids for fuel, because their mitochondria are not able to use carbs and fats very well, because of a partial block in the Krebs cycle caused by the oxidizing free radicals that rise, due to the glutathione depletion. Improving the function of the digestive system is one approach to countering this problem, such as by augmenting the stomach acid (such as with betaine-HCl), which is often low in PWCs, and taking digestive enzymes and probiotics. Another approach is to take free-form amino acids. which don't need to be digested. In severe cases, in which the gut is not able to absorb amino acids, and the person is losing weight and headed downhill, the person and their physician may need to consider installation of a picc line for intravenous nutrition.

    2. You may be low in the vitamin and/or mineral cofactors that are needed by the methylation and folate cycles and the transsulfuration pathway, as well as the antioxidant system. These include zinc, copper, manganese, magnesium, and/or selenium, or one or more of the other B vitamins. Vitamins B2, B3, and B6 are particularly important. These nutrients are in the multi that is part of the protocol, but you may need higher dosages. A red blood cell elements test will measure the minerals. A Genova Diagnostics Metabolic Analysis Profile will give indirect information about B vitamin levels.

    3. You may have KPU (better name is HPU), which depletes zinc, B6, manganese, biotin, and other nutrients. Dr. Klinghardt has found this in many of his patients, and depletion of these nutrients will block the methylation cycle. Health Diagnostics offers a KPU test, and Dr. Klinghardt has posted his views on how this test should be run and how the samples should be handled.

    4. You may have a high level of mercury, which can block some of the enzymes in this part of the metabolism. If so, it may be necessary to do chelation to get the mercury level down before the methylation cycle can be brought back up. This must be done carefully, with the help of an experienced physician, because mobilizing mercury can cause it to move to other locations in the body, such as the brain, and it is a potent neurotoxin.

    As I've posted several times before, my position is that a person doing the methylation treatment must be under the care of a licensed physician so that any serious adverse effects that may arise can be promptly and properly dealt with.

    Below are my general comments on the interpretation of this panel, if you want to consider more details:

    Interpretation of the Health Diagnostics and Research Institute
    Methylation Pathways Panel

    Rich Van Konynenburg, Ph.D.

    Several people have asked for help in interpreting the results of
    their Health Diagnostics and Research Institute 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., at the Health Diagnostics and Research Institute.

    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.

    I hope this is helpful.


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