My latest health issues re: macrocytosis

Discussion in 'Fibromyalgia Main Forum' started by jole, Jan 24, 2011.

  1. jole

    jole Member

    I haven't been on the board for awhile...busy with docs again, after being diagnosed with macrocytosis (large red blood cells). It was explained to me that my red blood cells are actually 'eating' themselves, so the new ones are produced larger to fill in the space. It has nothing to do with my fibro and just showed up in my lab work about 4 months ago. My PCP sent me to a hemotologist/oncologist for a consult, and here's what I was told.

    It could be caused by one of three things: 1) Low vitamin B levels 2) A side-effect of Neurontin 3) Bone marrow cancer
    Labs show my vitamin levels to be normal.

    I am off the Neurontin (gabapentin) for 2 months. This is the main reason I'm posting this, is to let all of you know how important it is to keep up with your lab checks as ordered by your docs. Many of our PCPs do not know these side effects of the meds, and when I looked Neurontin up it does not list it anywhere as an effect.

    So, if the MCV is still abnormal in 2 months they will do a bone marrow test looking for cancer. I'm praying the Neurontin is the culprit, even though it's been very hard for me to sleep without it, and my pain level is greater in the mornings. As most of you go through, it's so difficult to find meds that actually help with all the sensitivities we develop, so it's not easy to give up one that helps *sigh*.

    As I said, just a reminder to keep those lab appointments......never know what might show up when you least expect it! Here I always thought it was mostly just a check for liver Hope everyone has a great day! Hugs....Jole
    [This Message was Edited on 01/24/2011]
  2. spacee

    spacee Member

    I hope that it is the neurontin. Why are they waiting to do the bone marrow test though?
    Seems odd to me.

    My brother takes a large quantity of neurontin for his discs in his neck. I will let him know
    about this. He's a doc.

    ((((Hugs Jole))))

  3. DeborahLynn

    DeborahLynn Member

    I pray it's not anything serious, and that it's due to the meds, although I'm sorry you may have to give up a med that works for you. Hopefully you will be able to find something else that works for you.

    Hugs and prayers, Deb
  4. richvank

    richvank New Member

    Hi, jole.

    I want to suggest another possible cause of the macrocytosis. My research over the past four years has shown that in most cases of ME/CFS there is a partial block in the methylation cycle, which is associated with a functional deficiency in vitamin B12, caused by glutathione depletion. This is now supported by lab testing in hundreds of patients, under the care of several clinicians who specialize in the treatment of ME/CFS.

    This partial block causes folates to become depleted inside cells as a result of what is called the "methyl trap" mechanism.

    This drop in folates makes it difficult for the cells in the bone marrow, where new red blood cells are made, to produce DNA fast enough to keep up with the demand for making new red blood cells. Since hemoglobin continues to be produced at a near-normal rate (at least at first), more hemoglobin than normal is put into the fewer number of red blood cells that are made. The result is macrocytosis (elevated MCV and MCH on a complete blood count panel).

    Ordinary blood serum tests for B12 and folate can be normal or even high in this situation, but this does not reflect the functional problem that is going on inside the cells.

    If you want to test for this problem, the best panel is the methylation pathways panel offered by Health Diagnostics and Research Institute (contact info and interpretation guide are pasted below). The next best (an indirect test) is a urine organic acids panel that includes both MMA and figlu (the Genova Diagnostics Metabolic Analysis Profile is one that I use frequently). If both these metabolites are high, it is very likely that a partial methylation cycle block is present.

    In most of the PWMEs/PWCs whose test data I have seen, the MCV and MCH tend to be above the mean of the reference range, but they usually don't get above the reference range unless a person has a pretty severe folate draining problem.

    Given that you have ME/CFS, I would encourage you to get this checked out. Your physician likely will not be aware of this mechanism, since it is not yet widely known. Nonprescription treatment is available and has been found to produce significant benefit to more than two-thirds of the PWMEs/PWCs in a clinical study.

    More information on this pathogenesis mechanism and the treatment for it can be found at this site:

    Best regards,


    Methylation Pathways Panel

    This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

    The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinician’s letterhead.

    Available from:

    Health Diagnostics and Research Institute
    540 Bordentown Avenue, Suite 4930
    South Amboy, NJ 08879
    Phone: (732) 721-1234
    Fax: (732) 525-3288

    Lab Director: Elizabeth Valentine, M.D.

    Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone.

    Rich Van Konynenburg, Ph.D.
    Independent Researcher and Consultant

    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.

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