High folate a sign of MTHFR?

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  • #2674 Reply


    I was told that high folate can be a sign of an MTHFR mutation. Is there any truth to this? I have almost always had high folate on blood tests over the years, but I thought that it was from the B Vitamins I was taking.

    #2680 Reply


    Yes, high folate can be a sign of a MTHFR mutation. The commonly used folate test actually mesures the amount of folic acid in the plasma. A high level can mean the body doesn’t metabolize it so it stays pooled in the blood. There is also a RBC folate test, and perhaps it measures folate rather than folic acid. The lab tests sites I looked at say folate and folic acid are essentially the same, perhaps explaining the confusion about what they’re actually measuring.

    A methylation pathways panel will accurately determine wheter a high folate level is due to the body being replete or whether it is because folate is not being metabolized.

    #2700 Reply


    I had some urinary tests done and the practitioner said that my B levels were excellent. However I am not sure if that was a methylation pathways panel.

    If the methylation pathways panel was good, would that mean that I would be unlikely to have an MTHFR mutation?

    #2701 Reply


    If it was the right methylation pathway panel, and the results looked good, then I would say you probably didn’t have a MTHFR mutation. The panel I’m talking about is a blood test offered by Health Diagnostics and Research Institute (formerly Vitamin Diagnostics) in New Jersey and in the Netherlands. It’s described here http://www.mecfsforums.com/index.php?topic=290.0. Doctor’s Data also offers a methylation test, but it’s not as complete.

    Can you find out more information about what kind of test you had? I highly doubt it was a methylation pathway panel.

    #2836 Reply


    Hi Lynn_M

    It was a Metametrix Organix Profile.

    #2846 Reply


    Most of what I write next is gleaned from Freddd and Rich’s posts at forums.phoenixrising.me.

    The organic profile has two methylation cofactor markers, methylmalonate and foriminoglutamate (sometimes referred to as Figlu). Methylmalonate is a measure of adenosylcobalamin sufficiency. Adenosylcobalamin is used to make ATP, the body’s energy molecule. Because it goes into the mitochondria and is therefore not subject to the same demands that are placed on methylcobalamin, it tends to stay at much more stable levels than methylcobalamin. If you read about the best way to test for B12 sufficiency, usually you’ll read about urinary methylmalonate as the best test, and it is certainly better than a serum B12. However, methylmalonate can be masked by other B-vitamin deficiencies.

    Furthermore, it’s only an indirect measure of methylcobalamin sufficiency. Methylcobalamin is used up at a high rate by the nervous system, and some of it will also convert to adenosylcobalamin, but I imagine that conversion rate is variable among people . There are four possible types of cobalamin deficiencies. The body can be deficient in methylcobalamin. The central nervous system (CNS) can be deficient in methylcobalamin. The body can be deficient in adenosylcobalamin. The CNS can be deficient in adenosylcobalamin. So your methylmalonate level is only an indirect measure of your methylcobalamin sufficiency.

    A high formiminoglutamate indicates low folate. Even if methylmalonate is not high, someone could still have a functional B12 deficiency, if they have a high formiminoglutamate and low pyroglutamate (which indicates glutathione depletion). Low-normal histidine, B2, and perhaps B6 can mask the Figlu marker.

    A high formiminoglutamate specifically indicates that the cells are low in tetrahydrofolate. If the methylmalonate is also at least somewhat elevated, that indicates a deficiency in B12 function. The combination of these two is usually a good indication of a partial methylation cycle block.

    A low VMA and HVA indicate problems with the neurotransmitters metabolism. Methylation is involved in neurotransmitters metabolism, so this would at least be consistent with a methylation problem.

    The main marker for loss of folates from the cells is figlu. An elevated sarcosine is also consistent with low tetrahydrofolate, and a high ratio of phenylalanine to tyrosine suggests low tetrahydrobiopterin, which would be consistent with low intracellular folates.

    I think some of those references are to amino acids, which may not be measured on your test.

    The Metametrix Organic Profile is not a methylation pathways panel, which would show more definitely whether you are methylating well or not. I think your test gives some indirect measures. However, it’s possible for other deficiencies to mask results and confuse interpretation. MTHFR can cause problems in the methylation and folate cycle and also impact neurotransmitters. If you don’t have symptoms of problems in those areas, then maybe you don’t have a MTHFR mutation.

    #3588 Reply

    Dolores Seames

    Can anyone interperate my blood test for folate? We asked for RBC folate.
    Folate, Hemolysate 400.0 ng/mL Not Estab.
    Hematocrit 40.0 % 34.0 – 46.6
    Folate, RBC 1000 ng/mL 499 – 1504

    I don’t know what Hemolysate is, or Hematocrit, and don’t know if any of these show levels for methylfolate.

    #3621 Reply


    “A low VMA and HVA indicate problems with the neurotransmitters metabolism. Methylation is involved in neurotransmitters metabolism, so this would at least be consistent with a methylation problem.”

    This is where I have all my ND’s stumped. I have had both high blood/urine Histamine levels. My recent OAT tests showed a need for Folate but had high normal VMA and very elevated HVA. Other urine test showed low Epinephrine, DOPAC and 5HIAA.
    So,on one hand high histamine, low Epinephrine and need for Folate/B12 shows undermethylation.
    But elevated VMA and HVA says to me overmethylation…or at the least no need for methylation since COMT cannot break down into those metabolites without methylation. (MAO breaks down to diff metabolites)
    I’m wondering tho, if someone where over-methylated, if they’d show high Serotonin but low 5HIAA because it’s being methylated to form Melatonin which would not create the metabolite 5HIAA. Thoughts?
    Seeing as I have low DOPAC and 5HIAA then obviously something is going on with my MAO. which is not a methylation problem, but I’m working on supplementing with the enzyme’s cofactors.

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