MTHFR with Elevated B12 and Folate


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  • #2862 Reply


    Has anyone had experience with MTHFR “AND” extremely elevated B12 “AND” Folate? The other curious anomaly is that I am also Iron Poor and when I receive my iron infusions and my Ferritin levels reach normal by elevated B12 and Folate count come back down. Anyone?

    #2863 Reply


    A number of people have reported on this forum that their B12 and folate are quite
    elevated. I just responded to Yurgh on 7/13 about this. There’s a learn a lot from reading prior forum posts.

    When you have MTHFR, your body can’t convert inactive forms of folate and B12 to the active forms. So the inactive forms just build up in your blood, and they inhibit the active forms from being absorbed and taken up by the receptors. Most serum folate tests are actually measuring folic acid, which needed to be converted to methylfolate to be used metabolically. The B12 test is measuring inactive and active forms of B12. There are better tests of how well your methylation and folate cyles are working, such as the methylation pathways panel.

    My speculation on your iron infusions causing your folate and B12 levels to come down is that iron is a cofactor in the methylation/and or folate cycle. If you don’t have sufficient iron, it could be causing a roadblock in the conversion process. Even with homo MTHF mutations, the body can still produce some of the enzyme MTHFR, it just does it at a reduced rate. So having good levels of iron apparently is speeding up your conversion rate.

    #2918 Reply

    LuAnn King

    I just found out that I tested positive for MTHFR and my Dr has left the country so I am unable to talk to her and she did call me in a script for Deplin but I am kind of scared and don’t know anything about this. I have over the years had severly high B12 ( one over 2000) and I always asked my Drs and noone ever said what could cause it to be so high.

    I take severval supplements but I am really confused now. I have CFS and fibromyalgia along with Chronic pancreatitis.

    I have been totaly down since April because I am so weak and fatigued. My hormones are all off so I don’t know if the MTFR causes that too. Would like to hear from others!! Thanks

    #2929 Reply


    B12 serum levels can be high in certain hematological malignancies, but also in people who can’t convert inactive forms to metabolically active forms. So the inactive forms don’t get used up and just build up in the blood.

    MTHFR mutations do impact hormones. Dr. Ben has a lot of articles and audio presentations under the ARTICLES tab. He has ample resources to help you understand what MTHFR is all about.

    Some people have trouble starting with the high dose that is found in Deplin. You might want to start with 1/8 tablets or even less and see how you feel for a few days. If you tolerate it okay, you can incrementally build up the dose. Also, anyone that takes Metafolin (the active ingredient of Deplin) should also be taking sublingual methylcobalamin. Without mB12, the additional methyl groups from Metafolin get lost due to a phenomenon called methyl trapping, so you lose out on the benefit of the additional methyl groups. Yes, even though your serum B12 is high, you probably don’t have enough of the active B12 form, methylcobalamin.

    Since you have CFS and Fibro, you might benefit from following this forum

    Most people that post there have CFS.

    #2931 Reply


    Hi LuAnn
    For a good basic overview, have you seen Dr Ben’s presentation yet – it’s here

    You’ll see that it can affect hormones too.

    #3384 Reply

    Taunna Jarvimaki

    Thank you for answering the question regarding elevated B12/Folate and having MTHFR C677T. I still do not understand how treating it with the high doses of Folate will not create an even higher amount of B12/Folate in my system. Also, is the low iron/ferretin considered a symptom of MTHFR as is the elevated B12?

    Should a person who has positive MTHFR results also be tested for Factor V?

    #3388 Reply


    HI Taunna
    I thought Lynn had explained pretty well, but maybe I can break it down a bit more.

    Folate is a family of vitamins, folic acid is just one of them. When your test tells you that you have an excess of folic acid, it is not measuring any of the others in the family – and it is not measuring the form ‘methylfolate’ which is the form your body actually uses in its biochemical processes, so you have no idea how much of that you may have.

    Folic acid gets in the way of your body using methylfolate, so since your body is unable to use it (due to MTHFR) you need to get the levels down by avoiding it completely in supplements and processed foods. Natural foods like leafy greens contain other forms of folate and should be ok for most.

    In the meantime, because your body needs the active methylfolate, and is not able to manufacture it, that is the form to supplement.

    Similarly with B12, again a whole family of vitamins and not just one. In this instance (going by what Lynn says above) the blood test measures the amount of the whole B12 family that you have. So you have no idea how much of that reading relates to, for instance, cyanocobalamin (the synthetic form, again found in supplements and best avoided if you have MTHFR)and how much may be the methylcobalamin that your body will actually use in its detoxifying processes.

    So, adding methylfolate will not affect the amount of folic acid that has been measured in your blood test as they are two different things. If you stop adding folic acid to the system (that your body can’t use) that reading will go down. If you add methylfolate then you are getting the right form that your body can use.

    I imagine that adding methylB12 will potentially increase the amount of ‘total B12′ in your system, but what you are adding will be the usable form that your body is crying out for. Again, stop taking in any cyanocobalamin, which is useless if not actually having a negative impact.

    I don’t know whether this will help make things clearer, but I hope so :)

    #3829 Reply


    Thank you for these helpful explanations!  I have a questions along the same lines and I want to see if I am understanding this correctly:  My recent folate, serum test showed a result of >24 ng/ml with a referance range of >5.4 being considered normal.  To me having >24 seems very high since one only needs a level of >5.4 to be in the “normal” range.  My B12 level was 969 pg/ml with a referance range of normal being 200-1100 pg/ml.  So I read this to mean that I have a high level of folate in my system but normal levels af B12, correct?  According to the previous explanation, it most likely means I actually have a high level of the synthetic form of folate, folic acid, in my system.  In which case I need to supplement with the correct form of folate that my body needs which is methylfolate along with the correct form of B12, methylcobalamin.  Does that mean that once I begin taking the proper form of methylfolate and methylcobalamin that my body will be able to detox correctly?  Do I need to do anything else to help my body detox perhaps BEFORE I begin taking these supplements Dr. Ben suggests?  If I truly have such high levels of folic acid in my system, shouldn’t I try to get rid of that first because I would assume that those high levels are actually hurting me????  I am heterozygous for the C677T mutation.  Any thoughts on this from anyone????


    #3851 Reply


    Synthetic folic acid is found in fortified/enriched foods (usually grains and processed foods) and in many vitamins. So check the labels on all your foods and vitamins and quit eating or taking them if the synthetic forms are found.

    If you need a replacement multivitamin, Thorne Labs Basic Nutrients line has the active forms of folate and B12 in it, and none of the synthetic ones.

    Your B12 is on the high end of normal. My naturopath often points out labs to me that are “normal” but on the high or low end of the range as being significant.

    Yes, once you get the right forms of folate and B12, you will start to detox, assuming other things aren’t also blocking methylation. So start low and go slow. As the toxins come out, you may feel worse, so keep it at a level you can tolerate. You can gradually increase over time as tolerated.

    #3864 Reply



    Thank you so much for your answer!  I ordered Dr. Ben’s Chewable Multi and have been taking it for about a week and a half now.  I’ve also stopped eating any foods with folic acid in them and am trying to reduce all gluten and dairy as Dr. Ben suggests.  I feel pretty good on the Chewable Multi, but have noticed lately that I’ve been a lot more “wired” and am awake until about 2 or 3 am every night! (I’m just not tired, even though I should be after a long day).  I don’t drink caffeine so this is unusual for me.  Could it be that my body is overreacting to finally getting the proper forms of methylfolate and b12?  You mentioned I should start slow, but I thought that Dr. Ben’s Multi would be a good start since I’m only heterozygous for the C677T mutation and Dr. Ben said the amounts in the Multivitamin should be sufficient for those with only one copy.  I also am on an antidepressant though at a low dose.  I take 50 mg of Zoloft a day.  Could the antidepressant be blocking or affecting the methylation process?  How does one know how much methylfolate and B12 to take while on an antidepressant?  I’m afraid to just stop my antidepressant because I’ve tried to wean off several times in the past and have always spiraled down to a really low spot, but eventually I would like to not have to take it anymore.  You mentioned that the detox process should start now as long as other things are not blocking the methylation process.  What other things could be blocking it that I should watch for?

    Again, thanks so much for you help!

    #5076 Reply


    This is really interesting because I have the C677T mutation and my ferritin is very low in spite of supplements and even trasfustions, and my B12 and folate have always been extremely high. When I started taking Riboflavin-5-Phosphate from Thorne the folate came down, but the B12 is still almost 2000. I eat very little meat (maybe once a month) and I don’t take any B12. I do get a lot of whole grains and vegetables, but that shouldn’t be pushing the levels so high. I am taking active folate now. I wonder if it would be a problem to take an active B12 when serum levels are still so elevated.

    #5629 Reply

    J Claire

    I have recently been diagnosed with the MTHFR C677T.
    My doctor doesn’t know anything about this and has made it clear she is not going to treat this in any way.
    My B12 levels are high. the first time I was tested they were about 100 over normal, but have now gone up and are around 2000.
    I stopped taking cyanocobalmin years ago, and am currently taking sublingual methylcobalamin. (1,000mg twice a day)
    My doctor watns me to cut this dose in half, because she is assuming I am taking too much.
    I think it’s either an absorption problem or something else is wrong.
    Can this be related to MTHFR even though I have been taking the correct form?
    Are there other health conditions that can cause serum B12 levels to test high over a period of years?
    Have been dealing with Lyme, CFS, and environmental toxicity that went undiagnosed for years, and am now on disability. Can’t afford a doctor who actually knows about this kind of thing, so any information or advice is appreciated greatly.
    Thank you so much.

    #6802 Reply


    Hi. I just found out I had the C677t mutation. I have had high b12 and folate for a while and never understood why. Any additional information would be appreciated. what type of doctor should I see to learn more about this? Feel free to email. Thank you in advance.

    #6810 Reply

    Martin C

    Hi Everyone,

    I know this is an old thread but I felt like adding a few comments.

    The ranges for B12 in north america are ridiculously low. People often get worried about a B12 level of 1100 because it was flagged as HIGH on the lab report, 1100 is not high. There are populations on the planet where this is normal, B12 levels due to their diet, and they are very healthy.

    Here’s my thought on it.

    (1) If you are supplementing for a known illness and want extra B12, I wouldn’t relax my B12 intake unless I exceeded 2000. B12 is extremely safe, in fact I don’t think there is any toxicity at pretty much any level. So when supplementing, don’t worry about B12 levels. For myself, I consider my levels as “the higher the better”.

    (2) If your B12 levels are high and you do not supplement… then this could be worth investigating if you feel concerned. B12 can be elevated in some pathologies, most of which can be ruled out with the following simple and inexpensive test:

    (a) Liver Function Test.
    (b) Renal Function Test.
    (C) CBC with Differential.

    That’s to rule out the diseases that can cause elevated B12. In this case, the elevated B12 isn’t a problem, but it is a symptom of something else.

    If a,b & c come back normal… as they usually will, then I would recommend a Methyl Malonic Acid (MMA) test. This allows you to diagnose a functional deficit in B12 despite a high plasma level. If your MMA is high, then you have a functional B12 deficiency DESPITE what your B12 levels are. In this case, you may want to supplement with MethylB12 of HydroxyB12… Consult your practitioner.

    Oh, I would never supplement with CyanoB12… Methyl or HydoxyB12 ONLY for me. I recommend to the same to others.

    On the topic of Folate and MTHFR… High Folate is often seen in MTHFR SNP’s. That’s perfectly reasonable since the enzyme (MTHFR) cannot convert the substrate (folic acid) into the product (methylfolate). You end up with a buildup of the substrate and a deficit in the product. In the case of MTHFR this is not good since the substrate (folic acid) is inactive. You therefore should supplement with the product (methlyfolate) which is the active form you need and isn’t getting produced by your deficient enzyme.

    So, YES MTHFR can/does lead to elevated levels of FOLIC ACID… and YES, you should supplement with methylfolate in that case. It’s not counterintuitive, it’s perfectly intuitive once you understand the methylation cycle.

    I would also recommend measuring your Homocysteine… you may likely find it high. Looking at your Homocysteine levels can be used as an indicator for your supplementation. I say that with hesitation because it is not the only indicator to follow, you need to conside the big picture… but it is still informative.

    Hope this helps,


    #7372 Reply


    Martin C, thank you for your post.
    I am homozygous C677T MFTHR. My homocysteine is normal, but folic acid in my blood test is high. I am wondering if there is a way to cleanse the system of it? I just now started a generic of Metanx (Vitacirc-B – do you know anything about it?). Will this help my body to get rid of excess folic acid build up? Or will it be circulating in my blood forever?

    #7390 Reply

    Martin C


    As far as I know the only way to reduce your serum folic acid is to strictly avoid foods that contain large amounts of bit.

    Things to avoid are some breakfast cereals, breads & pasta made from enriched flour, orange juice, sunflower seeds… I’m sure you can find a list online.



    #376381 Reply

    Lynn D

    My B12 and folate serum levels were high for last sevarl years, tested for MTHFR and ++.
    Was interesting about them coming down in person who got the iron she needed.
    Am in a oxalate group that is lowering for health reasons and the Phd there said that
    B12 might be used up dealing with sulphites and not have enough for normal activity and that
    sulfites lower thiamine. Some have found that thiamin deficient and once taking that , their
    serum folate levels go to ” normal”. Read that we rid by urine of unneeded folate but others stated that its not good to
    have high levels , gets confusing
    Thanks for all the info

    #377139 Reply


    I am new to this community. Hi! :) I have homozygous MFTHR (I received one gene from my mother AND one from my father, but I’m not even sure of the strand (C677T? maybe?). I just received some test results back… any help would be greatly appreciated! Thank you in advance!

    Homocysteine 8.9
    Folate 21.5
    B12 542

    #377860 Reply


    Just found out that in the last 6 months, my b12 went from 1000 to >1500. I use a methl b12 spray that works really well, but I have only been using it once every 1 or 2 weeks. Could that have raised it that much in such a little amount of time? Should I stop using the spray, keep it the same, or increase the use? I’m heterozygous A1298C

    #378246 Reply


    I have a couple of questions and am in need of some guidance. About 6 or 7 years ago I was told I had a B12 deficiency level was 260. I was started on b12 injections my levels came up to 500. I was feeling good and stopped the injections. My folate levels started at 13 then went to 14 then rose to >24 and have remained there even with me stopping the B12. My doctor just recently told me and I started to feel some of the same old symptoms that I should never have stopped the B12 injections and he drew new lab work. My B12 was normal at 450, my MMA level was acutally low at 65, but my folate was still > 24 and now my homocysteine level is elevate at 12. I am wondering if any of this means I have a deficiency and need to take the supplements again or if everything is actually normal. Can someone with some educated intellengence in this area assist. I am waiting for my doctor to make a decision on what to do one recommended the b 12 injections again and the other did not. Thanks

    #378371 Reply


    Bacteria in your gut can convert the B12 in your food into B12 analogues. I suspect the standard tests for B12 counts these analogues as part of the total available B12, when that is not true. For some unknown reason, the B12 found in the blood can be adequate, while at the same time the B12 in the spinal fluid can be low.

    High folic acid is sometimes observed in cases of small bowel bacterial overgrowth (SIBO). I don’t know if this is because bacteria can make folates, or if it is because the folic acid in the diet is not being used.

    #383091 Reply


    Hi, I know this is an old thread and I am hoping that someone can help me with this bc this is so frustrating and scary and im nervous about it all. Over 3 years ago. Feb. 7, 2011, I came out of a spinal cervical surgery with 22 symptoms that are here 24/7, including seizures and tremors. I was tested for everything. So they put it off as a Functional Neurological Disorder(FND) or Conversion Disorder (CD). It all mimics MS., which they say i don’t have. I have a Homozygous MTHFR C677T. My B12 levels are climbing by the year. My medical Psychologist says that my body is storing my B12. That they are not being released. My neurologist says its ok. I told him with all of my problems, I want him to test me for anything and everything. Even my rdw blood level is higher. He is going to test me for everything. Im just really nervous. I have enough on my plate with this Fnd/cd diagnosis that im not 100% sure if that is what it is, and there is no cure. Just treatment. B12 blood tests Jan2012- level 1006 Aug 2012- level 1643 May 2014- level – way over 2000. Folate 19.9 Here it is June 2014, I still have all of my symptoms. Is this FND or is this aomething else?

    #383483 Reply


    Hello, I went off the protocol a year ago. I have been feeling sick, so I had several tests taken: CBC and liver functions ok (slightly off BUN/Creatinine ratio with normal BUN and Creatinine). Thyroid normal, slightly low iodine level. I ran a B12/Folate test: B12 about 2000, folate within normal. I suspect the B12 is a MTHFR problem (I am homozygous C677T). My real question: Wouldn’t my folate be high also if it were MTHFR? Thanks very much!

    #383574 Reply


    My six year old daughter has seizures, delay and alacrima (lack of tears) doctors are stumped. She has an extremely high folate and b12 count. Could it be MTHFR?

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    #496759 Reply

    Cathy chahalis

    I have mthfr c and a mutation. My b12 level has been 2000+ for yrs and high folate. I have too many serious health problems to list. I have taken methlcobalin by injection for yrs as well as b- complex shots and stopped about 1 yr ago with no change in levels. I have been worried about cancer but glad to have mthfr for an explanation instead

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    Tacrolimus is chemically known as a macrolide. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to get started calcineurin. Calcineurin then dephosphorylates the transcription factor NF-AT (atomic aspect of activated T-cells), which moves to the pith of the T-cell and increases the motion of genes coding to save IL-2 and related cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.[8] In detachment, Tacrolimus reduces peptidyl-prolyl isomerase occupation at hand binding to the immunophilin FKBP12 (FK506 binding protein) creating a fresh complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocytesignal transduction and IL-2 transcription.[9] Although this action is similar to ciclosporin, studies take shown that the occurrence of shrewd repudiation is reduced by tacrolimus exigency execrate done with ciclosporin.[10] Although short-term immunosuppression with an eye to submissive and scion survival is found to be similar between the two drugs, tacrolimus results in a more favorable lipid portrait, and this may acquire important long-term implications accepted the prognostic affect of denial on implant survival.[11]
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