MTHFR Screening

Question from a colleague:
Hey how’s it going. I have been trying to read all your stuff on MTHFR. but I am missing something. Is the first screen process getting a homocysteine level on all patients or just ones with depression, strong family hx of cardiovascular disease, etc. thanks

Not all those with MTHFR mutations will have an elevated homocysteine level – especially those with heterozygous mutations, taking supplements and eating well.

Screening for MTHFR is not set in stone and there is no set protocol out there as it is not on the radar yet. I believe it needs to be.

Patients that I recommended screening 100% for MTHFR mutations:

  • Pre-conception care: test both man and woman
  • Mental dysfunction including but not limited to depression, anxiety, irritability, mood swings, schizophrenia, bipolar
  • Infants and children of parents with MTHFR mutations
  • Family members related to someone with MTHFR mutations
  • Elevated folate (not processing to active 5-MTHF due to inability to methylate)
  • Elevated homocysteine (due to low active 5-MTHF and methylcobalamin)
  • Elevated s-adenosylhomocysteine (due to low active 5-MTHF and methylcobalamin)
  • Elevated serum cobalamin (due to inability to methylate cyanocobalamin to methylcobalamin)
  • Elevated methylmalonic acid (due to methylcobalamin deficiency)
  • Patients with syndromes: IBS, Chemical sensitivity, Fibromyalgia, Down Syndrome, Chronic fatigue syndrome
  • Neurological disorders: Multiple sclerosis, Autism, Alzheimer’s, Epilepsy, Parkinson’s to name a few
  • Cancer: family history of cancer or undergoing cancer treatment
  • Cervical dysplasia
  • Infertility
  • Cardiovascular risk: family history of strokes, embolisms, heart attacks, clots, essential hypertension
  • Birth defects: cleft palate, tetralogy of Fallot, spinal bifida, midline defects
  • Drug sensitivities: methotrexate, anti-epileptics, nitrous oxide, anesthesia

Here is a list of conditions potentially caused or worsened by MTHFR 

Now is this being overly cautious and over-the-top?

In my opinion, no.

The genetic testing for MTHFR mutations of 677 and 1298 costs only $150 – $200 and is often covered by insurance.

$150 to $200 is very inexpensive compared to a life of unresolved symptoms, mental anguish or worse – miscarrying a child.

Just a few years ago, vitamin D3 deficiency was not on the radar. It was not being tested for and countless patients and individuals were suffering needlessly from an increased risk of:

  • Fractures
  • Osteoporosis
  • Depression
  • SAD
  • Cancer
  • and others…

Now, patients and indidivuals are paying around $60 for vitamin D3 blood testing to monitor their levels – and they are ordering this test once or more each year.

A MTHFR genetic test is ordered ONCE in a lifetime.

I do recommend that a tag-along blood test be ordered and that is the Methylation Profile by Doctor’s Data.

UPDATE September 9, 2012:
I am now recommending a more comprehensive Methylation Pathways Panel as it measures a variety of folates, SAM, SAH, glutathione and some other markers.

This test along with the Methylation Profile by Doctor’s Data can provide insight how your methylation is doing.

If you need to choose one, then I recommend the Methylation Pathways Panel as you will obtain more information from it compared to the Methylation Profile by Doctor’s Data.

This helps guide nutrient recommendations and avoid the ‘guessing game’ of how much 5-MTHF to give and how much methylation support is needed.

We physicians know that excessive methylation may lead to cancer. We also know that hypomethylation can lead to cancer.

That said, it is very important in my mind to monitor the MTHFR mutation therapies by using the Methylation Profile.

Many doctors think that if an indidivual is not expressing any symptoms or signs of MTHFR defects and their homocysteine is fine, no lab testing is needed and no supplementation changes are needed.

I fully disagree.

Given the prevalence of the MTHFR mutations, over 50% for heterozygous A1298C (need source – saw it recently), I am adamant about testing for MTHFR mutations in pre-conception care.

Also, in terms of effective supplementation for the general public:
It is easy to give a prenatal or additional supplements with the active 5-MTHF, L-5-MTHF and active methylcobalamin – so why not do it for everyone – regardless if they have MTHFR mutations or not?

I look forward all of your comments.

This is a discussion that must be had and we cannot have a discussion without your input – so please – provide your twenty-five cents.

In health,
Dr Ben

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19 Responses to “MTHFR Screening”

  1. Hans Rudolf September 29, 2011 at 1:41 am # Reply

    Again and again … thanks Dr Ben!
    I lost one of my brother Peter 1957 stroke with 7 years and a other brother Jörg days after birth!
    .. and we have the MTHFR mutation and Factor V Leiden in our family!

  2. Cindy October 30, 2011 at 7:02 am # Reply

    Dr. Ben,

    I am so glad to have found this website! I have been researching what I can on MTHFR. My son is compound heterozygous for the C677 and 1298, and has many neuro challenges, all of them manifesting sometime after surgery at 10 months where he received Nitrous Oxide! (3 hour surgery) We always have told medical doctors/therapists about the change after surgery, and it means nothing to them. Now I have validation that the surgery was a trigger, and now I know why. He is 7 now. After researching MTHFR and deciding it sounds like something my son/relatives may have, I requested test from his neurologist, who looked at me like I had two heads! She finally relented, and we got the test and results. She was flabbergasted, and then sent us to a geneticist..who unfortunately was useless, and again dismissive about MTHFR relating to my son’s issues. I was teaching him more about it than the other way around. I requested and got visit with an RD, who also didn’t even want to discuss treating him with higher than 400mcg of folic acid, (RDA) and didn’t really even want to talk about our MTHFR test results..she also knew practically nothing. So, we have been left with crucial (I feel) information to help my son, and no one to guide us. I can do it myself, but I need more info/support/knowledge. My question now, is: what products are safe for kids? Active form of folate, which brands? I have written down to test for Factor V Leiden, Methylation Profile, Hcy levels, and maybe test folate and B vitamins by urine? I had his blood tested for these, and they were normal…but he seems to be a severe case of MTHFR, when I read the description. Even the RD told me that serum tests for those can be inaccurate. Also, where can I learn more about what makes a case of MTHFR a severe case of MTHFR, or is it just clinical signs of mostly neurological/motor dysfunction? Thank you for info!!!


    • Dr Ben November 1, 2011 at 6:24 am # Reply

      Hi Cindy –

      I am so sorry you are yet another person – and your son – that is left out to dry due to a complete lack of understanding MTHFR.

      I don’t get it. How can they not understand the seriousness?

      Your son obviously cannot handle the nitrous oxide (I must write an article why here and issue a warning).

      MTHFR is way more than homocysteine and that is what doctors do not get. It is also way more than just pushing high dose folate onto someone.

      The more I learn about MTHFR, the more I learn how other mutations are amplifying the problem.

      Your son having compound heterozygous MTHFR mutation is serious and I am glad you found that he has it – now you can address it.

      Homocysteine is a very difficult thing to measure as it is very unstable; but, I emphasize – it is way more than simply homocysteine.

      Those with compound heterozygous are more prone to blood clotting and toxicity. Both of these can lead to neurological symptoms.

      The more I learn about MTHFR mutations, the more I realize the things which improve the individual are exactly that – individualized.

      I wish there was a cookie cutter approach and simply say:
      - Take 1 mg of 5-MTHF
      - Take 50 mg of Nattokinase

      But I cannot.

      I am due to write another article here on MTHFR but I’ve been inundated with consults the last few weeks – which is great – but it does prevent me from helping others via a new article and video.

      I will make a point to make my next article here about nitrous oxide and MTHFR. We must get this fact out there.

      I am available for consults on a one-on-one basis. Your son doesn’t need to be present for it but I will send over some questions for you. These Q & A provide me a lot of useful information prior to the consult which allow us to focus more in depth and get to the heart of the matter more quickly.

      You may obtain consult minutes here along with scheduling a consult.

      To answer your question what makes a MTHFR mutation more severe, that I can answer quickly:
      - dietary choices
      - lifestyle
      - environmental exposures
      - in utero exposures
      - additional genetic mutations
      - additional epigenetic factors activating/deactivating genes
      - bacterial/viral/parasitic infections
      - co-infections

      All these contribute to a more severe expression of MTHFR mutations.

      One can have a compound heterozygous MTHFR mutation and be absolutely fine and living a very healthy normal life while another may be suffering immensely. It is all relating to how the individual’s life is led and the environment affects them on a daily basis.

      Those carrying the A1298C are more likely to present with neurological and motor dysfunction. The reasons are complex and have to do with toxic metabolites and the reduced capacity to eliminate/detoxify.

      This is why one on one consults are needed.

      I do all I can to provide useful information at no cost but there are times when that is not possible – nor wise to do.

      I would love the opportunity to help guide you a bit so you can take the reins more with your son.

      My goal is to empower people with MTHFR so they can make appropriate choices and understand what to look for – and what not to.

      Helping people overcome their symptoms is definitely right up there as well – there is nothing better than hearing something like this:
      “On the advice of a friend I met through a Pulmonary Embolism support group, I contacted Dr. Ben. Not only did he take the time to explain what MTHFR was and how it was affecting my body, he insisted that I understand that how I was feeling was temporary: that I would improve if I started getting the nutrients needed. Only one month earlier, I was told by a specialist from Yale that I would die prematurely, and he even went as far to detail how the pathologist would discover the fatal clots in my lungs or brain during my autopsy. At that point, I had already started Dr. Ben’s regimen to treat my MTHFR and depression-thankfully. I began feeling better in weeks. If I hadn’t died yet, I might as well give this a chance. After 34 years of unexplained illnesses and never having felt “happy”, I found a balance-and hope that I could finally overcome my depression, and that “my condition is not my conclusion”. I can’t say I feel better than ever-I never felt good. I have not a better life, but a new life. Dr. Ben’s medical knowledge is astounding-hundreds of physicians I had seen knew nothing about MTHFR, nor anything about treating the CAUSE of my depression. Each and every time I eat, I now look at food and supplements as a chance to heal even more. I am now functional for the first time ever. I’m finally alive. I owe this life to Dr. Ben. For those of you that have ever struggled with illness and have been let down by your physicians, “non illegitimi carborundum”. Here is your answer.”

      Awesome. I’d love to receive a letter like that regarding your son!

      In health,
      Dr Ben

  3. Sara Clark December 14, 2011 at 8:03 pm # Reply

    Dr. Ben, my husband who is 67 yrs old has the c677t & A1298c mutation. Weekly he is injected intraveniously with 3000 millegrams of GSH/NAC. This has stopped any tremors he had, which were slight. He also is taking Deplin once a day and B12 shots every 3 days. I ordered from you the Homocystex but he started tremoring again and had the masky face. I was told I was overdosing him because he was still on Deplin. Can you help us?

    We have gone to a neurologist, thinking he may have Parkinson’s, because it is a symptom driven disease they did not as yet give us a conclusive answer – as he passes all the physical tests given. He definitely is slower than he should be at his age, wondering if there is anything else we could be doing to help him?

  4. Charles December 19, 2011 at 3:49 am # Reply

    Dr. Ben —

    Have dealt w/ depression since my 20′s. Also migraine headaches (classical) which remitted as per normal circa age 52. Depression is variable: mild – moderate. 2 episodes of major depression each lasting 2-3 months, responsive to support and anti-depressants. I am a highly functional executive, although my effectiveness at work (and to a degree generally) is hampered by the fatigue, and emotional sequallae of the depression. Currently taking some zoloft, wellbutrin and a lamictal chaser. I tolerate these meds well, and am not on super high doses.

    Just recently had the MTHFR screening, with pos results — mutations are C677T and A1298C. I am in good health, and can be pretty active in sports and recreation when I have the strength, stamina and interest (all of which are variable). I have never had elevated homocystine levels except 1x on a routine blood screening (for my yearly physical). On repeated blood tests, it was not found again.

    I am going to start on Deplin 15mg.

    I’ve read, with interest, your website and your impressions. It was primarily your material that prompted me to get the genetic testing — and I thank you.

    I’d be interested in any impressions you have of my situation.

    • Dr Ben December 20, 2011 at 8:52 am # Reply


      Thank you for posting a comment and sharing your story.

      I’m glad that prompted you to get tested – that is excellent and makes my insane hours working here worth it.

      I do not agree with Deplin 15 mg for compound heterozygous – in fact, I don’t agree with Deplin 15 mg period. But that is my opinion and I do know some people find excellent results with it.

      I have many reasons why I am not a fan of high dose methylfolate alone but the biggest one is that one needs to have methylcobalamin with it otherwise the methyl in methylfolate gets ‘trapped’ and cannot get off. This makes the methylfolate worthless and not able to do its job.

      Some with A1298C mutations do not do well with methylcobalamin – there are numerous reasons for this but one is you may detox too quickly.

      If you find yourself becoming agitated, you may be taking too much methylfolate. If that is the case, talk with your doctor about switching to Deplin 7.5 mg.

      • Charles December 20, 2011 at 2:48 pm # Reply

        Dear Dr. Ben –

        Tnx for your prompt reply… you really have a palpable commitment to your readers/followers.

        I also have had some concerns re: an overflow/overproduction of serationin with the 15mg of Deplin. I had actually be planning to dial back the other meds (via titration), and plan to be very cautious about monitoring any signs of seratonin syndrome. I’m very aware that the SSRI and SNRI reuptake inhibitors + the Deplin may cause a surge. I’m expecting that it will. For this reason, my plan is to back off Zomig (from 100 to 50 mg), Wellbutrin (300 to 150 SR), and the Lamictal (200mg to 100mg). I plan to stabilize on this regime before adding the l-mythlfolate. I also plan to initiate the deplin @ 7.5

        I should mention that I am a medical professional, and based on my response may well consider this protocol for for other appropriate candidates.

        I will certainly look in to considering the methylcobalamin — I will need to get up to speed on this as a catalyst.

        Thanks for your suggestions, and I will report back to you with results as they occur


        • Dr Ben December 20, 2011 at 8:17 pm # Reply

          Charles –

          Great points and sounds like you are on it.

          I am thinking that you will respond quite well to the methylfolate given your mutation.

          There are other compounding mutations that may be present; thus, if you find you get worse or no improvement, it may be because of environmental toxicity blocking the other enzymes from functioning and/or these enzymes may be mutated (COMT, CBS, DHPR, MAO A, MTR to name a few).

          If this is the case, let me know. I am working with a genetics lab that will be covering these mutations on a new SNP panel. Once ready, I will put you in touch with the lab so you can offer it to your patients – I highly recommend it over simply testing for MTHFR. Disclosure: I receive no monetary benefit – only consulted with them on which SNP’s to use.

          If you research the ‘Methyl Folate Trap’, that will explain how methylcobalamin works as a required nutrient in order to utilize the methyl from the methylfolate. Basically, methylfolate lowers homocysteine by converting it to methionine. This happens by two enzymes: MTHFR and MTR. Methylfolate donates a methyl group to homocysteine in order to become methionine. This reaction is methylcobalamin dependent.

          This paper is quite good and provides a diagram of how methylcobalamin and methylfolate work together in converting homocysteine to methionine. Keep in mind that lowering homocysteine is not the only factor here because methylfolate is also required in the production of SAMe, adenosine, ATP, DNA/RNA, neurotransmitters to name a few.

          Consider testing your ammonia levels along with peroxynitrite, RBC methylfolate, super oxide, neopterin, biopterin, MMA and the amino acids via an amino acid profile.

          I look forward to your results and input.

          If you discover anything, please do share!

  5. Amy June 5, 2012 at 5:31 am # Reply

    I have a 3 year old soon who was diaginosed with Autism PDD-NOS.. I recently got the result back on genetic testing to find out his MTHFR A1298C GENE MUTATION: DETECTED – HETEROZYGOUS but the MTHFR C677T GENE MUTATION: NOT DETECTED what does that mean and should I look into anyspecial foods, vit etc

    • Dr Ben June 5, 2012 at 5:43 am # Reply

      Hi Amy –

      This means your son has 1 copy of the MTHFR A1298C mutation. This is not very significant.

      He likely has other mutations causing issues – such as MTR/MTRR, CBS, COMT, GAD1, GSTM1 to name a few. However, don’t get stuck on those right now. There is a lot you can do without knowing these genetic mutations.

      A 1/4 tablet of Sublingual Active B12 with Metafolin placed in his mouth first thing upon rising in the morning may help him a bit.

      There are plenty of other things which may support him as well:
      - probiotics
      - gut healing
      - gluten avoidance – completely
      - dairy avoidance – completely
      - protein every couple hrs with some form of healthy carbohydrates and veggies

      A chewable multivitamin may be useful as well – consider 1/2 tablet of Optimal Multivitamin Chewable after breakfast and 1/2 tablet after lunch.

      Have his doctors check his:
      - serum ferritin
      - MMA
      - TSH, T3, T4

      • Amy June 6, 2012 at 1:54 am # Reply

        Hello Dr Ben
        Thank you for answering me back – This was some of the blood work I have alot more if you have a email I can send it to you as a attachment.
        I so far have but him on the
        GFCF diet
        He takes agape as a multi vit, glutathione, calcium/magnisium and probiotics every day. I am trying to do everything I can.

        Test Result Abnormal Reference Units Previous Result Date

        EOS 0.7 0.0-4.1 %

        BASOS 0.3 0.1-0.6 %
        MMATURE GRANULOCYTES 0.1 0.0-0.8 %

        Platelet Count 566 HI 202-403 x10(3)/uL

        MPV 9.2 9.0-10.9 fL


        FERRITIN 58 See Below ng/mL
        Range (ng/mL)
        Newborn 25-200
        1 mo 200-600
        2-5 mo 50-200
        6 mo-15 yrs 7-140
        Male 22-322
        Female 10-291

        NOTE: Effective 2/7/2011, the reference ranges for FERRITIN have been changed.

        E.SEDIMENTATION RATE 18 <21 mm/hr

        VITAMIN B12 1223 HI 211-911 pg/mL

        SELENIUM,SERUM (30) 154 23-190 ug/L

        ZINC, SERUM 87 68-161 ug/dL

        25OH, VITAMIN D 30.4 LO 32.0-100.0 ng/mL

        VITAMIN C 11.6 2.0-20.0 mg/L

        VITB1,THIAMINE,FREE 26.3 HI 2.7-13.3 ng/mL

        VIT.B6,PYRIDOX.PHOS 22.3 5.0-50.0 ng/mL

        VITAMIN A, SERUM 39.9 30.0-75.0 ug/dL

        ALUMINUM,SERUM 10 HI <9 ug/L

        Thank you so much Amy

      • Amy June 6, 2012 at 2:08 am # Reply

        Clinical Abnormalities Summary: (May not contain all abnormal results; narrative results may not have
        abnormal flags. Please review entire report.)
        HCT 38.2 HI MCV 84.1 HI
        ——-* CHEMISTRY *——–
        Test Result Abnormal Reference Units Previous Result Date
        Iron 138 45-160 ug/dL was 154 11/02/2011
        ——* HEMATOLOGY *——–
        WBC 11.68 5.14-13.38 x10(3)/uL was 10.43 11/02/2011
        RBC 4.54 3.89-4.97 x10(6)/uL was 4.16 11/02/2011
        HGB 12.7 10.2-12.7 gm/dL was 11.7 11/02/2011
        HCT 38.2 HI 31.0-37.7 % was 34.4 11/02/2011
        MCV 84.1 HI 71.3-84.0 fL was 82.7 11/02/2011
        MCH 28.0 23.7-28.3 pg was 28.1 11/02/2011
        MCHC 33.2 32.0-34.7 gm/dL was 34.0 11/02/2011
        RDW 14.6 12.5-14.9 % was 14.0 11/02/2011
        POLYS 47.1 22.4-69.0 % was 35.5 11/02/2011
        LYMPHS 45.7 18.4-66.6 % was 57.0 11/02/2011
        MONOS 5.8 4.2-12.2 % was 6.4 11/02/2011
        EOS 0.9 0.0-4.1 % was 0.7 11/02/2011
        BASOS 0.3 0.1-0.6 % was0.3 11/02/2011
        IMMATURE GRANULOCYTES 0.2 0.0-0.8 % was 0.1 11/02/2011
        Platelet Count 367 202-403 x10(3)/uL was 566 HI 11/02/2011
        MPV 10.0 9.0-10.9 fL was 9.2 11/02/2011
        —–* MISCELLANEOUS *——
        FERRITIN 36 See Below ng/mL
        Range (ng/mL)
        Newborn 25-200
        1 mo 200-600
        2-5 mo 50-200
        6 mo-15 yrs 7-140

        IRON, % SAT. 45 20-55 % was 57 HI 11/02/2011
        TIBC 305 228-428 ug/dL was 270 11/02/2011

        Sorry This is the updated one. Once again thank you for helping me I look foward into hearing what you think after you see the results I have sent. Look foward thank you so much

  6. Lynne July 21, 2013 at 3:48 pm # Reply

    Hi Dr. Ben,

    My daughter and I recently received our 23andMe results and as I looked into the results I eventually stumbled upon your site! Turns out she is homozygous for

    MTHFR C677T
    MAO A R297R
    MTRR A66G
    BHMT 8
    CBS C669T

    And heterozygous for
    COMT V158M
    COMT H62H
    COMT P199P
    VDR Taq (TT)
    BHMT 2
    BHMT 4
    SHMT C1420T

    It sure sounds like this could explain her depression, anxiety and ADD!

    I’m homozygous

    COMT V158M & H62H
    MAO AR297R
    MTRR A66G

    and hetero for 10 others in the series … so I’m excited to find out more for myself as I’ve
    struggled with ADD type issues since I was a kid and lately depression and low energy.

    But my main questions is, do you know if any research is taking place on the west coast (maybe UCSF? that we might be able to participate in? My daughter is in school and I’m unemployed so I figure that may be one way we can address this.

    I also have a long-time friend who has been struggling with bipolar depression for over 30 years….and this gives me some hope that I might be able to help her too… do you know if anyone in the SF Bay Area Kaiser Permanente system is onto this?

    It’s so good to have some hope!


  7. Tiffany Youngren September 20, 2013 at 2:23 pm # Reply


    My husband just tested positive for MTHFR, so we are early on our journey of testing and therapies.

    The initial test cost us over $300 (and we have bee told it may cost more for our daughter). Is there some trick to getting it closer to the $150-200 you mention a couple of times on your site?



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Conversation Between Two Doctors on MTHFR

Comment from a colleague of mine from a forum: Hello Ben, We cannot go overboard about MTHFR gene mutations. It's just one...