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MTHFR and the Genetic Mutation That Could Be Affecting Your Migraine Treatment

MTHFR is the official symbol for a gene called methylenetetrahydrofolate reductase (NAD(P)H). This gene instructs the body to make an enzyme, methylenetetrahydrofolate reductase, which is involved in converting certain B-vitamins  into a form the body can use. The body then uses the converted vitamins in a multi-step process that eventually leads to the formulation of proteins and other vital compounds, including the neurotransmitters dopamine, serotonin, and norepinephrine.

A genetic mutation on this gene makes it difficult for a person to metabolize and use the B-vitamin Folate normally, especially the form of Folate most commonly added to foods: Folic Acid. The mutation also has been linked to a number of chronic and acute health conditions (though it is worth noting that not everyone with the mutation will experience any or all of these conditions):

  • myocardial infarction,
  • stroke,
  • venous thrombosis,
  • certain cancers,
  • congenital defects, especially neural tube defects and congenital heart defects,
  • inflammatory bowel disease,
  • Crohn’s disease,
  • Ulcerative colitis,
  • Parkinson’s disease,
  • Alzheimer’s disease,
  • Bipolar disorder,
  • Depression,
  • Anxiety,
  • Epilepsy, and
  • Migraine with aura.

Estimates vary, but many researchers believe about 50% of the population has some form of this mutation. I’m one of that 50%, though I had no idea the mutation even existed until my current neurologist asked if I had ever been tested for it.

When my results came back positive, several things changed. I started reading up on the mutation and realizing how significant the MTHFR enzyme is to our overall health. I started talking about the mutation with my family members and urging them to get tested. I started taking a very specific supplement that includes large doses of already methylated versions of Folate (5-MTHF) and Vitamin B-12 (methylcobalamin), and I started getting weekly methylcobalamin injections from my neurologist. I also started feeling better.

Though my neurologist warned me that supplementing with methylated versions of Folate and B-12 wouldn’t necessarily have a direct impact on my migraine, it seems to have had exactly that. This could be happening in a number of ways.

First, our bodies use methylated Folate to create the neurotransmitters that many of our migraine preventatives rely on to make us feel better. An antidepressant like amitriptyline, for example, which affects mood and migraine by preventing the reabsorption of serotonin in the brain isn’t going to have a strong effect on us if we aren’t creating enough serotonin in the first place. By giving our bodies the methylated version of the key vitamins we need to make serotonin and other vital compounds, those of us with the mutation are actively treating a very real deficit that is affecting our overall health. (Side note: My anxiety and depression, both of which are correlated with abnormal levels of serotonin and other neurotransmitters AND with the MTHFR mutation, have gotten significantly better since beginning this supplemental treatment.)

It might also be that by taking the supplements I am avoiding a chemical that was a secret trigger for me. Prior to supplementing with the methylated versions of these chemicals, I craved bread, cereal, and other foods fortified with folic acid. This may have been my body’s attempt at getting the Folate it needed for optimum health. Unfortunately, because of the particular version of the MTHFR mutation that I have, I cannot process Folic Acid very well. Attempting to do so may have been setting off a chemical process that triggered my migraines. Now that I’m taking the supplements, my appetite has significantly decreased and my cravings for these foods have all but disappeared completely.

Regardless of the exact mechanism, since beginning the treatment two months ago, I’ve noticed a sharp reduction in both the intensity and the frequency of my migraine attacks. I’ve also noticed that my aura and vertigo – often two of the most debilitating aspects of my illness – have significantly diminished. This improvement also went away (and my migraines returned with a vengeance) when I temporarily stopped the B-12 injections. Taken together, this makes me believe that these supplements are having a direct, preventative effect on my migraine disease. Whether or not this is actually true, I’m going to keep taking them.

If a look at your symptoms or family history makes you suspect you may have a version of the MTHFR mutation, ask your doctor about getting tested. It’s a simple blood test that most labs can preform, and the results don’t take long to come back. Mine was also covered by insurance, as are my B-12 injections (which are now considered medically necessary).

Those of us with migraine are constantly searching for something, anything we can do to feel better. I’ve stumbled, happily, on this. I hope at least some of you find the same relief from it as I have.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.


  • suzcollier
    2 months ago

    I was found to have MTHFR heterozygous 5 years ago, after the birth of my daughter left me with a DVT and postpartum anxiety. I have been encountering many symptoms that are common with this gene mutation, but NOBODY knows about MTHFR! I brought it up to my doctor in an effort to seek treatment, both for migraines and ice pick headaches, in a way that would take the MTHFR into consideration and she was so miffed that she wiped my appointment from the books so that I wouldn’t be billed! I need to find a doctor that knows about the mutation but I have no idea how to go about doing that. Any advice?

  • jojobaggins
    3 years ago

    I recently tested positive for the MTHFR gene mutation. My neuro (highly regarded in the field of migraines) also tested my homocysteine levels, and they were normal. If they had been elevated, that is a sign that supplementation is needed, because high homocysteine correlates with some bad cardiovascular stuff like atherosclerosis and blood clots.

    Since my homocysteine is normal, he changed his mind about having me take methylated forms of folate, pyroxidine and B12. He said taking folate long term can also be problematic. He said that we are not going to treat me for the mutation.

    My migraine diagnosis is episodic migraine not intractable without aura. Just mentioning all of this here in case it helps someone.

  • dlbecker217
    2 years ago

    How long were you on the supplements before you saw an improvement? I recently found out I have the mutation and was given the methylated folate (1mg a day) and methylated B12 (1mg) a day. I also have been taking a bunch of other supplements for a long time now.

  • Sarah Hackley moderator author
    2 years ago

    It was about 90 days for me, I think, which is about standard for any supplement or new medication. I hope that helps!

  • Sarah Hackley moderator author
    3 years ago

    Many of us with the mutation have different recommendations for treatment. The human body is so diverse! I’m glad you’re working with your doctor to learn what’s right for you. My homocysteine levels also are normal, which is common for the version of the mutation that I have. However, my doctor still recommended that I treat with supplements. Personally, I find I get along much better with supplementation than without, but again we are all so different. One of our other regular writers here on had a horrible experience with supplements. That’s why it is so essential to discuss any treatment, including supplements, with our doctors. Thank you for sharing!

  • Tate
    4 years ago

    This is very interesting stuff. I ran across a website run by Dr Ben Lynch who seems to be quite the expert in MTHFR. I have the supplement but I’m hesitant to take it based on some of the things on his site. I should probably go ahead and get the 23andme DNA testing done and run it through one of the analysis sites and verify the condition exists in me.

    I purchased some Boost Oxygen cannisters from Sporty’s pilot shop and they seem to help when I’m in the premigraine phase.

    But ultimately I’d like to see if the MTHFR is the real problem.

  • Sarah Hackley moderator author
    4 years ago


    Thank you for reading and commenting. I’m one of the ones that the MTHFR supplements have truly helped. Others of us, like Kerrie, experienced horrible side effects from taking the supplements. It’s always important to talk to your doctors about anything you’re thinking of trying to help make sure it’s the right thing for you.

    Warm regards,


  • Lifeguide
    5 years ago

    A new prescription supplement on the market is Enlyte with all of the L methylfolate and cofactors to aid migraine sufferers. When a MTHFR polymorphism causes homocysteine levels to rise then migraine is more likely to take place. This has all the B vitamins plus all of the folates necessary to lower homocysteine.

  • bureinato
    5 years ago

    Thank you for posting about this, I’ve gotten myself tested and it just came back that I’m compound heterozygous. Which means I now have new things to try. I’ve been in a “been there tried that” rut for a while now. I’m happy to be a mutant because it gives me something quantifiable to work with.

  • Mary B
    6 years ago

    Can someone please tell me the exact brand and the daily amount of these supplements to take? My neurologist does not know about this treatment. Thanks

  • Nancy Harris Bonk moderator
    6 years ago

    Hi Mary,

    The thing about this supplement is that taking too much can increase (trigger) migraine, suicidal thoughts and generally making us feel awful again. It’s important to follow your doctor’s instructions and have the blood done before starting this supplement.

    I can tell you what I take which is recommended by my doctor. This supplement tends to be expensive – my doctor found this site;

    I hope this helps,


  • Kerrie Smyres moderator
    6 years ago

    I’m so glad it has helped you, Sarah! I have the mutation, too, but supplementing with methyfolate triggered suicidal ideation and depression. When I stopped the supplement, the suicidal ideation stopped, but the depression required antidepressants. This is a VERY rare reaction, but I wanted to mention it so others could be aware that mood changes could be tied to the supplement.

  • Nancy Harris Bonk moderator
    6 years ago

    Oh Kerrie,

    I’m so sorry this didn’t help but created other issues. 🙁

    So far, 5 MTHFR supplement is working for me!!

    Take care,

  • Sarah Hackley moderator author
    6 years ago

    Wow, Kerrie! That’s intense. Thank you so much for sharing.

  • Donna Fiore-Willson
    6 years ago

    This is the first time I have heard this! I was tested several years ago by a doctor who on a hunch. I do not have the lab results in front of me but I believe I have two copies of this genetic mutation. I have never received treatment of any kind for it, but do have migraines. What kid of doctor would I go to for treatment of both?

  • Sarah Hackley moderator author
    6 years ago


    My neurologist handles both my migraines and my supplemental medications/injections.

  • Nancy Harris Bonk moderator
    6 years ago

    Thank you Sarah for writing on this neglected topic.
    I have recently found out I have one copy (heterozygous) of the c677t gene mutation.
    I have am being treated for this and hopefully will see improvement in some of my “issues.”


  • Sarah Hackley moderator author
    6 years ago


    That’s what I have, too. I wasn’t expecting so much improvement on mine, because I don’t have two copies of the mutation, but it’s been really phenomenal. I wish you success.

  • Jules2dl
    6 years ago

    Wow! this presents what could be quite a break through for many members of my family who suffer from various manifestations of this gene mutation.
    What I’m wondering is, if you take the test and find that you’re positive for the mutation, will your insurance and/or medicare still cover your treatment for whichever illness you are suffering due to that mutation?
    I was told that if I sought genetic testing for the dementia which both my mother and maternal grandmother had, and showed positive results, that no insurance company would ever cover me, and that went for medicare as well. For whatever reason, either the lab or the doctor was required to report the testing/results.
    Also, are you able to give yourself the necessary injections or must you go to the doctor to get them?
    Did your insurance cover the testing itself? If not, was it incredibly expensive?
    (sorry, I know $$ is a sensitive issue, but its a cogent issue for me).
    Most of all, thank you so much for opening up this invaluable information to those of us who hadn’t heard of it yet!

  • Sarah Hackley moderator author
    6 years ago


    I don’t know about that. Were you told that before or after healthcare reform went into effect? From what I understand, no company can deny you for preexisting conditions now. My insurance covered the testing and the supplemental injections. I have to pay for the supplement pills themselves, though if I had an FSA, I’m pretty sure I could use that to purchase the pills. I haven’t been told anything else at this point about coverage, though nothing has changed regarding my mental health benefits and I know that is affected by the mutation.

    Sorry if that doesn’t help. Perhaps ask your doctor the next time you go in?

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