MTHFR and Migraines

The MTHFR genetic variants have been well researched and linked to a number of different chronic conditions such as an increased risk of heart disease, depression, and neural tube defects.

In a nutshell, the MTHFR gene involves the final step of the conversion of folate (or folic acid) into the active form that the body uses called methylfolate. This active form gets used in a bunch of different ways in the body, which is why the MTHFR variants impact such a variety of different conditions. (Check out my MTHFR article for more detailed background on the gene.)

One topic that I haven’t seen written about very often is the link between the MTHFR variants and migraines. There have been many studies (50+) over the last few years that show an increased risk of migraines in people who carry the common MTHFR variants.

What do the studies show?

  • A meta-analysis in 2011 found that the MTHFR C677T variant increased the risk of migraines with aura in Caucasians, and it increased the risk (3-fold) of all migraines in non-Caucasians.[ref]
  • Another meta-analysis specifically looked at Asian populations and found associations between the MTHFR C677T variant and an increased risk of migraines.[ref]
  • A study that looked at the electrophysiological characteristics of migraines found that carriers of the MTHFR C677T variant were not only more likely to get migraines, but they were also more likely to have photophobia with migraines.[ref]
  • The A1298C variant was found to be associated with the risk of migraines in a North Indian population, but the C677T variant was not found to differ statistically between patients and the control group.[ref]

Why is MTHFR statistically associated with migraines?

Some studies indicate the association is due to higher homocysteine levels. One study with over 700 participants investigated the homocysteine levels, genetic variants, and migraine frequency in patients in a neurological clinic compared with a control group. The study found that homocysteine levels greater than 12microM doubled the risk for migraines with aura, and participants with homocysteine levels greater than 15 had a 6-fold increase in migraine risk. Homocysteine levels were associated with the MTHFR C677T variants – and thus with migraine risk.[ref]

Other studies show that it may be due to the role that MTHFR plays in the methylation cycle and differential methylation of certain genes.[ref]

Does this mean that you will get migraines if you carry the MTHFR variant?
Not necessarily. Keep in mind that the studies just show that MTHFR variant carriers, especially with high homocysteine levels, are somewhat more likely to get migraines. People without the variant are slightly less likely to get migraines. It is just statistics…But if you do get frequent migraines and have high homocysteine levels, then perhaps the MTHFR variants are playing a role here for you.

MTHFR genetic variants:

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It is easy to check your 23 and Me data to see if you carry the MTHFR variants.

Check your genetic results for rs1801133 (23andMe v4,v5; AncestryDNA):

  • G/G: typical
  • A/G: one copy of C677T allele (heterozygous), MTHFR efficiency reduced by 40%
  • A/A: two copies of C677T (homozygous), MTHFR efficiency reduced by 70 – 80%

Members: Your genotype for rs1801133 is .

Check your genetic results for rs1801131 (23andMe v4, v5; AncestryDNA):

  • T/T: typical
  • G/T: one copy of A1298C allele (heterozygous), MTHFR efficiency slightly reduced
  • G/G: two copies of A1298C (homozygous), MTHFR efficiency reduced

Members: Your genotype for rs1801131 is .


MTHFR not the problem?  Check out all the other genes involved in migraines.


Testing homocysteine levels:

You can easily test your homocysteine levels with a blood test. Talk with your doctor or order it yourself (in the US) online. There are quite a few places to order your own lab work online such as Ulta Lab Tests. But do shop around since the online lab ordering places all have different prices and offer coupons and sales.

Several studies show that lowering homocysteine levels (if high) through supplementing with vitamins is effective in reducing the number and severity of migraines. Most studies use methylfolate, methylcobalamin (active form of B12), and pyridoxal-5-phosphate (active form of vitamin B6). Additionally, riboflavin may also play a role in reducing homocysteine. [ref][ref][ref]

While some of the studies on homocysteine and migraines used higher dosages of methylfolate and B6, I would caution that some people may be sensitive to the active B vitamins. Personally, I like the Jarrow 400 mcg methylfolate. It did initially give me a weird headache across the top of my head. Backing off and only using about a quarter of a capsule each day for a while was the way to go for me.

Everyone is different! I just wanted to toss in this caution because, prior to supplementing with good quality vitamins that were right for my genes, I had never actually noticed an effect from a vitamin before. I just thought that vitamins were something you just took and hoped they were working… Turns out that the right supplement (or the wrong supplement!) can have a big effect.

Food sources for folate:

Not a fan of supplements? There are food sources of folate, B12, and B6. One of the best sources is beef liver and other organ meats. There is a reason our ancestors ate all of the animals, including the organ meats. Other good sources of folate include leafy greens (need lots of them!) and legumes.

One thing to keep in mind is that B12 is found mainly in animal foods, so if you are vegetarian, you may want to get your B12 levels tested and look into supplements.

Related Articles and Genes:

MTHFR and Depression
While there are many different causes of depression, research shows that diet and nutrient intake affects the risk of depression. A recently published study found that low levels of folate and vitamin B12 were linked to increased depression.

MTHFR: How to check your data for C677T and A1298C
It is easy to check your genetic results on 23andMe or AncestryDNA for the two main MTHFR variants known as C677T and A1298C. If you have done 23andMe, just click on the link below to check your MTHFR gene.

Hacking your migraines: solutions personalized for you
Your genes play a role in your susceptibility to migraines. Find out what is going on when you have a migraine and solutions that fit your genes.

Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.