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 is involved in the final step of converting folate (or folic acid) into the active form that the body uses called methylfolate. This active form is then 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 that the MTHFR C677T variant was associated with 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 it is due to the association with 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.
It is easy to check your 23 and Me data to see if you carry the MTHFR variants.
Check your 23andMe results for rs1801133 for the MTHFR C677T:
- GG: normal (wildtype)
- AG: one copy of C677T allele (heterozygous), MTHFR efficiency reduced by 40%
- AA: two copies of C677T (homozygous), MTHFR efficiency reduced by 70 – 80%
Check your 23andMe results for rs1801131 for the MTHFR A1298C:
- TT: normal (wildtype)
- GT: one copy of A1298C allele (heterozygous), MTHFR efficiency slightly reduced
- GG: two copies of A1298C (homozygous), MTHFR efficiency reduced
You can easily get your homocysteine levels tested with a blood test. You could talk with your doctor about getting it done, or you can order it yourself (in the US) online. There are quite a few places to order your own lab work online. One that I use frequently is Walk-in lab, since it offers the choice of either going to Quest or Lab Corp. 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 B6). [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 400mcg methylfolate (really inexpensive on Amazon!). It did initially give me a weird headache across the top of my head, but 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.
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 animal, 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 supplementing.
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