MTHFR, Migraine, and the C677T Variant

In 2014, I wrote my first article on migraine and the MTHFR variant. Since then, I’ve received dozens of emails from readers asking for additional information. In this piece, I’ll address some of the questions I’ve received since then, including the variant I have, how it affects migraine presentation, and what steps others can take to learn more.

C677T and migraine presentation

I am heterozygous for the C677T variant of the MTHFR gene, which means I have one copy of the C677T allele. Two copies are often considered more dangerous because that’s when homocysteine levels rise and the risk of heart problems and stroke increases. While my single variant means my homocysteine levels are generally within the normal range, the fact that I have the variant at all is clinically relevant to my migraine treatment.

A 2010 study comparing the C677T variant with migraine presentation found that those participants with migraine who had one or more copies of the C677T variant were significantly more likely to have unilateral head pain and to experience discomfort with physical activity during or prior to an attack than were participants with migraine who did not have the variant. While those with two copies of the variant were found to have the largest number of migraine symptoms and triggers overall, having only one copy of the variant, as I do, had some interesting correlations as well.

The same study found that people like me, who have only one copy of the C677T variant, “may be more susceptible to environmental triggers associated with migraine attacks” than either those with two copies of the C677T variant or those with zero copies. Interestingly, this was particularly true for stress as a trigger. We’re also more likely to experience nausea with our attacks. This matches well with my personal experiences.

Potential treatment effects

Three years have passed since I began treatment and wrote that first article, and I still feel a marked difference in the severity of migraine attacks when I am consistently getting my methylated B-12 injections compared to when I am not. When I skip doses, stop doses, or increase the number of weeks between them, my attacks always get more painful. (Generally, I see a two to three point jump on the pain scale during these times.)

While I initially saw a decrease in frequency from treatment, that is no longer the case. (Though I believe that is due to my personal migraine cycle and not the treatment itself.) Of note, however, is the frequency of my stabbing headaches, which greatly diminishes when I’m receiving regular injections. Nausea associated with my attacks also improves.

I don’t think I’m alone. While treatment with supplements isn’t right for everyone, a 2009 randomized, double-blind placebo, controlled study showed a significant reduction in migraine disability, frequency, and pain severity after six months of treatment with supplements. Interestingly enough, this improvement appeared to be greater in individuals with one copy of the C677T variant than in individuals with two copies.

Talk to your doctor

For this reason (and many others), it is vitally important to discuss any treatments – even over-the-counter treatments – with a qualified doctor before starting them. What works for one person won’t work for another. (One Migraine.com writer, for example, had a horrible reaction to B-vitamin supplementation.) Knowing what has worked for others, however, can offer insight into what may work for you.

If you haven’t been tested for the MTHFR variant, I encourage you to talk to your doctor about it. If you test positive, definitely work with him or her to find the right course of treatment for you. That’s the safest, most effective way to get relief.

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