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As with so many other conditions, the research shows that people with the MTHFR gene mutation are more likely to have migraines. Especially classic migraines with an aura, and especially homozygous MTHFR C677T polymorphism (although the research is limited, so I would assume all MTHFR polymorphisms have some effect, even if it isn’t as pronounced).

Migraines with aura are preceded by some kind of cue, or aura, which is usually a visual disturbance including flashing lights, halos, or blind spots. After the prodrome, extreme head pain begins, often with sensitivity to lights, sounds, and sometimes nausea or vomiting. Many people are completely unable to function with a migraine.

MTHFR and migraine both also have the commonality that they both increase the likelihood of having a stroke, which is an endpoint we all want to avoid. The most likely link here is through vascular disease, which is highly related to MTHFR, migraines, and stroke.

Vascular Disease and Migraines

Vascular disease is any issue affecting the blood vessels , including inflammation, blockage in the arteries, clotting and micro clotting, and anything that disrupts blood flow, temporarily or permanently. Stroke and heart attack are at the extreme end of this, disrupting blood flow enough to do permanent or fatal damage. Minor changes in blood flow to the brain could be a trigger for the abnormal electrical activity that characterizes a migraine, or the abnormal electrical activity may act as a trigger for blood flow issues.

In light of vascular disease, we want to manage methylation and MTHFR consequences, because MTHFR is so highly linked to vascular disease of all forms, we want to keep blood vessels open wide, and we want to make sure the blood is smooth and slippery, not sticky and prone to clotting.

Managing Migraines with MTHFR Gene Mutations

  1. Manage your Methylation and MTHFR Overall – Since MTHFR and migraines are linked, it stands to reason that managing your MTHFR can help your migraines. This involves following the basic steps to managing MTHFR:
    1. Avoid folic acid in enriched food, supplements, and all other sources
    2. Add a background of all the B vitamins
    3. Add an MTHFR-safe folate – either methyl folate or folinic acid
    4. If you don’t tolerate methyl folate, add a methyl donor separately
    5. With migraines particularly, add 400 mg riboflavin daily, which has been shown to cut migraine frequency in half.
  2. Keep your Blood Vessels Wide Open – Working to keep your blood vessels wide open and functioning normally is a fundamental step for anyone with migraines or any other form of cardiovascular disease. This involves the things we normally think of for cardiovascular disease like regular exercise, reducing animal fats in the diet, and maintaining a normal weight. It also includes supporting optimal blood vessel opening and relaxation with supplements like magnesium, which helps to relax the smooth muscle in blood vessel walls, and by supporting nitric oxide, which is your body’s most important vasodilator. Read more about MTHFR and nitric oxide here.
  3. Keep Your Blood Slippery and Free of Blood Clots – MTHFR has been associated with increased tendency to form blood clots – both in the form of micro-clotting and overt clotting. Many factors can help to reduce the likelihood of clotting, including reducing inflammation, taking omega-3 fatty acids, and also using baby aspirin regularly to help reduce clotting risk.

Other Ways to Control Migraines with MTHFR Mutations

MTHFR and migraine, migraine with aura, micro clots and migraine, vascular migraine,

Hormones, Migraines and MTHFR gene mutations:

There are other natural ways to help control migraines as well. Migraines happen most frequently in women, and like everything else that happens in women, hormones are a factor. Detoxifying estrogen can be slower and more difficult for people with the MTHFR gene mutation, so this becomes an especially relevant factor with MTHFR. Also, women with MTHFR and slow COMT polymorphisms, who have difficulty eliminating excess estrogen, are especially vulnerable.

Many women notice that their migraines recur regularly at some particular part of their menstrual cycle, most commonly when estrogen levels are falling, but it could be variable for different women. Because of this, gentle methods of balancing and regulating hormones, such as seed cycling, can help to prevent hormonally related migraines. See more about seed cycling here.

Histamine, Migraines, and MTHFR:

Histamine and MTHFR have a complicated relationship, because methylation is one way we eliminate histamine. Because of this, many MTHFR mutants have either excessively high histamine or excessively low histamine. High histamine leads to typical hay-fever-type seasonal allergies, whereas a low histamine picture seems to show more to food and chemical sensitivities and atypical allergies. Histamine appears to have a double-edged relationship with migraines.

High histamine has been long known to act as a trigger for migraines and other vascular headaches. New research shows that this could be due to the action of histamine receptors in the brain. Managing and balancing histamine may also prove helpful in preventing migraines.

Herbal Remedies for Migraines:

Two herbal medicines have been well-studied for migraines. They are feverfew and butterbur.


Feverfew is a lovely small daisy-like flower that has been used as a pain reliever for centuries. It’s a relative of the common daisy, and its leaves have been shown to prevent migraines. It is thought that feverfew prevents migraines by stopping blood vessels from contracting. It is not safe for pregnant women to use. Feverfew is also used for fevers, rheumatoid arthritis, psoriasis, and other pain. Dosages vary between 50 – 150 mg per day. For migraines, it is best to use regularly as a preventative.


Butterbur is a more controversial herb that has the potential for liver damage and so it is important to look for a preparation that is PA-free. The most common PA-free preparation is called petadolex.

Migraines and Homocysteine:

High homocysteine is always a risk with the MTHFR polymorphism, and homocysteine is the best blood test to use to determine how well you are managing your MTHFR polymorphism. It isn’t a perfect test, but it is the best one we’ve got. High homocysteine is also a risk factor for both migraines and stroke, so keeping your homocysteine managed is crucial to protect yourself from some of the negative outcomes of MTHFR. Again, go back and do the MTHFR things we talked about in the first section.

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MTHFR is a common genetic mutation that can contribute to anxiety, depression, fatigue, chronic pain, infertility, and more serious conditions like breast implant illness, heart attack, stroke, chronic fatigue syndrome, and some types of cancer. If you know or suspect you have an MTHFR variant, schedule a free 15-minute meet-and-greet appointment with MTHFR expert Dr. Amy today.

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Amy Neuzil
Amy Neuzil

Dr. Amy Neuzil, N.D. is a leading expert in MTHFR and epigenetics, and she is passionate about helping people achieve optimal health and wellness for their genetic picture. She has helped thousands of people overcome health challenges using a simple, step-by-step approach that starts with where they are today. Dr. Neuzil's unique approach to wellness has helped countless people improve their energy levels, lose weight, and feel better mentally and emotionally. If you're looking for a way to feel your best, Dr. Amy Neuzil can help. Contact her today to learn more about how she can help you achieve optimal health and wellness.

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