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Symptoms of Poor Methylation: Migraines


Migraines are a common neurological disorder, characterized by multiple symptoms including head pain, nausea, vomiting, and extreme sensitivity to light and sound.[1],[2] Attacks can last from 4 to 72 hours.[3],[4] Migraines are ranked as the 7th most disabling condition by the World Health Organization and are thought to be one of the symptoms of poor methylation.[5],[6] Migraines affect approximately 12% of the population, about 2/3 of which are female; the condition causes a large amount of lost productivity in the workplace.[7] There are two large categories of this condition: migraine with aura (MA) and migraine without aura (MO). MA is characterized by the presence of a visual disturbance, such as arcs of light or color, preceding a migraine attack.[8]

Studies on the prevalence of migraines within pairs of identical twins and within families show that a significant percentage of migraine occurrence is heritable (40-60%), but an almost equal percentage is due to environmental or epigenetic factors (35-55%).[9]

Symptoms of Poor Methylation

One of these other factors is believed to be the methylation cycle. What exactly is the methylation cycle? Methylation in the body is the addition of a carbon atom with three hydrogen atoms attached to it (a methyl group) to a substrate.[10] Methylation aids in the synthesis of neurotransmitters, proteins, phospholipids, DNA, RNA—basically everything you need for your body to function![11]

Methylation is a cyclical process in the body. To describe it simply, your body derives vitamin B12 and folate from the foods you eat, and those nutrients are used to create a molecule called SAMe (S-adenosylmethionine). SAMe has a methyl group attached to it, which it donates to a substrate. After the methyl group is donated, SAMe is converted into the molecule homocysteine. Homocysteine is converted into the amino acid, methionine, which eventually becomes SAMe again, and the cycle continues.

MTHFR (methlyenetetrahydrofolate reductase) is another important component in the methylation cycle. This enzyme converts the dietary folate derived from food into its active form in the body, methylfolate. This step is necessary for the generation of SAMe, and optimal methylation. Mutations in the gene encoding MTHFR can cause poor enzyme function, and thus suboptimal methylation. Problems with methylation can also stem from poor nutrition, stress, and exposure to toxins.[12]

Poor methylation is thought to be involved in conditions such as chronic fatigue, diabetes, cancer, hypothyroidism, and anxiety, to name a few.[13] Research indicates that methylation could play a role in migraines as well. Migraines are one of the symptoms of poor methylation.

When the methylation cycle is disrupted, excess homocysteine accumulates in the body. Research has found migraines with aura (MA) to be associated with mutations in the gene which encodes the MTHFR enzyme, and elevated homocysteine levels.[14],[15]

One study, which measured the amount of folate and folic acid consumed by people who experience migraines, found that the more folic acid people consumed, the less frequent their migraines were.[16] That is to say, if their methylation cycles were functioning well, they experienced fewer migraines. Other studies, including a meta-analysis of previously collected data, suggest MTHFR has a large role in migraine pathology.[17] It is thought that elevated homocysteine levels in the blood likely lead to inflammation and the dilation of cerebral blood vessels which is associated with migraines.[18]

Interestingly enough, migraines are associated with an increased risk of cardiovascular disease—a condition in which elevated homocysteine is also implicated.[19]

Alternative Treatment Options

Treating the symptoms of poor methylation is one way to get relief. There is a great need for better treatment options for those who suffer from migraines. Current treatments are effective in less than half of patients, and some have adverse side effects.[20] Simply providing the body with the vitamins and cofactors essential for optimal methylation could be an effective option. Supplementing with folate or folic acid, vitamin B6, and vitamin B12 can reduce homocysteine levels.[21] One study found that patients who took a combination of folic acid, B6, and B12 supplements all reduced homocysteine in their blood; furthermore, this correlated with reduced migraine (MA) severity and frequency.[22]

The reduction of stress, though difficult to achieve in our fast-paced working lives, can also help reduce migraine concerns. Short-lasting stressful periods of time are one of the most commonly reported trigger-factors for migraines, and early life stress may lead to an increased risk for migraines.[23]

Those who would like to improve their methylation should consider modifying their diet to include foods rich in methyl donors. Beets, spinach, broccoli, and spirulina are just a few foods that increase the efficiency of the methylation cycle.[24] Improving methylation and reducing migraines may be easier than you think!



[1] Stuart S, Cox HC, Lea RD, et. al. (2012). The Role of the MTHFR Gene in Migraine. Headache, 52, 3, 515-520.

[2] Roos-Araujo D, Stuart S, Lea RD, et. al. (2014). Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility. Gene, 543, 1-7

[3] Eising E, Datson NA, van den Maagdenberg AM, et al. (2013). Epigenetic mechanisms in migraine: a promising avenue? BMC Medicine, 11:26.

[4] Menon S, Nasir B, Avgan N, et al. (2016). The effect of 1 mg folic acid supplementation on clinical outcomes in female migraine with aura patients. The Journal of Headache and Pain, 17:60.

[5] Wan D, Hou L, Zhang X, et. al. (2015). DNA methylation of RAMP1 gene in migraine: an exploratory analysis. The Journal of Headache and Pain, 16:90.

[6] Roos-Araujo op. cit.

[7] Menon (2016) op. cit., Stuart op. cit., Roos-Araujo op. cit.

[8] Stuart op. cit

[9] Stuart op. cit., Roos-Araujo op. cit., Eising op. cit., Menon op. cit.

[10] Sorochan W. (2015). Methylation, Health Update. Retrieved from

[11] Sorochan op. cit.

[12] Ibid.

[13] Ibid.

[14] Menon S, Lea RD, Ingle S, et. al. (2015). Effects of Dietary Folate Intake on Migraine Disability

and Frequency. Headache, 55:301-309.

[15] Eising op. cit., Stuart op. cit., Menon (2016) op. cit.,

[16] Menon (2015) op. cit.

[17] Stuart op. cit.

[18] Ibid.

[19] Eising op. cit., Stuart op. cit.

[20] Eising op. cit., Menon (2016) op. cit., Roos-Araujo op. cit.

[21] Stuart op. cit.

[22] Ibid.

[23] Eising op. cit

[24] Sorochan op. cit.


Clinical Contributor

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Ramona Richard, MS, NC

Ramona Richard, MS, NC

Ramona Richard graduated with honors from the University of California with a Bachelor’s Degree in psychology and graduated summa cum laude with a Master’s Degree in Health and Nutrition Education. She also holds a Standard Designated Teaching Credential from the State of California, is a California state-certified Nutrition Consultant and a member of the National Association of Nutrition Professionals.

Ramona has participated in nutrition education in both public and private venues, including high school and college presentations, radio and public speaking for the past 20 years. She is the owner of Radiance, a nutrition consulting company, the Director of Education for Sanesco International, and a medical technical writer.

Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

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