MTHFR Gene May Be Causing Your Fatigue, Headaches, Depression, and More

A very common genetic defect in a gene called MTHFR may be the cause of your problems.

MTHFR gene test

If your MTHFR test reveals that you have one or more MTHFR gene mutations, remember that your genes are not your destiny and that you have the ability to bypass these genetic polymorphisms.

Do you struggle with fatigue,  migrainesfibromyalgia, or depression? Have you or has a family member suffered from a heart attack or stroke? Have you endured a miscarriage? Are you wondering what these conditions have in common? The answer is that all these conditions, plus more, are linked to a very common genetic defect in a gene called MTHFR.

What is MTHFR?

MTHFR, or methyltetrahydrofolate reductase, is a gene that creates an enzyme of the same name. This gene, and the enzyme it controls, are critical for the body’s ability to use the B vitamin, folate, and for the vital biochemical pathway, methylation.

You would die without methylation—the addition of a methyl group (CH3 – one carbon attached to three hydrogens) to another molecule. This process occurs billions of times every second within cells and plays a crucial role in many bodily functions, including detoxification, energy production, and mood balancing.

Methylation helps to regularly repair your DNA (which helps to prevent cancer), controls homocysteine (a dangerous compound that can damage blood vessels and lead to cardiovascular disease), and is involved in the production of neurotransmitters and the control of inflammation.

MTHFR Mutation and Depression, Fatigue, and More

Many people have MTHFR gene defect symptoms. When this key enzyme in the body is at a lower than normal rate, it can lead to a variety of health problems.[1]

With a MTHFR gene defect, you have what is called a single nucleotide polymorphism, or SNP (‘snip’). There are numerous MTHFR SNPs, but the two primary ones are C677T and A1298C.

The C677T variant is most commonly associated with early heart disease and stroke and the A1298C variant with a variety of chronic illnesses. Either anomaly, though, can cause a wide variety of health problems, including fibromyalgia[2], depression[3], fatigue, migraines[4], frequent miscarriage[5], frequent blood clots, and increased risk of cardiovascular disease[6].

Other conditions that may be associated with MTHFR gene mutations include autism[7], infertility, schizophrenia and other psychiatric disorders[8], cancer risk[9], Parkinson’s[10], Alzheimer’s[11], and increased susceptibility to the toxic side effects of certain medications[12].


To determine if you have these genetic variants, you or your doctor can order a blood or saliva test. Typically, the two most common MTHFR genes (C677T and A1298C) are measured when an MTHFR test is ordered. The test is commonly available through conventional laboratories such as LabCorp, as well as through popular functional laboratories such as Spectracell and Doctor’s Data.

The easiest and least expensive option, however, may be to go through a company that offers complete genetic profiles, such as 23andMe. They offer an easy-to-do salivary genetic test which tests 1,000s of your genes (including MTHFR) for only $99.

While 23andMe doesn’t offer health-related interpretation of your test results, you can run your raw data through a website like Genetic Genie for a small donation. This may sound confusing, but the process is actually quite simple and the reliable interpretation is easy to acquire.

MTHFR Mutation Treatment

If your MTHFR test reveals that you have one or more MTHFR gene mutations, remember that your genes are not your destiny and that you have the ability to bypass these genetic polymorphisms. You do this by supporting methylation with diet, supplements, and other natural therapies and lifestyle choices. These factors impact how your genes are expressed.

For MTHFR treatment, you can supplement with the active form of folate (5MTHF). You can also supplement with the active forms of other B vitamins that are involved in methylation and homocysteine breakdown: vitamin B12 (methylcobalamin), riboflavin (riboflavin-5’-phosphate), and vitamin B6 (pyridoxal-5’-phosphate). Taking acetyl-glutathione or n-acetylcysteine (NAC), as well as other nutrients can also be helpful.

The choice of nutrients and the most effective dose varies from person to person and depends on many factors, including the type of mutation you have, your health history, and your current symptoms.

In some cases, MTHFR mutation symptoms can simply be treated with B vitamins. It is not uncommon, however, for people with these genetic polymorphisms to be very sensitive to supplementation. For these reasons, if you have a chronic health condition that could be related to MTHFR gene mutations, it is best to find a naturopathic doctor or functional medicine trained physician. They can help you diagnose your MTHFR gene mutation symptoms and work with you on a comprehensive treatment plan.

[1] Nutrients. 2015 Aug 10;7(8):6670-87.

[2] Gene. 2015 Jun 15;564(2):188-92.

[3] Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:78-85.

[4] J Neurol Sci. 2014 Jan 15;336(1-2):68-73.

[5] Gene. 2013 Feb 10;514(2):105-11.

[6] Curr Pharm Des. 2013;19(14):2574-93.

[7] Autism Res. 2013 Oct;6(5):384-92.

[8] Brain Behav Immun. 2011 Nov;25(8):1530-43.

[9] Mol Biol Rep. 2013 Jan;40(1):625-37.

[10] J Neurol Sci. 2013 Dec 15;335(1-2):14-21.

[11] Mol Biol Rep. 2015 Mar;42(3):611-6.

[12] Clin Rheumatol. 2014 Dec;33(12):1715-24.

Originally published in 2015.

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Kathleen Jade, ND

Dr. Kathleen Jade is a naturopathic physician and served for many years as the Medical Director and Editor-In-Chief of Natural Health Advisory Institute. She has been licensed as a primary … Read More

View all posts by Kathleen Jade, ND

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