MTHFR: A Genetic Mutation to Watch
By Erica Zelfand


MTHFR stands for methylenetetrahydrofolate reductase, a gene that codes for an enzyme of the same name. However, if the MTHFR gene is mutated, the enzyme produced is imperfectly created.1 (Oh, and yes, doctors do joke amongst themselves about “MTHFR” resembling “Mother-Father,” as well as another word that I cannot write here!)

I explain the basics of the MTHFR mutation in the article below, as well as in this video:


What Does This Enzyme Do?

To put it simply, the enzyme helps the body utilize certain nutrients – particularly Vitamin B12 and Folic Acid (also known as Vitamin B9). Similar to how you can’t use a new tool before taking off the cellophane wrapper, you likewise can’t use B12, or Folic Acid properly until the MTHFR enzyme “methylates” – or unwraps – these vitamins. The body then uses these nutrients to make healthy new cells (thereby reducing the risk of cancer), balance inflammation, support cardiovascular health, make neurotransmitters important for mood support like serotonin and dopamine, and support the nervous system. When the MTHFR enzyme is defective, these nutrients – whether consumed through food or supplement form – cannot be properly utilized.


MTHFR Mutations:

Many people – especially Caucasians in North America – have a genetic mutation (also called a “single nucleotide polymorphism,” or “SNP” or “snip” for short) affecting the MTHFR gene. This genetic mutation, commonly referred to as a “methylation defect,” can be tested for through blood or saliva tests. It’s important to note, however, that having the gene does not necessarily mean any problems will occur. It’s entirely possible to have the gene mutation and have no health problems whatsoever. The mutation simply represents the potential for problems to occur. The more toxic our surroundings, diet, and lifestyle, the more likely we are to experience issues. In other words: “Genes load the gun; environment pulls the trigger.”


What are the Symptoms?

Many people with the mutation have no symptoms at all, while others have severe illness. More and more research is emerging about MTHFR, but so far it seems the mutation is linked with an increased risk of many ailments, including:

  • Brain: autism2,3,4 and learning disabilities, addictions, depression, bipolar 1,6,7,8,9
  • Cardiovascular: elevated levels of homocysteine (which causes inflammation of the heart and blood vessels), heart attack, stroke 1,5
  • Reproductive: miscarriages, birth defects (spina bifida, cleft palate), cervical dysplasia1
  • Energy: chronic fatigue syndrome, fibromyalgia1,6,,7,8,9
  • Neurological: multiple sclerosis, parkinsons1
  • Certain types of cancer1


How is it Diagnosed?

It’s relatively simple to be tested for the mutation. Testing options include a blood test, which is offered by most commercial laboratories, hospitals, and some specialty labs (and which you can self-order here). Fasting is not required for this blood draw. Alternately, salivary testing kits can be purchased online through companies like 23AndMe. Note that this is a genetic test, and therefore some labs require that you sign an informed consent before they can process your sample. (On that note, if you’re doing 23AndMe, I strongly suggest doing so under a fake name and fake date of birth.)


What Do My Test Results Mean?

Labs test for mutations affecting two important MTHFR genes: C677T and A1298C. Each gene in the body contains two chromosomes, so 4 chromosomes are therefore assessed.1

MTHFR C677T can be:

  • Unaffected (both chromosomes normal)
  • Heterozygous (half mutated; 1 of 2 chromosomes affected)
  • Homozygous (fully mutated; both chromosomes affected)

MTHFR A1298C can be:

  • Unaffected (both chromosomes normal)
  • Heterozygous (half mutated; 1 of 2 chromosomes affected)
  • Homozygous (fully mutated; both chromosomes affected)


How is it Treated?

Unfortunately, there is no known treatment for fixing a defective gene. (For this reason, it’s considered a waste of money to repeat the testing, as one’s genes don’t change.) Thankfully, the harmful risks of the mutation can be at least in part managed or prevented through the use of active B vitamins. The active vitamins skip over the MTHFR enzyme, allowing the body to be nourished regardless of the enzyme’s function. (Like buying a tool at the hardware store without there being any packaging to remove before you can start using it.)


When shopping for supplements, here’s what to look for on the label:

Nutrient Forms to AVOID Form to CHOOSE



✗ Hydroxycobalamin

✗ Cyanocobalamin






✗ Folic Acid



✓ Methylfolate

✓ 5-MTHF

✓ Methyltetrahydrofolate


More and more doctors and consumers are demanding products that contain methyl-B12 and folate, and in turn manufacturers are offering a greater selection of prenatal supplements, multivitamins, B complexes, and other nutraceuticals that cater to those with MTHFR mutations. Supplementation is typically recommended for life in those with an affected gene and symptoms (or a strong family history of associated disease).




[2] Suren P, et al. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA 13 Feb 2013;309(6):570–577.

[3] Roth C, Magnus P, Scjolberg S, et al. Folic acid supplements in pregnancy and severe language delay in children. JAMA. 2011;306(14):1566-1573.

[4] Schmidt RJ, Hansen RL, Hartiala J, et al. Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology. 2011;22(4):476-485.

[5] Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002; 288:2015.

[6] Gokcen C, Kocak N, Pekgor A. Methylenetetrahydrofolate reductase gene polymorphisms in children with attention deficit hyperactivity disorder Int. J. of Med. Sci. 2011; 8(7):523-528.

[7] Victoria L. Stevens, Marjorie L. McCullough, Alexandre L. Pavluck, et al. Association of polymorphisms in one-carbon metabolism genes and postmenopausal breast cancer incidence. Cancer Epidemiol Biomarkers Prev 2007;16:1140-1147.

[8] Boris M, Goldblatt A, Galanko J, James J. Association of MTHFR gene variants with autism. Journal of American Physicians and Surgeons. 2004;9(4):106-108.

[9] Ozdemir O, Yenicesu GI, Silan F, Köksal B, Atik S, Ozen F, Göl M, Cetin A. Recurrent pregnancy loss and its relation to combined parental thrombophilic gene mutations. Genet Test Mol Biomarkers. 2012 Apr;16(4):279-86.

Photo by Ludde Lorentz on Unsplash