Health risks of MTHFR gene variants

If you’ve heard anything about MTHFR variants, chances are it wasn’t good news. (And if you haven’t heard about MTHFR variants until right now, you’re probably worried. Sorry about that.) But are MTHFR variants really that bad? After all, they’re fairly common – nearly half of the population has at least one variant. So what’s the big deal?

As we take a deeper dive into how MTHFR variants happen in this blog, it’s important to note that MTHFR variants can have a big impact on your physical health. From infertility and miscarriages to heart disease, stroke, and cancer, MTHFR gene variants can be linked to a variety of serious health problems.

While the idea of having a gene variant can be scary, knowing the risk factors can help you take action – and there are simple action steps you can take if you do have a variant.

What is MTHFR?

We know you don’t have time to go back to school and get an advanced degree in genetics. So we’ll break down the basics of MTHFR for you.

MTHFR stands for methylenetetrahydrofolate reductase (say that five times fast). This gene activates the folate in our diet into L-methylfolate, which happens in a process called methylation. Simply put, MTHFR helps us turn folate into a form that our body can use.

Sometimes we inherit copies of genes from our parents that can create a partially functioning gene – which can be referred to as a variant, polymorphism, or mutation. (Find out more about how that process works in this blog.) For our purposes, we’ll be sticking with the term variant.

If you have an MTHFR variant, your body could have trouble converting the folate you need to use in other parts of the body, which can be connected to a variety of health problems.


MTHFR, Fertility, and Pregnancy

Planning to grow your family? One of the biggest concerns for MTHFR variants is when a woman plans to have a baby. Women with certain MTHFR variants are at increased risk for multiple miscarriages. Many women with MTHFR variants are first identified when they have difficulties staying pregnant, resulting in two or more consecutive miscarriages before 20 weeks gestation. [1]

Even when a woman with an MTHFR variant does conceive, she may not be able to support the rapid cell division that happens as her unborn child develops. This can result in DNA damage leading to abnormalities such as neural tube defects [2], congenital heart defects [3] and cleft palate. [4]

The MTHFR 677CT variant can also increase risk for preeclampsia, a pregnancy complication that can cause high blood pressure and organ damage in pregnant women while restricting the growth of the fetus. In one small study of 198 women, a higher frequency of the 677CT and 677TT variants were found in severe preeclamptic women compared to a control group. [5]

And MTHFR isn’t just a risk factor for women. Studies have found that MTHFR variants may be linked to fertility problems for men, too. One 2015 review of 26 studies found that the MTHFR 677CT polymorphism (variant) was significantly associated with the risk for male infertility. [6] A separate 2010 study of 291 men found that the MTHFR 1298CC variant was an additional risk factor for infertility. [7]

MTHFR, Heart Disease, and Stroke

MTHFR gene variants can also impact your heart and risk for stroke. According to a 2015 article published in Circulation, some people with an MTHFR variation can have elevated homocysteine levels. [8] Homocysteine is a common amino acid which, when elevated, has been linked to greater risk of blood clots and heart disease. One meta-analysis of 38 studies found that the MTHFR 677CT variant was associated with a greater risk of ischemic stroke. [9]

MTHFR and Cancer

Because MTHFR helps repair your DNA, MTHFR variants may put you at greater risk for cancer as you get older. If you have low folate levels and the MTHFR 677CT polymorphism, you may be more likely to have DNA damage and your body may be less able to remove toxins, leading to an increased risk of cancers. [10,11]

Specifically, the MTHFR C677T variant has been found to increase risk for breast and esophageal cancer. One 2018 review of 29 articles found a significant risk of the MTHFR 677CT variation and esophageal cancer. [12] Another 2009 study of 965 postmenopausal women published in Breast Cancer Research found that the MTHFR 677TT genotype is associated with a moderate increase of postmenopausal breast cancer. [13]

MTHFR and Mental Health

The MTHFR gene can also play a critical role in our mental health. MTHFR helps activate folate into a form called L-methylfolate. This serves as a building block for mood neurotransmitters like serotonin, norepinephrine, and dopamine, which help regulate how we feel. If your MTHFR gene isn’t able to convert enough folate, then your brain isn’t able to make enough of these chemical messengers to regulate your mood – which can result in mood disorders such as depression or anxiety. For more on the link between MTHFR and mental health, check out this blog.


So what can you do if you have an MTHFR variant?

We’ve outlined a lot of scary health conditions, and MTHFR variations can seem complicated. But the good news? There are ways you can take action.

If you find out you do have an MTHFR variant, you may be able to supplement your diet with L-methylfolate, the active form of folate.

In addition to supplementing your diet, making other healthy lifestyle choices can help reduce your risk for complications:

  • Get moderate exercise for at least 30 minutes per day.
  • Get 8 hours of sleep per night.
  • Eat a diet rich in fruits and vegetables.
  • If you’re planning to become pregnant, supplement your diet with at least 400 mcg of folate per day as recommended by the CDC. And if you have an MTHFR variant, ask your healthcare provider about taking a daily regime of methylated folate.

You can’t change your genes, but you do have the power to discover if you have an MTHFR variant. The sooner you know your MTHFR status, the sooner you can do something about it. Get tested today, and get the answers you need about your health.

Written by: Dr. Peg Daly, ND, FMNM, ABAAHP, FNP-BC, MBA

[1] Sah, Anil Kumar, et al. “Association of Parental Methylenetetrahydrofolate Reductase (MTHFR) C677T Gene Polymorphism in Couples with Unexplained Recurrent Pregnancy Loss.” BMC Research Notes, vol. 11, no. 1, 5 Apr. 2018, doi:10.1186/s13104-018-3321-x.
[2] Yan, Lifeng, et al. “Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies.” PLoS ONE, vol. 7, no. 10, 3 Oct. 2012, doi:10.1371/journal.pone.0041689.
[3] Zhang, Rui, et al. “Two Common MTHFR Gene Polymorphisms (C677T and A1298C) and Fetal Congenital Heart Disease Risk: An Updated Meta-Analysis with Trial Sequential Analysis.” Cellular Physiology and Biochemistry, vol. 45, no. 6, Apr. 2018, pp. 2483–2496., doi:10.1159/000488267.
[4] Abdollahi-Fakhim, Shahin et al. “Common Mutations of the Methylenetetrahydrofolate Reductase (MTHFR) Gene in Non-Syndromic Cleft Lips and Palates Children in North-West of Iran.” Iranian Journal of Otorhinolaryngology vol. 27, no. 78, Jan. 2015, pp. 7-14.
[5] Rahimi, Zohreh, et al. “MTHFR C677T and Enos G894T Variants in Preeclamptic Women: Contribution to Lipid Peroxidation and Oxidative Stress.” Clinical Biochemistry, vol. 46, no. 1-2, Jan. 2013, pp. 143–147., doi:10.1016/j.clinbiochem.2012.10.020.
[6] Gong, Mancheng, et al. “MTHFR 677CT Polymorphism Increases the Male Infertility Risk: A Meta-Analysis Involving 26 Studies.” PLoS ONE, vol. 10, no. 3, 20 Mar. 2015, doi:10.1371/journal.pone.0121147.
[7] Singh, K, et al. “MTHFR A1298C Polymorphism and Idiopathic Male Infertility.” Journal of Postgraduate Medicine, vol. 56, no. 4, Oct. 2010, pp. 267–269., doi:10.4103/0022-3859.70935.
[8] Moll, Stephan, and Elizabeth A. Varga. “Homocysteine and MTHFR Mutations.” Circulation, vol. 132, no. 1, 7 July 2015, doi:10.1161/circulationaha.114.013311.
[9] Cui, Tao. “MTHFR C677T Mutation Increased the Risk of Ischemic Stroke, Especially in Large-Artery Atherosclerosis in Adults: An Updated Meta-Analysis from 38 Researches.” International Journal of Neuroscience, vol. 126, no. 1, 7 Jan. 2015, pp. 10–19., doi:10.3109/00207454.2014.990559.
[10]: “MTHFR: Cancer Genetics Web.” MTHFR | Cancer Genetics Web, Accessed 24 June 2019,
[11] Kafadar, Ali Metin et al. “C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) in meningiomas and high-grade gliomas.” Anticancer Research, vol. 26, no. 3B, May 2006, pp. 2445-9.
[12] Kumar, Pradeep, and Vandana Rai. “MTHFR C677T Polymorphism and Risk of Esophageal Cancer: An Updated Meta-Analysis.” Egyptian Journal of Medical Human Genetics, vol. 19, no. 4, 2018, pp. 273–284., doi:10.1016/j.ejmhg.2018.04.003.
[13] Maruti, Sonia S, et al. “Mthfr C677T and Postmenopausal Breast Cancer Risk by Intakes of One-Carbon Metabolism Nutrients: A Nested Case-Control Study.” Breast Cancer Research, vol. 11, no. 6, 23 Dec. 2009, doi:10.1186/bcr2462.