What Is MTHFR?

What Is MTHFR?

Have you seen the term MTHFR in relation to B vitamin supplements and wondered what it meant? 

What is MTHFR?

MTHFR stands for methylenetetrahydrofolate reductase and it is an important enzyme in the body that helps us metabolise folate, a nutrient that is vitally important for so many functions. 

Up to two-thirds of the population carry a change 
or variation in the gene for this enzyme 
which is collectively referred to as MTHFR. 

A change to a gene’s activity is called a polymorphism. In the case of MTHFR, there are two genes people typically test for; 677CT and 1298AC. Depending on your own genetic signature, a polymorphism can mean that you might have an increase or decrease in the actions that the gene pathway performs. In those carrying MTHFR genetic changes, it will slow down how efficient their body is at absorbing folate and folic acid and, importantly, metabolising it to its biologically active form (see Fig.1). 

Figure 1. The folate metabolism pathway.

Folate Metabolism Pathways

How Does MTHFR Affect Health?

Because folate is a central coenzyme in many important pathways of the body, having an MTHFR gene variant can have widespread and varied health effects. The job of the MTHFR enzyme is to convert the inactive folate we eat (or supplement) into its active form, called methyl folate. The name methyl folate is so named because it contains a methyl group (also referred to as methyls), and these methyls are what the body uses to act as important ‘switches’ in our genes, turning them on and off. This process is called methylation. Without sufficient folate, these pathways become sluggish and operate poorly, which leads to a range of health issues. 

MTHFR is probably most well-known in connection to fertility. Often couples will discover they are carrying MTHFR genes when they have been trying for a baby without success. We know that pregnant women are routinely prescribed folate to prevent neural tube defects in the infant. This is because methyl groups are important for building healthy DNA, which is essential to produce healthy offspring. Without sufficient folate, errors occur in the DNA and this is how it can contribute to birth defects, miscarriage and infertility. 

However, the health effects don't end there. MTHFR can also contribute to hidden health issues that tend not to become obvious until later in life. The effect of a slow MTHFR pathway can build up over time. Poor methylation affects our detoxification pathways, neurotransmitter synthesis (mood chemicals) and the efficiency of our immune system. Those with MTHFR might have trouble detoxing chemicals they're exposed to or making happy mood hormones leading to depression, anxiety, brain fog and learning disorders. Because folate is important in how the body metabolises homocysteine, it can also have some detrimental effects on the circulatory and cardiovascular systems.

How MTHFR Influences Health

Symptoms will vary from person to person and can often go unnoticed. This is because each person has their own unique set of genetic blueprints, and they may have highly efficient genes in other areas that can compensate for the loss of function of another. Diet and lifestyle choices can also have positive or negative effects on long-term health outcomes. 

How Do You Find Out If You Have MTHFR?

Genetic testing is becoming way more common and accepted. You can speak to your health professional about getting a test done. The test is a simple collection of saliva and cells from a cheek swab. You can test for methylation genes in a stand-alone test or get a more comprehensive genetic profile done, which can give you a more detailed analysis of your personal health picture. 

What Do You Do If You Have MTHFR?

The number one thing anyone with MTHFR should know is that they need to be choosing active forms of folate (5-MTHF), like Quatrefolic® when supplementing. The MTHFR gene slows down their ability to convert both dietary folate and the synthetic form in foods and supplements known as folic acid. This can leave them deficient and will result in downstream health issues.

Another emerging factor is that MTHFR carriers need to be mindful of continuing to take folic acid in food or supplements and may also need to consider modifications so they aren’t consuming a high folate diet as it may lead to a build-up of the inactive forms circulating the body, waiting to be metabolised. Research is just starting to explore the negative health consequences of unmetabolised folic acid. If you discover that you have MTHFR, it’s worthwhile speaking to an expert to guide you through dietary changes you may need to make to reduce this backlog.   


Zhu Y, et al. (2018). Prevalent genotypes of methylenetetrahydrofolate reductase (MTHFR) in recurrent miscarriage and recurrent implantation failure. Journal of assisted reproduction and genetics. 2018 Aug35(8):1437–1442.

Obeid R, et al. The emerging role of unmetabolized folic acid in human diseases: myth or reality? Curr Drug Metab. 2012 Oct;13(8):1184-95.

Pfeiffer CM, et al. Unmetabolized Folic Acid Is Detected in Nearly All Serum Samples from US Children, Adolescents, and Adults. J Nut. 2015 Mar; 145(3):520–531

Tang JS, et al. MR1-dependence of unmetabolized folic acid side-effects. Front. Immunol. Sec. T Cell Biology. 2022 August 09.

Kelly P, et al. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements Am J Clin Nut. 1997 June 65(6):1790-1795.

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