MTHFR- What is it and why should you care?


Do you know anything about the MTHFR gene? For most of us, the answer is probably no. But maybe we should! As it turns out, the MTHFR gene plays a critical role in nutrient metabolism- particularly as it relates to folate.

So, let’s dive in and discuss more about what folate and MTHFR are, and why they are important!


We must understand the basics of folate and the folate cycle in order to understand the importance of folate metabolism. For starters, folate is an important vitamin. It plays a role in the production of lipids, proteins, and even DNA within our body (1,2). It is especially important for pregnant women, and women of reproductive age, as adequate folate promotes healthy pregnancies. In particular, adequate folate is thought to reduce the risk for a baby developing neural tube defects or spina bifida (3).

Folate is the general term commonly used to describe Vitamin B9. However, Vitamin B9 can be consumed in many other forms, including folic acid, and intermediate forms of folate (3). So to break it down- the foods we eat, such as legumes, green leafy vegetables, whole grains, and citrus fruits contain folate. Folic acid, on the other hand, is the form of Vitamin B9 that found in vitamin B9 fortified foods. Additionally, supplements may contain intermediate forms of folate. According to the NIH, folic acid is better absorbed in the body when compared with folate, and according to the CDC, folic acid is the most effective method of promoting healthy pregnancies (4). (Note: We recommend eating a healthy, whole food diet, with additional supplementation if necessary.)

In any form, ingested folate undergoes a series of reactions, collectively referred to as the folate cycle. The folate cycle is important, because it converts folate into a more “biologically useable form” while also producing byproducts that allow other important biological processes to occur within the body. One of the most important steps of the folate cycle involves the MTHFR gene. We will discuss this gene in more detail below, but generally, it is responsible for coding one of the enzymes that converts folate into its  more “biologically useable form.”


So we kind of know what MTHFR does, but what exactly is it? MTHFR is one of tens of thousands of genes present in the human genome. It contains the code required to create an enzyme called methylenetetrohydrofolate reductase. This enzyme is important, as it partially triggers that reaction to convert folate and/or folic acid into a biologically useable substance (2), as we discussed above. When MTHFR works efficiently, these processes run smoothly; however, in some cases MTHFR does not work efficiently, and impairs folate metabolism.

In fact, there are several known variants of the MTHFR gene. These variants may impact the effectiveness of the MTHFR gene, and the processing of folate in the body. Two commonly researched variants include C677T and A1298C. These variations can occur as a heterozygous variant, meaning the variant occurs on one side of the chromosome, or a homozygous variant, meaning the variant occurs on both sides of the chromosome. In the case of a heterozygous mutation, the MTHFR gene may only perform at 65% of its potential, while in the case of a homozygous mutation, the MTHFR gene may only perform at 30% of its potential (5).

So what does this mean? While the CDC reports that the C677T variant is common, and those with the gene can effectively process folate (4), this may not be the case for people with other MTHFR variants. Therefore, if you have signs of a folate deficiency, it may be worthwhile to talk to your doctor about MTHFR gene variants, and what that means for you. Some common signs of folate deficiency include anemia, diarrhea, weakness, depression, numb extremities, and/or reduced ability to taste (6).


The methionine cycle isn’t the focus of our discussion here. However, it is important to understand in the context of folate and MTHFR. So, for some more details on how MTHFR variants could be effecting you, lets’ return to the folate cycle. Remember those “byproducts” that result from the folate cycle? Well, one of them is a carbon group, and it is transferred to another important cycle that occurs in our bodies- the Methionine cycle.

In part, the methionine cycle, converts a protein called homocysteine into another protein called methionine. Methionine then undergoes a series of reactions in which it contributes to other important biological processes. This is important to consider for two reasons. Firstly, while the folate cycle is important to convert folate to the “useable form” the methionine cycle is where folate is ultimately used to promote the production of lipids, proteins, and even DNA within our body (2).

In addition, without the conversion of homocysteine to methionine, homocysteine may accumulate to unhealthy levels within the body. Research suggests high levels of homocysteine may increase chance for developing cardiovascular disease (7), although not specifically related to MTHFR gene variants. However, it is worth considering.


I know, I know, that was A LOT of information. But now you have a complete picture of what the MTHFR gene is, and why it matters- yay!

So let’s review. If someone has a variant MTHFR gene, they may not efficiently convert folate or folic acid into a useable form. On one hand, this may result in anemia, diarrhea, weakness, depression, numb extremities, and/or reduced ability to taste. On the other hand, MTHFR variants may be related to risk for developing CVD.

So, Whats the Bottom Line? Understanding the MTHFR gene and its variants may have important implications. It may help us better understand folate deficiency and CVD risk. However, much more research- particularly regarding the various types of MTHFR variants- should be completed before we can practically apply this knowledge on a general basis.

That being said, visit your doctor and talk to your dietitian for more individualized information if you are experiencing any of the symptoms associated with low folate! Even without a MTHFR gene variant, folate supplementation may have beneficial effects on overall health. Although the relationship continues to be studied, some research suggests that short term folate supplementation may have a particularly beneficial effect on lowering markers of inflammation in certain groups, such as those with type 2 diabetes.

Browse By Category





Get Started with a Culina Health Dietitian