What is MTHFR?

what is mthfr
Reading Time: 2 minutes

When a baby is conceived, they inherit 2 copies of every gene; one from each parent. MTHFR is the name of one such gene out of a genetic code of thousands. The gene codes for an enzyme called “methylenetetrahydrofolate reductase”, which is responsible for the conversion of dietary folate (vitamin B-9 or folic acid) into its biologically active form, L-methylfolate, to be used by your cells.

There is a certain version of this genetic code that makes the optimal amount of working enzyme so that every time folate or folic acid (the synthetic version of folate often in supplements or added to fortified foods) is consumed, cells convert it to L-methylfolate and continue their biological processes efficiently.

What Happens if I Have an MTHFR Variant?

Unfortunately, at least half of the population has a slight change to the code in either one or both copies of their MTHFR gene [1]. A difference in a code for a certain gene is known as a “mutation”, “variant”, or “polymorphism” depending on the context.

Even if only one nucleotide in the MTHFR gene code is different, the enzyme may either be produced incorrectly or be produced in such a low abundance that the normal, downstream biological processes cannot continue at a healthy rate.

The severity of this biological hold-up depends on where in the gene code the difference occurs and whether the person has inherited one or two copies of a dysfunctional gene [2].

Some of these changes to the code are more common than others. At least 40 different rare mutations have been documented in the MTHFR gene. But, there are 2 variants that are strikingly common [3].

The C677T mutation is the most common, best studied, and thought to be very biologically important. This is because of the number of diseases and defects with which it has been associated [2].

C677T and another variant, A1298C, have both been implicated in MTHFR enzyme insufficiency. They are also associated with high homocysteine levels in the blood. Healthy homocysteine levels are required for a healthy cardiovascular system [4].

Proper utilization of folate in the body affects numerous processes. Both variants, with and without elevated homocysteine levels, have been studied in relation to complications with the cardiovascular system, pregnancy, normal fetal development, and mental health [4]. 

Who is affected by MTHFR?

Interestingly, although variations in the MTHFR gene are quite common, they are not uniformly distributed worldwide. Certain regions of the world see far more cases of MTHFR-related deficiencies than others.

Scientists estimate that 50% of people carry at least one copy of a less effective MTHFR gene variant [5]. More than 40 different polymorphisms of the gene have been identified. 24% of the global population is likely to carry the C677T mutation specifically.

Continentally speaking, C677T is least common in Africans (at a frequency of 10.3%). It is more common in North Americans and Europeans (31.2% and 34%, respectively), with South America, Asia, and Australia falling in between.

An example of such was demonstrated in a study that stated the level of UV radiation in a region was a stronger predictor of C677T than latitude [6]. We also know that environmental toxins can have epigenetic effects on methylation and MTHFR expression.

It is important to remember that these factors may play a significant role in the health repercussions of MTHFR polymorphisms. There are differences in repercussions depending on where and how you live. 

Back to MethylPro Blog


  1. https://www.psychologytoday.com/us/blog/the-integrationist/201409/genetic-mutation-can-affect-mental-physical-health
  2. https://link.springer.com/article/10.1007/s12291-016-0619-0
  3. https://rarediseases.info.nih.gov/diseases/10953/mthfr-gene-mutation
  4. https://link.springer.com/article/10.1007/s10897-016-9956-7
  5. https://mydoctor.kaiserpermanente.org/ncal/Images/GEN_MTHFR_tcm63-938252.pdf
  6. https://www.nature.com/articles/jhg2012113

Leave a Reply

Your email address will not be published. Required fields are marked *