The Methylation Cycle & the MTHFR Gene

The Methylation Cycle

The methylation process plays a vital role in many biological processes. Methylation is the transformation of inactive substances into active elements the body can directly use. The methylation process itself is very complex and controlled by various enzyme reactions. To keep methylation running smoothly these enzymes require optimal levels of B vitamins, especially folate (Vitamin B9).


The process of methylation is involved with activities throughout the body such as:

  • Detoxification
  • Inflammation
  • Supporting neurotransmitter balance – the brain’s communication chemicals
  • Turning the stress response on and off
  • Processing hormones
  • Building immune cells
  • Producing energy
  • Repairing cell membranes
  • Repairing and building DNA and RNA

The methylation pathway can be disrupted by various factors including medications (antacids), nutritional deficiencies, environmental toxins, and genetic variations.

Folic Acid & the MTHFR Enzyme

The MTHFR enzyme (Full Scientific Name: Methylenetetrahydrofolate Reductase) is responsible for converting folic acid (Vitamin B9) and dietary folate into an activated form which the body can use , Methylfolate (5-MTHF). The body cannot use folic acid as it is a synthetic form of folate and MUST be converted into Methylfolate before the body can use it.

Methylfolate  is involved in many biochemical processes including the multistep breakdown of homocysteine and for the production of neurotransmitters (Dopamine, Norepinephrine, & Serotonin) through the Biopterin Cycle. Elevated homocysteine is an independent risk factor for cardiovascular disease including atherosclerosis, heart attack, stroke and venous thrombosis from increased blood clots.

Impact of Genetic Variation

You may have seen the acronym SNP (sounds like snip) used when discussing MTHFR genetics. It stands for Single Nucleotide Polymorphism. SNP is basically another word for a mutation on your gene.

The MTHFR gene, which is encoded in your DNA, produces the MTHFR enzyme. There are 50 different mutations that could occur on this important gene. These SNPs could be passed down by one, or both or your parents. Two of these SNPs are especially important: mutations on the points of C677T and A1298C.

People with a mutation on the MTHFR gene can produce an enzyme that does not properly convert folic acid into the biologically active and useful form called Methylfolate (5-MTHF).



SNPs of the C677T position are more frequently associated with cardiovascular and developmental issues where the A1298C position is associated with more neurological and cognitive issues.

It's important to know that increasing synthetic folic acid intake will not solve the problem and may even make conditions worse. Not everyone with a genetic variation will have the same set of symptoms because there are many other genetic and environmental differences that can complicate and influence health conditions.


Various health conditions  have been associated with MTHFR genetic mutations

What do genetic testing results look like?

Approximate loss of MTHFR enzyme function can be estimated by genetic testing

Many other genes can impact your body's methylation pathway.

Some tests may only target variations on the MTHFR gene. By using your raw DNA data from 23andme, you can submit your information to be translated for many more genetic variations that can impact the methylation process. This will allow for a more complete action plan based on your specific genetic makeup.