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What Is Methylation And Why Should You Care?

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What Is Methylation And Why Should You Care?

DNA double helix MTHFR gene folate folic acidThe topic of methylation is common in the Functional Medicine community. But what is methylation?

Simply put, methylation is a chemical reaction that occurs in every cell and tissue in your body.

Chemically speaking, methylation is the process of adding methyl groups to a molecule. A ‘methyl group’ is a chemical structure made of one carbon and three hydrogen atoms. Since methyl groups are chemically inert, adding them to a protein (the process of methylation) changes how that protein reacts to other substances in the body, thus affecting how that protein behaves. Enzymes, hormones, and even genes are proteins and the process of methylation affects them all.


In some instances, methylation of proteins helps the body detoxify. For example, the methylation process helps convert the toxic amino acid (homocysteine) into a beneficial amino acid (methionine). If your body cannot methylate properly, toxins build up in your bloodstream and will eventually cause disease.

Gene Expression & Enzymatic Activity

Another role of methylation is to help the enzymes in our bodies work efficiently. Enzymes are proteins that act like switches for chemical reactions – they initiate very important processes in every cell and tissue. In a similar way, methylation affects our genes, which are also made up of proteins. In fact, methylation can turn genes on or off, which can be good or bad for our health, depending on the gene.

Some nutrients affect the process of methylation quite dramatically – methyl donors (nutrients like folate and choline) actually donate methyl groups to proteins and methylating factors (nutrients like vitamin B12 and zinc) helps this process along by monitoring specific methylation reactions. How well your body methylates is important to your overall health.

What health issues can arise from impaired methylation?

As you continue to read, you will learn that disruptions in methylation processes can cause a variety of issues, including:

  • Heart Attack
  • Stroke
  • Dementia
  • Depression
  • Migraines
  • Autism
  • Fertility
  • Cancer
  • Birth defects
  • many more

What is MTHFR and how is it related to methylation?

MTHFR (methyletetrahydrofolate reductase) is an enzyme that converts folate into a usable form that our bodies need. It is a key enzyme in an important detoxification reaction in the body – one that converts homocysteine (toxic) to methionine (benign). If the enzyme is impaired, this detoxification reaction is impaired, leading to high homocysteine blood levels. Homocysteine is abrasive to blood vessels, essentially scratching them, leaving damage that causes heart attacks, stroke, dementia, and a host of other problems.

MTHFR converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. It is the 5-methyltetrahydrofolate that converts homocysteine to methionine by the enzyme methionine synthase. Homocysteine can also be converted to methionine by betaine-homocysteine methyltransferase. This enzyme does not require folic acid.

Additionally, when the enzyme MTHFR is impaired, other methylation reactions are compromised. Some of these methylation reactions affect neurotransmitters, which is why impaired MTHFR activity is linked with depression. Inefficiency of the MTHFR enzyme is also linked to migraines, autism, fertility, cancer, and birth defects, all of which depend on proper methylation.

What is the MTHFR Gene?

The MTHFR gene encodes for the MTHFR enzyme. There are variations in the gene that affect the function of the enzyme. This is explained in further detail below. A simple blood test can tell you if you have a variant copy of this gene.

If I have variant copies of the MTHFR gene, what can I do?

If the MTHFR enzyme is inefficient, you may be able to compensate for your body’s inability to methylate efficiently since this biological process is dependent on several B vitamins. You may simply need more B vitamins than someone without a variant copy of this gene, such as vitamin B6, B12 (methylcobalamin) and the active form of folate (5-methyl tetrahydrofolate). Other methyl donors such as SAMe and trimethylglycine (TMG) may also provide benefits. If you have a defective copy of the MTHFR gene, it is important for you to monitor your homocysteine level as well. Fortunately, lowering homocysteine can often be done with the nutrient supplements listed above.

Determining what copies of the MTHFR gene you have gives you the ability to compensate accordingly. The old paradigm that we are simply at the mercy of our genes is now challenged. Genetic testing empowers you to take control, launching you into a new age of truly individualized healthcare.

There are DNA sequence variants of MTHFR and the two most commonly evaluated are 677 & 1298. These two differ by one nucleotide at either of 2 locations. The 677 refers to the nucleotide at the 677 position and 1298 is the nucleotide position of the other abnormality. This difference is often referred to as a Single Nucleotide Polymorphism (SNP). Abnormal variants are considered ‘thermolabile’ meaning that they measure the amount of enzyme activity after the enzyme is inactivated by heat.

The 677 MTHFR Mutation

The 677 variant of MTHFR has 2 possibilities: Cysteine (C) and Thymine (T). There are 3 different options for expression of this gene:

  • C/C – “normal” or “wildtype”. About 45% of the population have this genotype.
  • C/T – called ‘heterozygous’ and are considered essentially normal since the normal MTHFR will be able to compensate for the thermolabile MTHFR and there doesn’t appear to be any increased risk. About 45% of the population have this one.
  • T/T – considered to have mild MTHFR deficiency. About 10% of the population

The 1298 MTHFR Mutation

There are 2 possibilities for the nucleotide at the 1298 position, A & C. ‘A’ encodes for the normal glutamine amino acid and ‘C’ substitutes an Alanine amino acid. The C variant does not appear to affect the MTHFR activity nor homocysteine levels.

Severe MTHFR deficiency is rare and results from mutations causing 0-20% enzyme activity. Patients with severe MTHFR deficiency may have developmental delay, motor abnormalities, high levels of homocysteine, seizures, and other neurologic impairment. They will also have low levels of methionine in their blood.