MTHFR Deficiency: What Is This Gene Mutation?

The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme is part of methylation, a process where a methyl group is transferred from one substance to another. This chemical reaction is involved in building and repairing DNA, managing inflammation, and producing energy.

A primary function of the MTHFR enzyme is to help process amino acids. It is responsible for converting vitamin B9, known as folate, into its active form, 5-methyltetrahydrofolate (L-methylfolate). The body requires this active form for a process that converts the amino acid homocysteine into methionine. An “MTHFR deficiency” refers to common genetic variations that make this conversion less efficient.

The MTHFR Gene and Its Variations

Genetic variations, or polymorphisms, in the MTHFR gene are changes in its DNA sequence. The most researched variations are C677T and A1298C, which indicate a specific nucleotide change at a particular position in the gene. For example, C677T means at position 677, cytosine (C) has been replaced with thymine (T).

Every person inherits two copies of the MTHFR gene, one from each parent. An individual can be “heterozygous” for a variation, having one altered gene and one standard copy. A person can also be “homozygous,” carrying two copies of the same altered gene.

The specific combination of these variations determines the degree to which enzyme efficiency is reduced. An individual who is homozygous for the C677T variant may experience a significant reduction in enzyme function, sometimes estimated to be 75% less efficient. Someone who is heterozygous for C677T or has the A1298C variation experiences a milder reduction.

Health Conditions Linked to MTHFR

A less efficient MTHFR enzyme can impair the body’s ability to process folate, leading to an accumulation of homocysteine in the blood (hyperhomocysteinemia). Elevated homocysteine can contribute to inflammation and damage to the inner lining of blood vessels. This has been studied for its connection to cardiovascular problems like blood clots and stroke.

Research has explored associations between MTHFR variations and various health conditions, particularly in individuals with elevated homocysteine. During pregnancy, impaired folate metabolism is a known risk factor for neural tube defects in a developing fetus. Some studies have also investigated links between MTHFR variants and recurrent miscarriages.

Because active folate is needed for the synthesis of neurotransmitters like serotonin, some research has looked into potential associations with depression and anxiety. These findings point to associations, not direct causation. Environmental factors, diet, and other genes all play a part in whether an individual develops a health condition.

Identifying MTHFR Gene Variations

MTHFR gene variations are identified through genetic testing of a DNA sample from blood or saliva. The lab analysis looks for specific single nucleotide polymorphisms (SNPs), such as C677T and A1298C, in the MTHFR gene sequence.

A healthcare provider might suggest testing for a patient with persistently elevated homocysteine levels without a clear cause. Other reasons include a personal or family history of premature cardiovascular disease, certain blood clotting disorders, or recurrent pregnancy loss. This information can help complete a patient’s overall clinical picture.

Direct-to-consumer genetic testing kits often include an analysis of MTHFR variations. While these tests provide access to personal genetic data, interpreting the results without professional guidance can be challenging. A qualified healthcare professional is best suited to explain what the results mean for an individual’s health.

Managing MTHFR-Related Concerns

For individuals with an MTHFR variation and related health concerns like elevated homocysteine, management focuses on supporting the methylation pathway. One approach involves optimizing folate intake through foods like leafy green vegetables, lentils, beans, and asparagus.

Since MTHFR variations hinder the conversion of folic acid, some providers recommend supplements containing the active form, L-methylfolate (5-MTHF). This form is body-ready and bypasses the compromised MTHFR conversion step. This may be a more effective way to support the body’s folate needs and help manage homocysteine levels.

The methylation cycle also relies on other B vitamins. Vitamins B12, B6, and B2 (riboflavin) are involved in homocysteine metabolism. Ensuring adequate intake of these nutrients through a balanced diet or supplementation can provide comprehensive support.

Lifestyle factors also play a supportive role. Regular physical activity, managing stress, avoiding tobacco, and limiting alcohol are beneficial for cardiovascular health and can help maintain balanced homocysteine levels. Any plan with significant dietary changes or new supplements should be monitored by a healthcare provider.