Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that breaks down the amino acid homocysteine. If the MTHFR gene that codes for this enzyme mutates, it may contribute to health issues, such as depression or some cancers.

People have two MTHFR genes, inheriting one from each of their parents. Mutations can affect one (heterozygous) or both (homozygous) of these genes.

The mutations can lead to high levels of homocysteine in the blood, which may contribute to health conditions, including birth anomalies and coronary heart disease.

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There are two common types, or variants, of MTHFR mutations: C677T and A1298C.

These gene variants are relatively common. According to a 2019 study, around 47% of people of Hispanic descent and 36% of Europeans are carriers of the C677T variant.

The same article suggests that around 43% of people of South East Asian descent and 31% of Europeans are carriers of the C677T variant.

Mutations in the MTHFR gene can affect the body’s ability to process amino acids — namely, homocysteine — which can lead to adverse health outcomes.

Research associates the following conditions with MTHFR gene variants:

  • Hyperhomocysteinemia: This is the term for abnormally high levels of homocysteine in the blood or urine.
  • Cardiovascular diseases: This may include coronary heart disease, blood clots, stroke, and heart attack.
  • Birth irregularities: This may include neural tube defects or conditions such as microcephaly, in which the head is smaller than expected at birth.
  • Dementia: Dementia involves symptoms of cognitive decline, such as memory loss, confusion, and mood changes.
  • Mental health conditions: People with the MTHFR gene variant may be at higher risk of depression.
  • Drug-induced toxicity: People with the MTHFR gene variant may have a higher risk of toxicity from medication affecting folate homeostasis, such as methotrexate (MTX).
  • Peripheral neuropathy: This is a neurological condition that damages the nerves.

Symptoms of MTHFR gene variants

Symptoms vary among individuals and depend on the type of mutation someone has. People may not know they have an MTHFR gene variant unless they experience severe symptoms or undergo genetic testing.

Having one or two MTHFR variants can increase the levels of homocysteine, an amino acid that the body produces by breaking down dietary proteins, present in the blood.

High levels of homocysteine can damage blood vessels and lead to blood clots. People with high homocysteine levels may have low levels of certain vitamins, such as vitamin B12.

Research associates certain complications with hyperhomocysteinemia due to MTHFR variants, including:

If a doctor suspects someone has an MTHFR gene variant, they may review a person’s medical history, consider their current symptoms, and perform a physical examination.

They may also order blood tests to check the person’s homocysteine levels or genetic testing.

Some companies offer direct-to-consumer genetic testing. A 2024 article suggests that, while this may be a more affordable and accessible option, it may be less accurate.

Direct-to-consumer testing may also lack counseling for people with positive results and proper genetic interpretations.

The article concludes that further research is necessary to understand the benefits of genetic testing for MTHFR gene variants and the risk of potential health conditions.

Having two copies of the MTHFR gene variant may increase the risk of certain pregnancy complications.

Healthcare professionals may suggest taking folic acid supplements to reduce the risk of certain pregnancy complications, such as neural tube defects, whether or not someone has an MTHFR gene variant.

The Centers for Disease Control and Prevention (CDC) recommends that pregnant people take 400 micrograms (mcg) of folic acid daily.

Existing research has not shown that testing for an MTHFR variant would have clinical value. For this reason, current guidelines from the American College of Medical Genetics and Genomics state not to screen for this variant routinely.

According to the CDC, doctors may recommend dietary and lifestyle changes to help offset any resulting nutritional deficiencies in people with an MTHFR variant.

For example, people with high homocysteine levels due to folate or vitamin B12 deficiencies can take folic acid or vitamin B12, respectively.

MTHFR gene variants will not change a person’s treatment plan for any other condition they happen to have.

If someone with an MTHFR variant has a blood clot, for example, they will usually receive the same treatment for the blood clot as someone who does not have this type of variant.

People inherit one copy of the MTHFR gene from each of their parents, meaning that everyone has two MTHFR genes. Mutations can occur in one or both of these genes.

MTHFR gene variants do not affect everyone in the same way. People with one or more MTHFR variants may have higher levels of homocysteine in their blood or urine.

Although existing research has identified associations between MTHFR variants and certain health conditions, more research is necessary to determine the exact effects of these gene mutations on health.

People can speak with a doctor about the benefits and risks of genetic testing or about dietary changes that may help to balance homocysteine levels.