MTHFR Gene Mutation (MTHFR Variant)

What the MTHFR enzyme does

MTHFR converts one form of folate into 5-methyltetrahydrofolate, the active form the body uses to convert homocysteine into methionine. When the enzyme works less well, homocysteine can rise, particularly if folate intake is low.

Common variants

These variants are called "polymorphisms" because they are so common in the general population. In countries where grains are fortified with folic acid, such as the US, homocysteine levels in people with these variants are usually normal.

What the evidence says

Blood clots

Large studies have found that MTHFR variants do not meaningfully increase the risk of venous blood clots such as deep vein thrombosis. The American College of Medical Genetics and Genomics recommends against MTHFR testing as part of a thrombophilia workup.

Pregnancy and miscarriage

ACOG does not recommend MTHFR testing for recurrent miscarriage, preeclampsia or other pregnancy complications, because there is no consistent evidence of a link and no proven treatment benefit.

Neural tube defects

Some studies suggest a small increased risk of neural tube defects such as spina bifida in babies of mothers with two copies of C677T, mainly when folate is low. The CDC states that people with MTHFR variants can process folic acid and that the standard recommendation applies: 400 micrograms of folic acid daily for anyone who could become pregnant, starting at least 1 month before conception.

Heart disease, depression and other conditions

MTHFR variants have been studied in heart disease, stroke, depression, migraine, autism and other conditions. Results are inconsistent, and lowering homocysteine with B vitamins has not reduced heart attacks or strokes in clinical trials.

Folic acid vs methylfolate

Some websites and supplement makers claim that people with MTHFR variants cannot use folic acid and need "methylated" folate (L-methylfolate). This is not supported by evidence. Folic acid from supplements and fortified foods raises folate levels and lowers homocysteine in people with MTHFR variants. Methylfolate is an acceptable alternative but not necessary.

Severe MTHFR deficiency

A rare inherited disorder, different from common polymorphisms, causes severe MTHFR deficiency with very high homocysteine and homocystinuria. It appears in infancy or childhood with developmental delay, seizures, low muscle tone, small head size and blood clots. It is detected through newborn screening in some areas or by specialist testing, and treated with betaine and vitamins under a metabolic specialist.

Testing

Routine MTHFR testing is not recommended by the American College of Medical Genetics and Genomics, ACOG or the American Heart Association. If there is a clinical concern, measuring homocysteine in the blood is more useful than genotyping. If homocysteine is high, doctors check vitamin B12, folate, kidney function and thyroid, which are more common causes of high homocysteine.

What to do if you have an MTHFR variant

• Eat a balanced diet with folate-rich foods: leafy greens, beans and fortified grains.
• If you could become pregnant, take 400 micrograms of folic acid daily.
• Do not start blood thinners or high-dose supplements based on MTHFR results alone.
• Discuss real risk factors for blood clots and pregnancy complications with your doctor.

Frequently asked questions

What does it mean to have an MTHFR gene mutation?

It usually means you carry one or two copies of a common variant, C677T or A1298C, that slightly lowers the activity of an enzyme involved in processing folate. For most people, this has no effect on health and needs no treatment.

What are the symptoms of an MTHFR mutation?

Common MTHFR variants do not cause symptoms. Lists of symptoms found online are not supported by evidence. Only the very rare severe MTHFR deficiency, a different condition, causes symptoms such as developmental delay and seizures in childhood.

Can I take folic acid if I have an MTHFR variant?

Yes. People with MTHFR variants process folic acid effectively. The CDC recommends that everyone who could become pregnant take 400 micrograms of folic acid daily, regardless of MTHFR status. Methylfolate is not necessary.

Should I be tested for MTHFR?

Routine testing is not recommended, including for blood clots, miscarriage or infertility, because results do not change care. If there is a concern, a homocysteine blood test is more useful. Discuss it with your doctor.

Does MTHFR cause miscarriages or blood clots?

Large studies have not shown that common MTHFR variants meaningfully increase the risk of blood clots or recurrent miscarriage. Medical societies advise against testing for these reasons and against treatment based on MTHFR status alone.