Guides · Supplements

MTHFR mutation: what it is and what it really means

An MTHFR "mutation" is usually a common gene variant, C677T or A1298C, that slightly lowers how well one folate enzyme works, and for most people it causes no health problems. More people in the United States carry at least one copy of C677T than carry none.

Two copies of C677T can mildly raise homocysteine. Links to blood clots, miscarriage, mood disorders and other conditions have not held up in large studies, so what matters is your homocysteine level and your folate and B12 status.

Updated · Facts checked against the sources listed below

Gabriel Optimal Range StandardTypical lab reference ranges vary by lab. Your lab's own flag decides what is abnormal; Gabriel's optimal range is a target to discuss with your clinician.
MarkerGabriel optimalTypical lab rangeFunctional range
Homocysteine5 to 7 umol/L15 or lower5 to 7.2

What the MTHFR gene does

MTHFR stands for methylenetetrahydrofolate reductase. The gene makes an enzyme that turns one form of folate (vitamin B9) into 5-methyltetrahydrofolate, the main form of folate in your blood. Your body uses that form to convert the amino acid homocysteine into methionine, which it needs to build proteins.

When the enzyme works less well, homocysteine can build up. Severe loss of the enzyme, from rare and different mutations, causes homocystinuria, a serious inherited condition usually found in infancy. The common variants are much milder.

C677T and A1298C: one copy or two

You have two copies of the MTHFR gene, one from each parent. So you can carry zero, one or two copies of a variant, or one copy each of two different variants.

Summary of MedlinePlus and CDC guidance. Your homocysteine level matters more than the genotype.
GenotypeWhat it means
One copy of C677T or A1298C (heterozygous)Very common. Unlikely to cause health problems on its own.
Two copies of C677T (homozygous, TT)The enzyme is less active. Can cause a mild rise in homocysteine.
One C677T plus one A1298C (compound heterozygous)May help explain a high homocysteine if one is found.
Two copies of A1298CProbably does not explain a high homocysteine.

MedlinePlus estimates that about 25% of Hispanic people and 10% to 15% of white North Americans carry two copies of C677T. The CDC adds that people with two copies have blood folate only about 16% lower than people with none at the same folic acid intake, and that intake matters more than genotype.

Real effects vs overstated claims

MTHFR variants are blamed online for a long list of symptoms and conditions. The research is weaker than those claims suggest.

  • Homocysteine: a real but usually mild effect, mainly with two copies of C677T.
  • Blood clots: large meta-analyses found no meaningful link between the common variants and clot risk. A 2023 Cleveland Clinic review advises focusing on known risks such as weight, smoking and inactivity instead.
  • Pregnancy: studies found a small increased risk of neural tube defects with C677T, but most carriers have unaffected pregnancies, and folic acid is still recommended. Links to recurrent miscarriage are inconclusive.
  • Mood, heart disease, cancer and other conditions: studies have had mixed results, and MedlinePlus says the gene's role remains unclear.

There are no specific "MTHFR mutation symptoms." If you feel unwell, the cause is far more likely to be something a clinician can test for directly, such as low B12, low iron or thyroid problems.

What to do if you have an MTHFR variant

  1. Check homocysteine, not the gene again. A homocysteine blood test shows whether the variant is having any effect. See the homocysteine lab guide.
  2. Check folate and B12 if homocysteine is high. See the folate and vitamin B12 lab guides.
  3. Eat folate-rich foods. See MTHFR diet.
  4. Don't stop folic acid if you could become pregnant. The CDC says people with MTHFR variants can process it. See folic acid vs methylfolate.
  5. Let your clinician choose any supplement. Treatment for high homocysteine is the same with or without a variant.

See a clinician promptly for signs of a blood clot (one swollen, painful leg; sudden shortness of breath or chest pain) or of a stroke (face drooping, arm weakness, trouble speaking), whatever your MTHFR result.

Common questions

Is an MTHFR mutation serious?

Usually not. The common variants are found in a large share of people and on their own rarely cause health problems. A rare, severe MTHFR deficiency is different and is usually found in infancy.

Is MTHFR inherited from both parents?

You get one copy of the gene from each parent. Two copies of a variant means each parent passed one on.

What is worse, C677T or A1298C?

C677T has the larger effect, especially with two copies. Two copies of A1298C probably do not raise homocysteine meaningfully, and the CDC says there isn't enough evidence A1298C alone affects folate processing much.

Can people with MTHFR take folic acid?

Yes. The CDC says people with an MTHFR variant can process all types of folate, including folic acid.

What are the symptoms of an MTHFR mutation?

The common variants have no specific symptoms. If you have symptoms, ask your clinician to test the likely causes directly, starting with homocysteine, B12 and folate.

Sources

  1. MTHFR gene MedlinePlus Genetics, U.S. National Library of Medicine
  2. MTHFR Gene Variant and Folic Acid Facts Centers for Disease Control and Prevention
  3. MTHFR Gene Test MedlinePlus, U.S. National Library of Medicine
  4. Is the MTHFR gene mutation associated with thrombosis? (Dhawan and Eng, 2023) Cleveland Clinic Journal of Medicine
  5. MTHFR gene testing (First do no harm) Royal Australian College of General Practitioners

This guide is general information, not medical advice. It does not replace a visit with a licensed clinician. Gabriel membership is not health insurance.