What is the MTHFR Gene and How Can It Affect You?

What is the MTHFR gene?

MTHFR is the gene that provides the instructions for producing an enzyme called methylenetetrahydrofolate reductase. That enzyme plays a central role in a process called methylation — which underpins DNA production and repair, the construction of amino acids, the regulation of gene expression, and the conversion of folate into its usable form.

Like any gene, the MTHFR sequence varies between people. Two common variants (polymorphisms) are found in humans, known as C677T and A1298C. Both can reduce the activity of the MTHFR enzyme to varying degrees.

It is worth stating clearly at the outset: these variants are common. Somewhere between a third and a half of people carry at least one copy of C677T. Carrying an MTHFR variant is not a disease and, for most people, has no noticeable effect on health.

How MTHFR variants can affect you

Homocysteine

In normal metabolism, a molecule called homocysteine acts as an intermediate step in producing certain amino acids. Usually it is short-lived and does not accumulate. The MTHFR enzyme is needed to help convert homocysteine into methionine.

When enzyme activity is reduced — particularly in people who carry two copies of C677T and have low folate intake — homocysteine can build up in the blood. Elevated homocysteine has been associated with damage to the lining of blood vessels and an increased tendency to form clots, which is why it has been studied in relation to deep vein thrombosis, pulmonary embolism and cardiovascular disease.

Importantly, the relationship is not straightforward. Large trials that lowered homocysteine using B vitamins did not consistently reduce cardiovascular events — so raised homocysteine appears to be a marker of risk rather than always a direct cause. Adequate folate intake matters, but the variant alone is not a verdict.

Folate

MTHFR variants can also reduce the efficiency with which folate is converted to its active form, methylfolate. Folate (vitamin B9) is needed for DNA synthesis, amino acid construction and red blood cell production. Insufficient usable folate can contribute to megaloblastic anaemia, in which red blood cells are abnormally large and unable to carry oxygen efficiently — causing fatigue, breathlessness, pallor and headaches.

Because the body cannot manufacture folate, it must come from diet or supplements.

What to do if you carry a variant

For the overwhelming majority of people, the answer is straightforward and unremarkable:

• Eat enough folate. Leafy greens, broccoli, asparagus, chickpeas, lentils, citrus fruit, beetroot, eggs and fortified cereals are all good sources. Steaming rather than boiling preserves more of it.
• Address the bigger levers. Smoking, blood pressure, cholesterol, physical activity and alcohol influence cardiovascular risk far more than an MTHFR variant does.
• Check B12 too. B12 works alongside folate in the same pathway, and deficiency can be masked by high-dose folic acid.
• Pregnancy. Standard folic acid supplementation is still the recommended approach in the UK. If you carry a variant and are planning a pregnancy, discuss it with your GP or midwife rather than self-prescribing high doses.

A word of caution

MTHFR has attracted a considerable amount of misinformation online, with variants blamed for everything from fatigue to complex chronic illness, and expensive supplement protocols sold on that basis. Mainstream genetics and haematology bodies do not support routine MTHFR testing in the general population, and generally advise against it outside specific clinical contexts. Treat any source that promises a supplement cure for an MTHFR variant with real scepticism.

Testing with Rightangled

Rightangled's DNA tests and blood tests can assess genetic variants alongside folate and B12 levels. Results are reviewed by our clinical team, which includes GPhC-registered independent prescribers, with medical oversight from our doctor, Dr Abdullah — so you get realistic context on what a result does and does not mean, rather than a number without interpretation.

Verify us with the General Pharmaceutical Council (registration 9011933), see our LegitScript certification, and read reviews on Trustpilot.

Related reading: folate deficiency and genetics and blood clots.

This article is for general information and does not replace personalised medical advice.