MTHFR mutation: what it is and what it does to your homocysteine

A sizeable share of the European population carries a variant in the MTHFR gene. That is not a rare defect, that is almost normal. And yet the MTHFR test gets sold online as though it reveals a hidden health secret. That tension is exactly what this article is about.

Let me say it straight away: chances are an MTHFR test changes nothing about what you would do. The American professional body for medical genetics even advises against the test in standard workups (PMID 23288205). Below I explain why, and what you can look at instead.

What is the MTHFR gene?

MTHFR stands for methylenetetrahydrofolate reductase, an enzyme that converts folate into the active form your body can use. That active form is needed to break homocysteine down again. The MTHFR gene holds the blueprint for that enzyme. If the enzyme works more slowly, homocysteine can build up.

The best known variant is called C677T and was described in 1995 (Frosst et al., PMID 7647779). Anyone with two copies of that variant is left with a clearly lower enzyme activity. With one copy the effect is a good deal smaller.

What does an MTHFR mutation do to your homocysteine?

With two copies of C677T your homocysteine sits somewhat higher on average than in people without the variant. The effect is real, but it is modest, and it depends heavily on how much folate you take in. With a good folate intake the difference largely disappears. So genetics does not set your value, it sets how sensitive you are.

Does an MTHFR variant raise your risk of heart disease?

Barely, and this is better studied than most people think. The MTHFR Studies Collaboration pooled data on the C677T variant and coronary heart disease in a meta-analysis and found at most a small effect (PMID 12387655). That study is also a strong test of the homocysteine story itself.

This comes down to the design. Your genotype is fixed at birth and is not influenced by your lifestyle, so if higher homocysteine truly causes heart disease, carriers of the slow variant should have more heart disease. That link proved small to absent. Together with the trials that tested lowering (Cochrane, PMID 28816346), it all points the same way.

Is an MTHFR test useful?

For most people, no. The American professional body for medical genetics concluded that MTHFR genotyping has minimal clinical utility and does not belong in a routine workup for thrombophilia (PMID 23288205). The reason is sober: the result rarely changes what happens next.

Say you test positive for two copies of C677T and your homocysteine is 11 micromol per litre. What changes then? Nothing, because your value is normal. Say your homocysteine is 22: then you look at your folate, your B12 and your kidney function. Exactly what you would have done without the gene test.

So my advice is simple: measure the consequence, not the predisposition. See the homocysteine marker page, and read why that value is mainly a signal in our spoke on homocysteine and your blood vessels.

What can you do with a high value?

With a raised homocysteine, looking into a B12 or folate shortage is the obvious step, alongside your kidney function. A shortage is worth knowing about in itself, quite apart from your vessels. What is sensible after that depends on your situation and belongs with your GP.

More about those shortages sits in our articles on vitamin B12 deficiency and folate deficiency. How all of this fits the vascular story sits in our pillar on narrowed blood vessels. The RIVM keeps the figures on cardiovascular disease in the Netherlands.

Frequently asked questions

Is an MTHFR mutation hereditary?

Yes, you get the variant from your parents. It is so common that carrying it is normal in many families. Carrying it alone says little about your health.

Should I take active folate with an MTHFR variant?

This gets advised a lot online, but the evidence that it achieves anything at a normal value is thin. Separate advice applies when trying to conceive. Discuss this with your GP.

What I would leave you with

Do not let yourself be talked into a gene test to answer a question an ordinary blood value answers better. If your homocysteine is raised, ask your GP about your folate, your B12 and your kidney function. Every blood test result at Vitalcheck includes a professional assessment from a BIG-registered doctor. Always discuss treatment decisions with your GP.

References

• Frosst P, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genetics. 1995. PMID 7647779
• Clarke R, et al. MTHFR 677C to T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA. 2002. PMID 12387655
• Hickey SE, et al. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genetics in Medicine. 2013. PMID 23288205
• Marti-Carvajal AJ, et al. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database of Systematic Reviews. 2017. PMID 28816346
• RIVM. Cardiovascular disease: figures and context. Volksgezondheid en Zorg. Accessed 2026.