MTHFR is the gene for methylenetetrahydrofolate reductase, the enzyme that converts dietary folate into the active form the body uses to recycle homocysteine back into methionine. Two common inherited variants of this gene slow the enzyme down, which is why MTHFR appears on consumer DNA reports and in arguments about B vitamin supplements. The effect is real but modest, and it is largely offset by eating enough folate. A fuller clinical reference is the MTHFR — the gene and the C677T polymorphism entry in the Smart Longevity glossary.
What it measures
MTHFR is not a blood level. It is a genotype, read once from saliva or blood and unchanged for life. Two positions are usually reported: C677T (rs1801133) and the milder A1298C (rs1801131). For C677T a result comes back as CC, CT or TT — no copies, one copy or two copies of the slower variant.
The enzyme sits at one step of the folate cycle. It converts folate into 5-methyltetrahydrofolate, the methyl donor that a vitamin B12-dependent enzyme then uses to turn homocysteine back into methionine. Methionine then feeds the body’s universal methyl donor. So the gene sits upstream of both homocysteine clearance and methyl group supply, and what it needs to work is enough Folate (vitamin B9) coming in.
Typical values
There is no reference range for a gene. What is reported is the genotype, and the widely published figures describe how much enzyme activity each one leaves:
| C677T genotype | What is usually reported |
|---|---|
| CC | No copy of the variant; full enzyme activity |
| CT | One copy; roughly two thirds of normal activity in laboratory assays |
| TT | Two copies; roughly one third of normal activity, and a modestly higher homocysteine level when folate intake is low |
Treat those percentages as laboratory descriptions, not as a diagnosis. The variant enzyme is thermolabile, so measured activity depends on assay conditions, and how common the TT genotype is varies a great deal by ancestry. The number a clinician actually acts on is homocysteine, whose cut-offs differ by lab and assay.
Why it matters for longevity
Carrying two copies of 677T is associated with a higher blood level of Homocysteine, and the size of that gap depends almost entirely on folate status: it is clear where folate intake is low and much smaller in countries that fortify flour with folic acid. Because the genotype is fixed at conception, researchers use it as a natural experiment for lifelong homocysteine exposure. Those genetic studies point toward a small effect on stroke risk and little or none on coronary heart disease, which matches the disappointing results of the B vitamin trials.
The best supported link is not a longevity one at all: maternal folate status and this variant relate to neural tube defect risk, which is why folic acid in early pregnancy is advised for everyone rather than for carriers only. There is no good evidence that MTHFR genotype meaningfully shortens lifespan, and the popular claims that it explains fatigue, anxiety, depression or an inability to detoxify are not supported by the evidence.
What changes it
Nothing changes the gene. What you can change is the folate supply running through it. Leafy greens, legumes, beets, citrus and fortified grains cover it for most people. If you have a result in hand and want to know whether it matters for you, test homocysteine, vitamin B12 and folate, and check kidney function, rather than treating the genotype itself.
Supplements sold as methylfolate deliver the product of the enzyme and so bypass the slow step. They work, but for most carriers ordinary folic acid works too, because enough residual activity remains. Two cautions hold regardless of genotype: high-dose folic acid taken without checking B12 can mask a B12 deficiency while nerve damage continues, and heavy drinking, smoking and several medications push homocysteine up through the same pathway.
Related reading
- Which Blood Tests Reflect Aging and How to Read Them
- How to Build a Longevity Supplement Plan
- How to Eat for Brain Health: A Cognitive Longevity Guide
- Homocysteine
Disclaimer. This article is for information only and does not replace medical advice. Talk to a qualified clinician before changing anything about your health.