# MTHFR C677T variant

The MTHFR C677T variant (rs1801133) is a common tweak in the MTHFR gene that makes a heat-sensitive, slower version of the enzyme. People with two copies (TT) keep only about 30% of normal activity, and those with one copy (CT) about 65%, especially when folate is low. The result is a modest rise in blood homocysteine. High homocysteine has been linked in population studies to heart disease and neural tube defects, and this variant is associated with those outcomes too, though whether homocysteine itself is the cause is still debated. Should you get tested for it? Major genetics and lab societies say no, not routinely: the effect is small, it is fixable with diet, and B-vitamin supplements to lower homocysteine have not reliably cut heart events in trials. Despite that, it stays one of the most over-ordered genetic tests in functional-medicine circles.

## Sources

- Frosst P, Blom HJ, Milos R, et al.. (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genetics. https://doi.org/10.1038/ng0595-111

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_Canonical: https://longevity-switzerland.com/en/glossary/mthfr-c677t · Part of Longevity Cities · Updated 2026-06-22_