Evidence check: MTHFR in the context of longevity

The relevance of MTHFR variants (e.g., C677T) for longevity is often overstated. The link is indirect via homocysteine: elevated levels are a risk factor for cardiovascular disease, which can affect lifespan. However, randomized trials show that lowering homocysteine with folic acid, B12, and B6 does not significantly reduce cardiovascular events or total mortality. Moreover, the homocysteine increase in MTHFR variants is usually mild and can be compensated by adequate nutrient intake. Longevity research focuses more on epigenetic clocks, inflammation markers, and telomere length. A single MTHFR SNP alone is not a strong predictor of lifespan. Consumer DNA tests tend to exaggerate its clinical importance. Evidence: mixed – mechanistic and epidemiological, but lacking robust interventional data for longevity. Caution against self-medication with high-dose methylfolate.