Définition
Methylfolate (5-MTHF) is the biologically active form of folate — the form your cells actually use. People with MTHFR gene variants convert dietary folate and synthetic folic acid poorly, making direct methylfolate supplementation essential for their methylation capacity.
Folate from food (in green leafy vegetables, legumes, liver) must be converted through several enzymatic steps to reach its active form, 5-methyltetrahydrofolate (5-MTHF). The final conversion is performed by MTHFR (methylenetetrahydrofolate reductase). Once active, 5-MTHF donates its methyl group to convert homocysteine to methionine — the entry point of the methylation cycle.
Roughly 40% of the population carries at least one variant in the MTHFR gene. The C677T variant is the most studied: heterozygotes (one copy) have approximately 30% reduced enzyme activity; homozygotes (two copies) have approximately 60% reduced activity. These individuals convert dietary folate and synthetic folic acid less efficiently, which can lead to elevated homocysteine, impaired DNA methylation, and in some cases mood disorders.
Folic acid — the synthetic form added to fortified foods and most prenatal vitamins — requires the same MTHFR conversion as dietary folate. Worse, unmetabolized folic acid can accumulate in the blood of individuals with MTHFR variants, potentially interfering with folate receptors. This is why longevity-oriented clinicians increasingly recommend methylfolate over folic acid, especially in prenatal and methylation support contexts.
Supplemental 5-MTHF bypasses the MTHFR conversion entirely. Common forms are L-methylfolate or Quatrefolic (a patented stable form). Typical dosing is 400–1000 mcg daily for general methylation support, with higher doses used in specific clinical protocols.
For women, methylfolate is particularly relevant in three contexts: before and during pregnancy (folate demands spike dramatically), during hormonal contraceptive use (which depletes folate status), and throughout perimenopause when methylation-dependent estrogen clearance becomes rate-limiting.
Ava Longevity · Built on the Ava Method · MMXXV