Folate (5-MTHF)

Folate (as 5-methyltetrahydrofolate, the active form) is essential for the methylation cycle — a critical biochemical pathway that affects DNA synthesis, neurotransmitter production, estrogen detoxification, and homocysteine metabolism. Unlike folic acid (the synthetic form), 5-MTHF does not require conversion by the MTHFR enzyme, making it effective even in individuals with MTHFR gene mutations (estimated 40–60% of the population).

Included in the active form specifically because MTHFR mutations are common and impair folic acid conversion. Adequate methylation is critical for estrogen clearance through the COMT pathway — impaired methylation contributes to estrogen dominance and hormonal imbalance.

The superiority of 5-MTHF over folic acid is well-established in individuals with MTHFR polymorphisms. Studies confirm that active folate supplementation improves methylation status, reduces homocysteine, and supports mood and cognitive function.

Best taken with B12 (methylcobalamin) as the two work synergistically in the methylation cycle. The active form is effective at lower doses than folic acid.