Folate (5-MTHF)

Tier 1 — strong evidence · Pregnancy · Methylation · Mood

The biologically active form of folate that enters the methylation cycle directly, bypassing the DHFR enzyme step that is impaired in carriers of the MTHFR C677T polymorphism (approximately 10-15% of the population are homozygous; ~40% carry at least one variant). Neural tube defects form by day 21-28 post-conception, making preconceptional supplementation essential. A 2025 study (Song, 39269865, Technology Health Care) confirmed 5-methyltetrahydrofolate more effectively reduces homocysteine and adverse pregnancy outcomes than synthetic folic acid in women with high-risk MTHFR genotypes.…

Dose: 400-600 mcg/day 5-MTHF for periconceptional use and throughout first trimester. MTHFR homozygous individuals: 800-1,000 mcg/day of 5-MTHF may be warranted. Depression adjunct use typically 400-800 mcg/day.