Folate (B9)
Folic acid / methylfolate / 5-MTHF · Foundation
One of the few supplements with a proven, population-scale preventive effect — and one specific interaction that matters.
What the evidence says
Folic acid before and during early pregnancy substantially reduces neural-tube defects — one of the most firmly established supplement findings anywhere, and the reason many countries fortify flour. Outside that, benefits are much less clear, and large trials of folate for cardiovascular prevention were null.
What studies used
Requirements sit near 400 mcg DFE/day; pregnancy-prevention guidance uses 400–800 mcg. Published studies had not established a preferred timing.
Reported from published studies and product labelling — a record of what was used in research, not a recommendation. What is right for you is a conversation with a clinician.
Watch out for
- High folic acid can mask the anaemia of B12 deficiency while the neurological damage progresses — the reason the two are assessed together
- The methylfolate-versus-folic-acid debate around MTHFR variants is far more settled in marketing than in the evidence
Evidence base
established literature
Large human evidence base: several phase 3 or 4 trial reports, plus multiple meta-analyses or systematic reviews.
This letter measures how much human research exists, not whether it works for you — the tier above (Strong) is the read on quality.
Research (12)
- Supplementation with Folic Acid or 5-Methyltetrahydrofolate and Prevention of Neural Tube Defects: An Evidence-Based Narrative ReviewNutrients · 2024
- Folate, folic acid and 5-methyltetrahydrofolate are not the same thingXenobiotica · 2014
- Folic acid versus 5- methyl tetrahydrofolate supplementation in pregnancyEur J Obstet Gynecol Reprod Biol · 2020
- Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation StatementJAMA · 2023
- Folic Acid, Folinic Acid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon CyclesBiomolecules · 2022
- Guideline No. 427: Folic Acid and Multivitamin Supplementation for Prevention of Folic Acid-Sensitive Congenital AnomaliesJ Obstet Gynaecol Can · 2022
- The Concept of Folic Acid in Health and DiseaseMolecules · 2021
- The epidemiology of global micronutrient deficienciesAnn Nutr Metab · 2015
- Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defectsNutrients · 2013
- How I treat anemia in pregnancy: iron, cobalamin, and folateBlood · 2017
- Folic acidCrit Rev Clin Lab Sci · 2001
- Folate receptors and neural tube closureCongenit Anom (Kyoto) · 2017
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