Vitamin B9 (Folate)
Water-soluble vitaminsYour intake
What each level of vitamin b9 (folate) does
Approximate dose-response bands. Individual response varies — these are starting points, not prescriptions.
- Severely lowYOU ARE HERE0 mcg – 132 mcg
Risk of neural tube defects in pregnancy, megaloblastic anemia, elevated homocysteine.
- Insufficient132 mcg – 400 mcg
Methylfolate (5-MTHF) is the active form most useful for MTHFR variants.
- Adequate400 mcg – 600 mcg
DV (400 mcg DFE) met. Critical for methylation, DNA synthesis, and red blood cell formation.
- Therapeutic600 mcg – 800 mcg
Pregnant people often need 600–800 mcg DFE; check with provider.
- High800 mcg – 1000 mcg
Approaching the 1000 mcg supplemental UL — can mask B12 deficiency.
- Over upper limit1000 mcg – +
Above UL — may mask B12 deficiency and contribute to unmetabolized folic acid in circulation.
Overview
Folate is a B vitamin essential for one-carbon transfer in DNA synthesis, methylation, and amino acid metabolism. Adequacy in early pregnancy prevents neural tube defects — one of the highest-leverage micronutrient interventions in public health. Folic acid (synthetic) and 5-MTHF (natural active form) have important practical differences.
Functions
- ●Carries one-carbon units for purine and thymidylate synthesis (DNA)
- ●Converts homocysteine to methionine (methylation cycle)
- ●Required for hematopoiesis
- ●Critical for embryonic neural tube closure (days 21–28)
Mechanism
Folate enters the cell as 5-MTHF, donates a methyl group to homocysteine via methionine synthase (B12-dependent), and re-enters the cycle as THF. THF is reloaded with one-carbon units from serine and recycled through MTHFR back to 5-MTHF. MTHFR 677T variants reduce enzyme efficiency — folate demand rises in homozygotes.
Benefits
- ●Periconception folic acid (400 mcg/day) reduces neural tube defect risk by 50–70%
- ●Lowers homocysteine when combined with B12 and B6
- ●Reduces megaloblastic anemia
- ●May modestly reduce stroke risk in folic-acid-naïve populations (CSPPT trial)
Deficiency
Reduced sharply by mandatory grain fortification (1998 in US), but still common in pregnancy, alcoholism, malabsorption, and on certain medications.
- ●Megaloblastic anemia (macrocytic, hypersegmented neutrophils)
- ●Glossitis, mouth ulcers
- ●Fatigue, irritability, cognitive slowing
- ●Elevated homocysteine on labs
- ●All pregnant or planning-to-conceive women
- ●Chronic alcoholism
- ●Methotrexate, sulfasalazine, phenytoin, trimethoprim users
- ●Celiac, IBD, gastric bypass
Excess
Folic acid above 1,000 mcg/day can mask B12 deficiency anemia while neurological damage progresses unchecked. Possible link between unmetabolised folic acid in serum and immune effects — clinical significance debated.
- ●Masked B12 deficiency (haematological correction without neurological correction)
- ●Possible increased risk of certain cancers (controversial)
Forms
- Folic acidSynthetic; stable; the fortification form; requires DHFR-mediated reduction
- Folinic acid (5-formyl-THF, leucovorin)Bypasses DHFR; used as methotrexate rescue
- 5-methyltetrahydrofolate (5-MTHF, methylfolate, Metafolin)Active circulating form; bypasses MTHFR
- Dietary folate (mixed polyglutamates)Natural food form; deconjugated to monoglutamate in gut
Food sources
- Beef liver (cooked) · 3 oz215 mcg DFE
- Lentils (cooked) · 1/2 cup180 mcg DFE
- Cooked spinach · 1 cup260 mcg DFE
- Asparagus (cooked) · 1/2 cup135 mcg DFE
- Avocado · 1 medium165 mcg DFE
- Fortified bread · 1 slice60 mcg DFE
Supplement forms
Methylfolate (5-MTHF, L-methylfolate) is the active form and bypasses the MTHFR step. For routine prenatal use, folic acid in the standard 400–800 mcg range remains the most clinically validated. Always pair high-dose folate with B12 — folate alone can mask B12 deficiency and let neurological damage progress.
Bioavailability
Folic acid is ~85% bioavailable; food folate is ~50% (hence the DFE conversion: 1 mcg food folate = 0.6 mcg folic acid taken with food). High doses of folic acid saturate DHFR, producing unmetabolised folic acid in serum — uncertain long-term significance. 5-MTHF is absorbed and used directly.
Longevity relevance
Adequacy reduces cardiovascular risk markers (homocysteine) and prevents major birth defects — both serious long-horizon benefits. Excess from over-fortification + supplements is the modern concern; aim for adequacy through food when not pregnant.
Relationships
- Vitamin B12 · Required co-substrate in methionine synthase; isolated folate masks B12 deficiency
- Vitamin B6 · Combined B6+B9+B12 protocol for homocysteine reduction
- Riboflavin · FAD-dependent MTHFR activity; matters most for 677T variants
- Methotrexate · DHFR inhibitor; folate antagonist (intentional); leucovorin rescue used
- Sulfasalazine, trimethoprim · Impair folate absorption/metabolism
- Phenytoin, phenobarbital, primidone · Reduce serum folate; may worsen seizure control if abruptly repleted
- Alcohol · Reduces absorption and accelerates urinary loss
References
About Vitamin B9 (Folate)
One-carbon metabolism; DNA synthesis, methylation, red blood cell formation.
- Role
- DNA synthesis
- Daily target
- 400 mcg (DV)
- Upper limit
- 1000 mcg
- Also called
- folate, folic acid, vitamin b9, vitamin b-9, methylfolate, 5-mthf
Forms with lower absorption: folic acid. Prefer better-absorbed forms when supplementing.
The mechanisms and systems this nutrient feeds. Click any to drill into what runs on it.
★ = load-bearing / primary cofactor. Track these in My Journey.