Synthetic form of folate (vitamin B9) that must be converted to active 5-MTHF (5-methyltetrahydrofolate) by MTHFR enzyme. Essential cofactor for one-carbon metabolism, providing methyl groups for DNA synthesis, methylation reactions, and homocysteine recycling.
Folic acid is reduced to dihydrofolate (DHF), then tetrahydrofolate (THF), then 5,10-methylene-THF, and finally 5-MTHF by MTHFR. 5-MTHF donates methyl groups to homocysteine (via B12-dependent methionine synthase) to regenerate methionine, which forms SAMe (S-adenosylmethionine), the universal methyl donor for DNA methylation, histone methylation, and neurotransmitter synthesis.
Essential for epigenome maintenance and repair, particularly DNA methylation and histone modification. Deficiency causes hypomethylation, neural tube defects, elevated homocysteine, and impaired neurotransmitter synthesis. MTHFR polymorphisms reduce conversion efficiency, requiring higher intake or direct 5-MTHF supplementation. Critical for preconception care and addressing methylation-related conditions.
- Converted to active 5-MTHF by MTHFR enzyme
- Essential cofactor for one-carbon metabolism and methylation
- Deficiency causes elevated homocysteine (>15 μmol/L)
- Required for DNA synthesis and repair
- Provides methyl groups for DNA and histone methylation
- MTHFR C677T polymorphism reduces conversion efficiency by 30-70%
- Works synergistically with vitamin B12 and B6
- Deficiency associated with neural tube defects, depression, cardiovascular disease
- Daily requirement ~400 μg, higher in pregnancy (600-800 μg)
- 5-MTHF — folic acid must be converted to active 5-MTHF form
- MTHFR — enzyme catalyzing rate-limiting conversion of folate to 5-MTHF
- methylation — folic acid provides methyl groups for methylation reactions
- DNA methylation — folate-derived methyl groups essential for DNA methylation
- histone modification — supports histone methylation as cofactor
- SAMe — folate cycle regenerates methionine, precursor to SAMe
- homocysteine — folate required to recycle homocysteine to methionine
- vitamin B12 — B12 required as cofactor for folate-dependent homocysteine recycling
- vitamin B6 — B6 cofactor for alternative homocysteine pathway (transsulfuration)
- one-carbon metabolism — folate is central carrier in one-carbon metabolism
- epigenetics — folate deficiency causes epigenetic dysregulation
- neurotransmitters — methylation required for serotonin, dopamine, norepinephrine synthesis
- Depression — folate deficiency linked to depression via impaired methylation
- neural tube defects — folate deficiency primary cause of neural tube defects
- cardiovascular disease — folate deficiency raises homocysteine, CVD risk factor
- pregnancy — increased folate requirements during pregnancy for fetal development
- DNA synthesis — folate required for thymidine synthesis in DNA replication
- methylfolate — active form bypassing MTHFR conversion step
- betaine — alternative methyl donor for homocysteine remethylation
- atherosclerosis — folate status inversely associated with atherosclerosis risk