Folate (B9)

•RCT evidence— NTD prevention; mortality data more mixed

Why supplementation matters in pregnancy

Folic acid supplementation 1 month before conception through the first trimester reduces neural tube defects (spina bifida, anencephaly) by ~70%. Many countries mandate folic-acid fortification of grain products as a public-health measure.

Outside pregnancy

• Folate deficiency causes megaloblastic anaemia (indistinguishable from B12 deficiency on smear).
• Severe deficiency is now uncommon in fortified countries.
• Cardiovascular benefit from folate supplementation (homocysteine lowering) has been disappointing in RCTs.

The unmetabolised folic acid (UMFA) concern

Folic acid (synthetic) must be reduced to active 5-MTHF by DHFR. The human DHFR pathway saturates around 200–400 μg/dose. High-dose supplementation produces circulating unmetabolised folic acid, with theoretical concerns about:

• Masking of B12 deficiency (well-established).
• Possible cancer-progression in established tumours (debated).
• Cognitive effects in low-B12 elderly (debated).

For non-pregnancy purposes, food folate + modest fortification is usually sufficient. Methylated forms (5-MTHF / L-methylfolate) may be preferred for MTHFR variant carriers and high-dose use.

Related entries

Vitamin B12, Homocysteine, Cancer.