Folic Acid

Folic Acid is a tier 2 form of Folate (Vitamin B9), used in 10,630 on-market products .

Why this tier: Extremely well-evidenced for neural-tube-defect prevention and highly stable/cheap, but requires multi-step enzymatic reduction (DHFR then MTHFR) to become active 5-MTHF -- a pathway that can be rate-limited in people with reduced-function MTHFR variants (C677T/A1298C). (The MTHFR rate-limitation point is mechanistic; the cited RCT found no outcome difference by genotype.)

Source: MRC Vitamin Study Research Group 1991, PMID 1677062; Hekmatdoost A et al. 2015, PLoS One 10(12):e0143569, PMID 26630680

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