Evidence Level
Strong
Folate has one of the most impactful public health evidence bases of any vitamin. The MRC Vitamin Study (1991, Lancet) definitively showed that 4 mg folic acid daily reduced neural tube defect recurrence by 72%, leading to mandatory fortification in 80+ countries. Since U.S. folic acid fortification began in 1998, NTD rates dropped by 28%. Homocysteine-lowering effects are well-established, with the Homocysteine Lowering Trialists' Collaboration (1998) meta-analysis showing 25% reduction. For depression, Papakostas et al. (2012) demonstrated in a multi-site RCT that L-methylfolate at 15 mg/day augmented SSRI response in treatment-resistant depression.