How to use folate supplements: why to start before pregnancy and folate's role in methylation

A Cochrane meta-analysis including 6,105 participants (De-Regil et al., 2015) found that periconceptional folic acid supplementation reduced the relative risk of neural tube defects (spina bifida, anencephaly, etc.) by approximately 72%. Since neural tube closure occurs around weeks 3–4 of pregnancy, supplementation must begin before pregnancy is confirmed.

~72%

Relative risk reduction for neural tube defects

6,105 participants

Meta-analysis sample size

Folate plays a central role in one-carbon metabolism (the methylation cycle). It is an indispensable cofactor for converting homocysteine to methionine, as well as for DNA methylation and synthesis. Individuals with MTHFR gene variants may have reduced efficiency converting folate to its active form (methyltetrahydrofolate), making active folate (methylfolate) supplements worth considering.

400–800 µg/day

Recommended folic acid dose periconceptionally

Folate is found in green leafy vegetables, legumes, and liver, but is readily destroyed by heat during cooking, and average intake in Japan often falls below recommended levels. The WHO and major health agencies recommend folate supplementation for all women planning pregnancy, with particular emphasis on the period from 4 weeks before conception through 12 weeks of gestation.

4 weeks pre-conception to 12 weeks gestation

Critical supplementation window