Quantifying the effect of folic acid

Background Folic acid is known to prevent neural-tube defects (NTDs) but th e size of the effect for a given dose is unclear. We aimed to quantify such an effect. Methods We used published data from 13 studies of folic acid supplementatio n on serum folate concentrations and results from a large cohort study of t he risk of NTDs according to serum folate, to measure the preventive effect of specified increases in intake of folic acid. Findings Serum folate concentrations increase by 0.94 ng/mL (95% Cl 0.77-1. 10) for every 0.1 mg/day increase in folic acid intake in women aged 20-35 years, and about double that in people aged 40-65. Every doubling of serum folate concentration roughly halves the risk of an NTD. These two effects c an be combined to predict the reduction in risk according to intake of extr a folic acid and background serum folate concentration. Such results predic t that the preventive effect is greater in women with low serum folate than in those with higher concentrations. The results have also been used to pr edict direct observations from large randomised trials and the effect of fo od fortification. From a typical western background serum folate of 5 ng/mL , about 0.2 mg/day (the US level of folic acid fortification) would be expe cted to reduce NTDs by about 20%; a similar effect can be expected from the current British recommendation (0.24 mg/day). An increase of 0.4 mg/day wo uld reduce risk by about 36%, of 1 mg/day by 57%, and taking a 5-mg tablet daily would reduce risk by about 85%. Interpretation Folic acid fortification levels should be increased. Additio nally women planning a pregnancy should take 5 mg folic acid tablets daily, instead of the 0.4 mg dose presently recommended.