A three-arm double-blind efficacy trial depicted that folic acid supplements that contained 2.8 mg of iron folic acid (IFA) elevated RBC folate levels more than supplements that contained 0.4 mg IFA This trial was conducted for determining the effectiveness of two doses of folic acid vs. placebo on red blood cell (RBC) folate levels, a biomarker of neural tube defect (NTD) risk.

Over 16 weeks, 331 non-pregnant women received 60 mg iron and 0, 2.8, or 0.4 mg folic acid once a week. At week 16, women who consumed 0.4 mg and 0.28 mg folic acid each week had a consistently higher RBC folate level than women who consumed 0 mg of folic acid each week. When women received 2.8 mg of folic acid, their mean RBC folate was 271 nmol/L higher than when they received 0.4 mg.

Compared to women in the 0.4 mg group, women in the 2.8 mg group had a seven-fold (RR 7.3, 95% CI 3.9 to 13.7) greater likelihood of reaching an RBC folate concentration of 748 nmol/L, indicating an exceptionally low risk of neural tube defects. RBC folate was increased greater with the use of IFA supplements containing 2.8 mg folic acid as compared to supplements containing 0.4 mg IFA. The 2.8 mg formulation must be made more widely available and accessible.