Supplementation with a multivitamin containing 800 µg of folic acid shortens the time to reach the preventive red blood cell folate concentration in healthy women

Background: The lowest risk of having a child with a neural tube defect (NTD) was related to red blood cell (RBC) folate concentrations of >906 nmol/L. For NTD prevention, it is recommended that women use periconceptional supplementation of 400 µg/day folic acid. Using this dose previous studies indicate that RBC folate >906 nmol/L was not reached within four weeks of supplementation. Objective: The effectiveness of a multivitamin/multimineral supplement containing 800 µg folic acid (verum) was evaluated using RBC folate concentration exceeding 906 nmol/L as primary endpoint. In addition, the time frame of achieving the threshold level was established as well as the effect of supplementation of other B vitamins on folate metabolism. Subjects and Methods: 46 healthy females received 800 µg/day of folic acid or placebo for 16 weeks. Blood samples were collected in four-week intervals. Plasma and RBC folate were measured with the microbiological method. Results: Mean (±SED) RBC folate increased over time to 1430±53 nmol/L, but did not reach a steady state after 16 weeks of intervention. Mean time to reach the target level was 4.2 ± 3.5 weeks in the verum group. Intake of verum also led to an increase over time of plasma folate. Conclusions: Preventive RBC folate concentration of more than 906 nmol/L can be reached within four weeks of supplementation with daily intake of 800 µg folic acid. With respect to NTD prevention, we suggest the re-evaluation of the current recommendation of folic acid supplementation.