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

Int J Vitam Nutr Res. 2009 Mar;79(2):61-70. doi: 10.1024/0300-9831.79.2.61.


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 microg/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 microg 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 microg/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 microg folic acid. With respect to NTD prevention, we suggest the re-evaluation of the current recommendation of folic acid supplementation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Diet
  • Diet Records
  • Dietary Supplements*
  • Double-Blind Method
  • Erythrocytes / chemistry*
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / analysis
  • Folic Acid / blood
  • Homocysteine / blood
  • Humans
  • Methionine
  • Micronutrients / administration & dosage*
  • Neural Tube Defects / prevention & control*
  • Nutritional Status*
  • Reference Values
  • Riboflavin / blood
  • Time Factors
  • Vitamin B 12 / blood
  • Vitamin B 6 / blood
  • Young Adult


  • Micronutrients
  • Homocysteine
  • Vitamin B 6
  • Folic Acid
  • Methionine
  • Vitamin B 12
  • Riboflavin