[Does 5-methyltetrahydrofolate offer any advantage over folic acid?]

J Pharm Belg. 2012 Dec:(4):16-22.
[Article in French]


Almost half of the women do not follow the guidelines around folate suppletion before and during pregnancy, despite the proven benefit in the prevention of neural tube defects, miscarriages and premature births. The Belgian Superior Health Council recommends a minimum of 400 micrograms of folic acid or folate suppletion per day from 4 weeks before conception to 8 weeks thereafter. Many studies point to the importance of a wider intake period, more particularly at least 3 months before conception and throughout pregnancy and lactation. In high-risk women 4 mg is recommended until after the first 3 months of pregnancy. Afterwards the usual dose of 400 micrograms is sufficient. About half of the European population appears to have a gene mutation on the gene coding for the production of methylenetetrahydrofolate reductase, the enzyme that is involved in the formation of 5-methyltetrahydrofolate, which is, in his turn, responsible for the conversion of the toxic homocysteine in methionine. Women with such a gene polymorphism have a significantly higher risk to have a miscarriage or a baby with neural tube defects. For this reason, a search for an alternative form of synthetic folic acid supplement "pteroylmonoglutamic acid (PMG)" was conducted, particularly the calcium salt of 5-methyltetrahydrofolate (Metafolin). This offers the possibility to deliver the reduced folate immediately, which no longer needs to be converted by the reductase enzyme. Furthermore, this avoids free PMG in the circulation, lowers the risk for drug interactions and a vitamin B2 deficiency will not be masked. Despite clear guidelines regarding dietary supplements before and during pregnancy, their implementation is poor. Not only gynecologists but also GPs and pharmacists, should make more efforts to provide women of childbearing age with personal information. Especially risk groups such as adolescents, low-skilled or less well-off women and immigrants deserve special attention.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Congenital Abnormalities / prevention & control*
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / therapeutic use*
  • Humans
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Neural Tube Defects / prevention & control
  • Pregnancy
  • Spine / abnormalities
  • Tetrahydrofolates / administration & dosage
  • Tetrahydrofolates / therapeutic use*
  • Vitamins / administration & dosage
  • Vitamins / therapeutic use*
  • Young Adult


  • Tetrahydrofolates
  • Vitamins
  • Folic Acid
  • 5-methyltetrahydrofolate