[6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation

Am J Clin Nutr. 2006 Apr;83(4):842-50. doi: 10.1093/ajcn/83.4.842.


Background: Studies in nonpregnant, nonlactating women suggest that folate supplementation in the form of 5-methyltetrahydrofolate ([6S]-5-methylTHF) is at least as effective as folic acid in increasing blood folate indexes. No data, however, are available on the effect of supplemental [6S]-5-methylTHF on blood folate concentrations during lactation.

Objective: We assessed the relative effectiveness of [6S]-5-methylTHF, a placebo, and folic acid in maintaining blood folate indexes during lactation in a sample of healthy Canadian women consuming folic acid-fortified foods.

Design: This study was designed as a 16-wk, randomized, placebo-controlled intervention. Pregnant women (n = 72) advised to consume a folic acid-containing prenatal supplement (1000 microg/d) during pregnancy were enrolled at 36 wk gestation. After delivery, the women were randomly assigned to receive [6S]-5-methylTHF (416 microg/d, 906 nmol/d) or a placebo or were assigned to a folic acid (400 microg/d, 906 nmol/d) reference group.

Results: At 16 wk of lactation, the mean red blood cell (RBC) folate concentration in women in the [6S]-5-methylTHF group (2178; 95% CI: 1854, 2559 nmol/L) was greater than that in the folic acid (1967; 1628, 2377 nmol/L; P < 0.05) and placebo (1390; 1198, 1613 nmol/L; P < 0.002) groups after adjustment for baseline concentrations (36 wk gestation). The distribution of folate forms in RBCs did not differ significantly between the [6S]-5-methylTHF and placebo groups. However, the folic acid group had greater amounts of 5-formylTHF (P < 0.03).

Conclusion: [6S]-5-MethylTHF appeared to be as effective as, and perhaps more effective than, folic acid in preserving RBC folate concentrations during lactation.

Publication types

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

MeSH terms

  • Adult
  • Biological Availability
  • Blood Chemical Analysis
  • Dietary Supplements
  • Double-Blind Method
  • Erythrocytes / chemistry*
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / blood*
  • Folic Acid / metabolism
  • Folic Acid Deficiency / prevention & control*
  • Humans
  • Lactation / blood*
  • Lactation / metabolism
  • Placebos
  • Pregnancy
  • Tetrahydrofolates / administration & dosage*
  • Tetrahydrofolates / blood
  • Tetrahydrofolates / metabolism
  • Treatment Outcome
  • Vitamin B Complex / administration & dosage*
  • Vitamin B Complex / blood
  • Vitamin B Complex / metabolism


  • Placebos
  • Tetrahydrofolates
  • Vitamin B Complex
  • Folic Acid
  • 5-methyltetrahydrofolate