Total folate and unmetabolized folic acid in the breast milk of a cross-section of Canadian women

Am J Clin Nutr. 2017 May;105(5):1101-1109. doi: 10.3945/ajcn.116.137968. Epub 2017 Mar 15.


Background: Folate requirements increase during pregnancy and lactation. It is recommended that women who could become pregnant, are pregnant, or are lactating consume a folic acid (FA)-containing supplement.Objectives: We sought to determine breast-milk total folate and unmetabolized folic acid (UMFA) contents and their relation with FA-supplement use and doses in a cohort of Canadian mothers who were enrolled in the MIREC (Maternal-Infant Research on Environmental Chemicals) study.Design: Breast-milk tetrahydrofolate (THF), 5-methyl-THF, 5-formyl-THF, 5,10-methenyl-THF, and UMFA were measured with the use of liquid chromatography-tandem mass spectrometry (n = 561). Total daily supplemental FA intake was based on self-reported FA-supplement use.Results: UMFA was detectable in the milk of 96.1% of the women. Total daily FA intake from supplements was associated with breast folate concentration and species. Breast-milk total folate was 18% higher (P < 0.001) in supplement users (n = 401) than in nonusers (n = 160), a difference driven by women consuming >400 μg FA/d (P ≤ 0.004). 5-Methyl-THF was 19% lower (P < 0.001) and UMFA was 126% higher (P < 0.001) in supplement users than in nonusers. Women who consumed >400 μg FA/d had proportionally lower 5-methyl-THF and higher UMFA than did women who consumed ≤400 μg FA/d.Conclusions: FA-supplement use was associated with modestly higher breast-milk total folate. Detectable breast-milk UMFA was nearly ubiquitous, including in women who did not consume an FA supplement. Breast-milk UMFA was proportionally higher than 5-methyl-THF in women who consumed >400 μg FA/d, thereby suggesting that higher doses exceed the physiologic capacity to metabolize FA and result in the preferential uptake of FA in breast milk. Therefore, FA-supplement doses >400 μg may not be warranted, especially in populations for whom FA fortification is mandatory.

Keywords: breast milk; folate; folic acid; supplements; unmetabolized folic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast
  • Canada
  • Cohort Studies
  • Dietary Supplements*
  • Female
  • Folic Acid / analogs & derivatives
  • Folic Acid / metabolism
  • Folic Acid / pharmacology*
  • Humans
  • Lactation / metabolism*
  • Milk, Human / metabolism*
  • Nutritional Requirements
  • Pregnancy
  • Tetrahydrofolates / metabolism
  • Vitamin B Complex / metabolism
  • Vitamin B Complex / pharmacology


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

Grant support