Folate-status response to a controlled folate intake in nonpregnant, pregnant, and lactating women

Am J Clin Nutr. 2012 Oct;96(4):789-800. doi: 10.3945/ajcn.112.037523. Epub 2012 Aug 29.

Abstract

Background: Folate dose-response studies in women of childbearing age who consumed a folic acid (FA)-containing multivitamin in the era of FA fortification are lacking.

Objective: We sought to investigate folate-status response to a known folate dose comprising an FA-containing prenatal supplement (750 μg/d) plus natural food folate (400 μg/d) in third-trimester pregnant women, lactating women 5-15 wk postpartum, and nonpregnant women.

Design: Pregnant (n = 26), lactating (n = 28), and nonpregnant (n = 21) women consumed the study folate dose under controlled intake conditions for 10-12 wk. Blood, urine, and breast milk were collected at baseline, study midpoint, and study end.

Results: Study-end serum total folate concentrations averaged ~30 ng/mL and did not differ by physiologic group (P = 0.876). Study-end urinary folate excretion represented ~9-43% of total folate intake and ranged from 100 to 500 μg/d. Third-trimester pregnant women excreted less urinary folate than did lactating (P = 0.075) and nonpregnant (P < 0.001) women. Lactating women excreted less (P < 0.001) urinary FA than did nonpregnant women. Breast-milk total folate concentrations remained constant (P = 0.244; 61.8 ng/mL at study end), whereas breast-milk FA concentrations increased (P = 0.003) to 24.1 ng/mL at study end.

Conclusions: The consumption of the study folate dose yielded a supranutritional folate status regardless of the physiologic state. Based on urinary folate excretion, folate use was greatest to least: pregnant > lactating > nonpregnant women. Breast-milk folate species were responsive to maternal folate intake, and FA made up ~40% of breast-milk total folate at study end. These findings warrant revisiting prenatal supplement FA formulation in populations exposed to FA-fortification programs.

Trial registration: ClinicalTrials.gov NCT01127022.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Biomarkers / urine
  • Diet*
  • Dietary Supplements* / adverse effects
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / blood
  • Folic Acid / metabolism
  • Folic Acid / urine
  • Food, Fortified
  • Genetic Association Studies
  • Humans
  • Lactation / blood
  • Lactation / metabolism*
  • Lactation / urine
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Milk, Human / metabolism
  • New York
  • Nutritional Status*
  • Patient Compliance
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Pregnancy Trimester, Third
  • Prenatal Nutritional Physiological Phenomena*
  • Tetrahydrofolates / blood
  • Tetrahydrofolates / metabolism
  • Tetrahydrofolates / urine

Substances

  • Biomarkers
  • Tetrahydrofolates
  • Folic Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • 5-methyltetrahydrofolate

Associated data

  • ClinicalTrials.gov/NCT01127022