Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet

J Nutr. 2014 Dec;144(12):1977-84. doi: 10.3945/jn.114.194472. Epub 2014 Aug 13.


Background: Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 μg/d, whereas 35 μg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states.

Objective: The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin.

Methods: To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 μg of dietary biotin/d as part of a mixed diet.

Results: Over the course of the study, pregnant women excreted 69% more (vs. control; P < 0.001) 3-hydroxyisovaleric acid (3-HIA), a metabolite that accumulates during the catabolism of leucine when the activity of biotin-dependent methylcrotonyl-coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation.

Conclusions: Overall, these data demonstrate significant alterations in markers of biotin metabolism during pregnancy and lactation and suggest that biotin intakes exceeding current recommendations are needed to meet the demands of these reproductive states. This trial was registered at as NCT01127022.

Keywords: 3-hydroxyisovaleric acid; biotin; bisnorbiotin; lactation; pregnancy.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biotin / analogs & derivatives*
  • Biotin / blood
  • Biotin / metabolism*
  • Biotin / urine
  • Carbon-Carbon Ligases / metabolism
  • Carnitine / analogs & derivatives
  • Carnitine / urine
  • Choline / administration & dosage
  • Chromatography, Liquid
  • Diet*
  • Dietary Supplements
  • Female
  • Humans
  • Lactation / blood*
  • Leucine / metabolism
  • Milk, Human / chemistry
  • New York
  • Patient Compliance
  • Pregnancy*
  • Tandem Mass Spectrometry
  • Valerates / urine
  • Young Adult


  • 3-hydroxyisovalerylcarnitine
  • Biomarkers
  • Valerates
  • bisnorbiotin
  • beta-hydroxyisovaleric acid
  • Biotin
  • Carbon-Carbon Ligases
  • methylcrotonoyl-CoA carboxylase
  • Leucine
  • Choline
  • Carnitine

Associated data