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

Abstract

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 clinicaltrials.gov as NCT01127022.

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

FIGURE 1

Functional and static biomarkers of biotin status in pregnant, lactating, and control women consuming 57 μg dietary biotin/d under controlled feeding conditions. Values are geometric means and 95% CIs; pregnant, n = 26; lactating, n = 28; control, n = 21. Plasma total biotin (A). *Change from week 0 to week 10 in the lactating group, P < 0.01. Urinary biotin excretion (B). *Change from week 0 to week 12 in the control group, P < 0.01. Urinary 3-HIA excretion (C). Means without a common letter (a > b > c) differ between the reproductive groups, P < 0.001. Urinary 3-HIA-Car excretion (D). Means without a common letter (a > b) differ between the reproductive groups, P = 0.03; Urinary bisnorbiotin excretion (E). Means without a common letter (a > b) differ between the reproductive groups, P < 0.001. 3-HIA, 3-hydroxyisovaleric acid; 3-HIA-Car, 3-hydroxyisovaleryl-carnitine.