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Am J Clin Nutr. 2002 Nov;76(5):1061-8.

Indicators of marginal biotin deficiency and repletion in humans: validation of 3-hydroxyisovaleric acid excretion and a leucine challenge.

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  • 1Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock 72205, USA. mockdonaldm@uams.edu

Abstract

BACKGROUND:

The results of clinical studies have provided evidence that marginal biotin deficiency is more common than was previously thought. A previous study of 10 subjects showed that the urinary excretion of biotin and 3-hydroxyisovaleric acid (3HIA) are early and sensitive indicators of marginal biotin deficiency.

OBJECTIVE:

Marginal biotin deficiency was experimentally induced and corrected to assess the utility of 3 indicators of biotin status: urinary excretion of biotin and 3HIA and the increase in 3HIA excretion after leucine loading.

DESIGN:

Eleven healthy adults consumed an egg white diet for 28 d. Blood and 24-h urine samples were collected before the start of the diet and twice weekly thereafter. In 5 subjects, an oral leucine challenge was performed weekly for 4 wk. After depletion, biotin status was restored with a general diet with or without a supplement containing 80 micro g biotin. Urinary excretion of biotin, bisnorbiotin, and biotin sulfoxides was determined by avidin-binding assay after HPLC. Excretion of 3HIA, an indicator of reduced activity of the biotin-dependent enzyme methylcrotonyl-CoA carboxylase (EC 6.4.1.4), was measured by gas chromatography-mass spectrometry.

RESULTS:

3HIA excretion increased significantly with time on the egg white diet (P < 0.0001), as did 3HIA excretion in response to the leucine challenge (P < 0.002); the excretion of both biotin and bisnorbiotin decreased significantly with time (P < 0.0001). In most subjects, biotin status returned to normal after 1 wk of a general diet.

CONCLUSIONS:

Excretion of 3HIA and of biotin are early and sensitive indicators of biotin deficiency. 3HIA excretion after a leucine challenge is at least as sensitive.

PMID:
12399279
PMCID:
PMC1435357
[PubMed - indexed for MEDLINE]
Free PMC Article
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