Journal
AMERICAN JOURNAL OF CLINICAL NUTRITION
Volume 76, Issue 5, Pages 1061-1068Publisher
AMER SOC CLINICAL NUTRITION
DOI: 10.1093/ajcn/76.5.1061
Keywords
biotin; leucine; metabolism; 3-hydroxyisovaleric acid; bisnorbiotin; egg whites
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Funding
- NCRR NIH HHS [RR 00059, M01 RR014288, M01RR14288, M01 RR000059] Funding Source: Medline
- NIDDK NIH HHS [R37 DK036823] Funding Source: Medline
- PHS HHS [36823] Funding Source: Medline
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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 mug 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 I 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.
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