Indicators of marginal biotin deficiency and repletion in humans: validation of 3-hydroxyisovaleric acid excretion and a leucine challenge.
Level 4 - case-series / case-control
Single-arm experimental depletion-repletion study in healthy volunteers without a concurrent control group
PubMed 12399279 · doi:10.1093/ajcn/76.5.1061
What was done
Eleven healthy adults were fed an egg white diet for 28 days to experimentally induce marginal biotin deficiency. Blood and 24-hour urine samples were collected at baseline and twice weekly throughout depletion. In 5 participants, an oral leucine challenge was performed weekly for 4 weeks. Following depletion, biotin status was restored with a general diet with or without an 80 µg biotin supplement. Urinary excretion of biotin, bisnorbiotin, and biotin sulfoxides was measured by HPLC avidin-binding assay, and urinary 3-hydroxyisovaleric acid (3HIA) was quantified by gas chromatography-mass spectrometry.
What was found
Urinary 3HIA excretion increased significantly over time on the egg white diet (P < 0.0001), and 3HIA excretion after leucine challenge also increased significantly (P < 0.002). Urinary excretion of both biotin and bisnorbiotin decreased significantly over time (P < 0.0001). Quantitative numerical values for excretion were not reported in the abstract. In most subjects, biotin status returned to normal after 1 week of a general diet.
Why it matters
This study demonstrates that urinary 3HIA excretion, with or without a leucine challenge, serves as a sensitive functional indicator to detect marginal biotin deficiency and monitor its resolution.
Limits
The study had a very small sample size (11 subjects total, 5 for the leucine challenge) and lacked a non-depleted control group. Specific numerical values and variance for biomarker concentrations were omitted from the abstract.
Cited by
- supports Raw egg whites block the absorption of biotin in the body.