INCREASED URINARY-EXCRETION OF 3-HYDROXYISOVALERIC ACID AND DECREASEDURINARY-EXCRETION OF BIOTIN ARE SENSITIVE EARLY INDICATORS OF DECREASED BIOTIN STATUS IN EXPERIMENTAL BIOTIN DEFICIENCY

To assess the utility of various indicators of biotin status, marginal biotin deficiency was induced experimentally in normal adults. Ten su bjects consumed a diet that contained enough avidin to bind seven time s more biotin than that in the diet. Blood and 24-h urine samples were collected before the diet began and twice weekly thereafter for 20 d. The urinary excretion and serum concentration of biotin and its two p rincipal inactive metabolites bisnorbiotin and biotin sulfoxide were d etermined after HPLC separation with an avidin-binding assay. The urin ary concentration of 3-hydroxyisovaleric acid, an indicator of reduced activity of a biotin-dependent enzyme, was quantitated by gas chromat ography-mass spectrometry. The urinary excretion of 3-hydroxyisovaleri c acid increased significantly (P < 0.0001). For all subjects, the uri nary excretion of both biotin and bisnorbiotin decreased significantly (P < 0.0001 for each). In contrast, the mean serum concentration of b iotin did not decrease significantly (P = 0.06). These data provide ev idence that the urinary excretion of 3-hydroxyisovaleric acid and the urinary excretion of biotin are early and sensitive indicators of biot in deficiency and that the serum concentration of biotin is not.