Increased urinary excretion of 3-hydroxyisovaleric acid and decreased urinary excretion of biotin are sensitive early indicators of decreased biotin status in experimental biotin deficiency

Abstract

To assess the utility of various indicators of biotin status, marginal biotin deficiency was induced experimentally in normal adults. Ten subjects consumed a diet that contained enough avidin to bind seven times 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 principal inactive metabolites bisnorbiotin and biotin sulfoxide were determined after HPLC separation with an avidin-binding assay. The urinary concentration of 3-hydroxyisovaleric acid, an indicator of reduced activity of a biotin-dependent enzyme, was quantitated by gas chromatography-mass spectrometry. The urinary excretion of 3-hydroxyisovaleric acid increased significantly (P < 0.0001). For all subjects, the urinary excretion of both biotin and bisnorbiotin decreased significantly (P < 0.0001 for each). In contrast, the mean serum concentration of biotin did not decrease significantly (P = 0.06). These data provide evidence that the urinary excretion of 3-hydroxyisovaleric acid and the urinary excretion of biotin are early and sensitive indicators of biotin deficiency and that the serum concentration of biotin is not.

Scientific Opinion on Dietary Reference Values for biotin

“…Between 7 and 11 subjects were involved in each study and depletion lasted for three to four weeks. The 24-hour urinary excretion of biotin was found to decrease significantly over the depletion period (Mock NI et al, 1997;Mock et al, 2002a), while plasma concentration of biotin was not significantly affected (Mock NI et al, 1997). Biotin insufficiency was also shown to affect markers of the activities of biotin-dependent carboxylase enzymes and related metabolic pathways.…”

“…The biotin that is not incorporated into carboxylase enzymes is catabolised through different pathways to form bisnorbiotin, tetranorbiotin and related intermediates, by β-oxidation of the valeric side-chain, or biotin sulphoxides and sulphone, by oxidation of the sulphur present in its heterocyclic ring (Mock, 2014). Biotin and its metabolites are excreted in the urine (Mock NI et al, 1997;Zempleni et al, 1997b). Biliary excretion of biotin and its metabolites is thought to be quantitatively negligible (Zempleni and Mock, 1999a), as indicated by data in rats and pigs (Zempleni et al, 1997a).…”

“…Biotin insufficiency was also shown to affect markers of the activities of biotin-dependent carboxylase enzymes and related metabolic pathways. The 24-hour urinary excretion of 3-hydroxyisovaleric acid (3HIA) and 3HIA-carnitine, as well as fasting plasma 3HIA-carnitine concentration, were found to increase significantly in male and female subjects over the depletion period, indicating a reduced activity of MCC (Mock NI et al, 1997;Mock et al, 2002a;Horvath et al, 2010b;Horvath et al, 2010a;Stratton et al, 2011). Pooling of data from two sources (Mock NI et al, 1997;Mock et al, 2002a) indicated that urinary excretion of 3HIA or biotin did not differ between sexes, either before egg white feeding or at day 21 of depletion (Mock et al, 2002a).…”

Biotin-deficient diet induces chromosome misalignment and spindle defects in mouse oocytes

“…[19][20][21][22][23] Concentrations of 3-HIA, a metabolite of L-leucine in 24 h urine samples on day 19 and day 39 were measured via high-performance liquid chromatography (HPLC) in accordance with the method described by Watanabe et al 19) The 3-HIA (Tokyo chemical industry Co., Ltd,. Tokyo, Japan) derivatized with 2-nitiophenylhydrazine hydrochloride (Tokyo chemical industry Co., Ltd. Tokyo, Japan) was detected using the HITACHI HPLC system (Hitachi, Ltd. Tokyo, Japan) and the HPLC column was a YMC-Pack FA (particle size 5 μm, 250 × 6.0 mm) (YMC Co., Ltd., Kyoto, Japan).…”

Evaluation of the Probabilistic Distribution of Dietary Biotin Intake in Japan Using Monte Carlo Simulation

“…Human cells have four biotin-dependent carboxylases that catalyze key reactions in gluconeogenesis, amino acid catabolism, and fatty acid synthesis ( 1 ). Biotin deficiency has been reported in various circumstances such as those following prolonged feeding of undenatured egg whites ( 2 ) and in cases of genetic biotinidase deficiency ( 3 ). Symptoms of biotin deficiency include hair loss, skin rash, and neurological symptoms.…”