ArticleThe Journal of nutrition2011
Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans.
Article in The Journal of nutrition, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Metabolome panels as potential noninvasive biomarkers for primary glomerulonephritis sub-types: meta-analysis of profiling metabolomics studies.Scientific reports · 2023Pooled it
- The Potential Neuroprotective Role of Biotin in Neurorehabilitation: A Review.Current nutrition reports · 2026Review
- Serum metabolomic profiling reveals load-specific adaptations to resistance training.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Rutin Attenuates Oxidative Stress Responses and Hepatocyte Metabolomics in β-Hydroxybutyric Acid-Induced Hepatocyte Injury in Calves.International journal of molecular sciences · 2025Article
- A comprehensive approach for detection of biotin deficiency from dried blood spot samples using liquid chromatography-mass spectrometry.Future science OA · 2024Article
- A new case of sodium-dependent multivitamin transporter defect occurring as a life-threatening condition responsive to early vitamin supplementation and literature review.Molecular genetics & genomic medicine · 2024Review
- A Study of the Metabolic Pathways Affected by Gestational Diabetes Mellitus: Comparison with Type 2 Diabetes.Diagnostics (Basel, Switzerland) · 2022Article
- Roles of vitamins in stem cells.Cellular and molecular life sciences : CMLS · 2020Review
- Causal Effects of Genetically Determined Metabolites on Risk of Polycystic Ovary Syndrome: A Mendelian Randomization Study.Frontiers in endocrinology · 2020Article
- The altered human serum metabolome induced by a marathon.Metabolomics : Official journal of the Metabolomic Society · 2018Article
- Biotin: From Nutrition to Therapeutics.The Journal of nutrition · 2017Review
- A (14)C-leucine absorption, distribution, metabolism and excretion (ADME) study in adult Sprague-Dawley rat reveals β-hydroxy-β-methylbutyrate as a metabolite.Amino acids · 2015Article
- In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.The Journal of nutrition · 2015Article
- Novel roles of holocarboxylase synthetase in gene regulation and intermediary metabolism.Nutrition reviews · 2014Review
- Identification and assessment of markers of biotin status in healthy adults.The British journal of nutrition · 2013Article
- Inhibition of 3-methylcrotonyl-CoA carboxylase explains the increased excretion of 3-hydroxyisovaleric acid in valproate-treated patients.Journal of inherited metabolic disease · 2012Article
- Marginal biotin deficiency can be induced experimentally in humans using a cost-effective outpatient design.The Journal of nutrition · 2012Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Experimentally increasing metabolic flux in a pathway in which an essential step is catalyzed by a vitamin-dependent enzyme (a challenge test) has been used in assessing functional vitamin status and elucidating common and alternate metabolic pathways. Conversion of 3-methylcrotonyl CoA to 3-methylglutaconyl CoA in the leucine catabolic pathway is catalyzed by the biotin-dependent enzyme methylcrotonyl-CoA carboxylase (MCC). Marginal biotin deficiency reduces MCC activity and increases urinary excretion of 3-hydroxyisovaleric acid (3HIA) and 3-hydroxyisovaleryl carnitine (3HIA-carnitine) measured in 24-h urine collections. We assessed urinary excretion of 3HIA and 3HIA-carnitine in response to a leucine challenge in humans made progressively biotin deficient by egg white consumption. In 2 cohorts of healthy adults (Study 1: n = 5; Study 2: n = 7) rendered biotin deficient over 28 d, urinary excretion of 3HIA and 3HIA-carnitine in response to a leucine challenge was quantitated weekly for 3 or 4 wk, respectively. In both studies, mean urinary excretion of both 3HIA and 3HIA-carnitine increased >2-fold by d 14 (P < 0.002 for both indicators for both studies). Diagnostically, both indicators were highly sensitive, but diagnostic sensitivities were not superior to those of 24-h excretion of 3HIA and 3HIA-carnitine. These studies provide evidence that urinary excretions of 3HIA and 3HIA-carnitine in response to an oral leucine challenge are early and sensitive indicators of marginal biotin deficiency in humans. The variability of the proportion of leucine catabolites excreted as 3HIA suggests substantial population heterogeneity in the metabolic capacity of the 3HIA-carnitine detoxification pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.