Metabolomic Analysis Reveals Extended Metabolic Consequences of Marginal Vitamin B-6 Deficiency in Healthy Human Subjects

• Type of Material: Article
• Authors: Jesse F. Gregory, University of Florida; Youngja Park, affiliation; Yvonne Lamers, University of Florida; Nirmalya Bandyopadhyay, University of Florida; Yueh-Yun Chi, University of Florida; Kichen Lee, Emory University; Steven Kim, Emory University; Vanessa da Silva, University of Florida; Nikolas Hove, Hanyang University; Sanjay Ranka, University of Florida; Tamer Kahveci, University of Florida; Keith E. Muller, University of Florida; Robert D. Stevens, Duke University; Christopher B. Newgard, Duke University; Peter W. Stacpoole, University of Florida; Dean P Jones, Emory University
• Language: English
• Date: 2013-06-11
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Gregory et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0063544
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 6
• Start Page: e63544
• End Page: e63544
• Grant/Funding Information: This study was supported by National Institutes of Health (NIH) Grant DK072398 (to Jesse F. Gregory) and NIH National Center for Research Resources CTSA Grant 1UL1RR029890.; Support of the Clinical Biomarkers Laboratory, Emory University was from NIH Grant ES016731 to Dean P. Jones, and support of the Sarah W. Stedman Nutrition and Metabolism Center, Duke University, was from NIH Grant PO1-DK-58398 to Christopher B. Newgard.; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: WOMEN; Science & Technology - Other Topics; INCREASED RISK; YOUNG MEN; PLASMA GLUTATHIONE; NUTRITIONAL-STATUS; Science & Technology; VASCULAR-DISEASE; CORONARY-ARTERY-DISEASE; HOMOCYSTEINE METABOLISM; RESTRICTION; FOLATE; Multidisciplinary Sciences
• Research Categories: Environmental Sciences; Health Sciences, Medicine and Surgery

Abstract

Marginal deficiency of vitamin B-6 is common among segments of the population worldwide. Because pyridoxal 5′-phosphate (PLP) serves as a coenzyme in the metabolism of amino acids, carbohydrates, organic acids, and neurotransmitters, as well as in aspects of one-carbon metabolism, vitamin B-6 deficiency could have many effects. Healthy men and women (age: 20-40 y; n = 23) were fed a 2-day controlled, nutritionally adequate diet followed by a 28-day low-vitamin B-6 diet ( < 0.5 mg/d) to induce marginal deficiency, as reflected by a decline of plasma PLP from 52.6±14.1 (mean ± SD) to 21.5±4.6 nmol/L (P < 0.0001) and increased cystathionine from 131±65 to 199±56 nmol/L (P < 0.001). Fasting plasma samples obtained before and after vitamin B6 restriction were analyzed by 1 H-NMR with and without filtration and by targeted quantitative analysis by mass spectrometry (MS). Multilevel partial least squares-discriminant analysis and S-plots of NMR spectra showed that NMR is effective in classifying samples according to vitamin B-6 status and identified discriminating features. NMR spectral features of selected metabolites indicated that vitamin B-6 restriction significantly increased the ratios of glutamine/glutamate and 2-oxoglutarate/glutamate (P < 0.001) and tended to increase concentrations of acetate, pyruvate, and trimethylamine-N-oxide (adjusted P < 0.05). Tandem MS showed significantly greater plasma proline after vitamin B-6 restriction (adjusted P < 0.05), but there were no effects on the profile of 14 other amino acids and 45 acylcarnitines. These findings demonstrate that marginal vitamin B-6 deficiency has widespread metabolic perturbations and illustrate the utility of metabolomics in evaluating complex effects of altered vitamin B-6 intake.