Metabolomic Analysis Reveals Extended Metabolic Consequences of Marginal Vitamin B-6 Deficiency in Healthy Human Subjects
- Authors
- Gregory, III J.F.; Park, Y.; Lamers, Y.; Bandyopadhyay, N.; Chi, Y.-Y.; Lee, K.; Kim, S.; da, Silva V.; Hove, N.; Ranka, S.; Kahveci, T.; Muller, K.E.; Stevens, R.D.; Newgard, C.B.; Stacpoole, P.W.; Jones, D.P.
- Issue Date
- 2013
- Citation
- PLoS ONE, v.8, no.6
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLoS ONE
- Volume
- 8
- Number
- 6
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/105886
- DOI
- 10.1371/journal.pone.0063544
- ISSN
- 1932-6203
- 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 1H-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. © 2013 Gregory et al.
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