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

• Published in: PloS one Vol. 8; no. 6; p. e63544
• Main Authors: Gregory, Jesse F., Park, Youngja, Lamers, Yvonne, Bandyopadhyay, Nirmalya, Chi, Yueh-Yun, Lee, Kichen, Kim, Steven, da Silva, Vanessa, Hove, Nikolas, Ranka, Sanjay, Kahveci, Tamer, Muller, Keith E., Stevens, Robert D., Newgard, Christopher B., Stacpoole, Peter W., Jones, Dean P.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.06.2013; Public Library of Science (PLoS)
• Subjects: a-Ketoglutaric acid; Acetates - blood; Acetic acid; Adult; Amino acids; Amino Acids - blood; Biology; Biomarkers; Carbohydrates; Carbon; Carnitine - analogs & derivatives; Carnitine - blood; Chemistry; Critical care; Cystathionine - blood; Discriminant analysis; Enzymes; Fatty acids; Female; Food science; Glutamic Acid - blood; Glutamine; Glutamine - blood; Humans; Industrial engineering; Information science; Ketoglutaric acid; Ketoglutaric Acids - blood; Laboratories; Male; Mass spectrometry; Mass spectroscopy; Medicine; Metabolism; Metabolites; Metabolomics; Multilevel; Neurotransmitters; NMR; Nuclear magnetic resonance; Nutrient deficiency; Nutrition; Organic acids; Phosphates; Physiological aspects; Plasma; Proline; Proline - blood; Pyridoxal Phosphate - blood; Pyruvic acid; Quantitative analysis; Rodents; Trimethylamine; Trimethylamine-N-oxide; Vitamin B; Vitamin B 6 - blood; Vitamin B 6 Deficiency - blood; Vitamin B 6 Deficiency - metabolism; Vitamin B6; Vitamin deficiency; Vitamins; Womens health; Young Adult; Atlanta Georgia; Georgia; Florida; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063544

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.