title: Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects.
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.
authors.affiliation: Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida, United States of America. jfgy@ufl.edu
authors.forename: Jesse F
authors.initials: JF
authors.lastname: Gregory
authors.forename: Youngja
authors.initials: Y
authors.lastname: Park
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lamers
authors.forename: Nirmalya
authors.initials: N
authors.lastname: Bandyopadhyay
authors.forename: Yueh-Yun
authors.initials: YY
authors.lastname: Chi
authors.forename: Kichen
authors.initials: K
authors.lastname: Lee
authors.forename: Steven
authors.initials: S
authors.lastname: Kim
authors.forename: Vanessa
authors.initials: V
authors.lastname: da Silva
authors.forename: Nikolas
authors.initials: N
authors.lastname: Hove
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ranka
authors.forename: Tamer
authors.initials: T
authors.lastname: Kahveci
authors.forename: Keith E
authors.initials: KE
authors.lastname: Muller
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stacpoole
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
mesh_terms: D000085:Acetates / Q000097:blood; D000328:Adult; D000596:Amino Acids / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D003540:Cystathionine / Q000097:blood; D005260:Female; D018698:Glutamic Acid / Q000097:blood; D005973:Glutamine / Q000097:blood; D006801:Humans; D007656:Ketoglutaric Acids / Q000097:blood; D008297:Male; D055432:Metabolomics; D011392:Proline / Q000097:blood; D011732:Pyridoxal Phosphate / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood; D026681:Vitamin B 6 Deficiency / Q000097:blood* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000085:Acetates; D000596:Amino Acids; D007656:Ketoglutaric Acids; C116917:acylcarnitine; D005973:Glutamine; D003540:Cystathionine; D018698:Glutamic Acid; D011732:Pyridoxal Phosphate; D025101:Vitamin B 6; D011392:Proline; D002331:Carnitine