title: Evidence for increased catabolism of vitamin B-6 during systemic inflammation.
abstract: BACKGROUND
  Plasma concentrations of PL 5'-phosphate (PLP), which is the active coenzyme form of vitamin B-6, are reduced during inflammation. The underlying mechanisms may include altered tissue distribution or increased catabolism via pyridoxal (PL) to pyridoxic acid (PA). Recently, we showed that catabolic enzyme activity could be assessed by substrate product ratios measured in plasma.
  
  
  OBJECTIVE
  We evaluated the ratios PA:PL, PA:PLP, and PA:(PL + PLP) as possible markers of vitamin B-6 catabolism.
  
  
  METHODS
  Cross-sectional and longitudinal data were derived from the Western Norway B-Vitamin Intervention Trial. We analyzed associations of ratios with inflammatory markers and other clinical variables by using multiple linear regression and partial correlation. In addition, intraclass correlation coefficients (ICCs) were used to assess the ability of plasma indexes to differentiate between subjects.
  
  
  RESULTS
  PA:(PL + PLP) had the highest ICC of all vitamin B-6 metabolites and ratios tested. In regression models, the inflammatory markers C-reactive protein, white blood cell count, neopterin, and kynurenine:tryptophan collectively accounted for 28% of the total and > 90% of the explained variation in PA:(PL + PLP). For individual B-6 metabolites, corresponding numbers were 19-25% and 20-44%, respectively, with vitamin supplement intake, smoking, and kidney function (estimated glomerular filtration rate) as additional predictors. In an analysis of receiver operating characteristics, PA:(PL + PLP) discriminated high inflammatory concentrations with an area under the curve (95% CI) of 0.85 (0.81, 0.89).
  
  
  CONCLUSIONS
  Broad-specificity enzymes upregulated to reduce oxidative and aldehyde stress could explain increased catabolism of vitamin B-6 during inflammation. The ratio PA:(PL + PLP) may provide novel insights into pathologic processes and potentially predict risk of future disease.
authors.affiliation: From Bevital A/S, Laboratoriebygget, Bergen, Norway (AU and ØM); the Section for Cardiology (ERP and ON), Department of Clinical Science (SJPME and PMU), University of Bergen, Bergen, Norway; the Department of Heart Disease (ON) and the Laboratory of Clinical Biochemistry (PMU), Haukeland University Hospital, Bergen, Norway (ON); and the Department of Epidemiology, School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands (SJPME).
authors.forename: Arve
authors.initials: A
authors.lastname: Ulvik
authors.affiliation: From Bevital A/S, Laboratoriebygget, Bergen, Norway (AU and ØM); the Section for Cardiology (ERP and ON), Department of Clinical Science (SJPME and PMU), University of Bergen, Bergen, Norway; the Department of Heart Disease (ON) and the Laboratory of Clinical Biochemistry (PMU), Haukeland University Hospital, Bergen, Norway (ON); and the Department of Epidemiology, School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands (SJPME).
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.affiliation: From Bevital A/S, Laboratoriebygget, Bergen, Norway (AU and ØM); the Section for Cardiology (ERP and ON), Department of Clinical Science (SJPME and PMU), University of Bergen, Bergen, Norway; the Department of Heart Disease (ON) and the Laboratory of Clinical Biochemistry (PMU), Haukeland University Hospital, Bergen, Norway (ON); and the Department of Epidemiology, School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands (SJPME).
authors.forename: Eva R
authors.initials: ER
authors.lastname: Pedersen
authors.affiliation: From Bevital A/S, Laboratoriebygget, Bergen, Norway (AU and ØM); the Section for Cardiology (ERP and ON), Department of Clinical Science (SJPME and PMU), University of Bergen, Bergen, Norway; the Department of Heart Disease (ON) and the Laboratory of Clinical Biochemistry (PMU), Haukeland University Hospital, Bergen, Norway (ON); and the Department of Epidemiology, School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands (SJPME).
authors.forename: Simone Jpm
authors.initials: SJ
authors.lastname: Eussen
authors.affiliation: From Bevital A/S, Laboratoriebygget, Bergen, Norway (AU and ØM); the Section for Cardiology (ERP and ON), Department of Clinical Science (SJPME and PMU), University of Bergen, Bergen, Norway; the Department of Heart Disease (ON) and the Laboratory of Clinical Biochemistry (PMU), Haukeland University Hospital, Bergen, Norway (ON); and the Department of Epidemiology, School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands (SJPME).
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
authors.affiliation: From Bevital A/S, Laboratoriebygget, Bergen, Norway (AU and ØM); the Section for Cardiology (ERP and ON), Department of Clinical Science (SJPME and PMU), University of Bergen, Bergen, Norway; the Department of Heart Disease (ON) and the Laboratory of Clinical Biochemistry (PMU), Haukeland University Hospital, Bergen, Norway (ON); and the Department of Epidemiology, School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands (SJPME).
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007737:Kynurenine / Q000097:blood; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D009664:Norway; D018384:Oxidative Stress / Q000502:physiology; D011730:Pyridoxal / Q000097:blood; D011732:Pyridoxal Phosphate / Q000097:blood; D011735:Pyridoxic Acid / Q000097:blood; D012372:ROC Curve; D014364:Tryptophan / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007737:Kynurenine; D011730:Pyridoxal; D011735:Pyridoxic Acid; D011732:Pyridoxal Phosphate; D019798:Neopterin; D025101:Vitamin B 6; D014364:Tryptophan; D002097:C-Reactive Protein