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Direct and Functional Biomarkers of Vitamin B6 Status.

ABSTRACT: Measures of B6 status are categorized as direct biomarkers and as functional biomarkers. Direct biomarkers measure B6 vitamers in plasma/serum, urine and erythrocytes, and among these plasma pyridoxal 5'-phosphate (PLP) is most commonly used. Functional biomarkers include erythrocyte transaminase activities and, more recently, plasma levels of metabolites involved in PLP-dependent reactions, such as the kynurenine pathway, one-carbon metabolism, transsulfuration (cystathionine), and glycine decarboxylation (serine and glycine). Vitamin B6 status is best assessed by using a combination of biomarkers because of the influence of potential confounders, such as inflammation, alkaline phosphatase activity, low serum albumin, renal function, and inorganic phosphate. Ratios between substrate-products pairs have recently been investigated as a strategy to attenuate such influence. These efforts have provided promising new markers such as the PAr index, the 3-hydroxykynurenine:xanthurenic acid ratio, and the oxoglutarate:glutamate ratio. Targeted metabolic profiling or untargeted metabolomics based on mass spectrometry allow the simultaneous quantification of a large number of metabolites, which are currently evaluated as functional biomarkers, using data reduction statistics.

SUBMITTER: Ueland PM

PROVIDER: S-EPMC5988249 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Direct and Functional Biomarkers of Vitamin B6 Status.

Ueland Per Magne PM Ulvik Arve A Rios-Avila Luisa L Midttun Øivind Ø Gregory Jesse F JF

Annual review of nutrition 20150513

Measures of B6 status are categorized as direct biomarkers and as functional biomarkers. Direct biomarkers measure B6 vitamers in plasma/serum, urine and erythrocytes, and among these plasma pyridoxal 5'-phosphate (PLP) is most commonly used. Functional biomarkers include erythrocyte transaminase activities and, more recently, plasma levels of metabolites involved in PLP-dependent reactions, such as the kynurenine pathway, one-carbon metabolism, transsulfuration (cystathionine), and glycine deca ...[more]

PMID: 25974692

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Project description:BackgroundFolate-mediated 1-carbon metabolism requires several nutrients, including vitamin B6. Circulating biomarker concentrations indicating high vitamin B6 status are associated with a reduced risk of colorectal cancer (CRC). However, little is known about the effect of B6 status in relation to clinical outcomes in CRC patients.ObjectivesWe investigated survival outcomes in relation to vitamin B6 status in prospectively followed CRC patients.MethodsA total of 2031 patients with stage I-III CRC participated in 6 prospective patient cohorts in the international FOCUS (folate-dependent 1-carbon metabolism in colorectal cancer recurrence and survival) Consortium. Preoperative blood samples were used to measure vitamin B6 status by the direct marker pyridoxal 5'-phosphate (PLP), as well as the functional marker HK-ratio (HKr)[3'-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3'-hydroxy anthranilic acid + anthranilic acid)]. Using Cox proportional hazards regression, we examined associations of vitamin B6 status with overall survival (OS), disease-free survival (DFS), and risk of recurrence, adjusted for patient age, sex, circulating creatinine concentrations, tumor site, stage, and cohort.ResultsAfter a median follow-up of 3.2 y for OS, higher preoperative vitamin B6 status as assessed by PLP and the functional marker HKr was associated with 16-32% higher all-cause and disease-free survival, although there was no significant association with disease recurrence (doubling in PLP concentration: HROS, 0.68; 95% CI: 0.59, 0.79; HRDFS, 0.84; 95% CI: 0.75, 0.94; HRRecurrence, 0.96; 95% CI: 0.84, 1.09; HKr: HROS, 2.04; 95% CI: 1.67, 2.49; HRDFS, 1.56; 95% CI: 1.31, 1.85; HRRecurrence, 1.21; 95% CI: 0.96,1. 52). The association of PLP with improved OS was consistent across colorectal tumor site (right-sided colon: HROS, 0.75; 95% CI: 0.59, 0.96; left-sided colon: HROS, 0.71; 95% CI: 0.55, 0.92; rectosigmoid junction and rectum: HROS, 0.61; 95% CI: 0.47, 0.78).ConclusionHigher preoperative vitamin B6 status is associated with improved OS among stage I-III CRC patients.

Project description:BackgroundDisordered mineral metabolism is characteristic of decreased kidney function. However, the prospective associations between circulating levels of vitamin D binding protein, vitamin D, and end-stage renal disease (ESRD) have not been extensively evaluated in epidemiologic studies.Study designNested case-control study.Setting & participantsMiddle-aged black and white men and women from 4 US communities.PredictorsBaseline levels of vitamin D binding protein, 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) were measured in blood samples collected at study visit 4 (1996-1998) of the ARIC (Atherosclerosis Risk in Communities) Study.OutcomeESRD cases (n=184) were identified through hospitalization diagnostic codes from 1996 to 2008 and were frequency matched to controls (n=251) on categories of estimated glomerular filtration rate, albuminuria, diabetes mellitus, sex, and race.MeasurementsLogistic regression was used to estimate the association between mineral metabolism biomarkers (vitamin D binding protein, 25(OH)D, and 1,25(OH)2D) and incident ESRD, adjusting for age, sex, race, estimated glomerular filtration rate, albuminuria, diabetes mellitus, hypertension, education, specimen type, and serum levels of calcium, phosphate, and parathyroid hormone.ResultsHigher vitamin D binding protein levels were associated with elevated risk for incident ESRD (OR, 1.76; 95% CI, 1.22-2.54; P=0.003). Higher free and bioavailable 25(OH)D levels were associated with reduced risk for incident ESRD (ORs of 0.65 [95% CI, 0.46-0.92; P=0.02] and 0.63 [95% CI, 0.43-0.91; P=0.02] for free and bioavailable 25[OH]D, respectively). There was no association between ESRD and overall levels of 25(OH)D (OR, 0.83; 95% CI, 0.58-1.19; P=0.3) or 1,25(OH)2D (OR, 0.73; 95% CI, 0.48-1.13; P=0.2).LimitationsLack of direct measurement of free and bioavailable vitamin D.ConclusionsIn the general population, blood levels of vitamin D binding protein were positively associated and blood levels of free and bioavailable 25(OH)D were inversely associated with new-onset ESRD during follow-up.

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Direct and Functional Biomarkers of Vitamin B6 Status.

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Direct and Functional Biomarkers of Vitamin B6 Status.

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