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Annu Rev Nutr. 2015;35:33-70. doi: 10.1146/annurev-nutr-071714-034330. Epub 2015 May 13.

Direct and Functional Biomarkers of Vitamin B6 Status.

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Department of Clinical Science, University of Bergen, and the Laboratory of Clinical Biochemistry, Haukeland University Hospital, 5021 Bergen, Norway; email:


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.


B6 vitamers; amino acids; direct biomarkers; functional biomarkers; kynurenines; metabolomics; one-carbon metabolites; targeted metabolic profiling; transaminase tests; transsulfuration metabolites

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