Direct and Functional Biomarkers of Vitamin B6 Status

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


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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acids / blood
  • Biomarkers / blood*
  • Biomarkers / urine
  • Body Mass Index
  • Female
  • Health Status
  • Humans
  • Infant
  • Infant, Newborn
  • Inflammation
  • Kynurenine / blood
  • Life Style
  • Male
  • Metabolome
  • Metabolomics
  • Nutritional Status*
  • Pregnancy
  • Pyridoxal / blood
  • Pyridoxal Phosphate / blood
  • Pyridoxic Acid / urine
  • Transaminases
  • Vitamin B 6 Deficiency / blood*
  • Vitamin B 6 Deficiency / urine
  • Vitamin B 6* / blood
  • Vitamin B 6* / physiology
  • Vitamin B 6* / urine


  • Amino Acids
  • Biomarkers
  • Kynurenine
  • Pyridoxal
  • Pyridoxic Acid
  • Pyridoxal Phosphate
  • Vitamin B 6
  • Transaminases