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N ovel biomarkers of B6-status and their relation to inflammation

N ovel biomarkers of B6-status and their relation to inflammation. B6 vitamers in serum/plasma. Metabolic markers. Reflect vitamin function in tissues Less affected by short-term vitamin intake and distribution Allow assessment of vitamin status during supplementation.

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N ovel biomarkers of B6-status and their relation to inflammation

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  1. Novel biomarkers of B6-status and theirrelation toinflammation

  2. B6 vitamers in serum/plasma

  3. Metabolic markers • Reflect vitamin function in tissues • Less affected by short-term vitamin intake and distribution • Allow assessment of vitamin status during supplementation

  4. Metabolic markers • Cystathionine • Creatine • 3-Hydroxykynurenine (HK) • HK/XA ratio

  5. Cystathionine and vitamin B6

  6. Kynurenines and vitamin B6

  7. 3-Hydroxykynurenine (HK) and B6 status From Midttun et al (2011) J Nutr 141: 611

  8. 3-Hydroxykynurenine (HK) as a marker of B6 status • A plausible mechanism in the sense that further metabolism of HK but not formation is dependent on PLP • Inflexion point at about 20 nmol/L PLP in a population including subjects with high inflammatory status • HK was more strongly associated with several inflammatory markers than with PLP • A marked reduction in HK after pyridoxine supplementation

  9. HK/XA and other ratios and B6 status From Ulvik et al (2013) Am J ClinNutr 98: 934

  10. HK/XA and other ratios and B6 status From Ulvik et al (2013) Am J ClinNutr 98: 934

  11. Dose-response for HK and HK/XA ratio versus PLP From Ulvik et al (2013) Am J ClinNutr 98: 934

  12. HK/XA ratio as a marker of B6 status • Compared to HK, HK/XA (and other ratios) better discriminated subjects with low PLP • PLP was the strongest predictor for HK/XA (and other ratios) • Ratios have the advantage of eliminating influences shared by metabolites • Associations with several variables, including inflammatory markers and kidney function, were attenuated. • A marked reduction in HK/XA after pyridoxine supplementation

  13. Vitamin B6 species in serum/plasma

  14. The vitamer B6 ratio, PAr • PAr = PA/(PLP+PL) • PAr has a higher ICC (of 0.75) than any other ratio and B6 vitamer • ICC of PAr was less affected by pyridoxine supplementation (reduced to 0.44) than ICC of any other ratio and B6 vitamer • Inflammatory markers (CRP +WBC+KTR+neopterin) accounted for > 90% of the explained variance of PAr. • Renal function (eGFR) has a strong impact on PA but only minor impact on PAr. • In ROC analysis, PAr discriminated high inflammatory levels assessed by a summary score (>95th percentile) with an area under the curve of 0.85. • Change in PAr over 28 days correlated with change in inflammatory markers over this time period

  15. ROC plot for the diagnostic accuracy of PAr (solid line) and PLP (dashed line) to detect high (> 95th percentile) summary score of CRP, neopterin and KTR Ulvik et al (2014) Am J ClinNutr, accepted

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