Novel 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

Metabolic markers

• Cystathionine

• Creatine

• 3-Hydroxykynurenine (HK)

• HK/XA ratio

Cystathionine

and

vitamin B6

Kynurenines

and

vitamin B6

3-Hydroxykynurenine (HK) and B6 status

From Midttun et al (2011) J Nutr 141: 611

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

HK/XA and other ratios and B6 status

From Ulvik et al (2013) Am J Clin Nutr 98: 934

HK/XA and other ratios and B6 status

From Ulvik et al (2013) Am J Clin Nutr 98: 934

Dose-response for HK and HK/XA ratio versus PLP

From Ulvik et al (2013) Am J Clin Nutr 98: 934

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

Vitamin B6

species

in

serum/plasma

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

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 Clin Nutr,

accepted