A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Abstract

Background: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health.

Objectives: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics.

Medthods: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP.

Results: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers.

Conclusions: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.

Keywords: PLP; dietary biomarkers; kynurenine pathway; transsulfuration pathway; vitamin B6.

FIGURE 1

Forest plot of estimated associations of PLP with Hcy:Cys (A) and PLP with Cysta:Cys (B) in 3 nested case-control cohorts within the EPIC study (n = 4608). Estimates are at specified covariate levels, holding other predictor variables constant at the mean or reference category. Categories for alcohol are number of drinks per day (12 g alcohol per drink). Values and 95% CrIs are derived from the posterior distributions of Bayesian models with pairwise interaction terms added to the fully adjusted model. The geometric means also assume mean/reference values for other predictors. The ELPD difference and SE of the difference compares the model with interaction term to the original model without interaction. The ELPD difference is positive if the model with an interaction term is a better fit. Abbreviations: CrI, credible interval; Cysta:Cys, cystathionine:cysteine; ELPD, expected log predictive density; EPIC, European Prospective Investigation into Cancer and Nutrition; Hcy:Cys, homocysteine:cysteine; PLP, pyridoxal 5′-phosphate.

FIGURE 2

Forest plot of estimated associations of PLP with HKr in 3 nested case-control cohorts within the EPIC study (n = 4608). Estimates are at specified covariate levels, holding other predictor variables constant at the mean or reference category. Categories for alcohol are number of drinks per day (12 g alcohol per drink). Values and 95% CrIs are derived from the posterior distributions of Bayesian models with pairwise interaction terms added to the fully adjusted model. The geometric means also assume mean/reference values for other predictors. The ELPD difference and SE of the difference compares the model with interaction term to the original model without interaction. The ELPD difference is positive if the model with an interaction term is a better fit. Abbreviations: CrI, credible interval; ELPD, expected log predictive density; EPIC, European Prospective Investigation into Cancer and Nutrition; HK, 3′-hydroxykynurenine; HKr, HK ratio; PLP, pyridoxal 5′-phosphate.