Mechanistic perspective on the relationship between pyridoxal 5'-phosphate and inflammation.

JM USDA HNRC, Tufts University, Boston, Massachusetts, USA.
Nutrition Reviews (Impact Factor: 4.6). 04/2013; 71(4):239-44. DOI: 10.1111/nure.12014
Source: PubMed

ABSTRACT A variety of inflammatory disease conditions have been found to be associated with low levels of plasma pyridoxal 5'-phosphate (PLP), the active form of vitamin B6 , without any indication of a lower dietary intake of vitamin B6 , excessive catabolism of the vitamin, or congenital defects in its metabolism. The present review was conducted to examine the existing literature in this regard. Current evidence suggests that the inverse association between plasma PLP and inflammation may be the result of mobilization of this coenzyme to the site of inflammation, for use by the PLP-dependent enzymes of the kynurenine pathway of tryptophan degradation, metabolism of the immunomodulatory sphingolipids, ceramide and sphingosine 1-phosphate, and for serine hydroxymethylase for immune cell proliferation.

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    ABSTRACT: Pyridoxal 5'-phosphate (PLP; a B6 vitamer) serves as an important cofactor in a myriad of metabolic reactions, including the transsulfuration (TS) pathway, which converts homocysteine (Hcy) to cysteine. While overt vitamin B6 deficiency is rare, moderate deficiency is common and may be exacerbated by anti-pyridoxine factors in the food supply. To this end, we developed a model of moderate B6 deficiency and a study was conducted to examine the in vivo effect of 1-amino d-proline (1ADP), an anti-pyridoxine factor found in flaxseed, on indices of Hcy metabolism through the TS pathway in moderately B6 deficient rats. Male weaning rats received a semi-purified diet containing either 7mg/kg (control; CD) or 0.7mg/kg (moderately deficient; MD) diet of pyridoxine·hydrochloride (PN∙HCl), each with 1 of 4 levels of 1ADP, viz. 0, 0.1, 1 and 10mg/kg diet for 5weeks. Perturbations in vitamin B6 biomarkers were more pronounced in the MD group. Plasma PLP was significantly reduced, while plasma Hcy (8-fold) and cystathionine (11-fold) were increased in rats consuming the highest amount of 1ADP in the MD group. The activities of hepatic cystathionine β-synthase and cystathionine γ-lyase enzymes were significantly reduced in rats consuming the highest 1ADP compared to the lowest, for both levels of PN∙HCl. Dilation of hepatic central veins and sinusoids, mild steatosis and increased liver triglycerides were present in MD rats consuming the highest 1ADP level. The current data provide evidence that the consumption of an anti-pyridoxine factor linked to flaxseed may pose a risk for subjects who are moderate/severe vitamin B6 deficient. Copyright © 2014 Elsevier Inc. All rights reserved.
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    ABSTRACT: The use of oral contraceptives (OCs) has been associated with low plasma pyridoxal 5'-phosphate (PLP). The functional consequences are unclear. To determine whether functional vitamin B-6 insufficiency occurs in OC users and is attributable to OCs, we investigated the associations of PLP with metabolites of one-carbon metabolism, tryptophan catabolism, and inflammation in OC users, and evaluated the effects of OCs on these metabolites. Plasma metabolite concentrations were measured in 157 OC users (20-40 y of age). Associations between PLP and the metabolites were analyzed through use of generalized additive models and partial least squares-discriminant analysis (PLS-DA). Additionally, data from 111 of the 157 OC users were compared to previously reported data from 11 nonusers, at adequate and low vitamin B-6 status, with use of multivariate ANOVA. PLP showed significant (P < 0.05) negative nonlinear association with homocysteine, glutathione, and ratios of asymmetric dimethylarginine to arginine, 3-hydroxykynurenine to 3-hydroxyanthranilic acid, and 3-hydroxykynurenine to kynurenic acid. PLS-DA supported these conclusions and identified 3-hydroxykynurenine and the 3-hydroxykynurenine-to-kynurenine ratio as discriminating biomarkers in women with PLP ≤30 nmol/L. Among the many differences, OC users had significantly higher plasma pyridoxal (157% at adequate and 195% at low vitamin B-6 status), 4-pyridoxic acid (154% at adequate and 300% at low vitamin B-6 status), xanthurenic acid (218% at low vitamin B-6 status), 3-hydroxyanthranilic acid (176% at adequate and 166% at low vitamin B-6 status), quinolinic acid (127% at low vitamin B-6 status), and nicotinamide (197% at low vitamin B-6 status). Biomarkers of inflammation were not associated with PLP, and no differences were found between the 2 groups. PLP is associated with biomarkers of one-carbon metabolism and tryptophan catabolism but not with biomarkers of inflammation in OC users. Independent of vitamin B-6 status, OCs have effects on metabolites and ratios of one-carbon metabolism and tryptophan catabolism but not on biomarkers of inflammation. This study was registered at as NCT01128244. The study from which data for nonusers was derived was registered as NCT00877812. © 2015 American Society for Nutrition.
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    ABSTRACT: Dietary intake and/or circulating concentrations of vitamin B6 have been associated with risk of cancer, but results are inconsistent and mechanisms uncertain. Pyridoxal 5’-phosphate (PLP) is the most commonly used marker of B6 status. We recently proposed the ratio 3-hydroxykynurenine/xanthurenic acid (HK/XA) as an indicator of functional vitamin B6 status, and the 4-pyridoxic acid (PA) /(pyridoxal (PL) +PLP) ratio (PAr) as a marker of vitamin B6 catabolism during inflammation. We compared plasma PLP, HK/XA and PAr as predictors of cancer incidence in a prospective community-based cohort in Norway. This study included 6539 adults without known cancer at baseline (1998-99) from the Hordaland Health Study (HUSK). HR and 95% CI were calculated for the risk of overall and site-specific cancers using multivariate Cox proportional hazards regression with adjustment for potential confounders. After a median follow-up time of 11.9 years, 963 cancer cases (501 men and 462 women) were identified. Multivariate-adjusted Cox-regression showed no significant relation of plasma PLP or HK/XA with risk of incident cancer. In contrast, PAr was significantly associated with risk of cancer with HR (95% CI) =1.31 (1.12-1.52) per 2 standard deviation (SD) increment (P < 0.01). Further analysis showed that PAr was a particular strong predictor of lung cancer with HR (95% CI) =2.46 (1.49-4.05) per 2 SD increment (P < 0.01). The present results indicate that associations of vitamin B6 with cancer may be related to increased catabolism of vitamin B6, in particular for lung cancer where inflammation may be largely involved in carcinogenesis. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 11/2014; DOI:10.1002/ijc.29345 · 6.20 Impact Factor