Plasma Plasma Pyridoxal 5'-phosphate Research Articles

Plasma pyridoxal-5-phosphate and future risk of myocardial infarction in the European Prospective Investigation into Cancer and Nutrition Potsdam cohort

Background: Retrospective studies indicate that low concentrations of plasma pyridoxal-5-phosphate (PLP) are associated with cardiovascular events; however, few prospective studies of this issue have been conducted.Objective: We therefore investigated whether PLP concentrations are independently associated with myocardial infarction (MI) in the European Investigation into Cancer and Nutrition (EPIC) Potsdam Study.Design: After exclusion of prevalent MI or stroke, incident cases of MI were identified among 26 761 participants (aged 35–65 y at baseline). The current analysis is based on a nested case-cohort study consisting of a control group of 810 subjects without MI or stroke at baseline and a case group of 148 subjects who had an MI during a mean follow-up period of 6.0 ± 1.5 y. Cox proportional hazard models were used to evaluate the association between plasma PLP and risk of MI.Results: In the age- and sex-adjusted analysis, subjects in the highest quintile of PLP had a significantly reduced risk of MI (hazard ratio: 0.50; 95% CI: 0.29, 0.83). Adjustment for either low-grade inflammation or smoking diminished this association. When both low-grade inflammation and smoking were adjusted for, the association was abolished. In addition, adjustment for established risk factors also abolished the association between PLP and risk of MI.Conclusion: These findings from a prospective German cohort study suggest that PLP is not independently associated with risk of MI.

Vitamin B-6 Status Indices Are Lower in Pregnant than in Nonpregnant Women but Urinary Excretion of 4-Pyridoxic Acid Does Not Differ1–4

The cause of reduced plasma pyridoxal-5'-phosphate (PLP) concentration and the validity of plasma PLP concentration as a vitamin B-6 status indicator during pregnancy are not well understood. In this study, pregnant and nonpregnant women consumed a controlled diet for 5 d to exclude dietary intake as a factor in altered vitamin B-6 metabolic utilization. Plasma PLP and pyridoxal (PL) concentrations were significantly lower and higher, respectively, and plasma PL+PLP concentration was significantly lower during pregnancy. When plasma PLP and PL concentrations were normalized based on plasma albumin concentration, the differences were less marked but were still significant. The erythrocyte aspartate aminotransferase activity coefficient was significantly greater in pregnant women which is a further indication of reduced vitamin B-6 concentrations in the blood. No difference was observed in the urinary excretion of 4-pyridoxic acid between the pregnant and nonpregnant women. Results of this study demonstrate that vitamin B-6 status indices are lower during pregnancy without differences in the urinary excretion of 4-pyridoxic acid.

Vitamin B-6 Status of Women with a Constant Intake of Vitamin B-6 Changes with Three Levels of Dietary Protein

To determine the effect of varying levels of dietary protein with a constant intake of vitamin B-6 (B-6) on B-6 status, nine women were fed diets providing daily intakes of 1.25 mg B-6 and 0.5, 1.0 and 2.0 g protein/kg body weight. After an 8-d adjustment period, the women consumed each level of dietary protein for 14 d in a Latin-square design. Several direct and indirect B-6 status indicators were measured in blood and urine. Significant differences among protein levels were found for urinary 4-pyridoxic acid (4-PA) excretion (P < 0.01), plasma pyridoxal 5′-phosphate (PLP) concentration (P < 0.05), and urinary excretion of volatile amines (VA, kynurenine plus acetylkynurenine) after a 2-g L-tryptophan load (P < 0.05). Nitrogen intake was significantly negatively correlated with urinary 4-PA excretion (r = -0.619, P < 0.001) and plasma PLP concentration (r = -0.549, P < 0.01), and positively correlated with erythrocyte alanine aminotransferase percentage stimulation (r = 0.418, P < 0.05) and urinary post-tryptophan load excretion of xanthurenic acid (r = 0.535, P < 0.05), kynurenic acid (r = 0.563, P < 0.05) and VA (r = 0.626, P < 0.01). Compared with men consuming diets with similar B-6 to protein ratios in a previous study, the women excreted a greater percentage of the B-6 intake as 4-PA, had lower plasma PLP concentrations and excreted greater amounts of postload urinary tryptophan metabolites at all three protein levels. If the Recommended Dietary Allowance (RDA) of vitamin B-6 is to be based on the dietary B-6 to protein ratio, gender differences in response to varying protein intakes should be considered. For the levels of protein intake used in this study and a B-6 intake of 1.25 mg/d, a B-6 to protein ratio of greater than 0.020 mg/g is required for adequate vitamin B-6 status in women.

Urine phosphoethanolamine is a specific biomarker for hypophosphatasia in adults.

We investigated the utility of urine phosphoethanolamine (PEA) as a marker to aid in diagnosing and/or confirming hypophosphatasia (HPP) in adults and for monitoring patients on enzyme replacement therapy (ERT). Data was collected from seventy-eight adults who were referred to the Vanderbilt Program for Metabolic Bone Disease for evaluation of a possible or confirmatory HPP diagnosis between July 2014 through December 2019. Fifty-nine patients were diagnosed with HPP and nineteen were excluded from a diagnosis of HPP. The urine PEA results of those patients with a confirmed diagnosis of HPP and those patients with a diagnosis of HPP excluded were captured and compared to other laboratory and clinical parameters consistent with HPP, including alkaline phosphatase (ALP) activity, plasma pyridoxal 5'-phosphate (PLP), the presence of musculoskeletal abnormalities, and genetic testing for pathogenic mutations in ALPL. Initial urine PEA values in patients in our HPP cohort and not on ERT were significantly higher (median=150.0nmol/mg creatinine, IQR=82.0-202.0) compared patients in our HPP negative group (median 18.0nmol/mg creatinine, IQR=14.0-30.0, p<0.0001) and higher than patients on ERT (median 65.0nmol/mg creatinine, IQR=45.3-79.8). Patients who began ERT had a decline in urine PEA levels after treatment with a mean decrease of 68.1%. Plasma ALP levels were significantly lower in the group of patients with HPP and not on ERT group (median=24.0U/L, IQR=15.0-29.50) compared to the patients without HPP (median=45.50U/L, IQR=34.0-62.0;) and plasma PLP levels were significantly higher in the HPP non-ERT group (median=284.0nmol/L, IQR=141.0-469.4) compared to the patients without HPP (median=97.5nmol/L, IQR=43.7-206.0;). The area under the curve (AUC) of urine PEA, ALP, and PLP to distinguish between HPP and non-HPP patients is 0.968, 0.927 and 0.781, respectively, in our cohort. Urine PEA had 100% specificity (95% CI of 83.2% to 100.0%) for diagnosing HPP at a value >53.50nmol/mg creatinine with a sensitivity of 88.4%; 95%CI 75.5 to 94.9%. ALP had a 100% specificity (95% CI of 82.4% to 100.0%) for diagnosing HPP at a value <30.5U/L with a sensitivity of 77.2%; (95%CI 64.8 to 86.2%). PLP had a 100% specificity (95% CI of 81.6% to 100.0%) for diagnosing HPP at a value >436nmol/L with a sensitivity of 26.9%; (95%CI 16.8 to 40.3%). The most common pathogenic or likely pathogenic mutations in our cohort were c.1250A>G (p.Asn417Ser), c.1133A>T (p.Asp378Val), c.881A>C (p.Asp294Ala), c.1171C>T (p.Arg391Cys), and c.571G>A, (p.Glu191Lys). Urine PEA is a promising diagnostic and confirmatory marker for HPP in patients undergoing investigation for HPP. Urine PEA also has potential use as a marker to monitor ERT compliance. Future studies are necessary to evaluate the association between PEA levels and clinical outcomes.

Gender Differences in the Associations of Plasma Pyridoxal 5'-Phosphate with Plasma Polyunsaturated Fatty Acids among US Young and Middle-Aged Adults: NHANES 2003-2004.

Vitamin B6-restricted diets and low plasma pyridoxal 5′-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20–59 years; 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires; plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (β) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (β = 0.138, b = 0.104, p = 0.0004), DHA (β = 0.101, b = 0.058, p = 0.036), EPA + DHA (β = 0.125, b = 0.073, p = 0.005), EPA/AA (β = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (β = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.

Vitamin B6, Inflammation, and Cardiovascular Outcome in a Population-Based Cohort: The Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study.

Background: a large number of studies have linked vitamin B6 to inflammation and cardiovascular disease in the general population. However, it remains uncertain whether vitamin B6 is associated with cardiovascular outcome independent of inflammation. Methods: we measured plasma pyridoxal 5’-phosphate (PLP), as an indicator of vitamin B6 status, at baseline in a population-based prospective cohort of 6249 participants of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study who were free of cardiovascular disease. As indicators of low-grade systemic inflammation, we measured high-sensitivity C-reactive protein and GlycA; Results: median plasma PLP was 37.2 (interquartile range, 25.1–57.0) nmol/L. During median follow-up for 8.3 (interquartile range, 7.8–8.9) years, 409 non-fatal and fatal cardiovascular events (composite outcome) occurred. In the overall cohort, log transformed plasma PLP was associated with the composite outcome, independent of adjustment for age, sex, smoking, alcohol consumption, body mass index (BMI), estimated glomerular filtration rate (eGFR), total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio, and blood pressure (adjusted hazard ratio per increment of log plasma PLP, 0.66; 95% confidence interval (CI), 0.47–0.93). However, adjustment for high-sensitivity C-reactive protein and GlycA increased the hazard ratio by 9% and 12% respectively, to non-significant hazard ratios of 0.72 (95% confidence interval, 0.51–1.01) and 0.74 (95% confidence interval, 0.53–1.05). The association of plasma PLP with cardiovascular risk was modified by gender (adjusted Pinteraction = 0.04). When stratified according to gender, in women the prospective association with cardiovascular outcome was independent of age, smoking, alcohol consumption, high-sensitivity C-reactive protein, and GlycA (adjusted hazard ratio, 0.50, 95% confidence interval, 0.27–0.94), while it was not in men (adjusted hazard, 0.99, 95% confidence interval, 0.65–1.51). Conclusions: in this population-based cohort, plasma PLP was associated with cardiovascular outcome, but this association was confounded by traditional risk factors and parameters of inflammation. Notably, the association of low plasma PLP with high risk of adverse cardiovascular outcome was modified by gender, with a stronger and independent association in women.

Vitamin B-6, Independent of Homocysteine, Is a Significant Factor in Relation to Inflammatory Responses for Chronic Kidney Disease and Hemodialysis Patients.

The purpose of this study was to investigate whether plasma pyridoxal 5′-phosphate (PLP) and homocysteine were dependent on or independent of each other in order to be associated with inflammatory markers in patients with chronic kidney disease (CKD) or those receiving hemodialysis treatment. This was a cross-sectional study. Sixty-eight stage 2–5 CKD patients and 68 hemodialysis patients had one time fasting blood drawn for measurements of plasma PLP, pyridoxal (PL), homocysteine, and several inflammatory markers. Early CKD stage (stages 2-3) patients showed significantly lower plasma PLP levels and homocysteine concentrations than patients in an advanced CKD stage (stages 4-5) and those undergoing hemodialysis. Plasma PLP significantly correlated with CRP levels (partial rs = −0.21, p < 0.05) and plasma PL significantly correlated with IL-10 levels (partial rs = −0.24, p < 0.01), while plasma PLP plus PL significantly correlated with both CRP levels (partial rs = −0.20, p < 0.05) and interleukin-1β (partial rs = 0.22, p < 0.05) levels after adjusting for plasma homocysteine and other potential confounders. Plasma homocysteine displayed no significant correlations with any inflammatory markers. Vitamin B-6 status, rather than homocysteine, appeared to be a significant factor in relation to inflammatory responses for CKD and hemodialysis patients.

Vitamin B-6 catabolism and long-term mortality risk in patients with coronary artery disease

Low vitamin B-6 status has been related to increased risk of coronary artery disease (CAD), which is a condition that is associated with inflammation. The most common status marker, plasma pyridoxal 5'-phosphate (PLP), decreases during inflammation; therefore, causal relations are uncertain. We evaluated the vitamin B-6 biomarkers PLP, pyridoxal, and pyridoxic acid (PA) and the pyridoxic acid:(pyridoxal + PLP) ratio (PAr), a proposed marker of vitamin B-6 catabolism during activated cellular immunity, as predictors of mortality. Associations with risks of long-term all-cause mortality and cardiovascular mortality were evaluated with the use of Cox regression in patients who were undergoing elective coronary angiography for suspected stable angina pectoris (SAP) (n = 4131) and an independent cohort of patients who were hospitalized for acute myocardial infarction (AMI) (n = 3665). Plasma PLP (AMI patients only) and PA predicted all-cause mortality in models that were adjusted for established risk predictors, but associations were attenuated or nonsignificant after additional adjustment for inflammatory markers. PAr was correlated with biomarkers of inflammation (Pearson's r ≥ 0.37) and predicted all-cause mortality and cardiovascular mortality after adjustment for established risk predictors. In SAP patients, PAr had greater predictive strength than did current smoking, diabetes, hypertension, apolipoproteins, or C-reactive protein. PAr provided multiadjusted HRs per SD of 1.45 (95% CI: 1.30, 1.63) and 1.31 (95% CI: 1.21, 1.41) in SAP and AMI patients, respectively. In both cohorts, PAr was a particularly strong predictor of all-cause mortality for patients with no previous CAD history (P-interaction ≤ 0.04). PAr may capture unique aspects of inflammatory activation and thus provide new insights into disease mechanisms that may aid in identifying patients at increased risk of future fatal events.

Folate and vitamin B-6 status are not associated with homocysteine, oxidative stress and antioxidant capacities in patients with hepatocellular carcinoma.

The purpose of this study was to study the effects of serum folate and plasma pyridoxal 5'-phosphate (PLP) on plasma homocysteine, oxidative stress and antioxidant capacities in 44 hepatocellular carcinoma (HCC) patients and 56 healthy controls. The responses of folate, vitamin B-6, homocysteine, oxidative stress and antioxidant enzyme activities in HCC patients before and after tumor resection were also determined. Patients with HCC before tumor resection had significantly lower folate, PLP, homocysteine, glutathione peroxidase and superoxide dismutase levels, but higher malondialdehyde, total antioxidant capacity and glutathione S-transferase activity when compared with healthy controls. Oxidative stress was significantly decreased to a level similar to that of healthy controls after tumor resection in the HCC group. There were no associations of folate and PLP with plasma homocysteine, indicators of oxidative stress and antioxidant capacities. Serum folate and plasma PLP were not significant factors affecting plasma homocysteine, oxidative stress and antioxidant capacities in patients with HCC.

Vitamin B6 status and its relationship with polyunsaturated fatty acid concentrations during pregnancy

RationaleSuboptimal vitamin B6 status was shown to alter polyunsaturated fatty acid (PUFA) profiles, decreasing plasma (n‐3) and (n‐6) PUFA concentrations, in healthy men and women.AimTo assess the relationships between plasma pyridoxal 5'‐phosphate (PLP) and docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AA) concentrations at different stages of pregnancy.MethodsProspective cohort study in 213 healthy pregnant women (aged 20‐40 y) followed across trimesters at 5‐13, 20‐26 and 30‐36 wk. The study was conducted in Rio de Janeiro, Brazil. Fasting plasma PLP (nmol/L) and serum PUFA (µg/mL) were measured by HPLC and GLC, respectively.ResultsPlasma PLP concentrations [median (IQR)] dropped from 35.8 (28.4‐43.6) in the 1st to 21.2 (16.2‐27.1) in the 2nd trimester (P&lt;0.0001) and further decreased to 16.9 (12.8‐21.6) in the 3rd trimester (P&lt;0.0001). Median (IQR) PUFA concentrations were 55.8 (44.0‐65.5), 70.7 (60.9‐84.7), 74.5 (63.6‐89.6) for DHA; 8.4 (6.6‐11.7), 8.4 (6.5‐12.0), 7.4 (5.2‐10.9) for EPA; and 206 (179‐245), 236 (205‐270), 237 (207‐279) for AA in the 1st, 2nd, and 3rd trimester, respectively. Plasma PLP and DHA were correlated (P&lt;0.05) in the 1st (ρ=0.14) and 2nd trimester (ρ=0.20); plasma PLP and EPA (ρ=0.24) and AA (ρ=0.18) were correlated in the 2nd trimester (P&lt;0.05); no significant correlations were observed between PLP and any PUFA in the 3rd trimester.ConclusionsPlasma PLP concentrations were correlated with DHA, EPA and AA in early pregnancy.Funding: CNPq, FAPERJ, VRF‐FNH‐UBC

A simple high-performance liquid chromatography (HPLC) method for the measurement of pyridoxal-5-phosphate and 4-pyridoxic acid in human plasma

BackgroundLow concentration of plasma pyridoxal-5-phosphate (PLP) is associated with hyperhomocysteinemia and inflammation. Most methods for the measurement of plasma PLP require large specimen volume and involve the use of toxic reagents. MethodsWe have developed a HPLC method for the measurement of PLP and 4-pyridoxic acid (4-PA) in plasma, which requires small specimen volume. The samples are prepared without adding any toxic reagents. Furthermore, we have examined whether intake of vitamin B6 affects the concentration of plasma PLP and 4-PA. ResultsThe coefficient of variation of the method was 6% and the recovery of the added vitamin in plasma was about 100%. The concentrations of plasma PLP and 4-PA in 168 healthy subjects were 40.6 (8.4–165.0) nmol/L, median and (range) and 17.5 (3.7–114.79) nmol/L, median and (range) respectively. In the multiple regression analyses, the concentration of plasma PLP was associated with the concentration of plasma 4-PA (p<0.0001), BMI, (p=0.02) and sex, (p=0.0008). The concentration of plasma 4-PA was associated with plasma PLP (p<0.0001), serum folate (p=0.004), smoking (p=0.03) and vitamin B6 intake (p=0.01). ConclusionThe present method is suitable for large clinical studies for the measurement of plasma PLP and 4-PA. Our findings demonstrate that plasma 4-PA, BMI and sex are the major determinants of plasma PLP in healthy individuals.

Evaluation of vitamin B6 intake and status of 20- to 64-year-old Koreans.

BACKGROUND/OBJECTIVESRecent research regarding vitamin B6 status including biochemical index is limited. Thus, this study estimated intakes and major food sources of vitamin B6; determined plasma pyridoxal 5'-phosphate (PLP); and assessed vitamin B6 status of Korean adults.MATERIALS/METHODSThree consecutive 24-h diet recalls and fasting blood samples were collected from healthy 20- to 64-year-old adults (n = 254) living in the Seoul metropolitan area, cities of Kwangju and Gumi, Korea. Vitamin B6 intake and plasma PLP were analyzed by gender and by vitamin B6 supplementation. Pearson's correlation coefficient was used to determine associations of vitamin B6 intake and plasma PLP.RESULTSThe mean dietary and total (dietary plus supplemental) vitamin B6 intake was 1.94 ± 0.64 and 2.41 ± 1.45 mg/day, respectively. Median (50th percentile) dietary intake of men and women was 2.062 and 1.706 mg/day. Foods from plant sources provided 70.61% of dietary vitamin B6 intake. Only 6.3% of subjects consumed total vitamin B6 less than Estimated Average Requirements. Plasma PLP concentration of all subjects was 40.03 ± 23.71 nmol/L. The concentration of users of vitamin B6 supplements was significantly higher than that of nonusers (P < 0.001). Approximately 16% of Korean adults had PLP levels < 20 nmol/L, indicating a biochemical deficiency of vitamin B6, while 19.7% had marginal vitamin B6 status. Plasma PLP concentration showed positive correlation with total vitamin B6 intake (r = 0.40984, P < 0.0001).CONCLUSIONSIn this study, vitamin B6 intake of Korean adults was generally adequate. However, one-third of subjects had vitamin B6 deficiency or marginal status. Therefore, in some adults in Korea, consumption of vitamin B6-rich food sources should be encouraged.

Dietary vitamin B6 intake modulates colonic inflammation in the IL10−/− model of inflammatory bowel disease

Pyridoxal-5-phosphate, the biologically active form of vitamin B6, is a cofactor for over 140 biochemical reactions. Although severe vitamin B6 deficiency is rare, mild inadequacy [plasma pyridoxal 5’-phosphate (PLP) <20 nmol/L] is observed in 19–27% of the US population. Plasma PLP concentrations are inversely related to markers of inflammation such as C-reactive protein. Furthermore, plasma PLP is diminished in those with inflammatory conditions and, in the case of inflammatory bowel disease (IBD), more so in those with active versus quiescent disease. Restricting B6 intake attenuates IBD pathology in mice; however, the effects of supplementation are unclear. We therefore sought to determine the effects of mild inadequacy and moderate supplementation of B6 on the severity of colonic inflammation. Weanling IL-10−/− (positive for Helicobacter hepaticus) mice were fed diets containing 0.5 (deficient), 6.0 (replete) or 24 (supplemented) mg/kg pyridoxine HCl for 12 weeks and then assessed for histological and molecular markers of colonic inflammation. Both low and high plasma PLP were associated with a significant suppression of molecular (TNFα, IL-6, IFN-γ, COX-2 and iNOS expression) and histological markers of inflammation in the colon. PLP is required for the breakdown of sphingosine 1-phosphate (S1P), a chemotactic lipid, by S1P lyase. Colonic concentrations of S1P and PLP were significantly and inversely correlated. If confirmed, vitamin B6 supplementation may offer an additional tool for the management of IBD. Although B6 is required in dozens of reactions, its role in the breakdown of S1P may explain the biphasic relationship observed between PLP and inflammation.

Effects of vitamin B6 on one‐carbon metabolism in oral contraceptive users

Oral contraceptive (OC) usage is associated with low plasma pyridoxal phosphate (PLP) indicating low vitamin B6 status. PLP serves as a coenzyme in several steps in 1C metabolism, including the entry of 1C units from serine via the glycine‐cleavage system and serine hydroxymethyltransferase (SHMT), as well as the transsulfuration pathway in which cystathionine β‐synthase (CBS) catalyzes the condensation of homocysteine with serine to form cystathionine, and cystathionine γ‐lyase (CTGL) catalyzes the cleavage of cystathionine to form cysteine. Whether vitamin B6 deficiency in OC users functionally affects 1C metabolism is uncertain. Therefore, we examined PLP‐related 1C metabolism in healthy OC users (20–40y, with plasma PLP &lt; 30 nmol/L) before and after 4 wk of supplementation with pyridoxine (10 mg/d). We used an intravenous primed, constant infusion of stable isotopically‐labeled [13C5]methionine, [3‐13C]serine and [2H3]leucine to determine the effect of vitamin B6 supplementation on homocysteine remethylation from serine, methionine and serine fluxes, and fractional cystathionine synthesis. Preliminary data showed an expected increase in plasma PLP and changes in PLP‐dependent aspects of 1C metabolism due to supplementation. In conclusion, these findings imply a functional effect of vitamin B6 supplementation on 1C metabolism. Supported by NIH Grant DK072398 and NIH CTSA grant 1UL1RR029890.

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

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.

Higher Plasma Homocysteine Is Associated with Increased Risk of Developing Colorectal Polyps

Colorectal adenomas are considered to be precursors of colorectal cancer. B-vitamins (i.e., folate, vitamin B6 and B12) are involved in homocysteine metabolism and play an important role as coenzymes in 1-carbon metabolism, which is thought to have a critical role in the progression of colorectal polyps. The purpose of this study was to examine the effects of B-vitamins and homocysteine on the risk of developing colorectal polyps. Forty-eight participants with colorectal polyps [29 adenomatous polyps (AP), 19 hyperplastic polyps (HP)], and 96 age- and sex-matched healthy controls were recruited. Fasting blood was drawn from each participant to measure hematological parameters, plasma pyridoxal 5′-phosphate (PLP), serum folate and vitamin B12, and plasma homocysteine. Participants with AP and HP had significantly higher plasma homocysteine levels than did healthy controls. There was no significant difference in serum folate and vitamin B12 and plasma PLP among the 3 groups. B-vitamins had no significant effect on the risk of colorectal polyps. However, participants with higher plasma homocysteine [odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.13, 3.08) level exhibited significantly increased risk of colorectal polyps after adjusting for potential confounders. Plasma homocysteine was a strong predictor of the risk of colorectal polyps in participants with adequate B-vitamins status.

Prediagnostic plasma vitamin B6 (pyridoxal 5'-phosphate) and survival in patients with colorectal cancer.

Higher plasma pyridoxal 5'-phosphate (PLP) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma PLP on survival of patients with colorectal cancer is unknown. We prospectively examined whether prediagnostic plasma PLP levels are associated with mortality among colorectal cancer patients. We included 472 incident cases of colorectal cancer identified in the Nurses' Health Study, the Health Professionals Follow-up Study, and the Physicians' Health Study from 1984 to 2002. The patients provided blood samples two or more years before cancer diagnosis. Stratified Cox proportional hazards models were used to calculate hazard ratios (HR) with 95 % confidence intervals (CI) adjusted for other risk factors for cancer survival. Higher plasma PLP levels were not associated with a significant reduction in colorectal cancer-specific (169 deaths) or overall mortality (259 deaths). Compared with patients who had less than 45 pmol/ml of plasma PLP (median: 33.6 pmol/ml), those who had 110 pmol/ml or higher levels (median: 158.8 pmol/ml) had multivariable HRs of 0.85 (95 % CI 0.50-1.45, p trend = 0.37) and 0.87 (95 % CI 0.56-1.35, p trend = 0.24) for colorectal cancer-specific and overall mortality. Higher plasma PLP levels, however, seemed to be associated with better survival among patients who had lower circulating 25-hydroxyvitamin D3 levels (<26.5 ng/ml) (p interaction ≤.005). Higher prediagnostic plasma PLP levels were not associated with an improvement on colorectal cancer survival overall. Further research is needed to clarify the influence of vitamin B6 on colorectal cancer progression and survival.

Adequate vitamin B‐6 is associated with increased antioxidant enzyme activity in critically ill surgical patients

Inadequate vitamin B‐6 status may increase oxidative stress and compromise antioxidant capacity. The purpose of this study was to understand the association between vitamin B‐6 status and oxidative stress, antioxidant enzyme capacities in critically ill surgical patients. Patients were allocated into either adequate B‐6 (n = 11) or deficient B‐6 (n = 10) group based on their fasting plasma pyridoxal 5′‐phosphate (PLP) concentration at admission to the surgical intensive care unit (SICU). Plasma and erythrocyte PLP, serum malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione S‐transferase (GST) and glutathione peroxidase (GPx) were determined on the 1st, 4th, 7th and 10th d of admission. There was no significant difference in TAC and MDA levels, GST and GPx activities between the 2 groups on the 1st, 4th, 7th and 10th in the SICU. The mean SOD activity level was significantly higher in the adequate B‐6 group when compared to the deficient B‐6 group on the 1st and 4th after admission. The change of plasma PLP (rs = 0.68, p &lt; 0.01) significantly correlated with the change of SOD activities after adjusting for potential factors. Higher plasma PLP at admission would be an important contributing factor to increased antioxidant enzyme activity in SICU patients. This study was supported by Taichung Veterans General Hospital (TCVGH‐994101B), Taiwan.

Vitamin B6 status of 20–59 y old adults in South Korea

To determine dietary vitamin B6 intakes and plasma pyridoxal 5‐ phosphate (PLP) concentrations and to evaluate vitamin B6 status of Korean adults, three consecutive 24‐h food recalls and fasting blood samples were collected from healthy 20–59 y old adults (n=105) living in Seoul and Gyeonggi areas, South Korea. The mean intake of vitamin B6 was 2.06 mg/day. The average ratio of vitamin B6 intake to daily protein intake was 0.027 mg/g protein. Only 4.8% of subjects consumed less than Korean Estimated Average Requirements and 6.2% consumed less than Recommended Nutrient intakes for vitamin B6. None of the subjects consumed vitamin B6 over Tolerable Upper Intake Level for Koreans. The mean plasma PLP level (mean/SD) was 24.6/14.2 nmol/L. There was no significant correlation in vitamin B6 intakes and plasma PLP concentrations (P&gt;=0.05). Approximately 49% of subjects had plasma PLP concentrations &lt;20 nmol/L, which is indicative of vitamin B6 inadequacy status. In conclusion, although vitamin B6 intakes of the subjects were generally adequate, a half of these Korean adults had inadequate vitamin B6 status. Supported by 2011 research fund of National Research Foundation of Korea (2011‐0003749).

Plasma Pyridoxal 5′-Phosphate Is Not Associated with Inflammatory and Immune Responses after Adjusting for Serum Albumin in Patients with Rheumatoid Arthritis: A Preliminary Study

Background/Aims: Plasma pyridoxal 5′-phosphate (PLP) has been shown to be associated with inflammatory and immune responses.Rheumatoid arthritis (RA) is an autoimmune and chronic systemic inflammatory disease and patients with RA have lower plasma PLP levels. We studied the relationship between plasma PLP and inflammatory or immune responses in patients with RA. Methods: This study was designed as an observational cross-sectional study. Forty-three patients with RA were allocated to the adequate (PLP ≥20 nmol/l) (n = 30) or deficient vitamin B₆ (PLP <20 nmol/l) (n = 13) group according to their fasting plasma PLP concentration on the day blood was taken. Plasma PLP, inflammatory parameters [i.e. high-sensitivity CRP (hs-CRP), erythrocyte sedimentation rate, interleukin-6, tumor necrosis factor-α] and immune parameters (i.e. white blood cells, total lymphocytes, neutrophils, T lymphocytes, B lymphocytes, T helper cells and T suppressor cells) were measured. Results: Patients with deficient plasma PLP concentration were mostly considered to have a systemic inflammatory status (hs-CRP >3 mg/l) and apparently had significantly higher mean hs-CRP levels and immune parameters than patients with adequate plasma PLP concentration. There was no significant association between plasma PLP levels and inflammatory parameters. The significantly inverse correlation of plasma PLP with the numbers of white blood cells, neutrophils, total lymphocytes, T lymphocytes and T helper cells remained after adjusting for serum hemoglobin concentration, but the significant correlation disappeared after serum albumin concentration was also considered. Conclusions: RA patients with deficient plasma PLP concentration had more severe inflammatory and immune responses than patients with adequate plasma PLP concentration. However, there was a lack of association of low plasma PLP concentration with inflammatory and immune parameters after serum albumin concentration was considered in patients with RA.