Plasma Pyridoxal Phosphate Research Articles

Substrate product ratios of enzymes in the kynurenine pathway measured in plasma as indicators of functional vitamin B-6 status

Tryptophan metabolism through the kynurenine pathway includes 2 vitamin B-6 [pyridoxal 5'-phosphate (PLP)]-dependent enzymes. We recently showed that plasma 3-hydroxykynurenine (HK) was elevated at low PLP concentrations. We further evaluated and characterized kynurenine-based indexes as possible markers of functional B-vitamin status in plasma. Cross-sectional and longitudinal data were derived from the Western Norway B-vitamin Intervention Trial, including PLP, kynurenine, HK, kynurenic acid (KA), anthranilic acid, xanthurenic acid (XA), and 3-hydroxyanthranilic acid (HAA) measured in plasma at 2 time points. Partial Spearman's correlation, generalized additive models, and receiver operating characteristic (ROC) analysis were used to assess associations of kynurenines with PLP. Ratios HK:XA, HK:HAA, and HK:KA showed markedly stronger negative correlations with PLP than did HK alone (Spearman's ρ = -0.36, -0.29, and -0.31 compared with -0.18, respectively). All associations were nonlinear, with the strongest relation at low PLP. In the ROC analysis, areas under the curve for discriminating low PLP (less than the fifth percentile; 18.6 nmol/L) were 0.78, 0.78, and 0.74, respectively, compared with 0.65 for HK. Oral treatment with 40 mg pyridoxin hydrochloride for 28 d reduced the ratios by up to 60%, with strongest reductions for subjects with low plasma PLP at baseline. Whereas HK was associated with kidney function and several inflammatory markers, such associations were abolished or attenuated for the ratios. Plasma values of HK:XA and HK:HAA, which are substrate-product pairs for kynurenine transaminase and kynureninase, respectively, may reflect the intracellular availability of the cofactor (PLP) and, therefore, present as potential markers of functional vitamin B-6 status.

Metabolomic Analysis Reveals Extended Metabolic Consequences of Marginal Vitamin B-6 Deficiency in Healthy Human Subjects

Marginal deficiency of vitamin B-6 is common among segments of the population worldwide. Because pyridoxal 5′-phosphate (PLP) serves as a coenzyme in the metabolism of amino acids, carbohydrates, organic acids, and neurotransmitters, as well as in aspects of one-carbon metabolism, vitamin B-6 deficiency could have many effects. Healthy men and women (age: 20-40 y; n = 23) were fed a 2-day controlled, nutritionally adequate diet followed by a 28-day low-vitamin B-6 diet (<0.5 mg/d) to induce marginal deficiency, as reflected by a decline of plasma PLP from 52.6±14.1 (mean ± SD) to 21.5±4.6 nmol/L (P<0.0001) and increased cystathionine from 131±65 to 199±56 nmol/L (P<0.001). Fasting plasma samples obtained before and after vitamin B6 restriction were analyzed by 1H-NMR with and without filtration and by targeted quantitative analysis by mass spectrometry (MS). Multilevel partial least squares-discriminant analysis and S-plots of NMR spectra showed that NMR is effective in classifying samples according to vitamin B-6 status and identified discriminating features. NMR spectral features of selected metabolites indicated that vitamin B-6 restriction significantly increased the ratios of glutamine/glutamate and 2-oxoglutarate/glutamate (P<0.001) and tended to increase concentrations of acetate, pyruvate, and trimethylamine-N-oxide (adjusted P<0.05). Tandem MS showed significantly greater plasma proline after vitamin B-6 restriction (adjusted P<0.05), but there were no effects on the profile of 14 other amino acids and 45 acylcarnitines. These findings demonstrate that marginal vitamin B-6 deficiency has widespread metabolic perturbations and illustrate the utility of metabolomics in evaluating complex effects of altered vitamin B-6 intake.

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.

In vivo Effect of 1‐Amino D‐Proline, an Anti‐pyridoxine Factor, on the Metabolism of Vitamin B6‐dependent Enzymes in Moderately Vitamin B6 Deficient Rats

Pyridoxal 5′‐phosphate (PLP) serves as an important cofactor in numerous metabolic pathways, including the transsulfuration pathway which converts homocysteine (Hcy) to cysteine (Cys). While overt deficiency is rare, marginal deficiency is common, and may be exacerbated by anti‐pyridoxine factors in the food supply. To this end, 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 sulphur amino acid metabolism in moderately B6‐deficient rats. Male weaning rats (n=6/treatment) received a semi‐purified diet (AIN‐93G) containing either 7 (control; C) or 0.7 mg/Kg diet PN·HCl (moderately deficient; MD), each with one of 4 levels of 1ADP, viz. 0, 0.1,1 and 10 mg/Kg, diet for 5 weeks. For rats receiving the C diet, final body weight was not affected by 1ADP, however rats consuming the highest 1ADP levels in the MD group were significantly lighter (p&lt;0.001). Plasma biomarkers are given in Table 1. The data provide evidence that the consumption of an anti‐pyridoxine factor linked to flaxseed does not pose challenges for subjects who are vitamin B6‐replete. However, this may not be the case for subjects with marginal B6 status, as supported by dose‐dependent reductions in plasma PLP and increases in plasma Hcy.Grant Funding Source: Natural Sciences and Engineering Research Council of Canada (NSERC).

Anthranilic acid and 3‐hydroxyanthranilic acid, but not kynurenic acid, are associated with plasma pyridoxal‐5 phosphate levels

Both high inflammation and low pyridoxal 5′‐phosphate (PLP) status are associated with chronic diseases such as cardiovascular disease and diabetes. A hallmark of inflammation is the induction of indoleamine‐2,3‐dioxygenase (IDO) by the inflammatory cytokine interferon‐γ, leading to the degradation of tryptophan through the kynurenine pathway. Since PLP is a cofactor for many of the enzymes in the kynurenine pathway, we hypothesize that plasma PLP levels could modulate the formation of some of the kynurenines that require PLP as a cofactor for synthesis. To test this, a secondary data analysis was performed on metabolomics data from 1,868 subjects from Framingham Offspring cohort, Exam 5. Using generalized linear models, anthranilic acid (AA) and 3‐hydroxyanthranilic acid (OH‐AA) were found to be positively associated with PLP after adjusting for age, sex, BMI, creatinine, smoking status, and NSAID use (p=0.04 and 0.02, respectively). A 10 nmol/L increase in PLP status was associated with 0.5% and 1.1% increases in AA and OH‐AA, respectively. Kynurenic acid (KA) was not found to be associated with PLP (p = 0.41). Results suggest that AA and OHAA are weakly associated with plasma PLP. Supported by USDA cooperative agreement 51520–008‐045 and NHLBI Framingham Heart Study (Contract No.N01‐HC‐25195).Grant Funding Source: USDA cooperative agreement 51520–008‐045 and NHLBI Framingham Heart Study (Contract No.N01‐HC‐25195).

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.

Changes in Plasma Pyridoxal 5'-Phosphate Concentration during Pregnancy Stages in Japanese Women

Most Japanese women do not consume the estimated average requirement of vitamin B6 (1.7 mg/d) during pregnancy. Nevertheless, these deficiencies are not reported. We investigated a nutritional biomarker of vitamin B6 in pregnant Japanese women as well as their vitamin B6 intakes. Vitamin B6 intakes in the first, second, and third trimesters of pregnancy, and 1 mo after delivery were 0.79±0.61 (n=56), 0.81±0.29 (n=71), 0.90±0.35 (n=92), and 1.00±0.31 (n=44) mg/d, respectively. Plasma pyridoxal 5'-phosphate (PLP) concentrations in the first, second, and third trimesters of pregnancy, and 1 mo after delivery were 57.1±27.6 (n=56), 23.3±16.7 (n=71), 18.3±12.5 (n=92), and 43.9±33.4 (n=44) nmol/L, respectively. The plasma concentrations significantly decreased in the second and third trimesters of pregnancy compared to values from the first trimester (p<0.05), and these concentrations returned to the values of the first trimester of pregnancy 1 mo after birth.

Higher Plasma Pyridoxal Phosphate Is Associated with Increased Antioxidant Enzyme Activities in Critically Ill Surgical Patients

Critically ill patients experience severe stress, inflammation and clinical conditions which may increase the utilization and metabolic turnover of vitamin B-6 and may further increase their oxidative stress and compromise their antioxidant capacity. This study was conducted to examine the relationship between vitamin B-6 status (plasma and erythrocyte PLP) oxidative stress, and antioxidant capacities in critically ill surgical patients. Thirty-seven patients in surgical intensive care unit of Taichung Veterans General Hospital, Taiwan, were enrolled. The levels of plasma and erythrocyte PLP, serum malondialdehyde, total antioxidant capacity, and antioxidant enzyme activities (i.e., superoxide dismutase (SOD), glutathione S-transferase, and glutathione peroxidase) were determined on the 1st and 7th days of admission. Plasma PLP was positively associated with the mean SOD activity level on day 1 (r = 0.42, P < 0.05), day 7 (r = 0.37, P < 0.05), and on changes (Δ (day 7 − day 1)) (r = 0.56, P < 0.01) after adjusting for age, gender, and plasma C-reactive protein concentration. Higher plasma PLP could be an important contributing factor in the elevation of antioxidant enzyme activity in critically ill surgical patients.

Prediagnostic Plasma Pyridoxal 5′-Phosphate (Vitamin B6) Levels and Invasive Breast Carcinoma Risk: The Multiethnic Cohort

Evidence from experimental and epidemiologic studies suggests that vitamin B6 may reduce the risk of breast cancer. We examined the association of prediagnostic plasma concentrations of pyridoxal-5'-phosphate (PLP), an active form of vitamin B6, with postmenopausal breast cancer risk in a case-control study nested in the multiethnic cohort in Hawaii and Southern California, including 706 cases and 706 controls matched on date of birth, ethnicity, study site, date of blood draw, time of blood draw, hours of fasting before blood draw, and use of menopausal hormones. OR and 95% confidence intervals (CI) were calculated using conditional logistic regression models. Women with plasma PLP concentrations in the highest quartile had a 30% reduced risk of invasive breast cancer (CI: 0.50-0.98) as compared with the women in the lowest PLP quartile (P for trend = 0.02). The association seemed to be limited in cases with hormone receptor-positive tumors (P for heterogeneity = 0.04); and remained unchanged in the analysis restricted to women with blood samples collected more than one year before cancer diagnosis (OR = 0.69; CI: 0.48-0.99; P for trend = 0.03). These data suggest that higher circulating levels of vitamin B6 are associated with a reduced risk of invasive postmenopausal breast cancer. These results, in combination with information from two other prospective studies, suggest a role for vitamin B6 in the prevention of postmenopausal breast cancer. Additional studies are needed to further investigate potential heterogeneity of the vitamin B6 association with breast cancer risk by tumor hormone receptor status.

Folic acid and vitamin B6 deficiencies related hyperhomocysteinemia in apparently healthy Pakistani adults; is mass micronutrient supplementation indicated in this population?

To determine the plasma/serum levels of homocysteine, and vitamins folate, B6 and B12, in Pakistani healthy adults. Cross-sectional study. The Aga Khan University, from October 2006 to April 2008. Fasting levels of plasma/serum folic acid, pyridoxal phosphate (PLP), vitamin B12 and homocysteine were determined in 290 apparently healthy hospital personnel from institutions in two cities of Pakistan. Spearman correlation test and linear regression analysis was conducted. There were 219 males and 71 females with mean age of 46+/-10.5 years and mean body mass index of 23.5 +/-3.8. Mean plasma homocysteine levels in Pakistani normal adults were found to be 17.95+/-8.4 micromol/l. Mean concentrations of plasma/serum folate, vitamin B12 and PLP were found to be 5+/-3.9 ng/ml, 522+/-296 pg/ml and 21.6+/-14 nmol/l, respectively. Serum/plasma levels of folate, vitamin B12 and PLP were negatively correlated with plasma homocysteine (rho coefficient=-0.367, p<0.001; -0.173, p=0.004; -0.185, p=0.002, respectively). Serum folate and plasma PLP levels were inversely related with plasma homocysteine, adjusted for gender, age, smoking and body mass index (p<0.001 and p=0.003, respectively). Percent deficiency values of folate, vitamin B6 and vitamin B12 were 39.7%, 52.8% and 6.6% respectively. The high levels of plasma homocysteine could indicate a reason for mass micronutrient supplementation to prevent the high incidence of cardiovascular disease observed in Pakistani population.

Higher Plasma Homocysteine Is Associated With Lower Vitamin B6 Status in Critically Ill Surgical Patients

Hyperhomocysteinemia might be at least partially due to compromised B vitamin status in critically ill patients and has been linked with critical illness. This study was conducted to examine the association between plasma homocysteine with B vitamins and clinical outcomes in critically ill surgical patients. Thirty-two patients in the surgical intensive care unit (SICU) were enrolled. Disease severity (Acute Physiology and Chronic Health Evaluation II score), hematological values, serum and erythrocyte folate, serum vitamin B₁₂, plasma, and erythrocyte pyridoxal 5'-phosphate (PLP) were determined within 24 hours of admission and again after 7 days. The prevalence of hyperhomocysteinemia in the patients was either 46.9% (plasma homocysteine ≥12 µmol/L) or 31.3% (plasma homocysteine ≥15 µmol/L) on day 1 in the SICU and increased to 62.5% (plasma homocysteine ≥12 µmol/L) and 37.5% (plasma homocysteine ≥15 µmol/L) on day 7 after admission to the SICU. Plasma homocysteine, serum folate, and vitamin B₁₂ significantly increased by day 7, whereas plasma and erythrocyte PLP remained constant throughout the study. Plasma homocysteine was not correlated with serum folate and vitamin B₁₂. However, plasma and erythrocyte PLP on day 1 were adversely associated with day 1 levels of plasma homocysteine after adjusting for potential confounders. Plasma homocysteine on day 1 or changes (Δ day 7-day 1) did not show any association with clinical outcomes. Lower plasma PLP might be a significant factor for increased plasma homocysteine in critically ill surgical patients. The association between plasma homocysteine and clinical outcomes was not found.

Plasma Pyridoxal-5-Phosphate Is Inversely Associated with Systemic Markers of Inflammation in a Population of U.S. Adults1–3

Low vitamin B-6 status, based on plasma concentrations of pyridoxal-5-phosphate (PLP), has been identified in inflammatory diseases, including cardiovascular disease, rheumatoid arthritis, inflammatory bowel disease, and diabetes. Our objective was to examine the association between plasma PLP and multiple markers of inflammation in a community-based cohort [n = 2229 participants (55% women, mean age 61 #x00B1; 9 y)]. We created an overall inflammation score (IS) as the sum of standardized values of 13 individual inflammatory markers. Multivariable-adjusted regression analysis was used to assess the associations between the IS and plasma PLP. Geometric mean plasma PLP concentrations were lower in the highest tertile category of IS relative to the lowest (61 vs. 80 nmol/L; P-trend < 0.0001). Similarly, the prevalence of PLP insufficiency was significantly higher for participants in the highest compared with the lowest tertiles for IS categories. These relationships persisted after accounting for vitamin B-6 intake. Also, there were significant inverse relationships between plasma PLP and 4 IS based on functionally related markers, including acute phase reactants, cytokines, adhesion molecules, and oxidative stress. In addition, secondary analyses revealed that many of the individual inflammatory markers were inversely associated with plasma PLP after adjusting for plasma C-reactive protein concentration. This study, in combination with past findings, further supports our hypothesis that inflammation is associated with a functional deficiency of vitamin B-6. We discuss 2 possible roles for PLP in the inflammatory process, including tryptophan metabolism and serine hydroxymethyltransferase activity.

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).

Vitamin B-6 Vitamer Levels in Plasma and Related Symptoms in Hemodialysis Subjects Taking low- and High-Dose Renal Multivitamin Supplements

The purpose of this study was to evaluate the B-6 vitamers in plasma and related symptoms in hemodialysis subjects taking high- or low-dose vitamins. A total of 24 hemodialysis (HD) subjects were divided into two groups. Twelve subjects received a high-dose vitamin supplement [50 mg pyridoxine hydrochloride (PN-HCl) /tablet] and 12 received a low-dose vitamin supplements containing (10 mg PN-HCl/tablet) for 6+ months. Plasma B-6 vitamers were analyzed using HPLC. Other data were obtained from subjects' medical records. Subjects were assessed for vitamin B-6 related symptoms. Cluster analysis was used to form symptom groups. Student t-tests and analysis of variance were used to determine differences (p < 0.05) in group means. The mean ± SD plasma B-6 vitamer and 4-pyridoxic acid concentrations (nmol/L) were as follows in the 10-mg and 50-mg PN-HCl groups, respectively: pyridoxal- 5'-phosphate (PLP) 10 ± 3 and 16 ± 8 (p = 0.04); pyridoxal (PL) 50 ± 96 and 68 ± 06; pyridoxine (PN) 26 ± 50 and 191 ± 107; and 4-pyridoxic acid (4-PA) 43 ± 64 and 99 ± 361. The cluster group with a significantly higher (p = 0.04) plasma 4-PA concentration of 167 ± 697 nmol/L reported more tingling hands, tachycardia, and diarrhea. Plasma PLP levels and symptoms related to B-6 in HD subjects are impacted by dose of PN-HCl.

The Relationships Between Plasma and Red Cell Vitamin B2 and B6 Concentrations and the Systemic and Local Inflammatory Responses in Patients With Colorectal Cancer

B vitamins have been implicated in cancer pathogenesis. It is therefore of interest that plasma B6 falls as part of the systemic inflammatory response (SIR), whereas red cell concentrations do not. The modified Glasgow Prognostic Score (mGPS) is a validated inflammation-based prognostic score that consists of a combination of albumin and C-reactive protein concentrations. The aim of this study was to examine the relationships between the concentrations of plasma and red cell vitamin B concentrations, the local and systemic inflammatory response in patients with colorectal cancer. Preoperative venous blood of 108 patients with colorectal cancer were analyzed for C-reactive protein, albumin, flavin adenine dinucleotide (FAD), and pyridoxal phosphate (PLP), and lymphocyte counts. Pathological slides were retrieved for assessment of inflammatory cell infiltration. Increasing mGPS was associated with lower plasma PLP concentrations (P < 0.01) but not plasma and red cell FAD and red cell PLP concentrations. Increasing tumor stage was associated with the presence of venous invasion (P < 0.01) and low-grade inflammatory cell infiltrate (P < 0.05) but not the SIR, FAD, or PLP concentrations. A low-grade inflammatory cell infiltrate was not significantly associated with any other parameter. The presence of a SIR was associated with lower concentrations of plasma PLP but not red cell PLP concentrations in patients with colorectal cancer. Neither FAD and PLP were associated with the tumor inflammatory cell infiltrate.

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.

Type 1 diabetes impairs vitamin B6 metabolism at an early stage of women’s adulthood

Vitamin B(6) (pyridoxine) metabolism in diabetes has never been investigated except for a few reports on plasma pyridoxal 5'-phosphate (PLP). These studies indicated that this most active (coenzyme) vitamer can be reduced. The present clinical investigation aimed to measure all vitamers in blood and urine by high performance liquid chromatography as well as important related factors, in women during active reproductive years. Thirty-two insulin-treated type 1 diabetic (T1D) patients, without renal complication, and 27 well-matched healthy controls, aged 30 to 40 years old, were recruited using rigorous criteria. Both groups had normal hemoglobin and serum albumin levels. Plasma PLP and pyridoxal (PL) did not differ significantly in the T1D group but alkaline phosphatase (ALP) activity was greater (p < 0.01). This produced a shift in plasma PLP-PL profile, as evidenced by a lower plasma PLP/PL ratio (p < 0.05). Enhanced ALP activity meant more PLP being dephosphorylated to PL (the membrane transfer form), with more ending up in erythrocytes to be rephosphorylated in its active form, as suggested by the significant positive correlation (p < 0.001) between plasma PL and erythrocyte PLP. More PL into blood circulation also means more oxidation of this vitamer to 4'-pyridoxic acid in kidneys, as confirmed by the positive correlation between plasma PL and urinary 4'-pyridoxic acid (p < 0.001). The positive correlation (p < 0.001) between ALP activity and glycosylated hemoglobin indicated a direct effect of the disease. The T1D-induced alteration in vitamin B(6) metabolism, consecutive to enhanced ALP activity, may put patients at greater risk of vitamin B(6) deficiency and diabetic complications.