Plasma Pyridoxal Phosphate Research Articles

Prediction of all-cause mortality by B group vitamin status in the elderly

Little is known about the direct relationship of B vitamins to mortality in the elderly. All-cause mortality by vitamin B status, using dietary (B-1, B-2, niacin, B-6) or biochemical data (erythrocyte transketolase reductase, erythrocyte glutathione reductase, plasma pyridoxal-phosphate, folate and serum B-12) was evaluated. The Taiwanese Elderly Nutrition and Health Survey (1999-2000) provided 1747 participants 65 years and over. Dietary and biochemical data were collected at baseline. Survivorship was determined until December 31, 2008. Survivors had higher vitamin B-1 and niacin intakes and pyridoxal-phosphate and folate concentrations. Controlled for confounders, and relative to the lowest tertile of vitamin B-1 or B-6 intakes, the hazard ratios (95% confidence interval) for tertile 3 were 0.74 (0.58-0.95) and 0.74 (0.57-0.97); both p for trend values were <0.05. Further adjustment for dietary diversity led to insignificant findings. For pyridoxal-phosphate, compared to those with deficiency levels, the multivariable-adjusted hazard ratios (95% confidence interval) for adequacy was 0.52 (0.38-0.71) with p for trend <0.0001 and unchanged with dietary diversity adjustment. Higher vitamin B-1 and B-6 intakes and plasma pyridoxal-phosphate were associated with lower risk of mortality up to 10 years and could be achieved by increased dietary diversity.

Moderate Vitamin B-6 Restriction Does Not Alter Postprandial Methionine Cycle Rates of Remethylation, Transmethylation, and Total Transsulfuration but Increases the Fractional Synthesis Rate of Cystathionine in Healthy Young Men and Women1–3

AbstractMethionine is the precursor for S-adenosylmethionine (SAM), the major 1-carbon donor involved in >100 transmethylation reactions. Homocysteine produced from SAM must be metabolized either by remethylation for recycling of methionine or transsulfuration to form cystathionine and then cysteine. Pyridoxal 5′-phosphate (PLP) serves as a coenzyme in enzymes involved in transsulfuration as well as for primary acquisition of 1-carbon units used for remethylation and other phases of 1-carbon metabolism. Because the intake of vitamin B-6 is frequently low in humans and metabolic consequences of inadequacy may be amplified in the postprandial state, we aimed to determine the effects of marginal vitamin B-6 deficiency on the postprandial rates of remethylation, transmethylation, overall transsulfuration, and cystathionine synthesis. Healthy, young adults (4 male, 5 female; 2035 y) received a primed, constant infusion of [1-13C]methionine, [methyl-2H3]methionine, and [5,5,5-2H3]leucine to quantify in vivo kinetics at normal vitamin B-6 status and after a 28-d dietary vitamin B-6 restriction. Vitamin B-6 restriction lowered the plasma PLP concentration from 49 ± 4 nmol/L (mean ± SEM) to 19 ± 2 nmol/L (P < 0.0001). Mean remethylation, transsulfuration, and transmethylation rates did not change in response to vitamin B-6 restriction; however, the responses to vitamin B-6 restriction varied greatly among individuals. The plasma cystathionine concentration increased from 142 ± 8 to 236 ± 9 nmol/L (P < 0.001), whereas the fractional cystathionine synthesis rate increased by a mean of 12% in 8 of 9 participants. Interrelationships among plasma concentrations of glycine and cystathionine and kinetic results suggest that individual variability occurs in normal postprandial 1-carbon metabolism and in the response to vitamin B-6 restriction.

Low Plasma Vitamin B-6 Status Affects Metabolism through the Kynurenine Pathway in Cardiovascular Patients with Systemic Inflammation1–4

It is unclear whether reduced plasma pyridoxal 5'-phosphate (PLP) during inflammation reflects an altered distribution or increased requirement of vitamin B-6 that may impair overall vitamin B-6 status in tissues. In plasma from 3035 patients undergoing coronary angiography for suspected coronary heart disease, we investigated if plasma concentrations of any metabolites in the kynurenine pathway, which depend on PLP as cofactor, may serve as metabolic marker(s) of vitamin B-6 status. We also examined the association of vitamin B-6 status with serum or plasma concentrations of several inflammatory markers. Among the kynurenines, only 3-hydroxykynurenine (HK) was inversely related to PLP and showed a positive relation to 4 investigated inflammatory markers. A segmented relationship was observed between PLP and HK, with a steep slope at PLP concentrations < 18.4 nmol/L, corresponding to the 5th percentile, and an almost zero slope at higher PLP concentrations. Low PLP and the steep PLP-HK slope were essentially confined to participants with 1 or more inflammatory markers in the upper tertile. Oral supplementation with pyridoxine hydrochloride (40 mg/d) for 1 mo increased plasma PLP 8-fold, reduced the geometric mean (95% CI) of HK from 29.5 to 20.2 nmol/L (P< 0.001), and abolished the steep segment of the PLP-HK curve. The steep inverse relationship of plasma PLP with HK at low plasma PLP and the lowering of HK by pyridoxine suggest plasma HK as a metabolic marker of vitamin B-6 status. Thus, low plasma PLP during inflammation may reflect impaired cellular vitamin B-6 status, as indicated by the concurrent increase in plasma HK.

Higher plasma pyridoxal 5′-phosphate is associated with better blood glucose responses in critically ill surgical patients with inadequate vitamin B-6 status

Stress, inflammation, and clinical conditions may increase the utilization and metabolic turnover of vitamin B-6 and lower the body pool of vitamin B-6. There is the possibility that hyperglycemia in critically ill patients might be at least partially due to compromised vitamin B-6 status. The purpose of this study was to compare blood glucose responses between critically ill surgical patients with adequate and deficient vitamin B-6 status. The study was designed as a cross-sectional observational study. Thirty-four patients in the surgical intensive care unit (SICU) were enrolled. The severity of illness (APACHE II score), the length of ventilation dependency, and the lengths of SICU and hospital stay were recorded. The levels of serum hemoglobin, hematocrit, albumin, prealbumin, C-reactive protein, glucose, insulin, glycated hemoglobin, C-peptide and creatinine were determined. Vitamin B-6 intake was recorded for 7 days. Vitamin B-6 status was assessed by direct measures [plasma and erythrocyte pyridoxal 5'-phosphate (PLP), pyridoxal (PL) and 4-pyridoxic acid (4-PA), and urinary 4-PA] and indirect measures [erythrocyte alanine and aspartate aminotransaminase activity coefficient]. Fourteen patients were classified into the deficient vitamin B-6 group (plasma PLP<20nmol/L), while there were 20 patients in the adequate vitamin B-6 group. The mean serum glucose concentration of both groups indicated patients was in the hyperglycemic state (serum glucose>126mg/dL). However, mean serum glucose concentration significantly decreased by day 7 in the adequate vitamin B-6 group, whereas patients still remained in the hyperglycemic state (serum glucose>126mg/dL) in the deficient vitamin B-6 group. There were significantly correlations of relatively higher plasma PLP at admission (day 1) with the reduction of blood glucose concentration (r(s)=0.72, p=0.029) on day 7 in the deficient vitamin B-6 group. However, erythrocyte PLP concentration was positively associated with blood glucose level (r(s)=0.88, p=0.002) at admission in the deficient vitamin B-6 group after adjusting for age, gender, APACHE II score, diabetic history and insulin therapy. Surgically ill patients with adequate plasma PLP concentration at admission showed improved blood glucose response at day 7. Higher plasma PLP at admission was a major contributing factor in the reduction of glucose concentration in critically ill surgical patients with deficient vitamin B-6 status.

Assessment of vitamin B6status in Korean patients with newly diagnosed type 2 diabetes

The purpose of this study was to assess vitamin B6 intake and status in Korean patients with newly diagnosed type 2 diabetes. Sixty-four patients with newly diagnosed type 2 diabetes and 8-11% glycated hemoglobin (A1C), along with 28 age-matched non-diabetic subjects, participated. Dietary vitamin B6 intake was estimated by the 24 hour recall method and plasma pyridoxal 5'-phosphate (PLP) was measured. There was a significant difference in daily total calorie intake between the diabetic and non-diabetic groups (1,917 ± 376 vs 2,093 ± 311 kcal). There were no differences in intake of total vitamin B6 (2.51 ± 0.91 vs 2.53 ± 0.81 mg/d) or vitamin B6/1,000 kcal (1.31 ± 0.42 vs 1.20 ± 0.32 mg) between the diabetic and non-diabetic groups, andI intakes of total vitamin B6 were above the Korean RDA in both groups (180.0 ± 57.9 vs 179.0 ± 65.4). There was a higher percentage of diabetic subjects whose plasma PLP concentration was < 30 nmol/L compared to non-diabetic group. Plasma PLP levels tended to be lower in the diabetic subjects than in the non-diabetic subjects, although the difference was not statistically significant due to a large standard deviation (80.0 ± 61.2 nmol/L vs 68.2 ± 38.5 nmol/L). Nevertheless, plasma PLP levels should be monitored in pre-diabetic patients with diabetic risk factors as well as in newly diagnosed diabetic patients for long-term management of diabetes, even though this factor is not a major risk factor that contributes to the development of degenerative complications in certain patients.

Dietary Intake of Vitamin B-6, Plasma Pyridoxal 5′-Phosphate, and Homocysteine in Puerto Rican Adults

Background Vitamin B-6 is an important cofactor in many metabolic processes. However, vitamin B-6 intake and plasma status have not been well studied in the Puerto Rican population, a group with documented health disparities. Objective To assess dietary intake of vitamin B-6, food sources, and plasma status of pyridoxal 5′-phosphate (PLP), and their associations with plasma homocysteine in 1,236 Puerto Rican adults, aged 45 to 75 years, living in the greater Boston area. Design Baseline data were analyzed cross-sectionally. Method Questionnaire data were collected by home interview. Dietary intake was assessed with a semiquantitative food frequency questionnaire. Plasma PLP and homocysteine were assayed from blood samples collected in the home. Results The mean daily intake of vitamin B-6 was 2.90±1.28 mg for men and 2.61±1.29 mg for women ( P<0.001). Approximately 11% were deficient (PLP <4.94 ng/mL [PLP <20 nmol/L]) and another 17% insufficient (PLP ≥4.94 but <7.41 ng/mL [PLP ≥20 but <30 nmol/L]). Household income below the poverty threshold, physical inactivity, and current smoking were significantly associated with lower plasma PLP ( P<0.05). Food groups contributing most to vitamin B-6 intake included ready-to-eat cereals, poultry, rice, potatoes, and dried beans. However, only intake of ready-to-eat cereals and use of supplements with vitamin B-6 were significantly associated with plasma PLP sufficiency (≥7.41 vs <7.41 ng/mL [PLP ≥30 vs <30 nmol/L], P<0.01). Both vitamin B-6 intake and PLP were significantly associated with plasma total homocysteine ( P<0.001). The association between PLP and homocysteine remained statistically significant after further adjustment for plasma vitamin B-12 and folate ( P=0.028). Conclusions Given the known importance of vitamin B-6 to health, the high prevalence of low vitamin B-6 status in this Puerto Rican population is of concern. Further work is needed to clarify the potential role that insufficient vitamin B-6 may have in relation to the observed health disparities in this population.

Vitamin B6 supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis

The purpose of this study was to investigate whether vitamin B(6) supplementation had a beneficial effect on inflammatory and immune responses in patients with rheumatoid arthritis (RA). This was a single-blind co-intervention study performed at the Division of Allergy, Immunology and Rheumatology of Chung Shan Medical University Hospital, Taiwan. Patients were diagnosed with RA according to the 1991 American College of Rheumatology criteria for RA. Patients were randomly allocated into two groups: control (5 mg/day folic acid only; n=15) or vitamin B(6) (5 mg/day folic acid plus 100 mg/day vitamin B(6); n=20) for 12 weeks. Plasma pyridoxal 5'-phosphate (PLP), serum folate, inflammatory parameters (that is, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha)) and immune parameters (that is, white blood cell, total lymphocyte, T-cell (CD3), B-cell (CD19), T-helper cell (CD4), T-suppressor (CD8)) were measured on day 1 (week 0) and after 12 weeks (week 12) of the intervention. In the group receiving vitamin B(6), plasma IL-6 and TNF-alpha levels significantly decreased at week 12. There were no significant changes with respect to immune responses in both groups except for the percentage of total lymphocytes in the vitamin B(6) group when compared with week 0 and week 12. Plasma IL-6 level remained significantly inversely related to plasma PLP after adjusting for confounders (beta=-0.01, P=0.01). A large dose of vitamin B(6) supplementation (100 mg/day) suppressed pro-inflammatory cytokines (that is, IL-6 and TNF-alpha) in patients with RA.

Chronic and acute effects of walnuts on antioxidant capacity and nutritional status in humans: a randomized, cross-over pilot study

BackgroundCompared with other common plant foods, walnuts (Juglans regia) are consistently ranked among the highest in antioxidant capacity. In vitro, walnut polyphenols inhibit plasma and LDL oxidation, while in animal models they lower biomarkers of oxidative stress and raise antioxidant capacity. A limited number of human feeding trials indicate that walnuts improve some measures of antioxidant status, but not others.MethodsA 19 wk, randomized crossover trial was conducted in 21 generally healthy men and postmenopausal women ≥50 y to study the dose-response effects of walnut intake on biomarkers of antioxidant activity, oxidative stress, and nutrient status. Subjects were randomized to receive either 21 or 42 g raw walnuts/d during each 6 wk intervention phase with a 6 wk washout between phases. Subjects were instructed to consume their usual diet, but refrain from eating any other tree nuts, seeds, peanuts, or ellagitannin-rich foods during the entire study, and other polyphenol-rich foods for 2 d prior to each study visit.ResultsCompared to baseline levels, red blood cell (RBC) linoleic acid and plasma pyridoxal phosphate (PLP) were significantly higher after 6 wk with 42 g/d walnuts (P < 0.05 for both). Overall, changes in plasma total thiols, and other antioxidant biomarkers, were not significant with either walnut dose. However, when compared to fasting levels, plasma total thiols were elevated within 1 h of walnut consumption with both doses during the baseline and end visits for each intervention phase (P < 0.05 for all). Despite the observed increase in RBC linoleic and linolenic acids associated with walnut consumption, this substrate for lipid peroxidation only minimally affected malondialdehyde (MDA) and antioxidant capacity. The proportional changes in MDA and Oxygen Radical Absorbance Capacity (ORAC) were consistent with a dose-response effect, although no significant within- or between-group differences were observed for these measures.ConclusionsWalnut consumption did not significantly change the plasma antioxidant capacity of healthy, well-nourished older adults in this pilot study. However, improvements in linoleic acid and pyridoxal phosphate were observed with chronic consumption, while total plasma thiols were enhanced acutely. Future studies investigating the antioxidant effects of walnuts in humans are warranted, but should include either a larger sample size or a controlled feeding intervention.Trial RegistrationClinicalTrials.gov: NCT00626691

Iron status and serine hydroxymethyltransferase (SHMT) activity and abundance in pre‐ and postmenopausal women

To explore relationships between iron status and lymphocyte SHMT activity (ACT) and abundance (ABN), 118 postmenopausal women (54.3 y) enrolled in SIRBL (Soy Isoflavones for Reducing Bone Loss) study and 105 young women (21.2 y) were studied. Serum ferritin, folate, and vitamin B‐12, plasma total homocysteine (tHcy) and pyridoxal phosphate (PLP), lymphocyte SHMT ACT and ABN were determined. Subjects in the first (4.8 ng/mL; 93% premenopausal) and fifth (92.6 ng/mL; 98% postmenopausal) quintiles of serum ferritin were compared. The fifth quintile had higher median BMI (25 vs 22 kg/m2; p&lt;0.02), plasma PLP (p&lt;0.0001), total homocysteine (p&lt;0.05), and SHMT ABN (p&lt;0.0001), but significantly lower SHMT ACT (p&lt;0.02) than first quintile. Ferritin quintile Folate ng/mL B‐12 pg/mL PLP nmol/L tHcy nmol/L SHMT ACT cpm/ug protein SHMT ABN relative density First (n) 14.2 (45) 597 (45) 61.7 (45) 6.4 (45) 43.6 (27) 1.1 (21) Fifth (n) 13.1 (45) 521 (45) 93.9 (45) 6.6 (45) 13.0 (14) 12.3 (31) Increased iron status may enhance SHMT expression, favoring thymidine synthesis over Hcy remethylation, thus warranting further investigation.Funded by USDA Special Grant, NWRC, Iowa State University.

Long‐term, physiological dose of prednisolone treatment alters vitamin B6 metabolism in vivo

Earlier studies reported that B6 metabolic enzymes were reduced in adrenalectomized rats that could be restored by short‐term injection of very high dose glucocorticoids. Prednisolone (PSL) is a glucocorticoid commonly used for long‐term treatment of chronic inflammatory and autoimmune disorders. In the present study we investigated the impacts of long‐term physiological dose of PSL on vitamin B6 metabolism in vivo. Male C57BL/6J mice received either PBS (control), 0.1 mg PSL/kg (low dose), or 1 mg PSL/kg (medium dose) i.p. once every other day for up to 7 months, to mimic the regimen of PSL in humans with chronic disorders. PSL did not alter steady state B6 vitamers or B6 metabolic enzymes in erythrocytes. However, PSL (1mg/kg) significantly increased plasma pyridoxal 5′‐phosphate (PLP), pyridoxal (PL) and 4‐pyridoxic acid (PA) levels (P&lt;0.05). Furthermore, PSL increased PL level in the muscle in a dose dependent manner. PSL significantly induced hepatic pyridoxal kinase (PDXK) and pyridoxamine 5′‐phosphate oxidase activity (PMPO), but reduced hepatic pyridoxamine 5′‐phosphate (PMP) concentrations. Our study suggests that long‐term low/medium dose PSL can induce hepatic PDXK and PMPO activities that may convert hepatic PMP to PLP, leading to increased PL in the circulation and promote mobilization of B6 vitamers among tissues. ( This project was supported by Dept of Health in Taiwan DOH 97‐TD‐D‐113‐97011)Grant Funding Source: ASN

Pyridoxal‐5‐phosphate plasma concentrations in children receiving tuberculosis chemotherapy including isoniazid

Little is known about pyridoxine nutriture of children treated with isoniazid (INH) regimens. This study documents plasma pyridoxal 5'-phosphate (PLP) concentrations in children, HIV-infected and HIV-uninfected, receiving INH regimens. Children from the Western Cape of South Africa hospitalized for tuberculosis (TB) management were studied. Plasma PLP concentrations were determined on enrolment, 1-month after commencing TB treatment, and again after 4-month's treatment. The children received a supplement meeting pyridoxine requirements. Nineteen HIV-infected and 33 HIV-uninfected children received INH (dosage range 4-20 mg/kg) daily. Mean PLP plasma concentrations on enrolment were 8.32 (SD 6.75) ng/mL and 11.28 (SD 3.02) ng/mL in HIV-infected and HIV-uninfected children, respectively (p = 0.11) and after 4-month's treatment 6.75 (SD 2.71) ng/mL and 14.76 (SD 7.96) ng/mL (p < 0.001). On enrolment 9 (50%) HIV-infected and 5 (15%) HIV-uninfected children (p = 0.016) had suboptimal PLP concentrations (<6 ng/mL); after 4-month's treatment 8 (42%) and 2 (6%) (p = 0.004). Plasma PLP concentrations in children treated for TB were low on enrolment in HIV-infected and HIV-uninfected children; after 4-month's treatment low values were still common in HIV-infected children. Additional pyridoxine supplementation of malnourished children treated for tuberculosis is advisable, particularly those HIV-infected.

Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study

Low vitamin B-6 status has been linked to an increased risk of cardiovascular diseases. The cardioprotective effects of vitamin B-6 independent of homocysteine suggest that additional mechanisms may be involved. Our objective was to examine the cross-sectional association of vitamin B-6 status with markers of inflammation and oxidative stress. We measured plasma pyridoxal-5'-phosphate (PLP), C-reactive protein (CRP), and an oxidative DNA damage marker, urinary 8-hydroxydeoxyguanosine (8-OHdG), in Puerto Rican adults who were living in Massachusetts (n = 1205, aged 45-75 y). There was a strong dose-response relation of plasma PLP concentration with plasma CRP. Increasing quartiles of PLP were significantly associated with lower CRP concentrations (geometric means: 4.7, 3.6, 3.1, and 2.5 mg/L; P for trend < 0.0001) and with lower urinary 8-OHdG concentrations (geometric means: 124, 124, 117, and 108 ng/mg creatinine; P for trend: 0.025) after multivariate adjustment. These negative associations persisted after plasma homocysteine was controlled for. Plasma PLP concentrations were significantly correlated with plasma fasting glucose (r = -0.1, P = 0.0006), glycated hemoglobin (r = -0.08, P = 0.006), and homeostasis model assessment of beta cell function (r = 0.082, P = 0.005). Metabolic syndrome, obesity, and diabetes were also significantly associated with low plasma PLP concentrations (P = 0.011, 0.0007, and 0.004, respectively). Low vitamin B-6 concentrations are associated with inflammation, higher oxidative stress, and metabolic conditions in older Puerto Rican adults. Our data suggest that vitamin B-6 may influence cardiovascular disease risk through mechanisms other than homocysteine and support the notion that nutritional status may influence the health disparities present in this population.

Vitamin B6Requirement: Indicators and Factors Affecting

The purpose of this study was to establish the selection of indicators for estimating and factors affecting the requirement of vitamin B6. There has been a need to establish the human requirements of vitamin since vitamin is thought to be involved in more than one hundred biochemical reactions as a coenzyme in the metabolism of amino acids, glucose, and lipid, and the synthesis of neurotransmitters. For the review of the literature, this study included from early findings of the sixties to studies of 2009. This study suggests that plasma pyridoxal 5' phosphate (PLP) is the best single indicator of vitamin status for the healthy but not for the non-healthy. Erythrocyte aspartate aminotransferase and alanine aminotransferase activation by PLP as an indirect measure and urinary 4-pyridoxic acid excretion as a direct measure are useful as supporting indicators. Bioavailability, nutrient interaction, physiological need, and chronic diseases may increase the requirement for vitamin . However, these effects can not be quantified due to insufficient evidences.

Vitamin B-6 Intake Is Inversely Related to, and the Requirement Is Affected by, Inflammation Status

Low circulating pyridoxal 5′-phosphate (PLP) concentrations have been linked to inflammatory markers and the occurrence of inflammatory diseases. However, the implications of these findings are unclear. The measurement of PLP and C-reactive protein (CRP) in blood samples collected from participants in the 2003–2004 NHANES afforded us the opportunity to investigate this relationship in the general U.S. population. Dietary and laboratory data were available for 3864 of 5041 interviewed adults, 2686 of whom were eligible (i.e. provided reliable dietary data and were not diabetic, pregnant, lactating, or taking hormones or steroidal antiinflammatory drugs). Vitamin B-6 intake was assessed using 2 24-h diet recalls and supplement use data. After multivariate adjustment for demographics, smoking, BMI, alcohol use, antioxidant vitamin status, intakes of protein and energy, and serum concentrations of creatinine and albumin, high vitamin B-6 intake was associated with protection against serum CRP concentrations >10 mg/L compared with ≤3 mg/L. However, plasma PLP ≥20 nmol/L compared with <20 nmol/L was inversely related to serum CRP independently of vitamin B-6 intake (P < 0.001). Among participants with vitamin B-6 intakes from 2 to 3 mg/d, the multivariate-adjusted prevalence of vitamin B-6 inadequacy was <10% in participants with serum CRP ≤3 mg/L but close to 50% in those with serum CRP > 10 mg/L (P < 0.001). In conclusion, higher vitamin B-6 intakes were linked to protection against inflammation and the vitamin B-6 intake associated with maximum protection against vitamin B-6 inadequacy was increased in the presence compared to absence of inflammation.

Vitamin B6 Metabolism in Chronic Kidney Disease – Relation to Transsulfuration, Advanced Glycation and Cardiovascular Disease

Background: Vitamin deficiency is common in chronic kidney disease (CKD). Data on B₆ supply and possible relationships to cardiovascular events (CVE) in CKD are rare. Pyridoxamine exerts inhibitory effects on the formation of advanced glycation endproducts (AGE) implicated in the pathogenesis of CKD and atherosclerosis. Methods: In 48 CKD patients at stage 2–4, 72 hemodialysis patients (HD), 38 renal transplant recipients (RTR) and 141 healthy controls (mean age 58 ± 13, 61 ± 12, 50 ± 12 and 54 ± 16 years, respectively), plasma and red blood cell (RBC) concentrations of pyridoxal-5′-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (PA), pyridoxamine-5′-phosphate (PMP) and of the AGE pentosidine were measured by high-performance liquid chromatography, N^Ε-(carboxymethyl)lysine and imidazolone by an ELISA, and total homocysteine and cystathionine by gas chromatography-mass spectrometry. Results: Despite routine low-dose vitamin supplementation in HD, plasma PLP was decreased in HD (79 ± 69 nmol/l) compared with CKD stage 2–4 patients (497 ± 944 nmol/l), RTR (416 ± 604 nmol/l) and controls (159 ± 230 nmol/l; p < 0.001). Plasma PA was significantly increased in HD (11,667 ± 17,871 nmol/l) in comparison with CKD stage 2–4 (435 ± 441 nmol/l), RTR (583 ± 668 nmol/l) and controls (46 ± 49 nmol/l; p < 0.001). B₆ forms were significantly affected by renal function (R = 0.792, p < 0.001 for CKD stage 2–4). There was no relation of vitamers with a history of CVE. Relationships between B₆ forms and AGE (RBC-PMP with pentosidine in CKD stage 2–4: R = –0.351, p < 0.05) were found. Conclusion: HD patients showed a deficiency in PLP in plasma but not in RBC. Prospective trials are needed to elucidate the potential role of elevated PA on cardiovascular and renal outcome in CKD. Vitamin B₆ supplementation might be successful in preventing AGE-related pathologies.

Vitamin B-6 restriction tends to reduce the red blood cell glutathione synthesis rate without affecting red blood cell or plasma glutathione concentrations in healthy men and women

Background:Glutathione plays various protective roles in the human body. Vitamin B-6 as pyridoxal-5′-phosphate (PLP) is required as the coenzyme in the formation of glutathione precursors. Despite this obligatory role of PLP, previous studies from this laboratory showed that vitamin B-6 deficiency caused elevated glutathione concentrations in rat liver and human plasma. Objective:Our aim was to determine the effect of marginal vitamin B-6 deficiency (plasma PLP 20–30 nmol/L) on the rate of red blood cell (RBC) glutathione synthesis. Design:We measured plasma and RBC glutathione concentrations and the fractional and absolute synthesis rates of RBC glutathione using the stable-isotope-labeled glutathione precursor [1,2-13C2]glycine in 13 healthy volunteers aged 21–39 y. Results:Dietary vitamin B-6 restriction did not significantly affect the glutathione concentration in plasma (6.9 ± 1.9 compared with 6.7 ± 1.1μmol/L) or RBCs (2068 ± 50 compared with 2117 ± 48μmol/L). For RBC glutathione, the mean fractional synthesis rates were 54 ± 5%/d and 43 ± 4%/d (P = 0.10), and the absolute synthesis rates were 1116 ± 100 and 916 ± 92μmol · L−1 · d−1 (P = 0.14) before and after vitamin B-6 restriction, respectively. Conclusions:Marginal vitamin B-6 deficiency tended to decrease mean RBC glutathione synthesis with no effect on RBC glutathione concentration, but the responses varied widely among individuals. Because the cysteine concentration in plasma and RBC did not change during vitamin B-6 restriction, we conclude that the effects of marginal vitamin B-6 deficiency on glutathione synthesis are not caused by altered precursor concentrations.

Evaluation of Vitamin B6 Status of Adult Saudis in Al-Qassim Region-Saudi Arabia

The aim of this study was to evaluate vitamin B status of adult Saudis in Al-Qassim region-Saudi 6 Arabia. A sample of 239 (127 males and 112 females) healthy Saudi adults was recruited. Vitamin B status 6 was evaluated by dietary intake and biochemical measurements. Results of dietary intake measurements showed that means of vitamin B intake and intake of vitamin B to protein ratio for males and females were 6 6 1.97±0.58 mg/day, 0.021±0.003 and 1.89±0.61 mg/day, 0.020±0.04, respectively. Results of biochemica l measurements showed that means of plasma pyridoxal phosphate (PLP) concentration and average urinary 4-Pyridoxic Acid (4-PA) excretion for males and females were 29.6±9.6 nmol L and 7.0±2.4 µmol day and -1 -1 31.7±10.4 nmol L and 6.8±2.5 µmol day , respectively. The study also investigated and discussed other -1 -1 health indicators that are related to vitamin B status including Body Mass Index (BMI), plasma albumin 6 concentration and alkaline phosphatase activity. Results of dietary intakes and biochemical measurements indicated an adequate status of vitamin B. There were no significant differences between males and 6 females in any of the previous measurements. This study indicated an adequate status of vitamin B among 6 healthy adult Saudis in Al-Qassim region, however due to the numerous functions and the importance of the vitamin, the study suggested a further evaluation in various groups of the Saudi population in other regions of the country.

Risks of nutritional deficiencies in young adult type 1 diabetic (T1D) women

Although nutrition plays a crucial role in the treatment of T1D, there are few studies on the nutritional status. This study aimed to evaluate a target group at risk of nutritional deficiencies. Women with well‐controlled T1D and without renal complications (n=22) and healthy controls (n=27), aged 30‐40 yr‐old, were rigorously selected, having normal body weight and being not pregnant nor vegetarian, among other selection criteria. The two groups were comparable in many aspects. T1D, diagnosed since 21 yrs in average, was monitored by HbA1c level. Serum transferrin (P&lt;0.02) and IGF‐1 concentrations (P&lt;0.001) were reduced in the T1D group. There was no significant difference for albumin. Serum iron concentration was also reduced (P&lt;0.03), although body stores (ferritin) were not affected. Contrarily to other studies, serum Mg and plasma pyridoxal phosphate (PLP, vitamin B6 coenzyme) were not reduced, although alkaline phosphatase, which regulates the concentration of this vitamin, was increased (P&lt;0.01). Plasma PLP was below reference value. Erythrocyte folate was greater (P&lt;0.03) in TID group due to a greater number of subjects taking supplements and more control subjects with values in the low range. This study evidenced T1D‐induced metabolic changes in regard to protein and iron status. It also showed a risk of deficiency for vitamin B6.

Determination of plasma glucose enrichment in human subjects after primed, constant infusions of 13C‐glycine before and after dietary vitamin B‐6 restriction

Pyridoxal 5′‐phosphate (PLP) is involved in the production of glucogenic substrates via its role as a coenzyme for transamination reactions. A deficiency of vitamin B‐6 leads to impaired availability of glucogenic amino acids in rats and may affect glucose synthesis rates. This study aims to assess the impact of marginal vitamin B‐6 deficiency (plasma PLP 20 ‐30 nM) on gluconeogenesis from glycine in humans. We report here the feasibility of determining the rate and extent of glucose synthesis from an infused precursor. Thirteen healthy men and women received primed, constant infusions of 9.26 µmol/(kg*h) [1,2‐13C2]glycine before and after a 28‐d dietary vitamin B‐6 restriction. Plasma glucose was analyzed by positive chemical ionization gas chromatography‐mass spectrometry following preparation of glucose aldonitrile pentaacetate derivatives. This infusion protocol yields glycine M+2 enrichment of 5.2 mole % excess (MPE), with serine M+1 and serine M+2 enrichment of 0.7 and 1.4 MPE, respectively. Plasma glucose M+1 enrichment in this protocol was approximately 0.4 MPE. Investigation is underway to determine glucose synthesis rates and evaluate the effect of vitamin B‐6 status on gluconeogenesis. Supported by NIH grant DK072398 and GCRC grant M01‐RR00082.Grant Funding SourceNIH

Impairments in pyridoxine-dependent sulphur amino acid metabolism are highly sensitive to the degree of vitamin B6 deficiency and repletion in the pig

The objectives of the current study included the characterization of the temporal changes in indices of sulphur amino acid metabolism in piglets in response to vitamin B6 deficiency and repletion with graded levels of pyridoxine hydrochloride. In Experiment 1, 12 piglets (average initial weight = 5.3 kg; n = 6 per group) were fed a semi-purified diet containing either 0 (deficiency group) or 3 mg (control group) pyridoxine·HCl/kg diet, using a pair-feeding design, for 6 weeks. Piglets consuming vitamin B6-deficient diets exhibited decreased average daily gains on the 4th week and feed conversion efficiency from the 4th week until the end of the trial (P < 0.05). Plasma pyridoxal-5′-phosphate (PLP), in pigs consuming vitamin B6-deficient diets, was significantly lower than controls throughout the experiment (P < 0.01), reaching a nadir of 14% of the control animals’ value by the end of the trial. Indices of sulphur amino acid metabolism, including activities of hepatic cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CGL) and serine hydroxymethyltransferase, as well as hepatic-free cysteine concentrations were markedly decreased after 6 weeks of B6 deficiency (P < 0.05). Total hepatic mRNA expressions for CBS and CGL were not affected. Concurrently, hepatic-free homocysteine concentrations increased by more than eight-fold (P < 0.01) at the end of the trial. An examination of plasma total homocysteine and cysteine concentrations revealed significant (P < 0.05) differences between treatments, with evidence of an abrupt shift in concentrations at 3 weeks post-initiation of dietary treatments (>25-fold increase in homocysteine; halving of cysteine values). At the end of Experiment 1, vitamin B6 deficiency significantly increased plasma methionine and serine levels, but decreased plasma glycine concentrations (P < 0.05). In Experiment 2, 20 pigs of 14 days old (initial BW = 5.0 kg) were subjected to a 4-week vitamin B6 depletion protocol, based on results obtained in Experiment 1. After the depletion period and assessment of baseline status (four pigs), remaining pigs were allocated to one of four dietary vitamin B6 repletion treatments: 0.75, 1.5, 2.25 and 3 mg/kg diet as pyridoxine·HCl (n = 4 per level) for 14 days. Significant dose-dependent increases in plasma PLP and cysteine, and decreases in homocysteine were observed, and these were sensitive to the duration of repletion. In conclusion, data from the current studies support the use of both plasma PLP and homocysteine as sensitive indices of vitamin B6 status in the pig. Additionally, the observed patterns of responses in vitamin B6-sensitive metabolites are supportive of an inclusion level of 2.25 mg/kg diet, as pyridoxine·HCl, in diets for young pigs.