Plasma PLP Concentrations Research Articles

Impact of lifestyle factors on dietary vitamin B6 intake and plasma pyridoxal 5'-phosphate level in UK adults: National Diet and Nutrition Survey Rolling Programme (NDNS) (2008-2017).

Reduction in dietary vitamin B6 intake is associated with an increased relative risk of diseases such as cancer, atherosclerosis and cognitive dysfunction. The current research has assessed vitamin B6 intakes and PLP concentrations as a marker of vitamin B6 status among the UK adult (≥ 19 years) population. This study was carried out using a cross-sectional analysis of the National Diet and Nutrition Survey Rolling Programme (NDNS) (2008-2017). The impacts of lifestyle factors, including type of diet, smoking, alcohol consumption, and commonly used medications grouped by therapeutic usage, were determined, and data were analysed using IBM SPSS®. Results are expressed as medians (25th-75th percentiles), with P values ≤ 0·05 considered statistically significant. Among UK adults, the median intakes of total population of dietary vitamin B6 met the reference nutrient intake and median plasma PLP concentrations were above the cut-off of vitamin B6 deficiency; however, we found an association between reduction in vitamin B6 intake and plasma PLP concentration and age group (P < 0·001). Smokers had significantly lower plasma PLP concentrations than non-smokers (P < 0·001). Moreover, regression analysis showed some commonly used medications were associated with plasma PLP levels reduction (P < 0·05). Taken together, we report on a tendency for dietary vitamin B6 intake and plasma PLP concentrations to decrease with age and lifestyle factors such as smoking and medication usage. This information could have important implications for smokers and in the elderly population using multiple medications (polypharmacy).

Associations Between Vitamin B6 Status and Plasma Polyunsaturated Fatty Acids Among US Older Adults: NHANES 2003–2004

ObjectivesPrevious evidence suggests that vitamin B6 deficiency may have a deleterious impact on aging and the metabolism of polyunsaturated fatty acids (PUFA). However, the relationship of aging with vitamin B6 status and PUFA metabolism is poorly understood; population-based studies to assess the relationship between plasma pyridoxal 5′-phosphate (PLP; an active form of vitamin B6) and PUFA status for older adults are lacking. Thus, we examined the associations between plasma PLP concentration and plasma PUFA concentrations and ratios [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA] among US older adults. We further investigated the association of adequate (PLP ≥ 20 nmol/L) versus deficient (PLP < 20 nmol/L) vitamin B6 status in those participants with plasma PUFA concentration above the median. MethodsA cross-sectional study analyzed 467 participants aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2003–2004. Nutrient intake data were estimated from two 24-h recalls and from questionnaires on the use of supplements. Plasma PLP and PUFA concentrations were measured. We used multivariable linear regression for obtaining unstandardized (b) and standardized (β) coefficients; multivariable logistic regression for adjusted odds ratios. Covariates included demographic, socioeconomic, dietary variables, physical activity, smoking, alcohol consumption, prescription medication use, and BMI. ResultsPlasma PLP was directly associated with plasma EPA (β = 0.176, b = 0.101, P = 0.002), DHA (β = 0.109, b = 0.046, P = 0.004), EPA + DHA (β = 0.137, b = 0.060, P = 0.002), EPA/AA (β = 0.169, b = 0.089, P = 0.009). The odds of having plasma EPA/AA and (EPA + DHA)/AA concentration above the median were greater in those with adequate vitamin B6 compared with those who were deficient [adjusted OR (aOR): 1.32, 95% CI: 0.8–2.17, P = 0.0001; aOR: 2.08, 95% CI: 1.0–4.33, P = 0.049, respectively]. ConclusionsIn US older adults, plasma PLP was directly associated with plasma EPA, DHA, EPA + DHA, EPA/AA. Adequate vitamin B6 status was associated with having above the median EPA/AA and (EPA + DHA)/AA. These findings suggest that adequate B6 status may positively influence PUFA metabolism in the older US population. Funding SourcesNo funding sources.

Riboflavin Is an Important Determinant of Vitamin B-6 Status in Healthy Adults

Riboflavin is required to generate the active form of vitamin B-6 (pyridoxal 5'-phosphate; PLP) in tissues, but the relevance of this metabolic interaction for nutritional status of vitamin B-6 is unclear because riboflavin biomarkers are rarely measured in human studies. The purpose of this study was to identify the determinants of biomarkers of vitamin B-6 and riboflavin status and to examine the relationship between these nutrients in healthy adults. Multiple linear regression was performed on observational data in 407 healthy adults aged 18-92 y who did not use B-vitamin supplements. Vitamin B-6 status was assessed by plasma PLP concentrations and erythrocyte glutathione reductase activation coefficient (EGRac) was used as a functional indicator of riboflavin status. Dietary intakes of vitamin B-6 and riboflavin were below the average requirements in 10% and 29% of participants, respectively. Suboptimal status of vitamin B-6 (PLP ≤30.0nmol/L) was more prevalent in adults aged ≥60 y than in younger participants (i.e., 14% compared with 5%), whereas a high proportion (i.e., overall 37%) of both age groups had deficient riboflavin status (EGRac ≥1.40). In multiple regression analysis, EGRac (P=0.019) was a significant determinant of plasma PLP, along with dietary vitamin B-6 intake (P=0.003), age (P<0.001), BMI (kg/m2) (P=0.031), and methylenetetrahydrofolate reductase gene (MTHFR) genotype (P<0.001).Significant determinants of EGRac were dietary riboflavin intake (P<0.001), age (P<0.001)and MTHFR genotype (P=0.020). Plasma PLP showed a stepwise decrease across riboflavin status categories from optimal (EGRac ≤1.26) to low (EGRac 1.27-1.39) to deficient status (P=0.001), independent of dietary vitamin B-6 intake. The findings are consistent with the known metabolic dependency of vitamin B-6 on riboflavin status and indicate that riboflavin may be the limiting nutrient, particularly in older people, for maintaining adequate vitamin B-6 status.

Blood plasma B vitamins in depression and the therapeutic response to electroconvulsive therapy

A growing body of research has indicated a role for B vitamins in depression, with some previous studies suggesting that B vitamin status in patients with depression can impact on antidepressant response. Here we aimed to investigate B vitamin plasma concentrations in medicated patients with depression (n ​= ​94) compared to age- and sex-matched healthy controls (n ​= ​57), and in patients with depression after electroconvulsive therapy (ECT) in a real-world clinical setting. Our results show that nicotinamide (vitamin B3), N1-methylnicotinamide (vitamin B3 metabolite), and pyridoxal 5′-phosphate (PLP; vitamin B6) concentrations were significantly reduced in patients with depression compared to controls. The Cohen’s d effect sizes for nicotinamide, N1-methylnicotinamide, and PLP were moderate–large (−0.47, −0.51, and −0.59, respectively), and likely to be of clinical relevance. Functional biomarkers of vitamin B6 status (PAr index, 3-hydroxykynurenine: hydroxyanthranilic acid ratio, 3-hydroxykynurenine: xanthurenic acid ratio, and HKr) were elevated in depressed patients compared to controls, suggestive of reduced vitamin B6 function. Over 30% of the patient cohort were found to have low to deficient PLP concentrations, and exploratory analyses revealed that these patients had higher IL-6 and CRP concentrations compared to patients with PLP levels within the normal range. Treatment with ECT did not alter B vitamin concentrations, and B vitamin concentrations were not associated with depression severity or the therapeutic response to ECT. Overall, reduced plasma PLP, nicotinamide, and N1-methylnicotinamide concentrations could have wide ranging effects on pathways and systems implicated in depression. Further studies are required to understand the reasons why patients with depression present with low plasma B vitamin concentrations.

Suboptimal maternal and cord plasma pyridoxal 5' phosphate concentrations are uncommon in a cohort of Canadian pregnant women and newborn infants.

Vitamin B6 is important in fetal development, but little is known of the vitamin B6 status of pregnant women and newborns in North America and potential modifying factors. This prospective study determined maternal and cord plasma concentrations of pyridoxal 5' phosphate (PLP; an indicator of vitamin B6 status) in a convenience sample of 368 Canadian pregnant women and their newborns. The association of maternal intake of vitamin B6 and fetal genetic variants with cord plasma PLP and homocysteine concentrations was also examined. Dietary and supplemental intakes of vitamin B6 were assessed in early and mid to late pregnancy. PLP concentrations were measured in maternal plasma in early pregnancy and at delivery, and in cord plasma. Six fetal variants of the MTHFR and CβS genes were assessed for their association with cord plasma PLP and homocysteine concentrations. Geometric mean (95% CI) PLP concentrations were 107 (98, 116) nmol/L in early pregnancy and 58 (53, 62) nmol/L at delivery, respectively, and 296 (275, 319) nmol/L in cord blood (p<.0001). During early pregnancy and at delivery, 3.6% and 5.5% of women had plasma PLP concentrations <20nmol/L, respectively. Ninety eight percent of the women with supplemental B6 intake of at least the recommended dietary allowance had PLP concentrations >20nmol/L. Fetal genetic variants were not associated with cord PLP and homocysteine concentrations. Vitamin B6 deficiency is uncommon in a cohort of Canadian pregnant women due largely to prevalent vitamin B6 supplement use.

Vitamin B-6 Status in Unsupplemented Pregnant Women Is Associated Positively with Serum Docosahexaenoic Acid and Inversely with the n–6-to-n–3 Fatty Acid Ratio

BackgroundVitamin B-6–deficient diets decrease plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) concentrations in healthy adults. These fatty acids (FAs) are important for fetal neurodevelopment, but the relation between vitamin B-6 status and circulating polyunsaturated FAs (PUFAs) during pregnancy is unknown. ObjectiveWe sought to assess the relation between plasma pyridoxal 5′ phosphate (PLP; the active form of vitamin B-6) and serum DHA, EPA, AA, linoleic acid, eicosadienoic, and α-linolenic acid concentrations during pregnancy. MethodsA prospective cohort study in 186 healthy pregnant Brazilian women (aged 20–40 y) who were not using supplements was conducted in Rio de Janeiro, Brazil. Participants were enrolled in the first trimester of pregnancy (5–13 gestational weeks) and were followed up twice between 20–26 and 30–36 wk of gestation. Longitudinal linear mixed-effects regression models were used to evaluate the associations between 1) first-trimester PLP and PUFA concentrations across pregnancy and 2) ΔPLP (i.e., difference between third- and first-trimester plasma PLP concentrations) and PUFA concentrations across pregnancy. Models were adjusted for gestational week, first-trimester body mass index, smoking habit, and dietary intakes of vitamin B-6, fish, total fat, and PUFAs. ResultsPlasma PLP concentrations (median, IQR) substantially declined during pregnancy from 35.8 nmol/L (28.6–44.3 nmol/L) in the first trimester to 21.0 nmol/L (15.8–26.3 nmol/L) in the second trimester, and 16.8 nmol/L (12.9–20.3 nmol/L) in the third trimester (both P < 0.0001). Changes in plasma PLP concentrations across trimesters were positively associated with serum DHA concentrations (β = 0.252, P = 0.012) and inversely associated with serum n–6-to-n–3 (ω-6-to-ω-3) FA ratio (β = −0.010; P = 0.015), after adjustments for confounders. ConclusionsMaternal vitamin B-6 status during pregnancy was positively associated with the circulating concentration of DHA and inversely associated with n–6:n–3 FAs in Brazilian women who were not taking vitamin supplements. Further study is required to determine the impact of poor vitamin B-6 status on fetal neurodevelopment.

Plasma PLP Concentration and Depressive Symptomatology in older Latino Adults: A Longitudinal Analysis with time‐varying Covariates

BackgroundLow vitamin B‐6 status has been linked to depressive symptomatology. However, most studies have been cross‐sectional and may not have controlled for relevant confounders. Few studies have examined this association in Latino populations at high risk for major depression.ObjectiveOur objective was to examine the longitudinal association of vitamin B‐6 status with depressive symptomatology in a cohort of older Puerto Rican adults, a population previously identified to be at high risk for depressive symptomatology and clinical depression.ResultsIn two level hierarchical linear regression models that account for the clustering of measures of participant's depressive symptomatology (Level‐1) at three different points in time nested within participants (Level‐2); plasma pyridoxyl‐5′‐phosphate (PLP) concentration, a time‐varying predictor, was significantly associated with higher depressive symptomatology over the three time points. This negative association persisted after adjusting for body mass index (BMI), level of physical activity, smoking, alcohol use, hypertension, diabetes, time‐varying vitamins B‐12, folate and D; and baseline dietary intake of magnesium, allostatic load (physiological stress), stressful life events (social stress) and perceived stress (psychological stress), plasma homocysteine concentration (tHCY), and use of antidepressant medication. The slope of the decline in depressive symptomatology over time was steeper in participants with PLP&gt;30 nmol/L vs. participants with suboptimal PLP plasma concentration; however, this difference was not statistically significant.ConclusionsWe found significantly higher depressive symptoms in participants with suboptimal plasma PLP compared to participants with adequate PLP concentration over three time points. Findings from our study highlight the need to adjust for physiological, psychological and social stress when examining the effect of micro‐nutrients on depressive symptoms. Our data suggest that identification and treatment of vitamin B‐6 deficiency may be a useful preventive and intervention approach in older Puerto Rican adults, and potentially other Hispanic subgroups.Support or Funding InformationThis study was funded by the National Heart, Lung, and Blood Institute; National Institutes of Health (Grant 5P50HL105185, Katherine L. Tucker, PhD, Principal Investigator) Longitudinal Associations between Depressive symptomatology (CES‐D) and time‐varying suboptimal PLP status in the Puerto Rican Health study participants Model 1a Model 2b Model 3c Model 4d Model 5e Model 6f β (SE) p‐value β (SE) p‐value β (SE) p‐value β (SE) p‐value β (SE) p‐value β (SE) p‐value Suboptimal Vitamin B‐6 (plasma PLP&lt;30 nmol/L) No use ‐ref ‐ ‐ ‐ ‐ ‐ ‐ Yes 0.68 0.56 0.23 0.57 0.56 0.31 0.52 0.57 0.36 0.34 0.65 0.60 1.16 0.57 0.04 1.06 0.57 0.06 Time −0.47 0.10 &lt; 0.0001 −0.72 0.10 &lt;0.0001 −0.42 0.10 &lt;0.0001 −0.44 0.11 &lt;0.0001 −0.64 0.11 &lt;0.0001 −0.66 0.11 &lt;0.0001 Suboptimal Vitamin B‐6 * Time No use ‐ref ‐ ‐ ‐ ‐ ‐ ‐ Yes 0.23 0.19 0.24 0.15 0.19 0.43 0.17 0.20 0.39 0.11 0.22 0.62 0.09 0.23 0.68 0.11 0.22 0.64 Goodness of fit N 12 15 17 21 24 26 df 3016 2985 2933 2350 2187 2187 Log Likelihood −11537.92 −11394.91 −11198.46 −9008.93 −8011.75 −7996.55 AIC 23099.84 22819.83 22430.92 18059.85 16071.51 16045.09 BIC 23171.98 22909.85 22532.65 18180.86 16208.08 16193.04 Model 1: age + sex + education + BMI Model 2: Model 1 + smoking + alcohol use + physical activity Model 3: Model 2 + hypertension + diabetes Model 4: Model 3 + time‐varying plasma vitamins (B‐12, Folate, D) + baseline energy adjusted magnesium diet intake Model 5: Model 4 + allostatic load + stressful life events + perceived stress Model 6: Model 5 + tHCY + antidepressant drug use

Decrease in pyridoxal-5′-phosphate concentration and increase in pyridoxal concentration in rat plasma by 4′-O-methylpyridoxine administration

Food poisoning from Ginkgo biloba seeds can cause epilepsy because of a decrease in γ-aminobutyric acid (GABA) concentrations in the brain. We previously demonstrated that 4′-O-methylpyridoxine (MPN) is responsible for this observed toxicity of G biloba seeds; however, the mechanism for the decrease in GABA and plasma concentration profile of MPN has not been clarified. Our hypothesis is that MPN induces a decrease in vitamin B6 concentrations, resulting in a decrease in GABA concentration. This study aimed to characterize the plasma concentration profile of MPN and intrinsic vitamin B6 concentrations (pyridoxal [PL], PL-5′-phosphate [PLP], and 4-pyridoxic acid) using a rat model. Plasma concentrations of B6 vitamers after intravenous MPN administration (5 mg/kg) were determined using high-performance liquid chromatography with a fluorescence detector. The half-life of MPN (0.91 ± 0.05 hours) was shorter in rats than the previously reported value in humans. We found a significant decrease in the plasma concentration of PLP, an active form of vitamin B6, after MPN administration. We also observed an increase in plasma PL and 4-pyridoxic acid concentrations; the increase in PL concentration may be caused by either metabolism of MPN to PL or by MPN-mediated inhibition of PL kinase. The present study is the first in vivo study showing relatively rapid elimination of MPN in rats and a decrease in plasma PLP concentration caused by MPN.

A proteomic approach identifies plasma proteins correlated with vitamin B6 in Nepalese children (804.14)

Vitamin B6 is a coenzyme for &gt;140 distinct enzymes involved in amino acid metabolism. In the plains of Nepal, we have reported 43% of children age 6‐8 years of age to be B6 deficient (pyridoxal‐5’‐phosphate, PLP &lt;20nmol/L), revealing a public health problem. This study identified differentially abundant plasma proteins in relation to B6 status in 500 6‐8 yr old Nepalese children that represent possible B6 biomarkers with the potential to predict B6 status. Plasma PLP concentration was analyzed by HPLC, and relative abundance of plasma proteins by isobaric tags for relative and absolute quantification (iTRAQ) tandem mass spectrometry. A total of 87 proteins were associated with PLP (for all, q&lt;0.1, p&lt;0.008), defining a plasma B6 proteome: 39 and 48 were positively and negatively correlated (r from 0.51 to 0.29 and ‐0.56 to ‐0.21) with PLP, respectively. Identified proteins are involved in numerous metabolic pathways, including cell proliferation, proteolysis, adhesion, acute phase reaction, coagulation and transport. Linear mixed effects analysis estimated ~60% of the variance (R²) in plasma PLP could be estimated by the relative abundance of 5 proteins (complement 9, cyclin D‐type binding‐protein 1, dynein, axonemal, heavy chain 10, leucine rich repeat containing 47, and NOP2/Sun domain family, member 6). A predictive plasma PLP proteome may exist for assessing population B6 status.Grant Funding Source: Supported by Bill and Melinda Gates Foundation Grants 614 and 5241

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, serves as a cofactor for over 140 distinct biochemical reactions. Although severe vitamin B6 deficiency is rare, mild inadequacy (plasma PLP &lt; 20 nmol/L) is observed in 19–27% of the US population, depending on age and sex. Plasma PLP concentrations are inversely related to markers of systemic inflammation such as CRP. Furthermore, plasma PLP is depleted 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 has been shown to attenuate IBD pathology in mice; however the effects of supplementation are unclear. Thus, we tested the effect of mild inadequacy and moderate supplementation of vitamin B6 on the severity of colonic inflammation in the IL10−/− mouse model of IBD. We observed a bell‐shaped relationship between histologic inflammation and expression of inflammatory mediators (TNFalpha, IL‐6, IFN‐gamma, COX‐2, iNOS), whereby both low and high plasma PLP was associated with a suppression of inflammation. These results raise the possibility that vitamin B6 supplementation might be used to complement existing therapies for the treatment of IBD. Studies to reproduce these results and uncover mechanisms are underway.

Highlights of This Issue

Using cases from several Australian pediatric oncology centers, Milne and colleagues investigated the protective effects of maternal folic acid against childhood brain tumors. Their work represents the largest study of its kind and provides evidence of an inverse association between childhood brain tumors and folic acid use before pregnancy. These findings are intriguing given that the folic acid/brain cancer connection is biologically plausible through established mechanisms.Previous studies have suggested that vitamin B6 may reduce the risk of breast cancer. Lurie and colleagues examined the association of plasma concentrations of PLP (an active form of vitamin B6) with postmenopausal breast cancer risk. They report that women with high plasma PLP concentrations had a 30% reduced risk of invasive breast cancer compared with women with lower PLP levels. This association appeared to be limited to cases with hormone receptor–positive tumors. These results suggest a role for vitamin B6 in the prevention of postmenopausal breast cancer and indicate a potential heterogeneity of the association by tumor hormone receptor status.Although cervical infection with high-risk human papillomavirus (HPV) is considered a cause of cervical cancer, smoking has also been associated with cervical cancer. Jensen and colleagues used structured interviews, HPV DNA analysis, and up to 13 years of cervical lesion follow-up to explore the relationships among smoking, HPV, and cervical cancer. The authors report that among woman with persistent, high-risk HPV infection, the risk for future high-grade cervical lesions was associated with both long- term and heavy smoking. This work strengthens the role of smoking in the natural history of HPV and cervical carcinogenesis.In the United States, prostate cancer incidence rates are dramatically low in Latino and Japanese men. To explore the reasons for this, Cheng and colleagues conducted genomewide association studies, tested prostate cancer risk variants, and developed genetic risk models in U.S. Japanese and Latino populations. Although no new genome-wide significant prostate cancer loci were uncovered, the authors report that known risk variants contribute to prostate cancer susceptibility in both populations. This important study helps define the risk alleles that contribute to prostate cancer in Japanese and Latino men.

Plasma Vitamins, Amino Acids, and Renal Function in Postexercise Hyperhomocysteinemia

Several studies have assessed the effect of the physical activity on plasma homocysteine (Hcy) concentrations, although the findings have been contradictory, and the exact mechanism by which plasma Hcy concentrations varied after an acute intense exercise remains unknown. We studied the effect of different acute aerobic intense exercises on plasma, reduced, and total Hcy (rHcy, tHcy) and cysteine (rCys, tCys) and on its metabolically related vitamins and amino acids. Parallel effects on renal function were assessed by plasma creatinine. Fifteen cyclists and 14 kayakers were examined before and 30 +/- 5 min after a specific test to exhaustion during a low-intensity training period. After a bout of specific exercise, the concentrations of aminothiols were increased regardless of the group considered. Plasma concentrations were higher than baseline values in tHcy (17.7 +/- 1.5%; P < 0.001), rHcy (10.6 +/- 1.6%; P < 0.001), tCys (9.9 +/- 1.6%; P < 0.001), and rCys (7.6 +/- 2.2%; P < 0.01). Both groups showed significant elevations of pyridoxal-5'-phosphate (PLP; P < 0.01), vitamin B12 (P < 0.001), and creatinine concentrations (P < 0.001) after acute exercises, but no changes were seen in folate. Changes in plasma aminothiols after exercise did not reach significant correlation with changes in free amino acids or baseline vitamins, but significant and positive correlations were observed with changes in plasma PLP, vitamin B12, and creatinine concentrations, when the pooled data were considered. Our results show that higher plasma concentrations of tHcy after an acute intense exercise are associated to higher concentrations of rHcy, and this effect is independent of the type of exercise, vitamin status, or amino acid metabolic stress but could be related to potential changes in the renal function.

Moderate Dietary Vitamin B-6 Restriction Raises Plasma Glycine and Cystathionine Concentrations While Minimally Affecting the Rates of Glycine Turnover and Glycine Cleavage in Healthy Men and Women

Glycine is a precursor of purines, protein, glutathione, and 1-carbon units as 5,10-methylenetetrahydrofolate. Glycine decarboxylation through the glycine cleavage system (GCS) and glycine-serine transformation by serine hydroxymethyltransferase (SHMT) require pyridoxal 5′-phosphate (PLP; active form of vitamin B-6) as a coenzyme. The intake of vitamin B-6 is frequently low in humans. Therefore, we determined the effects of vitamin B-6 restriction on whole-body glycine flux, the rate of glycine decarboxylation, glycine-to-serine conversion, use of glycine carbons in nucleoside synthesis, and other aspects of 1-carbon metabolism. We used a primed, constant infusion of [1,2-13C2]glycine and [5,5,5-2H3]leucine to quantify in vivo kinetics in healthy adults (7 males, 6 females; 20–39 y) of normal vitamin B-6 status or marginal vitamin B-6 deficiency. Vitamin B-6 restriction lowered the plasma PLP concentration from 55 ± 4 nmol/L (mean ± SEM) to 23 ± 1 nmol/L (P < 0.0001), which is consistent with marginal deficiency, whereas the plasma glycine concentration increased (P < 0.01). SHMT-mediated conversion of glycine to serine increased from 182 ± 7 to 205 ± 9 μmol·kg−1·h−1 (P < 0.05), but serine production using a GCS-derived 1-carbon unit (93 ± 9 vs. 91 ± 6 μmol·kg−1·h−1) and glycine cleavage (163 ± 11 vs. 151 ± 8 μmol·kg−1·h−1) were not changed by vitamin B-6 restriction. The GCS produced 1-carbon units at a rate (∼140–170 μmol·kg−1·h−1) that greatly exceeds the demand for remethylation and transmethylation processes (∼4–7 μmol·kg−1·h−1). We conclude that the in vivo GCS and SHMT reactions are quite resilient to the effects of marginal vitamin B-6 deficiency, presumably through a compensatory effect of increasing substrate concentration.

Plasma pyridoxal 5′-phosphate is a significant indicator of immune responses in the mechanically ventilated critically ill

Objectives This study assessed the effect of vitamin B6 status on immune responses in mechanically ventilated, critically ill patients and compared the results with those of healthy controls. Methods This was designed as a cross-sectional observational study. Forty patients in the intensive care unit successfully completed this study. Vitamin B6 intake was recorded for 8 d. Severity of illness (Second Acute Physiology and Chronic Health Evaluation score) was recorded. Thirty-eighty healthy controls were recruited from the physical check unit of Taichung Veterans General Hospital (Taichung, Taiwan). All control subjects were given instruction on how to complete a 24-d diet recall. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5′-phosphate [PLP] and 4-pyridoxic acid) and indirect measures (erythrocyte alanine and aspartate aminotransferase activity coefficients). Levels of serum albumin, hemoglobin, hematocrit, high-sensitivity C-reactive protein, and immune responses (white blood cell, neutrophil, total lymphocytes, T lymphocytes [CD3], B lymphocytes [CD19], T-helper cells [CD4], and suppressor cells [CD8]) were determined. Results Critically ill patients had sufficient vitamin B6 intake but showed marginal PLP deficiency (20.9 ± 1.5 nmol/L). In addition, critically ill patients had significantly lower and abnormal immune responses than did healthy controls. There was no significant correlation of vitamin B6 intake and erythrocyte alanine and aspartate aminotransaminase activity coefficients with immune indices. Plasma PLP concentration was strongly negatively correlated with high-sensitivity C-reactive protein level. However, plasma PLP was significantly associated with immune responses after adjustment for age, sex, high-sensitivity C-reactive protein, and the other four vitamin B6 indicators. Conclusions Plasma PLP is a significant indicator of immune responses in human subjects. Further research is warranted to study whether vitamin B6 supplementation in critically ill patients improves their immune responses.

Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study

The results of prospective studies on the relations between the plasma concentration of total homocysteine (tHcy) and B-vitamins, on the one hand, and coronary heart disease (CHD) mortality, on the other hand, are inconclusive and scarce considering the relation with B-vitamins. We prospectively determined these relations in a case-cohort study. The full-cohort existed in ∼36,000 Dutch adults aged 20–59 years at baseline. The statistical analyses were done with a random sample from the cohort ( n=630) complemented with all subjects who died of CHD ( n=102) during a mean follow-up of 10.3 years. All subjects reported the absence of cardiovascular diseases (CVDs) at baseline. The plasma concentrations of tHcy, folate, PLP, and vitamin B12 were determined in samples obtained at baseline. Men with a tHcy concentration in the highest tertile (T3) compared with men in the lowest tertile (T1) had a relative risk (RR) of 1.14 for CHD (95% confidence interval (CI): 0.50, 2.61) after adjusting for age, study center, hypertension, HDL and total cholesterol, smoking, and creatinine. For women, this RR was 2.04 (95% CI: 0.48, 8.62). For each 5 μmol/l increase in tHcy, the RR of CHD was 1.03 (95% CI: 0.83–1.29) for men and women combined. In women only, high folate levels were associated with a statistically significant protection of fatal CHD (T3 versus T1; RR: 0.22, 95% CI: 0.06, 0.87). Plasma PLP (B6) and vitamin B12 concentrations were not associated with CHD risk. We conclude that elevated tHcy concentrations do not seem to be a risk factor for CHD mortality in these relatively young healthy Dutch subjects free of baseline CVD. Higher folate concentrations may be protective of CHD, but this needs confirmation.

Homocysteine, B vitamins, and vascular-access thrombosis in patients treated with hemodialysis

To evaluate whether increased plasma homocysteine concentrations (hyperhomocysteinemia) are associated with thrombosis of arteriovenous (AV) grafts, we determined plasma homocysteine, plasma and erythrocyte folate, plasma vitamin B12, and vitamin B6 (pyridoxal-5'-phosphate [PLP]) in 48 patients (45 black patients and three white patients) with end-stage renal disease who received hemodialysis. 5,10- Methylenetetrahydrofolate reductase (MTHFR) genotypes were also analyzed. The patients were divided into two groups, including a thrombosis-prone group with frequent graft loss (n = 24) and a control group with prolonged graft survival who were matched by age and duration of dialysis (n = 24). Hyperhomocysteinemia (>15 micromol/L) was found in 42 patients. There were no significant differences in all values, including the concentrations of homocysteine and vitamins between the two groups. Based on plasma folate and PLP concentrations, over 70% of patients appeared to have inadequate folate and/or vitamin B6 nutriture. Plasma homocysteine concentrations showed significant negative correlations with plasma and erythrocyte folate, and plasma vitamin B12 in all patients combined, whereas no significant correlation was found between plasma PLP and homocysteine concentrations. Among 48 patients, the heterozygous mutation (Val/Ala) of MTHFR was found only in three patients, two of whom belonged to the thrombosis-prone group and one to the control group, and there were no individuals with homozygous thermolabile mutation (Val/Val). All three white patients had Ala/Ala genotype, and 3 in 45 black patients (6.7%) were heterozygotes (Val/Ala). (Am J Kidney Dis 1998 Sep;32(3):475-81)

Vitamin B6, vitamin C, and carpal tunnel syndrome. A cross-sectional study of 441 adults.

As part of an ongoing study of carpal tunnel syndrome (CTS) in industry, we measured plasma concentrations of pyridoxal 5'-phosphate (PLP, a measure of vitamin B6 status) and total ascorbate (ASC, a measure of vitamin C status) in 441 adult volunteers from six industries and a university exercise study. In the entire study group and in non-vitamin users (n = 218), there were no significant differences in mean plasma PLP or ASC concentrations between controls (neither symptoms nor slowing), subjects with symptoms only, subjects with median nerve slowing only, or subjects with CTS (symptoms + slowing). In male non-vitamin users (n = 137), there were significant inverse univariate associations between plasma PLP concentration and the prevalence of pain, the frequency of tingling and nocturnal awakening, and the Phalen test result. In this same subgroup, the ASC/PLP ratio was directly associated with the prevalence of pain and nocturnal awakening, and with the frequency of pain, tingling, and nocturnal awakening. In multivariate analyses, plasma ASC concentration predicted more median nerve slowing and confirmed CTS, and vitamin or vitamin interaction variables were independent predictors of 20 CTS-related outcomes. These multivariate relationships often occurred only after adjustment for age, gender, body mass index, serum alkaline phosphatase activity, or tobacco use. We conclude that there are significant relationships between plasma vitamin levels and both components of CTS (specific symptoms and median nerve slowing). The interaction between plasma PLP and ASC appears to be particularly important with respect to symptoms.

Change in blood levels of vitamin B-6 derivatives in pregnant and lactating rats.

By using an HPLC method which we have developed, concentration changes of vitamin B-6 derivatives in blood of pregnant and lactating rats were studied. PLP and PL were the main derivatives in plasma and erythrocytes, and occasionally, PMP was found in the plasma of rats fed a normal solid diet which contained 8.3 mg PN.HCl/kg diet. Upon pregnancy, the plasma PLP concentration decreased significantly (p < 0.01), whereas plasma PL tended to increase (p < 0.05). PLP concentration in erythrocytes tended to increase upon pregnancy. These results suggest that metabolism or utilization of vitamin B-6 is altered upon pregnancy and that plasma PLP concentrations alone may not be a good indicator of nutritional status. Further confirmation was needed for so from erythrocyte samples under our analytical conditions was not so from erythrocyte samples under our analytical conditions was not converted to PIC-P via PLP, after the sample was treated with glyoxylic acid and then with KCN.

Separation and quantification of the B6 vitamers in plasma and 4-pyridoxic acid in urine of adolescent girls by reversed-phase high-performance liquid chromatography

The vitamin B6 status of seemingly healthy adolescent girls was determined using several accepted and proposed parameters in an effort to establish guidelines for status evaluation. High-performance liquid chromatography-derived plasma B6 vitamers (pyridoxal phosphate, PLP; pyridoxine phosphate. PNP; pyridoxamine phosphate, PMP; pyridoxal, PL; pyridoxine, PN; and pyridoxamine, PM) and 4-pyridoxic acid (4-PA) concentrations and urinary 4-PA levels of 28 white adolescent females, 12-15 years, having radiomonitored plasma PLP concentrations and coenzyme stimulation of erythrocyte alanine aminotransferase activities indicative of adequate status were determined. Mean vitamin B6 and protein intakes were 1.48 mg and 78.3 g. Ranges for plasma B6 vitamer and 4-PA concentrations (nmol/l) were: PLP, 40.9-122.2; PNP, non-detectable (ND)-16.1; PMP, ND-8.1; PL, ND-15; PN, ND-21.9; PM, ND-17.8; and 4-PA, ND-55.7. PLP was the only vitamer found in plasma of all subjects. Urinary 4-PA concentrations ranged from 0.11 to 2.50 mumol/mmol of creatinine. B6 vitamer values of these girls should be of use in the establishment of normal ranges for vitamin B6 status parameters.

Impaired collagen maturity in vitamins B 2 and B 6 deficiency—Probable molecular basis of skin lesions

Solubility of collagen was increased and the proportion of insoluble collagen was reduced in the skin of both riboflavin as well as pyridoxine-deficient rats. Collagen content of the skin, and aldehyde concentration of salt-soluble collagen were also lower in the deficient groups. The α:β subunit ratio of salt-soluble collagen was higher in riboflavin deficiency. In food-restricted weight-matched control groups, similar changes in collagen solubility, but of lesser magnitude were observed. Both food restriction and riboflavin deficiency decreased plasma PLP concentration. Increase in the solubility of collagen, decrease in the aldehyde content of soluble collagen and increase in the α:β subunit ratio of soluble collagen, suggest that the maturation of collagen may be affected in pyridoxine or riboflavin deficiency. These molecular events may be etiologically related to the pathogenesis of the skin lesions in vitamin B 2 or B 6 deficiency.