Novel synthesis of a dual fluorimetric sensor for the simultaneous analysis of levodopa and pyridoxine.

Herein, a fluorimetric sensor was fabricated based on molecularly imprinted polymers (MIPs) with two types of carbon dots as fluorophores. The MIPs produced had similar excitation wavelengths (400 nm) and different emission wavelengths (445 and 545 nm). They were used for the simultaneous analysis of levodopa and pyridoxine. First, two types of carbon dots, i.e. nitrogen-doped carbon dots (NCDs) with a quantum yield of 43%, and carbon dots from o-phenylenediamine (O-CDs) with a quantum yield of 17%, were prepared using the hydrothermal method. Their surfaces were then covered with MIPs through the reverse microemulsion method. Finally, a mixture of powdered NCD@MIP and O-CD@MIP nanocomposites was used for the simultaneous fluorescence measurement of levodopa and pyridoxine. Under optimal conditions using response surface methodology and Design-Expert software, a linear dynamic range of 38 to 369 nM and 53 to 457 nM, and detection limits of 13 nM and 25 nM were obtained for levodopa and pyridoxine, respectively. The capability of the proposed fluorimetric sensor was investigated in human blood serum and urine samples. Graphical Abstract Schematic representation of nitrogen-doped carbon dots (NCDs), carbon dots from o-phenylenediamine (O-CDs), NCDs coated with imprinted polymers (NCD@MIPs), and O-CDs coated with imprinted polymers (O-CD@MIPs) in the presence and absence of levodopa and pyridoxine.

Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis.

BACKGROUND: Migraine, especially migraine with aura (MA), has been linked to increased risk for ischemic cerebrovascular disease. The possible role of elevated serum homocysteine (Hcy, a cause of thrombophilia) in migraine has been demonstrated by several studies. OBJECTIVE: The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls (HC), as well as between patients with MA and migraine without aura (MO). METHODS: Literature search involved MEDLINE, Embase, CENTRAL, Google Scholar, and trial registries. The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies. Standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) were calculated. Funnel-plots were utilized for the evaluation of publication bias. RESULTS: Overall, 29 (28 case-control and 1 cross-sectional) studies were retrieved. Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [adults and children: 16 studies, I2  = 81%, SMD = 0.41, 95%CI = (0.20, 0.61)]. Hcy was consistently elevated in adults with migraine [adults: 12 studies, I2  = 76%, SMD = 0.35, 95%CI = (0.15, 0.54); children: 1 study, SMD = 0.37, 95%CI = (-0.05, 0.79)]. Subgroup analyses reproduced the results for both adults with MA [7 studies, I2  = 83%, SMD = 0.37, 95%CI = (0.03, 0.71)] and MO [5 studies, I2  = 84%, SMD = 0.46, 95%CI = (0.03, 0.89)]. Figures for serum folate were lower in the overall comparison of migraine patients with HC [adults and children: 11 studies, I2  = 87%, SMD = -0.36, 95%CI = (-0.68, -0.05); adults: 8 studies, I2  = 6%, SMD = -0.11, 95%CI = (-0.22, 0.01); children: 1 study, SMD = -0.71, 95%CI = (-1.14, -0.29); MA adults: 4 studies, I2  = 44%, SMD = -0.16, 95%CI = (-0.35, 0.04); MO adults: 4 studies, I2  = 47%, SMD = -0.17, 95%CI = (-0.44, 0.10)]. Serum vitamin B12 levels were not different between migraine patients and HC [adults and children: 11 studies, I2  = 88%, SMD = -0.24, 95%CI = (-0.57, 0.09); adults: 8 studies, I2  = 57%, SMD = -0.10, 95%CI = (-0.28, 0.08); children: 1 study, SMD = 0.29, 95%CI = (-0.13, 0.71); MA adults: 4 studies, I2  = 63%, SMD = -0.14, 95%CI = (-0.48, 0.20); MO adults: 4 studies, I2  = 59%, SMD = -0.15, 95%CI = (-0.45, 0.15)]. Serum Hcy was lower in MO than MA [adults and children: 10 studies, I2  = 39%, SMD = 0.30, 95%CI = (0.14, 0.46), adults: 6 studies, I2  = 29%, SMD = 0.21, 95%CI = (0.09, 0.36), children: 1 study, SMD = 0.51, 95%CI = (0.22, 0.80)]. Serum folate and vitamin B12 did not differ between MA and MO. CONCLUSIONS: Our results suggest that there is a possible link between migraine, mainly MA, and elevated serum Hcy.

Relationship between Vitamin Deficiencies and Co-Occurring Symptoms in Autism Spectrum Disorder.

Recently, connections have been made between feeding and eating problems and autism spectrum disorder (ASD) and between autism pathophysiology and diet issues. These could explain some of the mechanisms which have not yet been discovered or are not sufficiently characterized. Moreover, there is an increased awareness for micronutrients in ASD due to the presence of gastrointestinal (GI) problems that can be related to feeding issues. For example, levels of vitamins B1, B6, B12, A and D are often reported to be low in ASD children. Thus, in the present mini review we focused on describing the impact of some vitamins deficiencies and their relevance in ASD patients.

Homocysteine, Pyridoxine, Folate and Vitamin B12 Levels in Children with Attention Deficit Hyperactivity Disorder.

BACKGROUND: In our study, we aimed to evaluate the serum homocysteine levels, pyridoxine, folate and vitamin B12 levels in children with attention deficit hyperactivity disorders (ADHD). SUBJECTS AND METHODS: This study included 30 newly diagnosed drug-naive children with ADHD (23 males and 7 female, mean age 9.3±1.8 years) and 30 sex-and age matched healthy controls. The diagnosis of ADHD was made according to DSM-V criteria. Children and adolescents were administered the Schedule for Affective Disorders and Schizophrenia for School Aged Children, Present and Lifetime Version, the Conners' Parent Rating Scale-Revised, Long Form, the Conners' Teacher Rating Scale and the Wechsler Intelligence Scale for Children Revised (WISC-R) for all participants. Homocysteine, pyridoxine, folate and vitamin B12 levels were measured with enzyme-linked immunosorbent assay. RESULTS: Homocysteine, pyridoxine, folate and vitamin B12 levels were significantly lower in children with ADHD compared with their controls (p<0.05). A positive significant correlation was observed between the all WISC-R scores and vitamin B12 level in patients (r=0.408, p=0.025). CONCLUSIONS: The results obtained in this study showed that reduced homocysteine, pyridoxine, folate and vitamin B12 levels could be a risk factor in the etiology of ADHD.

Vitamin B6 is essential for serine de novo biosynthesis.

Pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug-resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6-deprived Neuro-2a cells. Significant alterations were observed in a range of metabolites. The most surprising observation was a decrease of serine and glycine, two amino acids that are known to be elevated in the plasma of vitamin B6 deficient patients. To investigate the cause of the low concentrations of serine and glycine, a metabolic flux analysis on serine biosynthesis was performed. The metabolic flux results showed that the de novo synthesis of serine was significantly reduced in vitamin B6-deprived cells. In addition, formation of glycine and 5-methyltetrahydrofolate was decreased. Thus, vitamin B6 is essential for serine de novo biosynthesis in neuronal cells, and serine de novo synthesis is critical to maintain intracellular serine and glycine. These findings suggest that serine and glycine concentrations in brain may be deficient in patients with vitamin B6 responsive epilepsy. The low intracellular 5-mTHF concentrations observed in vitro may explain the favourable but so far unexplained response of some patients with pyridoxine-dependent epilepsy to folinic acid supplementation.

The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies.

BACKGROUND: Recent decades have unravelled the molecular background of a number of inborn errors of metabolism (IEM) causing vitamin B6-dependent epilepsy. As these defects interfere with vitamin B6 metabolism by different mechanisms, the plasma vitamin B6 profile can give important clues for further molecular work-up. This has so far been investigated in only a small number of patients. METHODS: We evaluated the vitamin B6 vitamers pyridoxal 5'-phosphate (PLP), pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN) and the catabolite pyridoxic acid (PA) in the so far largest patient cohort: reference (n = 50); pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency (n = 6); antiquitin (ATQ) deficiency (n = 21); tissue non-specific alkaline phosphatase (TNSALP) deficiency (n = 2) and epileptic encephalopathy (EE) of unknown etiology tested negative for ATQ and PNPO deficiency (n = 64). RESULTS: High plasma PM concentration was found in all patients with PNPO deficiency irrespective of vitamin B6 supplementation. Their PM concentration and the PM/PA ratio was significantly higher (p < 0.0001), compared to any other patients analysed. One patient with TNSALP deficiency and sampling prior to PN supplementation had markedly elevated plasma PLP concentration. On PN supplementation, patients with TNSALP deficiency, ATQ deficiency and patients of the EE cohort had similar plasma vitamin B6 profiles that merely reflect the intake of supra-physiological doses of vitamin B6. The interval of sampling to the last PN intake strongly affected the plasma concentrations of PN, PL and PA. CONCLUSIONS: PM concentrations and the PM/PA ratio clearly separated PNPO-deficient patients from the other cohorts. The plasma PM/PA ratio thus represents a robust biomarker for the selective screening of PNPO deficiency.

Pyridoxine deficiency in adult patients with status epilepticus.

An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 µg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels.

Plasma total homocysteine level in association with folate, pyridoxine, and cobalamin status among Iranian primary breast cancer patients.

Recently the elevated plasma total homocysteine (tHcy) concentration has been concerned as the secondary feature of tumoral proliferation and enhances the likelihood of thrombogenesis in cancer patients. The objective of this study was to determine the associations between folate, cobalamin, and pyridoxine with fasting plasma tHcy concentration in breast cancer (BC) patients. The intake levels of nutrients were assessed using a validated food frequency questionnaire in 141 newly diagnosed BC patients. The plasma tHcy and pyridoxal-5-phosphate were measured using high performance liquid chromatography with fluorescence detector. Plasma tHcy levels were observed to be significantly higher among BC participants with Stage III where the plasma concentrations of folate was also comparatively less (P < 0.05) than other stages. Dietary pyridoxine was even being consumed less at this stage (P < 0.05). The plasma, dietary, and residual variables of folate were inversely correlated with plasma tHcy concentration (P < 0.05). Dietary cobalamin was also associated negatively with tHcy (P < 0.05). The odds ratio of comparing the highest tertile of plasma cobalamin (>394 pmol/l) and folate (>11.4 ng/ml) vs. the lowest categories were associated with reduced odds of high tHcy occurrence with 0.20 (95% confidence interval: 0.04-0.98) and 0.14 (95% confidence interval: 0.03-0.64), respectively. In conclusion, nutrition-related methyl-group insufficiency could lead to imbalance in tHcy metabolism, as a possible cancer marker.

Measurement of plasma B6 vitamer profiles in children with inborn errors of vitamin B6 metabolism using an LC-MS/MS method.

Vitamin B(6) dependent seizure disorders are an important and treatable cause of childhood epilepsy. The molecular and biochemical basis for some of these disorders has only recently been elucidated and it is likely that inborn errors affecting other parts of this complex metabolic pathway are yet to be described. In man vitamin B(6) ingested from the diet exists as six different vitamers, pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), pyridoxal 5'-phosphate (PLP), pyridoxamine 5'- phosphate (PMP) and pyridoxine 5'-phosphate (PNP). Its breakdown product, 4-pyridoxic acid (PA), is excreted in urine. Here we describe an analytical LC-MS/MS method to measure all vitameric B(6) forms in plasma and have subsequently applied this methodology to investigate children with vitamin B(6) responsive seizure disorders. We show that patients with inborn errors of B(6) metabolism such as pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency have characteristic B(6) profiles which allow them to be differentiated from each other and control populations, even when on treatment with B(6). Regardless of diagnosis, patients on treatment doses of pyridoxine hydrochloride and pyridoxal phosphate have markedly elevated levels of some vitameric forms (PLP, PL and PA). Such mega doses of B(6) treatment are known to be associated with neurotoxicity. This LC-MS/MS method will be a useful tool for treatment monitoring and may help further our understanding of mechanisms of neurotoxicity in patient groups.

Vitamin B6 and the immunity in kidney transplant recipients.

OBJECTIVE: The study aimed to determine vitamin B6 status in elderly (age ≥ 60 years) and younger (age <60 years) recipients of allogeneic kidney graft and to investigate associations between vitamin B6 status and immunity markers. DESIGN: A retrospective observational study. SETTING: The study was conducted at the Medical University of Gdansk, Poland. SUBJECTS: We recruited 34 kidney allograft recipients (17 males and 17 females) and allocated them into 2 groups: patients aged ≥ 60 years (18 patients) and those aged <60 years (16 patients). Exclusion criteria included patients receiving vitamin B6 supplementation or drugs known to influence vitamin B6 metabolism. MAIN OUTCOME MEASURE: Plasma levels of pyridoxal 5'-phosphate (PLP), pyridoxal, pyridoxine, pyridoxamine, pyridoxamine 5'-phosphate, and 4 pyridoxic acid were determined by high-performance liquid chromatography. Measured immunity markers were serum cytokines (interleukin-6, interleukin-10, and transforming growth factor-ß), levels of T-lymphocyte subsets, and the proliferative ability of peripheral blood mononuclear cells. RESULTS: Concentrations of all vitamin B6 vitamers in plasma (PLP, pyridoxal, pyridoxamine 5'-phosphate, pyridoxamine, pyridoxine, 4 pyridoxic acid) were comparable in the 2 studied groups. There were no cases of PLP deficiency in the study population, but 29% of patients had PLP concentrations more than the upper reference limit. Vitamin B6 vitamer concentrations were not influenced by gender, estimated glomerular filtration rate, and circulating phosphate concentration. There was no difference in immunity markers according to age. However, the plasma concentrations of vitamin B6 vitamers were inversely associated with levels of CD28(+) lymphocyte subsets, as well as with the proliferative response of peripheral blood mononuclear cells in both groups. CONCLUSIONS: No cases of vitamin B6 deficiency were found among kidney allograft recipients, and we report inverse links between vitamin B6 vitamer concentrations and markers of cellular immunity, suggesting that bioactive vitamin B6 concentration in kidney allograft recipients merits further investigation.

Vitamin B6: deficiency diseases and methods of analysis.

Vitamin B6 (pyridoxine) is closely associated with the functions of the nervous, immune and endocrine systems. It also participates in the metabolic processes of proteins, lipids and carbohydrates. Pyridoxine deficiency may result in neurological disorders including convulsions and epileptic encephalopathy and may lead to infant abnormalities. The Intravenous administration of pyridoxine to patients results in a dramatic cessation of seizures. A number of analytical methods were developed for the determination of pyridoxine in different dosage forms, food materials and biological fluids. These include UV spectrometric, spectrofluorimetric, mass spectrometric, thin-layer and high-performance liquid chromatographic, electrophoretic, electrochemical and enzymatic methods. Most of these methods are capable of determining pyridoxine in the presence of other vitamins and complex systems in µg quantities. The development and applications of these methods in pharmaceutical and clinical analysis mostly during the last decade have been reviewed.

Alterations of homocysteine serum levels during alcohol withdrawal are influenced by folate and riboflavin: results from the German Investigation on Neurobiology in Alcoholism (GINA).

AIMS: Various studies have shown that plasma homocysteine (HCY) serum levels are elevated in actively drinking alcohol-dependent patients a during alcohol withdrawal, while rapidly declining during abstinence. Hyperhomocysteinemia has been associated not only with blood alcohol concentration (BAC), but also with deficiency of different B-vitamins, particularly folate, pyridoxine and cobalamin. METHODS: Our study included 168 inpatients (110 men, 58 women) after admission for detoxification treatment. BAC, folate, cobalamin, pyridoxine, thiamine and riboflavin were obtained on admission (Day 1). HCY was assessed on Days 1, 7 and 11. RESULTS: HCY levels significantly declined during withdrawal. General linear models and linear regression analysis showed an influence of BAC, folate and riboflavin on the HCY levels on admission as well as on HCY changes occurring during alcohol withdrawal. No significant influence was found for thiamine, cobalamin and pyridoxine. CONCLUSIONS: These findings show that not only BAC and plasma folate levels, but also plasma levels of riboflavin influence HCY plasma levels in alcohol-dependent patients.

Vitamin B-6 vitamer levels in plasma and related symptoms in hemodialysis subjects taking low- and high-dose renal multivitamin supplements.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Plasma PLP levels and symptoms related to B-6 in HD subjects are impacted by dose of PN-HCl.

Systemic bioavailability and pharmacokinetics of the doxylamine-pyridoxine delayed-release combination (Diclectin).

BACKGROUND: Diclectin, composed of 10 mg doxylamine succinate (DOX) and 10 mg pyridoxine hydrochloride, is the drug combination of choice for the management of nausea and vomiting during pregnancy in Canada. However, there is large variability in its onset and duration of action among women. To understand and improve its effectiveness, the variability in the pharmacokinetics of the ingredients in this doxylamine succinate/pyridoxine hydrochloride combination must be studied. OBJECTIVES: To determine the pharmacokinetics of DOX and pyridoxine after oral administration of two tablets of this drug combination in the form of Diclectin and to calculate their respective relative bioavailability by comparison with intravenous administration in another population. METHODS: Eighteen nonpregnant, nonlactating, healthy females between 18 and 45 years of age were administered two tablets of Diclectin with 240 mL of water under empty stomach conditions. Blood samples were analyzed for DOX and pyridoxine along with its four active metabolites: pyridoxal, pyridoxal-5'-phosphate (PLP), pyridoxamine, and pyridoxamine-5'-phosphate using tandem mass spectrometry. For the purpose of this study, pharmacokinetic values for DOX and PLP were adjusted for body weight. RESULTS: The mean DOX-AUC0→∞ was calculated to be 3137.22 ± 633.57 ng·hr/mL (range, 2056.59-4376.06 ng·hr/mL). The mean PLP-AUC0→∞ was calculated to be 5513.10 ± 2362.35 ng·hr/mL (range, 1572.56-10,153.77 ng·hr/mL). Based on literature values of the PLP-AUC0→∞ after intravenous administration and data from the current study, the relative bioavailability of pyridoxine in Diclectin was calculated at 100%. CONCLUSION: There was a 2.1-fold variability in the DOX-AUC0→∞ and 6.5-fold variability in the PLP-AUC0→∞ after oral administration of 20 mg Diclectin. Using literature values and data from the current study, we estimated the oral bioavailability of pyridoxine to be 100%. Therefore, interindividual differences in metabolism, and not in bioavailability, may be important sources of variability that need to be addressed in dosing guidelines.

Evaluation of Serum Thiamine and Pyridoxine Levels in Patients Undergoing Liver Transplant: A Prospective Study.

OBJECTIVES: This prospective study aimed to compare changes in serum thiamine and pyridoxine levels of patients who underwent liver transplant or living donor hepatectomy. MATERIALS AND METHODS: Between January 2013 and November 2013, 35 patients with chronic liver disease who underwent liver transplant (the recipient group) and 30 healthy individuals who underwent living donor hepatectomy (the control group) during the same period were prospectively compared in terms of both preoperative and postoperative serum thiamine and pyridoxine levels. The groups were also subjected to intragroup analysis of preoperative and postoperative changes in serum vitamin levels to determine how a major surgical procedure affected serum vitamin levels. Mann-Whitney U test and Wilcoxon signed-rank test were used for intergroup comparisons and intragroup repeated measurements, respectively. RESULTS: The intergroup comparisons revealed significant differences in favor of the control group with respect to preoperative thiamine (P < .026) and postoperative thiamine (P < .017) levels, whereas there were statistically significant differences in favor of the recipient group with respect to the preoperative pyridoxine (P < .006) and postoperative pyridoxine (P < .001) levels. The intragroup comparisons showed significant increases in serum thiamine (P < .001) and pyridoxine (P < .031) levels compared with the preoperative serum levels of both vitamins at postoperative day 5 in the recipient group. In the control group, serum thiamine level (P < .001) at postoperative day 5 was significantly different from the preoperative level. On the other hand, a drop in serum pyridoxine level was detected at postoperative day 5, although this was not statistically significant (P < .21). CONCLUSIONS: This study showed a lower serum thiamine level but a higher serum pyridoxine level in patients with chronic liver disease versus healthy controls. This difference persisted into the early postoperative period. This study also showed significant increases in thiamine and pyridoxine levels after transplant surgery.

Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine.

BACKGROUND AND AIMS: Vitamin B6 is involved in a large spectrum of physiological processes and comprises of the vitamers pyridoxamine (PM), pyridoxal (PL), pyridoxine (PN), and their phosphorylated derivatives including the biological active pyridoxal 5'-phosphate (PLP). While PN toxicity is known to complicate several treatments, PM has shown promise in relation to the treatment of metabolic and age-related diseases by blocking oxidative degradation and scavenging toxic dicarbonyl compounds and reactive oxygen species. We aimed to assess the metabolization of oral PM supplements in a single and three daily dose. MATERIALS AND METHODS: We optimized and validated a method for the quantification of the B6 vitamers in plasma and urine using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five healthy volunteers were recruited to study PM metabolization after a single oral dose of 200 mg PM or a three daily dose of 67 mg PM. A third protocol was implemented as control for dietary intake. Venous blood samples, 24 h urine and fasted second void urine samples were collected. RESULTS: After a single oral dose of 200 mg PM, plasma PM increased in the first 3 h to a maximum of 2324 ± 266 nmol/L. While plasma PM levels returned to baseline after ~10 h of PM intake, PLP increased to a maximum of 2787 ± 329 nmol/L and reached a plateau. We found a small increase of PN to a maximum of 13.5 ± 2.1 nmol/L; it was nearly undetectable after ~12 h. With a three daily dose of 67 mg PM we observed an increase and decline of plasma PM, PL, and PN concentrations after each PM intake. PLP showed a similar increase as in the single dose protocol and accumulated over time. CONCLUSION: In this study we showed high plasma levels of PM after oral PM supplementation. We found steadily increasing levels of the biologically active PLP, with minimal formation of PN. The B6 vitamer PM is an interesting supplement as an inhibitor of harmful processes in metabolic diseases and for the treatment of vitamin B6 deficiency. CLINICAL TRIAL REGISTRY: The study was approved by the Medical Ethics Committee of Maastricht University (NL) and was registered at ClinicalTrials.gov as NCT02954588.

Isolated Pyridoxine Deficiency Presenting as Muscle Spasms in a Patient With Type 2 Diabetes: A Case Report and Literature Review.

Pyridoxine is an important co-factor for many biochemical reactions in cellular metabolism related to the synthesis and catabolism of amino acids, fatty acids, neurotransmitters. Deficiency of pyridoxine results in impaired transcellular signaling between neurons and presents with muscular convulsions, hyperirritability, and peripheral neuropathy. Deficiency of pyridoxine is usually found in association with other vitamin B deficiencies such as folate (vitamin B9) and cobalamin (vitamin B12). Isolated pyridoxine deficiency is extremely rare. We present the case of a 59-year old female with type 2 diabetes who complained of painful muscle spasms. Her muscle spasms involved in both feet, which have spread proximally to her legs. She also experienced intermittent muscle spasms in her left arm, which is not alleviated by baclofen, cyclobenzaprine. Her plasma pyridoxal 5-phosphate confirmed pyridoxine deficiency. Vitamins B1, B3, B12, and folate were within normal limits. The patient received standard-dose intramuscular pyridoxine injections for three weeks followed by oral supplements for 3 months and her symptoms resolved. This case illustrates the rare instance of isolated pyridoxine deficiency in type 2 diabetes patient manifesting as myoclonic muscle spasms involving the legs and arms in the absence of objective polyneuropathy. Pyridoxine level should, therefore, be assessed in patients with type 2 diabetes, including newly diagnosed patients.

An Adult Case of Generalized Convulsions Caused by the Ingestion of Ginkgo biloba Seeds with Alcohol.

A 64-year-old woman developed symptoms of vomiting and tonic-clonic convulsions 9.5 h after eating 50 roasted Ginkgo biloba seeds with 100 g of alcohol. The intravenous administration of pyridoxal phosphate effectively improved the symptoms. Blood samples were collected and stored over 35 h. The assessment of 4'-O-methylpyridoxine and vitamin B6 vitamers indicated high levels of both, but the pyridoxal phosphate levels were low during the acute stage. These results suggest that 4'-O-methylpyridoxine inhibits the transformation of vitamin B6 analogues to the active form, pyridoxal phosphate. In our case, alcohol may have extended the period until ginkgo intoxication appeared.

The implications of vitamin content in the plasma in reference to the parameters of carbohydrate metabolism and hormone and lipid profiles in PCOS.

So far, there have been no analyses of correlations between the level of water-soluble vitamins in women with polycystic ovary syndrome (PCOS) and hormone and lipid profiles as well as carbohydrate metabolism. The unpopular concept that PCOS may also be conditioned by a chronic infection leads to a suspicion that water-soluble vitamins may be involved in the struggle against PCOS. This is why the aim of this research was to determine whether there are any indications that could confirm this hypothesis. The study included 64 women of Caucasian race: 50 patients aged 29.52 ±â€¯7.01 years with PCOS, diagnosed according to the Rotterdam criteria. The control group consisted of 14 women aged 30.23 ±â€¯6.3 years with correct BMI. HPLC Infinity1260 Binary LC (Agilent Technologies, Waldbronn, Germany) was used to analyze nine vitamins. The vitamins were separated using the gradient method, a buffer of 25 mM HK2PO4 with pH equal to 7.0, and 100 % methanol buffer. The acquired results were compared using Statistica 12.0 (Statsoft, Tulsa, Oklahoma, USA). Non-parametric tests were used: Mann-Whitney tests for comparisons between groups (PCOS and control group, CG), in which p < 0.05 was considered statistically significant. Subsequently, we performed a correlation matrix of the biochemical parameters of blood with vitamins at p ≤ 0.05. Higher concentrations of ascorbic acid were observed in PCOS. The content of the remaining vitamins was higher in the control group, and the statistical differences were significant in reference to thiamine, riboflavin, pyridoxine and folic acid in comparison to the control group. A significant positive correlation was observed between vitamin C and testosterone/insulin, another between riboflavin and androstenedione/testosterone, next between biotin and thyrotropic hormone (TSH), between pantothenic acid and dehydroepiandrosteron (DHEA-SO4), and finally between pyridoxine and androstenedione. A negative correlation was observed in the case of niacin with sex hormone binding protein (SHBG) and high density lipoprotein (HDL). Water-soluble vitamins play an important role in the therapy of women with PCOS through the reduction of antioxidative stress and low-intensity inflammation caused by various factors, including chronic infection.

B-vitamins in Relation to Depression in Older Adults Over 60 Years of Age: The Trinity Ulster Department of Agriculture (TUDA) Cohort Study.

OBJECTIVES: Mental health disorders are major contributors to disease burden in older people. Deficient status of folate and the metabolically related B vitamins may be implicated in these conditions. This study aimed to investigate folate, vitamin B12, vitamin B6, and riboflavin in relation to depression and anxiety in aging and also considered the role of fortified foods as a means of optimizing B-vitamin status and potentially reducing the risk of these mental health disorders. DESIGN: The Trinity Ulster Department of Agriculture (TUDA) aging study was a cross-sectional cohort study. SETTING AND PARTICIPANTS: Community-dwelling adults (n = 5186; ≥60 years) recruited from 2 jurisdictions within the island of Ireland from 2008 to 2012. MEASURES: Depression and anxiety were assessed using the Centre for Epidemiological Studies Depression (CES-D) and the Hospital Anxiety and Depression (HAD) scales, respectively. The following B-vitamin biomarkers were measured: red blood cell folate, serum total vitamin B12, plasma pyridoxal-5-phosphate (PLP; vitamin B6), and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin). RESULTS: Biomarker values in the lowest 20% of status for folate (odds ratio [OR] 1.79; 95% CI 1.23-2.61), vitamin B6 (OR 1.45, 95% CI 1.01-2.06), or riboflavin (OR 1.56, 95% CI 1.10-2.00), but not vitamin B12, were each associated with an increased risk of depression (CES-D score ≥16). Correspondingly, B vitamin-fortified foods if consumed daily were associated with a reduced risk of depression (OR 0.54, 95% CI 0.41-0.70). A deficient status of vitamin B6 (OR 1.73, 95% CI 1.07-2.81), but not other vitamins, was associated with increased anxiety. CONCLUSIONS/IMPLICATIONS: Better B-vitamin status may have a role in impacting positively on mental health in older adults. Regular intake of fortified foods can provide a means of optimizing B-vitamin status and thus could contribute to reducing depression. If confirmed by a randomized trial, these results may have implications for nutrition and mental health policy, and thus quality of life, in older people.