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.

4-Pyridoxic Acid in the Spent Dialysate: Contribution to Fluorescence and Optical Monitoring.

AIM: In this work we estimated the contribution of the fluorescence of 4-pyridoxic acid (4-PA) to the total fluorescence of spent dialysate with the aim of evaluating the on-line monitoring of removal of this vitamin B-6 metabolite from the blood of patients with end-stage renal disease (ESRD). METHODS: Spectrofluorometric analysis of spent dialysate, collected from hemodialysis and hemodiafiltration sessions of 10 patients receiving regularly pyridoxine injections after dialysis treatment, was performed in the range of Ex/Em 220-500 nm. 4-PA in dialysate samples was identified and quantified using HPLC with fluorescent and MS/MS detection. RESULTS: Averaged HPLC chromatogram of spent dialysate had many peaks in the wavelength region of Ex320/Em430 nm where 4-PA was the highest peak with contribution of 42.2±17.0% at the beginning and 47.7±18.0% in the end of the dialysis. High correlation (R = 0.88-0.95) between 4-PA concentration and fluorescence intensity of spent dialysate was found in the region of Ex310-330/Em415-500 nm, respectively. CONCLUSION: 4-PA elimination from the blood of ESRD patients can be potentially followed using monitoring of the fluorescence of the spent dialysate during dialysis treatments.

Vitamin B6 deficiency and diseases in elderly people--a study in nursing homes.

BACKGROUND: Vitamin deficiency is a cause of health related problems in elderly people. The aims were to study associations between vitamin B6 (B6) and diseases (primarily functional gastrointestinal disorders) in elderly people in nursing homes, the prevalence of B6 deficiency and factors associated with B6 deficiency. METHODS: This cross-sectional study included residents in nursing homes. Demographics, nutritional status (Mini Nutritional Assessment, MNA®), physical activity, activity of daily living (Katz Index), dietary habits, use of drugs, and psychiatric and somatic diseases were recorded. A blood sample was collected for haematological and biochemical screening, including B6 (p-PLP); p-PLP values < 20 nmol/l indicates B6 deficiency. The results are given as mean (SD). RESULTS: Sixty-one residents (men/women: 22/39) with an age of 85.3 (6.8) years and BMI 25.7 (4.5) kg/m2 were included. Malnutrition and risk of malnutrition were present in 11.5% and 61% respectively. Dietary intake of B6 (mg/day) in men and women were 1.60 (0.30) and 1.18 (0.31) (recommended 1.6 and 1.2 respectively), and 14 (23%) used B6 supplements. Median p-PLP was 20.7 (range <4.0-175.8), 30 subjects (49%) had B6 deficiency. B6 deficiency was associated with old age, low s-alanine aminotransferase and s-albumin, elevated s-homocysteine and inactivity (p-values 0.01-0.03). There were no clinically significant associations between B6 deficiency and somatic or psychiatric disorders, and B6 deficiency was not observed in subjects given B6 supplements. CONCLUSIONS: Half of the residents had vitamin B6 deficiency. Vitamin supplement was effective prophylaxis for deficiency and should be recommended to all elderly people in nursing homes.

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

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

Vitamin B6 status, deficiency and its consequences - an overview / Estado de vitamina B6, deficiencia y sus consecuencias — una revisión

Background: Vitamin B6 is thought to be a most versatile coenzyme that participates in more than 100 biochemical reactions. It is involved in amino acid and homocysteine metabolism, glucose and lipid metabolism, neurotransmitter production and DNA/RNA synthesis. Vitamin B6 can also be a modulator of gene expression. Nowadays, clinically evident vitamin B6 deficiency is not a common disorder, at least in the general population. Nevertheless, a subclinical, undiagnosed deficiency may be present in some subjects, particularly in the elderly.Objective: This review gives a complete overview over the metabolism and interactions of vitamin B6. Further, we show which complications and deficiency symptoms can occur due to a lack of vitamin B6 and possibilities for public health and supplemental interventions. Methods: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "vitamin B6", "pyridoxal", "cancer", "homocysteine", etc. For a complete understanding, we included studies with early findings from the forties as well as recent results from 2006. These studies were summarised and compared in different chapters. Result and conclusion: In fact, it has been proposed that suboptimal vitamin B6 status is associated with certain diseases that particularly afflict the elderly population: impaired cognitive function, Alzheimer's disease, cardiovascular disease, and different types of cancer. Some of these problems may be related to the elevated homocysteine concentrations associated to vitamin B6 deficiency, but there is also evidence for other mechanisms independent of homocysteine by which a suboptimal vitamin B6 status could increase the risk for these chronic diseases (AU)

Antecedentes: se piensa que la vitamina B6 es la coenzima más versátil que participa en más de 100 reacciones bioquímicas. Está implicada en el metabolismo de los aminoácidos y de la homocisteína, el metabolismo de la glucosa y los lípidos, en la producción de neurotransmisores y en la síntesis de ADN/ARN. Esta vitamina también puede ser un modulador de la expresión génica. Hoy en día, la deficiencia clínicamente evidente de vitamina B6 no es una afección habitual, al menos en la población general. Sin embargo, puede ocurrir una deficiencia subclínica no diagnosticada en algunos individuos, especialmente en los ancianos. Objetivo: esta revisión aporta una visión de conjunto completa sobre el metabolismo y las interacciones de la vitamina B6. Además, mostramos qué complicaciones y síntomas por deficiencia pueden ocurrir por la falta de vitamina B6 y las posibilidades de intervenciones de salud pública y de suplementos. Métodos: se buscó en la base de datos Medline (www.ncvi.nlm.nih.gov) con los términos "vitamin B6", "pyridoxal", "cancer", "homocysteine", etc. Para una mayor comprensión, incluimos estudios con hallazgos iniciales de los años cuarenta, así como estudios recientes del año 2006. Se resumieron estos estudios y se compararon por capítulos diferentes. Resultados y Conclusión: de hecho, se ha propuesto que el estado sub-óptimo de vitamina B6 se asocia con ciertas enfermedades que afligen en especial a la población anciana: función cognitiva alterada, enfermedad de Alzheimer, cardiopatía y distintos tipos de cáncer. Algunos de estos problemas podrían relacionarse con concentraciones elevadas de homocisteína asociadas con una deficiencia de vitamina B6, pero también existe la evidencia de otros mecanismos independientes de la homocisteína por los que un estado sub-óptimo de vitamina B6 podría aumentar el riesgo de padecer estas enfermedades crónicas (AU)

Vitamin B6 status, deficiency and its consequences--an overview.

BACKGROUND: Vitamin B6 is thought to be a most versatile coenzyme that participates in more than 100 biochemical reactions. It is involved in amino acid and homocysteine metabolism, glucose and lipid metabolism, neurotransmitter production and DNA/RNA synthesis. Vitamin B6 can also be a modulator of gene expression. Nowadays, clinically evident vitamin B6 deficiency is not a common disorder, at least in the general population. Nevertheless, a subclinical, undiagnosed deficiency may be present in some subjects, particularly in the elderly. OBJECTIVE: This review gives a complete overview over the metabolism and interactions of vitamin B6. Further, we show which complications and deficiency symptoms can occur due to a lack of vitamin B6 and possibilities for public health and supplemental interventions. METHODS: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "vitamin B6", "pyridoxal", "cancer", "homocysteine", etc. For a complete understanding, we included studies with early findings from the forties as well as recent results from 2006. These studies were summarised and compared in different chapters. RESULTS AND CONCLUSION: In fact, it has been proposed that suboptimal vitamin B6 status is associated with certain diseases that particularly afflict the elderly population: impaired cognitive function, Alzheimer's disease, cardiovascular disease, and different types of cancer. Some of these problems may be related to the elevated homocysteine concentrations associated to vitamin B6 deficiency, but there is also evidence for other mechanisms independent of homocysteine by which a suboptimal vitamin B6 status could increase the risk for these chronic diseases.

The effect of vitamin B6 on cognition.

BACKGROUND: Micronutrient status can affect cognitive function at all ages. Vitamin deficiencies could influence memory function and might contribute to age-associated cognitive impairment and dementia. Vitamin B6, comprising three chemically distinct compounds pyridoxal, pyridoxamine, and pyridoxine, is involved in the regulation of mental function and mood. Vitamin B6 is also an essential homocysteine re-methylation cofactor, and deficiency is associated with increase in blood homocysteine levels. Homocysteine is a risk factor for cerebrovascular disease and may also have directly toxic effects on neurons of the central nervous system. Neuropsychiatric disorders including seizures, migraine, chronic pain and depression have been linked to vitamin B6 deficiency. Epidemiological studies indicate that poor vitamin B6 status is common among older people. Hyperhomocysteinaemia has been suggested as a cause or mechanism in the development Alzheimer's disease and other forms of dementia. Supplementation with B vitamins including vitamin B6 has been shown to reduce blood homocysteine levels. OBJECTIVES: To assess the efficacy of vitamin B6 supplementation in reducing the risk of developing cognitive impairment by older healthy people, or improving cognitive functioning of people with cognitive decline and dementia, whether or not vitamin B6 deficiency has been diagnosed. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 20 May 2003 using the terms: vitamin B6, pyridoxine, pyridoxamine, pyridoxal. For relevant trials on healthy elderly people MEDLINE, EMBASE and CENTRAL were searched using the previously mentioned terms as well as the term cognit * SELECTION CRITERIA: All unconfounded, double-blind randomized controlled trials in which the intervention with vitamin B6 was compared with placebo for healthy older people or people with cognitive decline or dementia. The primary outcome of interest was the efficacy of vitamin B6 supplementation on cognitive function. DATA COLLECTION AND ANALYSIS: The two reviewers independently evaluated all studies identified as possibly meeting the criteria for inclusion. One reviewer independently extracted the data. Studies were rated for their overall quality. The weighted mean differences between treatment and placebo groups, with 95% confidence intervals, were calculated for each outcome. Review Manager version 4.2 was used to analyse the variance. MAIN RESULTS: No trials of vitamin B6 involving people with cognitive impairment or dementia were found. The two trials included in the review (Bryan 2002; Deijen 1992) used a double-blind, randomized, placebo-controlled design and involved 109 healthy older people. One trial restricted enrolment to women and the other to men. Vitamin B6 supplementation and healthy older women: Bryan 2002 enrolled 211 healthy women from various age groups into a 5-week study. The trial was of multifactorial design with folic acid, vitamin B12, vitamin B6 and placebo in its four arms. Twelve healthy women aged 65 to 92 years received 75 mg vitamin B6 orally per day and were compared with 21 healthy women who were allocated to placebo. No statistically significant benefits from vitamin B6 on mood or cognition were observed. Vitamin B6 supplementation and healthy older men: Deijen 1992 recruited 76 healthy men aged 70 to 79 years. They were divided into 38 matched pairs, one member of each pair randomly allocated to 20 mg of vitamin B6 (pyridoxine hydrochloride) per day for 12 weeks the other to placebo. No statistically significant differences between treatment and placebo were found in their effects on cognition or mood. Effect of vitamin B6 supplementation on vitamin B6 status: Deijen 1992 reported that 20 mg of pyridoxine hydrochloride per day for 12 weeks increased blood vitamin B6 activity as assessed as by plasma pyridoxal-5'-phosphate (WMD 238, 95%CI 211.58 to 264.42, P<0.00001) and erythrocyte enzyme asparate aminotransferase (WMD 0.43, 95%CI 0.30 to 0.56, P<0.00001). Effect of vitamin B6 supplementation on blood homocysteine concentration: Neither of the included trials measured homocysteine levels. Drop-outs: All participants allocated to vitamin B6 or placebo completed the trial protocol. Adverse Events: No adverse effects were reported. Effect of vitamin B6 on carer burden, care costs and institutionalization rate: We found no trials in which these outcomes were assessed. REVIEWER'S CONCLUSIONS: This review found no evidence for short-term benefit from vitamin B6 in improving mood (depression, fatigue and tension symptoms) or cognitive functions. For the older people included in one of the two trials included in the review, oral vitamin B6 supplements improved biochemical indices of vitamin B6 status, but potential effects on blood homocysteine levels were not assessed in either study. This review found evidence that there is scope for increasing some biochemical indices of vitamin B6 status among older people. More randomized controlled trials are needed to explore possible benefits from vitamin B6 supplementation for healthy older people and those with cognitively impairment or dementia.

Vitamin B6 deficiency in elderly patients on chronic peritoneal dialysis.

Polyneuropathy is one of the most frequent manifestations in chronic uremia. Among the factors related to polyneuropathy, vitamin B6 deficiency is well known. The exact prevalence of vitamin B6 deficiency related to neurological manifestations has not been previously reported. We studied vitamin B6 status, collected self-reported symptoms, and carried out full neurological examinations in 66 patients on chronic peritoneal dialysis. Vitamin B6 status was estimated by direct measurement of pyridoxal phosphate. In general, symptoms related to vitamin B6 deficiency are peripheral neuropathies, such as paresthesia, burning and painful dysesthesias, and thermal sensations. These symptoms were reported and assigned one of five grade scores. Of our 66 patients, 12 patients complained at least one sensory abnormality. The levels of vitamin B6 in the patients varied between 1.0 ng/mL and 30 ng/mL. Patients who complained of neurological symptoms owing to vitamin B6 deficiency were significantly older than the other patients. In analyzing the symptomatic cases before and after vitamin B6 supplementation, a significant correlation was seen between the level of vitamin B6 and symptoms. Within one month after initiation of oral vitamin B6 supplementations (30 mg daily), levels of pyridoxal phosphate rose, and sensory abnormalities improved in 8 of 12 patients. When peripheral neuropathy is suspected in elderly patients on chronic peritoneal dialysis, vitamin B6 deficiency should be taken into consideration as the cause. If vitamin B6 deficiency is appropriately treated by oral supplementation, sensory abnormalities can be eliminated.

B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse.

Alcohol misuse and alcohol withdrawal are associated with a variety of neuropsychiatric syndromes, some of which are associated with significant morbidity and mortality. B vitamin deficiency is known to contribute to the aetiology of a number of these syndromes, and B vitamin supplementation thus plays a significant part in prophylaxis and treatment. In particular, the Wernicke Korsakoff syndrome (WKS). due to thiamine deficiency, is a common condition in association with alcohol misuse, and is associated with high morbidity and mortality. Nicotinamide deficiency may result in a rarer condition, alcoholic pellagra encephalopathy, which often has a similar clinical presentation to WKS. This review considers the role of B vitamins in the aetiology and treatment of neuropsychiatric syndromes associated with alcohol misuse, with particular emphasis on WKS.

Vitamin status of eating disorder patients: relationship to clinical indices and effect of treatment.

Vitamin abnormalities in eating disorder patients may contribute to altered neuropsychological status and the development of sequelae such as cognitive dysfunction. We examined the relationship between vitamin status and clinical indices in 13 low-weight patients with anorexia or bulimia nervosa at admission to a treatment program. Vitamin status was evaluated again at discharge (2-6 weeks later) in nine of these patients. Four patients (31%) initially had erythrocyte enzyme activity indices suggesting deficiency for riboflavin and for vitamin B-6. Patients with biochemical evidence for riboflavin deficiency had lower relative body weight than those with normal riboflavin status (p < .02). Three patients (23%) had elevated plasma cholesterol concentrations (> 5.69 mmol/L). Plasma retinol concentrations were within the normal range. Plasma alpha-tocopherol concentrations were positively associated with serum albumin (p < .04), cholesterol (p < .0003), and total lipids (p < .0003), and were inversely associated with body mass index (p < .04). At discharge, thiamin, riboflavin and vitamin B-6 status indicators were normal in all cases examined. Suboptimal vitamin status is common in eating disorder patients but is normalized with dietary intervention and nutritional rehabilitation.