Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation.

BACKGROUND AND AIMS: We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5'-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT). METHODS: We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings. Furthermore, we included a longitudinal PSC cohort (n = 158) sampled prior to and serially after LT, and cohorts of people with inflammatory bowel disease (IBD) without PSC (n = 51) or with primary biliary cholangitis (PBC) (n = 100), as disease controls. We used Cox regression to measure the added value of PLP to predict outcomes before and after LT. RESULTS: In different cohorts, 17-38% of people with PSC had PLP levels below the biochemical definition of a vitamin B6 deficiency. The deficiency was more pronounced in PSC than in IBD without PSC and PBC. Reduced PLP was associated with dysregulation of PLP-dependent pathways. The low B6 status largely persisted after LT. Low PLP independently predicted reduced LT-free survival in both non-transplanted people with PSC and in transplant recipients with recurrent disease. CONCLUSIONS: Low vitamin B6 status with associated metabolic dysregulation is a persistent feature of PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation. IMPACT AND IMPLICATIONS: We previously found that people with PSC had reduced gut microbial potential to produce essential nutrients. Across several cohorts, we find that the majority of people with PSC are either vitamin B6 deficient or have a marginal deficiency, which remains prevalent even after liver transplantation. Low vitamin B6 levels strongly associate with reduced liver transplantation-free survival as well as deficits in biochemical pathways dependent on vitamin B6, suggesting that the deficiency has a clinical impact on the disease. The results provide a rationale for measuring vitamin B6 and to investigate whether vitamin B6 supplementation or modification of the gut microbial community can help improve outcomes for people with PSC.

[A microcytic sideroblastic anemia successfully treated with B6 vitamin]. / Une anémie microcytaire sidéroblastique carentielle traitée efficacement par de la vitamine B6.

INTRODUCTION: Sideroblastic anemia is a rare cause of microcytic anemia, which is characterized by ring sideroblasts on bone marrow aspirate. This anemia can be congenital or acquired. CASE REPORT: We report the case of an alcoholic 49-year-old man who presented with a severe microcytic sideroblastic anemia related to pyridoxine (B6 vitamin) deficiency. Acid folic deficiency was associated. The blood count normalized within one month after vitamin supplementation. CONCLUSION: Pyridoxine deficiency must be sought in sideroblastic anemia in patients at risk.

Accumulation of Liver Lipids Induced by Vitamin B6 Deficiency Was Effectively Ameliorated by Choline and, to a Lesser Extent, Betaine.

Despite previous studies suggesting that choline and betaine ameliorate lipid accumulation in rat livers, the relative effectiveness of the two nutrients is unclear. We examined the efficacy of dietary supplementation with choline or betaine in ameliorating lipid accumulation induced by vitamin B6 (B6) deficiency in the rat liver. Male Wistar rats were fed control, B6-deficient, choline-supplemented B6-deficient, betaine-supplemented B6-deficient, or both choline and betaine-supplemented B6-deficient diets (all containing 9 g of l-methionine (Met)/kg) for 35 d. Two experiments were performed, i.e., one using 17 mmol/kg diet choline bitartrate, betaine anhydrous, and the combination and another using 8.5 mmol/kg diet. Rats fed a B6-deficient diet developed lipid accumulation in the liver with a reduction of plasma lipids induced by the disruption of Met metabolism. However, the addition of 17 mmol/kg diet choline or betaine was sufficient to ameliorate the disruptions of lipid and Met metabolism. Additionally, 8.5 mmol/kg diet choline ameliorated liver lipid deposition, while the same amount of betaine had no significant effects on liver or plasma lipid profiles. Supplementation with choline resulted in a higher liver betaine than that found using the same amount of betaine alone, although the overall liver betaine content was reduced in B6-deficient rats. Our findings indicate that choline is more effective than betaine in ameliorating B6 deficiency-related disruptions in Met metabolism and liver lipid accumulation by increasing liver betaine levels.

B6 and Bleeding: A Case Report of a Novel Vitamin Toxicity.

Pyridox(am)ine-5-phosphate oxidase deficiency is an inborn error of vitamin B6 metabolism that is characterized by neonatal seizures, requiring lifelong therapy with pyridoxal-5-phosphate. We present the first case of a patient with pyridox(am)ine-5-phosphate oxidase deficiency and mild hemophilia A, whose bleeding symptoms were exacerbated by the vitamin B6 therapy essential for his epileptic disorder. This report expands the spectrum of known vitamin B6 toxicity and demonstrates a need for vigilance in monitoring for bleeding symptoms in patients requiring pyridoxine or pyridoxal-5-phosphate supplementation.

Acute nutritional axonal neuropathy.

INTRODUCTION: This study describes clinical, laboratory, and electrodiagnostic features of a severe acute axonal polyneuropathy common to patients with acute nutritional deficiency in the setting of alcoholism, bariatric surgery (BS), or anorexia. METHODS: Retrospective analysis of clinical, electrodiagnostic, and laboratory data of patients with acute axonal neuropathy. RESULTS: Thirteen patients were identified with a severe, painful, sensory or sensorimotor axonal polyneuropathy that developed over 2-12 weeks with sensory ataxia, areflexia, variable muscle weakness, poor nutritional status, and weight loss, often with prolonged vomiting and normal cerebrospinal fluid protein. Vitamin B6 was low in half and thiamine was low in all patients when obtained before supplementation. Patients improved with weight gain and vitamin supplementation, with motor greater than sensory recovery. DISCUSSION: We suggest that acute or subacute axonal neuropathy in patients with weight loss or vomiting associated with alcohol abuse, BS, or dietary deficiency is one syndrome, caused by micronutrient deficiencies. Muscle Nerve 57: 33-39, 2018.

Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess.

Pyridoxine deficiency and excess have been implicated as a cause for peripheral neuropathy. As a result, unrelated neuropathies are often treated with pyridoxine based on questionable evidence. However, neurological practitioners frequently discourage patients from taking pyridoxine in excess of 50 mg/d given concerns around the development of a toxic sensory neuronopathy. There is no systematic review to support either of the 2 practices. To address this gap in knowledge, we reviewed the available literature on neuropathy attributed to pyridoxine deficiency and excess. Based on the current limited data, it can be concluded that very low doses of daily pyridoxine are required to prevent peripheral neuropathy. There is inadequate evidence to support routine pyridoxine supplementation in patients with disorders of peripheral nervous system. Supplementation with pyridoxine at doses greater than 50 mg/d for extended duration may be harmful and should be discouraged.

Sensory polyneuropathy in human immunodeficiency virus-infected patients receiving tuberculosis treatment.

SETTING: Human immunodeficiency virus (HIV) infection and treatments for HIV infection and tuberculosis (TB) are associated with the risk of developing sensory polyneuropathy (SPN). Vitamin B6 and genetically determined slow isoniazid (INH) acetylation are believed to play key roles in the development of SPN in a TB treatment setting. OBJECTIVE: To investigate slow acetylation and risk factors for SPN in HIV-infected patients receiving TB treatment, and establish vitamin B6 status and its association with SPN. METHODS: HIV-infected in-patients were prospectively assessed after initiating TB treatment and vitamin B6 supplementation, and monthly during hospitalisation. SPN was defined as ≥1 symptom plus ≥1 sign. NAT2 genotyping predicted acetylation status, and plasma high performance liquid chromatography estimated vitamin B6 status. A survival analysis estimated hazard ratios (HRs) for SPN during TB treatment. RESULTS: Of 116 participants, 56% had SPN at study entry. Participants developed SPN at a rate of 26/100 person-months (95%CI 18-35) during TB treatment, which was independently associated with slow acetylation (HR 2.5; 95%CI 1.1-5.9), as well as black race, previous TB and extra-pulmonary/disseminated TB. Vitamin B6 status was normal, irrespective of SPN. CONCLUSIONS: Risk factors for SPN suggest a multi-factorial pathogenesis related to INH and other potential nervous system insults. SPN developed despite normal vitamin B6 status, suggesting other mechanisms of injury.

Pyridoxine and pyridoxalphosphate-dependent epilepsies.

To date we know of four inborn errors of autosomal recessive inheritance that lead to vitamin B6-dependent seizures. Among these, pyridoxine-dependent seizures due to antiquitin deficiency is by far the most common, although exact incidence data are lacking. In PNPO deficiency, samples have to be collected prior to treatment, while PDE, hyperprolinemia type II and congenital HPP can be diagnosed while on vitamin B6 supplementation. A vitamin B6 withdrawal for diagnostic purposes is nowadays only indicated in patients with a clear vitamin B6 response but normal biochemical work-up. In the presence of therapy-resistant neonatal seizures, early consideration of a vitamin B6 trial over 3 consecutive days is crucial in order to prevent irreversible brain damage. While PLP would be effective in all four disorders, pyridoxine fails to treat seizures in PNPO deficiency. As PLP is unlicensed within Europe and North America, pyridoxine is widely used as the first line drug, but if it is ineffective it should be followed by a trial with PLP, especially in neonates. As severe apnea has been described in responders, resuscitation equipment should be at hand during a first pyridoxine/PLP administration. Patients and parents have to be informed about the lifelong dependency and recurrence risks in forthcoming pregnancies.

High incidence of lipid deposition in the liver of rats fed a diet supplemented with branched-chain amino acids under vitamin B6 deficiency.

Male Wistar rats were fed four diets composed of purified 20% vitamin-free casein diet with (+) or without (-) vitamin B(6) (7.0 mg of pyridoxine HCl/kg of diet) and with (+) or without (-) branched-chain amino acids (BCAAs) of valine, leucine, and isoleucine (4.75%): B(6)(+)BCAA(-); B(6)(+)BCAA(+); B(6)(-)BCAA(-); and B(6)(-)BCAA(+) for 21 d. Among rats fed the B(6)(-)BCAA(+) diet, about a half showed lipid deposition in the liver. On the other hand, serum triacylglycerol levels in the B(6)(-)BCAA(+) group tended to be decreased. Hepatic triacylglycerol and cholesterol levels tended to increase in the B(6)(-)BCAA(+) group compared with the other three groups. Serum apolipoprotein B and apolipoprotein E (apo E) levels in the B(6)(-)BCAA(+) group were the lowest among the three groups. In contrast, hepatic apo E levels in the B(6)(-)BCAA(+) group were the highest among the three groups. High-performance liquid chromatography of pooled serum of rats with lipid deposits revealed that triacylglycerol and cholesterol levels in very low-density lipoprotein (VLDL) were decreased compared with other diet groups. These results strongly suggest that one of the mechanisms of lipid deposition in rats fed a B(6)(-)BCAA(+) diet is due to impaired secretion of VLDL.

Involvement of 5-methyltetrahydrofolate in the amelioration of hyperhomocysteinemia caused by vitamin B(6) deficiency and L-methionine supplementation.

We attempted to clarify the reason why folate fortification ameliorates hyperhomocysteinemia induced by vitamin B(6) deficiency. Hyperhomocysteinemia caused by vitamin B(6) deficiency significantly decreased the rat liver 5-methyltetrahydrofolate level which was significantly improved by folate fortification. This result suggests that the amelioration of hyperhomocysteinemia in response to folate supplementation had enhanced the removal of homocysteine via methionine synthase.

Folic acid fortification ameliorates hyperhomocysteinemia caused by a vitamin B6-deficient diet supplemented with L-methionine.

Vitamin B6 (B6) deficiency affects homocysteine metabolism, and this leads to hyperhomocysteinemia. In this study, we examined i) the effects of B6-deficiency and graduated levels of dietary methionine on homocysteine metabolism, and ii) the effects of fortified folate on homocysteine metabolism. In experiment 1, Wistar male rats were fed a control or a B6-deficient diet supplemented with L-methionine at a level of 3, 6, or 9 g/kg of diet for 5 weeks. The resulting plasma homocysteine levels in the B6-deficient groups increased in relation to the increase in dietary methionine level. Next, in experiment 2, rats were fed a control, B6-deficient, or folate enriched (10 mg pteroylmonoglutamic acid/kg) B6-deficient diet containing L-methionine at 9 g/kg for 5 weeks. Although the B6-deficient diet induced hyperhomocysteinemia, folate fortification ameliorated the plasma homocysteine concentration. Overall, our results indicate that folate fortification ameliorates the hyperhomocysteinemia induced by B6 deficiency and supplemental methionine intake.

Vitamin B6 supplementation in pregnant women with nausea and vomiting.

OBJECTIVE: To determine whether supplementation with vitamin B(6) improves nausea and/or vomiting in pregnancy. METHODS: This experimental study was conducted with 60 pregnant women experiencing nausea and/or vomiting prior to the 12th gestational week. Of these women, 30 were treated daily with 10mg and the remaining 30 with 1.28 mg of pyridoxine hydrochloride for 2 weeks. The primary outcome was the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score in each group at the end of treatment. RESULTS: The women experiencing nausea and/or vomiting in pregnancy had significantly lower levels of circulating vitamin B(6) (P=0.007) compared with those without this symptom. Vitamin B(6) supplementation significantly increased plasma vitamin B(6) concentration (P<0.05 in both groups). There were no significant differences in PUQE score or in plasma concentration levels of protein, dopamine, serotonin, unconjugated estriol, and ghrelin after supplementation between the 2 groups at baseline, but there was a significantly lesser decrease in PUQE score and a greater increase in vitamin B(6) level and vitamin B(6) concentration to plasma protein concentration ratios in group 1 than in group 2 after supplementation (P<0.05 for all). CONCLUSION: Although the high-supplementation group had a greater decrease in PUQE score in comparison to the low-supplementation group, the difference is unlikely to affect the severity of symptoms.

Vitamin B6 deficiency: a potential cause of refractory seizures in adults.

OBJECTIVE: In children, vitamin B(6) (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B(6) deficiency) that resolved after pyridoxine treatment. DESIGN: Case series. SETTING: Tertiary care surgical intensive care unit. PATIENTS: In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an intraventricular bleed and developed new onset of refractory seizures. INTERVENTIONS: Intravenous pyridoxine followed by oral pyridoxine. MEASUREMENT AND MAIN RESULTS: In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5'-phosphate concentrations normalized with pyroxidine administration. CONCLUSIONS: Although refractory seizures caused by vitamin B(6) deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures.

Vitamin B(6) treatment of intractable seizures.

Vitamin B(6) (VB(6))-related seizures include clinical seizures associated with VB(6) deficiency and dependency. Both types of seizures are suppressed by VB(6). We proposed VB(6)-responsive seizures as the third category of VB(6)-related seizures in 1977. Vitamin B(6)-responsive seizures decrease or disappear in response to high-dose oral VB(6). Seizure onset in most of our cases occurred within the first year of life, although this varied between 3 months and 5 years. Etiologically, such cases were not only idiopathic or cryptogenic, but also symptomatic and associated with organic brain lesions. The tryptophan load test was usually negative. Vitamin VB(6)-responsive seizures or epilepsy were usually West syndrome (WS), however may also include Lennox-Gastaut syndrome, grand mal or partial motor seizures. High-dose VB(6) treatment administered to 216 consecutive WS cases had an overall response rate of 13.9%, being high not only in cryptogenic cases (32%), but also in symptomatic WS (11.5%) associated with identifiable brain pathologies. Notably, responsive patients had excellent long-term seizure and mental outcomes without the need for conventional antiepileptic medication. A gradual increase in clinical response to VB(6) was noted with increasing the VB(6) dose from 30 to 50-100mg/day, and a dramatic increase in clinical response with high-dose VB(6) (100-400mg). Little clinical response was noted with administration of low dose VB(6) (10-30 mg/day). Thus, high-dose oral VB(6) treatment is recommended in all WS patients at time of initial treatment for a minimum of 10 days, considering the safety and rapid onset of efficacy, usually within 1 week, of this treatment.

[Does diet affect our mood? The significance of folic acid and homocysteine]. / Czy dieta ma wplyw na nasz nastrój? Znaczenie kwasu foliowego i homocysteiny.

UNLABELLED: In recent years, there has been growing interest in the association between national diet and the possibility of developing various mental disorders, as well as between deficiency of such vitamins as, e.g. folic acid, vitamin B12, B6, and others (e.g., omega-3 fatty acids), elevated serum homocysteine level and the functioning of human brain as well as the occurrence of such disorders as dementia, central nervous system vascular disorders and depression. THE AIM OF THE STUDY: was to present the current state of knowledge about the role of folic acid and homocysteine in the human organism as well as the significance of vitamin deficiency, mainly folic acid and hyperhomocysteinemy for the occurrence of mood disorders. METHOD: The authors conducted the search of the Internet database Medline (www.pubmed.com) using as key words: depression, mood, homocysteine, vitamin deficiencies: folic acid, B6 and 812 and time descriptors: 1990-2007. RESULTS: In depression, folate, vitamins B12 and B6, as well as unsaturated omega-3 fatty acids deficiency affects the biochemical processes in the CNS, as folic acid and vitamin B12, participate in the metabolism of S-adenosylmethionine (SAM), a donator of methyl groups, which play a decisive role in the functioning of the nervous system; they are, among others, active in the formation of neurotransmitters (e.g. serotonin), phospholipids that are a component of neuronal myelin sheaths, and cell receptors. The deficiency of the vitamins in question results in hyperhomocysteinemia (the research shows that approximately 45-55% of patients with depression develop significantly elevated serum homocysteine), which causes a decrease in SAM, followed by impaired methylation and, consequently, impaired metabolism of neurotransmitters, phospholipids, myelin, and receptors. Hyperhomocysteinemia also leads to activation of NMDA receptors, lesions in vascular endothelium, and oxidative stress. All this effects neurotoxicity and promotes the development of various disorders, including depression. Vitamins B12 and B6, folic acid and omega-3 fatty acids supplementation is thus important in patients suffering from their deficiency; national diet as a significant factor in prevention of numerous CNS disorders, including depression, is also worth consideration.

Folate and vitamin B6 intake and risk of colon cancer in relation to p53 expression.

BACKGROUND & AIMS: Considerable evidence suggests that a low-folate diet increases the risk of colorectal cancer, although the results of a recent randomized trial indicate that folate supplementation may not reduce the risk of adenoma recurrence. In laboratory models, folate deficiency appears to induce p53 mutation. METHODS: We immunohistochemically assayed p53 expression in paraffin-fixed colon cancer specimens in a large prospective cohort of women with 22 years of follow-up to examine the relationship of folate intake and intake of other one-carbon nutrients to risks by tumor p53 expression. RESULTS: A total of 399 incident colon cancers accessible for p53 expression were available. The effect of folate differed significantly according to p53 expression (P(heterogeneity) = .01). Compared with women reporting folate intake <200 microg/day, the multivariate relative risks (RRs) for p53-overexpressing (mutated) cancers were 0.54 (95% confidence interval [CI], 0.36-0.81) for women who consumed 200-299 microg/day, 0.42 (95% CI, 0.24-0.76) for women who consumed 300-399 microg/day, and 0.54 (95% CI, 0.35-0.83) for women who consumed >or=400 microg/day. In contrast, total folate intake had no influence on wild-type tumors (RR, 1.05; 95% CI, 0.73-1.51; comparing >or=400 with <200 microg/day). Similarly, high vitamin B(6) intake conferred a protective effect on p53-overexpressing cancers (top versus bottom quintile: RR, 0.57; 95% CI, 0.35-0.94; P(heterogeneity) = .01) but had no effect on p53 wild-type tumors. CONCLUSIONS: We found that low folate and vitamin B(6) intake was associated with an increased risk of p53-overexpressing colon cancers but not wild-type tumors.

Elevated plasma homocysteine and low vitamin B-6 status in nonsupplementing older women with rheumatoid arthritis.

OBJECTIVE: The purpose of this study was to determine if nonsupplementing older women (aged >or=55 years) with rheumatoid arthritis had higher plasma homocysteine and lower B-vitamin status compared to healthy controls. Elevated plasma homocysteine, a risk factor for cardiovascular disease, may help explain why individuals with rheumatoid arthritis have an increased risk of cardiovascular disease. METHODS: Older, free-living women were classified as rheumatoid arthritis (n=18) or healthy control (n=33). Participants were not using B-vitamin supplements. Fasting blood samples were measured for pyridoxal 5'phosphate (PLP) (the metabolically active coenzyme form of vitamin B-6), folate, red blood cell folate, vitamin B-12, transcobalamin II, homocysteine, C-reactive protein, and lipid concentrations. Participants completed 7-day weighed food records, the Stanford Health Assessment Questionnaire (HAQ), and a visual analog pain scale. RESULTS: PLP concentrations were lower in the rheumatoid arthritis vs healthy control participants (4.93+/-3.85 vs 11.35+/-7.11 ng/mL [20+/-16 vs 46+/-29 nmol/L]; P<0.01) whereas plasma homocysteine was higher in the rheumatoid arthritis group (1.63+/-0.74 vs 1.15+/-0.38 mg/L [12.1+/-5.5 vs 8.5+/-2.8 micromol/L]; P=0.02). Red blood cell folate concentrations were lower in the rheumatoid arthritis vs healthy control participants [414+/-141 vs 525+/-172 ng/mL [938+/-320 vs 1,190+/-390 nmol/L]; P=0.02). No significant differences were found for plasma folate, vitamin B-12, and transcobalamin II. An inverse correlation was found between PLP concentrations and the HAQ disability index (r=-0.37; P<0.01). A positive correlation was found between homocysteine concentrations and the HAQ disability index (r=0.36; P=0.01). Total cholesterol and low-density lipoprotein cholesterol levels were lower in the rheumatoid arthritis group (cholesterol 191+/-43 vs 218+/-33 mg/dL [4.95+/-1.11 vs 5.65+/-0.85 mmol/L]; P=0.02; low-density lipoprotein cholesterol 110+/-36 vs 137+/-29 mg/dL [2.85+/-0.93 vs 3.55+/-0.75 mmol/L]; P<0.01). No significant differences were seen between groups for protein (g/day), fat (g/day), cholesterol (mg/day), folate (microg/day), vitamin B-12 (microg/day), and vitamin B-6 (mg/day) dietary intakes. CONCLUSIONS: Poor vitamin B-6 status and elevated plasma homocysteine concentrations were seen in older women with rheumatoid arthritis compared to healthy controls and may contribute to their increased risk of cardiovascular disease.

[Case of an 81-year-old woman with theophylline-associated seizures followed by partial seizures due to vitamin B6 deficiency].

We report an 81-year-old woman who suffered from theophylline-associated seizures followed by partial seizures due to vitamin B6 deficiency. She developed complex partial seizures. She had been treated with theophylline for two months because of chronic bronchitis. Brain diffusion-weighted magnetic resonance imaging (MRI) showed high intensity lesions in unilateral cerebral cortex and thalamus. Electroencephalogram presented periodic lateralized epileptiform discharges (PLEDs), and single photon emission computed tomography (SPECT) using 123I-IMP revealed increased blood flow in the same side of the cerebrum. We diagnosed as theophylline-associated seizures though blood theophylline concentration disclosed its therapeutic dose, and her symptom improved after theophylline was discontinued. She developed partial seizures again, after she suffered from diarrhea for two days. Laboratory examination showed that serum vitamin B6 was under the limitation of measurement, and intravenous supplementation of vitamin B6 stopped her seizures immediately. Theophylline may induce seizures independent of its blood concentration, and vitamin B6 deficiency may exist in the case of theophylline-associated seizures.

Vitamin B6 related epilepsy during childhood.

In some patients without vitamin B6 deficiency, epilepsy can not be controlled without an extra supplement of vitamin B6. The therapeutic role of pyridoxal phosphate (PLP), the active form of vitamin B6, may not be replaced with other forms of vitamin B6 sometimes. Until now, four inborn errors of metabolism are known to affect vitamin B6 concentrations in the brain. Three of them are hyperprolinemia type 2, antiquitin deficiency, and pyridoxine phosphate oxidase deficiency. The fourth disorder occurs in neonates with hypophosphatasia and congenital rickets. All patients with these conditions present with early-onset epilepsy that is resistant to conventional antiepileptic medications. Patients with three of the conditions respond to any form of vitamin B6. Only those with pyridoxine phosphate oxidase deficiency respond to PLP instead of pyridoxine. Interestingly, the authors have successfully treated many patients without the above four disorders using vitamin B6, and have found that the treatment was more effective with PLP than with pyridoxine, though the mechanism is not known. Since PLP is as inexpensive as pyridoxine, we suggest replacing PLP for pyridoxine when treating children with epilepsy.

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)