Vitamin B12 therapies

BACKGROUND: Methylmalonic acid (MMA) is a dicarboxylic acid whose concentration can be increased in blood and urine in patients with an inborn error of metabolism or vitamin B(12) deficiency. We developed a method for the selective analysis of dicarboxylic acids that exploits the high specificity of tandem mass spectrometry (MS/MS) and the substantial difference in fragmentation patterns of the isomers methylmalonic (MMA) and succinic acid (SA). METHODS: Dicarboxylic acids were extracted from samples with methyl-tert-butyl ether and derivatized with butanolic HCl to form dibutyl esters...

BACKGROUND: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization is robust and allows accurate measurement of both low- and high-molecular weight components of complex mixtures. We developed a LC-MS/MS method for the analysis of methylmalonic acid (MMA), a biochemical marker for inherited disorders of propionate metabolism and acquired vitamin B(12) deficiency. METHODS: We added 1 nmol of the internal standard MMA-d(3) to 500 microL of plasma or 100 microL of urine before solid-phase extraction...

OBJECTIVE: Prenatally diagnosed methylmalonic aciduria (MMA) has been treated in only a few fetuses, and has been done empirically with maternally administered cyanocobalamin (B12) in attempts to ameliorate sequelae that include failure to thrive, developmental delay, dehydration, and coma. There has not been a systematic attempt to titrate doses to fetal response. We investigated the alterations in maternal dosage necessary to keep maternal plasma (MP) and urine (MU) levels of MMA in the normal range secondary to the ability of pharmacological doses of B12 to catalyze the reaction of methylmalonyl-coenzyme A to succinyl-coenzyme A...

Recent studies have suggested a neuroprotective effect for vitamin B12. The present study investigated the effects of vitamin B12, diclofenac and celecoxib in separate and combined treatments on functional recovery of crushed tibial nerve in rats. In ketamine plus xylazin anesthetized rats, right tibial nerve was crushed using a small hemoatatic forceps. Footprints were recorded 1 day before and on days 7, 14 and 21 after induction of nerve injury. Tibial functional index (TFI) was used to evaluate the recovery of tibial nerve function...

BACKGROUND: Suboptimal vitamin B status might affect cognitive performance in early childhood. We tested the hypothesis that short-term supplementation with folic acid and selected B vitamins improves cognitive function in healthy children in a population with relatively low folate status. METHODS: We screened 1,002 kindergarten children for suboptimal folate status by assessing the total urinary para-aminobenzoylglutamate excretion. Two hundred and fifty low ranking subjects were recruited into a double blind, randomized, controlled trial to receive daily a sachet containing 220 μg folic acid, 1...

BACKGROUND: Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis. Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer. METHODS: We prospectively examined the association between self-reported intakes of folate, methionine, vitamin B6, and vitamin B12 and gastric and esophageal cancer in 492,293 men and women. RESULTS: We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate (relative risk (95% confidence interval): Q1 vs Q3, 1...

UNLABELLED: Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new (99m)Tc-cobalamin derivative ((99m)Tc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin, (99m)Tc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is recognized by haptocorrin, a protein present in the circulation and notably expressed in many tumor cells...

IMPORTANCE: Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs) suppress the production of gastric acid and thus may lead to malabsorption of vitamin B12. However, few data exist regarding the associations between long-term exposure to these medications and vitamin B12 deficiency in large population-based studies. OBJECTIVE: To study the association between use of PPIs and H2RAs and vitamin B12 deficiency in a community-based setting in the United States...

BACKGROUND: A substantial proportion of patients referred for plasma vitamin B12 (cobalamin [Cbl]) measurement present with high Cbl levels, which have been reported in patients with different cancer types. However, the cancer risk among patients with newly diagnosed high Cbl levels has not been adequately examined. METHODS: We conducted this cohort study using population-based Danish medical registries. Patients referred for Cbl measurement with levels greater than the lower reference limit (≥200 pmol/L) were identified from the population of Northern Denmark during the period of 1998 to 2009 using a database of laboratory test results covering the entire population...

Global agricultural emissions of the greenhouse gas nitrous oxide (N2O) have increased by around 20% over the last 100 y, but regulation of these emissions and their impact on bacterial cellular metabolism are poorly understood. Denitrifying bacteria convert nitrate in soils to inert di-nitrogen gas (N2) via N2O and the biochemistry of this process has been studied extensively in Paracoccus denitrificans. Here we demonstrate that expression of the gene encoding the nitrous oxide reductase (NosZ), which converts N2O to N2, is regulated in response to the extracellular copper concentration...

BACKGROUND: Epidemiological studies evaluating the association of vitamin B6, vitamin B12 and methionine with breast cancer risk have produced inconsistent results. METHODS: Pertinent studies were identified by a search in PubMed and Web of Knowledge. Random-effect model was used. Dose-response relationship was assessed by restricted cubic spline. RESULTS: The combined relative risk (95% confidence interval) of breast cancer for the highest vs lowest category of serum pyridoxal 5'-phosphate (PLP, active form of vitamin B6) levels and dietary methionine intake was 0...

Vitamin B12 (cobalamin, cbl) is a cofactor of methionine synthase (MTR) in the synthesis of methionine, the precursor of the universal methyl donor S-Adenosylmethionine (SAM), which is involved in epigenomic regulatory mechanisms. We have established a neuronal cell model with stable expression of a transcobalamin-oleosin chimer and subsequent decreased cellular availability of vitamin B12, which produces reduced proliferation, increased apoptosis and accelerated differentiation through PP2A, NGF and TACE pathways...

Current recommendations on vitamin B12 intake vary from 1.4 to 3.0 μg per day and are based on the amount needed for maintenance of hematologic status or on the amount needed to compensate obligatory losses. This systematic review evaluates whether the relation between vitamin B12 intake and cognitive function should be considered for underpinning vitamin B12 recommendations in the future. The authors summarized dose-response evidence from randomized controlled trials and prospective cohort studies on the relation of vitamin B12 intake and status with cognitive function in adults and elderly people...

Contradictory results for concentrations of vitamin B12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) have been reported. We tested the hypothesis that the extracellular vitamin B12 markers are not reflecting the intracellular vitamin B12-dependent biochemical reactions in individuals with type 2 diabetes. The study included 92 patients with diabetes and 72 controls with similar age and sex distribution. We measured vitamin B12 markers [MMA, total serum vitamin B12, holoTC, total homocysteine (tHcy)], red blood cell (RBC)-B12, and the plasma concentrations of the methylation markers [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)]...

Inherited disorders of vitamin B12 (cobalamin) have provided important clues to how this vitamin, which is essential for hematological and neurological function, is transported and metabolized. We describe a new disease that results in failure to release vitamin B12 from lysosomes, which mimics the cblF defect caused by LMBRD1 mutations. Using microcell-mediated chromosome transfer and exome sequencing, we identified causal mutations in ABCD4, a gene that codes for an ABC transporter, which was previously thought to have peroxisomal localization and function...

BACKGROUND: In vitro, vitamin B12 acts as a natural inhibitor of hepatitis C virus (HCV) replication. OBJECTIVE: To assess the effect of vitamin B12 on virological response in patients with chronic HCV hepatitis naïve to antiviral therapy. METHODS: Ninety-four patients with chronic HCV hepatitis were randomly assigned to receive pegylated interferon α plus ribavirin (standard-of-care; SOC) or SOC plus vitamin B12 (SOC+B12). Viral response-namely, undetectable serum HCV-RNA, was evaluated 4 weeks after starting treatment (rapid viral response), 12 weeks after starting treatment (complete early viral response) and 24 or 48 weeks after starting treatment (end-of-treatment viral response) and 24 weeks after completing treatment (sustained viral response (SVR))...

BACKGROUND & AIMS: We describe an observational study in critically ill medical patients showing the association between serum Vitamin B12 levels measured on or near admission and the outcome in these patients. METHODS: We used the database of patients admitted to the Medical Intensive Care Unit (MICU) at the Hadassah-Hebrew University Medical Center in Jerusalem, Israel, to analyze associations between patient demographics, background, diagnoses and serum Vitamin B12 levels with hospital and 90 day outcomes...

OBJECTIVE: Antiepileptic drugs (AEDs) are important for the treatment of epilepsy, psychiatric diseases, and pain syndromes. Small studies have suggested that AED treatment reduces serum levels of folate and vitamin B12. METHODS: This prospective monocenter study aimed at testing the hypothesis that AED treatment is associated with folate and vitamin B12 serum levels in a large population. A total of 2730 AED-treated and 170 untreated patients with epilepsy and 200 healthy individuals were enrolled...