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Sample records for vitamin b12 uptake

  1. Vitamin B1 and B12 Uptake and Cycling by Plankton Communities in Coastal Ecosystems

    PubMed Central

    Koch, Florian; Hattenrath-Lehmann, Theresa K.; Goleski, Jennifer A.; Saudo-Wilhelmy, Sergio; Fisher, Nicholas S.; Gobler, Christopher J.

    2012-01-01

    While vitamin B12 has recently been shown to co-limit the growth of coastal phytoplankton assemblages, the cycling of B-vitamins in coastal ecosystems is poorly understood as planktonic uptake rates of vitamins B1 and B12 have never been quantified in tandem in any aquatic ecosystem. The goal of this study was to establish the relationships between plankton community composition, carbon fixation, and B-vitamin assimilation in two contrasting estuarine systems. We show that, although B-vitamin concentrations were low (pM), vitamin concentrations and uptake rates were higher within a more eutrophic estuary and that vitamin B12 uptake rates were significantly correlated with rates of primary production. Eutrophic sites hosted larger bacterial and picoplankton abundances with larger carbon normalized vitamin uptake rates. Although the >2??m phytoplankton biomass was often dominated by groups with a high incidence of vitamin auxotrophy (dinoflagellates and diatoms), picoplankton (<2??m) were always responsible for the majority of B12-vitamin uptake. Multiple lines of evidence suggest that heterotrophic bacteria were the primary users of vitamins among the picoplankton during this study. Nutrient/vitamin amendment experiments demonstrated that, in the Summer and Fall, vitamin B12 occasionally limited or co-limited the accumulation of phytoplankton biomass together with nitrogen. Combined with prior studies, these findings suggest that picoplankton are the primary producers and users of B-vitamins in some coastal ecosystems and that rapid uptake of B-vitamins by heterotrophic bacteria may sometimes deprive larger phytoplankton of these micronutrients and thus influence phytoplankton species succession. PMID:23091470

  2. Vitamin b(1) and b(12) uptake and cycling by plankton communities in coastal ecosystems.

    PubMed

    Koch, Florian; Hattenrath-Lehmann, Theresa K; Goleski, Jennifer A; Saudo-Wilhelmy, Sergio; Fisher, Nicholas S; Gobler, Christopher J

    2012-01-01

    While vitamin B(12) has recently been shown to co-limit the growth of coastal phytoplankton assemblages, the cycling of B-vitamins in coastal ecosystems is poorly understood as planktonic uptake rates of vitamins B(1) and B(12) have never been quantified in tandem in any aquatic ecosystem. The goal of this study was to establish the relationships between plankton community composition, carbon fixation, and B-vitamin assimilation in two contrasting estuarine systems. We show that, although B-vitamin concentrations were low (pM), vitamin concentrations and uptake rates were higher within a more eutrophic estuary and that vitamin B(12) uptake rates were significantly correlated with rates of primary production. Eutrophic sites hosted larger bacterial and picoplankton abundances with larger carbon normalized vitamin uptake rates. Although the >2??m phytoplankton biomass was often dominated by groups with a high incidence of vitamin auxotrophy (dinoflagellates and diatoms), picoplankton (<2??m) were always responsible for the majority of B(12)-vitamin uptake. Multiple lines of evidence suggest that heterotrophic bacteria were the primary users of vitamins among the picoplankton during this study. Nutrient/vitamin amendment experiments demonstrated that, in the Summer and Fall, vitamin B(12) occasionally limited or co-limited the accumulation of phytoplankton biomass together with nitrogen. Combined with prior studies, these findings suggest that picoplankton are the primary producers and users of B-vitamins in some coastal ecosystems and that rapid uptake of B-vitamins by heterotrophic bacteria may sometimes deprive larger phytoplankton of these micronutrients and thus influence phytoplankton species succession. PMID:23091470

  3. Vitamin B-12

    MedlinePLUS

    MENU Return to Web version Vitamin B-12 Vitamin B-12 What is vitamin B-12? Vitamin B-12 is an important nutrient that is found naturally ... shellfish, meat, eggs, dairy products, and fortified foods. Vitamin B-12 helps make red blood cells and ...

  4. Vitamin B12

    MedlinePLUS

    ... been added to a food product, check the nutrition fact panel on the food label. The body absorbs animal sources of vitamin B12 much better than plant sources. Non-animal sources of vitamin B12 vary ...

  5. Vitamin B-12

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin B-12 is a cofactor for 2 enzymes. In the cytoplasm, methionine synthase requires vitamin B-12 in the form of methylcobalamin and catalyzes the conversion of homocysteine to methionine by transfer of a methyl group from methyltetrahydrofolate.This enzyme links the methylation pathway through ...

  6. Vitamin B12

    MedlinePLUS

    ... multiple sclerosis, preventing the eye disease age-related macular degeneration (AMD), Lyme disease and gum disease. It is ... of homocysteine. An eye disease called age-related macular degeneration (AMD). Some research shows that taking vitamin B12 ...

  7. MEASUREMENT OF TOTAL VITAMIN B12 AND HOLOTRANSCOBALAMIN, SINGLY AND IN COBMINATION, IN SCREENING FOR METABOLIC VITAMIN B12 DEFICIENCY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The standard screening test for vitamin B12 deficiency, measurement of total plasma vitamin B12, has limitations of sensitivity and specificity. Plasma vitamin B12 bound to transcobalamin (holoTC) is the fraction of total vitamin B12 available for tissue uptake and therefore has been pro...

  8. Vitamin B12 benefits (image)

    MedlinePLUS

    Vitamin B12 is important for metabolism. Metabolism within the body includes the processes of energy generation and use; including nutrition, digestion, absorption, elimination, respiration, circulation, and temperature ...

  9. Vitamin B12 level

    MedlinePLUS

    ... urine. Conditions that can increase B12 level include: Liver disease (such as cirrhosis or hepatitis ) Myeloproliferative disorders (for example, polycythemia vera and chronic myelocytic leukemia )

  10. Bioavailability of vitamin B12

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin B12 deficiency is common in people of all ages who consume a low intake of animal-source foods, including populations in developing countries. It is also prevalent among the elderly, even in wealthier countries, due to their malabsorption of B12 from food. Several methods have been applied t...

  11. A water soluble vitamin B12-ReI fluorescent conjugate for cell uptake screens: use in the confirmation of cubilin in the lung cancer line A549.

    PubMed

    Vortherms, Anthony R; Kahkoska, Anna R; Rabideau, Amy E; Zubieta, Jon; Andersen, Louise Lund; Madsen, Mette; Doyle, Robert P

    2011-09-21

    A water soluble vitamin B(12)-rhenium conjugate was synthesized and used in concert with intrinsic factor to screen for cubilin receptor-mediated uptake in lung cancer cells. Internalization of the conjugate demonstrated that it could be used to rapidly screen for the cubilin receptor in living cells, subsequently confirmed with Western blotting and RT-PCR. PMID:21818500

  12. How common is vitamin B12 deficiency?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In considering the vitamin B-12 fortification of flour, it is important to know who is at risk of vitamin B-12 deficiency and whether those individuals would benefit from flour fortification.This article reviews current knowledge of the prevalence and causes of vitamin B-12 deficiency and considers ...

  13. Vitamin B12 and Cognitive Function

    PubMed Central

    2013-01-01

    Background More than 2.9 million serum vitamin B12 tests were performed in 2010 in Ontario at a cost of $40 million. Vitamin B12 deficiency has been associated with a few neurocognitive disorders. Objective To determine the clinical utility of B12 testing in patients with suspected dementia or cognitive decline. Methods Three questions were addressed: Is there an association between vitamin B12 deficiency and the onset of dementia or cognitive decline? Does treatment with vitamin B12 supplementation improve cognitive function in patients with dementia or cognitive decline and vitamin B12 deficiency? What is the effectiveness of oral versus parenteral vitamin B12 supplementation in those with confirmed vitamin B12 deficiency? A literature search was performed using MEDLINE, Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the Centre for Reviews and Dissemination database, from January 2002 until August 2012. Results Eighteen studies (7 systematic reviews and 11 observational studies) were identified to address the question of the association between B12 and the onset of dementia. Four systematic reviews were identified to address the question of the treatment of B12 on cognitive function. Finally, 3 randomized controlled trials were identified that compared oral B12 to intramuscular B12. Conclusions Based on very low quality evidence, there does appear to be an association between elevated plasma homocysteine levels (a by-product of B vitamins) and the onset of dementia. Based on moderate quality evidence, but with less than optimal duration of follow-up, treatment with B12 supplementation does not appreciably change cognitive function. Based on low to moderate quality of evidence, treatment with vitamin B12 and folate in patients with mild cognitive impairment seems to slow the rate of brain atrophy. Based on moderate quality evidence, oral vitamin B12 is as effective as parenteral vitamin B12 in patients with confirmed B12 deficiency. Plain Language Summary Low levels of vitamin B12 have been associated with neurocognitive disorders. This evidence-based analysis assessed the usefulness of serum vitamin B12 testing as it relates to brain function. This review found very low quality evidence that suggests a connection between high plasma homocysteine levels (a by-product of B vitamin metabolism in the body) and the onset of dementia. Moderate quality of evidence indicates treatment with vitamin B12 does not improve brain function. Moderate quality of evidence also indicates treatment using oral vitamin B12 supplements is as effective as injections of vitamin B12. PMID:24379897

  14. [Vitamin B12 deficiency in the elderly].

    PubMed

    Leischker, A H; Kolb, G F

    2015-01-01

    The prevalence of vitamin B12 deficiency increases with age. Patients with dementia and spouses of patients with dementia are at special risk for the development of vitamin B12 deficiency. In a normal diet this vitamin is present only in animal source foods; therefore, vegans frequently develop vitamin B12 deficiency if not using supplements or foods fortified with cobalamin. Apart from dementia, most of these manifestations are completely reversible under correct therapy; therefore it is crucial to identify and to treat even atypical presentations of vitamin B12 deficiency as early as possible. This article deals with the physiology and pathophysiology of vitamin B12 metabolism. A practice-oriented algorithm which also considers health economic aspects for a rational laboratory diagnosis of vitamin B12 deficiency is presented. In cases with severe neurological symptoms, therapy should be parenteral, especially initially. For parenteral treatment, hydroxocobalamin is the drug of choice. PMID:25586321

  15. Vitamin B12 in Health and Disease

    PubMed Central

    O’Leary, Fiona; Samman, Samir

    2010-01-01

    Vitamin B12 is essential for DNA synthesis and for cellular energy production.This review aims to outline the metabolism of vitamin B12, and to evaluate the causes and consequences of sub-clinical vitamin B12 deficiency. Vitamin B12 deficiency is common, mainly due to limited dietary intake of animal foods or malabsorption of the vitamin. Vegetarians are at risk of vitamin B12 deficiency as are other groups with low intakes of animal foods or those with restrictive dietary patterns. Malabsorption of vitamin B12 is most commonly seen in the elderly, secondary to gastric achlorhydria. The symptoms of sub-clinical deficiency are subtle and often not recognized. The long-term consequences of sub-clinical deficiency are not fully known but may include adverse effects on pregnancy outcomes, vascular, cognitive, bone and eye health. PMID:22254022

  16. Update on vitamin B12 deficiency.

    PubMed

    Langan, Robert C; Zawistoski, Kimberly J

    2011-06-15

    Vitamin B(12) (cobalamin) deficiency is a common cause of megaloblastic anemia, a variety of neuropsychiatric symptoms, and elevated serum homocysteine levels, especially in older persons. There are a number of risk factors for vitamin B(12) deficiency, including prolonged use of metformin and proton pump inhibitors. No major medical organizations, including the U.S. Preventive Services Task Force, have published guidelines on screening asymptomatic or low-risk adults for vitamin B(12) deficiency, but high-risk patients, such as those with malabsorptive disorders, may warrant screening. The initial laboratory assessment of a patient with suspected vitamin B(12) deficiency should include a complete blood count and a serum vitamin B(12) level. Measurements of serum vitamin B(12) may not reliably detect deficiency, and measurement of serum homocysteine and/or methylmalonic acid should be used to confirm deficiency in asymptomatic high-risk patients with low normal levels of vitamin B(12). Oral administration of high-dose vitamin B(12) (1 to 2 mg daily) is as effective as intramuscular administration in correcting the deficiency, regardless of etiology. Because crystalline formulations are better absorbed than naturally occurring vitamin B(12), patients older than 50 years and strict vegetarians should consume foods fortified with vitamin B(12) and vitamin B(12) supplements, rather than attempting to get vitamin B(12) strictly from dietary sources. Administration of vitamin B(12) to patients with elevated serum homocysteine levels has not been shown to reduce cardiovascular outcomes in high-risk patients or alter the cognitive decline of patients with mild to moderate Alzheimer disease. PMID:21671542

  17. Vitamin B-12 and Perinatal Health.

    PubMed

    Finkelstein, Julia L; Layden, Alexander J; Stover, Patrick J

    2015-09-01

    Vitamin B-12 deficiency (<148 pmol/L) is associated with adverse maternal and neonatal outcomes, including developmental anomalies, spontaneous abortions, preeclampsia, and low birth weight (<2500 g). The importance of adequate vitamin B-12 status periconceptionally and during pregnancy cannot be overemphasized, given its fundamental role in neural myelination, brain development, and growth. Infants born to vitamin B-12-deficient women may be at increased risk of neural tube closure defects, and maternal vitamin B-12 insufficiency (<200 pmol/L) can impair infant growth, psychomotor function, and brain development, which may be irreversible. However, the underlying causal mechanisms are unknown. This review was conducted to examine the evidence that links maternal vitamin B-12 status and perinatal outcomes. Despite the high prevalence of vitamin B-12 deficiency and associated risk of pregnancy complications, few prospective studies and, to our knowledge, only 1 randomized trial have examined the effects of vitamin B-12 supplementation during pregnancy. The role of vitamin B-12 in the etiology of adverse perinatal outcomes needs to be elucidated to inform public health interventions. PMID:26374177

  18. Vitamin B12--folate interrelations.

    PubMed

    Das, K C; Herbert, V

    1976-10-01

    Megaloblastic anaemia is due to a derangement of DNA synthesis caused by insufficient supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) precursors of DNA synthesis or by direct inhibition of one or other DNA polymerase. Reduced supply of the pyrimidine deoxythymidine triphosphate (dTTP) may be caused by folate or vitamin B12 deficiencies or by the action of dihydrofolate reductase inhibitors (e.g. methotrexate, pyrimethamine or trimethoprim), all of which cause reduced supply of the coenzyme 5, 10 methylene tetrahydrofolate (pentaglutamate) needed for thymidylate synthetase. Reduced dTTP supply may also be caused by direct inhibition of thymidylate synthetase by 5-fluorouracil. Reduced supply of both purines, deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP), may be caused by hydroxyurea, 6-mercaptopurine (and probably by another purine antagonist azaserine), whilst reduced supply of both pyrimidine DNA precursors, dTTP and dCTP (deoxycytidine triphosphate) may be due to inherited orotic aciduria or to treatment with azauridine. Cytosine arabinoside directly inhibits DNA polymerase. DNA replication is a discontinuous process and a number of enzymes are concerned with different aspects of the process. The parental strands partly unwind and a large number of initiation points or origins are activated on both strands. A primer RNA is first synthesised using the parental strand of DNA as template. Fragments of new DNA are then synthesised on the parental DNA template, starting at the RNA primer, under the action of one or other DNA polymerase (probably gamma). The RNA primer is then removed and the gap left is filled by further DNA synthesis under the action of a different DNA polymerase (probably alpha). The fragments of new DNA are joined to give newly synthesised stretches of DNA (replicons) which are then liigated together to form bulk DNA of enormous molecular weight. It is suggested here that reduced supply of one or other of the four deoxyribonucleoside triphosphate (dNTP) during the 'S' phase of the cell cycle (due to vitamin B12 or folate deficiency, drug treatment or other congenital or acquired abnormality in synthesis of the dNTP) impairs the cell's ability to elongate newly initiated DNA fragments by preventing gap-filling, the polymerase needed for gap-filling requiring substantially greater concentrations of the deoxyribonucleoside triphosphates than the polymerase involved in chain initiation. Cytosine arabinoside, which also may cause megaloblastosis, may affect principally the synthesis of new DNA fragments. Since active protein synthesis is needed for the cell to enter the S phase and RNA synthesis is needed to prime new DNA synthesis, megaloblastic anaemia may be expected to occur only when DNA synthesis is inhibited but protein and RNA synthesis are relatively unimpaired... PMID:10122

  19. Assay for vitamin B12 absorption and method of making labeled vitamin B12

    DOEpatents

    Anderson, Peter J.; Dueker, Stephen; Miller, Joshua; Green, Ralph; Roth, John; Carkeet, Colleen; Buchholz,; Bruce A.

    2012-06-19

    The invention provides methods for labeling vitamin B12 with .sup.14C, .sup.13C, tritium, and deuterium. When radioisotopes are used, the invention provides for methods of labeling B12 with high specific activity. The invention also provides labeled vitamin B12 compositions made in accordance with the invention.

  20. Isolation of Vitamin B12 Transport Mutants of Escherichia coli

    PubMed Central

    Di Girolamo, Paula M.; Kadner, Robert J.; Bradbeer, Clive

    1971-01-01

    Escherichia coli KBT001, a methionine-vitamin B12 auxotroph, was found to require a minimum of 20 molecules of vitamin B12 (CN-B12) per cell for aerobic growth in the absence of methionine. After mutagenesis with N-methyl-N?-nitro-N-nitrosoguanidine and penicillin selection, two kinds of B12 transport mutant were isolated from this strain. Mutants of class I, such as KBT069, were defective in the initial rapid binding of CN-B12 to the cell and were unable to grow in the absence of methionine even with CN-B12 concentrations as high as 100 ng/ml. The class II mutants possessed intact initial phases of CN-B12 uptake but were defective in the secondary energy-dependent phase. These strains were also unable to convert the CN-B12 taken up into other cobalamins. In the absence of methionine, some of these strains (e.g., KBT103) were able to grow on media containing 1 ng of CN-B12/ml, whereas others (e.g., KBT041) were unable to grow with any of the CN-B12 concentrations used. Osmotic shock treatment did not affect the initial rate of uptake of CN-B12 but gave a substantial decrease in the secondary rate. Trace amounts of B12-binding macromolecules were released from the cells by the osmotic shock, but only from strains such as KBT001 and KBT041 which possessed an active initial phase of CN-B12 uptake. These results are interpreted as being consistent with the view that the initial CN-B12 binding site which functions in this transport system is probably bound to the cell membrane. PMID:4326741

  1. Vitamin B12 deficiency: the great masquerader.

    PubMed

    Dobrozsi, Sarah; Flood, Veronica H; Panepinto, Julie; Scott, J Paul; Brandow, Amanda

    2014-04-01

    Vitamin B12 deficiency is rare in children, with nonspecific symptoms including failure to thrive, vomiting, anorexia, and neurologic changes with or without hematologic disturbances. The neuropathy can be severe and irreversible. We report four cases of children with B12 deficiency secondary to adult type pernicious anemia, a presumed transport protein abnormality, and a metabolic defect. All demonstrated neurologic compromise that improved after initiation of B12 therapy. Hematologic manifestations may be preceded by constitutional, gastrointestinal, or neurologic changes, and must raise concern for B12 deficiency. Therapy should be initiated promptly in this setting to prevent irreversible neuropathy. PMID:24115632

  2. A vitamin B12 transporter in Mycobacterium tuberculosis

    PubMed Central

    Gopinath, Krishnamoorthy; Venclovas, Česlovas; Ioerger, Thomas R.; Sacchettini, James C.; McKinney, John D.; Mizrahi, Valerie; Warner, Digby F.

    2013-01-01

    Vitamin B12-dependent enzymes function in core biochemical pathways in Mycobacterium tuberculosis, an obligate pathogen whose metabolism in vivo is poorly understood. Although M. tuberculosis can access vitamin B12 in vitro, it is uncertain whether the organism is able to scavenge B12 during host infection. This question is crucial to predictions of metabolic function, but its resolution is complicated by the absence in the M. tuberculosis genome of a direct homologue of BtuFCD, the only bacterial B12 transport system described to date. We applied genome-wide transposon mutagenesis to identify M. tuberculosis mutants defective in their ability to use exogenous B12. A small proportion of these mapped to Rv1314c, identifying the putative PduO-type ATP : co(I)rrinoid adenosyltransferase as essential for B12 assimilation. Most notably, however, insertions in Rv1819c dominated the mutant pool, revealing an unexpected function in B12 acquisition for an ATP-binding cassette (ABC)-type protein previously investigated as the mycobacterial BacA homologue. Moreover, targeted deletion of Rv1819c eliminated the ability of M. tuberculosis to transport B12 and related corrinoids in vitro. Our results establish an alternative to the canonical BtuCD-type system for B12 uptake in M. tuberculosis, and elucidate a role in B12 metabolism for an ABC protein implicated in chronic mycobacterial infection. PMID:23407640

  3. 21 CFR 862.1810 - Vitamin B 12 test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Vitamin B 12 test system. 862.1810 Section 862....1810 Vitamin B 12 test system. (a) Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in...

  4. 21 CFR 862.1810 - Vitamin B12 test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Vitamin B12 test system. 862.1810 Section 862.1810....1810 Vitamin B12 test system. (a) Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in...

  5. 21 CFR 862.1810 - Vitamin B 12 test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Vitamin B 12 test system. 862.1810 Section 862....1810 Vitamin B 12 test system. (a) Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in...

  6. 21 CFR 862.1810 - Vitamin B12 test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Vitamin B12 test system. 862.1810 Section 862.1810....1810 Vitamin B12 test system. (a) Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in...

  7. 21 CFR 862.1810 - Vitamin B12 test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vitamin B12 test system. 862.1810 Section 862.1810....1810 Vitamin B12 test system. (a) Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in...

  8. Folate, vitamin B12 and human health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During the past decade the role of folate and vitamin B12 in human nutrition have been under constant re-examination. Basic knowledge on the metabolism and interactions between these essential nutrients has expanded and multiple complexities have been unraveled. These micronutrients have shared func...

  9. 21 CFR 184.1945 - Vitamin B12.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin B12. 184.1945 Section 184.1945 Food and... Substances Affirmed as GRAS § 184.1945 Vitamin B12. (a) Vitamin B12, also known as cyanocobalamin (C63H88Co... is used in food at levels not to exceed current good manufacturing practice. Vitamin B12 also may...

  10. 21 CFR 184.1945 - Vitamin B12.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Vitamin B12. 184.1945 Section 184.1945 Food and... Substances Affirmed as GRAS § 184.1945 Vitamin B12. (a) Vitamin B12, also known as cyanocobalamin (C63H88Co... is used in food at levels not to exceed current good manufacturing practice. Vitamin B12 also may...

  11. 21 CFR 184.1945 - Vitamin B 12..

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Vitamin B 12.. 184.1945 Section 184.1945 Food and... Substances Affirmed as GRAS § 184.1945 Vitamin B 12.. (a) Vitamin B12, also known as cyanocobalamin (C63H88Co... is used in food at levels not to exceed current good manufacturing practice. Vitamin B12 also may...

  12. 21 CFR 184.1945 - Vitamin B12.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Vitamin B12. 184.1945 Section 184.1945 Food and... Substances Affirmed as GRAS § 184.1945 Vitamin B12. (a) Vitamin B12, also known as cyanocobalamin (C63H88Co... is used in food at levels not to exceed current good manufacturing practice. Vitamin B12 also may...

  13. 21 CFR 184.1945 - Vitamin B12.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Vitamin B12. 184.1945 Section 184.1945 Food and....1945 Vitamin B12. (a) Vitamin B12, also known as cyanocobalamin (C63H88CoN14O14P, CAS Reg. No. 68-0919... exceed current good manufacturing practice. Vitamin B12 also may be used in infant formula in...

  14. 21 CFR 582.5945 - Vitamin B 12.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin B 12. 582.5945 Section 582.5945 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5945 Vitamin B 12. (a) Product. Vitamin B12. (b) Conditions of use. This substance...

  15. 21 CFR 582.5945 - Vitamin B12.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin B12. 582.5945 Section 582.5945 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5945 Vitamin B12. (a) Product. Vitamin B12. (b) Conditions of use. This substance...

  16. 21 CFR 582.5945 - Vitamin B 12.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin B 12. 582.5945 Section 582.5945 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5945 Vitamin B 12. (a) Product. Vitamin B12. (b) Conditions of use. This substance...

  17. 21 CFR 582.5945 - Vitamin B12.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin B12. 582.5945 Section 582.5945 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5945 Vitamin B12. (a) Product. Vitamin B12. (b) Conditions of use. This substance...

  18. 21 CFR 582.5945 - Vitamin B12.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin B12. 582.5945 Section 582.5945 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5945 Vitamin B12. (a) Product. Vitamin B12. (b) Conditions of use. This substance...

  19. Radiolysis of cyanocobalamin (vitamin B 12)

    NASA Astrophysics Data System (ADS)

    Juanchi, X.; Albarran, G.; Negron-Mendoza, A.

    2000-03-01

    Research on the radiolysis of vitamins is of considerable interest since these compounds are important nutritional constituents in foods and in dietetic supplements. In spite of these considerations there are few data and very often difficult to compare for the radiolytic behavior of vitamins. In this work we focused our attention on to the study of the radiolysis of cyanocobalamin (vitamin B 12) in solid state and in aqueous solutions. The procedure was followed by HPLC and UV-spectroscopy. The results obtained in aqueous solutions showed a dependence of the decomposition as a linear function of the dose. The G of decomposition for a 110 -5 M solution was 3.3. In the solid state the vitamin was very stable towards the irradiation in the conditions used in this study with a G=2.110 -3. A study made with Serratia marcescens as a microbiological contaminant showed that at the sterilization dose there is a destruction of the vitamin in aqueous solution. In the solid state the degree of decomposition was 7%.

  20. Vitamin B12 Uptake by the Gut Commensal Bacteria Bacteroides thetaiotaomicron Limits the Production of Shiga Toxin by Enterohemorrhagic Escherichia coli

    PubMed Central

    Cordonnier, Charlotte; Le Bihan, Guillaume; Emond-Rheault, Jean-Guillaume; Garrivier, Annie; Harel, Josée; Jubelin, Grégory

    2016-01-01

    Enterohemorrhagic Escherichia coli (EHEC) are foodborne pathogens responsible for the development of bloody diarrhea and renal failure in humans. Many environmental factors have been shown to regulate the production of Shiga toxin 2 (Stx2), the main virulence factor of EHEC. Among them, soluble factors produced by human gut microbiota and in particular, by the predominant species Bacteroides thetaiotaomicron (B. thetaiotaomicron), inhibit Stx2 gene expression. In this study, we investigated the molecular mechanisms underlying the B. thetaiotaomicron-dependent inhibition of Stx2 production by EHEC. We determined that Stx2-regulating molecules are resistant to heat treatment but do not correspond to propionate and acetate, two short-chain fatty acids produced by B. thetaiotaomicron. Moreover, screening of a B. thetaiotaomicron mutant library identified seven mutants that do not inhibit Stx2 synthesis by EHEC. One mutant has impaired production of BtuB, an outer membrane receptor for vitamin B12. Together with restoration of Stx2 level after vitamin B12 supplementation, these data highlight vitamin B12 as a molecule produced by gut microbiota that modulates production of a key virulence factor of EHEC and consequently may affect the outcome of an infection. PMID:26742075

  1. Vitamin B12 Uptake by the Gut Commensal Bacteria Bacteroides thetaiotaomicron Limits the Production of Shiga Toxin by Enterohemorrhagic Escherichia coli.

    PubMed

    Cordonnier, Charlotte; Le Bihan, Guillaume; Emond-Rheault, Jean-Guillaume; Garrivier, Annie; Harel, Josée; Jubelin, Grégory

    2016-01-01

    Enterohemorrhagic Escherichia coli (EHEC) are foodborne pathogens responsible for the development of bloody diarrhea and renal failure in humans. Many environmental factors have been shown to regulate the production of Shiga toxin 2 (Stx2), the main virulence factor of EHEC. Among them, soluble factors produced by human gut microbiota and in particular, by the predominant species Bacteroides thetaiotaomicron (B. thetaiotaomicron), inhibit Stx2 gene expression. In this study, we investigated the molecular mechanisms underlying the B. thetaiotaomicron-dependent inhibition of Stx2 production by EHEC. We determined that Stx2-regulating molecules are resistant to heat treatment but do not correspond to propionate and acetate, two short-chain fatty acids produced by B. thetaiotaomicron. Moreover, screening of a B. thetaiotaomicron mutant library identified seven mutants that do not inhibit Stx2 synthesis by EHEC. One mutant has impaired production of BtuB, an outer membrane receptor for vitamin B12. Together with restoration of Stx2 level after vitamin B12 supplementation, these data highlight vitamin B12 as a molecule produced by gut microbiota that modulates production of a key virulence factor of EHEC and consequently may affect the outcome of an infection. PMID:26742075

  2. Determination of vitamin B12 using the enzyme glycerol dehydrase.

    PubMed

    Yamada, S; Yamada, K; Nishikawa, N; Hioki, R; Nirasawa, M; Kii, K; Ryugo, H; Iwama, M; Fukuda, M

    2004-01-01

    Glycerol dehydrase is an enzyme that catalyzes dehydration of glycerol into beta-propionaldehyde. It requires 5'-deoxyadenosylcobalamin, one of the forms of vitamin B12, as a coenzyme. The enzyme is inactivated in vitro by all forms of vitamin B12 stoichiometrically. The objective of this study was to determine vitamin B12 content by utilizing the inactivation of the enzyme by vitamin B12. After various examinations, an excellent standard curve was obtained up to 1 pmol vitamin B12 using 14 mU of the enzyme per tube. Glycerol dehydrase does not respond to vitamin B12 if it is bound to haptocorrin, a vitamin B12-binding protein. This necessitates a procedure for extraction of vitamin B12 from samples before assay. The enzyme was less inactivated by 5'-deoxyadenosylcobalamin than any other form of vitamin B12. However, this did not matter because all forms of vitamin B12 were converted into cyanocobalamin during the extraction procedure cited above, which was performed in a buffer containing potassium cyanide. PMID:15222628

  3. Genetic Variation in Vitamin B-12 Content of Bovine Milk and Its Association with SNP along the Bovine Genome

    PubMed Central

    Rutten, Marc J. M.; Bouwman, Aniek C.; Sprong, R. Corinne; van Arendonk, Johan A. M.; Visker, Marleen H. P. W.

    2013-01-01

    Vitamin B-12 (also called cobalamin) is essential for human health and current intake levels of vitamin B-12 are considered to be too low. Natural enrichment of the vitamin B-12 content in milk, an important dietary source of vitamin B-12, may help to increase vitamin B-12 intake. Natural enrichment of the milk vitamin B-12 content could be achieved through genetic selection, provided there is genetic variation between cows with respect to the vitamin B-12 content in their milk. A substantial amount of genetic variation in vitamin B-12 content was detected among raw milk samples of 544 first-lactation Dutch Holstein Friesian cows. The presence of genetic variation between animals in vitamin B-12 content in milk indicates that the genotype of the cow affects the amount of vitamin B-12 that ends up in her milk and, consequently, that the average milk vitamin B-12 content of the cow population can be increased by genetic selection. A genome-wide association study revealed significant association between 68 SNP and vitamin B-12 content in raw milk of 487 first-lactation Dutch Holstein Friesian cows. This knowledge facilitates genetic selection for milk vitamin B-12 content. It also contributes to the understanding of the biological mechanism responsible for the observed genetic variation in vitamin B-12 content in milk. None of the 68 significantly associated SNP were in or near known candidate genes involved in transport of vitamin B-12 through the gastrointestinal tract, uptake by ileum epithelial cells, export from ileal cells, transport through the blood, uptake from the blood, intracellular processing, or reabsorption by the kidneys. Probably, associations relate to genes involved in alternative pathways of well-studied processes or to genes involved in less well-studied processes such as ruminal production of vitamin B-12 or secretion of vitamin B-12 by the mammary gland. PMID:23626813

  4. Vitamin B12-Containing Plant Food Sources for Vegetarians

    PubMed Central

    Watanabe, Fumio; Yabuta, Yukinori; Bito, Tomohiro; Teng, Fei

    2014-01-01

    The usual dietary sources of Vitamin B12 are animal-derived foods, although a few plant-based foods contain substantial amounts of Vitamin B12. To prevent Vitamin B12 deficiency in high-risk populations such as vegetarians, it is necessary to identify plant-derived foods that contain high levels of Vitamin B12. A survey of naturally occurring plant-derived food sources with high Vitamin B12 contents suggested that dried purple laver (nori) is the most suitable Vitamin B12 source presently available for vegetarians. Furthermore, dried purple laver also contains high levels of other nutrients that are lacking in vegetarian diets, such as iron and n-3 polyunsaturated fatty acids. Dried purple laver is a natural plant product and it is suitable for most people in various vegetarian groups. PMID:24803097

  5. Vitamin B12 deficiency after irradiation for bladder carcinoma

    SciTech Connect

    Kinn, A.C.; Lantz, B.

    1984-05-01

    Vitamin B12 deficiency was found in 10 of 41 patients who underwent radiotherapy before cystectomy with Bricker urinary diversion for carcinoma of the bladder. Of 13 patients given full irradiation because of inoperable bladder cancer 5 had malabsorption of vitamin B12. Serum folic acid was normal in these patients, indicating predominantly ileal irradiation sequelae. Routine evaluation of serum vitamin B12 after radiotherapy is recommended so that appropriate medication can be given, if possible before neurological symptoms appear.

  6. Vitamin B12 assays compared by use of patients sera with low vitamin B12 content

    SciTech Connect

    Sheridan, B.L.; Pearce, L.C.

    1985-05-01

    The authors compared four radioisotope dilution (RD) methods and a microbiological assay for measuring concentrations of vitamin B12 in a selected panel of serum samples from patients known to be deficient in the vitamin. Low (less than 100 ng/L) and borderline (100-180 ng/L) results were similar between methods, but use of the manufacturers recommended ranges for borderline results would have changed the diagnostic classifications for 22 of 38 samples. Results of all the RD methods inter-correlated well, but less so with the microbiological assay. Borderline, nondiagnostic results were common to all methods, and no apparent advantage was gained from using the microbiological assay.

  7. Vegan diet, subnormal vitamin B-12 status and cardiovascular health.

    PubMed

    Woo, Kam S; Kwok, Timothy C Y; Celermajer, David S

    2014-08-01

    Vegetarian diets have been associated with atherosclerosis protection, with healthier atherosclerosis risk profiles, as well as lower prevalence of, and mortality from, ischemic heart disease and stroke. However, there are few data concerning the possible cardiovascular effects of a vegan diet (with no meat, dairy or egg products). Vitamin B-12 deficiency is highly prevalent in vegetarians; this can be partially alleviated by taking dairy/egg products in lact-ovo-vegetarians. However, metabolic vitamin B-12 deficiency is highly prevalent in vegetarians in Australia, Germany, Italy and Austria, and in vegans (80%) in Hong Kong and India, where vegans rarely take vitamin B-12 fortified food or vitamin B-12 supplements. Similar deficiencies exist in northern Chinese rural communities consuming inadequate meat, egg or dairy products due to poverty or dietary habits. Vascular studies have demonstrated impaired arterial endothelial function and increased carotid intima-media thickness as atherosclerosis surrogates in such metabolic vitamin B-12 deficient populations, but not in lactovegetarians in China. Vitamin B-12 supplementation has a favourable impact on these vascular surrogates in Hong Kong vegans and in underprivileged communities in northern rural China. Regular monitoring of vitamin B-12 status is thus potentially beneficial for early detection and treatment of metabolic vitamin B-12 deficiency in vegans, and possibly for prevention of atherosclerosis-related diseases. PMID:25195560

  8. Vegan Diet, Subnormal Vitamin B-12 Status and Cardiovascular Health

    PubMed Central

    Woo, Kam S.; Kwok, Timothy C.Y.; Celermajer, David S.

    2014-01-01

    Vegetarian diets have been associated with atherosclerosis protection, with healthier atherosclerosis risk profiles, as well as lower prevalence of, and mortality from, ischemic heart disease and stroke. However, there are few data concerning the possible cardiovascular effects of a vegan diet (with no meat, dairy or egg products). Vitamin B-12 deficiency is highly prevalent in vegetarians; this can be partially alleviated by taking dairy/egg products in lact-ovo-vegetarians. However, metabolic vitamin B-12 deficiency is highly prevalent in vegetarians in Australia, Germany, Italy and Austria, and in vegans (80%) in Hong Kong and India, where vegans rarely take vitamin B-12 fortified food or vitamin B-12 supplements. Similar deficiencies exist in northern Chinese rural communities consuming inadequate meat, egg or dairy products due to poverty or dietary habits. Vascular studies have demonstrated impaired arterial endothelial function and increased carotid intima-media thickness as atherosclerosis surrogates in such metabolic vitamin B-12 deficient populations, but not in lactovegetarians in China. Vitamin B-12 supplementation has a favourable impact on these vascular surrogates in Hong Kong vegans and in underprivileged communities in northern rural China. Regular monitoring of vitamin B-12 status is thus potentially beneficial for early detection and treatment of metabolic vitamin B-12 deficiency in vegans, and possibly for prevention of atherosclerosis-related diseases. PMID:25195560

  9. Causes of Vitamin B12 and Folate Deficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review describes current knowledge of the main causes of vitamin B12 and folate deficiency. The most common explanations for poor B12 status are a low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and malabsorption. Although it has long been known that strict vegetar...

  10. Regulation of phytoplankton dynamics by vitamin B12

    NASA Astrophysics Data System (ADS)

    Saudo-Wilhelmy, S. A.; Gobler, C. J.; Okbamichael, M.; Taylor, G. T.

    2006-02-01

    Despite the biological necessity of vitamin B12 (cobalamin), its importance in phytoplankton ecology has been ignored for nearly three decades. Here we report strong and selective responses of phytoplankton communities to varying low levels (5-87 pM) of dissolved B12 in several coastal embayments. The ecological importance of this vitamin is inferred from observed declines in dissolved B12 levels as field populations of large (>5 ?m) phytoplankton increased. In contrast, biomass of small (<5 ?m) phytoplankton varied independently of B12 concentrations. These observations were corroborated by field-based nutrient amendment experiments, in which B12 additions stimulated growth of large phytoplankton taxa 6-fold over unamended controls. In contrast, small taxa (<5 ?m) were largely unaffected. This study provides the first evidence of vitamin B12's influence on phytoplankton field population dynamics based on direct chemical measurements of cobalamin, and implicates B12 as an important organic regulator of photoautotrophic fertility in marine systems.

  11. West syndrome due to vitamin B12 deficiency

    PubMed Central

    Serin, Hepsen Mine; Kara, Aslıhan Oruçoğlu; Oğuz, Baran

    2015-01-01

    Vitamin B12 is one of the essential vitamins affecting various systems of the body. Vitamin B12 deficiency in infants often produces haematological and neurological deficits including macrocyticanaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor andseizures. In this article, we report the case of a six-month-old male patient diagnosed with West syndrome associated with vitamin B12 deficiency. Although the patient had no evidence of macrocytic anemia in complete blood count, we measured the level of vitamin B12 because the patient had hypotonicity and found it to be low. No other problem was found in the other investigations directed to the etiology of West syndrome. He was being exclusively breast-fed and vitamin B12 deficiency was related with nutritional inadequacy of his mother. Vitamin B12 deficiency should be considered in the differential diagnosis of patients presenting with different neurological findings. In addition, vitamin B12 deficiency should be considered as a rare cause in West syndrome which has a heterogeneous etiology. PMID:26884697

  12. Synthesis, characterization and pharmacodynamics of vitamin-B(12)-conjugated glucagon-like peptide-1.

    PubMed

    Clardy-James, Susan; Chepurny, Oleg G; Leech, Colin A; Holz, George G; Doyle, Robert P

    2013-04-01

    Clearing the way: Glucagon-like peptide-1 (GLP-1) receptor agonists are proving a potent weapon in the treatment of type II diabetes. A new vitamin B(12)-GLP-1 conjugate is investigated and shown to have insulinotropic properties similar to the unmodified peptide. These results are critical to the exploitation of the vitamin B(12) oral uptake pathway for peptide delivery. PMID:23203941

  13. Vitamin B12 in meat and dairy products.

    PubMed

    Gille, Doreen; Schmid, Alexandra

    2015-02-01

    Vitamin B12 is synthesized exclusively by microorganisms; therefore, humans must absorb it from food. Excellent sources of B12 are foods of ruminant origin, so dairy and meat products play an important role in efforts to meet the official daily B12 intake recommendation of 3.0 ?g. Concentrations of the vitamin vary within foods of ruminant origin, with the highest concentrations found in offal such as liver and kidney. In comparison, dairy products have much lower quantities of the vitamin. In bovine milk, the B12 concentration is stable with regard to breed, feed, season, and stage of lactation, but in ruminant meat, the amount of B12 can vary based on the feeding and husbandry of the animal as well as the cut of meat chosen and its preparation. Processing of ruminant food, including thermal treatment, usually diminishes the vitamin B12 concentration. This review summarizes the vitamin B12 content of foods and discusses the impact of food processing on vitamin content. The contribution of ruminant food sources to B12 intake is specifically evaluated, with its bioavailability taken into account. PMID:26024497

  14. Considering the case for vitamin B12 fortification of flour

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reasons to fortify flour with vitamin B12 are considered, which include the high prevalence of depletion and deficiency of this vitamin that occurs in persons of all ages in resource-poor countries and in elderly in wealthier countries, as well as the adverse functional consequences of poor vitamin ...

  15. Characterization of vitamin B12 in Dunaliella salina.

    PubMed

    Kumudha, Anantharajappa; Sarada, Ravi

    2016-01-01

    Vitamin B12 is one of nature's complex metabolite which is industrially produced using certain bacteria. Algae could be an alternative source of vitamin B12 and in this study, vitamin B12 from a halotolerant green alga, Dunaliella salina V-101 was purified and characterized. The extract of Dunaliella was purified by passing through Amberlite XAD-2 and EASI-extract vitamin B12 immunoaffinity column. The total vitamin B12 content in purified sample fractions was 422?g/100g dry weight as determined by the chemiluminescence method which was almost close to 492?g/100g dry weight as estimated by microbiological method. Further quantification of total vitamin B12 using gold nanoparticle (AUNPs) based aptamer showed 400.8/100g dry weight. There was a good correlation among all the methods of quantification. Adenosylcobalamin, a form of vitamin B12 which is a cofactor for methylmalonyl CoA mutase was identified by HPLC. Upon quantification, Dunaliella was found to contain 344?g of adenosylcobalamin for 100g dry biomass. Authenticity of adenosylcobalmin was confirmed by tandem mass spectrometry (MS/MS), selected ion recording (SIR) and multiple reaction monitoring (MRM) studies. PMID:26788012

  16. Vitamin B12 Intramuscular Injections Versus Oral Supplements

    PubMed Central

    Masucci, L; Goeree, R

    2013-01-01

    Background Vitamin B12 deficiency can lead to adverse health effects such as anemia and, in some cases, permanent neurologic damage. In Canada, patients with vitamin B12 deficiency are typically given intramuscular injections, which incur considerable cost and inconvenience. The clinical evidence-based analysis has found that oral supplementation is as effective as intramuscular injections. Objectives This economic analysis aimed to estimate the cost savings of switching from intramuscular injections to high-dose oral supplements for patients aged 18 years and older with confirmed vitamin B12 deficiency. Data Sources Population-based administrative databases for Ontario were used to identify patients receiving vitamin B12 intramuscular injections in any fiscal year between 2006 and 2011. The Ontario Drug Benefit (ODB) database was used to identify patients who were prescribed vitamin B12 injections, and the Ontario Health Insurance Plan database was used to identify all physician claims for intramuscular injections as well as laboratory tests assessing vitamin B12 levels. The Registered Physicians Database was used to identify the type of physician; the analysis was restricted to family physicians and internists. Review Methods Two cohorts of patients were identified. For cohort 1, the ODB database was used to identify patients who were prescribed vitamin B12 injections. Those covered under the ODB are 65 years of age or older and are economically deprived. A second cohort was created to capture those 18 to 64 years of age receiving injections. Cohort 2 consisted of patients (not in cohort 1) who received 6 or more intramuscular injections within 1 year and had a laboratory test 2 months before the intramuscular injection claim. Physician experts were consulted to estimate the resources and costs of converting patients to oral supplements. The Ministry of Health and Long-Term Care perspective was taken, and all costs are expressed in 2013 Canadian dollars. Results The budget impact analysis demonstrated costs of $2.8 million to the Ministry of Health and Long-Term Care in the first year of conversion; however, in subsequent years there are savings of $4.2 million per year. The cumulative 5-year budget impact demonstrates savings of $14.2 million to the health care system. Limitations This analysis represents the cost of conversion for those currently receiving intramuscular injections. There are no conversion costs for those who are prescribed oral supplements as an initial therapy, and so the savings could be even greater than reported. As well, an underlying assumption of this analysis is that patients will comply with oral supplementation. Conclusions Over 5 years, there are savings of $14.2 million to the health care system from switching to vitamin B12 oral supplements. Plain Language Summary Vitamin B12 deficiency has long been thought to be associated with dementia and other neurocognitive disorders. In a separate report, Health Quality Ontario (HQO) reviewed the published research on this issue and found only weak evidence that vitamin B12 deficiency is associated with the onset of dementia. That review also found moderate evidence that treatment with vitamin B12 does not improve dementia and that oral supplements are as effective as injections of vitamin B12. In 2010, more than 2.9 million serum vitamin B12 tests were performed in Ontario at a cost of $40 million. Each year, approximately 110,000 residents receive vitamin B12 injections to boost their levels of vitamin B12. HQO commissioned an economic analysis to estimate the cost savings of switching from vitamin B12 injections to high-dose oral supplements for patients aged 18 years and older with confirmed B12 deficiency. This study concluded that the Ontario health care system could save $14.5 million in 5 years by switching to oral supplements, assuming that patients took the oral supplements as required. PMID:24379898

  17. Neuroenhancement with Vitamin B12—Underestimated Neurological Significance

    PubMed Central

    Gröber, Uwe; Kisters, Klaus; Schmidt, Joachim

    2013-01-01

    Vitamin B12 is a cofactor of methionine synthase in the synthesis of methionine, the precursor of the universal methyl donor S-Adenosylmethionine (SAMe), which is involved in different epigenomic regulatory mechanisms and especially in brain development. A Vitamin B12 deficiency expresses itself by a wide variety of neurological manifestations such as paraesthesias, skin numbness, coordination disorders and reduced nerve conduction velocity. In elderly people, a latent Vitamin B12 deficiency can be associated with a progressive brain atrophy. Moderately elevated concentrations of homocysteine (>10 µmol/L) have been associated with an increased risk of dementia, notably Alzheimer’s disease, in many cross-sectional and prospective studies. Raised plasma concentrations of homocysteine is also associated with both regional and whole brain atrophy, not only in Alzheimer’s disease but also in healthy elderly people. Clinician awareness should be raised to accurately diagnose and treat early Vitamin B12 deficiency to prevent irreversible structural brain damage. PMID:24352086

  18. Causes of vitamin B12 and folate deficiency.

    PubMed

    Allen, Lindsay H

    2008-06-01

    This review describes current knowledge of the main causes of vitamin B12 and folate deficiency. The most common explanations for poor vitamin B12 status are a low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and malabsorption. Although it has long been known that strict vegetarians (vegans) are at risk for vitamin B12 deficiency, evidence now indicates that low intakes of animal-source foods, such as occur in some lacto-ovo vegetarians and many less-industrialized countries, cause vitamin B12 depletion. Malabsorption of the vitamin is most commonly observed as food-bound cobalamin malabsorption due to gastric atrophy in the elderly, and probably as a result of Helicobacter pylori infection. There is growing evidence that gene polymorphisms in transcobalamins affect plasma vitamin B12 concentrations. The primary cause of folate deficiency is low intake of sources rich in the vitamin, such as legumes and green leafy vegetables, and the consumption of these foods may explain why folate status can be adequate in relatively poor populations. Other situations in which the risk of folate deficiency increases include lactation and alcoholism. PMID:18709879

  19. Vitamin B12 deficiency: Characterization of psychometrics and MRI morphometrics.

    PubMed

    Hsu, Yen-Hsuan; Huang, Ching-Feng; Lo, Chung-Ping; Wang, Tzu-Lan; Tu, Min-Chien

    2016-02-01

    Objectives Vitamin B12 is essential for the integrity of the central nervous system. However, performances in different cognitive domains relevant to vitamin B12 deficiency remain to be detailed. To date, there have been limited studies that examined the relationships between cognitions and structural neuroimaging in a single cohort of low-vitamin B12 status. The present study aimed to depict psychometrics and magnetic resonance imaging (MRI) morphometrics among patients with vitamin B12 deficiency, and to examine their inter-relations. Methods We compared 34 consecutive patients with vitamin B12 deficiency (serum level ?250pg/ml) to 34 demographically matched controls by their cognitive performances and morphometric indices of brain MRI. The correlations between psychometrics and morphometrics were analyzed. Results The vitamin B12 deficiency group had lower scores than the controls on total scores of Mini-Mental Status Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) (both P<0.05), language (P<0.01), orientation (P<0.01), and mental manipulation (P<0.05). The patients also showed a greater frontal horn ratio than the controls (P<0.05). Bicaudate ratio, fronto-occipital ratio, uncotemporal index, and normalized interuncal distance all showed a strong correlation with the total score of MMSE and CASI (all P<0.01). Among these psychometric and morphometric indices, pronounced correlations between bicaudate ratio and long-term memory, mental manipulation, orientation, language, and verbal fluency were noted (all P<0.01). Discussion Vitamin B12 deficiency is associated with a global cognition decline with language, orientation, and mental manipulation selectively impaired. Preferential atrophy in frontal regions is the main neuroimaging feature. Although the frontal ratio highlights the relevant atrophy among patients, the bicaudate ratio might be the best index on the basis of its strong association with global cognition and related cognitive domains, implying dysfunction of fronto-subcortical circuits as the fundamental pathogenesis related to vitamin B12 deficiency. PMID:26339714

  20. A Rare Case of Vitamin B12 Deficiency with Ascites

    PubMed Central

    Reddy, Mugannagari Maheshwar; Vaddera, Sameeraja; Rajini, G; Tikeli, Vinil

    2014-01-01

    Vitamin B12 deficiency is widespread than assumed in population. At risk are older people, pregnant women, vegans, patients with renal and intestinal diseases. Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. In the population, the prevalence of vitamin B12 deficiency in younger people is 5% to 7% which is less compared to elderly people. In developing countries, deficiency is much more common, starting in early life and persisting across the life span. Here, we present a 16-year-old female patient presenting with ascites since 2 months who was subsequently investigated and diagnosed to have nutritional megaloblastic anaemia secondary to vitamin B12 deficiency after exclusion of other infective, neoplastic, autoimmune and inflammatory diseases. Inspite, patient was treated with antitubercular drugs but she did not respond. After supplementation of Vitamin B12, ascites responded well. Inadequate intake due to low consumption of animal source foods is the main cause of low serum vitamin B12 in younger adults and likely the main cause in poor population worldwide. PMID:25177593

  1. A rare case of vitamin B12 deficiency with ascites.

    PubMed

    Rajsekhar, Putta; Reddy, Mugannagari Maheshwar; Vaddera, Sameeraja; Rajini, G; Tikeli, Vinil

    2014-07-01

    Vitamin B12 deficiency is widespread than assumed in population. At risk are older people, pregnant women, vegans, patients with renal and intestinal diseases. Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. In the population, the prevalence of vitamin B12 deficiency in younger people is 5% to 7% which is less compared to elderly people. In developing countries, deficiency is much more common, starting in early life and persisting across the life span. Here, we present a 16-year-old female patient presenting with ascites since 2 months who was subsequently investigated and diagnosed to have nutritional megaloblastic anaemia secondary to vitamin B12 deficiency after exclusion of other infective, neoplastic, autoimmune and inflammatory diseases. Inspite, patient was treated with antitubercular drugs but she did not respond. After supplementation of Vitamin B12, ascites responded well. Inadequate intake due to low consumption of animal source foods is the main cause of low serum vitamin B12 in younger adults and likely the main cause in poor population worldwide. PMID:25177593

  2. The electronic structure and chemical bonding of vitamin B12

    NASA Astrophysics Data System (ADS)

    Kurmaev, E. Z.; Moewes, A.; Ouyang, L.; Randaccio, L.; Rulis, P.; Ching, W. Y.; Bach, M.; Neumann, M.

    2003-05-01

    The electronic structure and chemical bonding of vitamin B12 (cyanocobalamin) and B12-derivative (methylcobalamin) are studied by means of X-ray emission (XES) and photoelectron (XPS) spectroscopy. The obtained results are compared with ab initio electronic structure calculations using the orthogonalized linear combination of the atomic orbital method (OLCAO). We show that the chemical bonding in vitamin B12 is characterized by the strong Co-C bond and relatively weak axial Co-N bond. It is further confirmed that the Co-C bond in cyanocobalamin is stronger than that of methylcobalamin resulting in their different biological activity.

  3. Vitamin-B12 deficiency following therapy in gynecologic oncology

    SciTech Connect

    Bandy, L.C.; Clarke-Pearson, D.L.; Creasman, W.T.

    1984-03-01

    Vitamin-B12 deficiency results from inadequate absorption of the vitamin by the distal ileum and depletion of available stores. Both radiotherapy and intestinal resection can contribute to development of this condition. The significance of this problem in gynecologic oncology is discussed and two patients are described.

  4. MICROBIAL DEGRADATION OF CORRINOIDS I. Vitamin B12

    PubMed Central

    Scott, W. M.; Burgus, R. C.; Hufham, J. B.; Pfiffner, J. J.

    1964-01-01

    Scott, W. M. (Wayne State University, Detroit, Mich.), R. C. Burgus, J. B. Hufham, and J. J. Pfiffner. Microbial degradation of corrinoids. I. Vitamin B12. J. Bacteriol. 88:581585. 1964.Microorganisms isolated from a variety of soil, sewage, and mud samples, and stock cultures, were examined for the ability to degrade vitamin B12. More than 200 isolates which attack the vitamin were examined, and they all demonstrated reversible fading of the red vitamin. The color was restored by aeration. Very few microorganisms were able to degrade the vitamin to permanently colorless products, although many were able to degrade it partially, to produce new pigments. Some of these pigments appeared similar, if not identical, although they were produced by different bacteria. Radiotracer and electrophoretic mobility data are presented to show that the transformation products are derived from the vitamin. All the degradative microorganisms isolated were bacteria, and the most active was Pseudomonas rubescens. PMID:14208491

  5. Assessment of the Vitamin B12 Status of Pregnant Women in Nigeria Using Plasma Holotranscobalamin

    PubMed Central

    VanderJagt, Dorothy J.; Ujah, Innocent A. O.; Ikeh, Eugene I.; Bryant, Jessica; Pam, Victor; Hilgart, Amelia; Crossey, Michael J.; Glew, Robert H.

    2011-01-01

    Maternal vitamin B12 deficiency during pregnancy is an independent risk factor for neural tube defects and other neurological problems in infants. We determined the vitamin B12 status of 143 pregnant women in Nigeria representing all trimesters who presented to an antenatal clinic in Jos, Nigeria, using holotranscobalamin II levels (holoTCII), which is a measure of the vitamin B12 that is available for uptake into tissues. The holoTCII concentration ranged from 13 to 128?pmol/L. Using a cutoff of 40?pmol/L, 36% of the women were classified as vitamin B12-deficient. HoloTCII concentrations correlated negatively with plasma homocysteine levels (r = ?0.24, P = 0.003) and positively with red blood cell folate concentrations (r = 0.28, P < 0.001). These data underscore the importance of supplementing pregnant women in Nigeria with vitamin B12 in order to ensure adequate vitamin B12 status and decrease the risk for neural tube defects. PMID:21789284

  6. Involuntary movements due to vitamin B12 deficiency.

    PubMed

    de Souza, Aaron; Moloi, M W

    2014-12-01

    Deficiency of vitamin B12 produces protean effects on the nervous system, most commonly neuropathy, myelopathy, cognitive and behavioural symptoms, and optic atrophy. Involuntary movements comprise a relatively rare manifestation of this readily treatable disorder. Both adults and infants deficient in vitamin B12 may present with chorea, tremor, myoclonus, Parkinsonism, dystonia, or a combination of these, which may precede diagnosis or become apparent only a few days after parenteral replacement therapy has begun. The pathogenesis of these movement disorders shows interesting parallels to certain neurodegenerative conditions. The clinical syndrome responds well to vitamin B12 supplementation in most cases, and an early diagnosis is essential to reverse the haematological and neurological dysfunction characteristic of this disorder. In this article, we elucidate the association of vitamin B12 deficiency with movement disorders in adults and in infants, discuss the pathogenesis of this association, review previously reported cases, and present a young adult male with severe generalized chorea that showed a salutary response to vitamin B12 supplementation. PMID:24852503

  7. Oral contraceptives: effect of folate and vitamin B12 metabolism.

    PubMed Central

    Shojania, A. M.

    1982-01-01

    Women who use oral contraceptives have impaired folate metabolism as shown by slightly but significantly lower levels of folate in the serum and the erythrocytes and an increased urinary excretion of formiminoglutamic acid. The vitamin B12 level in their serum is also significantly lower than that of control groups. However, there is no evidence of tissue depletion of vitamin B12 associated with the use of oral contraceptives. The causes and clinical significance of the impairment of folate and vitamin B12 metabolism in these women is discussed in this review of the literature. Clinicians are advised to ensure that women who shop taking "the pill" because they wish to conceive have adequate folate stores before becoming pregnant. PMID:7037144

  8. Dietary Sources of Vitamin B-12 and Their Association with Vitamin B-12 Status Markers in Healthy Older Adults in the B-PROOF Study.

    PubMed

    Brouwer-Brolsma, Elske M; Dhonukshe-Rutten, Rosalie A M; van Wijngaarden, Janneke P; Zwaluw, Nikita L van der; Velde, Nathalie van der; de Groot, Lisette C P G M

    2015-09-01

    Low vitamin B-12 concentrations are frequently observed among older adults. Malabsorption is hypothesized to be an important cause of vitamin B-12 inadequacy, but serum vitamin B-12 may also be differently affected by vitamin B-12 intake depending on food source. We examined associations between dietary sources of vitamin B-12 (meat, fish and shellfish, eggs, dairy) and serum vitamin B-12, using cross-sectional data of 600 Dutch community-dwelling adults (?65 years). Dietary intake was assessed with a validated food frequency questionnaire. Vitamin B-12 concentrations were measured in serum. Associations were studied over tertiles of vitamin B-12 intake using P for trend, by calculating prevalence ratios (PRs), and splines. Whereas men had significantly higher vitamin B-12 intakes than women (median (25th-75th percentile): 4.18 (3.29-5.38) versus 3.47 (2.64-4.40) ?g/day), serum vitamin B-12 did not differ between the two sexes (mean standard deviation (SD): 275 104 pmol/L versus 290 113 pmol/L). Higher intakes of dairy, meat, and fish and shellfish were significantly associated with higher serum vitamin B-12 concentrations, where meat and dairy-predominantly milk were the most potent sources. Egg intake did not significantly contribute to higher serum vitamin B-12 concentrations. Thus, dairy and meat were the most important contributors to serum vitamin B-12, followed by fish and shellfish. PMID:26389945

  9. Dietary Sources of Vitamin B-12 and Their Association with Vitamin B-12 Status Markers in Healthy Older Adults in the B-PROOF Study

    PubMed Central

    Brouwer-Brolsma, Elske M.; Dhonukshe-Rutten, Rosalie A. M.; van Wijngaarden, Janneke P.; van der Zwaluw, Nikita L.; van der Velde, Nathalie; de Groot, Lisette C. P. G. M.

    2015-01-01

    Low vitamin B-12 concentrations are frequently observed among older adults. Malabsorption is hypothesized to be an important cause of vitamin B-12 inadequacy, but serum vitamin B-12 may also be differently affected by vitamin B-12 intake depending on food source. We examined associations between dietary sources of vitamin B-12 (meat, fish and shellfish, eggs, dairy) and serum vitamin B-12, using cross-sectional data of 600 Dutch community-dwelling adults (≥65 years). Dietary intake was assessed with a validated food frequency questionnaire. Vitamin B-12 concentrations were measured in serum. Associations were studied over tertiles of vitamin B-12 intake using P for trend, by calculating prevalence ratios (PRs), and splines. Whereas men had significantly higher vitamin B-12 intakes than women (median (25th–75th percentile): 4.18 (3.29–5.38) versus 3.47 (2.64–4.40) μg/day), serum vitamin B-12 did not differ between the two sexes (mean ± standard deviation (SD): 275 ± 104 pmol/L versus 290 ± 113 pmol/L). Higher intakes of dairy, meat, and fish and shellfish were significantly associated with higher serum vitamin B-12 concentrations, where meat and dairy—predominantly milk were the most potent sources. Egg intake did not significantly contribute to higher serum vitamin B-12 concentrations. Thus, dairy and meat were the most important contributors to serum vitamin B-12, followed by fish and shellfish. PMID:26389945

  10. Involuntary movements misdiagnosed as seizure during vitamin B12 treatment.

    PubMed

    Carman, Kursat Bora; Belgemen, Tugba; Yis, Uluc

    2013-11-01

    Seizures and epilepsy are a common problem in childhood. Nonepileptic paroxysmal events are conditions that can mimic seizure and frequent in early childhood. Nonepileptic paroxysmal events can be due to physiological or exaggerated physiological responses, parasomnias, movement disorders, behavioral or psychiatric disturbances, or to hemodynamic, respiratory, or gastrointestinal dysfunction. Vitamin B12 deficiency is a treatable cause of failure to thrive and developmental regression, involuntary movements, and anemia. Involuntary movements rarely may appear a few days after the initiation of vitamin B12 treatments and might be misdiagnosed as seizure. Here, we report 2 patients who presented with involuntary movements with his video image. PMID:24196096

  11. Vitamin B12 Deficiency in Infancy: The Case for Screening.

    PubMed

    Singh, Gurpreet; Le, Doan; Schnabl, Kareena; Leaker, Michael T; Steele, MacGregor; Sparkes, Rebecca L

    2016-04-01

    The classic principles put forth by Wilson and Jungner are often applied to determine the suitability of a condition for universal newborn screening. The three cases described here portray the harmful effects of vitamin B12 deficiency in infancy. The challenges and opportunities of early recognition and treatment are highlighted. Screening newborns would allow early detection and prevention of severe neurological damage in vitamin B12 -deficient infants and enable diagnosis of unrecognized maternal pernicious anemia in asymptomatic mothers. However, lack of standardized methodology and screening cutoffs present challenges to the use of current tandem mass spectrometry technologies for screening. PMID:26806811

  12. High-dose compared with low-dose vitamin B-12 supplement use is not associated with higher vitamin B-12 status in children, adolescents, and older adults.

    PubMed

    MacFarlane, Amanda J; Shi, Yipu; Greene-Finestone, Linda S

    2014-06-01

    Over-the-counter vitamin supplements on the Canadian market are permitted to contain a daily vitamin B-12 dose of up to 1000 μg. Our objective was to determine the association between total daily vitamin B-12 supplement dose and markers of vitamin B-12 status in Canadians. Blood collected from a nationally representative sample aged 6-79 y (n = ∼5600) in the Canadian Health Measures Survey (2007-2009) was analyzed for serum vitamin B-12 and plasma total homocysteine (tHcy). Total daily intake of vitamin B-12 from single and multivitamin supplements was calculated. Individuals that indicated proton pump inhibitor or vitamin B-12 injection treatment were excluded from the supplement dose and tHcy analyses; folate-deficient individuals were also excluded from the tHcy analysis. Twenty-three percent of children, 12.3% of adolescents, and 25.5% of adults consumed a vitamin B-12-containing supplement. Supplement users had 33% higher serum vitamin B-12 and 4.2% higher prevalence of adequacy than did non-supplement users. Children and adolescents consuming >10 μg/d supplemental vitamin B-12 did not demonstrate higher serum vitamin B-12, higher prevalence of serum vitamin B-12 adequacy, or lower tHcy than did those consuming >0-10 μg/d. The association between serum vitamin B-12 reached a plateau at doses of >25 and >10-25 μg/d in adults aged 46-59 and 60-79 y, respectively. The prevalences of serum vitamin B-12 adequacy and normal tHcy, and tHcy did not differ by vitamin B-12 supplement dose in adults >45 y. In this cross-sectional study, vitamin B-12 supplement doses >10-25 μg/d were not associated with higher vitamin B-12 status in children, adolescents, or older adults compared with lower doses. PMID:24699807

  13. How prevalent is vitamin B(12) deficiency among vegetarians?

    PubMed

    Pawlak, Roman; Parrott, Scott James; Raj, Sudha; Cullum-Dugan, Diana; Lucus, Debbie

    2013-02-01

    Vegetarians are at risk for vitamin B(12) (B12) deficiency due to suboptimal intake. The goal of the present literature review was to assess the rate of B12 depletion and deficiency among vegetarians and vegans. Using a PubMed search to identify relevant publications, 18 articles were found that reported B12 deficiency rates from studies that identified deficiency by measuring methylmalonic acid, holo-transcobalamin II, or both. The deficiency rates reported for specific populations were as follows: 62% among pregnant women, between 25% and almost 86% among children, 21-41% among adolescents, and 11-90% among the elderly. Higher rates of deficiency were reported among vegans compared with vegetarians and among individuals who had adhered to a vegetarian diet since birth compared with those who had adopted such a diet later in life. The main finding of this review is that vegetarians develop B12 depletion or deficiency regardless of demographic characteristics, place of residency, age, or type of vegetarian diet. Vegetarians should thus take preventive measures to ensure adequate intake of this vitamin, including regular consumption of supplements containing B12. PMID:23356638

  14. Iron limitation of a springtime bacterial and phytoplankton community in the ross sea: implications for vitamin b(12) nutrition.

    PubMed

    Bertrand, Erin M; Saito, Mak A; Lee, Peter A; Dunbar, Robert B; Sedwick, Peter N; Ditullio, Giacomo R

    2011-01-01

    The Ross Sea is home to some of the largest phytoplankton blooms in the Southern Ocean. Primary production in this system has previously been shown to be iron limited in the summer and periodically iron and vitamin B(12) colimited. In this study, we examined trace metal limitation of biological activity in the Ross Sea in the austral spring and considered possible implications for vitamin B(12) nutrition. Bottle incubation experiments demonstrated that iron limited phytoplankton growth in the austral spring while B(12), cobalt, and zinc did not. This is the first demonstration of iron limitation in a Phaeocystis antarctica-dominated, early season Ross Sea phytoplankton community. The lack of B(12) limitation in this location is consistent with previous Ross Sea studies in the austral summer, wherein vitamin additions did not stimulate P. antarctica growth and B(12) was limiting only when bacterial abundance was low. Bottle incubation experiments and a bacterial regrowth experiment also revealed that iron addition directly enhanced bacterial growth. B(12) uptake measurements in natural water samples and in an iron fertilized bottle incubation demonstrated that bacteria serve not only as a source for vitamin B(12), but also as a significant sink, and that iron additions enhanced B(12) uptake rates in phytoplankton but not bacteria. Additionally, vitamin uptake rates did not become saturated upon the addition of up to 95?pM B(12). A rapid B(12) uptake rate was observed after 13?min, which then decreased to a slower constant uptake rate over the next 52?h. Results from this study highlight the importance of iron availability in limiting early season Ross Sea phytoplankton growth and suggest that rates of vitamin B(12) production and consumption may be impacted by iron availability. PMID:21886638

  15. Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: B vitamins such as folate, vitamin B-6, and vitamin B-12 are coenzymes that are important for DNA integrity and stability. Deficiency in these B vitamins may promote tumor carcinogenesis. Objective: We prospectively evaluated plasma concentrations of folate, pyridoxal 5'-phosphate (PLP; ...

  16. Folate–vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous reports on pernicious anemia treatment suggested that high folic acid intake adversely influences the natural history of vitamin B-12 deficiency, which affects many elderly individuals. However, experimental investigation of this hypothesis is unethical, and the few existing observational d...

  17. Folate and vitamin B12 in idiopathic male infertility.

    PubMed

    Murphy, Laurel E; Mills, James L; Molloy, Anne M; Qian, Cong; Carter, Tonia C; Strevens, Helena; Wide-Swensson, Dag; Giwercman, Aleksander; Levine, Richard J

    2011-11-01

    Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been associated with idiopathic male infertility, few studies have examined other folate-related metabolites and genes. We investigated whether idiopathic male infertility is associated with variants in folate, vitamin B(12) (B12) and total homocysteine (tHcy)-related genes and measured these metabolites in blood. We conducted a case-control study that included 153 men with idiopathic infertility and 184 fertile male controls recruited at the Fertility Center and Antenatal Care Center, University Hospital, Malm and Lund, Sweden. Serum folate, red cell folate (RCF), serum B12, plasma tHcy and semen quality were measured. Subjects were genotyped for 20 common variants in 12 genes related to folate/B12/homocysteine metabolism. Metabolite concentrations and genotype distributions were compared between cases and controls using linear and logistic regression with adjustment for covariates. The phosphatidylethanolamine N-methyltransferase (PEMT) M175V and TCblR rs173665 polymorphisms were significantly associated with infertility (P=0.01 and P=0.009, respectively), but not with semen quality. Among non-users of supplements, infertile men had lower serum folate concentrations than fertile men (12.89 vs. 14.73 nmol l(-1); P=0.02), but there were no significant differences in RCF, B12 or tHcy. Folate, B12 and tHcy concentrations were not correlated with any semen parameters. This study provides little support for low folate or B12 status in the pathogenesis of idiopathic male infertility. Although additional data are needed to confirm these initial findings, our results suggest that PEMT and TCblR, genes involved in choline and B12 metabolism, merit further investigation in idiopathic male infertility. PMID:21857689

  18. Effect of combined folic acid, Vitamin B6, and Vitamin B12 on colorectal adenoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma. The Women's Antioxidant and Folic Acid Cardiovascular Study was a rand...

  19. Vitamin B12 as a modulator of gut microbial ecology.

    PubMed

    Degnan, Patrick H; Taga, Michiko E; Goodman, Andrew L

    2014-11-01

    The microbial mechanisms and key metabolites that shape the composition of the human gut microbiota are largely unknown, impeding efforts to manipulate dysbiotic microbial communities toward stability and health. Vitamins, which by definition are not synthesized in sufficient quantities by the host and can mediate fundamental biological processes in microbes, represent an attractive target for reshaping microbial communities. Here, we discuss how vitamin B12 (cobalamin) impacts diverse host-microbe symbioses. Although cobalamin is synthesized by some human gut microbes, it is a precious resource in the gut and is likely not provisioned to the host in significant quantities. However, this vitamin may make an unrecognized contribution in shaping the structure and function of human gut microbial communities. PMID:25440056

  20. Vitamin B12 as a modulator of gut microbial ecology

    PubMed Central

    Degnan, Patrick H.; Taga, Michiko E.; Goodman, Andrew L.

    2014-01-01

    The microbial mechanisms and key metabolites that shape the composition of the human gut microbiota are largely unknown, impeding efforts to manipulate dysbiotic microbial communities towards stability and health. Vitamins, which by definition are not synthesized in sufficient quantities by the host and can mediate fundamental biological processes in microbes, represent an attractive target for reshaping microbial communities. Here, we discuss how vitamin B12 (cobalamin) impacts diverse host-microbe symbioses. Although cobalamin is synthesized by some human gut microbes, it is a precious resource in the gut and is likely not provisioned to the host in significant quantities. However, this vitamin may make an unrecognized contribution in shaping the structure and function of human gut microbial communities. PMID:25440056

  1. Anaerobic biosynthesis of the lower ligand of vitamin B12

    PubMed Central

    Hazra, Amrita B.; Han, Andrew W.; Mehta, Angad P.; Mok, Kenny C.; Osadchiy, Vadim; Begley, Tadhg P.; Taga, Michiko E.

    2015-01-01

    Vitamin B12 (cobalamin) is required by humans and other organisms for diverse metabolic processes, although only a subset of prokaryotes is capable of synthesizing B12 and other cobamide cofactors. The complete aerobic and anaerobic pathways for the de novo biosynthesis of B12 are known, with the exception of the steps leading to the anaerobic biosynthesis of the lower ligand, 5,6-dimethylbenzimidazole (DMB). Here, we report the identification and characterization of the complete pathway for anaerobic DMB biosynthesis. This pathway, identified in the obligate anaerobic bacterium Eubacterium limosum, is composed of five previously uncharacterized genes, bzaABCDE, that together direct DMB production when expressed in anaerobically cultured Escherichia coli. Expression of different combinations of the bza genes revealed that 5-hydroxybenzimidazole, 5-methoxybenzimidazole, and 5-methoxy-6-methylbenzimidazole, all of which are lower ligands of cobamides produced by other organisms, are intermediates in the pathway. The bza gene content of several bacterial and archaeal genomes is consistent with experimentally determined structures of the benzimidazoles produced by these organisms, indicating that these genes can be used to predict cobamide structure. The identification of the bza genes thus represents the last remaining unknown component of the biosynthetic pathway for not only B12 itself, but also for three other cobamide lower ligands whose biosynthesis was previously unknown. Given the importance of cobamides in environmental, industrial, and human-associated microbial metabolism, the ability to predict cobamide structure may lead to an improved ability to understand and manipulate microbial metabolism. PMID:26246619

  2. Anaerobic biosynthesis of the lower ligand of vitamin B12.

    PubMed

    Hazra, Amrita B; Han, Andrew W; Mehta, Angad P; Mok, Kenny C; Osadchiy, Vadim; Begley, Tadhg P; Taga, Michiko E

    2015-08-25

    Vitamin B12 (cobalamin) is required by humans and other organisms for diverse metabolic processes, although only a subset of prokaryotes is capable of synthesizing B12 and other cobamide cofactors. The complete aerobic and anaerobic pathways for the de novo biosynthesis of B12 are known, with the exception of the steps leading to the anaerobic biosynthesis of the lower ligand, 5,6-dimethylbenzimidazole (DMB). Here, we report the identification and characterization of the complete pathway for anaerobic DMB biosynthesis. This pathway, identified in the obligate anaerobic bacterium Eubacterium limosum, is composed of five previously uncharacterized genes, bzaABCDE, that together direct DMB production when expressed in anaerobically cultured Escherichia coli. Expression of different combinations of the bza genes revealed that 5-hydroxybenzimidazole, 5-methoxybenzimidazole, and 5-methoxy-6-methylbenzimidazole, all of which are lower ligands of cobamides produced by other organisms, are intermediates in the pathway. The bza gene content of several bacterial and archaeal genomes is consistent with experimentally determined structures of the benzimidazoles produced by these organisms, indicating that these genes can be used to predict cobamide structure. The identification of the bza genes thus represents the last remaining unknown component of the biosynthetic pathway for not only B12 itself, but also for three other cobamide lower ligands whose biosynthesis was previously unknown. Given the importance of cobamides in environmental, industrial, and human-associated microbial metabolism, the ability to predict cobamide structure may lead to an improved ability to understand and manipulate microbial metabolism. PMID:26246619

  3. Vitamin B12 deficiency presenting as acute ataxia.

    PubMed

    Crawford, John Ross; Say, Daphne

    2013-01-01

    A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient. PMID:23536622

  4. [Rare Case of Strongyloides stercoralis with Vitamin B12 Deficiency].

    PubMed

    Kad?lar, zlem; Bozkurt, Berna; Karakee, Engin; Kaya, Tezcan; ifti, ?hsan Hakk?; Tamer, Ali

    2015-09-01

    Strongyloidiyasis is endemic in tropical and subtropical regions, and mostly soil transmitted nematode disease that is seen as sporadic cases in Turkey. As may be asymptomatic in healthy individuals, it may even cause death in immunosuppressive people. We report a case of Strongyloides stercoralis infection in a patient, 29 years old young male was admitted to our institution with diarrhea who has got vitamin B12 deficiency and eosinophilia. The case represents an extremely rare and in our knowledge, it is the first case in Sakarya. PMID:26470934

  5. Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects.

    PubMed

    Watanabe, Fumio; Yabuta, Yukinori; Tanioka, Yuri; Bito, Tomohiro

    2013-07-17

    The usual dietary sources of vitamin B12 are animal-source based foods, including meat, milk, eggs, fish, and shellfish, although a few plant-based foods such as certain types of dried lavers (nori) and mushrooms contain substantial and considerable amounts of vitamin B12, respectively. Unexpectedly, detailed characterization of vitamin B12 compounds in foods reveals the presence of various corrinoids that are inactive in humans. The majority of edible blue-green algae (cyanobacteria) and certain edible shellfish predominately contain an inactive corrinoid known as pseudovitamin B12. Various factors affect the bioactivity of vitamin B12 in foods. For example, vitamin B12 is partially degraded and loses its biological activity during cooking and storage of foods. The intrinsic factor-mediated gastrointestinal absorption system in humans has evolved to selectively absorb active vitamin B12 from naturally occurring vitamin B12 compounds, including its degradation products and inactive corrinoids that are present in daily meal foods. The objective of this review is to present up-to-date information on various factors that can affect the bioactivity of vitamin B12 in foods. To prevent vitamin B12 deficiency in high-risk populations such as vegetarians and elderly subjects, it is necessary to identify plant-source foods that contain high levels of bioactive vitamin B12 and, in conjunction, to prepare the use of crystalline vitamin B12-fortified foods. PMID:23782218

  6. Vitamin B-12 Supplementation during Pregnancy and Early Lactation Increases Maternal, Breast Milk, and Infant Measures of Vitamin B-12 Status12

    PubMed Central

    Duggan, Christopher; Srinivasan, Krishnamachari; Thomas, Tinku; Samuel, Tinu; Rajendran, Ramya; Muthayya, Sumithra; Finkelstein, Julia L.; Lukose, Ammu; Fawzi, Wafaie; Allen, Lindsay H.; Bosch, Ronald J.; Kurpad, Anura V.

    2014-01-01

    Pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and indicators of low vitamin B-12 status have been associated with adverse pregnancy outcomes, including anemia, low birth weight, and intrauterine growth retardation. To evaluate whether daily oral vitamin B-12 supplementation during pregnancy increases maternal and infant measures of vitamin B-12 status, we performed a randomized, placebo-controlled clinical trial. Pregnant women <14 wk of gestation in Bangalore, India, were randomly assigned to receive daily oral supplementation with vitamin B-12 (50 ?g) or placebo through 6 wk postpartum. All women were administered iron and folic acid supplements throughout pregnancy. One hundred eighty-three women were randomly assigned to receive vitamin B-12 and 183 to receive placebo. Compared with placebo recipients, vitamin B-12supplemented women had significantly higher plasma vitamin B-12 concentrations at both the second (median vitamin B-12 concentration: 216 vs. 111 pmol/L, P < 0.001) and third (median: 184 vs. 105 pmol/L, P < 0.001) trimesters. At 6 wk postpartum, median breast milk vitamin B-12 concentration was 136 pmol/L in vitamin B-12supplemented women vs. 87 pmol/L in the placebo group (P < 0.0005). Among vitamin B-12supplemented women, the incidence of delivering an infant with intrauterine growth retardation was 33 of 131 (25%) vs. 43 of 125 (34%) in those administered placebo (P = 0.11). In a subset of infants tested at 6 wk of age, median plasma vitamin B-12 concentration was 199 pmol/L in those born to supplemented women vs. 139 pmol/L in the placebo group (P = 0.01). Infant plasma methylmalonic acid and homocysteine concentrations were significantly lower in the vitamin B-12 group as well. Oral supplementation of urban Indian women with vitamin B-12 throughout pregnancy and early lactation significantly increases vitamin B-12 status of mothers and infants. It is important to determine whether there are correlations between these findings and neurologic and metabolic functions. This trial was registered at clinicaltrials.gov as NCT00641862. PMID:24598885

  7. Vitamin B12 deficiency in the institutionalized elderly: A regional study.

    PubMed

    Wong, C W; Ip, C Y; Leung, C P; Leung, C S; Cheng, J N; Siu, C Y

    2015-09-01

    The prevalence of vitamin B12 deficiency increases with age and is suggested to be even higher in the elderly living in institutions. This retrospective study evaluated the vitamin B12 and folate status of 1996 institutionalized elderly residents aged over 65years. Among them, 34.9% had vitamin B12 deficiency (serum vitamin B12 <150pmol/L), 11.8% had folate deficiency (serum folate <6.8nmol/L), and 4.9% had both. The majority of vitamin B12 deficient residents (68%) had serum vitamin B12 between 100pmol/L and 149pmol/L. Macrocytosis was found in 24.2% of vitamin B12 deficient residents. A significant increase in macrocytosis was associated with a decrease in serum vitamin B12 below 100pmol/L. Macrocytosis was most common in those with vitamin B12 ?69pmol/L (50.9%). Overall, vitamin B12 deficiency is common in the institutionalized elderly, however macrocytosis cannot predict deficiency. More liberal testing for vitamin B12 status in the institutionalized elderly may be warranted. PMID:26122132

  8. Enhancing the vitamin B12 production and growth of Propionibacterium freudenreichii in tofu wastewater via a light-induced vitamin B12 riboswitch.

    PubMed

    Yu, Yue; Zhu, Xuan; Shen, Yubiao; Yao, Huanghong; Wang, Peiheng; Ye, Kun; Wang, Xiaofeng; Gu, Qing

    2015-12-01

    The vitamin B12-dependent riboswitch is a crucial factor that regulates gene transcription to mediate the growth of and vitamin B12 synthesis by Propionibacterium freudenreichii. In this study, the effect of various wavelengths of light on the growth rate and vitamin B12 synthesis was studied. Red, green, and blue light-emitting diodes (LEDs) were selected, and a dark condition was used as the control. The microorganism growth rate was measured using a spectrophotometer and plate counting, while the vitamin B12 content was determined using an HPLC-based method. The optical density at 600nm (OD600) values indicated that P. freudenreichii grew better under the continuous and discontinuous blue light conditions. Moreover, under the blue light condition, P. freudenreichii tended to have a higher growth rate (0.332h(-1)) and vitamin B12 synthesis (ca. 10?g/mL) in tofu wastewater than in dark conditions. HPLC analysis also showed that more methylcobalamin was produced under the blue light conditions than in the other conditions. The cbiB gene transcription results showed that blue light induced the synthesis of this vitamin B12 synthesis enzyme. Moreover, the results of inhibiting the expression of green fluorescent protein indicated that blue light removed the inhibition by the vitamin B12-dependent riboswitch. This method can be used to reduce fermentation time and produce more vitamin B12 in tofu wastewater. PMID:26373724

  9. Breast milk vitamin B-12 concentrations of Guatemalan women are correlated with maternal but not infant vitamin B12 status at 12 months postpartum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In our previous studies one third of lactating Guatemalan women, infants and children had deficient or marginal serum vitamin B-12 concentrations. Relationships among maternal and infant status and breast milk vitamin B-12, however, have not been investigated in such populations. Our purpose was to ...

  10. [Vitamin B12 and folate in non-institutionalized urban older people].

    PubMed

    Ramrez Pereda, Abraham; Pacheco, Bertha I; Astiazarn-Garca, Humberto; Esparza-Romero, Julin; Alemn-Mateo, Heliodoro

    2006-06-01

    Vitamin B12 and folate deficiencies are the main nutritional determinants of hyperhomocysteinemia, which is an independent risk factor for cardiovascular diseases. There is scarce information about nutritional status on vitamin B12 and serum levels of folate in Mexican older people. The objective was to evaluate the nutritional status of vitamin B12 and folic acid concentration in non-institutionalized, urban elderly men and women subjects. One hundred volunteers over 60 years were included in this cross-sectional study. Serum levels of vitamin B12 and folate were measured. In addition some biochemical and anthropometric indicators were also evaluated. Considering serum values of vitamin, 30% had vitamin B12 deficiency, 52% normal status and 18% with high levels. None subjects had folic acid deficiency, by the contrary, a high proportion (62%) showed elevated levels in serum. There was an effect of sex on vitamin B12 status. Elderly men showed significantly lower levels of vitamin B12, and it was according with significant higher prevalence of vitamin B12 deficiency in this group as compared with the women group. The high proportion of vitamin B12 deficiency found in this study underline a possible public health problem and guarantee further survey-studies about vitamin B12 status and to explore causes and consequences of the deficiency. Finally, due the sample size and the design of the study, the results must be seen with caution and not try to generalize. PMID:17024957

  11. VITAMIN B-12 SUPPLEMENTATION OF DEFICIENT LACTATING GUATEMALAN WOMEN IMPROVES MATERNAL BUT NOT INFANT STATUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin B-12 deficiency is common in mothers and infants where maternal intake of animals source foods is low. The first six months post-partum is a critical period of neurological development requiring vitamin B-12. A pilot study was designed to determine the dose of B-12 to the mothers that would ...

  12. Vitamin B12 deficiency in the elderly: is it worth screening?

    PubMed

    Wong, C W

    2015-04-01

    Vitamin B12 deficiency is common among the elderly. Elderly people are particularly at risk of vitamin B12 deficiency because of the high prevalence of atrophic gastritis-associated food-cobalamin (vitamin B12) malabsorption, and the increasing prevalence of pernicious anaemia with advancing age. The deficiency most often goes unrecognised because the clinical manifestations are highly variable, often subtle and non-specific, but if left undiagnosed the consequences can be serious. Diagnosis of vitamin B12 deficiency, however, is not straightforward as laboratory tests have certain limitations. Setting a cut-off level to define serum vitamin B12 deficiency is difficult; though homocysteine and methylmalonic acid are more sensitive for vitamin B12 deficiency, it may give false result in some conditions and the reference intervals are not standardised. At present, there is no consensus or guideline for diagnosis of this deficiency. It is most often based on the clinical symptoms together with laboratory assessment (low serum vitamin B12 level and elevated serum homocysteine or methylmalonic acid level) and the response to treatment to make definitive diagnosis. Treatment and replacement with oral vitamin B12 can be as effective as parenteral administration even in patients with pernicious anaemia. The suggested oral vitamin B12 dose is 1 mg daily for a month, and then maintenance dose of 125 to 250 g for patients with dietary insufficiency and 1 mg daily for those with pernicious anaemia. Vitamin B12 replacement is safe and without side-effects, but prompt treatment is required to reverse the damage before it becomes extensive or irreversible. At present, there is no recommendation for mass screening for vitamin B12 in the elderly. Nevertheless, the higher prevalence with age, increasing risk of vitamin B12 deficiency in the elderly, symptoms being difficult to recognise, and availability of safe treatment options make screening a favourable option. However, the unavailability of reliable diagnostic tool or gold standard test makes screening difficult to carry out. PMID:25756278

  13. [Effects of Vitamin B12 in Patients with Amyotrophic Lateral Sclerosis and Peripheral Neuropathy].

    PubMed

    Nodera, Hiroyuki; Izumi, Yuishin; Kaji, Ryuji

    2015-09-01

    Vitamin B(12)(vB(12)) deficient is regarded as iatrogenic in some cases. Although the recommended oral intake of vB(12) has been determined, administration of vB(12) exceeding the recommended dose could have multiple pharmacological effects. "Ultra-high dose" vB(12) therapy has been used for peripheral neuropathy and amyotrophic lateral sclerosis, suggesting its promising neuroprotective effects. PMID:26329154

  14. Vitamin B12 deficiency and gastric histopathology in older patients

    PubMed Central

    Dholakia, KR; Dharmarajan, TS; Yadav, D; Oiseth, S; Norkus, EP; Pitchumoni, CS

    2005-01-01

    AIM: To compare upper gastric endoscopic and histopathologic findings in older adults in the presence and absence of B12 deficiency. METHODS: A prospective analysis of upper gastric endoscopic and gastric histopathologic findings from 30 newly identified B12-deficient patients (11 males, 19 females) and 16 controls with normal B12 status (6 males, 10 females) was performed. For all subjects, the indication for upper endoscopy and gastric biopsy were unrelated to B12 status. A single pathologist, blinded to B12 status, processed and interpreted the biopsy samples. Endoscopic and histopathologic findings were correlated with age, gender, hematocrit (Hct), MCV and B12 status. RESULTS: The B12-deficient group had significantly lower mean serum B12 levels compared to the controls (P<0.00005) while their mean Hct, MCV and serum albumin levels were similar. Iron deficiency (ferritin-based) was present in 21% of B12-deficient patients and intrinsic factor antibodies were present in 29% (5/17) of B12-deficient patients. The endoscopic findings revealed significantly different rates of gastritis and atrophy between the B12-deficient and control groups (P?= 0.017). B12-deficient patients had significantly less superficial gastritis (62% vs 94%) and significantly more atrophic gastritis (28% vs 0%) as compared to the controls (P?=?0.039). Intestinal metaplasia was similar in both groups. Helicobacter pylori infection rates were similar in the B12-deficient patients and controls (40% vs 31%). CONCLUSION: Significantly different endoscopic findings and types of gastritis could often be observed in the presence and absence of B12 deficiency. Atrophy, based on endoscopy, and atrophic gastritis, based on histopathology, suggest the presence of B12 deficiency. Gastric histopathology is not influenced by the age, gender, Hct or MCV of the patients. PMID:16437651

  15. Daily milk intake improves vitamin B-12 status in young vegetarian Indians: an intervention trial

    PubMed Central

    2013-01-01

    Background Asymptomatic Indian lacto vegetarians, who make up more than half of the Indian population in different geographic regions, have distinctly low vitamin B-12 concentrations than non- vegetarians. Vegetarians consume milk but it seems that the amount is not enough to improve vitamin B-12 status or vitamin B-12 concentration in milk itself may be low. The aim of this study was to determine if daily milk consumption can improve vitamin B-12 status. Methods Fifteen male and 36 female, young healthy post-graduate volunteers participated. Blood from ten participants (4 males and 6 females) was collected (day-1). They continued their regular diet for next fourteen days and on day-15, blood of all 51 participants was collected, plasma vitamin B-12 concentration was measured and were divided into two groups; Normal (vitamin B-12 >148 pmol/L, n?=?22) and Vitamin B-12 deficient (<148 pmol/L, n?=?29), the remaining plasma was stored. All participants consumed 600ml. of non-enriched buffalo milk (200 3) during the day along with their usual diet. Next day blood was collected for plasma holotranscobalamin II measurement. Subjects from deficient group continued to drink 400ml of milk daily for next 14days and blood was collected on day-30. Plasma holotranscoabalamin II (day-1, 15, 16, 30), vitamin B-12, folate, total homocysteine, creatinine and hematoloical parameters (day-1, 15, 30), and milk vitamin B-12 concentrations (day-15, 16, 30) were measured. Results Fifty seven per cent of the participants were vitamin B-12 deficient and 65% were hyperhomocysteinemic. No significant difference in biomarkers was observed when there was no intervention. Plasma holotranscobalamin II concentration increased from 19.6 to 22.27 pmol/L (p?vitamin B-12 increased from 92.5 to 122 pmol/L and tHcy concentrations decreased from 31.9 to 24.9?mol/L (p?vitamin B-12 deficient subjects. Conclusions Regular intake of milk improved vitamin B-12 status of vitamin B-12 deficient vegetarians indicating a potential dietary strategy to improve the vitamin status. PMID:24107225

  16. Vitamin B-12 supplementation of rural Mexican women changes biochemical B-12 status indicators but does not affect hematology or a bone turnover marker

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Based on the high prevalence of low serum vitamin B-12 concentrations and low dietary intake of the vitamin in Latin American studies including research in Mexico, it appears that vitamin B-12 deficiency is common. Whether this is associated with adverse effects on human function is unknown. To eval...

  17. Interventions with vitamins B6, B12 and C in pregnancy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The water-soluble vitamins B6, B12 and C play important roles in maternal health as well as fetal development and physiology during gestation. This systematic review evaluates the risks and benefits of interventions with vitamins B6, B12 and C during pregnancy on maternal, neonatal and child health ...

  18. Vitamin B-12 and homocysteine status among vegetarians: a global perspective.

    PubMed

    Elmadfa, Ibrahim; Singer, Ingrid

    2009-05-01

    Evidence exists that well-planned vegetarian diets provide numerous health benefits and are appropriate for all stages of the life cycle. It is also known that animal foods provide micronutrients that are nonexistent or available only in limited amounts in plant foods. Restriction or exclusion of all animal foods may therefore result in low intake of certain micronutrients such as vitamin B-12, thereby affecting vitamin B-12 status and elevating plasma homocysteine concentrations. Overall, the studies we reviewed showed reduced mean vitamin B-12 status and elevated mean homocysteine concentrations in vegetarians, particularly among vegans. Low vitamin B-12 intake may lead to decreased bioavailability and functional deficiency of cobalamin. Although early noticeable symptoms of vitamin B-12 deficiency are nonspecific (unusual fatigue, digestion problems, frequent upper respiratory infections), the best-known clinical manifestations of cobalamin malabsorption are hematologic (pernicious anemia) and neurologic symptoms. Hyperhomocysteinemia is associated with an increased risk of atherosclerosis and cardiovascular disease. Given these health concerns, vegetarians, particularly vegans, must be advised to carefully plan their diets, to monitor their plasma vitamin B-12 on a regular basis to facilitate early detection of low cobalamin status, and to use vitamin B-12-fortified foods or take vitamin B-12 supplements if necessary. PMID:19357223

  19. False-normal vitamin B12 results in a patient with pernicious anaemia.

    PubMed

    Wainwright, P; Narayanan, S; Cook, P

    2015-12-01

    Pernicious anaemia is a common autoimmune disorder with a prevalence of approximately 4% amongst Europeans. If untreated, it can result in permanent neurological disability or death. Central to the diagnosis is establishing the presence of vitamin B12 deficiency. Concern has been raised recently regarding false-normal results obtained with competitive-binding vitamin B12 assays performed on automated biochemistry platforms in patients with pernicious anaemia due to the presence of interfering anti-intrinsic factor antibodies in the patient sample. We report a case in which diagnosis of pernicious anaemia was delayed due to false-normal vitamin B12 results. Questioning the results in light of high pre-test probability, and knowledge of the role of functional markers of vitamin B12 deficiency enabled the correct diagnosis to be made so that effective treatment could be initiated. It is crucial that those who frequently request vitamin B12 are aware of the potential problems with the available assays and how these problems can be addressed. We suggest that all patients with normal vitamin B12 levels where there is a high clinical suspicion for deficiency such as a macrocytic anaemia, neurological symptoms or megaloblastic bone marrow should have a functional assay of vitamin B12 (plasma homocysteine or methylmalonic acid) checked to further investigate for vitamin B12 deficiency. PMID:26277634

  20. Loss of vitamin B(12) in fish (round herring) meats during various cooking treatments.

    PubMed

    Nishioka, Michiko; Kanosue, Fuki; Yabuta, Yukinori; Watanabe, Fumio

    2011-01-01

    The loss of vitamin B(12) in round herring meats during various cooking treatments was evaluated. Although amounts of vitamin B(12) were three times greater in the viscera (37.5 10.6 g/100 g fresh weight) than in the meats, about 73% of total vitamin B(12) found in the whole fish body (except for head and bones) were recovered in the meats (5.1 1.0 g of vitamin B(12)). The vitamin B(12) contents of the round herring's meats were significantly decreased up to ~62% during cooking by grilling, boiling, frying, steaming, and microwaving. There was, however, no loss of vitamin B(12) during vacuum-packed pouch cooking. Model experiment using hydroxocobalamin suggest that loss of vitamin B(12) is dependent on the degree of temperature and time used in conventional cooking, and is further affected by the concomitant ingredients of food. Retention of vitamin B(12) was not dependent on vacuum or temperature (or both) used in the vacuum-packed pouch cooking. PMID:22472286

  1. Folate and vitamin B12 status in Latin America and the Caribbean: An update

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The current magnitude of folate and vitamin B12 deficiency in Latin America and the Caribbean is uncertain. Objective: To summarize data on plasma or serum vitamin B12 and folate concentrations in Latin America and the Caribbean reported since 1990, a period that covers the era before an...

  2. Competitive chemiluminescent enzyme immunoassay for vitamin B12 analysis in human milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND Few accurate data exist on the concentration of vitamin B12 in human milk. Binding of the vitamin to haptocorrin (HC) can interfere with the assay if not removed by pretreatment, and very low values can occur in women with poor B12 status. This study evaluated two competitive enzyme bind...

  3. Intestinal synthesis and absorption of vitamin B-12 in channel catfish

    SciTech Connect

    Limsuwan, T.; Lovell, R.T.

    1981-12-01

    A feeding experiment conducted in a controlled environment and using a vitamin B12-deficient, but otherwise nutritionally complete, purified diet revealed that intestinal microorganisms in channel catfish synthesized approximately 1.4 ng of vitamin B12 per gram of bodyweight per day. Removal of cobalt from the diet or supplementation with an antibiotic (succinylsulfathiazole) significantly reduced the rate of intestinal synthesis and liver stores of vitamin B12. Radiolabeled vitamin B12 in the blood, liver, kidneys, and spleen of fish fed 60Co in the diet indicated that the intestinally synthesized vitamin was absorbed by the fish. The primary route of absorption was directly from the digestive tract into the blood because coprophagy was prevented in the rearing aquariums and the amount of vitamin B12 dissolved in the aquarium water was too low for gill absorption. Dietary supplementation of vitamin B12 was not necessary for normal growth and erythrocyte formation in channel catfish in a 24-week feeding period. A longer period, however, may have caused a vitamin deficiency since liver-stored vitamin B 12 decreased between the 2nd and 24th weeks.

  4. Acute bilateral useless hand syndrome: a rare presenting manifestation of vitamin B12 deficiency.

    PubMed

    Biyani, Sumant; Jha, Sneh Kumar; Pandey, Suchit; Shukla, Rakesh

    2015-01-01

    We report a case of bilateral useless hand syndrome, a rare presenting manifestation of vitamin B12 deficiency. A 38-year-old man, a strict vegetarian and a teacher by occupation, presented with acute onset clumsiness of both hands while performing fine movements. Detailed history-taking, examination of the patient and relevant investigations (complete blood count, serum vitamin B12 and MRI of the cervical spinal cord) were carried out. Laboratory analysis was suggestive of vitamin B12 deficiency and MRI demonstrated a lesion involving the posterior columns of the cervical cord. The patient was diagnosed as a case of non-compressive cervical myelopathy predominantly involving the posterior column due to vitamin B12 deficiency. Acute bilateral useless hand syndrome can be a rare presenting feature of vitamin B12 deficiency. PMID:26475874

  5. Vitamin B12 Status in Children with Cystic Fibrosis and Pancreatic Insufficiency

    PubMed Central

    Maqbool, Asim; Schall, Joan I.; Mascarenhas, Maria R.; Dougherty, Kelly A.; Stallings, Virginia A.

    2014-01-01

    Objective Unexpectedly high serum B12 concentrations were noted in most study subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI) participating in a nutrition intervention at the baseline evaluation. The objectives of this study were to determine dietary, supplement-based and enzyme-based B12 intake, serum B12 concentrations, and predictors of vitamin B12 status in children with CF and PI. Study Design Serum B12 status was assessed in subjects (5-18 yrs) and categorized as elevated (Hi-B12) or within reference range (RR-B12) for age and sex. Serum homocysteine, plasma B6, red blood cell folate, height, weight, and body mass index Z scores, pulmonary function, energy, dietary and supplement-based vitamin intake were assessed. Results 106 subjects, mean age 10.4 3.0 years participated. Median serum B12 was 1083 pg/ml, with 56% in the Hi-B12 group. Dietary and supplement-based B12 intake were both high representing 376% and 667% Recommended Dietary Allowance (RDA). The Hi-B12 group had significantly greater supplement-based B12 intake than the RR-B12 group (1000 vs. 583% RDA, p<0.001). By multiple logistic regression analysis, high supplement-based B12 intake and age >12 years increased risk for Hi-B12, while higher FEV1 decreased risk (Pseudo-R2=0.18, P<0.001). Conclusions Serum B12 was elevated in the majority of children with CF and PI. Supplement-based B12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum B12 status. The health consequences of lifelong high supplement-based B12 intake and high serum B12 are unknown and require further study, as does the inversed correlation between serum B12 and FEV1. PMID:24445504

  6. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?

    PubMed

    Pawlak, Roman

    2015-06-01

    The goal of this paper is to describe the role of vitamin B12 deficiency in cardiovascular disease development among vegetarians. Vegetarians have a high prevalence of vitamin B12 deficiency. Deficiency of this vitamin is associated with a variety of atherogenic processes that are mainly, but not exclusively, due to vitamin B12 deficiency-induced hyperhomocysteinemia. Each 5-μmol/L increase above 10 μmol/L of serum homocysteine is associated with a 20% increased risk of circulatory health problems. Mean homocysteine concentration >10 μmol/L among vegetarians was reported in 32 of 34 reports. Macrocytosis associated with vitamin B12 deficiency is also associated with fatal and non-fatal coronary disease, myocardial infarction, stroke, and other circulatory health problems. Compared with non-vegetarians, vegetarians have an improved profile of the traditional cardiovascular disease risk factors, including serum lipids, blood pressure, serum glucose concentration, and weight status. However, not all studies that assessed cardiovascular disease incidence among vegetarians reported a protective effect. Among studies that did show a lower prevalence of circulatory health problems, the effect was not as pronounced as expected, which may be a result of poor vitamin B12 status due to a vegetarian diet. Vitamin B12 deficiency may negate the cardiovascular disease prevention benefits of vegetarian diets. In order to further reduce the risk of cardiovascular disease, vegetarians should be advised to use vitamin B12 supplements. PMID:25998928

  7. Vitamin B12 intake and status in early pregnancy among urban South Indian women

    PubMed Central

    Samuel, Tinu Mary; Duggan, Christopher; Thomas, Tinku; Bosch, Ronald; Rajendran, Ramya; Virtanen, Suvi M; Srinivasan, Krishnamachari; Kurpad, Anura V

    2015-01-01

    Aim To evaluate the vitamin B12 status of South Indian women in early pregnancy and its relationship with sociodemographic, anthropometry and dietary intake. Methods Cross-sectional study among 366 pregnant urban South Indian women ≤14 weeks of gestation with outcome variables defined as low vitamin B12 blood concentration (<150 pmol/L) and impaired vitamin B12 status [low vitamin B12 plus elevated methylmalonic acid (MMA) >0.26 μmol/L)]. Results Low plasma vitamin B12 concentration was observed in 51.1% of the women, while 42.4% had impaired B12 status. Elevated MMA, elevated homocysteine ( >10 μmol/L) and low erythrocyte folate (<283 nmol/L) was observed among 75.8%, 43.3% and 22.2% of women, respectively. The median (25th, 75th percentile) dietary intake of vitamin B12 was 1.25 (0.86, 1.96) μg/day. Lower maternal body weight was associated with higher vitamin B12 concentration [prevalence ratios (PR) (95% CI) 0.57 (0.39, 0.84)). The predictors of impaired vitamin B12 status were non-use of yoghurt [PR (95%CI) 1.63 (1.03, 2.58)], non-use of fish [PR (95% CI) 1.32 (1.01, 1.71)] and primiparity [PR (95% CI) 1.41 (1.05, 1.90)]. Conclusion A high prevalence of vitamin B12 deficiency in early pregnancy among urban South Indian women was related to primiparity and to a low consumption of yoghurt and fish. PMID:23344013

  8. Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer

    PubMed Central

    Vashi, Pankaj; Edwin, Persis; Popiel, Brenten; Lammersfeld, Carolyn; Gupta, Digant

    2016-01-01

    Background/Aims Normal or high serum vitamin B-12 levels can sometimes be seen in a B-12 deficient state, and can therefore be misleading. High levels of Methymalonic Acid (MMA) and Homocysteine (HC) have been identified as better indicators of B-12 deficiency than the actual serum B-12 level itself. We evaluated the prevalence of vitamin B-12 deficiency using appropriate cut-off levels of vitamin B-12, MMA and HC, and determined the relationship between serum levels of vitamin B-12, MMA and HC in cancer. Methods This is a cross-sectional study using a consecutive case series of 316 cancer patients first seen at Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center between April 2014 and June 2014. All patients were evaluated at baseline for vitamin B-12 (pg/mL), MMA (nmol/L) and HC (μmol/L) levels. In accordance with previously published research, the following cut-offs were used to define vitamin B-12 deficiency: <300 pg/mL for vitamin B-12, >260 nmol/L for MMA and >12 μmol/L for HC. The relationship between B-12, MMA and HC was evaluated using Spearman's rho correlation coefficient and cross-tabulation analysis. Receiver Operating Characteristic (ROC) curves were estimated using the non-parametric method to further evaluate the diagnostic accuracy of vitamin B-12 using Fedosov quotient as the "gold standard". Results Mean age at presentation was 52.5 years. 134 (42.4%) patients were males while 182 (57.6%) were females. Median vitamin B-12, MMA and HC levels were 582.5 pg/mL, 146.5 nmol/L and 8.4 μmol/L respectively. Of 316 patients, 28 (8.9%) were vitamin B-12 deficient based on vitamin B-12 (<300pg/mL), 34 (10.8%) were deficient based on MMA (>260 nmol/L) while 55 (17.4%) were deficient based on HC (>12 μmol/L). Correlation analysis revealed a significant weak negative correlation between vitamin B-12 and MMA (rho = -0.22) as well as B-12 and HC (rho = -0.35). ROC curves suggested MMA to have the best discriminatory power in predicting B-12 deficiency. Conclusion Vitamin B-12 is poorly correlated with MMA and HC in cancer. Using serum vitamin B-12 alone to evaluate B-12 status in cancer may fail to identify those with functional deficiency. A thorough clinical assessment is important to identify patients that may have risk factors and/or symptoms suggestive of deficiency. These patients should have additional testing of MMA and HC regardless of their B-12 levels. PMID:26807790

  9. Subjective well-being in older adults: folate and vitamin B12 independently predict positive affect.

    PubMed

    Edney, Laura C; Burns, Nicholas R; Danthiir, Vanessa

    2015-10-28

    Vitamin B12, folate and homocysteine have long been implicated in mental illness, and growing evidence suggests that they may play a role in positive mental health. Elucidation of these relationships is confounded due to the dependence of homocysteine on available levels of vitamin B12 and folate. Cross-sectional and longitudinal relationships between vitamin B12, folate, homocysteine and subjective well-being were assessed in a sample of 391 older, community-living adults without clinically diagnosed depression. Levels of vitamin B12, but not folate, influenced homocysteine levels 18 months later. Vitamin B12, folate and their interaction significantly predicted levels of positive affect (PA) 18 months later, but had no impact on the levels of negative affect or life satisfaction. Cross-sectional relationships between homocysteine and PA were completely attenuated in the longitudinal analyses, suggesting that the cross-sectional relationship is driven by the dependence of homocysteine on vitamin B12 and folate. This is the first study to offer some evidence of a causal link between levels of folate and vitamin B12 on PA in a large, non-clinical population. PMID:26346363

  10. Maternal Crohn's disease-related vitamin B12 deficient megaloblastic anemia in an infant.

    PubMed

    Ohyama, Wataru; Yamaoka, Masayoshi; Yokoi, Kentaro; Iwahashi, Megumi; Inage, Yuka; Arihiro, Seiji; Koganei, Kazutaka; Sugita, Akira; Ida, Hiroyuki; Akiyama, Masaharu

    2016-01-01

    We report an 11-month-old breast-fed boy with feeding difficulties, lethargy, and developmental delay. Blood examination showed pancytopenia and decreased serum levels of vitamin B12. Anisocytosis and poikilocytes were detected in his peripheral blood, and increased megaloblastosis without leukemic cells was detected in his bone marrow. After the diagnosis of megaloblastic anemia due to vitamin B12 deficiency, symptoms were improved by vitamin B12 administration. Further investigation of the mother identified Crohn's disease and suggested that the supply of vitamin B12 from the mother to the infant, via the placenta during pregnancy and via breast milk after birth, was decreased due to impaired absorption of vitamin B12 in the mother's small intestine. Magnetic resonance imaging of the boy's brain on admission showed cerebral cortex atrophy which had improved by the age of 1 year and 10 months after vitamin B12 treatment, though developmental delay was still evident at the age of 3 years. Infantile vitamin B12 deficiency often presents with nonspecific manifestations, such as developmental delay and failure to thrive, in addition to anemia and is thus not easily diagnosed. To prevent severe neurological sequelae, this condition must be rapidly diagnosed, because a prolonged duration increases the risk of permanent disabilities. PMID:26861098

  11. Neurology of Nutritional Vitamin B12 Deficiency in Infants: Case Series From India and Literature Review.

    PubMed

    Goraya, Jatinder Singh; Kaur, Sukhjot; Mehra, Bharat

    2015-11-01

    We studied 27 infants aged 6 to 27 months with vitamin B12 deficiency also known as "infantile tremor syndrome" in India. All were exclusively breast-fed by vegetarian mothers. Developmental delay or regression, pallor, skin hyperpigmentation, and sparse brown hair were present in all. Majority were hypotonic and involuntary movements were encountered in 18. Anemia and macrocytosis was found in 83% and 71% infants, respectively. Low serum vitamin B12 was present in 12 of 21 infants. Seven of the 9 infants with normal serum vitamin B12 had received vitamin B12 before referral. Twelve mothers had low serum vitamin B12. Cerebral atrophy was present in all the 9 infants who underwent neuroimaging. Treatment with vitamin B12 resulted in dramatic improvement in general activity and appetite within 48 to 72 hours followed by return of lost milestones. Tremors resolved in all by 3 to 4 weeks. Nutritional vitamin B12 deficiency is a treatable cause of neurologic dysfunction in infants. PMID:25953825

  12. Effects of intracortical microinjection of vitamin B12 on penicillin-induced epileptiform activity in rats.

    PubMed

    Erfanparast, Amir; Tamaddonfard, Esmaeal

    2015-01-01

    There are increasing studies indicating neuroprotective effects for vitamin B12. In the present study, the effect of intracortical microinjection of vitamin B12 was investigated on penicillin-induced epileptiform activity. We also examined the effects of intracortical microinjection of diazepam (a GABA-benzodiazepine receptor agonist) and flumazenil (a GABAbenzodiazepine receptor antagonist) to clarify the possible mechanism of vitamin B12. In urethane-anesthetized rats, epileptiform activity was induced by intracortical microinjection of penicillin (300 IU, 1.5 microL), and the number and amplitude of spike waves were analyzed using electroencephalographic (EEG) recordings. Intracortical microinjections of vitamin B12 at doses of 100 and 200 ng/site, diazepam at a dose of 200 ng/site and their ineffective doses (50 ng/site of vitamin B12 with 50 ng/site of diazepam) co-microinjection treatment significantly (P less than 0.05) reduced both the number and amplitude of spike waves. In addition, combined microinjection of effective doses of vitamin B12 (100 ng/site) and diazepam (200 ng/site) produced more antiepileptiform effect in comparison with their alone used doses. The antiepileptic effects induced by microinjection of vitamin B12 and diazepam at a same dose of 200 ng/site were prevented by the same site microinjection of 50 ng/site of flumazenil. The results showed antiepileptiform activities for vitamin B12 and diazepam AT the cerebral cortex level. A central GABA-benzodiazepine receptor complex-mediated mechanism might be involved in the antiepileptiform activity of vitamin B12. PMID:26232996

  13. Vitamin B12 absorption capacity in healthy children

    SciTech Connect

    Hjelt, K.; Krasilnikoff, P.A.

    1986-03-01

    B12 absorption was investigated in 47 healthy children aged 7 months to 15.8 years (median 4.9 years). The patients had either recovered from giardiasis, the post-gastroenteritis syndrome, or had celiac disease in remission (treated with a gluten-free diet). The B12 absorption was measured by a double-isotope technique using /sup 57/CoB12 and /sup 51/CrCl/sub 3/, the latter being the inabsorbable marker. The radiation dose was minimal. The results were presented as fractional absorption of B12 (FAB12). Within the different age groups, the absorption test was performed by means of the following oral amounts of B12: 0- less than 1 year, 0.5 microgram; 1-3 years: 1.7 micrograms, 4-6 years, 2.5 micrograms; 7-10 years; 3.3 micrograms; and 11-15 years, 4.5 micrograms. When using these oral amounts of B12, the medians (and ranges) of FAB12 were found to be: 1-3 years (n = 18), 37% (16-80%); 4-6 years (n = 10), 27% (19-40%); 7-10 years (n = 9), 32% (21-44%); and 11-15 years (n = 8), 27% (19-59%). The FAB12 in two children aged 7 and 11 months was 31% and 32%, respectively. These results may be interpretated as reference values for B12 absorption in children. Further absorption tests were performed in seven children representing the four age groups from 1 to 15 years. When a high oral amount of B12 was given (i.e., three times the saturation dose), the FAB12 ranged from 0 to 20% (median 9%), whereas a low amount (i.e., one-ninth of the saturation dose) produced fractional absorptions from 65 to 82% (median 74%).

  14. Most harmful algal bloom species are vitamin B1 and B12 auxotrophs.

    PubMed

    Tang, Ying Zhong; Koch, Florian; Gobler, Christopher J

    2010-11-30

    Eutrophication can play a central role in promoting harmful algal blooms (HABs), and therefore many HAB studies to date have focused on macronutrients (N, P, Si). Although a majority of algal species require exogenous B vitamins (i.e., auxotrophic for B vitamins), the possible importance of organic micronutrients such as B vitamins (B(1), B(7), B(12)) in regulating HABs has rarely been considered. Prior investigations of vitamins and algae have examined a relatively small number of dinoflagellates (n = 26) and a paucity of HAB species (n = 4). In the present study, the vitamin B(1), B(7), and B(12) requirements of 41 strains of 27 HAB species (19 dinoflagellates) were investigated. All but one species (two strains) of harmful algae surveyed required vitamin B(12), 20 of 27 species required B(1), and 10 of 27 species required B(7), all proportions higher than the previously reported for non-HAB species. Half-saturation (K(s)) constants of several HAB species for B(1) and B(12) were higher than those previously reported for other phytoplankton and similar to vitamin concentrations reported in estuaries. Cellular quotas for vitamins suggest that, in some cases, HAB demands for vitamins may exhaust standing stocks of vitamins in hours to days. The sum of these findings demonstrates the potentially significant ecological role of B-vitamins in regulating the dynamics of HABs. PMID:21068377

  15. Most harmful algal bloom species are vitamin B1 and B12 auxotrophs

    PubMed Central

    Tang, Ying Zhong; Koch, Florian; Gobler, Christopher J.

    2010-01-01

    Eutrophication can play a central role in promoting harmful algal blooms (HABs), and therefore many HAB studies to date have focused on macronutrients (N, P, Si). Although a majority of algal species require exogenous B vitamins (i.e., auxotrophic for B vitamins), the possible importance of organic micronutrients such as B vitamins (B1, B7, B12) in regulating HABs has rarely been considered. Prior investigations of vitamins and algae have examined a relatively small number of dinoflagellates (n = 26) and a paucity of HAB species (n = 4). In the present study, the vitamin B1, B7, and B12 requirements of 41 strains of 27 HAB species (19 dinoflagellates) were investigated. All but one species (two strains) of harmful algae surveyed required vitamin B12, 20 of 27 species required B1, and 10 of 27 species required B7, all proportions higher than the previously reported for non-HAB species. Half-saturation (Ks) constants of several HAB species for B1 and B12 were higher than those previously reported for other phytoplankton and similar to vitamin concentrations reported in estuaries. Cellular quotas for vitamins suggest that, in some cases, HAB demands for vitamins may exhaust standing stocks of vitamins in hours to days. The sum of these findings demonstrates the potentially significant ecological role of B-vitamins in regulating the dynamics of HABs. PMID:21068377

  16. Enhanced Peptide Stability Against Protease Digestion Induced by Intrinsic Factor Binding of a Vitamin B12 Conjugate of Exendin-4

    PubMed Central

    Bonaccorso, Ron L.; Chepurny, Oleg G.; Becker-Pauly, Christoph; Holz, George G.; Doyle, Robert P.

    2015-01-01

    Peptide digestion from proteases is a significant limitation in peptide therapeutic development. It has been hypothesized that the dietary pathway of vitamin B12 (B12) may be exploited in this area, but an open question is whether B12-peptide conjugates bound to the B12 gastric uptake protein intrinsic factor (IF) can provide any stability against proteases. Herein, we describe a new conjugate of B12 with the incretin peptide exendin 4 that demonstrates picomolar agonism of the glugacon-like peptide-1 receptor (GLP1-R). Stability studies reveal that Ex-4 is digested by pancreatic proteases trypsin and chymotrypsin and by the kidney endopeptidase meprin β. Prebinding the B12 conjugate to IF, however, resulted in up to a 4-fold greater activity of the B12-Ex-4 conjugate relative to Ex-4, when the IF-B12-Ex-4 complex was exposed to 22 µg/mL of trypsin, 2.3-fold greater activity when exposed to 1.25 µg/mL of chymotrypsin, and there was no decrease in function at up to 5 µg/mL of meprin β. PMID:26260673

  17. Enhanced Peptide Stability Against Protease Digestion Induced by Intrinsic Factor Binding of a Vitamin B12 Conjugate of Exendin-4.

    PubMed

    Bonaccorso, Ron L; Chepurny, Oleg G; Becker-Pauly, Christoph; Holz, George G; Doyle, Robert P

    2015-09-01

    Peptide digestion from proteases is a significant limitation in peptide therapeutic development. It has been hypothesized that the dietary pathway of vitamin B12 (B12) may be exploited in this area, but an open question is whether B12-peptide conjugates bound to the B12 gastric uptake protein intrinsic factor (IF) can provide any stability against proteases. Herein, we describe a new conjugate of B12 with the incretin peptide exendin 4 that demonstrates picomolar agonism of the glugacon-like peptide-1 receptor (GLP1-R). Stability studies reveal that Ex-4 is digested by pancreatic proteases trypsin and chymotrypsin and by the kidney endopeptidase meprin ?. Prebinding the B12 conjugate to IF, however, resulted in up to a 4-fold greater activity of the B12-Ex-4 conjugate relative to Ex-4, when the IF-B12-Ex-4 complex was exposed to 22 ?g/mL of trypsin, 2.3-fold greater activity when exposed to 1.25 ?g/mL of chymotrypsin, and there was no decrease in function at up to 5 ?g/mL of meprin ?. PMID:26260673

  18. Prevalent vitamin B-12 deficiency in twelve-month-old Guatemalan infants is predicted by maternal B-12 deficiency and infant diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marginal (<148 pmol/L) or deficient (148-220 pmol/L) plasma vitamin B-12 concentrations were reported previously in approximately one third of low-income women and children studied in Guatemala. Since vitamin B-12 deficiency can adversely affect infant development and cognitive function, this study ...

  19. Therapeutic role of Vitamin B12 in patients of chronic tinnitus: A pilot study.

    PubMed

    Singh, Charu; Kawatra, Rahul; Gupta, Jaya; Awasthi, Vishnu; Dungana, Homnath

    2016-01-01

    True tinnitus is a phantom auditory perception arising from a source or trigger in the cochlea, brainstem, or at higher centers and has no detectable acoustic generator. The most accepted is the famous neurophysiologic model of Jastreboff, which stresses that tinnitus, is a subcortical perception and results from the processing of weak neural activity in the periphery. The aim of this study is to determine the role of Vitamin B12 in treatment of chronic tinnitus. In this randomized, double-blind pilot study, total 40 patients were enrolled, of which 20 in Group A (cases) received intramuscular therapy of 1 ml Vitamin B12 (2500 mcg) weekly for a period of 6 weeks and Group B (20) patients received placebo isotonic saline 01 ml intramuscular. The patients were subjected to Vitamin B12 assay and audiometry pre- and post-therapy. Of the total patients of tinnitus, 17 were Vitamin B12 deficient that is 42.5% showed deficiency when the normal levels were considered to be 250 pg/ml. A paired t-test showed that in Group A, patients with Vitamin B12 deficiency showed significant improvement in mean tinnitus severity index score and visual analog scale (VAS) after Vitamin B12 therapy. This pilot study highlights the significant prevalence of Vitamin B12 deficiency in North Indian population and improvement in tinnitus severity scores and VAS in cobalamin-deficient patients receiving intramuscular Vitamin B12 weekly for 6 weeks further provides a link between cobalamin deficiency and tinnitus thereby suggestive of a therapeutic role of B12 in cobalamin-deficient patients of tinnitus. PMID:26960786

  20. Vitamin B12, folate and iron levels in primary nocturnal enuresis

    PubMed Central

    Albayrak, Sebahattin; Zengin, Krsad; Tanik, Serhat; Daar, Ghaniya; Ozdamar, Mustafa Yasar; Bakirtas, Hasan; Imamoglu, M. Abdurrahim; Gurdal, Mesut

    2015-01-01

    Objective: Folate, vitamin B12 and iron are important vitamin and minerals which play role in the development of nervous system. The aim of this study was looking at the presence of folate, vitamin B12 and iron deficiency among patients with Primary nocturnal enuresis (PNE) and possible relation between the delay of central nervous system (CNS) development, PNE and folate, vitamin B12 and iron states. Methods: Consecutively applied forty patients with PNE (23 girls and 17 boys) and otherwise normal thirty control subjects (17 girls and 13 boys) were included in the study. Average ages (in range) of PNE and the control group were 9.2(6-12) years and 9.3 (6-12) years accordingly. Age, height, weight, complete blood count, blood vitamin B12, folate, ferritin and iron values of both groups were recorded and compared to each other. Results: Average vitamin B12 and folate levels of patients with PNE were significantly and statistically lower compared to those of the control group. Average blood iron of patients with PNE was significantly higher than that of the control group and also average ferritin level of the PNE group was detected to be higher than the control group but this relation was statistically insignificant. Conclusion: Primary nocturnal enuresis is related to the delay in CNS maturation so it was thought that low vitamin B12 and folate which were found in patients with PNE may have role in the delay of CNS maturation. Additionally, further studies are needed to investigate the role of vitamin B12 and folate either alone or as combination in treatment of patients with PNE who have low vitamin B12and folate level. PMID:25878620

  1. The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In recent years there has been growing interest in the vitamins folic acid and vitamin B12 because of the realization that the status of these vitamins in populations is less than adequate, and that such inadequacy may be linked to adverse public health outcomes. This concern has prompted the United...

  2. Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke.

    PubMed

    Spence, J David

    2016-02-01

    The purpose of this narrative review is to highlight insights into the importance and frequency of metabolic vitamin B12 (B12) deficiency, reasons why it is commonly missed, and reasons for the widespread but mistaken belief that treatment of B12 deficiency does not prevent stroke or improve cognitive function. Metabolic B12 deficiency is common, being present in 10%-40% of the population; is frequently missed; is easily treated; and contributes importantly to cognitive decline and stroke in older people. Measuring serum B12 alone is not sufficient for diagnosis; it is necessary to measure holotranscobalamin or functional markers of B12 adequacy such as methylmalonic acid or plasma total homocysteine. B-vitamin therapy with cyanocobalamin reduces the risk of stroke in patients with normal renal function but is harmful (perhaps because of thiocyanate accumulation from cyanide in cyanocobalamin) in patients with renal impairment. Methylcobalamin may be preferable in renal impairment. B12 therapy slowed gray matter atrophy and cognitive decline in the Homocysteine and B Vitamins in Cognitive Impairment Trial. Undiagnosed metabolic B12 deficiency may be an important missed opportunity for prevention of dementia and stroke; in patients with metabolic B12 deficiency, it would be prudent to offer inexpensive and nontoxic supplements of oral B12, preferably methylcobalamin or hydroxycobalamin. Future research is needed to distinguish the effects of thiocyanate from cyanocobalamin on hydrogen sulfide, and effects of treatment with methylcobalamin on cognitive function and stroke, particularly in patients with renal failure. PMID:26597770

  3. FRACTION OF TOTAL PLASMA VITAMIN B12 BOUND TO TRANSCOBALAMIN CORRELATES WITH COGNITIVE FUNCTION IN ELDERLY LATINOS WITH DEPRESSIVE SYMPTOMS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The fraction of total plasma vitamin B12 bound to transcobalamin (holoTC/B12 ratio) may reflect tissue levels of the vitamin, but its clinical relevance is unclear. Methods: associations between cognitive function and total B12, holoTC, and holoTC/B12 ratio were assessed in a cohort of ...

  4. Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Severe vitamin B12 deficiency produces a cluster of neurological symptoms in infants, including irritability, failure to thrive, apathy, anorexia, and developmental regression, which respond remarkably rapidly to supplementation. The underlying mechanisms may involve delayed myelination or demyelina...

  5. Maternal Milk and Serum Vitamin B12, Folic Acid, and Protein Levels in Indian Subjects

    PubMed Central

    Jathar, V. S.; Kamath, S. A.; Parikh, M. N.; Rege, D. V.; Satoskar, R. S.

    1970-01-01

    Serum vitamin B12 and folic acid activity levels were studied in 47 mothers. The mean serum vitamin B12 value in non-vegetarian mothers was 228 ??g./ml. 389 SE, as compared to mean values 97 ??g./ml. 207 SE in lacto-vegetarians. There was no significant difference in folic acid levels, haemoglobin, and total proteins among the different dietetic groups. Analysis of milk revealed mean vitamin B12 values of 103 ??g./ml. in non-vegetarians as compared to 91 ??g./ml. in lacto-vegetarians; the difference was not statistically significant. Mean total protein and folic acid levels for milk were similar in different dietetic groups. The figures obtained for vitamin B12 content of human milk in these mothers are considerably lower than those reported in similar studies from Western countries. PMID:5419992

  6. Neglect-induced pseudo-thrombotic thrombocytopenic purpura due to vitamin B12 deficiency.

    PubMed

    Asano, Takeshi; Narazaki, Hidehiko; Kaizu, Kiyohiko; Matsukawa, Shouhei; Takema-Tochikubo, Yuki; Fujii, Shuichi; Saitoh, Nobuyuki; Mashiko, Kunihiko; Fujino, Osamu

    2015-10-01

    Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15-year-old girl who had been neglected, which might have caused pseudo-TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect. PMID:26387768

  7. Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother.

    PubMed

    Kocaoglu, Celebi; Akin, Fatih; Caksen, Hseyin; Bke, Saltuk Bu?ra; Arslan, Skr; Aygn, Serhat

    2014-06-01

    In developed countries, vitamin B12 (cobalamin) deficiency usually occurs in children, exclusively breastfed ones whose mothers are vegetarian, causing low body stores of vitamin B12. The haematologic manifestation of vitamin B12 deficiency is pernicious anaemia. It is a megaloblastic anaemia with high mean corpuscular volume and typical morphological features, such as hyperlobulation of the nuclei of the granulocytes. In advanced cases, neutropaenia and thrombocytopaenia can occur, simulating aplastic anaemia or leukaemia. In addition to haematological symptoms, infants may experience weakness, fatigue, failure to thrive, and irritability. Other common findings include pallor, glossitis, vomiting, diarrhoea, and icterus. Neurological symptoms may affect the central nervous system and, in severe cases, rarely cause brain atrophy. Here, we report an interesting case, a 12-month old infant, who was admitted with neurological symptoms and diagnosed with vitamin B12 deficiency. PMID:25076673

  8. A new role for glutathione: protection of vitamin B12 from depletion by xenobiotics.

    PubMed

    Watson, William P; Munter, Tony; Golding, Bernard T

    2004-12-01

    NADPH in microsomes reduces the hydroxocob(III)alamin form of vitamin B12 to cob(II)alamin and the supernucleophilic cob(I)alamin, which are both highly reactive toward xenobiotic epoxides formed by mammalian metabolism of dienes such as the industrially important chemicals chloroprene and 1,3-butadiene. With styrene, the metabolically formed styrene oxide is reactive toward cob(I)alamin but not cob(II)alamin. Such reactions in humans could lead to vitamin B12 deficiency, which is implicated in pernicious anemia, cancer, and degenerative diseases. However, glutathione inhibits the reduction of hydroxocob(III)alamin by formation of the 1:1 complex glutathionylcobalamin. This blocks reactions of the cobalamins with metabolically formed epoxides. The interaction between glutathione and vitamin B12 could protect against diseases related to vitamin B12 depletion. PMID:15606130

  9. Cerebral Atrophy in a Vitamin B12-deficient Infant of a Vegetarian Mother

    PubMed Central

    Akin, Fatih; Çaksen, Hüseyin; Böke, Saltuk Buğra; Arslan, Şükrü; Aygün, Serhat

    2014-01-01

    ABSTRACT In developed countries, vitamin B12 (cobalamin) deficiency usually occurs in children, exclusively breastfed ones whose mothers are vegetarian, causing low body stores of vitamin B12. The haematologic manifestation of vitamin B12 deficiency is pernicious anaemia. It is a megaloblastic anaemia with high mean corpuscular volume and typical morphological features, such as hyperlobulation of the nuclei of the granulocytes. In advanced cases, neutropaenia and thrombocytopaenia can occur, simulating aplastic anaemia or leukaemia. In addition to haematological symptoms, infants may experience weakness, fatigue, failure to thrive, and irritability. Other common findings include pallor, glossitis, vomiting, diarrhoea, and icterus. Neurological symptoms may affect the central nervous system and, in severe cases, rarely cause brain atrophy. Here, we report an interesting case, a 12-month old infant, who was admitted with neurological symptoms and diagnosed with vitamin B12 deficiency. PMID:25076673

  10. AB156. Homocysteine and vitamin B12: risk factors for erectile dysfunction

    PubMed Central

    Lu, Zheng; Mo, Zengnan

    2014-01-01

    Background Increasing levels of homocysteine (Hcy) is associated with cardiovascular disease, and erectile dysfunction (ED) has close relation with cardiovascular disease, therefore, high homocysteine may be one of the risk factors of ED. During the metabolism of homocysteine, vitamin B12 plays an important role and could be the main factor in causing erectile dysfunction as well. Purpose To investigate the relationship between Hcy, vitamin B12 and ED in sample. Methods The study included 1,457 men aged 20-69 who participated in a series of physical examination at the Medical Centre in Fangchenggang First Peoples Hospital from September 2009 to December 2009. ED was identified by the five-item International Index of Erectile Function (IIEF-5) questionnaire. All participants were measured for plasma Hcy, vitamin B12, folic acid, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), fasting plasma glucose, triglyceride and high-density lipoprotein cholesterol (HDL). Smoking, alcoholic drinking and physical activity were collected by face to face communication. Results A total of 691 (47.4%) men were identified as ED in this study, participants with ED were older or more likely to drink alcohol than the non-ED. It was higher Hcy (P=0.032), vitamin B12 (P=0.008) and fasting plasma glucose (P=0.014) in the participants with ED. There were significant positive correlation between ED status (none, mile, moderate and severe) and Hcy (P=0.024), vitamin B12 (P=0.015) and fasting plasma glucose (P=0.002). Logistic regression analysis showed that age, Hcy and vitamin B12 were the main determinants in ED. Hcy was positively associated with ED in the men more than 45, but vitamin B12 was positively related with ED in the men less than 45. Conclusions Hcy was positively associated with ED in elder, however, vitamin B12 was positively related with ED in younger.

  11. Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes.

    PubMed

    Ko, Sun-Hye; Ko, Sun-Hee; Ahn, Yu-Bae; Song, Ki-Ho; Han, Kyung-Do; Park, Yong-Moon; Ko, Seung-Hyun; Kim, Hye-Soo

    2014-07-01

    We evaluated the prevalence of vitamin B12 deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B12 and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12 ≤ 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B12 level was 662.5 ± 246.7 pg/mL. Vitamin B12 deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of ≤ 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and ≥ 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and ≥ 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B12 deficiency, especially at higher dosages (> 1,000 mg) and longer durations (≥ 4 yr) of treatment. PMID:25045229

  12. Quantitation of vitamin B 12 by first-derivative absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Kar?ilayan, Huriye

    1996-08-01

    Quantitation of vitamin B 12 by first-derivative absorption spectroscopy is described. Peak-to-peak (355 nm to 370 nm) amplitudes were measured from the first derivative spectra. The method permits rapid determination of vitamin B 12, and increases the detection limit while decreasing interference by impurities. The effects of the majority of other absorbing macromolecules which may also be present in biological samples are eliminated or very considerably minimized by this method.

  13. Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis.

    PubMed

    Kang, Dezhi; Shi, Baochen; Erfe, Marie C; Craft, Noah; Li, Huiying

    2015-06-24

    Various diseases have been linked to the human microbiota, but the underlying molecular mechanisms of the microbiota in disease pathogenesis are often poorly understood. Using acne as a disease model, we aimed to understand the molecular response of the skin microbiota to host metabolite signaling in disease pathogenesis. Metatranscriptomic analysis revealed that the transcriptional profiles of the skin microbiota separated acne patients from healthy individuals. The vitamin B12 biosynthesis pathway in the skin bacterium Propionibacterium acnes was significantly down-regulated in acne patients. We hypothesized that host vitamin B12 modulates the activities of the skin microbiota and contributes to acne pathogenesis. To test this hypothesis, we analyzed the skin microbiota in healthy subjects supplemented with vitamin B12. We found that the supplementation repressed the expression of vitamin B12 biosynthesis genes in P. acnes and altered the transcriptome of the skin microbiota. One of the 10 subjects studied developed acne 1 week after vitamin B12 supplementation. To further understand the molecular mechanism, we revealed that vitamin B12 supplementation in P. acnes cultures promoted the production of porphyrins, which have been shown to induce inflammation in acne. Our findings suggest a new bacterial pathogenesis pathway in acne and provide one molecular explanation for the long-standing clinical observation that vitamin B12 supplementation leads to acne development in a subset of individuals. Our study discovered that vitamin B12, an essential nutrient in humans, modulates the transcriptional activities of skin bacteria, and provided evidence that metabolite-mediated interactions between the host and the skin microbiota play essential roles in disease development. PMID:26109103

  14. Associations between Vitamin B-12 Status and Oxidative Stress and Inflammation in Diabetic Vegetarians and Omnivores.

    PubMed

    Lee, Yau-Jiunn; Wang, Ming-Yang; Lin, Mon-Chiou; Lin, Ping-Ting

    2016-01-01

    Diabetes is considered an oxidative stress and a chronic inflammatory disease. The purpose of this study was to investigate the correlations between vitamin B-12 status and oxidative stress and inflammation in diabetic vegetarians and omnivores. We enrolled 154 patients with type 2 diabetes (54 vegetarians and 100 omnivores). Levels of fasting glucose, glycohemoglobin (HbA1c), lipid profiles, oxidative stress, antioxidant enzymes activity, and inflammatory makers were measured. Diabetic vegetarians with higher levels of vitamin B-12 (>250 pmol/L) had significantly lower levels of fasting glucose, HbA1c and higher antioxidant enzyme activity (catalase) than those with lower levels of vitamin B-12 (?250 pmol/L). A significant association was found between vitamin B-12 status and fasting glucose (r = -0.17, p = 0.03), HbA1c (r = -0.33, p = 0.02), oxidative stress (oxidized low density lipoprotein-cholesterol, r = -0.19, p = 0.03), and antioxidant enzyme activity (catalase, r = 0.28, p = 0.01) in the diabetic vegetarians; vitamin B-12 status was significantly correlated with inflammatory markers (interleukin-6, r = -0.33, p < 0.01) in diabetic omnivores. As a result, we suggest that it is necessary to monitor the levels of vitamin B-12 in patients with diabetes, particularly those adhering to a vegetarian diet. PMID:26927168

  15. Quantifying the Electrocatalytic Turnover of Vitamin?B12 -Mediated Dehalogenation on Single Soft Nanoparticles.

    PubMed

    Cheng, Wei; Compton, Richard G

    2016-02-01

    We report the electrocatalytic dehalogenation of trichloroethylene (TCE) by single soft nanoparticles in the form of Vitamin?B12 -containing droplets. We quantify the turnover number of the catalytic reaction at the single soft nanoparticle level. The kinetic data shows that the binding of TCE with the electro-reduced vitamin in the Co(I) oxidation state is chemically reversible. PMID:26806226

  16. Congenital disorders of vitamin B12 transport and their contributions to concepts. II.

    PubMed Central

    Hall, C. A.

    1981-01-01

    Congenital deficiencies of Transcobalamin II (TC II) and R binders of vitamin B12 (B12, cobalamin, Cbl) have been described in several families. The deficiency of TC II exists as at least three variants. The deficiency of TC II is expressed by a profound megaloblastic pancytopenia during the first few weeks of life, but the serum Cbl is normal. In contrast, the deficiency of R binder is asymptomatic, tissues are replete in Cbl, but the serum Cbl is low. All of the R binder in the several body sources is under the same genetic control. Studies of the congenital deficiency TC II suggest the following: (1) The function of TC II is the promotion of cell uptake of physiologic amounts of Cbl, which can also be accomplished by very large amounts of Cbl, and not in any intracellular process. (2) TC II is essential for the absorption, postabsorptive distribution, and recycling of TC II. (3) The metabolic consequences of TC II deficiency are expressed primarily in rapidly dividing cells probably because they are dependent upon the constant need for new Cbl. PMID:7342493

  17. Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations

    PubMed Central

    Tanaka, Toshiko; Scheet, Paul; Giusti, Betti; Bandinelli, Stefania; Piras, Maria Grazia; Usala, Gianluca; Lai, Sandra; Mulas, Antonella; Corsi, Anna Maria; Vestrini, Anna; Sofi, Francesco; Gori, Anna Maria; Abbate, Rosanna; Guralnik, Jack; Singleton, Andrew; Abecasis, Goncalo R.; Schlessinger, David; Uda, Manuela; Ferrucci, Luigi

    2009-01-01

    The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated with coronary heart disease, stroke and neurological disease. To investigate genetic factors that affect circulating vitamin B6, vitamin B12, folate and homocysteine, a genome-wide association analysis was conducted in the InCHIANTI (N = 1175), SardiNIA (N = 1115), and BLSA (N = 640) studies. The top loci were replicated in an independent sample of 687 participants in the Progetto Nutrizione study. Polymorphisms in the ALPL gene (rs4654748, p = 8.30 10?18) were associated with vitamin B6 and FUT2 (rs6022662, p = 2.83 10?20) with vitamin B12 serum levels. The association of MTHFR, a gene consistently associated with homocysteine, was confirmed in this meta-analysis. The ALPL gene likely influences the catabolism of vitamin B6 while FUT2 interferes with absorption of vitamin B12. These findings highlight mechanisms that affect vitamin B6, vitamin B12 and homocysteine serum levels. PMID:19303062

  18. Folate and vitamin B12 status of adolescent girls in northern Nigeria.

    PubMed Central

    VanderJagt, D. J.; Spelman, K.; Ambe, J.; Datta, P.; Blackwell, W.; Crossey, M.; Glew, R. H.

    2000-01-01

    The diets of populations in many developing countries are low in folate and vitamin B12 and a deficiency of either of these vitamins results in increased risk for cardiovascular disease and neural tube defects. The rates of neural tube defects in Nigeria are among the highest reported worldwide. Since many girls marry at an early age in northern Nigeria, we therefore determined the folate and vitamin B12 status of adolescent girls between 12 and 16 years of age in Maiduguri, Nigeria. The mean serum folate concentration for subjects was 15.3 +/- 5.2 nmol/L. Whereas only four subjects (2.4%) had serum folate concentrations lower than 6.8 nmol/L, a level indicative of negative folate balance, 9% of the subjects had serum vitamin B12 concentrations at or below 134 pmol/L, the lower limit of the reference range for their age group. Serum homocysteine was measured in 56 of the 162 subjects and the mean level was 15.9 +/- 5.0 mumol/L. The majority of subjects had serum homocysteine concentrations above the upper limit of the reference range for their age group. We conclude that the adolescent girls we studied were at greater risk for vitamin B12 deficiency than folate deficiency. This conclusion is consistent with the fact that their diet included few foods that contained vitamin B12. PMID:10946529

  19. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B(12) and folate.

    PubMed

    Klee, G G

    2000-08-01

    Vitamin B(12) and folate are two vitamins that have interdependent roles in nucleic acid synthesis. Deficiencies of either vitamin can cause megaloblastic anemia; however, inappropriate treatment of B(12) deficiency with folate can cause irreversible nerve degeneration. Inadequate folate nutrition during early pregnancy can cause neural tube defects in the developing fetus. In addition, folate and vitamin B(12) deficiency and the compensatory increase in homocysteine are a significant risk factor for cardiovascular disease. Laboratory support for the diagnosis and management of these multiple clinical entities is controversial and somewhat problematic. Automated ligand binding measurements of vitamin B(12) and folate are easiest to perform and widely used. Unfortunately, these tests are not the most sensitive indicators of disease. Measurement of red cell folate is less dependent on dietary fluctuations, but these measurements may not be reliable. Homocysteine and methylmalonic acid are better metabolic indicators of deficiencies at the tissue level. There are no "gold standards" for the diagnosis of these disorders, and controversy exists regarding the best diagnostic approach. Healthcare strategies that consider the impact of laboratory tests on the overall costs and quality of care should consider the advantages of including methylmalonic acid and homocysteine in the early evaluation of patients with suspected deficiencies of vitamin B(12) and folate. PMID:10926922

  20. Enhancing vitamin B12 content in soy-yogurt by Lactobacillus reuteri.

    PubMed

    Gu, Qing; Zhang, Chen; Song, Dafeng; Li, Ping; Zhu, Xuan

    2015-08-01

    More attention from the aged and vegetarians has been paid to soy-product due to its taste, easy digestibility, as well as the association with health. However, soy-product has a defect of low vitamin content, mainly the water-soluble vitamin B12. This study was to investigate co-fermentation of glycerol and fructose in soy-yogurt to enhance vitamin B12 production by Lactobacillus reuteri. After a serial combination experiments, the co-fermentation was confirmed to enhance the production of vitamin B12 up to 18 ?g/100mL. Both supplementations induced the expression of cobT and cbiA and functioned to balance the redox reaction. Meanwhile, high content of fructose supplementation reduced the production of vitamin B12 and suppressed expression of cobT in bacteria. It was proved that the vitamin B12 content of this soy-yogurt is higher than other fermented soybean based food and thus can be served as an alternative food for the aged and vegetarians. PMID:25955289

  1. Are vitamin B12 and folate deficiency clinically important after roux-en-Y gastric bypass?

    PubMed

    Brolin, R E; Gorman, J H; Gorman, R C; Petschenik, A J; Bradley, L J; Kenler, H A; Cody, R P

    1998-01-01

    Although iron, vitamin B12, and folate deficiency have been well documented after gastric bypass operations performed for morbid obesity, there is surprisingly little information on either the natural course or the treatment of these deficiencies in Roux-en-Y gastric bypass (RYGB) patients. During a 10-year period, a complete blood count and serum levels of iron, total iron-binding capacity, vitamin B12, and folate were obtained in 348 patients preoperatively and postoperatively at 6-month intervals for the first 2 years, then annually thereafter. The principal objectives of this study were to determine how readily patients who developed metabolic deficiencies after Roux-en-Y gastric bypass responded to postoperative supplements of the deficient micronutrient and to learn whether the risk of developing these deficiencies decreases over time. Hemoglobin and hematocrit levels were significantly decreased at all postoperative intervals in comparison to preoperative values. Moreover, at each successive interval through 5 years, hemoglobin and hematocrit were decreased significantly compared to the preceding interval. Folate levels were significantly increased compared to preoperative levels at all time intervals. Iron and vitamin B12 levels were lower than preoperative measurements and remained relatively stable postoperatively. Half of the low hemoglobin levels were not associated with iron deficiency. Taking multivitamin supplements resulted in a lower incidence of folate deficiency but did not prevent iron or vitamin B12 deficiency. Oral supplementation of iron and vitamin B12 corrected deficiencies in 43% and 81% of cases, respectively. Folate deficiency was almost always corrected with multivitamins alone. No patient had symptoms that could be attributed to either vitamin B12 or folate deficiency Conversely, many patients had symptoms of iron deficiency and anemia. Lack of symptoms of vitamin B12 and folate deficiency suggests that these deficiencies are not clinically important after RYGB. Conversely, iron deficiency and anemia are potentially serious problems after RYGB, particularly in younger women. Hence we recommend prophylactic oral iron supplements to premenopausal women who undergo RYGB. PMID:9843603

  2. Vitamin B12, folate, and homocysteine levels in patients with obsessivecompulsive disorder

    PubMed Central

    Trksoy, Nuray; Bilici, Rabia; Yal?ner, Altan; zdemir, Y zay; rnek, Ibrahim; Tufan, Ali Evren; Kara, Ay?e

    2014-01-01

    It is known that elevated serum homocysteine, decreased folate, and low vitamin B12 serum levels are associated with poor cognitive function, cognitive decline, and dementia. Current literature shows that some psychiatric disorders, mainly affective and psychotic ones, can be related to the levels of vitamin B12, folate, and homocysteine. These results can be explained by the importance of vitamin B12, folate, and homocysteine in carbon transfer metabolism (methylation), which is required for the production of serotonin as well as for other monoamine neurotransmitters and catecholamines. Earlier studies focused on the relationship between folate deficiency, hyperhomocysteinemia, and depressive disorders. Although depressive and anxiety disorders show a common comorbidity pattern, there are few studies addressing the effect of impaired one-carbon metabolism in anxiety disorders especially in obsessivecompulsive disorder (OCD). This study aimed to measure the levels of vitamin B12, folate, and homocysteine specifically in order to see if eventual alterations have an etiopathogenetic significance on patients with OCD. Serum vitamin B12, folate, and homocysteine concentrations were measured in 35 patients with OCD and 22 controls. In addition, the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, Text Revision, YaleBrown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, and Hamilton Rating Scale for Anxiety were conducted for each patient. It was found that vitamin B12 levels were decreased and homocysteine levels were increased in some OCD patients. Homocysteine levels were positively correlated with YaleBrown compulsion and YaleBrown total scores. In conclusion, findings of this study suggest that some OCD patients might have vitamin B12 deficiency and higher homocysteine levels. PMID:25228807

  3. Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism.

    PubMed

    Coelho, David; Kim, Jaeseung C; Miousse, Isabelle R; Fung, Stephen; du Moulin, Marcel; Buers, Insa; Suormala, Terttu; Burda, Patricie; Frapolli, Michele; Stucki, Martin; Nrnberg, Peter; Thiele, Holger; Robenek, Horst; Hhne, Wolfgang; Longo, Nicola; Pasquali, Marzia; Mengel, Eugen; Watkins, David; Shoubridge, Eric A; Majewski, Jacek; Rosenblatt, David S; Fowler, Brian; Rutsch, Frank; Baumgartner, Matthias R

    2012-10-01

    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. Our results show that ABCD4 colocalizes with the lysosomal proteins LAMP1 and LMBD1, the latter of which is deficient in the cblF defect. Furthermore, we show that mutations altering the putative ATPase domain of ABCD4 affect its function, suggesting that the ATPase activity of ABCD4 may be involved in intracellular processing of vitamin B12. PMID:22922874

  4. Unraveling Vitamin B12-Responsive Gene Regulation in Algae1[W

    PubMed Central

    Helliwell, Katherine E.; Scaife, Mark A.; Sasso, Severin; Araujo, Ana Paula Ulian; Purton, Saul; Smith, Alison G.

    2014-01-01

    Photosynthetic microalgae play a vital role in primary productivity and biogeochemical cycling in both marine and freshwater systems across the globe. However, the growth of these cosmopolitan organisms depends on the bioavailability of nutrients such as vitamins. Approximately one-half of all microalgal species requires vitamin B12 as a growth supplement. The major determinant of algal B12 requirements is defined by the isoform of methionine synthase possessed by an alga, such that the presence of the B12-independent methionine synthase (METE) enables growth without this vitamin. Moreover, the widespread but phylogenetically unrelated distribution of B12 auxotrophy across the algal lineages suggests that the METE gene has been lost multiple times in evolution. Given that METE expression is repressed by the presence of B12, prolonged repression by a reliable source of the vitamin could lead to the accumulation of mutations and eventually gene loss. Here, we probe METE gene regulation by B12 and methionine/folate cycle metabolites in both marine and freshwater microalgal species. In addition, we identify a B12-responsive element of Chlamydomonas reinhardtii METE using a reporter gene approach. We show that complete repression of the reporter occurs via a region spanning −574 to −90 bp upstream of the METE start codon. A proteomics study reveals that two other genes (S-Adenosylhomocysteine hydrolase and Serine hydroxymethyltransferase2) involved in the methionine-folate cycle are also repressed by B12 in C. reinhardtii. The strong repressible nature and high sensitivity of the B12-responsive element has promising biotechnological applications as a cost-effective regulatory gene expression tool. PMID:24627342

  5. Vitamin B12 Levels of Subjects Aged 0-24 Year(s) in Konya, Turkey

    PubMed Central

    Yavuz, Haluk; Bodur, Said; Kiyici, Aysel

    2014-01-01

    ABSTRACT Research reports indicate that vitamin B12 levels show racial differences, which suggests that using the reference ranges of varied populations may lead to inaccurate results. This study aimed to determine normal serum levels of vitamin B12 among children and young people in the Konya region of Turkey. It evaluated 1,109 samples; 54 were from cord-blood and 1,055 were from healthy subjects aged 0-24 year(s), who were admitted to primary healthcare centres. The normal reference levels obtained for vitamin B12 at 2.5-97.5 percentile (P2.5-P97.5) range were 127-606 pg/mL for girls, 127-576 pg/mL for boys, and 127-590 pg/mL for the entire study group. The reported reference values for vitamin B12 in other studies were higher than the current results. Vitamin B12 levels vary from country to country; comparisons between countries may not be valid, and normal levels for each population should be obtained. PMID:25895195

  6. Stability of added and in situ-produced vitamin B12 in breadmaking.

    PubMed

    Edelmann, Minnamari; Chamlagain, Bhawani; Santin, Marco; Kariluoto, Susanna; Piironen, Vieno

    2016-08-01

    Vitamin B12 exists naturally in foods of animal origin and is synthesised only by certain bacteria. New food sources are needed to ensure vitamin B12 intake in risk groups. This study aimed to investigate the stability of added cyanocobalamin (CNCbl, chemically modified form) and hydroxocobalamin (OHCbl, natural form) and in situ-synthesised vitamin B12 in breadmaking. Samples were analysed both with a microbiological (MBA) and a liquid chromatographic (UHPLC) method to test applicability of these two methods. Proofing did not affect CNCbl and OHCbl levels. By contrast, 21% and 31% of OHCbl was lost in oven-baking steps in straight- and sponge-dough processes, respectively, whereas CNCbl remained almost stable. In sourdough baking, 23% of CNCbl and 44% of OHCbl were lost. In situ-produced vitamin B12 was almost as stable as added CNCbl and more stable than OHCbl. The UHPLC method showed its superiority to the MBA in determining the active vitamin B12. PMID:26988471

  7. Vitamin B12 supplementation in end stage renal diseases: a systematic review

    PubMed Central

    Amini, Maryam; Khosravi, Maryam; Baradaran, Hamid Reza; Atlasi, Rasha

    2015-01-01

    Background: Hyperhomocysteinemia is a risk factor for cardiovascular disease particularly in patients with end stage renal disease (ESRD). Vitamin B12 supplementation on its own still remains as a controversial issue for clinicians in decreasing the level of homcysteine in this group of patients. Methods: Using all randomized controlled trials (RCTs), clinical trials and pre-post-trial studies found during January 1999 to March 2014, we conducted a systematic review which assessed the effects of vitamin B12 in decreasing homocysteine levels in patients with ESRD. Results: The findings of this study revealed that, overall, the greatest effect of B12 supplementation on decreasing homocysteine levels in patients with ESRDs occurred when it was combined with folate supplementation. It was also demonstrated that injection treatments might be more beneficial than oral intake treatments. Conclusion: More rigorous studies are needed to draw a firm conclusion about B12 therapy and the level of homocyteine in patients with ESRD. PMID:26000261

  8. Distributions of dissolved vitamin B 12 and Co in coastal and open-ocean environments

    NASA Astrophysics Data System (ADS)

    Panzeca, Caterina; Beck, Aaron J.; Tovar-Sanchez, Antonio; Segovia-Zavala, Jose; Taylor, Gordon T.; Gobler, Christopher J.; Sañudo-Wilhelmy, Sergio A.

    2009-11-01

    Distributions of dissolved vitamin B 12 and total dissolved Co were measured to gain an understanding of the cycling of these interdependent micronutrients in six marine settings including; an upwelling location, a semi-enclosed bay, two urban coastal systems, and two open ocean locations. Along the coast of Baja California, Mexico, concentrations of B 12 and dissolved Co varied from 0.2 to 11 pM and 180 to 990 pM, respectively. At a nearby upwelling station, vitamin B 12 and Co concentrations ranged from 0.3 to 7.0 pM and 22 to 145 pM, and concentrations did not correlate with upwelling intensity. Concentrations of B 12 were highest within Todos Santos Bay, a semi-enclosed bay off the coast of Baja California, Mexico, during a dinoflagellate bloom, ranging from 2 to 61 pM, while Co concentrations varied between 61 and 194 pM. In the anthropogenically impacted Long Island Sound, NY, U.S.A., B 12 levels were between 0.1 and 23 pM and Co concentrations varied from 60 to 1900 pM. However, anthropogenic inputs were not evident in B 12 levels in the San Pedro Basin, located outside Los Angeles, Ca, U.S.A., where concentrations of B 12 were 0.2-1.8 pM, approximating observed open ocean B 12 concentrations. In the Southern Ocean and North Atlantic Ocean, B 12 levels were 0.4-4 pM and 0.2-2 pM, respectively. Total Co concentrations in the Southern Ocean and North Atlantic tended to be low; measuring 26-59 pM and 15-80 pM, respectively. These low Co concentrations may limit B 12 synthesis and its availability to B 12-requiring phytoplankton because the total dissolved Co pool is not necessarily entirely bioavailable.

  9. Isolated cerebellar involvement in vitamin B12 deficiency: a case report.

    PubMed

    Chakrabarty, Biswaroop; Dubey, Rachana; Gulati, Sheffali; Yoganathan, Sangeetha; Kumar, Ajay; Kumar, Atin

    2014-11-01

    Deficiency of vitamin B12 causes megaloblastic anemia and nervous system demyelination. Structures affected in the nervous system include spinal cord, cranial and peripheral nerves, and brain white matter. A 9-year-old boy presented with knuckle hyperpigmentation and oral ulcers for 3 years, pallor and easy fatigability for 6 months, gait abnormalities for 3 months, and abnormal speech and behavioral abnormalities for 3 days. On examination, he had physical signs of megaloblastic anemia, mood swings with intermittent hallucinations, and features of cerebellar impairment. Blood investigations revealed megaloblastic anemia, and pernicious anemia was ruled out. Brain magnetic resonance imaging (MRI) revealed bilateral cerebellar signal changes. He received treatment for vitamin B12 deficiency and appropriate nutritional counseling. Three months later, he showed significant clinical and radiologic resolution. To our knowledge, isolated cerebellar involvement as the sole neurologic manifestation of vitamin B12 deficiency has not been described previously in children. PMID:24346315

  10. [Neurological disorders related to vitamin B12 deficiency in prisons in Guinea: a 22-case study].

    PubMed

    Cisse, F A; Bah, H; Konate, F; Camara, N; Camara, M I; Conde, K; Kassory, I F B; Sanogo, A; Diakhate, I; Cisse, A

    2013-08-01

    Neurological disorders related to vitamin B12 deficiency are common in prisons of tropical Africa. We collected 22 cases (20 men and 2 women). They all showed vitamin B12 deficiency associated with neurological signs that were represented by sclerosis combined with bone marrow (n = 9), peripheral neuropathy (n = 6), cerebellar syndrome (n = 2), a pyramidal syndrome of the lower limbs (n = 4) and optic neuropathy (n = 1). Laboratory tests showed a mean hemoglobin concentration of 7.2 1.5 g/dl, mean 104 28 fl, macrocytic anemia in 10 patients. Biermer's disease was identified in 9 patients, 3 patients showed the syndrome of non dissociation of vitamin B12, a gastrectomy in 2 patients and no etiology was identified in 8 patients. PMID:23793871

  11. Low serum vitamin B12 levels among psychiatric patients admitted in Butabika mental hospital in Uganda

    PubMed Central

    2014-01-01

    Background Psychiatric manifestations have been noted in patients with low serum vitamin B12 levels even in the absence of other neurologic and/or haematologic abnormalities. There is no literature on low serum B12 prevalence among Ugandans with psychiatric illnesses. The aim of this study was to establish the prevalence, risk factors, and clinical manifestations of low serum vitamin B12 among psychiatric patients admitted in a Mental Health Hospital in Uganda. Method Using a cross sectional descriptive study design, 280 in-patients selected by systematic sampling were studied using a standardized protocol. Low serum vitamin B12 was defined as a level?B12 in 28.6% of the participants. Absent vibration sense which was significantly associated (58.3% Vs. 26.7%: OR?=?3.84 (95% C.I. 1.18, 12.49); p-value?=?0.025) with low vitamin B12 was observed among 12 participants. Macro-ovalocytes present among 23 participants on peripheral film were significantly associated with low serum levels (73.9% Vs. 26.2%: OR?=?7.99 (95% C.I. 3.01, 21.19) p-value?B12 levels included psychiatric diagnosis of schizophrenia (AOR 1.74 (95% C.I. 1.00, 3.02); p-value?=?0.049), duration of psychiatric illness?>?or?=?3years (AOR 2.27 (95% C.I. 1.29, 3.98); p-value?=?0.004), and hospitalization?B12 is common among hospitalized psychiatric patients with the majority having no haematological findings. Associated risk factors included having a psychiatric diagnosis of schizophrenia, a shorter duration of hospitalization and longer duration of psychiatric illness. Female participants were less likely to have low serum vitamin B12 levels. Routine screening for serum vitamin B12 levels should be adopted by all hospitals for admitted psychiatric patients. PMID:24533701

  12. Decreased vitamin B12 availability induces ER stress through impaired SIRT1-deacetylation of HSF1

    PubMed Central

    Ghemrawi, R; Pooya, S; Lorentz, S; Gauchotte, G; Arnold, C; Gueant, J-L; Battaglia-Hsu, S-F

    2013-01-01

    Vitamin B12 (cobalamin) is a key determinant of S-adenosyl methionine (SAM)-dependent epigenomic cellular regulations related to methylation/acetylation and its deficiency produces neurodegenerative disorders by elusive mechanisms. Sirtuin 1 deacetylase (SIRT1) triggers cell response to nutritional stress through endoplasmic reticulum (ER) stress. Recently, we have established a N1E115 dopaminergic cell model by stable expression of a transcobalaminoleosin chimera (TO), which impairs cellular availability of vitamin B12, decreases methionine synthase activity and SAM level, and reduces cell proliferation. In contrast, oleosin-transcobalamin chimera (OT) does not modify the phenotype of transfected cells. Presently, the impaired cellular availability of vitamin B12 in TO cells activated irreversible ER stress pathways, with increased P-eIF-2?, P-PERK, P-IRE1?, ATF6, ATF4, decreased chaperon proteins and increased pro-apoptotic markers, CHOP and cleaved caspase 3, through reduced SIRT1 expression and consequently greater acetylation of heat-shock factor protein 1 (HSF1). Adding either B12, SIRT1, or HSF1 activators as well as overexpressing SIRT1 or HSF1 dramatically reduced the activation of ER stress pathways in TO cells. Conversely, impairing SIRT1 and HSF1 by siRNA, expressing a dominant negative form of HSF1, or adding a SIRT1 inhibitor led to B12-dependent ER stress in OT cells. Addition of B12 abolished the activation of stress transducers and apoptosis, and increased the expression of protein chaperons in OT cells subjected to thapsigargin, a strong ER stress stimulator. AdoX, an inhibitor of methyltransferase activities, produced similar effects than decreased B12 availability on SIRT1 and ER stress by a mechanism related to increased expression of hypermethylated in cancer 1 (HIC1). Taken together, these data show that cellular vitamin B12 has a strong modulating influence on ER stress in N1E115 dopaminergic cells. The impaired cellular availability in vitamin B12 induces irreversible ER stress by greater acetylation of HSF1 through decreased SIRT1 expression, whereas adding vitamin B12 produces protective effects in cells subjected to ER stress stimulation. PMID:23519122

  13. Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease.

    PubMed

    Rush, E C; Katre, P; Yajnik, C S

    2014-01-01

    This review brings together human and animal studies and reviews that examine the possible role of maternal vitamin B12 (B12) on fetal growth and its programming for susceptibility to chronic disease. A selective literature review was undertaken to identify studies and reviews that investigate these issues, particularly in the context of a vegetarian diet that may be low in B12 and protein and high in carbohydrate. Evidence is accumulating that maternal B12 status influences fetal growth and development. Low maternal vitamin B12 status and protein intake are associated with increased risk of neural tube defect, low lean mass and excess adiposity, increased insulin resistance, impaired neurodevelopment and altered risk of cancer in the offspring. Vitamin B12 is a key nutrient associated with one carbon metabolic pathways related to substrate metabolism, synthesis and stability of nucleic acids and methylation of DNA which regulates gene expression. Understanding of factors regulating maternal-fetal one carbon metabolism and its role in fetal programming of non communicable diseases could help design effective interventions, starting with maternal nutrition before conception. PMID:24219896

  14. Potential cobalt limitation of vitamin B12 synthesis in the North Atlantic Ocean

    NASA Astrophysics Data System (ADS)

    Panzeca, C.; Beck, A. J.; Leblanc, K.; Taylor, G. T.; Hutchins, D. A.; SaUdo-Wilhelmy, S. A.

    2008-06-01

    While recent studies have confirmed the ecological importance of vitamin B12, it is unclear whether the production of this vitamin could be limited by dissolved Co, a trace metal required for B12 biosynthesis, but found at only subnanomolar concentrations in the open ocean. Herein, we demonstrate that the spatial distribution of dissolved B12 (range: 0.13-5 pmol L-1) in the North Atlantic Ocean follows the abundance of total dissolved Co (range: 15-81 pmol L-1). Similar patterns were observed for bacterial productivity (range: 20-103 pmol 3H leucine L-1 hr-1) and algal biomass (range: 0.4-3.9 ?g L-1). In contrast, vitamin B1 concentrations (range: 0.7-30 pM) were decoupled from both Co and B12 concentrations. Cobalt amendment experiments carried out in low-dissolved Co waters (20 pmol L-1) enhanced B12 production two-fold over unamended controls. This study provides evidence that B12 synthesis could be limited by the availability of Co in some regions of the world ocean.

  15. Studies on the spin Hamiltonian parameters of vitamin B 12r

    NASA Astrophysics Data System (ADS)

    Wu, Shao-Yi; Wei, Li-Hua; Zhang, Zhi-Hong; Wang, Xue-Feng

    2009-01-01

    The spin Hamiltonian parameters g factors gi ( i = x, y, z) and the hyperfine structure constants Ai of vitamin B 12r have been theoretically studied from the perturbation formulas of these parameters for a Co 2+(3d 7) ion with low spin ( S = 1/2) in rhombically distorted octahedra. The related crystal-field parameters are determined from the point-charge-dipole model and the local structure around Co 2+ in vitamin B 12r. The theoretical spin Hamiltonian parameters are in good agreement with the experimental data.

  16. Biosynthesis of vitamin B12: concerning the origin of the methine protons of the corrin nucleus

    SciTech Connect

    Scott, A.I.; Kajiwara, M.; Santander, P.J.

    1987-10-01

    13C NMR spectroscopy has been used to locate six deuterium atoms incorporated biosynthetically on the periphery of the corrin nucleus of vitamin B12 (cyanocobalamin) derived from cells of Propionibacterium shermanii grown in a medium containing 50% /sup 2/H/sub 2/O and /sup 13/C-enriched delta-aminolevulinic acid. The implications of these results for the mechanism of vitamin B12 biosynthesis are discussed, and it is concluded that the same oxidation level of the intermediates is maintained throughout the biosynthetic pathway, from delta-aminolevulinic acid to corrin.

  17. Pernicious anemia presenting as catatonia: correlating vitamin B12 levels and catatonic symptoms.

    PubMed

    Bram, Damien; Bubrovszky, Maxime; Durand, Jean-Paul; Lefevre, Guillaume; Morell-Dubois, Sandrine; Vaiva, Guillaume

    2015-01-01

    Pernicious anemia has been associated with various psychiatric manifestations, such as depression, mania and psychosis. Psychiatric symptoms can sometimes occur without hematological and neurological abnormalities and can be prodromal of vitamin B12 deficiency. We report a case of autoimmune B12 deficiency presenting as catatonia without signs of anemia or macrocytosis, in which a correlation was found between the patient's B12 blood levels and catatonic symptoms over time. This catatonic episode was successfully treated with only lorazepam and adequate doses of cyanocobalamin. PMID:25774050

  18. An appraisal of the value of vitamin B12 in the prevention of motion sickness

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Lacey, C. L.; Homick, J. L.

    1983-01-01

    It has been suggested that vitamin B12 given by intramuscular injection can significantly reduce the occurrence of motion sickness in susceptible individuals (Banks, 1980). Since it is known that B12 influences the metabolism of histidine and choline, dietary precursors to neurotransmitters with established roles in motion sickness, an experimental evaluation has been undertaken of the efficacy of B12 in the prevention of motion sickness induced by controlled coriolis simulation. Subjects executed standardized head movements at successively higher rpm until a malaise III endpoint was reached. Following two baseline tests with this motion stressor, subjects received a B12 injection, a second injection two weeks later, and a final motion sickness test three weeks later. No significant differences in the susceptibility to motion sickness were noted after B12.

  19. BluB cannibalizes flavin to form the lower ligand of vitamin B12

    PubMed Central

    Taga, Michiko E.; Larsen, Nicholas A.; Howard-Jones, Annaleise R.; Walsh, Christopher T.; Walker, Graham C.

    2009-01-01

    Vitamin B12 (cobalamin) is among the largest known non-polymeric natural products, and the only vitamin synthesized exclusively by microorganisms1. The biosynthesis of the lower ligand of vitamin B12, 5,6-dimethylbenzimidazole (DMB), is poorly understood13. Recently, we discovered that a Sinorhizobium meliloti gene, bluB, is necessary for DMB biosynthesis4. Here we show that BluB triggers the unprecedented fragmentation and contraction of the bound flavin mononucleotide cofactor and cleavage of the ribityl tail to form DMB and D-erythrose 4-phosphate. Our structural analysis shows that BluB resembles an NAD(P)H-flavin oxidoreductase, except that its unusually tight binding pocket accommodates flavin mononucleotide but not NAD(P)H. We characterize crystallographically an early intermediate along the reaction coordinate, revealing molecular oxygen poised over reduced flavin. Thus, BluB isolates and directs reduced flavin to activate molecular oxygen for its own cannibalization. This investigation of the biosynthesis of DMB provides clarification of an aspect of vitamin B12 that was otherwise incomplete, and may contribute to a better understanding of vitamin B12-related disease. PMID:17377583

  20. BluB cannibalizes flavin to form the lower ligand of vitamin B12.

    PubMed

    Taga, Michiko E; Larsen, Nicholas A; Howard-Jones, Annaleise R; Walsh, Christopher T; Walker, Graham C

    2007-03-22

    Vitamin B12 (cobalamin) is among the largest known non-polymeric natural products, and the only vitamin synthesized exclusively by microorganisms. The biosynthesis of the lower ligand of vitamin B(12), 5,6-dimethylbenzimidazole (DMB), is poorly understood. Recently, we discovered that a Sinorhizobium meliloti gene, bluB, is necessary for DMB biosynthesis. Here we show that BluB triggers the unprecedented fragmentation and contraction of the bound flavin mononucleotide cofactor and cleavage of the ribityl tail to form DMB and D-erythrose 4-phosphate. Our structural analysis shows that BluB resembles an NAD(P)H-flavin oxidoreductase, except that its unusually tight binding pocket accommodates flavin mononucleotide but not NAD(P)H. We characterize crystallographically an early intermediate along the reaction coordinate, revealing molecular oxygen poised over reduced flavin. Thus, BluB isolates and directs reduced flavin to activate molecular oxygen for its own cannibalization. This investigation of the biosynthesis of DMB provides clarification of an aspect of vitamin B12 that was otherwise incomplete, and may contribute to a better understanding of vitamin B12-related disease. PMID:17377583

  1. Effects of Formulation Variables and Storage Conditions on Light Protected Vitamin B12 Mixed Parenteral Formulations

    PubMed Central

    Monajjemzadeh, Farnaz; Ebrahimi, Fatemeh; Zakeri-Milani, Parvin; Valizadeh, Hadi

    2014-01-01

    Purpose: In this research the effect of vitamin B1 and B6 on cyanocobalamin stability in commercial light protected parenteral formulations and upon adding stabilizing agents will be investigated and best formulation composition and proper storage condition will be introduced. Methods: In this research some additives such as co solvents and tonicity adjusters, surfactants, antioxidants and chelating agents as well as buffer solutions, were used to improve the stability of the parenteral mixed formulations of B12 in the presence of other B vitamins (B1 and B6). Screening tests and accelerated stability tests were performed according to ICH guidelines Q1A (R2). Results: Shelf life evaluation revealed the best formulation and the proper storage condition. The results indicated the first kinetic models for all tested formulations and the optimum pH value was determined to be 5.8. There was no evidence of B12 loss when mixed with B1 and B6 in a medical syringe at room temperature for maximum of 8 hours. Conclusion: It is necessary to formulate vitamin B12 mixed parenteral solutions using proper phosphate buffers (pH=5.8) and to indicate Store in refrigerator on the mixed parenteral formulations of vitamin B12 with other B vitamins, which has not been expressed on the label of tested Brand formulations at the time of this study. PMID:25436187

  2. Effect of vitamin B12 supplementation on B12 status and neurophysiological function in older Chileans analyzed by the combined indicator of B12 status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2005 the National Feeding Program for the Elderly (PACAM) in Chile has provided a B12 fortified milk drink (1.7 g B12/d) which is insufficient to ensure B12 adequacy in many individuals. The objective was to evaluate effects of adding 1 mg B12/d to PACAM vs 1 mg B12/d as a pill with PACAM on ...

  3. Comparative genomics of the vitamin B12 metabolism and regulation in prokaryotes.

    PubMed

    Rodionov, Dmitry A; Vitreschak, Alexey G; Mironov, Andrey A; Gelfand, Mikhail S

    2003-10-17

    Using comparative analysis of genes, operons, and regulatory elements, we describe the cobalamin (vitamin B12) biosynthetic pathway in available prokaryotic genomes. Here we found a highly conserved RNA secondary structure, the regulatory B12 element, which is widely distributed in the upstream regions of cobalamin biosynthetic/transport genes in eubacteria. In addition, the binding signal (CBL-box) for a hypothetical B12 regulator was identified in some archaea. A search for B12 elements and CBL-boxes and positional analysis identified a large number of new candidate B12-regulated genes in various prokaryotes. Among newly assigned functions associated with the cobalamin biosynthesis, there are several new types of cobalt transporters, ChlI and ChlD subunits of the CobN-dependent cobaltochelatase complex, cobalt reductase BluB, adenosyltransferase PduO, several new proteins linked to the lower ligand assembly pathway, l-threonine kinase PduX, and a large number of other hypothetical proteins. Most missing genes detected within the cobalamin biosynthetic pathways of various bacteria were identified as nonorthologous substitutes. The variable parts of the cobalamin metabolism appear to be the cobalt transport and insertion, the CobG/CbiG- and CobF/CbiD-catalyzed reactions, and the lower ligand synthesis pathway. The most interesting result of analysis of B12 elements is that B12-independent isozymes of the methionine synthase and ribonucleotide reductase are regulated by B12 elements in bacteria that have both B12-dependent and B12-independent isozymes. Moreover, B12 regulons of various bacteria are thought to include enzymes from known B12-dependent or alternative pathways. PMID:12869542

  4. Vitamin B12 Deficiency: An Important Reversible Co-Morbidity in Neuropsychiatric Manifestations

    PubMed Central

    Issac, Thomas Gregor; Soundarya, Soundararajan; Christopher, Rita; Chandra, Sadanandavalli Retnaswami

    2015-01-01

    Background: Vitamin B12 deficiency is a common condition causing neurologic, cognitive, psychiatric, and mood symptoms. With varied religious, ethnic, and socioeconomic heterogeneity among the people in India greatly influencing their dietary habits and with the high prevalence of Helicobacter pylori infection, Vitamin B12 deficiency is not uncommon, but is often under recognized due to the lack of classical symptomatic presentation. Materials and Methods: Retrospective study on Vitamin B12 deficiency with neuropsychiatric symptoms in patients who attended neurology, psychiatry, and geriatric OPDs for a period of 1 year in a specialized neuropsychiatric institute in South India. Results: Out of 259 patients who had Vitamin B12 deficiency (<220 pmol/L), 60 had neuropsychiatric symptoms. Among them the Vitamin B12 levels were <150 (severe), 150-200 (moderate), and 201-220 pmol/L (mild) in 19, 24, 17 patients, respectively. Twenty one were diagnosed with Posterior dementias, 20 with frontotemporal dementia, 7 with Schizophrenia, 4 each with Parkinson's disease and alcohol-dependent syndromes (ADS), 3 with bipolar affective disorder, and 1 with Creutzfeldt-Jakob disease. Eight patients also had hypothyroidism. First symptom of presentation was behavioral disturbances in 30 (50%), memory loss in 20 (33.9%), and sensorimotor and movement disorders in 9 (15.3%), and 56.7% were vegetarians while 43.3% were nonvegetarians. In our study, Vitamin B12 deficiency was more prevalent in elderly males (56.67%) and was associated with increased severity of behavioral disturbances (P = 0.043) which was the most common presentation. Memory loss was present in 16 (84.2%) patients of severe Vitamin B12 deficiency. Hindi mental status examination (HMSE) score was graded as <20, 20-24, 24-31 in 37 (61.7%), 10 (16.7%), and 13 (21.7%) patients, respectively. Cognitive decline in Vitamin B12 deficiency was significantly associated with increased serum cholesterol (P = 0.019) and was significantly prevalent in neurological disorders when compared with primary psychiatric illnesses (P = 0.001). Mean folate and mean homocysteine in our study was 11.7 6.44 ng/ml and 17.77 5.45 ?mol/L, respectively. Eighty percent of the population had normal folate levels whereas mean homocysteine values were much higher than that of the western population (10-12 ?mol/L). Conclusion: Vitamin B12 deficiency though common in India is often overlooked. It increases the load of cognitive decline and accentuates vascular risk factors in neuropsychiatric illnesses. Vitamin B12 deficiency also increases homocysteine levels contributing to the vascular comorbidity in cerebro and cardiovascular illnesses. So prevention, early detection, and management of this reversible Vitamin B12 deficiency state is of profound importance. PMID:25722508

  5. [Homocysteine, vitamin B-12, folic acid and the cognitive decline in the elderly].

    PubMed

    Smach, M A; Naffeti, S; Charfeddine, B; Ben Abdallah, J; Othmen, L B; Letaef, A; Limem, K

    2013-10-01

    Hyperhomocysteinemia is a risk factor for neurological diseases, but the underlying pathophysiology has not been adequately explained. Mild hyperhomocysteinemia, which is sometimes associated with a low plasma level of vitamin B9, B12 and folic acid, is responsible in the toxicity in neural cell by activating NMDA receptor. Indeed, even if vitamin supplementation has clearly proven its efficiency on lowering plasma levels of homocysteine, recent studies do not show any positive effect of vitamin therapy on cognitive function. The hypothesis that this therapy is inefficient has been recently reinforced by two randomized trials on the effects of vitamin supplementation. Several hypotheses still need to be explored: Mechanisms of homocysteine toxicity and that of total uselessness of vitamin supplementation; the possible need to complete the actual data with further, more powerful studies in order to prove the role of homocysteine in the development of neurodegenerative diseases and a clinical effect of vitamin therapy. PMID:22647793

  6. Treatment of depression: time to consider folic acid and vitamin B12.

    PubMed

    Coppen, Alec; Bolander-Gouaille, Christina

    2005-01-01

    We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression. PMID:15671130

  7. Elevation of urinary methylmolonic acid induces the suppression of megalin-mediated endocytotic cycles during vitamin B12 deficiency.

    PubMed

    Shiga, Takahiro; Kawata, Tetsunori; Furusho, Tadasu; Tadokoro, Tadahiro; Suzuki, Tsukasa; Yamamoto, Yuji

    2015-09-18

    Megalin is a scavenger receptor that serves in the endocytosis of a highly diverse group of ligands that includes Vitamin B12. We found an accumulation of megalin closed to apical region in renal proximal tubule cells of Vitamin B12-deficient rats. Interestingly, Vitamin B12 levels also controlled resorption of renal retinol binding protein. Using L2 yolk sac cells, megalin localized to the submembrane compartment by methylmalonic acid (MMA), which accumulates during vitamin B12 deficiency. In addition, MMA inhibited megalin-mediated endocytosis via YWTD repeats motif in an ectodomain of megalin. Therefore, megalin endocytosis may be regulated by MMA. PMID:26248135

  8. Folate and vitamin B12-related genes and risk for omphalocele.

    PubMed

    Mills, James L; Carter, Tonia C; Kay, Denise M; Browne, Marilyn L; Brody, Lawrence C; Liu, Aiyi; Romitti, Paul A; Caggana, Michele; Druschel, Charlotte M

    2012-05-01

    Both taking folic acid-containing vitamins around conception and consuming food fortified with folic acid have been reported to reduce omphalocele rates. Genetic factors are etiologically important in omphalocele as well; our pilot study showed a relationship with the folate metabolic enzyme gene methylenetetrahydrofolate reductase (MTHFR). We studied 169 non-aneuploid omphalocele cases and 761 unaffected, matched controls from all New York State births occurring between 1998 and 2005 to look for associations with single nucleotide polymorphisms (SNPs) known to be important in folate, vitamin B12, or choline metabolism. In the total study population, variants in the transcobalamin receptor gene (TCblR), rs2232775 (p.Q8R), and the MTHFR gene, rs1801131 (c.1298A>C), were significantly associated with omphalocele. In African-Americans, significant associations were found with SNPs in genes for the vitamin B12 transporter (TCN2) and the vitamin B12 receptor (TCblR). A SNP in the homocysteine-related gene, betaine-homocysteine S-methyltransferase (BHMT), rs3733890 (p.R239Q), was significantly associated with omphalocele in both African-Americans and Asians. Only the TCblR association in the total population remained statistically significant if Bonferroni correction was applied. The finding that transcobalamin receptor (TCblR) and transporter (TCN2) SNPs and a BHMT SNP were associated with omphalocele suggests that disruption of methylation reactions, in which folate, vitamin B12, and homocysteine play critical parts, may be a risk factor for omphalocele. Our data, if confirmed, suggest that supplements containing both folic acid and vitamin B12 may be beneficial in preventing omphaloceles. PMID:22116453

  9. STM investigations of Au(1 1 1) electrodes coated with vitamin B 12 derivatives

    NASA Astrophysics Data System (ADS)

    Szőcs, E.; Durrer, L.; Luginbühl, R.; Simic, N.; Viana, A. S.; Abrantes, L. M.; Keese, R.; Siegenthaler, H.

    2006-01-01

    Vitamin B 12 derivatives immobilized at flame-annealed Au(1 1 1) electrode surfaces have been investigated in close correlation with their structural properties and spatial arrangement at the electrode substrate by scanning tunneling microscopy (STM) in air and in aqueous 0.1 M NaClO 4 solution. The investigated compounds were symmetrical (B 12C 10S-SC 10B 12) and nonsymmetrical (B 12C 10S-SC 10) dialkyl disulfide derivatives of vitamin B 12, attached to the electrode surfaces by the S-Au bond. The ex situ and in situ STM experiments show the formation of a surface layer, whose packing density and structure is presumably controlled by the spatial arrangement of the large cobyrinate head groups. In presence of the symmetrical B 12 compound, a disordered surface layer is observed. Voltammetric investigations show that, in 0.1 M NaClO 4, this layer becomes unstable at potentials approximately ⩽ -1000 mV vs. MSE and is almost completely removed at more negative potentials. The STM imaging properties of the nonsymmetrical B 12 surface layer show a significant dependence on the tunneling distance. In particular, at small tunneling distances, a highly regular hexagonal surface pattern is observed that suggests strongly the presence of an ordered surface assembly. Modeling of the B 12 head group has been performed to provide information for a structure-related interpretation of the high-resolution STM images. The investigations are first STM results obtained at such B 12 modified electrodes.

  10. Total serum homocysteine as an indicator of vitamin B12 and folate status

    SciTech Connect

    Chu, R.C.; Hall, C.A.

    1988-10-01

    Presented is a modification of an assay for total serum homocysteine (Hcy) in which the Hcy plus radioactive adenosine is converted enzymatically to labeled S-adenosylhomocysteine (AdoHcy). The modifications included a commerical source for the AdoHcy hydrolase, adenosine labeled with either /sup 14/C or /sup 3/H, and separation of the AdoHcy by thin layer chromatography. The assay was sensitive to 25 pmol. Hcy levels in sera from 18 controls ranged from 6.9 to 12.1 mumol/L with a mean of 9.1 and a SD of 1.5 mumol/L. The total serum Hcy was increased in vitamin B12 and folate deficiency. The level was high in congenital defects of vitamin B12 metabolism, blocking the methylation of Hcy regardless of the serum vitamin B12 levels, but was normal in the absence of tissue deficiency even if the serum vitamin B12 levels were low. The procedure has been found practical in two years of use and requires only 0.1 mL of serum.

  11. Genomic Sequence of Klebsiella pneumoniae IIEMP-3, a Vitamin B12-Producing Strain from Indonesian Tempeh.

    PubMed

    Yulandi, Adi; Sugiokto, Febri Gunawan; Febrilina; Suwanto, Antonius

    2016-01-01

    Klebsiella pneumoniae strain IIEMP-3, isolated from Indonesian tempeh, is a vitamin B12-producing strain that exhibited a different genetic profile from pathogenic isolates. Here we report the draft genome sequence of strain IIEMP-3, which may provide insights on the nature of fermentation, nutrition, and immunological function of Indonesian tempeh. PMID:26950331

  12. Mesoporous carbon derived from vitamin B12: a high-performance bifunctional catalyst for imine formation.

    PubMed

    Chen, Bo; Shang, Sensen; Wang, Lianyue; Zhang, Yi; Gao, Shuang

    2016-01-11

    Mesoporous carbon derived from natural vitamin B12 is applied for the first time in organic synthesis and exhibits exceptionally high dual activity for imine formation via the cross-coupling of alcohols with amines and the self-coupling of primary amines using molecular oxygen or air as the terminal oxidant. PMID:26529323

  13. Competitive chemiluminescent anzyme immunoassay for vitamin B12 analysis in human milk.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent discoveries of matrix interferences by haptocorrin (HC) in human milk and serum show that past analyses of vitamin B12 in samples with high HC content might have been inaccurate (Lildballe et al., 2009; Carmel & Agrawal, 2012). We evaluated two competitive enzyme-binding immunoassays for seru...

  14. Brief Report: Childhood Disintegrative Disorder as a Likely Manifestation of Vitamin B12 Deficiency

    ERIC Educational Resources Information Center

    Malhotra, Savita; Subodh, B. N.; Parakh, Preeti; Lahariya, Sanjay

    2013-01-01

    Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case

  15. Review of the magnitude of folate and vitamin B12 deficiencies worldwide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human deficiencies of folate and vitamin B12 result in adverse effects which may be of public health significance, but the magnitude of these deficiencies is unknown. Therefore, we examine the prevalence data currently available, assess global coverage of surveys, determine the frequency with which...

  16. Enhanced pharmacological activity of Vitamin B12 and Penicillin as nanoparticles

    PubMed Central

    Yariv, Inbar; Lipovsky, Anat; Gedanken, Aharon; Lubart, Rachel; Fixler, Dror

    2015-01-01

    Sonochemistry has become a well-known technique for fabricating nanomaterials. Since one of the advantages of nanomaterials is that they have higher chemical activities compared with particles in the bulk form, efforts are being made to produce nano organic compounds with enhanced biological activities that could be exploited in the medical area. This study uses the sonication technique to prepare nano Vitamin B12 and nano Penicillin, and demonstrates their enhanced biological and pharmacological activity. The size and morphology of the nano Penicillin and nano Vitamin B12 were investigated using electron microscopy as well as dynamic light scattering techniques. The sizes of Penicillin and Vitamin B12 nanoparticles (NPs) were found to be 70 and 120–180 nm, respectively. The bactericidal effect of nano Penicillin was studied and found to be higher than that of the bulk form. Reducing the size of Vitamin B12 resulted in their enhanced antioxidative activity as observed using the electron paramagnetic spectroscopy technique. The penetration depth of these organic NPs can be detected by an optical iterative method. It is believed that nano organic drugs fabrication will have a great impact on the medical field. PMID:26028970

  17. Brief Report: Childhood Disintegrative Disorder as a Likely Manifestation of Vitamin B12 Deficiency

    ERIC Educational Resources Information Center

    Malhotra, Savita; Subodh, B. N.; Parakh, Preeti; Lahariya, Sanjay

    2013-01-01

    Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case…

  18. Copper control of bacterial nitrous oxide emission and its impact on vitamin B12-dependent metabolism.

    PubMed

    Sullivan, Matthew J; Gates, Andrew J; Appia-Ayme, Corinne; Rowley, Gary; Richardson, David J

    2013-12-01

    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. We show that elevated levels of N2O released as a consequence of decreased cellular NosZ activity lead to the bacterium switching from vitamin B12-dependent to vitamin B12-independent biosynthetic pathways, through the transcriptional modulation of genes controlled by vitamin B12 riboswitches. This inhibitory effect of N2O can be rescued by addition of exogenous vitamin B12. PMID:24248380

  19. Vitamin B12-binders in human body fluids. I. Antigenic and physico-chemical characteristics

    PubMed Central

    Hurlimann, J.; Zuber, Cecile

    1969-01-01

    Three factors binding vitamin B12 are detected in human gastric juice by autoradiographs of immunoelectrophoresis. Binder 1 is present only in gastric juice and gastric mucosa extract and corresponds to intrinsic factor. Binder 2 is present also in other excretions such as bile, lactoserum, saliva, in serum and leucocyte extracts. Binder 3 present in saliva and gastric juice in lower quantity than binder 2, seems derived from this last one by attachment of sialic acid molecules. There is no immunological identity between intrinsic factor and the other binders without intrinsic factor activity. Binder 3 is resistant to proteolysis in vivo and in vitro. Binder 2 is modified by peptic digestion in vivo but not in vitro. Binder 1 is insensitive to proteolysis if saturated by vitamin B12, but loses its binding capacity and/or immunological properties if the digestion takes place before fixation of vitamin B12. The three binders seem to have the same affinity for vitamin B12 as judged by dialysis experiments, and the same molecular weight of 60,000 as judged by volume exclusion on Sephadex G-200. ImagesFIG. 1FIG. 2FIG. 3FIG. 5FIG. 6FIG. 7 PMID:5819225

  20. Effects of vitamin B12 supplementation on the quality of Ovine spermatozoa

    PubMed Central

    Hamedani, M.A.; Tahmasbi, A.M.; Ahangari, Y.J.

    2013-01-01

    The present study was undertaken to investigate the effect of various levels of vitamin B12 in Tris extender on semen quality of Dallagh rams following the cooling and freeze/thawing process. Semen was collected from six healthy and mature rams with an average body weight of 60.0 ± 5.0 Kg using an electro ejaculator. High quality samples were mixed and diluted in Tris extender supplemented with different concentrations of vitamin B12 (0, 1, 2 and 3 mg/ml). The semen aliquots were cooled and preserved at 5°C and their qualities were evaluated during pre-freezing and then the cooled semen samples were packaged into 0.25 ml straws. Straws were frozen in the vapor of liquid nitrogen, and were then stored at -196ºC. Straws were thawed seven days later and the characteristics of spermatozoa were examined. Results of this study showed that the effect of vitamin B12 on characteristics such as viability, motility, progressive motility and normality of spermatozoa were significant in pre and post freezing conditions (P<0.05). In conclusion, for long term storage of semen of Dallagh rams, we recommend using 2 mg/ml of vitamin B12 in semen extender. PMID:26623328

  1. Expeditious synthesis of noble metal nanoparticles using Vitamin B12 under microwave irradiation

    EPA Science Inventory

    A greener synthesis protocol for noble nanometals is developed using vitamin B12 as a reducing and capping agent in conjunction with the use of microwaves. Successful assembly of nanoparticles or microparticles with varied shapes and sizes have been demonstrated. The synthesized ...

  2. Genomic Sequence of Klebsiella pneumoniae IIEMP-3, a Vitamin B12-Producing Strain from Indonesian Tempeh

    PubMed Central

    Yulandi, Adi; Sugiokto, Febri Gunawan; Febrilina

    2016-01-01

    Klebsiella pneumoniae strain IIEMP-3, isolated from Indonesian tempeh, is a vitamin B12-producing strain that exhibited a different genetic profile from pathogenic isolates. Here we report the draft genome sequence of strain IIEMP-3, which may provide insights on the nature of fermentation, nutrition, and immunological function of Indonesian tempeh. PMID:26950331

  3. Basal Gnathostomes Provide Unique Insights into the Evolution of Vitamin B12 Binders

    PubMed Central

    Lopes-Marques, Mnica; Ruivo, Raquel; Delgado, Ins; Wilson, Jonathan M.; Aluru, Neelakanteswar; Castro, L. Filipe C.

    2015-01-01

    The uptake and transport of vitamin B12 (cobalamin; Cbl) in mammals involves a refined system with three evolutionarily related transporters: transcobalamin 1 (Tcn1), transcobalamin 2 (Tcn2), and the gastric intrinsic factor (Gif). Teleosts have a single documented binder with intermediate features to the human counterparts. Consequently, it has been proposed that the expansion of Cbl binders occurred after the separation of Actinopterygians. Here, we demonstrate that the diversification of this gene family took place earlier in gnathostome ancestry. Our data indicates the presence of single copy orthologs of the Sarcopterygii/Tetrapoda duplicates Tcn1 and Gif, and Tcn2, in Chondrichthyes. In addition, a highly divergent Cbl binder was found in the Elasmobranchii. We unveil a complex scenario forged by genome, tandem duplications and lineage-specific gene loss. Our findings suggest that from an ancestral transporter, exhibiting large spectrum and high affinity binding, highly specific Cbl transporters emerged through gene duplication and mutations at the binding pocket. PMID:25552533

  4. Basal Gnathostomes provide unique insights into the evolution of vitamin B12 binders.

    PubMed

    Lopes-Marques, Mónica; Ruivo, Raquel; Delgado, Inês; Wilson, Jonathan M; Aluru, Neelakanteswar; Castro, L Filipe C

    2015-02-01

    The uptake and transport of vitamin B12 (cobalamin; Cbl) in mammals involves a refined system with three evolutionarily related transporters: transcobalamin 1 (Tcn1), transcobalamin 2 (Tcn2), and the gastric intrinsic factor (Gif). Teleosts have a single documented binder with intermediate features to the human counterparts. Consequently, it has been proposed that the expansion of Cbl binders occurred after the separation of Actinopterygians. Here, we demonstrate that the diversification of this gene family took place earlier in gnathostome ancestry. Our data indicates the presence of single copy orthologs of the Sarcopterygii/Tetrapoda duplicates Tcn1 and Gif, and Tcn2, in Chondrichthyes. In addition, a highly divergent Cbl binder was found in the Elasmobranchii. We unveil a complex scenario forged by genome, tandem duplications and lineage-specific gene loss. Our findings suggest that from an ancestral transporter, exhibiting large spectrum and high affinity binding, highly specific Cbl transporters emerged through gene duplication and mutations at the binding pocket. PMID:25552533

  5. [Vitamin B(12) deficiency anaemia in a 7.5 months old girl].

    PubMed

    Jarosz, Malgorzata; Irga, Ninela; Wierzba, Jolanta

    2004-01-01

    Vitamin B(12) stores at birth are adequate for infants until the end of the first year of life even if it 's concentration in maternal breast milk is low. However, there are some situations in which infants have depleted vitamin B(12) stores and in addition have a low dietary intake of cobalamin. Vitamin B(12) depletion occurs in infants who are exclusively breastfed by mothers who have unrecognized pernicious anemia or are strict vegetarians for many years. In those infants symptoms of bone marrow disfunction and impaired development of the central nervous system appear already in the first months of life. Unrecognized cobalamin deficiency may lead to serious neurologic consequences, and even to the death of the child. The authors present a case of a 7.5 month old girl admitted to the Department of Paediatrics, Haematology, Oncology and Endocrinology. Gdańsk Medical University suspected of acute leukaemia. Based on a detailed diagnostic procedure a final diagnosis of vitamin B(12) deficiency anaemia was established. The child was exclusively breast-fed. Results of investigations into the reason for cobalamin deficiency in the patient s organism. Led to the diagnosis of pernicious anaemia in the mother. Such a suspicion had been made during pregnancy, but no continuation of investigations nor appropriate treatment were implemented. After treatment with vitamin B(12) supplements and modification of the diet the patient improved quickly and remarkably. A few months follow-up was enough to observe remarkable improvement of psychomotor development of this child. PMID:15738604

  6. Serum vitamin B12 and folate concentrations and the effect of the Mediterranean diet on vulnerable populations.

    PubMed

    Balcı, Yasemin Işık; Ergin, Ahmet; Karabulut, Aysun; Polat, Aziz; Doğan, Mustafa; Küçüktaşcı, Kazım

    2014-02-01

    Low vitamin B12 and folate levels in expectant mothers may lead to low stores in babies. The aim of this study was to determine the frequencies of vitamin B12 and folate deficiencies in pregnant women and neonates, and to assess the effect of maternal vitamin status on babies' vitamin levels in the Aegean region of Turkey, where the Mediterranean diet (mainly fresh fruits and vegetables) is adopted. We studied 72 pregnant women and their singleton-term babies. Venous blood samples of expectant mothers were collected 1 h before delivery and cord blood of babies were obtained at birth. The mean vitamin B12 in maternal and cord blood serum was 163.1 ± 72.0 pg/mL and 146.2 ± 102.5 pg/mL, and the mean folate, 9.8 ± 4.8 ng/mL and 15.8 ± 3.8 ng/mL, respectively. There were statistically significant correlation between maternal and cord blood serum vitamin B12 (r = 0.61, P = .04) and folate levels (r = 0.65, P < .001). 70.8% of the mothers and 83.9% of the babies were vitamin B12 deficient (<200 pg/mL). Neither group showed folate deficiency. The mean level of vitamin B12 in mothers significantly varied by the type of diet (241.6 (72.1) pg/mL versus 155.9 (68.2) pg/mL; P = .012). Vitamin B12 deficiency in pregnant women and neonates may be a public health problem in our community. The Mediterranean diet in these vulnerable groups may be an aggravating factor for vitamin B12 deficiency. Prenatal screening of all expectant mothers, prenatal supplementation of vitamin B12, and an increase in animal-source food intake may improve expectant mother's vitamin B12 level. PMID:24088029

  7. Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose Poor vitamin B12 (B12) status is associated with adverse outcomes in pregnancy and infancy. Little is known about effects of B12 supplementation on immune function. The present study aimed to evaluate effects of pre- and postnatal B12 supplementation on biomarkers of B12 status and vaccine-s...

  8. [N2O-induced acute funicular myelosis in latent vitamin B 12 deficiency].

    PubMed

    Takcs, J

    1996-10-01

    The neurotoxicity of nitrous oxide ("laughing gas") had already been observed in 1956 when using N2O in the long-term sedation of tetanus patients. In 1967 Parbrook described leukopenic effects during long-term exposure to N2O. It was only in 1978 that further studies were conducted on myeloneuropathies and myelodepression under the influence of N2O. The basic cause is vitamin B12 deficiency and the irreversible oxidation of coenzyme B12 by N2O. Between 1986 and 1995 eight cases of acute funicular myelosis associated with latent vitamin B12 deficiency subsequent to nitrous oxide anaesthesia were reported. In our hospital, two further patients now have this disease. Two observations must be emphasised when assessing the 10 patients mentioned above: 1. There was no long-term exposure to N2O (> 6 hrs); the periods of anaesthesia were between 1.5 and 3.5 hrs. 2. Vitamin B12 deficiency was not known preoperatively, and there was no marked pernicious anaemia, so that the only pointers to the risk patients were supplied by the mean corpuscular haemoglobin (MCH) and the mean corpuscular volume (MCV) of the blood picture. PMID:9019188

  9. Dietary pectin shortens the biologic half-life of vitamin B-12 in rats by increasing fecal and urinary losses

    SciTech Connect

    Cullen, R.W.; Oace, S.M. )

    1989-08-01

    As little as 5% of pectin added to a fiber-free diet elevates urinary methylmalonic acid (MMA) severalfold in vitamin B-12--deprived rats. The present study examines whether increased urinary MMA reflects lower vitamin B-12 status or occurs only because of fermentation of pectin by intestinal bacteria and increased production of propionate, a precursor of MMA. By monitoring urinary and fecal excretion of {sup 57}Co after a tracer dose of ({sup 57}Co)vitamin B-12, we found the biologic half-life of vitamin B-12 to be 59 d for rats fed a fiber-free diet and only 19 d for rats fed a 5% pectin diet. Also, pectin-fed rats oxidized only 12% of a 1-mmol dose of ({sup 14}C)propionate to {sup 14}CO{sub 2} in 2 h, whereas rats fed the fiber-free diet expired 33% of the dose. Finally, high urinary MMA persisted even after the removal of pectin from the diet. We conclude that dietary pectin accelerates vitamin B-12 depletion in rats, possibly by interfering with enterohepatic recycling of vitamin B-12. By stimulating microbial propionate production, pectin and other fermentable fibers may also contribute to increased urinary MMA in vitamin B-12 deficiency, but a larger propionate pool does not account for the other effects of pectin on vitamin B-12 status.

  10. LOW ERYTHROCYTE FOLATE, BUT NOT PLASMA VITAMIN B-12 OR HOMOCYSTEINE, IS ASSOCIATED WITH DEMENTIA IN ELDERLY LATINOS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The relationship between B vitamin status and cognitive function has been of interest for many years. There is evidence of relationships between intake and status of folate and vitamin B-12 with neurological, cognitive, and memory impairment, but results have been inconsistent. Plasma B-12, erythroc...

  11. Geographical gradients of dissolved Vitamin B12 in the Mediterranean Sea

    PubMed Central

    Bonnet, S.; Tovar-Snchez, A.; Panzeca, C.; Duarte, C. M.; Ortega-Retuerta, E.; Saudo-Wilhelmy, S. A.

    2013-01-01

    Most eukaryotic phytoplankton require vitamin B12 to grow. However, the cycling of this organic growth factor has received substantially less attention than other bioactive substances such as trace metals in the marine environment. This is especially true in the Mediterranean Sea, where direct measurements of dissolved vitamins have never been reported. We report here the first direct measurements of dissolved vitamin B12 across longitudinal gradients in Mediterranean waters. The range of vitamin B12 concentrations measured over the whole transect was 0.56.2 pM, which is slightly higher than the range (undetectable4 pM) of ambient concentrations measured in other open ocean basins in the Pacific and Atlantic oceans. The concentrations measured in the western basin were significantly higher (p < 0.05) than those of the eastern basin. They were positively correlated with chlorophyll concentrations in the most western part of the basin, and did not show any significant correlation with any other biological variables in other regions of the sampling transect. PMID:23772225

  12. Insights into dechlorination of PCE and TCE from carbon isotope fractionation by vitamin B12

    NASA Astrophysics Data System (ADS)

    Slater, G.; Sherwood Lollar, B.; Lesage, S.; Brown, S.

    2003-04-01

    Reductive dechlorination of perchloroethylene (PCE) and trichloroethylene (TCE) by vitamin B12 is both a potential remediation technique and an analogue of the microbial reductive dechlorination reaction. Stable carbon isotopic analysis, an effective and powerful tool for the investigation and monitoring of contaminant remediation, was used to characterize the isotopic effects of reductive dechlorination of PCE and TCE by vitamin B12 in laboratory microcosms. 10 mg/L vitamin B12 degraded greater than 90% of an initial concentration of PCE of 20 mg/L. TCE, the primary product of PCE degradation, accounted for between 64 - 72% of the PCE degraded. In experiments with TCE, 147 mg/L vitamin B12 degraded greater than 90% of an initial concentration of TCE of 20 mg/L. Cis-dichloroethene (cDCE), the primary product of TCE degradation, accounted for between 30 - 35% of the TCE degraded. Degradation of both PCE and TCE exhibited first order kinetics. Strong isotopic fractionation of the reactant PCE and of the reactant TCE was observed over the course of degradation. This fractionation could be described by a Rayleigh model with enrichment factors between -16.5 ppm and -15.8 ppm for PCE, and -17.2 ppm and -16.6 ppm for TCE. Fractionation was similar in all four experiments, with a mean enrichment factor of -16.5 +/- 0.6 ppm. These large enrichment factors indicate that isotopic analysis can be used to assess the occurrence of dechlorination of PCE and TCE by vitamin B12 in remediation situations. Significantly, the Rayleigh model could be used to predict the isotopic compositions of the major products of the reaction as well as the reactant, notwithstanding the lack of complete mass balance observed between product and reactant. This evidence suggests that isotopic fractionation is taking place during complexation of the chlorinated ethenes to vitamin B12, as has been suggested for reductive dechlorination by zero valent iron. The differences between e for this reaction and those observed for microbial biodegradation of the chlorinated ethenes suggest that there may be differences in the rate determining step for these two processes. Determining which steps are rate determining during degradation may allow optimization of contaminant remediation.

  13. High prevalence of suboptimal vitamin B12 status in young adult women of South Asian and European ethnicity.

    PubMed

    Quay, Teo A W; Schroder, Theresa H; Jeruszka-Bielak, Marta; Li, Wangyang; Devlin, Angela M; Barr, Susan I; Lamers, Yvonne

    2015-12-01

    Suboptimal vitamin B12 (B12) status has been associated with an increased risk of congenital anomalies, preterm birth, and childhood insulin resistance. South Asians - Canada's largest minority group - and women of reproductive age are vulnerable to B12 deficiency. This study aimed to assess the prevalence of and factors associated with B12 deficiency and suboptimal B12 status in a convenience sample of young adult women of South Asian and European descent in Metro Vancouver. We measured serum B12, holotranscobalamin, plasma methylmalonic acid, red blood cell and plasma folate, and hematologic parameters in 206 nonpregnant, healthy women aged 19-35 years. Categorization for B12 status adhered to serum B12 cutoffs for deficiency (<148 pmol/L) and suboptimal B12 status (148-220 pmol/L). We collected demographic, lifestyle, and dietary intake data and conducted genotyping for common genetic variants linked to B-vitamin metabolism. The prevalence of deficiency and suboptimal B12 status were 14% and 20%, respectively. Serum vitamin B12 concentrations were negatively associated with oral contraceptive use and first-generation immigrant status, and positively with dietary B12 intake and B12 supplement use. The prevalence of B12 inadequacy in this sample of highly educated women is higher than in the general Canadian population. In light of maternal and fetal health risks associated with B12 inadequacy in early-pregnancy, practitioners should consider monitoring B12 status before and during early pregnancy, especially in immigrants and women with low dietary B12 intakes including non-users of vitamin supplements. PMID:26579949

  14. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature.

    PubMed

    Pawlak, R; Lester, S E; Babatunde, T

    2014-05-01

    Individuals following vegetarian diets are at risk for developing vitamin B12 deficiency owing to suboptimal intake. As vitamin B12 is essential for the synthesis of nucleic acids, erythrocytes and in the maintenance of myelin, deficiency may result in a variety of symptoms. Some of these symptoms may be severe while others may be irreversible. The objective of this review was to assess vitamin B12 deficiency, based on reported serum vitamin B12, among individuals adhering to different types of vegetarian diets. A systematic literature search was carried out using multiple search engines including PubMed, Medline, CINAHL plus, ERIC, Nursing and Allied Health Collection and Nursing/Academic Edition. The inclusion criteria consisted of original studies that assessed serum vitamin B12, studies written in English, non-case studies and studies that reported actual percentages of vitamin B12 deficiency. Forty research studies were included. The deficiency prevalence among infants reached 45%. The deficiency among the children and adolescents ranged from 0 to 33.3%. Deficiency among pregnant women ranged from 17 to 39%, dependent on the trimester. Adults and elderly individuals had a deficiency range of 0-86.5%. Higher deficiency prevalence was reported in vegans than in other vegetarians. Thus, with few exceptions, the reviewed studies documented relatively high deficiency prevalence among vegetarians. Vegans who do not ingest vitamin B12 supplements were found to be at especially high risk. Vegetarians, especially vegans, should give strong consideration to the use of vitamin B12 supplements to ensure adequate vitamin B12 intake. Vegetarians, regardless of the type of vegetarian diet they adhere to, should be screened for vitamin B12 deficiency. PMID:24667752

  15. Neonatal Hyperbilirubinemia in a Turkish Cohort: Association of Vitamin B12

    PubMed Central

    Eroglu, Nilgun; Kandur, Yasar; Kalay, Salih; Kalay, Zuhal; Guney, Ozgur

    2015-01-01

    Background Deficiency of vitamin B12 (VitB12) causes failure of erytrocyte maturation leading to cell lysis. Red blood cell lysis causes excess heme production that ends with hyperbilirubinemia. In this study, we aimed to evaluate the role of VitB12 in neonatal hyperbilirubinemia (NNH) with prolonged jaundice and to compare patients with control group who did not develop hyperbilirubinemia. Methods A total of 20 patients (M/F = 13/7) with jaundice and 20 healthy controls (M/F = 11/9) were included in the study. Results The mean indirect bilirubin level of patient group was 9.91 1.90 mg/dL (6.71 - 15.2 mg/dL) and control group was 3.18 1.24 mg/dL (1.16 - 4.96 mg/dL). The mean VitB12 level of patient group was 119.9 43.9 ng/L (42.35 - 178 ng/L) and the control group was 286.17 97.43 ng/L (207.90 - 624.10 ng/L). There was a statistically significant difference in terms of VitB12 level (< 0.001) between the study groups. Conclusion To our knowledge, this study is the first study showing that low VitB12 level has been observed as a risk factor in NNH for the first time in the literature. We suggest that prophylactic use of VitB12 by pregnant women so will greatly benefit to prevent VitB12 deficiency and its complications in the first years of life such as NNH. PMID:26015822

  16. Theoretical analysis of electronic absorption spectra of vitamin B12 models

    NASA Astrophysics Data System (ADS)

    Andruniow, Tadeusz; Kozlowski, Pawel M.; Zgierski, Marek Z.

    2001-10-01

    Time-dependent density-functional theory (TD-DFT) is applied to analyze the electronic absorption spectra of vitamin B12. To accomplish this two model systems were considered: CN-[CoIII-corrin]-CN (dicyanocobinamide, DCC) and imidazole-[CoIII-corrin]-CN (cyanocobalamin, ImCC). For both models 30 lowest excited states were calculated together with transition dipole moments. When the results of TD-DFT calculations were directly compared with experiment it was found that the theoretical values systematically overestimate experimental data by approximately 0.5 eV. The uniform adjustment of the calculated transition energies allowed detailed analysis of electronic absorption spectra of vitamin B12 models. All absorption bands in spectral range 2.0-5.0 eV were readily assigned. In particular, TD-DFT calculations were able to explain the origin of the shift of the lowest absorption band caused by replacement of the-CN axial ligand by imidazole.

  17. [Metabolic and nutritional neuropathies: update in diabetes, vitamin B12 and copper deficiency].

    PubMed

    Franques, J; Gazzola, S

    2013-12-01

    Metabolic and deficiency neuropathies retain a growing interest because of their important prevalence. The dismemberment of diabetic neuropathies is proceeded, letting distinct pathophysiological mechanisms appear. So, even if glycaemic control remains determining for preventing the neuropathy associated with type 1 diabetes, it seems to have a restricted role with type 2 diabetes in which other metabolic factors are involved. The diagnosis of neuropathy due to B12 vitamin deficiency remains a real challenge for the clinician. Indeed, positive and negative predictive values of serum B12 and metabolites assay are weak, only a good therapeutic response allows a reliable diagnostic. It is so recommended to know the clinical and contextual particularities of this etiology in order to not delay the vitamin substitution, determining for the functional outcome. Finally, copper deficiency remains an unknown cause of neuropathy which is suitable to raise in case of malabsorption but also and especially in case of abuse of dental adhesive rich in zinc. PMID:24269115

  18. Ultrafast electronic relaxation of excited state vitamin B 12 in the gas phase

    NASA Astrophysics Data System (ADS)

    Shafizadeh, Niloufar; Poisson, Lionel; Soep, Beno?t

    2008-06-01

    The time evolution of electronically excited vitamin B 12 (cyanocobalamin) has been observed for the first time in the gas phase. It reveals an ultrafast decay to a state corresponding to metal excitation. This decay is interpreted as resulting from a ring to metal electron transfer. This opens the observation of the excited state of other complex biomimetic systems in the gas phase, the key to the characterisation of their complex evolution through excited electronic states.

  19. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia

    PubMed Central

    Zhang, Yiting; Hodgson, Nathaniel W.; Trivedi, Malav S.; Abdolmaleky, Hamid M.; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C.

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders. PMID:26799654

  20. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

    PubMed

    Zhang, Yiting; Hodgson, Nathaniel W; Trivedi, Malav S; Abdolmaleky, Hamid M; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders. PMID:26799654

  1. Development of a two-step cultivation strategy for the production of vitamin B12 by Bacillus megaterium

    PubMed Central

    2014-01-01

    Background Vitamin B12 is a fascinating molecule which acts as a co-factor in the metabolism of many organisms, especially affecting DNA synthesis and regulation, fatty acid synthesis and energy production. The synthesis of vitamin B12 is limited to a few of bacteria and archaea. Therefore, industrial microbial fermentation is used to meet annual demands worldwide of vitamin B12 and as an alternative method to the chemical synthesis which requires at least 60 steps that is uneconomical. Bacillus megaterium is one of vitamin B12 producers and an ideal host for many biotechnology applications and being one of the best tools for the industrial production of several enzymes. Therefore, a two-step optimization strategy was established to produce high yield of vitamin B12 by B. megaterium through the provision of the production requirements and the suitable conditions for the biosynthesis of vitamin B12. Results We achieved the optimum conditions for the fermentation process of B. megaterium to produce high yield of vitamin B12 in a practical way based on statistical design and analysis which allowed vitamin B12 production to increase up to 759-fold (204.46?g/l) as compared with control without parameters (0.26?g/L). High performance liquid chromatography coupled to variable wavelength detector and mass spectrometry has been used to identify vitamin B12 forms and confirm the results. Conclusions We developed the fermentation process of B. megaterium to enhance the production of vitamin B12 by providing the required supplements for the synthesis of vitamin B12 (CoCl2, ?-aminolevulinic acid (ALA) and 5,6-dimethylbenzimidazole (DMB)) and dividing the fermentation process into three stages. In addition, the optimum incubation times of the three fermentation stages were investigated and performed with reducing number of experimental and evaluated multiple parameters and their interactions by using statistical experimental design and analysis. All of these strategies has proven successful in enhancing the production of vitamin B12 up to 204.46?g/l and demonstrated that B. megaterium could be a good candidate for the industrial production of vitamin B12. PMID:25023574

  2. Vitamin B12 and vitamin d deficiencies: an unusual cause of Fever, severe hemolytic anemia and thrombocytopenia.

    PubMed

    Mishra, Vikas A; Harbada, Rishit; Sharma, Akhilesh

    2015-01-01

    The array of diagnostic workup for pyrexia of unknown origin (PUO) generally revolves in searching for infections, inflammatory/autoimmune, and endocrine etiologies. A differential diagnosis of fever, hemolytic anemia, and thrombocytopenia can have etiologies varying from infections like malaria, dengue, cytomegalovirus, Ebstein barr virus, Parvovirus, infective endocarditis, to autoimmune disorder (systemic lupus erythromatosis), vasculitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), autoimmune hemolytic anemia/Evan's syndrome, paroxysmal nocturnal hemoglobinuri (PNH), or drugs. Nutritional deficiencies (especially vitamin B12 deficiency) as a cause of fever, hemolytic anemia, and thrombocytopenia are very rare and therefore rarely thought of. Severe vitamin B12 deficiency may cause fever and if accompanied by concurrent hyper-homocysteinemia and hypophosphatemia can sometimes lead to severe hemolysis mimicking the above-mentioned conditions. We present a case that highlights vitamin B12 and vitamin D deficiency as an easily treatable cause of PUO, hemolytic anemia, and thrombocytopenia, which should be actively looked for and treated before proceeding with more complicated and expensive investigation or starting empiric treatments. PMID:25811010

  3. Vitamin B12 and Vitamin D Deficiencies: An Unusual Cause of Fever, Severe Hemolytic Anemia and Thrombocytopenia

    PubMed Central

    Mishra, Vikas A.; Harbada, Rishit; Sharma, Akhilesh

    2015-01-01

    The array of diagnostic workup for pyrexia of unknown origin (PUO) generally revolves in searching for infections, inflammatory/autoimmune, and endocrine etiologies. A differential diagnosis of fever, hemolytic anemia, and thrombocytopenia can have etiologies varying from infections like malaria, dengue, cytomegalovirus, Ebstein barr virus, Parvovirus, infective endocarditis, to autoimmune disorder (systemic lupus erythromatosis), vasculitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), autoimmune hemolytic anemia/Evan's syndrome, paroxysmal nocturnal hemoglobinuri (PNH), or drugs. Nutritional deficiencies (especially vitamin B12 deficiency) as a cause of fever, hemolytic anemia, and thrombocytopenia are very rare and therefore rarely thought of. Severe vitamin B12 deficiency may cause fever and if accompanied by concurrent hyper-homocysteinemia and hypophosphatemia can sometimes lead to severe hemolysis mimicking the above-mentioned conditions. We present a case that highlights vitamin B12 and vitamin D deficiency as an easily treatable cause of PUO, hemolytic anemia, and thrombocytopenia, which should be actively looked for and treated before proceeding with more complicated and expensive investigation or starting empiric treatments. PMID:25811010

  4. Disposable pencil graphite electrode modified with peptide nanotubes for Vitamin B12 analysis

    NASA Astrophysics Data System (ADS)

    Pala, Betül Bozdoğan; Vural, Tayfun; Kuralay, Filiz; Çırak, Tamer; Bolat, Gülçin; Abacı, Serdar; Denkbaş, Emir Baki

    2014-06-01

    In this study, peptide nanostructures from diphenylalanine were synthesized in various solvents with various polarities and characterized with Scanning Electron Microscopy (SEM) and Powder X-ray Diffraction (PXRD) techniques. Formation of peptide nanofibrils, nanovesicles, nanoribbons, and nanotubes was observed in different solvent mediums. In order to investigate the effects of peptide nanotubes (PNT) on electrochemical behavior of disposable pencil graphite electrodes (PGE), electrode surfaces were modified with fabricated peptide nanotubes. Electrochemical activity of the pencil graphite electrode was increased with the deposition of PNTs on the surface. The effects of the solvent type, the peptide nanotube concentration, and the passive adsorption time of peptide nanotubes on pencil graphite electrode were studied. For further electrochemical studies, electrodes were modified for 30 min by immobilizing PNTs, which were prepared in water at 6 mg/mL concentration. Vitamin B12 analyses were performed by the Square Wave (SW) voltammetry method using modified PGEs. The obtained data showed linearity over the range of 0.2 μM and 9.50 μM Vitamin B12 concentration with high sensitivity. Results showed that PNT modified PGEs were highly simple, fast, cost effective, and feasible for the electro-analytical determination of Vitamin B12 in real samples.

  5. Influence of maternal vitamin B12 and folate on growth and insulin resistance in the offspring.

    PubMed

    Deshmukh, Urmila; Katre, Prachi; Yajnik, Chittaranjan S

    2013-01-01

    The burden of chronic noncommunicable diseases (NCDs) such as diabetes, obesity and cardiovascular disease is shifting rapidly to low- and middle-income countries. It calls for a review of the classic 'dogma' of genetic predisposition, precipitated by adult lifestyle. The paradigm of early life origins of chronic disease has focused attention on maternal health and nutrition as major determinants of the health of the offspring. India has high burden of maternal ill health and also of diabetes and cardiovascular disease, offering unique opportunities to study the links between the two. Pune studies showed that the Indian babies were thin but fat (more adipose) compared to European babies, and that maternal micronutrient status during pregnancy was a determinant of offspring size and body composition. Two thirds of the mothers had low vitamin B12 concentrations, while folate deficiency was rare. Higher circulating concentrations of homocysteine predicted smaller baby size. Follow-up studies revealed that higher maternal folate in pregnancy predicted higher adiposity and insulin resistance in the child at 6 years of age, and that low maternal vitamin B12 exaggerated the risk of insulin resistance. Low maternal vitamin B12 status is also associated with increased risk of neural tube defects and poor offspring cognitive functions. Our results suggest an important role for maternal one-carbon metabolism in offspring growth and programming of NCD risk. These ideas are supported by animal studies. Improvement of adolescent nutrition could effect intergenerational prevention of chronic diseases. PMID:23887113

  6. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity.

    PubMed

    Fenech, Michael

    2012-05-01

    Folate plays a critical role in the prevention of uracil incorporation into DNA and hypomethylation of DNA. This activity is compromised when vitamin B12 concentration is low because methionine synthase activity is reduced, lowering the concentration of S-adenosyl methionine (SAM) which in turn may diminish DNA methylation and cause folate to become unavailable for the conversion of dUMP to dTMP. The most plausible explanation for the chromosome-breaking effect of low folate is excessive uracil misincorporation into DNA, a mutagenic lesion that leads to strand breaks in DNA during repair. Both in vitro and in vivo studies with human cells clearly show that folate deficiency causes expression of chromosomal fragile sites, chromosome breaks, excessive uracil in DNA, micronucleus formation, DNA hypomethylation and mitochondrial DNA deletions. In vivo studies show that folate and/or vitamin B12 deficiency and elevated plasma homocysteine (a metabolic indicator of folate deficiency) are significantly correlated with increased micronucleus formation and reduced telomere length respectively. In vitro experiments indicate that genomic instability in human cells is minimised when folic acid concentration in culture medium is greater than 100nmol/L. Intervention studies in humans show (a) that DNA hypomethylation, chromosome breaks, uracil incorporation and micronucleus formation are minimised when red cell folate concentration is greater than 700nmol/L and (b) micronucleus formation is minimised when plasma concentration of vitamin B12 is greater than 300pmol/L and plasma homocysteine is less than 7.5?mol/L. These concentrations are achievable at intake levels at or above current recommended dietary intakes of folate (i.e. >400?g/day) and vitamin B12 (i.e. >2?g/day) depending on an individual's capacity to absorb and metabolise these vitamins which may vary due to genetic and epigenetic differences. PMID:22093367

  7. Indicators for assessing folate and vitamin B-12 status and for monitoring the efficacy of intervention strategies123

    PubMed Central

    Green, Ralph

    2011-01-01

    Deficiencies of folate or of vitamin B-12 are widespread and constitute a major global burden of morbidity that affect all age groups. Detecting or confirming the presence of folate or vitamin B-12 deficiency and distinguishing one from the other depends, ultimately, on laboratory testing. Tests to determine the presence of folate or vitamin B-12 deficiency are used singly or in combination to establish the nutritional status and prevalence of deficiencies of the vitamins in various populations. The efficacy of interventions through the use of fortification or supplements is monitored by using the same laboratory tests. Tests currently in use have limitations that can be either technical or have a biological basis. Consequently, each single test cannot attain perfect sensitivity, specificity, or predictive value. Laboratory indicators of vitamin B-12 or folate status involve the measurement of either the total or a physiologically relevant fraction of the vitamin in a compartment such as blood. Thus, assays to measure vitamin B-12 or folate in plasma or serum as well as folate in red blood cells are in widespread use, and more recently, methods to measure vitamin B-12 associated with the plasma binding protein transcobalamin (holotranscobalamin) have been developed. Alternatively, concentrations of surrogate biochemical markers that reflect the metabolic function of the vitamin can be used. Surrogates most commonly used are plasma homocysteine, for detection of either vitamin B-12 or folate deficiency, and methylmalonic acid for detection of vitamin B-12 deficiency. The general methods as well as their uses, indications, and limitations are presented. PMID:21733877

  8. Regulation of the vitamin B12 metabolism and transport in bacteria by a conserved RNA structural element

    PubMed Central

    VITRESCHAK, ALEXEY G.; RODIONOV, DMITRY A.; MIRONOV, ANDREY A.; GELFAND, MIKHAIL S.

    2003-01-01

    Cobalamin in the form of adenosylcobalamin (Ado-CBL) is known to repress expression of genes for vitamin B12 biosynthesis and be transported by a posttranscriptional regulatory mechanism, which involves direct binding of Ado-CBL to 5?untranslated gene regions (5?UTR). Using comparative analysis of genes and regulatory regions, we identified a highly conserved RNA structure, the B12-element, which is widely distributed in 5?UTRs of vitamin B12-related genes in eubacteria. Multiple alignment of approximately 200 B12-elements from 66 bacterial genomes reveals their common secondary structure and several extended regions of sequence conservation, including the previously known B12-box motif. In analogy to the model of regulation of the riboflavin and thiamin biosynthesis, we suggest Ado-CBL-mediated regulation based on formation of alternative RNA structures including the B12-element. In Gram-negative proteobacteria, as well as in cyanobacteria, actinobacteria, and the CFB group, the cobalamin biosynthesis and vitamin B12 transport genes are predicted to be regulated by inhibition of translation initiation, whereas in the Bacillus/Clostridium group of Gram-positive bacteria, these genes seem to be regulated by transcriptional antitermination. Phylogenetic analysis of the B12-elements reveals a large number of likely duplications of B12-elements in several bacterial genomes. These lineage-specific duplications of RNA regulatory elements seem to be a major evolutionary mechanism for expansion of the vitamin B12 regulon. PMID:12923257

  9. Localised Skin Hyperpigmentation as a Presenting Symptom of Vitamin B12 Deficiency Complicating Chronic Atrophic Gastritis

    PubMed Central

    El-Shafie, Kawther; Samir, Nafisa; Lakhtakia, Ritu; Davidson, Robin; Al-Waili, Ahmed; Al-Mamary, Muna; Al-Shafee, Mohammed

    2015-01-01

    Vitamin B12 deficiency is common in developing countries and should be suspected in patients with unexplained anaemia or neurological symptoms. Dermatological manifestations associated with this deficiency include skin hyper- or hypopigmentation, angular stomatitis and hair changes. We report a case of a 28-year-old man who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in November 2013 with localised hyperpigmentation of the palmar and dorsal aspects of both hands of two months’ duration. Other symptoms included numbness of the hands, anorexia, weight loss, dizziness, fatigability and a sore mouth and tongue. There was no evidence of hypocortisolaemia and a literature search revealed a possible B12 deficiency. The patient had low serum B12 levels and megaloblastic anaemia. An intrinsic factor antibody test was negative. A gastric biopsy revealed chronic gastritis. After B12 supplementation, the patient’s symptoms resolved. Family physicians should familiarise themselves with atypical presentations of B12 deficiency. Many symptoms of this deficiency are reversible if detected and treated early. PMID:26357561

  10. Localised Skin Hyperpigmentation as a Presenting Symptom of Vitamin B12 Deficiency Complicating Chronic Atrophic Gastritis.

    PubMed

    El-Shafie, Kawther; Samir, Nafisa; Lakhtakia, Ritu; Davidson, Robin; Al-Waili, Ahmed; Al-Mamary, Muna; Al-Shafee, Mohammed

    2015-08-01

    Vitamin B12 deficiency is common in developing countries and should be suspected in patients with unexplained anaemia or neurological symptoms. Dermatological manifestations associated with this deficiency include skin hyper- or hypopigmentation, angular stomatitis and hair changes. We report a case of a 28-year-old man who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in November 2013 with localised hyperpigmentation of the palmar and dorsal aspects of both hands of two months' duration. Other symptoms included numbness of the hands, anorexia, weight loss, dizziness, fatigability and a sore mouth and tongue. There was no evidence of hypocortisolaemia and a literature search revealed a possible B12 deficiency. The patient had low serum B12 levels and megaloblastic anaemia. An intrinsic factor antibody test was negative. A gastric biopsy revealed chronic gastritis. After B12 supplementation, the patient's symptoms resolved. Family physicians should familiarise themselves with atypical presentations of B12 deficiency. Many symptoms of this deficiency are reversible if detected and treated early. PMID:26357561

  11. Vitamin B(12) and folic acid imbalance modifies NK cytotoxicity, lymphocytes B and lymphoprolipheration in aged rats.

    PubMed

    Partearroyo, Teresa; beda, Natalia; Montero, Ana; Achn, Mara; Varela-Moreiras, Gregorio

    2013-12-01

    Different vitamin B12 and folic acid concentrations could exacerbate the immune response. The aim was to evaluate different dietary folic acid and vitamin B12 levels on the immune response in aged rats. Male Sprague Dawley aged rats were assigned to three folic acid groups (deficient, control, supplemented) each in absence of vitamin B12 for 30 days. Several parameters of innate and acquired immune responses were measured. Serum and hepatic folate levels increased according to folic acid dietary level, while vitamin B12 levels decreased. There was a significant decrease in natural killer cell-mediated cytotoxicity in the spleen for the vitamin B12 deficient diet and folic acid control diet groups. Significant changes in CD45 lymphocyte subsets were also observed according to dietary imbalance. Lymphoproliferative response to concanavalin A and phytohemagglutinin did not differ significantly between groups. The spleen response to lipopolysaccharide increased significantly, but was unmodified for the other organs. An imbalance between dietary vitamin B12 and folic acid concentrations alters some immunological parameters in aged rats. Therefore, the ratio between folate and vitamin B12 could be as important as their absolute dietary concentrations. PMID:24288024

  12. Vitamin B12 and Folic Acid Imbalance Modifies NK Cytotoxicity, Lymphocytes B and Lymphoprolipheration in Aged Rats

    PubMed Central

    Partearroyo, Teresa; beda, Natalia; Montero, Ana; Achn, Mara; Varela-Moreiras, Gregorio

    2013-01-01

    Different vitamin B12 and folic acid concentrations could exacerbate the immune response. The aim was to evaluate different dietary folic acid and vitamin B12 levels on the immune response in aged rats. Male Sprague Dawley aged rats were assigned to three folic acid groups (deficient, control, supplemented) each in absence of vitamin B12 for 30 days. Several parameters of innate and acquired immune responses were measured. Serum and hepatic folate levels increased according to folic acid dietary level, while vitamin B12 levels decreased. There was a significant decrease in natural killer cell-mediated cytotoxicity in the spleen for the vitamin B12 deficient diet and folic acid control diet groups. Significant changes in CD45 lymphocyte subsets were also observed according to dietary imbalance. Lymphoproliferative response to concanavalin A and phytohemagglutinin did not differ significantly between groups. The spleen response to lipopolysaccharide increased significantly, but was unmodified for the other organs. An imbalance between dietary vitamin B12 and folic acid concentrations alters some immunological parameters in aged rats. Therefore, the ratio between folate and vitamin B12 could be as important as their absolute dietary concentrations. PMID:24288024

  13. Effect of vitamin B12 on functional recovery and histopathologic changes of tibial nerve-crushed rats.

    PubMed

    Tamaddonfard, E; Farshid, A A; Samadi, F; Eghdami, K

    2014-09-01

    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. Histological changes of tibial nerve were investigated by light microscopy. The recovery of TFI values were significantly accelerated with 10 consecutive days treatments with 0.1 and 0.5?mg/kg of vitamin B12, 5?mg/kg of diclofenac and 1 and 5?mg/kg of celecoxib. The severity of Wallerian degeneration was reduced by above-mentioned doses of vitamin B12, diclofenac and celecoxib. Documented effects were observed when 0.1?mg/kg of vitamin B12 was concurrently used with 1?mg/kg of diclofenac and or 0.2?mg/kg of celecoxib. In the present study, vitamin B12, celecoxib and diclofenac (at a high dose) showed neuroprotective effects. Inhibition of cyclooxygenase (COX) 1 and 2 pathways may be involved in neuroprotective effect of vitamin B12. PMID:24470311

  14. A Study of the Prevalence of Serum Vitamin B12 and Folic Acid Deficiency in Western Maharashtra

    PubMed Central

    Mahajan, Sanket K.; Aundhakar, Swati C.

    2015-01-01

    Context: This study summarizes the prevalence of vitamin B12 and folic acid deficiency in the population coming to tertiary care center in Western Maharashtra along with the main presenting symptom routinely misinterpreted in daily practice. Aims and Objectives: 1. To study the prevalence of vitamin B12 and folic acid deficiency in the population of western Maharashtra. 2. To correlate the symptoms with serum vitamin B12 and folic acid levels. Materials and Methods: The present study is a cross-sectional observation study carried out on patients from western Maharashtra seeking medical attention on outpatient and inpatient basis in the medicine department of a teaching institute in Karad. One-hundred patients were selected on basis of below mentioned symptoms viz. tingling and numbness in extremities, dizziness, unsteady gait, early tiredness, forgetfulness, proximal weakness, distal weakness, chronic headache, less interest in work, chronic loose stools, strict vegetarians, alcoholics, intake of medications like anti-tubercular treatment, surgery involving terminal ileum. Serum vitamin B12 and folic acid levels of these patients were observed. Deficiency of vitamin B12 and folic acid was studied in 4 groups: (a) Absolute vitamin B12 deficiency; (b) Absolute folic acid deficiency; (c) Borderline vitamin B12 deficiency; (d) Combined vitamin B12 and folic acid deficiency. Results: Of the 100 cases, 33% patients were vegetarian. Folic acid deficiency formed the major chunk of deficiency group. Six percent patients had neuropsychiatric manifestations. Depressive illness in 1% patients, dementia in 0% patients, forgetfulness in 1% patients, mania/hallucination in 0% patients each, and chronic headache in 1% patients. Neuropathy in form of loss of reflexes, decreased touch sensation was present in 9% patients. Posterior column involvement viz. Loss of joint position, vibration, positive Romberg's sign were present in 34% patients of vitamin B12 and folic acid deficiency. Conclusion: In a small study, it was found that megaloblastic anemia may have symptoms and signs referable to several systems including hematology, dermatology, gastrointestinal, neurology, and neuropsychiatry. PMID:25810991

  15. The bluF gene of Rhodobacter capsulatus is involved in conversion of cobinamide to cobalamin (vitamin B12).

    PubMed Central

    Pollich, M; Wersig, C; Klug, G

    1996-01-01

    The bluF gene of Rhodobacter capsulatus is the first gene of the bluFEDCB operon which is involved in late steps of the cobalamin synthesis. To determine the function of the bluF gene product, a bluF::omega-Km mutant strain was constructed and characterized. This vitamin B12 auxotrophic mutant strain shows a 3.5-times higher vitamin B12 requirement under phototrophic growth conditions than under chemotrophic growth conditions. Surprisingly, the bluF promoter activity does not respond to alterations to the oxygen tension or vitamin B12 concentration. PMID:8955417

  16. Folate, vitamin B6, vitamin B12, methionine and alcohol intake in relation to ovarian cancer risk

    PubMed Central

    Harris, Holly R.; Cramer, Daniel W.; Vitonis, Allison F.; DePari, Mary; Terry, Kathryn L.

    2011-01-01

    Folate, methionine, vitamin B6, and vitamin B12 may influence carcinogenesis due to their roles in the one-carbon metabolism pathway which is critical for DNA synthesis, methylation, and repair. Low intake of these nutrients has been associated with an increased risk of breast, colon, and endometrial cancers. Previous studies that have examined the relation between these nutrients and ovarian cancer risk have been inconsistent and have had limited power to examine the relation by histologic subtype. We investigated the association between folate, methionine, vitamin B6, vitamin B12, and alcohol among 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008. Diet was assessed via food frequency questionnaire. Participants were asked to recall diet one-year before diagnosis or interview. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CIs). We also examined whether the associations varied by ovarian cancer histologies using polytomous logistic regression. We observed an inverse association between dietary vitamin B6 (covariate-adjusted OR=0.76, 95% CI 0.640.92; ptrend=0.002) and methionine intake (covariate-adjusted OR=0.72, 95% CI=0.600.87; ptrend<0.001) and ovarian cancer risk comparing the highest to lowest quartile. The association with dietary vitamin B6 was strongest for serous borderline (covariate-adjusted OR=0.49, 95% CI=0.320.77; ptrend=0.001) and serous invasive (covariate-adjusted OR=0.74, 95% CI=0.580.94; ptrend=0.012) subtypes. Overall, we observed no significant association between folate and ovarian cancer risk. One-carbon metabolism related nutrients, especially vitamin B6 and methionine, may lower ovarian cancer risk. PMID:21953625

  17. A riboswitch sensor to determine vitamin B12 in fermented foods.

    PubMed

    Zhu, Xuan; Wang, Xiaofeng; Zhang, Chen; Wang, Xiaoqi; Gu, Qing

    2015-05-15

    We describe a sensitive and selective method for determination of vitamin B12 content in fermented foods using riboswitch sensor. A riboswitch amplicon from Propionibacterium freudenreichii was cloned in p519NGFP vector in Escherichia coli BL21 (DE3). The expression of green fluorescence protein was revers correlated to the concentrations of adenosylcobalamin. Adenosylcobalamin directly binds to riboswitch region leading to conformational changes in the secondary structure of mRNA, thus inhibiting expression. After various examinations, a standard curve was obtained from 10 to 1000 ng/mL of cyanocobalamin. The limit of determination is 10 ng/mL. The inter-assay coefficients of variation were 7.5% for the range of 10-1000 ng/mL. The recovery of this method was 92.3%. This method has no or less responses to nucleic acid, pseudovitamin B12, vitamin B12 bound to intrinsic factor and haptocorrin. The riboswitch sensor results were similar with HPLC, but they were Ca. 24% lower than the microbiological assay results. PMID:25577115

  18. Vitamin B12 deficiency-induced increase of osteoclastic bone resorption caused by abnormal renal resorption of inorganic phosphorus via Napi2a.

    PubMed

    Shiga, Takahiro; Kimira, Yoshifumi; Mano, Hiroshi; Kawata, Tetsunori; Tadokoro, Tadahiro; Suzuki, Tsukasa; Yamamoto, Yuji

    2016-03-01

    Vitamin B12 deficiency is a risk factor for bone disorders via mechanisms not fully understood. In this study, an increase in serum inorganic phosphorus (Pi) concentrations was associated with a vitamin B12 deficiency. Napi2a, a renal cotransporter for Pi reabsorption, accumulated on plasma membranes in a vitamin B12 deficiency suggests that vitamin B12 plays an important role in Pi homeostasis. PMID:26460967

  19. Genetic Architecture of Vitamin B12 and Folate Levels Uncovered Applying Deeply Sequenced Large Datasets

    PubMed Central

    Thorleifsson, Gudmar; Ahluwalia, Tarunveer S.; Steinthorsdottir, Valgerdur; Bjarnason, Helgi; Gudbjartsson, Daniel F.; Magnusson, Olafur T.; Spars, Thomas; Albrechtsen, Anders; Kong, Augustine; Masson, Gisli; Tian, Geng; Cao, Hongzhi; Nie, Chao; Kristiansen, Karsten; Husemoen, Lise Lotte; Thuesen, Betina; Li, Yingrui; Nielsen, Rasmus; Linneberg, Allan; Olafsson, Isleifur; Eyjolfsson, Gudmundur I.; Jrgensen, Torben; Wang, Jun; Hansen, Torben; Thorsteinsdottir, Unnur; Stefnsson, Kari; Pedersen, Oluf

    2013-01-01

    Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B12 (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B12 and folate measurements, respectively. We found six novel loci associating with serum B12 (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B12 and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B12 or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations. PMID:23754956

  20. Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets.

    PubMed

    Grarup, Niels; Sulem, Patrick; Sandholt, Camilla H; Thorleifsson, Gudmar; Ahluwalia, Tarunveer S; Steinthorsdottir, Valgerdur; Bjarnason, Helgi; Gudbjartsson, Daniel F; Magnusson, Olafur T; Spars, Thomas; Albrechtsen, Anders; Kong, Augustine; Masson, Gisli; Tian, Geng; Cao, Hongzhi; Nie, Chao; Kristiansen, Karsten; Husemoen, Lise Lotte; Thuesen, Betina; Li, Yingrui; Nielsen, Rasmus; Linneberg, Allan; Olafsson, Isleifur; Eyjolfsson, Gudmundur I; Jrgensen, Torben; Wang, Jun; Hansen, Torben; Thorsteinsdottir, Unnur; Stefnsson, Kari; Pedersen, Oluf

    2013-06-01

    Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B(12) (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B(12) and folate measurements, respectively. We found six novel loci associating with serum B(12) (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B(12) and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B(12) or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations. PMID:23754956

  1. Folate, Vitamin B12, and Homocysteine as Risk Factors for Cognitive Decline in the Elderly

    PubMed Central

    Kim, Jae-Min; Kim, Sung-Wan; Shin, Il-Seon; Yang, Su-Jin; Park, Woo-Young; Kim, Sung-Jin; Shin, Hee-Young

    2008-01-01

    Objective Cross-sectional studies have shown that the dysregulation of one-carbon metabolism is associated with cognitive impairment. However, the findings of longitudinal studies investigating this association have been inconsistent. This study investigated the prospective associations between cognitive decline and the levels of folate, vitamin B12 and homocysteine both at baseline and over course of the study period. Methods A total of 607 (83%) elderly individuals were selected from a group of 732 elderly individuals without dementia at baseline and followed over a 2.4-year study period. The Mini-Mental State Examination (MMSE) was administered to the subjects, and the serum levels of folate, vitamin B12 and homocysteine were assayed both at baseline and at follow-up examinations. Covariates included demographic data, disability, depression, alcohol consumption, physical activity, vascular risk factors, serum creatinine level, vitamin intake, and apolipoprotein E genotype. Results Cognitive decline was associated with decreasing quintiles of folate at baseline, a relative decline in folate and an increase in homocysteine across the two examinations after adjustment for relevant covariates. Conclusion These results suggest that folate and homocysteine are involved in the etiology of cognitive decline in the elderly. PMID:20046406

  2. Surface-enhanced Raman spectroscopy of Vitamin B 12 on silver particles in colloid and in atmosphere

    NASA Astrophysics Data System (ADS)

    Zhang, Zhenlong; Wang, Bo; Yin, Yanfeng; Mo, Yujun

    2009-06-01

    The surface-enhanced Raman scattering (SERS) spectra of Vitamin B 12 molecules on silver surface in colloid and in atmosphere were obtained with very low laser power. The SERS on silver surface in atmosphere shows more intense enhancement with sharper and narrower Raman peaks compared with the SERS in colloid. The adsorption geometries of Vitamin B 12 molecules were analyzed based on the SERS data. Vitamin B 12 molecule is supposed to adsorb on the silver particle in colloid with the corrin ring plane nearly vertical to the surface, while Vitamin B 12 molecule is supposed to adsorb on silver surface with the corrin ring plane tilted to the surface. This could be due to the water effect of the molecular conformation and the characteristic of silver particles.

  3. Phylogenetic analysis of vitamin B12-related metabolism in Mycobacterium tuberculosis.

    PubMed

    Young, Douglas B; Comas, Iaki; de Carvalho, Luiz P S

    2015-01-01

    Comparison of genome sequences from clinical isolates of Mycobacterium tuberculosis with phylogenetically-related pathogens Mycobacterium marinum, Mycobacterium kansasii, and Mycobacterium leprae reveals diversity amongst genes associated with vitamin B12-related metabolism. Diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms (SNPs) with predicted impact on protein function and transcriptional regulation. Differences in the B12 synthesis pathway, methionine biosynthesis, fatty acid catabolism, and DNA repair and replication are consistent with adaptations to different environmental niches and pathogenic lifestyles. While there is no evidence of further gene acquisition during expansion of the M. tuberculosis complex, the emergence of other forms of genetic diversity provides insights into continuing host-pathogen co-evolution and has the potential to identify novel targets for disease intervention. PMID:25988174

  4. Phylogenetic analysis of vitamin B12-related metabolism in Mycobacterium tuberculosis

    PubMed Central

    Young, Douglas B.; Comas, Iaki; de Carvalho, Luiz P. S.

    2015-01-01

    Comparison of genome sequences from clinical isolates of Mycobacterium tuberculosis with phylogenetically-related pathogens Mycobacterium marinum, Mycobacterium kansasii, and Mycobacterium leprae reveals diversity amongst genes associated with vitamin B12-related metabolism. Diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms (SNPs) with predicted impact on protein function and transcriptional regulation. Differences in the B12 synthesis pathway, methionine biosynthesis, fatty acid catabolism, and DNA repair and replication are consistent with adaptations to different environmental niches and pathogenic lifestyles. While there is no evidence of further gene acquisition during expansion of the M. tuberculosis complex, the emergence of other forms of genetic diversity provides insights into continuing host-pathogen co-evolution and has the potential to identify novel targets for disease intervention. PMID:25988174

  5. Micronutrient Status in Female University Students: Iron, Zinc, Copper, Selenium, Vitamin B12 and Folate

    PubMed Central

    Fayet-Moore, Flavia; Petocz, Peter; Samman, Samir

    2014-01-01

    Young women are at an increased risk of micronutrient deficiencies, particularly due to higher micronutrient requirements during childbearing years and multiple food group avoidances. The objective of this study was to investigate biomarkers of particular micronutrients in apparently healthy young women. Female students (n = 308; age range 1835 year; Body Mass Index 21.5 2.8 kg/m2; mean SD) were recruited to participate in a cross-sectional study. Blood samples were obtained from participants in the fasted state and analysed for biomarkers of iron status, vitamin B12, folate, homocysteine, selenium, zinc, and copper. The results show iron deficiency anaemia, unspecified anaemia, and hypoferritinemia in 3%, 7% and 33.9% of participants, respectively. Low vitamin B12 concentrations (<120 pmol/L) were found in 11.3% of participants, while 4.7% showed sub-clinical deficiency based on serum methylmalonic acid concentrations >0.34 ?mol/L. Folate concentrations below the reference range were observed in 1.7% (serum) or 1% (erythrocytes) of participants, and 99.7% of the participant had erythrocyte-folate concentrations >300 nmol/L. Serum zinc concentrations <10.7 ?mol/L were observed in 2% of participants. Serum copper and selenium concentrations were below the reference range in 23% and 11% of participants, respectively. Micronutrient deficiencies including iron and vitamin B12, and apparent excess of folate are present in educated Australian female students of childbearing age, including those studying nutrition. The effects of dietary behaviours and food choices on markers of micronutrient status require further investigation. PMID:25401503

  6. Simultaneous determination of vitamin B12 and its derivatives using some of multivariate calibration 1 (MVC1) techniques

    NASA Astrophysics Data System (ADS)

    Samadi-Maybodi, Abdolraouf; Darzi, S. K. Hassani Nejad

    2008-10-01

    Resolution of binary mixtures of vitamin B12, methylcobalamin and B12 coenzyme with minimum sample pre-treatment and without analyte separation has been successfully achieved by methods of partial least squares algorithm with one dependent variable (PLS1), orthogonal signal correction/partial least squares (OSC/PLS), principal component regression (PCR) and hybrid linear analysis (HLA). Data of analysis were obtained from UV-vis spectra. The UV-vis spectra of the vitamin B12, methylcobalamin and B12 coenzyme were recorded in the same spectral conditions. The method of central composite design was used in the ranges of 10-80 mg L -1 for vitamin B12 and methylcobalamin and 20-130 mg L -1 for B12 coenzyme. The models refinement procedure and validation were performed by cross-validation. The minimum root mean square error of prediction (RMSEP) was 2.26 mg L -1 for vitamin B12 with PLS1, 1.33 mg L -1 for methylcobalamin with OSC/PLS and 3.24 mg L -1 for B12 coenzyme with HLA techniques. Figures of merit such as selectivity, sensitivity, analytical sensitivity and LOD were determined for three compounds. The procedure was successfully applied to simultaneous determination of three compounds in synthetic mixtures and in a pharmaceutical formulation.

  7. Dual isotope Schilling test for measuring absorption of food-bound and free vitamin B12 simultaneously

    SciTech Connect

    Doscherholmen, A.; Silvis, S.; McMahon, J.

    1983-10-01

    A prototype food-bound vitamin B12 (food-B12) absorption test has been developed in which /sup 57/Co-B12 was incorporated in vitro into egg yolk (yolk-B12) and served to volunteers in 50-g cooked portions together with toast and coffee for breakfast. Six hours later, 1 mg nonlabeled B12 was given intramuscularly and 24-hour urine was collected for radioactivity measurement. In separate tests, the absorption of yolk-B12 and crystalline /sup 57/Co-B12 was equally poor in patients with pernicious anemia. However, in patients with simple gastric achlorhydria and those who had undergone gastric surgery, the assimilation of yolk-B12 was impaired greatly, whereas the absorption of crystalline radio-B12 was normal. Egg yolk labeled with /sup 58/Co-B12 was administered together with crystalline /sup 57/Co-B12 in a dual isotope test with results similar to those obtained when the tests were prepared separately. This yolk-/sup 58/Co-B12 test with its ability to detect malabsorption of food-B12 may be considered as an addition to the first part of the Schilling test.

  8. Nutritional Supplementation with Chlorella pyrenoidosa Lowers Serum Methylmalonic Acid in Vegans and Vegetarians with a Suspected Vitamin B12 Deficiency.

    PubMed

    Merchant, Randall Edward; Phillips, Todd W; Udani, Jay

    2015-12-01

    Since vitamin B12 occurs in substantial amounts only in foods derived from animals, vegetarians and particularly vegans are at risk of developing deficiencies of this essential vitamin. The chlorella used for this study is a commercially available whole-food supplement, which is believed to contain the physiologically active form of the vitamin. This exploratory open-label study was performed to determine if adding 9 g of Chlorella pyrenoidosa daily could help mitigate a vitamin B12 deficiency in vegetarians and vegans. Seventeen vegan or vegetarian adults (26-57 years of age) with a known vitamin B12 deficiency, as evidenced by a baseline serum methylmalonic acid (MMA) level above 270 nmol/L at screening, but who otherwise appeared healthy were enrolled in the study. Each participant added 9 g of C. pyrenoidosa to their daily diet for 60 ± 5 days and their serum MMA, vitamin B12, homocysteine (Hcy) levels as well as mean corpuscular volume (MCV), hemoglobin (Hgb), and hematocrit (Hct) were measured at 30 and 60 days from baseline. After 30 and 60 days, the serum MMA level fell significantly (P < .05) by an average ∼34%. Fifteen of the 17 (88%) subjects showed at least a 10% drop in MMA. At the same time, Hcy trended downward and serum vitamin B12 trended upward, while MCV, Hgb, and Hct appeared unchanged. The results of this work suggest that the vitamin B12 in chlorella is bioavailable and such dietary supplementation is a natural way for vegetarians and vegans to get the vitamin B12 they need. PMID:26485478

  9. Improved propionic acid and 5,6-dimethylbenzimidazole control strategy for vitamin B12 fermentation by Propionibacterium freudenreichii.

    PubMed

    Wang, Peng; Zhang, Zhiwei; Jiao, Youjing; Liu, Shouxin; Wang, Yunshan

    2015-01-10

    An efficient fermentation-strengthening approach was developed to improve the anaerobic production of vitamin B12 by cultivation process optimization with Propionibacterium freudenreichii. The effects of the byproduct propionic acid and the precursor 5,6-dimethylbenzimidazole (DMB) on vitamin B12 biosynthesis were investigated. Byproduct inhibition experiments showed that maintaining propionic acid concentration in broth below 10-20 g/L in the early stage and 20-30 g/L in the late stage can efficiently improve vitamin B12 biosynthesis. Batch fermentation indicated the occurrence of feed-back inhibition in intracellular intermediate biosynthesis. In addition, the incorporation of the precursor DMB depended on the fermentation level of the vitamin B12 intermediate. High vitamin B12 concentration (58.8 mg/L) and production (0.37 mg/g) were obtained with an expanded bed adsorption bioreactor by using the propionic acid and DMB control method. The optimum concentration and production of 59.5 and 0.59 mg/L h for vitamin B12 production were respectively achieved after five continuous batches. PMID:25455014

  10. Comparative genomic analyses of nickel, cobalt and vitamin B12 utilization

    PubMed Central

    Zhang, Yan; Rodionov, Dmitry A; Gelfand, Mikhail S; Gladyshev, Vadim N

    2009-01-01

    Background Nickel (Ni) and cobalt (Co) are trace elements required for a variety of biological processes. Ni is directly coordinated by proteins, whereas Co is mainly used as a component of vitamin B12. Although a number of Ni and Co-dependent enzymes have been characterized, systematic evolutionary analyses of utilization of these metals are limited. Results We carried out comparative genomic analyses to examine occurrence and evolutionary dynamics of the use of Ni and Co at the level of (i) transport systems, and (ii) metalloproteomes. Our data show that both metals are widely used in bacteria and archaea. Cbi/NikMNQO is the most common prokaryotic Ni/Co transporter, while Ni-dependent urease and Ni-Fe hydrogenase, and B12-dependent methionine synthase (MetH), ribonucleotide reductase and methylmalonyl-CoA mutase are the most widespread metalloproteins for Ni and Co, respectively. Occurrence of other metalloenzymes showed a mosaic distribution and a new B12-dependent protein family was predicted. Deltaproteobacteria and Methanosarcina generally have larger Ni- and Co-dependent proteomes. On the other hand, utilization of these two metals is limited in eukaryotes, and very few of these organisms utilize both of them. The Ni-utilizing eukaryotes are mostly fungi (except saccharomycotina) and plants, whereas most B12-utilizing organisms are animals. The NiCoT transporter family is the most widespread eukaryotic Ni transporter, and eukaryotic urease and MetH are the most common Ni- and B12-dependent enzymes, respectively. Finally, investigation of environmental and other conditions and identity of organisms that show dependence on Ni or Co revealed that host-associated organisms (particularly obligate intracellular parasites and endosymbionts) have a tendency for loss of Ni/Co utilization. Conclusion Our data provide information on the evolutionary dynamics of Ni and Co utilization and highlight widespread use of these metals in the three domains of life, yet only a limited number of user proteins. PMID:19208259

  11. Nitrous Oxide Abuse and Vitamin B12 Action in a 20-Year-Old Woman: A Case Report.

    PubMed

    Duque, Miriam Andrea; Kresak, Jesse L; Falchook, Adam; Harris, Neil S

    2015-01-01

    Herein, we report a case of a 20-year-old (ethnicity not reported) woman with a history of nitrous oxide abuse and clinical symptoms consistent with spinal cord subacute combined degeneration with associated low serum concentrations of vitamin B12, elevated methylmalonic acid levels, and radiologic evidence of demyelination of the dorsal region of the spinal column. The health of the patient improved dramatically with B12 supplementation. In this case, we discuss the interaction of nitrous oxide with the enzymatic pathways involved in the biochemistry of vitamin B12. PMID:26489675

  12. Effect of isotretinoin treatment on plasma holotranscobalamin, vitamin B12, folic acid, and homocysteine levels: non-controlled study.

    PubMed

    Karadag, Ayse Serap; Tutal, Emre; Ertugrul, Derun Taner; Akin, Kadir Okhan

    2011-12-01

    Isotretinoin (Iso) has been used for the treatment of acne. Some previous studies reported elevated homocysteine (Hcy) levels after treatment with Iso. Some side effects have clinical presentations similar to vitamin B12, folic acid deficiencies, and hyperhomocysteinemia. In the present study we evaluated the plasma Hcy levels, the vitamins involved in its metabolism (vitamin B12 and folic acid), and holotranscobalamin (HoloTC), a transport system for vitamin B12 absorption in patients receiving Iso treatment for acne vulgaris. A total of 66 patients with acne vulgaris between the ages of 18 and 40 years were included. Screening for hemoglobin, creatinine, SGOT, SGPT, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C), folic acid, vitamin B12, Hcy, and HoloTC were done just before initiation (pretreatment) and after four months of Iso treatment (posttreatment). Posttreatment vitamin B12, folic acid, and HoloTC levels were significantly lower while Hcy levels were significantly higher compared with initial values. Posttreatment total cholesterol, LDL-C, triglycerides, VLDL-C, SGPT, and SGOT levels were also higher, and HDL-C levels were lower compared with initial values while there was no change in hemoglobin levels during Iso treatment. We found that Iso usage might cause decreased vitamin B12, folic acid, and HoloTC. These Iso side effects might contribute to the missing link between Iso usage, hyperhomocysteinemia, and neuropsychiatric disorders. Trials may be made with the aim of demonstrating (clearly) if starting vitamin B12 and folic acid replacement therapies with Iso treatment initialization could be useful for preventing hyperhomocysteinemia and possibly related disorders. PMID:22098008

  13. Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12)

    PubMed Central

    2012-01-01

    Background The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency. Methods/design The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain), and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm). Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3–8,and 1 mg/month in weeks 9–52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml), adherence to treatment, quality of life (EuroQoL-5D questionnaire), patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses. Discussion The results of this study should help establish, taking quality of life into account, whether the oral administration of vitamin B12 is an effective alternative to its intramuscular administration. If this administration route is effective, it should provide a cheaper means of treating vitamin B12 deficiency while inducing fewer adverse effects. Having such an alternative would also allow patient preferences to be taken into consideration at the time of prescribing treatment. Trial registration This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20. PMID:22650964

  14. Iron, folate and vitamin B12 levels in first trimester pregnancies in the Southwest region of Turkey

    PubMed Central

    Karabulut, Aysun; Şevket, Osman; Acun, Ayhan

    2011-01-01

    Objective Iron, folate and vitamin B12 play important roles in the healthy development of the fetus in pregnancy. Preconceptional levels of these micronutrients is influenced by dietary habits. The purpose of this study was to investigate the status of iron, vitamin B12 and folate in first trimester pregnancies in the southwest region of Turkey where the Mediterranean Cuisine, rich in fresh fruit and vegetables is commonly consumed. Material and Methods Two hundred and one low-middle income pregnant women were recruited during their first prenatal visit. Hemoglobin, ferritin, folate and vitamin B12 levels were evaluated and a structured questionnaire was given to gather information including age, gravida, parity, frequency of pregnancy, history of abortion, and intrauterine device usage. Based on WHO and international guidelines, anemia was defined as hemoglobin <11 g/dl, and iron deficiency as ferritin <15 μg/L. Serum folate and vitamin B12 deficiencies were defined as levels below 3 ng/ml and 200 pg/ml respectively. Results The mean age and gestational week were 26.4±5.3 years and 9±3 weeks respectively. Mean plasma concentrations were 12.8±9.7 g/dl for hemoglobin, 22.7±17.2 μg/L for ferritin, 12.2±5.6 ng/ml for folate and 266.6±100.2 pg/ml for vitamin B12. Anemia was detected in 4.5% of pregnant women, iron deficiency in 40.3%, vitamin B12 deficiency in 29.8% and folate deficiency in 0.5% of patients. In 10.9% of patients, both vitamin B12 and iron iron deficiency was detected. There was no significant difference for age, body mass index, gravida, parity, frequency of pregnancy, history of abortion, and intrauterine device usage between women with low and normal levels of vitamin B12 and Ferritin (p>0.05). Conclusion Iron and vitamin B12 deficiencies were relatively common in the pregnant population consuming vegetable based diets. Iron and vitamin B12 supplementation in addition to folate must be considered for the wellbeing of the fetus in pregnant women living in areas where dietary patterns are mainly vegetable based. PMID:24591983

  15. Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial12

    PubMed Central

    Dangour, Alan D; Allen, Elizabeth; Clarke, Robert; Elbourne, Diana; Fletcher, Astrid E; Letley, Louise; Richards, Marcus; Whyte, Ken; Uauy, Ricardo; Mills, Kerry

    2015-01-01

    Background: Moderate vitamin B-12 deficiency is relatively common in older people. However, there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life. Objective: We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12–deficient older people. Design: We conducted a double-blind, randomized, placebo-controlled trial in 7 general practices in South East England, United Kingdom. Study participants were aged ≥75 y and had moderate vitamin B-12 deficiency (serum vitamin B-12 concentrations: 107–210 pmol/L) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo. Peripheral motor and sensory nerve conduction, central motor conduction, a clinical neurologic examination, and cognitive function were assessed before and after treatment. Results: A total of 201 participants were enrolled in the trial, and 191 subjects provided outcome data. Compared with baseline, allocation to vitamin B-12 was associated with a 177% increase in serum concentration of vitamin B-12 (641 compared with 231 pmol/L), a 331% increase in serum holotranscobalamin (240 compared with 56 pmol/L), and 17% lower serum homocysteine (14.2 compared with 17.1 μmol/L). In intention-to-treat analysis of covariance models, with adjustment for baseline neurologic function, there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo (mean difference: −0.2 mV; 95% CI: –0.8, 0.3 mV). There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome, or on cognitive function or clinical examination. Conclusion: Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency, in the absence of anemia and of neurologic and cognitive signs or symptoms, has beneficial effects on neurologic or cognitive function in later life. This trial was registered at www.isrctn.com as ISRCTN54195799. PMID:26135351

  16. Electronic structure of vitamin B12 within the framework of the Haldane-Anderson impurity model

    NASA Astrophysics Data System (ADS)

    Kandemir, Zafer; Mayda, Selma; Bulut, Nejat

    2015-03-01

    We study the electronic structure of vitamin B12 (cyanocobalamine C63H88CoN14O14P) by using the framework of the multi-orbital single-impurity Haldane-Anderson model of a transition-metal impurity in a semiconductor host. Here, our purpose is to understand the many-body effects originating from the transition-metal impurity. In this approach, the cobalt 3 d orbitals are treated as the impurity states placed in a semiconductor host which consists of the rest of the molecule. The parameters of the resulting effective Haldane-Anderson model are obtained within the Hartree-Fock approximation for the electronic structure of the molecule. The quantum Monte Carlo technique is then used to calculate the one-electron and magnetic correlation functions of this effective Haldane-Anderson model for vitamin B12. We find that new states form inside the semiconductor gap due to the on-site Coulomb interaction at the impurity 3 d orbitals and that these states become the highest occupied molecular orbitals. In addition, we present results on the charge distribution and spin correlations around the Co atom. We compare the results of this approach with those obtained by the density-functional theory calculations.

  17. Structural Basis of Multifunctionality in a Vitamin B12-processing Enzyme*

    PubMed Central

    Koutmos, Markos; Gherasim, Carmen; Smith, Janet L.; Banerjee, Ruma

    2011-01-01

    An early step in the intracellular processing of vitamin B12 involves CblC, which exhibits dual reactivity, catalyzing the reductive decyanation of cyanocobalamin (vitamin B12), and the dealkylation of alkylcobalamins (e.g. methylcobalamin; MeCbl). Insights into how the CblC scaffold supports this chemical dichotomy have been unavailable despite it being the most common locus of patient mutations associated with inherited cobalamin disorders that manifest in both severe homocystinuria and methylmalonic aciduria. Herein, we report structures of human CblC, with and without bound MeCbl, which provide novel biochemical insights into its mechanism of action. Our results reveal that CblC is the most divergent member of the NADPH-dependent flavin reductase family and can use FMN or FAD as a prosthetic group to catalyze reductive decyanation. Furthermore, CblC is the first example of an enzyme with glutathione transferase activity that has a sequence and structure unrelated to the GST superfamily. CblC thus represents an example of evolutionary adaptation of a common structural platform to perform diverse chemistries. The CblC structure allows us to rationalize the biochemical basis of a number of pathological mutations associated with severe clinical phenotypes. PMID:21697092

  18. Low plasma vitamin B-12 in Kenyan school children is highly prevalent and improved by supplemental animal source foods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The high prevalence of vitamin B-12 deficiency in many regions of the world is becoming recognized as a widespread public health problem, but it is not known to what extent this deficiency results from a low intake of the vitamin or from its malabsorption from food. In rural Kenya, where a previous ...

  19. VITAMIN B6, B12 AND FOLIC ACID SUPPLEMENTATION AND COGNITIVE FUNCTION: A SYSTEMATIC REVIEW OF RANDOMIZED TRIALS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite their important role in cognitive function, the value of B vitamin supplementation is unknown. A systematic review of the effect of vitamins B6, B12, and folic acid supplementation on cognitive function was performed. Literature search conducted in MEDLINE with supplemental articles from re...

  20. HETEROGENEITY AND LACK OF GOOD QUALITY STUDIES LIMIT ASSOCIATION BETWEEN FOLATE, VITAMIN B-6 AND B-12, AND COGNITIVE FUNCTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite their important role in cognitive function, the value of B vitamin supplementation is unknown. A systematic review of the effect of vitamins B6, B12, and folic acid supplementation on cognitive function was performed. Literature search conducted in MEDLINE with supplemental articles from rev...

  1. PREVALENCE OF VITAMINS E AND B12 IN DIETARY SUPPLEMENTS REPORTED IN NATIONAL HEALTH AND NUTRITION EVALUATION SURVEY (NHANES)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: Public health concerns regarding excessive Vitamin E and deficient Vitamin B12 intake warrant evaluation of total dietary intake for these nutrients. A Dietary Supplement Ingredient Database is being developed by the Nutrient Data Laboratory with the Office of Dietary Supplements and oth...

  2. Impact of vitamin B12 on formation of the tetrachloroethene reductive dehalogenase in Desulfitobacterium hafniense strain Y51.

    PubMed

    Reinhold, Anika; Westermann, Martin; Seifert, Jana; von Bergen, Martin; Schubert, Torsten; Diekert, Gabriele

    2012-11-01

    Corrinoids are essential cofactors of reductive dehalogenases in anaerobic bacteria. Microorganisms mediating reductive dechlorination as part of their energy metabolism are either capable of de novo corrinoid biosynthesis (e.g., Desulfitobacterium spp.) or dependent on exogenous vitamin B(12) (e.g., Dehalococcoides spp.). In this study, the impact of exogenous vitamin B(12) (cyanocobalamin) and of tetrachloroethene (PCE) on the synthesis and the subcellular localization of the reductive PCE dehalogenase was investigated in the gram-positive Desulfitobacterium hafniense strain Y51, a bacterium able to synthesize corrinoids de novo. PCE-depleted cells grown for several subcultivation steps on fumarate as an alternative electron acceptor lost the tetrachloroethene-reductive dehalogenase (PceA) activity by the transposition of the pce gene cluster. In the absence of vitamin B(12), a gradual decrease of the PceA activity and protein amount was observed; after 5 subcultivation steps with 10% inoculum, more than 90% of the enzyme activity and of the PceA protein was lost. In the presence of vitamin B(12), a significant delay in the decrease of the PceA activity with an ?90% loss after 20 subcultivation steps was observed. This corresponded to the decrease in the pceA gene level, indicating that exogenous vitamin B(12) hampered the transposition of the pce gene cluster. In the absence or presence of exogenous vitamin B(12), the intracellular corrinoid level decreased in fumarate-grown cells and the PceA precursor formed catalytically inactive, corrinoid-free multiprotein aggregates. The data indicate that exogenous vitamin B(12) is not incorporated into the PceA precursor, even though it affects the transposition of the pce gene cluster. PMID:22961902

  3. Impact of Vitamin B12 on Formation of the Tetrachloroethene Reductive Dehalogenase in Desulfitobacterium hafniense Strain Y51

    PubMed Central

    Reinhold, Anika; Westermann, Martin; Seifert, Jana; von Bergen, Martin; Schubert, Torsten

    2012-01-01

    Corrinoids are essential cofactors of reductive dehalogenases in anaerobic bacteria. Microorganisms mediating reductive dechlorination as part of their energy metabolism are either capable of de novo corrinoid biosynthesis (e.g., Desulfitobacterium spp.) or dependent on exogenous vitamin B12 (e.g., Dehalococcoides spp.). In this study, the impact of exogenous vitamin B12 (cyanocobalamin) and of tetrachloroethene (PCE) on the synthesis and the subcellular localization of the reductive PCE dehalogenase was investigated in the Gram-positive Desulfitobacterium hafniense strain Y51, a bacterium able to synthesize corrinoids de novo. PCE-depleted cells grown for several subcultivation steps on fumarate as an alternative electron acceptor lost the tetrachloroethene-reductive dehalogenase (PceA) activity by the transposition of the pce gene cluster. In the absence of vitamin B12, a gradual decrease of the PceA activity and protein amount was observed; after 5 subcultivation steps with 10% inoculum, more than 90% of the enzyme activity and of the PceA protein was lost. In the presence of vitamin B12, a significant delay in the decrease of the PceA activity with an ?90% loss after 20 subcultivation steps was observed. This corresponded to the decrease in the pceA gene level, indicating that exogenous vitamin B12 hampered the transposition of the pce gene cluster. In the absence or presence of exogenous vitamin B12, the intracellular corrinoid level decreased in fumarate-grown cells and the PceA precursor formed catalytically inactive, corrinoid-free multiprotein aggregates. The data indicate that exogenous vitamin B12 is not incorporated into the PceA precursor, even though it affects the transposition of the pce gene cluster. PMID:22961902

  4. Is there an association of vitamin B12 status with neurological function in older people? A systematic review.

    PubMed

    Miles, Lisa M; Mills, Kerry; Clarke, Robert; Dangour, Alan D

    2015-08-28

    Low vitamin B12 status is common in older people; however, its public health significance in terms of neurological manifestations remains unclear. The present systematic review evaluated the association of vitamin B12 status with neurological function and clinically relevant neurological outcomes in adults aged 50+ years. A systematic search of nine bibliographic databases (up to March 2013) identified twelve published articles describing two longitudinal and ten cross-sectional analyses. The included study populations ranged in size (n 28-2287) and mean/median age (range 65-81 years). Studies reported various neurological outcomes: nerve function; clinically measured signs and symptoms of nerve function; self-reported neurological symptoms. Studies were assessed for risk of bias, and results were synthesised qualitatively. Among the general population groups of older people, one longitudinal study reported no association, and four of seven cross-sectional studies reported limited evidence of an association of vitamin B12 status with some, but not all, neurological outcomes. Among groups with clinical and/or biochemical evidence of low vitamin B12 status, one longitudinal study reported an association of vitamin B12 status with some, but not all, neurological outcomes and three cross-sectional analyses reported no association. Overall, there is limited evidence from observational studies to suggest an association of vitamin B12 status with neurological function in older people. The heterogeneity and quality of the evidence base preclude more definitive conclusions, and further high-quality research is needed to better inform understanding of public health significance in terms of neurological function of vitamin B12 status in older people. PMID:26202329

  5. Supplementing lactating dairy cows with a vitamin B12 precursor, 5,6-dimethylbenzimidazole, increases the apparent ruminal synthesis of vitamin B12.

    PubMed

    Brito, A; Chiquette, J; Stabler, S P; Allen, R H; Girard, C L

    2015-01-01

    Cobalamin (CBL), the biologically active form of vitamin B12, and its analogs, are produced by bacteria only if cobalt supply is adequate. The analogs differ generally by the nucleotide moiety of the molecule. In CBL, 5,6-dimethylbenzimidazole (5,6-DMB) is the base in the nucleotide moiety. The present study aimed to determine if a supplement of 5,6-DMB could increase utilization of dietary cobalt for synthesis of CBL and change ruminal fermentation, nutrient digestibility, omasal flow of nutrients and ruminal protozoa counts. Eight ruminally cannulated multiparous Holstein cows (meanstandard deviation=23821 days in milk and 73647 kg of BW) were used in a crossover design. Cows were randomly assigned to a daily supplement of a gelatin capsule containing 1.5 g of 5,6-DMB via the rumen cannula or no supplement. Each period lasted 29 days and consisted of 21 days for treatment adaptation and 8 days for data and samples collection. Five corrinoids, CBL and four cobamides were detected in the total mixed ration and the omasal digesta from both treatments. The dietary supplement of 5,6-DMB increased (P=0.02) apparent ruminal synthesis of CBL from 14.6 to 19.6 (s.e.m. 0.8) mg/day but had no effect (P>0.1) on apparent ruminal synthesis of the four analogs. The supplement of 5,6-DMB had no effect (P>0.1) on milk production and composition, or on protozoal count, ruminal pH and concentrations of volatile fatty acids and ammonia nitrogen in rumen content. The supplement had also no effect (P>0.1) on intake, omasal flow and apparent ruminal digestibility of dry matter, organic matter, NDF, ADF and nitrogenous fractions. Plasma concentration of CBL was not affected by treatments (P=0.98). Providing a preformed part of the CBL molecule, that is, 5,6-DMB, increased by 34% the apparent ruminal synthesis of CBL by ruminal bacteria but had no effect on ruminal fermentation or protozoa count and it was not sufficient to increase plasma concentrations of the vitamin. Even though the efficiency of cobalt utilization for apparent synthesis of CBL was increased from 2.0% to 2.7% by the 5,6-DMB supplement, this improved efficiency was still very low. Further research is needed to identify the factors affecting efficiency of utilization of cobalt for synthesis of CBL by the bacterial populations in rumen. PMID:25171056

  6. Fundamental shift in vitamin B12 eco-physiology of a model alga demonstrated by experimental evolution

    PubMed Central

    Helliwell, Katherine E.; Collins, Sinéad; Kazamia, Elena; Purton, Saul; Wheeler, Glen L.; Smith, Alison G.

    2014-01-01

    A widespread and complex distribution of vitamin requirements exists over the entire tree of life, with many species having evolved vitamin dependence, both within and between different lineages. Vitamin availability has been proposed to drive selection for vitamin dependence, in a process that links an organism’s metabolism to the environment, but this has never been demonstrated directly. Moreover, understanding the physiological processes and evolutionary dynamics that influence metabolic demand for these important micronutrients has significant implications in terms of nutrient acquisition, and in microbial organisms, can affect community composition and metabolic exchange between coexisting species. Here, we investigate the origins of vitamin dependence, using an experimental evolution approach with the vitamin B12-independent model green alga Chlamydomonas reinhardtii. In fewer than 500 generations of growth in the presence of vitamin B12, we observe the evolution of a B12-dependent clone that rapidly displaces its ancestor. Genetic characterization of this line reveals a type-II Gulliver-related transposable element (GR-TE) integrated into the B12-independent methionine synthase gene (METE), knocking out gene function and critically altering the physiology of the alga. PMID:25526368

  7. Fundamental shift in vitamin B12 eco-physiology of a model alga demonstrated by experimental evolution.

    PubMed

    Helliwell, Katherine E; Collins, Sinéad; Kazamia, Elena; Purton, Saul; Wheeler, Glen L; Smith, Alison G

    2015-06-01

    A widespread and complex distribution of vitamin requirements exists over the entire tree of life, with many species having evolved vitamin dependence, both within and between different lineages. Vitamin availability has been proposed to drive selection for vitamin dependence, in a process that links an organism's metabolism to the environment, but this has never been demonstrated directly. Moreover, understanding the physiological processes and evolutionary dynamics that influence metabolic demand for these important micronutrients has significant implications in terms of nutrient acquisition and, in microbial organisms, can affect community composition and metabolic exchange between coexisting species. Here we investigate the origins of vitamin dependence, using an experimental evolution approach with the vitamin B(12)-independent model green alga Chlamydomonas reinhardtii. In fewer than 500 generations of growth in the presence of vitamin B(12), we observe the evolution of a B(12)-dependent clone that rapidly displaces its ancestor. Genetic characterization of this line reveals a type-II Gulliver-related transposable element integrated into the B(12)-independent methionine synthase gene (METE), knocking out gene function and fundamentally altering the physiology of the alga. PMID:25526368

  8. Parallel computing and first-principles calculations: Applications to complex ceramics and Vitamin B12

    NASA Astrophysics Data System (ADS)

    Ouyang, Lizhi

    A systematic improvement and extension of the orthogonalized linear combinations of atomic orbitals method was carried out using a combined computational and theoretical approach. For high performance parallel computing, a Beowulf class personal computer cluster was constructed. It also served as a parallel program development platform that helped us to port the programs of the method to the national supercomputer facilities. The program, received a language upgrade from Fortran 77 to Fortran 90, and a dynamic memory allocation feature. A preliminary parallel High Performance Fortran version of the program has been developed as well. To be of more benefit though, scalability improvements are needed. In order to circumvent the difficulties of the analytical force calculation in the method, we developed a geometry optimization scheme using the finite difference approximation based on the total energy calculation. The implementation of this scheme was facilitated by the powerful general utility lattice program, which offers many desired features such as multiple optimization schemes and usage of space group symmetry. So far, many ceramic oxides have been tested with the geometry optimization program. Their optimized geometries were in excellent agreement with the experimental data. For nine ceramic oxide crystals, the optimized cell parameters differ from the experimental ones within 0.5%. Moreover, the geometry optimization was recently used to predict a new phase of TiNx. The method has also been used to investigate a complex Vitamin B12-derivative, the OHCbl crystals. In order to overcome the prohibitive disk I/O demand, an on-demand version of the method was developed. Based on the electronic structure calculation of the OHCbl crystal, a partial density of states analysis and a bond order analysis were carried out. The calculated bonding of the corrin ring of OHCbl model was coincident with the big open-ring pi bond. One interesting find of the calculation was that the Co-OH bond was weak. This, together with the ongoing projects studying different Vitamin B12 derivatives, might help us to answer questions about the Co-C cleavage of the B12 coenzyme, which is involved in many important B12 enzymatic reactions.

  9. Plasma Homocysteine, Vitamin B12 and Folate Levels in Multiple System Atrophy: A Case-Control Study

    PubMed Central

    Mao, Chengyuan; Song, Bo; Hou, Haiman; Wu, Jun; Liu, Xinjing; Luo, Haiyang; Sun, Shilei; Xu, Yuming

    2015-01-01

    Background Multiple system atrophy (MSA) is a neurodegenerative disease, and its pathological hallmark is the accumulation of α-synuclein proteins. Homocysteine (Hcy) is an intermediate amino acid generated during the metabolism of methionine. Hcy may contribute to the pathogenesis of neurodegenerative disorders. Vitamin B12 and folate are cofactors necessary for the methylation of homocysteine. Methods This study compared the levels of serum Hcy, vitamin B12 and folate in patients with MSA with those in healthy people to reveal the possible association between MSA and plasma levels of Hcy, vitamin B12 and folate. We enrolled 161 patients with MSA and 161 healthy people in this study. The association between MSA and the levels of Hcy, vitamin B12 and folate were analyzed using binary logistic regression. Results The mean level of Hcy in patients with MSA was significantly higher than that in healthy controls (16.23 ± 8.09 umol/l vs 14.04 ± 4.25 umol/l, p < 0.05). After adjusting for age, sex and medical history, the odds ratio for Hcy was 1.07 (95% CI = 1.01–1.13, p < 0.05) for patients with MSA. Vitamin B12 and folate levels were not significantly different between patients with MSA and controls. Conclusion Our data suggest that higher levels of Hcy may be associated with an increased risk for MSA. PMID:26291976

  10. Novel insights into the effect of vitamin B12 and omega-3 fatty acids on brain function.

    PubMed

    Rathod, Richa; Kale, Anvita; Joshi, Sadhana

    2016-01-01

    The prevalence of psychiatric disorders which are characterized by cognitive decline is increasing at an alarming rate and account for a significant proportion of the global disease burden. Evidences from human and animal studies indicate that neurocognitive development is influenced by various environmental factors including nutrition. It has been established that nutrition affects the brain throughout life. However, the mechanisms through which nutrition modulates mental health are still not well understood. It has been suggested that the deficiencies of both vitamin B12 and omega-3 fatty acids can have adverse effects on cognition and synaptic plasticity. Studies indicate a need for supplementation of vitamin B12 and omega-3 fatty acids to reduce the risk of cognitive decline, although the results of intervention trials using these nutrients in isolation are inconclusive. In the present article, we provide an overview of vitamin B12 and omega-3 fatty acids, the possible mechanisms and the evidences through which vitamin B12 and omega-3 fatty acids modulate mental health and cognition. Understanding the role of vitamin B12 and omega-3 fatty acids on brain functioning may provide important clues to prevent early cognitive deficits and later neurobehavioral disorders. PMID:26809263

  11. Novel fermentation process strengthening strategy for production of propionic acid and vitamin B12 by Propionibacterium freudenreichii.

    PubMed

    Wang, Peng; Jiao, Youjing; Liu, Shouxin

    2014-12-01

    An efficient fermentation-strengthening approach was developed to improve the anaerobic production of propionic acid and vitamin B12 by co-fermentation with Propionibacterium freudenreichii. Vitamin B12 production from glucose resulted in relatively high productivity (0.35mg/Lh) but a low propionic acid yield (0.55g/g). By contrast, glycerol gave a high propionic acid yield (0.63g/g) but low productivity (0.16g/Lh). Co-fermentation of glycerol and glucose with a gradual addition strategy gave high yields (propionic acid: 0.71g/g; vitamin B12: 0.72mg/g) and productivities (propionic acid: 0.36g/Lh; vitamin B12: 0.36mg/Lh). Finally, the integrated feedstock and fermentation system strengthening strategy was demonstrated as an efficient method for the economic production of bio-based propionic acid and vitamin B12. PMID:25261985

  12. Effect of vitamin B12 pulse addition on the performance of cobalt deprived anaerobic granular sludge bioreactors.

    PubMed

    Fermoso, Fernando G; Bartacek, Jan; Lens, Piet N L

    2010-07-01

    The effect of a pulse addition of vitamin B(12) as cobalt source to restore the performance of cobalt depleted methanol-fed bioreactors was investigated. One upflow anaerobic sludge bed (UASB) reactor was supplied with a pulse of vitamin B(12), and its operation was compared to that of another cobalt depleted UASB reactor to which a pulse of CoCl(2) was given. The addition of cobalt in the form of CoCl(2) supplies enough cobalt to restore methanogenesis and maintain full methanol degradation coupled to methane production during more than 35 days after the CoCl(2) pulse. Similar to CoCl(2), pulse addition of vitamin B(12) supplies enough cobalt to maintain full methanol degradation during more than 35 days after the pulse. However, the specific methanogenic activities (SMAs) of the sludge in the vitamin B(12) supplied reactor were around 3 times higher than the SMA of the sludge from the CoCl(2) supplied reactor at the same sampling times. An appropriate dosing strategy (repeated pulse dosing) combined with the choice of vitamin B(12) as the cobalt species is suggested as a promising dosing strategy for methanol-fed anaerobic bioreactors limited by the micronutrient cobalt. PMID:20304635

  13. Response to Vitamin B12 and Folic Acid in Myalgic Encephalomyelitis and Fibromyalgia

    PubMed Central

    Regland, Bjrn; Forsmark, Sara; Halaouate, Lena; Matousek, Michael; Peilot, Birgitta; Zachrisson, Olof; Gottfries, Carl-Gerhard

    2015-01-01

    Background Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections, in vital combination with oral folic acid. However, there is no established algorithm for individualized optimal dosages, and rate of improvement may differ considerably between responders. Objective To evaluate clinical data from patients with ME, with or without fibromyalgia, who had been on B12 injections at least once a week for six months and up to several years. Methods 38 patients were included in a cross-sectional survey. Based on a validated observers rating scale, they were divided into Good (n = 15) and Mild (n = 23) responders, and the two groups were compared from various clinical aspects. Results Good responders had used significantly more frequent injections (p<0.03) and higher doses of B12 (p<0.03) for a longer time (p<0.0005), higher daily amounts of oral folic acid (p<0.003) in good relation with the individual MTHFR genotype, more often thyroid hormones (p<0.02), and no strong analgesics at all, while 70% of Mild responders (p<0.0005) used analgesics such as opioids, duloxetine or pregabalin on a daily basis. In addition to ME, the higher number of patients with fibromyalgia among Mild responders was bordering on significance (p<0.09). Good responders rated themselves as very much or much improved, while Mild responders rated much or minimally improved. Conclusions Dose-response relationship and long-lasting effects of B12/folic acid support a true positive response in the studied group of patients with ME/fibromyalgia. Its important to be alert on co-existing thyroid dysfunction, and we suspect a risk of counteracting interference between B12/folic acid and certain opioid analgesics and other drugs that have to be demethylated as part of their metabolism. These issues should be considered when controlled trials for ME and fibromyalgia are to be designed. PMID:25902009

  14. Vitamin B12 Metabolism during Pregnancy and in Embryonic Mouse Models

    PubMed Central

    Moreno-Garcia, Maira A.; Rosenblatt, David S.; Jerome-Majewska, Loydie A.

    2013-01-01

    Vitamin B12 (cobalamin, Cbl) is required for cellular metabolism. It is an essential coenzyme in mammals for two reactions: the conversion of homocysteine to methionine by the enzyme methionine synthase and the conversion of methylmalonyl-CoA to succinyl-CoA by the enzyme methylmalonyl-CoA mutase. Symptoms of Cbl deficiency are hematological, neurological and cognitive, including megaloblastic anaemia, tingling and numbness of the extremities, gait abnormalities, visual disturbances, memory loss and dementia. During pregnancy Cbl is essential, presumably because of its role in DNA synthesis and methionine synthesis; however, there are conflicting studies regarding an association between early pregnancy loss and Cbl deficiency. We here review the literature about the requirement for Cbl during pregnancy, and summarized what is known of the expression pattern and function of genes required for Cbl metabolism in embryonic mouse models. PMID:24025485

  15. CdTe quantum dot as a fluorescence probe for vitamin B12 in dosage form

    NASA Astrophysics Data System (ADS)

    Vaishnavi, E.; Renganathan, R.

    2013-11-01

    We here report the CdTe quantum dot (CdTe QDs)-based sensor for probing vitamin B12 derivatives in aqueous solution. In this paper, simple and sensitive fluorescence quenching measurements has been employed. The Stern-Volmer constant (KSV), quenching rate constant (kq) and binding constant (K) were rationalized from fluorescence quenching measurement. Furthermore, the fluorescence resonance energy transfer (FRET) mechanism was discussed. This method was applicable over the concentration ranging from 1 to 14 ?g/mL (VB12) with correlation coefficient of 0.993. The limit of detection (LOD) of VB12 was found to be 0.15 ?g/mL. Moreover, the present approach opens a simple pathway for developing cost-effective, sensitive and selective QD-based fluorescence sensors/probes for biologically significant VB12 in pharmaceutical sample with mean recoveries in the range of 100-102.1%.

  16. The cis influence of the corrin in vitamin B12 models

    NASA Astrophysics Data System (ADS)

    Govender, Penny P.; Navizet, Isabelle; Perry, Christopher B.; Marques, Helder M.

    2012-10-01

    Density Functional Theory (DFT) and Quantum Theory of Atoms in Molecules (QTAIM) calculations on [NH3[Co(III)(C10-X-corrin)]-CH3]+, where the C10-H of corrin is replaced by electron-donating or -withdrawing groups, X, explore the cis influence in these vitamin B12 models. As the electron donating ability of X increases, a normal trans influence is observed: the Co-NH3 bond weakens while the Co-CH3 bond strengthens. Surprisingly, though, the Co-CH3 bond dissociation energy decreases monotonically as the Co-C bond strengthens. This is found to be a consequence of the extent of shortening of the Co-NH3 during the homolysis reaction.

  17. Multiple micronutrient supplementation improves vitamin B12 and folate concentrations of HIV infected children in Uganda: a randomized controlled trial

    PubMed Central

    2011-01-01

    Background The effect of multiple micronutrient supplementation on vitamin B12 and folate has hither to not been reported in African HIV infected children. This paper describes vitamin B12 and folate status of Ugandan HIV infected children aged 1-5 years and reports the effect of multiple micronutrient supplementation on serum vitamin B12 and folate concentrations. Methods Of 847 children who participated in a multiple micronutrient supplementation trial, 214 were assessed for vitamin B12 and folate concentrations pre and post supplementation. One hundred and four children were randomised to two times the recommended dietary allowance (RDA) of a 14 multiple micronutrient supplement (MMS) and 114 to a 'standard of care' supplement of 6 multivitamins (MV). Serum vitamin B12 was measured by an electrochemiluminescence immunoassay and folate by a competitive protein-binding assay using Modular E (Roche) automatic analyzer. Vitamin B12 concentrations were considered low if less than 221picomoles per litre (pmol/L) and folate if < 13.4 nanomoles per litre (nmol/L). The Wilcoxon Signed Ranks test was used to measure the difference between pre and post supplementation concentrations. Results Vitamin B12 was low in 60/214 (28%) and folate in 62/214 (29.0%) children. In the MMS group, the median concentration (IQR) of vitamin B12 at 6 months was 401.5 (264.3 - 518.8) pmol/L compared to the baseline of 285.5 (216.5 - 371.8) pmol/L, p < 0.001. The median (IQR) folate concentrations increased from 17.3 (13.5 - 26.6) nmol/L to 27.7 (21.1 - 33.4) nmol/L, p < 0.001. In the 'standard of care' MV supplemented group, the median concentration (IQR) of vitamin B12 at 6 months was 288.5 (198.8 - 391.0) pmol/L compared to the baseline of 280.0 (211.5 - 386.3) pmol/L while the median (IQR) folate concentrations at 6 months were 16.5 (11.7 - 22.1) nmol/L compared to 15.7 (11.9 - 22.1) nmol/L at baseline. There was a significant difference in the MMS group in both vitamin B12 and folate concentrations but no difference in the MV group. Conclusions Almost a third of the HIV infected Ugandan children aged 1-5 years had low serum concentrations of vitamin B12 and folate. Multiple micronutrient supplementation compared to the 'standard of care' supplement of 6 multivitamins improved the vitamin B12 and folate status of HIV infected children in Uganda. Trial registration http://ClinicalTrials.govNCT00122941) PMID:21600005

  18. What should I know before ordering a bone marrow aspiration/biopsy in patients with vitamin B12 deficiency?

    PubMed

    Randhawa, Jaskirat; Ondrejka, Sarah L; Setrakian, Sebouh; Taylor, Harris

    2013-01-01

    Vitamin B12 deficiency is a well recognised cause of macrocytic anaemia and bone marrow failure. Bone marrow aspiration/biopsy is infrequently indicated for the diagnosis in this setting. However, if a bone marrow aspiration/biopsy is performed, it is important to recognise that it may show dysplastic changes mimicking myelodysplastic syndrome (MDS) or acute leukaemia. We report a case of a 66-year-old non-vegetarian man presenting with generalised weakness for 1 month and misdiagnosed on bone marrow biopsy as MDS. However, laboratory investigations revealed severe deficiency of vitamin B12. Four weeks after starting vitamin B12 replacement the patient's complete blood counts reverted to normal. PMID:23839610

  19. Vitamin B12 and derivatives-In vitro permeation studies across Caco-2 cell monolayers and freshly excised rat intestinal mucosa.

    PubMed

    Netsomboon, Kesinee; Feler, Andrea; Erletz, Lena; Prfert, Felix; Ruetz, Markus; Kieninger, Christoph; Krutler, Bernhard; Bernkop-Schnrch, Andreas

    2016-01-30

    The purpose of this study was to compare the intestinal permeation of vitamin B12 and various derivatives thereof. Permeation behavior and cytotoxicity of four derivatives (coenzyme B12, hydroxocobalamin, methylcobalamin and 4-ethylphenylcobalamin) in comparison to vitamin B12 were evaluated in two different in vitro models, Caco-2 cells and freshly excised rat intestinal mucosa. Resazurin assay was used to evaluate cytotoxicity of the test substances. All test compounds were used at a concentration of 200?g/ml. Permeation experiments were carried out for 3h and test compounds were quantified via reversed phase high performance liquid chromatography (HPLC). Cytotoxicity studies showed all test compounds are not toxic to cells. HPLC analyses of test compounds revealed the following rank order of increasing hydrophobicity: hydroxocobalamin<vitamin B12B12B12, hydroxocobalamin, methylcobalamin and 4-ethylphenylcobalamin were 10.2, 0.3, 9.4 and 31.3 fold of vitamin B12 on Caco-2 cells while 0.2, 0.4, 2.6 and 1.9 fold of vitamin B12 on rat intestine, respectively. As various vitamin B12 derivatives showed a significantly higher permeation coefficient than vitamin B12, the use of certain derivatives might be a promising strategy for oral vitamin B12 substitution. PMID:26638881

  20. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study

    PubMed Central

    Deshpande, S. S.; Jackson, A. A.; Refsum, H.; Rao, S.; Fisher, D. J.; Bhat, D. S.; Naik, S. S.; Coyaji, K. J.; Joglekar, C. V.; Joshi, N.; Lubree, H. G.; Deshpande, V. U.; Rege, S. S.; Fall, C. H. D.

    2007-01-01

    Aims/hypothesis Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6years. Methods In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy and methylmalonic acid (MMA) at 18 and 28weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6years. Results Two-thirds of mothers had low vitamin B12 (<150pmol/l), 90% had high MMA (>0.26?mol/l) and 30% had raised tHcy concentrations (>10?mol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28weeks predicted higher offspring adiposity and higher HOMA-R (both p?vitamin B12 (18weeks; p?=?0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant. Conclusions/interpretation Low maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India. Electronic supplementary material The online version of this article (doi:10.1007/s00125-007-0793-y) contains supplementary material, which is available to authorised users. PMID:17851649

  1. Lactobacillus rossiae, a Vitamin B12 Producer, Represents a Metabolically Versatile Species within the Genus Lactobacillus

    PubMed Central

    De Angelis, Maria; Bottacini, Francesca; Fosso, Bruno; Kelleher, Philip; Calasso, Maria; Di Cagno, Raffaella; Ventura, Marco; Picardi, Ernesto; van Sinderen, Douwe; Gobbetti, Marco

    2014-01-01

    Lactobacillus rossiae is an obligately hetero-fermentative lactic acid bacterium, which can be isolated from a broad range of environments including sourdoughs, vegetables, fermented meat and flour, as well as the gastrointestinal tract of both humans and animals. In order to unravel distinctive genomic features of this particular species and investigate the phylogenetic positioning within the genus Lactobacillus, comparative genomics and phylogenomic approaches, followed by functional analyses were performed on L. rossiae DSM 15814T, showing how this type strain not only occupies an independent phylogenetic branch, but also possesses genomic features underscoring its biotechnological potential. This strain in fact represents one of a small number of bacteria known to encode a complete de novo biosynthetic pathway of vitamin B12 (in addition to other B vitamins such as folate and riboflavin). In addition, it possesses the capacity to utilize an extensive set of carbon sources, a characteristic that may contribute to environmental adaptation, perhaps enabling the strain's ability to populate different niches. PMID:25264826

  2. Lactobacillus rossiae, a vitamin B12 producer, represents a metabolically versatile species within the Genus Lactobacillus.

    PubMed

    De Angelis, Maria; Bottacini, Francesca; Fosso, Bruno; Kelleher, Philip; Calasso, Maria; Di Cagno, Raffaella; Ventura, Marco; Picardi, Ernesto; van Sinderen, Douwe; Gobbetti, Marco

    2014-01-01

    Lactobacillus rossiae is an obligately hetero-fermentative lactic acid bacterium, which can be isolated from a broad range of environments including sourdoughs, vegetables, fermented meat and flour, as well as the gastrointestinal tract of both humans and animals. In order to unravel distinctive genomic features of this particular species and investigate the phylogenetic positioning within the genus Lactobacillus, comparative genomics and phylogenomic approaches, followed by functional analyses were performed on L. rossiae DSM 15814T, showing how this type strain not only occupies an independent phylogenetic branch, but also possesses genomic features underscoring its biotechnological potential. This strain in fact represents one of a small number of bacteria known to encode a complete de novo biosynthetic pathway of vitamin B12 (in addition to other B vitamins such as folate and riboflavin). In addition, it possesses the capacity to utilize an extensive set of carbon sources, a characteristic that may contribute to environmental adaptation, perhaps enabling the strain's ability to populate different niches. PMID:25264826

  3. Vitamin B12 biosynthesis over waste frying sunflower oil as a cost effective and renewable substrate.

    PubMed

    Hajfarajollah, Hamidreza; Mokhtarani, Babak; Mortaheb, Hamidreza; Afaghi, Ali

    2015-06-01

    Statistical experimental designs were used to develop a medium based on waste frying sunflower oil (WFO) and other nutrient sources for production of vitamin B12 (VB12) by Propionibacterium freudenreichii subsp. freudenreichii PTCC 1674. The production of acetic acid and propionic acid were also evaluated using the same microorganism. The amount of WFO in the media was initially optimized. The amount of 4%w/v of oil found to be an appropriate amount for production of VB12. A Plackett Burman design was then employed to identify nutrients that have significant effect on the production of VB12 in the WFO media. Dimethylbenzimidazolyl (DMB), cobalt chloride, ferrous sulfate, and calcium chloride were the most important compounds. The level optimization of nutrients as the significant factors was finally performed using response surface methodology based on a central composite design. The model predicted that a medium containing 35.56mg/L DMB, 14.69mg/L CoCl2.6H2O, 5.82mg/L FeSO4.7H2O, and 11.41mg/L CaCl2.2H2O gives the maximum VB12 production of 2.60mg/L. The optimized medium provides a final concentration of vitamin 170% higher than that by the original medium. This study offers valuable insights on a cost-effective carbon source for industrial production of food-grade VB12. PMID:26028708

  4. Secondary palatal closure in rats in association with relative maternofetal levels of folic acid, vitamin B12, and homocysteine.

    PubMed

    Weingrtner, Jens; Maile, Sergei; Proff, Peter; Reicheneder, Claudia; Bienengrber, Volker; Fanghnel, Jochen; Gedrange, Tomas

    2007-01-01

    Animal experiments are used in embryological and teratological studies of matters relevant to humans. In gravid rats, a decrease in the levels of folic acid and vitamin B12 was observed in maternal blood and in amniotic fluid. At the time of secondary palatal closure (14th day of pregnancy), the folic acid level of the amniotic fluid was 73% lower than that of the maternal blood. A drop in vitamin B12 in conjunction with an increase in amniotic homocysteine levels is seen as a risk factor for malformation of the palate. The understanding of causes of cleft generation could lead to a prophylactic treatment approach. PMID:17534029

  5. Investigation on the pH-dependent binding of vitamin B12 and lysozyme by fluorescence and absorbance

    NASA Astrophysics Data System (ADS)

    Li, Daojin; Yang, Yumin; Cao, Xinxiang; Xu, Chen; Ji, Baoming

    2012-01-01

    The binding reaction between vitamin B12 (B12, cyanocobalamin) and lysozyme (Lys) has been investigated by fluorescence, synchronous fluorescence, ultraviolet-vis (UV) absorbance, and three-dimensional fluorescence. The intrinsic fluorescence of Lys was strongly quenched by the addition of B12 in different pH buffer solutions (pH 3.4, 7.4, and 9.0) and the spectroscopic observations are mainly rationalized in terms of a static quenching process at lower concentration of B12 ( CB12/ CLys < 5) and a combined quenching process at higher concentration of B12 ( CB12/ CLys > 5). The structural characteristics of B12 and Lys were probed, and their binding affinities were determined under different pH conditions (pH 3.4, 7.4, and 9.0). The effect of B12 on the conformation of Lys was analyzed using UV, synchronous fluorescence and three-dimensional fluorescence under different pH conditions. These results indicate that the binding of B12 to Lys causes apparent change in the secondary or tertiary structures of Lys. Furthermore, the effect of Zn 2+ on the binding constant of B12 with Lys under various pH conditions (pH 3.4, 7.4, and 9.0) was also studied.

  6. Serum alpha tocopherol, vitamin B12, and folate levels in childhood acute lymphoblastic leukemia survivors with and without neuropathy.

    PubMed

    Jain, Puneet; Gulati, Sheffali; Toteja, G S; Bakhshi, Sameer; Seth, Rachna; Pandey, R M

    2015-05-01

    Various micronutrients are essential for optimal functioning of the peripheral nervous system. Serum vitamin E, vitamin B12, and folic acid were estimated in childhood acute lymphoblastic leukemia survivors aged between 5 and 18 years in first continuous remission within 3 years of completion of vincristine-based chemotherapy with and without electrophysiologically defined neuropathy. A total of 80 children were studied. Neuropathy was seen in 27 (33.75%) children electrophysiologically. None of the children had vitamin E deficiency. However, the alpha tocopherol/(cholesterol + triglyceride) ratio was significantly lower in children with neuropathy (P = .05). The prevalence of folate (P = .48) and vitamin B12 (P = .21) deficiency in children with and without neuropathy was not significantly different. Thus, the prevalence of deficiencies of these micronutrients was not significantly different in childhood acute lymphoblastic leukemia survivors with or without electrophysiologically defined neuropathy. PMID:24859786

  7. Vitamin B12 production from crude glycerol by Propionibacterium freudenreichii ssp. shermanii: optimization of medium composition through statistical experimental designs.

    PubMed

    Ko?mider, Alicja; Bia?as, Wojciech; Kubiak, Piotr; Dro?d?y?ska, Agnieszka; Czaczyk, Katarzyna

    2012-02-01

    A two-step statistical experimental design was employed to optimize the medium for vitamin B(12) production from crude glycerol by Propionibacterium freudenreichii ssp. shermanii. In the first step, using Plackett-Burman design, five of 13 tested medium components (calcium pantothenate, NaH(2)PO(4)2H(2)O, casein hydrolysate, glycerol and FeSO(4)7H(2)O) were identified as factors having significant influence on vitamin production. In the second step, a central composite design was used to optimize levels of medium components selected in the first step. Valid statistical models describing the influence of significant factors on vitamin B(12) production were established for each optimization phase. The optimized medium provided a 93% increase in final vitamin concentration compared to the original medium. PMID:22178491

  8. Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report.

    PubMed

    Tufan, Ali Evren; Bilici, Rabia; Usta, Genco; Erdoğan, Ayten

    2012-01-01

    Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were "irritability, regressive behavior, apathy, crying and truancy" which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg's sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5 mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg's sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3 months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6 months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features especially with accompanying extrapyramidal symptoms lacking a clear etiology may be rare manifestation of vitamin B12 and/or folate deficiency in children and adolescents and be potentially amenable to treatment. PMID:22726236

  9. Vitamin B12: a tunable, long wavelength, light-responsive platform for launching therapeutic agents.

    PubMed

    Shell, Thomas A; Lawrence, David S

    2015-11-17

    Light-responsive agents offer the promise of targeted therapy, whose benefits include (i) prolonged action at the target site, (ii) overall reduced systemic dosage, (iii) reduced adverse effects, and (iv) localized delivery of multiple agents. Although photoactivated prodrugs have been reported, these species generally require short wavelengths (<450 nm) for activation. However, maximal tissue penetrance by light occurs within the "optical window of tissue" (600-900 nm), well beyond the wavelength range of most existing photocleavable functional groups. Furthermore, since multidrug therapy holds promise for the treatment of complex diseases, from cancer to neurological disorders, controlling the action of multiple drugs via wavelength modulation would take advantage of a property that is unique to light. However, discrimination between existing photoresponsive moieties has thus far proven to be limited. We have developed a vitamin B12/light-facilitated strategy for controlling drug action using red, far-red, and NIR light. The technology is based on a light-triggered reaction displayed by a subset of B12 derivatives: alkyl-cob(III)alamins suffer photohomolysis of the C-Co(III) bond. The C-Co(III) bond is weak (<30 kcal/mol), and therefore all wavelengths absorbed by the corrin ring (330-580 nm) induce photocleavage. In addition, by appending fluorophores to the corrin ring, long wavelength light (>600 nm) is readily captured and used to separate the Co-appended ligand (e.g., a drug) from B12. Consequently, it is now feasible to preassign the wavelength of homolysis by simply installing a fluorescent antenna with the desired photophysical properties. The wavelength malleability inherent within this strategy has been used to construct photoresponsive compounds that launch different drugs by simply modulating the wavelength of illumination. In addition, these phototherapeutics have been installed on the surface and interior of cells, such as erythrocytes or neural stem cells, and released upon expoure to the appropriate wavelength. We have shown that cytotoxic agents, such as doxorubicin, anti-inflammatories, such as dexamethasone, and anti- and pro-vascular agents are readily released from cellular vehicles as biologically active agents. We have also demonstrated that the concept of "optical window of tissue" phototherapeutics is not just limited to prodrugs. For example, stem cells have received considerable attention in the area of regenerative medicine. Hydrogels serve as scaffolds for stem cell growth and differentiation. We have shown that the formation of hydrogels can be triggered, in the presence of cells, using appropriately designed alkyl-cob(III)alamins and long wavelength light. The potential applications of phototherapeutics are broad and include drug delivery for a variety of indications, tissue engineering, and surgery. PMID:26479305

  10. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study.

    PubMed

    Aroda, Vanita R; Edelstein, Sharon L; Goldberg, Ronald B; Knowler, William C; Marcovina, Santica M; Orchard, Trevor J; Bray, George A; Schade, David S; Temprosa, Marinella G; White, Neil H; Crandall, Jill P

    2016-04-01

    Participants from DPP/DPPOS were assigned to placebo (n=1082) or metformin (n=1073) for 3.2 years, followed by metformin in the metformin group for 9 years. Metformin use was associated with increased risk of vitamin B12 deficiency. PMID:26900641

  11. Vitamin B12 Deficiency and Elevated Folate Levels: An Unusual Cause of Generalized Tonic-Clonic Seizure

    PubMed Central

    Lubana, Sandeep Singh; Alfishawy, Mostafa; Singh, Navdeep; Atkinson, Sharon

    2015-01-01

    Patient: Male, 49 Final Diagnosis: Generalized tonic-clonic seizures in the setting of vitamin B12 deficiency and elevated folate levels Symptoms: Seizures Medication: Clinical Procedure: None Specialty: Neurology Objective: Unknown ethiology Background: Vitamin B12 deficiency leads to abnormal myelination or demyelination, resulting in sub-acute combined degeneration, peripheral neuropathy, and psychiatric problems, including delusions, hallucinations, cognitive changes, depression, and dementia. Vitamin B12 deficiency also leads to brain shrinkage and neurodegenerative disorders. Case Report: We report the case of a 49-year-old man presenting with new-onset seizures one and a half years following subtotal gastrectomy due to stage IV gastric adenocarcinoma. The patient did not have any history of head injury. Laboratory tests were negative for any metabolic derangements. There were no signs of infection. MRI brain and EEG were normal and there were no changes in medications. Conclusions: In case of unexplained new-onset seizures, patients should be tested for vitamin B12 and folic acid levels and these should be done as part of the initial work-up. PMID:26101427

  12. Acupuncture and vitamin B12 injection for Bell’s palsy: no high-quality evidence exists

    PubMed Central

    Wang, Li-li; Guan, Ling; Hao, Peng-liang; Du, Jin-long; Zhang, Meng-xue

    2015-01-01

    OBJECTIVE: To assess the efficacy of acupuncture combined with vitamin B12 acupoint injection versus acupuncture alone to reduce incomplete recovery in patients with Bell’s palsy. DATA RETRIEVAL: A computer-based online retrieval of Medline, Web of Science, CNKI, CBM databases until April 2014 was performed for relevant trials, using the key words “Bell’s palsy or idiopathic facial palsy or facial palsy” and “acupuncture or vitamin B12 or methylcobalamin”. STUDY SELECTION: All randomized controlled trials that compared acupuncture with acupuncture combined with vitamin B12 in patients with Bell’s palsy were included in the meta-analysis. The initial treatment lasted for at least 4 weeks. The outcomes of incomplete facial recovery were monitored. The scoring index varied and the definition of healing was consistent. The combined effect size was calculated by using relative risk (RR) with 95% confidence interval (CI) using the fixed effect model of Review Manager. MAIN OUTCOME MEASURES: Incomplete recovery rates were chosen as the primary outcome. RESULTS: Five studies involving 344 patients were included in the final analysis. Results showed that the incomplete recovery rate of Bell’s palsy patients was 44.50% in the acupuncture combined with vitamin B12 group but 62.57% in the acupuncture alone group. The major acupoints were Taiyang (EX-HN5), Jiache (ST6), Dicang (ST4) and Sibai (ST2). The combined effect size showed that acupuncture combined with vitamin B12 was better than acupuncture alone for the treatment of Bell’s palsy (RR = 0.71, 95%CI: 0.58–0.87; P = 0.001), this result held true when 8 patients lost to follow up in one study were included into the analyses (RR = 0.70, 95%CI: 0.58–0.86; P = 0.0005). In the subgroup analyses, the therapeutic effect in patients of the electroacupuncture subgroup was better than in the non-electroacupuncture subgroup (P = 0.024). There was no significant difference in the incomplete recovery rate by subgroup analysis on drug types and treatment period. Most of the included studies were moderate or low quality, and bias existed. CONCLUSION: In patients with Bell’s palsy, acupuncture combined with vitamin B12 can reduce the risk of incomplete recovery compared with acupuncture alone in our meta-analysis. Because of study bias and methodological limitations, this conclusion is uncertain and the clinical application of acupuncture combined with vitamin B12 requires further exploration. PMID:26109959

  13. Chlamydomonas reinhardtii thermal tolerance enhancement mediated by a mutualistic interaction with vitamin B12-producing bacteria

    PubMed Central

    Xie, Bo; Bishop, Shawn; Stessman, Dan; Wright, David; Spalding, Martin H; Halverson, Larry J

    2013-01-01

    Temperature is one of the most important environmental factors affecting the growth and survival of microorganisms and in light of current global patterns is of particular interest. Here, we highlight studies revealing how vitamin B12 (cobalamin)-producing bacteria increase the fitness of the unicellular alga Chlamydomonas reinhardtii following an increase in environmental temperature. Heat stress represses C. reinhardtii cobalamin-independent methionine synthase (METE) gene expression coinciding with a reduction in METE-mediated methionine synthase activity, chlorosis and cell death during heat stress. However, in the presence of cobalamin-producing bacteria or exogenous cobalamin amendments C. reinhardtii cobalamin-dependent methionine synthase METH-mediated methionine biosynthesis is functional at temperatures that result in C. reinhardtii death in the absence of cobalamin. Artificial microRNA silencing of C. reinhardtii METH expression leads to nearly complete loss of cobalamin-mediated enhancement of thermal tolerance. This suggests that methionine biosynthesis is an essential cellular mechanism for adaptation by C. reinhardtii to thermal stress. Increased fitness advantage of METH under environmentally stressful conditions could explain the selective pressure for retaining the METH gene in algae and the apparent independent loss of the METE gene in various algal species. Our results show that how an organism acclimates to a change in its abiotic environment depends critically on co-occurring species, the nature of that interaction, and how those species interactions evolve. PMID:23486253

  14. Circadian rhythms in vitamin B12 content of the rat brain.

    PubMed

    Ikeda, M; Inou, S

    1997-06-01

    The whole brain content of vitamin B12 (VB12) in the rat was assayed by the chemiluminescent immunoassay at 4 h intervals in 12:12 h light-dark cycles (LD) and five different circadian times (CTs) under constant dim illumination (dim LL). In LD-entrained rats, the content of VB12 exhibited a day-night rhythm with a peak 2 h after the dark onset time and a trough 2 h before the light onset time. In freerunning rats under dim LL, the content of VB12 also exhibited a circadian variation with a peak ca. 2 h after the activity onset time (CT14) and a trough ca. 12 h after the activity onset time (CT 0). These findings clearly indicate that the brain VB12 content decreased during the active phase and increased during the resting phase regardless of the lighting schedule. On the other hand, the drinking behavior, as an index of the intake activity, was observed less frequently in the light phase of LD cycles and the resting phase of dim LL. Since most of the digested VB12 is known to be continuously stored in the liver, it is demonstrated that the rhythm of the brain content of VB12 may be caused by brain consumption of VB12 during the active phase and the transportation from the peripheral storage during the resting phase, independent of intake activities. PMID:9209116

  15. The chemistry of vitamin B12. The coordination of biologically important molecules

    PubMed Central

    Hill, H. A. O.; Pratt, J. M.; Thorp, R. G.; Ward, B.; Williams, R. J. P.

    1970-01-01

    The following equilibrium constants (given as logK in units of m?1) were determined for the substitution of co-ordinated H2O in aquocobalamin by glycine (bound through N) 5.8, cysteine (bound through S) 6.0 or 8.3, depending on the value chosen for the pK of the thiol group, and phenolate 2.9. The spectrum of the phenolate cobalamin shows an additional intense absorption band at 468nm with a molar extinction coefficient of 1.1104, which is assigned to a charge transfer from the phenolate to the cobalt ion. Equilibrium constants have also been determined for the equilibria between adenylcobamide cyanide and CN?, HO? and H+, which show that the adenine is more easily displaced by CN? and HO? than is 5,6-dimethylbenziminazole in vitamin B12, but can be protonated by acid while still remaining co-ordinated to the cobalt. It is shown that in the binding of corrinoids to proteins and polypeptides the formation of hydrogen bonds is far more important than co-ordination by the metal. PMID:5493853

  16. The chemistry of vitamin B 12. The co-ordination of biologically important molecules.

    PubMed

    Hill, H A; Pratt, J M; Thorp, R G; Ward, B; Williams, R J

    1970-11-01

    The following equilibrium constants (given as logK in units of m(-1)) were determined for the substitution of co-ordinated H(2)O in aquocobalamin by glycine (bound through N) 5.8, cysteine (bound through S) 6.0 or 8.3, depending on the value chosen for the pK of the thiol group, and phenolate 2.9. The spectrum of the phenolate cobalamin shows an additional intense absorption band at 468nm with a molar extinction coefficient of 1.1x10(4), which is assigned to a charge transfer from the phenolate to the cobalt ion. Equilibrium constants have also been determined for the equilibria between adenylcobamide cyanide and CN(-), HO(-) and H(+), which show that the adenine is more easily displaced by CN(-) and HO(-) than is 5,6-dimethylbenziminazole in vitamin B(12), but can be protonated by acid while still remaining co-ordinated to the cobalt. It is shown that in the binding of corrinoids to proteins and polypeptides the formation of hydrogen bonds is far more important than co-ordination by the metal. PMID:5493853

  17. Chlamydomonas reinhardtii thermal tolerance enhancement mediated by a mutualistic interaction with vitamin B12-producing bacteria.

    PubMed

    Xie, Bo; Bishop, Shawn; Stessman, Dan; Wright, David; Spalding, Martin H; Halverson, Larry J

    2013-08-01

    Temperature is one of the most important environmental factors affecting the growth and survival of microorganisms and in light of current global patterns is of particular interest. Here, we highlight studies revealing how vitamin B12 (cobalamin)-producing bacteria increase the fitness of the unicellular alga Chlamydomonas reinhardtii following an increase in environmental temperature. Heat stress represses C. reinhardtii cobalamin-independent methionine synthase (METE) gene expression coinciding with a reduction in METE-mediated methionine synthase activity, chlorosis and cell death during heat stress. However, in the presence of cobalamin-producing bacteria or exogenous cobalamin amendments C. reinhardtii cobalamin-dependent methionine synthase METH-mediated methionine biosynthesis is functional at temperatures that result in C. reinhardtii death in the absence of cobalamin. Artificial microRNA silencing of C. reinhardtii METH expression leads to nearly complete loss of cobalamin-mediated enhancement of thermal tolerance. This suggests that methionine biosynthesis is an essential cellular mechanism for adaptation by C. reinhardtii to thermal stress. Increased fitness advantage of METH under environmentally stressful conditions could explain the selective pressure for retaining the METH gene in algae and the apparent independent loss of the METE gene in various algal species. Our results show that how an organism acclimates to a change in its abiotic environment depends critically on co-occurring species, the nature of that interaction, and how those species interactions evolve. PMID:23486253

  18. Folate and Vitamin B12 Transport Systems in the Developing Infant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    B vitamin transport systems in infants are not as well studied as those for amino acids and glucose. For most B vitamins, a 2-step process allows for digestion of coenzyme forms of the vitamins in food, followed by specific transport systems for the free vitamin in the intestine. Folate and vitamin ...

  19. Effect of pH on the interaction of vitamin B12 with bovine serum albumin by spectroscopic approaches

    NASA Astrophysics Data System (ADS)

    Li, Daojin; Zhang, Tian; Xu, Chen; Ji, Baoming

    2011-12-01

    The interaction mechanism between vitamin B12 (B12, cyanocobalamin) and bovine serum albumin (BSA) has been investigated by fluorescence, synchronous fluorescence, ultraviolet-vis (UV) absorbance, and three-dimensional fluorescence. The intrinsic fluorescence of BSA was strongly quenched by the addition of B12 in different pH buffer solutions (pH 2.5, 3.5, 5.0, 7.4, and 9.0) and spectroscopic observations are mainly rationalized in terms of a static quenching process at lower concentration of B12 ( CB12/ CBSA < 5) and a combined quenching process at higher concentration of B12 ( CB12/ CBSA > 5). The structural characteristics of B12 and BSA were probed, and their binding affinities were determined under different pH conditions. The results indicated that the binding abilities of B12 to BSA in the acidic and basic pH regions (pH 2.5, 3.5, 5.0, and 9.0) were lower than that at simulating physiological condition (pH 7.4). In addition, the efficiency of energy transfer from tryptophan fluorescence to B12 was found to depend on the binding distance r between the donor and acceptor calculated using Förster's theory. The effect of B12 on the conformation of BSA was analyzed using UV, synchronous fluorescence and three-dimensional fluorescence under different pH conditions. These results showed that the binding of B12 to BSA causes apparent change in the secondary and tertiary structures of BSA.

  20. Effects of intramuscular administration of folic acid and vitamin B12 on granulosa cells gene expression in postpartum dairy cows.

    PubMed

    Gagnon, A; Khan, D R; Sirard, M-A; Girard, C L; Laforest, J-P; Richard, F J

    2015-11-01

    The fertility of dairy cows is challenged during early lactation, and better nutritional strategies need to be developed to address this issue. Combined supplementation of folic acid and vitamin B12 improve energy metabolism in the dairy cow during early lactation. Therefore, the present study was undertaken to explore the effects of this supplement on gene expression in granulosa cells from the dominant follicle during the postpartum period. Multiparous Holstein cows received weekly intramuscular injection of 320 mg of folic acid and 10 mg of vitamin B12 (treated group) beginning 24 (standard deviation=4) d before calving until 56 d after calving, whereas the control group received saline. The urea plasma concentration was significantly decreased during the precalving period, and the concentration of both folate and vitamin B12 were increased in treated animals. Milk production and dry matter intake were not significantly different between the 2 groups. Plasma concentrations of folates and vitamin B12 were increased in treated animals. Daily dry matter intake was not significantly different between the 2 groups before [13.5 kg; standard error (SE)=0.5] and after (23.6 kg; SE=0.9) calving. Average energy-corrected milk tended to be greater in vitamin-treated cows, 39.7 (SE=1.4) and 38.1 (SE=1.3) kg/d for treated and control cows, respectively. After calving, average plasma concentration of ?-hydroxybutyrate tended to be lower in cows injected with the vitamin supplement, 0.47 (SE=0.04) versus 0.55 (SE=0.03) for treated and control cows, respectively. The ovarian follicle ?12 mm in diameter was collected by ovum pick-up after estrus synchronization. Recovered follicular fluid volumes were greater in the vitamin-treated group. A microarray platform was used to investigate the effect of treatment on gene expression of granulosa cells. Lower expression of genes involved in the cell cycle and higher expression of genes associated with granulosa cell differentiation before ovulation were observed. Selected candidate genes were analyzed by reverse transcription quantitative PCR. Although the effects of intramuscular injections of folic acid and vitamin B12 on lactational performance and metabolic status of animals were limited, ingenuity pathway analysis of gene expression in granulosa cells suggests a stimulation of cell differentiation in vitamin-treated cows, which may be the result of an increase in LH secretion. PMID:26298749

  1. Opportunistic Screening of Vitamin B12 Deficiency in IT Professionals Presenting for Routine Health Check-up

    PubMed Central

    Patel, Rishi Devilal; Ingole, Sonali Jitendra; Pandave, Harshal Tukaram

    2015-01-01

    Introduction Vitamin B12 deficiency is mainly diagnosed in symptomatic patients. However, the deficiency may also be prevalent in asymptomatic patients. Our aim was to study the prevalence of Vit B12 deficiency in IT professionals (Information Technology Professionals from Software industry) who presented for routine health screening and to correlate the deficiency to various parameters. Materials and Methods This was single centre, observational study comprising of 84 IT professionals. The data was collected in structured format. The study was designed to identify prevalence of Vit B12 deficiency and correlate to other factors such as type of diet, income level & regular use of medication (such as Antacid & Metformin). Results Total 28 individuals were found to be deficient (33.34%). Prevalence of Vit B12 deficiency amongst Vegetarian and non vegetarian diet adhering subjects was 47.5% and 20.45% respectively. B12 deficiency was also prevalent in high income age group. Further chronic intake of PPI (Proton pump inhibitor) and Metformin was associated with prevalence of 37.5% and 33.34% in the present study. Conclusion During health screening of IT Professionals, significant prevalence of Vit B12 deficiency was noted across all income groups & non vegetarian diet consuming subjects also. There is significant correlation between Vit B12 deficiency with chronic use of PPI and Metformin. PMID:26816929

  2. Isotope-dilution assay for urinary methylmalonic acid in the diagnosis of vitamin B12 deficiency. A prospective clinical evaluation

    SciTech Connect

    Matchar, D.B.; Feussner, J.R.; Millington, D.S.; Wilkinson, R.H. Jr.; Watson, D.J.; Gale, D.

    1987-05-01

    Vitamin B12 deficiency is a frequently considered diagnosis for which there is no single, commonly available and accurate test. A urinary methylmalonic acid assay using gas chromatography-mass spectrometry has been proposed as the preferred test. We reviewed vitamin B12 assays on 1599 consecutive patients and prospectively studied all patients with low serum B12 levels (n = 75) and a random sample of patients with normal levels (n = 68). Of 96 evaluable patients, 7 had clinical deficiency. All 7 deficient patients had urinary methylmalonic acid levels greater than 5 micrograms/mg creatine (sensitivity, 100%; confidence interval, 65% to 100%). Of the 89 patients who were not clinically deficient, 88 had urinary methylmalonic acid levels less than or equal to 5 micrograms/mg creatinine (specificity, 99%). The overall test accuracy in this population was 99%. If the high sensitivity and specificity of the gas chromatography-mass spectrometry assay for urinary methylmalonic acid is supported by other clinical studies, the methylmalonic acid assay may become the reference standard for the diagnosis of vitamin B12 deficiency.

  3. Vitamin B-12 and folate status in relation to decline in scores on the Mini-Mental State Examination in the Framingham Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biochemical evidence of low vitamin B-12 status is common in seniors, but its clinical relevance is unclear. Vitamin B-12 deficiency can result in rapid, irreversible cognitive decline – a phenomenon that has been linked to high folate status. Our objective was to investigate the cognitive significa...

  4. Response to Quinlivan: Post-fortification, folate intake in vitamin B12 deficiency is positively related to homocysteine and methylmalonic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    With cross-sectional data, causes and effects are difficult to distinguish, and Quinlivan suggests that high circulating concentrations of homcysteine (Hcy), methylmalonic acid (MMA), and folate observed among vitamin B12-deficient survey participants all resulted from a lack of vitamin B12 (1). How...

  5. A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to the risk of ischemic stroke.

    PubMed

    Wei, Loo Keat; Sutherland, Heidi; Au, Anthony; Camilleri, Emily; Haupt, Larisa M; Gan, Siew Hua; Griffiths, Lyn R

    2015-01-01

    Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR) gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B12, and homocysteine) were determined using immunoassays. Methylation profiles for CpGs A and B in the MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke. PMID:25705649

  6. A Potential Epigenetic Marker Mediating Serum Folate and Vitamin B12 Levels Contributes to the Risk of Ischemic Stroke

    PubMed Central

    Keat Wei, Loo; Sutherland, Heidi; Au, Anthony; Camilleri, Emily; Haupt, Larisa M.; Gan, Siew Hua; Griffiths, Lyn R.

    2015-01-01

    Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR) gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B12, and homocysteine) were determined using immunoassays. Methylation profiles for CpGs A and B in the MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke. PMID:25705649

  7. Properties and reactivity of chlorovinylcobalamin and vinylcobalamin and their implications for vitamin B12-catalyzed reductive dechlorination of chlorinated alkenes.

    PubMed

    McCauley, Kevin M; Pratt, Derek A; Wilson, Scott R; Shey, Justin; Burkey, Theodore J; van der Donk, Wilfred A

    2005-02-01

    Vitamin B12-catalyzed reductive dechlorination of perchloroethylene (PCE) and trichloroethylene (TCE) is a potential strategy for cleanup of polluted environments. Presented are crystal structures of vinylcobalamin 2 and cis-chlorovinylcobalamin 1. They show a strong resistance toward photolysis. Reduction of 2 is difficult, but reduction of 1 occurs readily and produces 2. The mechanism of this latter reaction involves acetylene as an intermediate. These and other findings are discussed in the context of environmental studies on B12-catalyzed dechlorination of PCE and TCE and investigations of the haloalkene reductive dehalogenases that catalyze similar reactions. PMID:15669852

  8. The effect of folic acid, vitamin B6 and vitamin B12 on the homocysteine levels in rabbits fed by methionine-enriched diets.

    PubMed

    Narin, Figen; Narin, Nazmi; Akcakus, Mustafa; Ustdal, Muzaffer; Karakk, Inci; Halici, Canan

    2002-10-01

    Atherosclerosis is an important cause of cardiovascular morbidity and mortality in recent years. Hyperhomocysteinemia is recognized as an independent risk factor for premature atherosclerosis and venous thrombosis. It is suggested that administration of folic acid, vitamin B6 and vitamin B12 may decrease homocysteine levels. In our study, we induced hyperhomocysteinemia in rabbits by giving methionine and studied the effects of folic acid, vitamin B6 and vitamin B12 on homocysteine levels. A total of 40 (20 female, 20 male New Zealand rabbits) were divided into four groups, each consisting of 10 rabbits. Methionine (100 mg/kg/day), methionine (100 mg/kg/day) plus vitamin B6 (30 mg/kg/day), methionine (100 mg/kg/day) plus vitamin B12 (80 mg/kg/day) and methionine (100 mg/kg/day) plus folic acid (20 mg/kg/day) were given to the first, second, third and forth groups respectively. These rabbits were followed up for two months. We studied homocysteine levels on the 0, 20th, 40th and 60th days in all groups. In rabbits we induced hyperhomocysteinemia by giving methionine for 2 months. The decreases of homocysteine levels in the forth group were significant with respect to the second and third groups. Folic acid supplementation clearly resulted in a reduction of plasma homocysteine levels, whereas vitamin B12 was little effective and vitamin B6 failed to show an effect. We conclude that even folic acid treatment alone may be sufficient for decreasing negative effects of homocysteine. PMID:12512994

  9. Combined Spectroscopic/Computational Studies of Vitamin B12 Precursors: Geometric and Electronic Structures of Cobinamides

    PubMed Central

    Reig, Amanda J.; Conrad, Karen S.; Brunold, Thomas C.

    2015-01-01

    Vitamin B12 (cyanocobalamin) and its biologically active derivatives, methylcobalamin and adenosylcobalamin, are members of the family of corrinoids, which also includes cobinamides. As biological precursors to cobalamins, cobinamides possess the same structural core, consisting of a low-spin Co3+ ion that is ligated equatorially by the four nitrogens of a highly substituted tetrapyrrole macrocycle (the corrin ring), but differ with respect to the lower axial ligation. Specifically, cobinamides possess a water molecule instead of the nucleotide loop that coordinates axially to Co3+cobalamins via its dimethylbenzimidazole (DMB) base. Compared to the cobalamin species, cobinamides have proven much more difficult to study experimentally, thus far eluding characterization by X-ray crystallography. In this study, we have utilized combined quantum mechanics/molecular mechanics (QM/MM) computations to generate complete structural models of a representative set of cobinamide species with varying upper axial ligands. To validate the use of this approach, analogous QM/MM geometry optimizations were carried out on entire models of the cobalamin counterparts, for which high-resolution X-ray structural data are available. The accuracy of the cobinamide structures was assessed further by comparing electronic absorption spectra computed using time-dependent density functional theory to those obtained experimentally. Collectively, the results obtained in this study indicate that the DMB?H2O lower axial ligand switch primarily affects the energies of the Co 3dz2-based molecular orbital (MO) and, to a lesser extent, the other Co 3d-based MOs as well as the corrin ?-based highest energy MO. Thus, while the energies of the lowest-energy electronic transition of cobalamins change considerably as a function of the upper axial ligand, they are nearly invariant for the cobinamides. PMID:22332807

  10. Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking*

    PubMed Central

    Froese, D. Sean; Kopec, Jolanta; Fitzpatrick, Fiona; Schuller, Marion; McCorvie, Thomas J.; Chalk, Rod; Plessl, Tanja; Fettelschoss, Victoria; Fowler, Brian; Baumgartner, Matthias R.; Yue, Wyatt W.

    2015-01-01

    Conversion of vitamin B12 (cobalamin, Cbl) into the cofactor forms methyl-Cbl (MeCbl) and adenosyl-Cbl (AdoCbl) is required for the function of two crucial enzymes, mitochondrial methylmalonyl-CoA mutase and cytosolic methionine synthase, respectively. The intracellular proteins MMACHC and MMADHC play important roles in processing and targeting the Cbl cofactor to its destination enzymes, and recent evidence suggests that they may interact while performing these essential trafficking functions. To better understand the molecular basis of this interaction, we have mapped the crucial protein regions required, indicate that Cbl is likely processed by MMACHC prior to interaction with MMADHC, and identify patient mutations on both proteins that interfere with complex formation, via different mechanisms. We further report the crystal structure of the MMADHC C-terminal region at 2.2 Å resolution, revealing a modified nitroreductase fold with surprising homology to MMACHC despite their poor sequence conservation. Because MMADHC demonstrates no known enzymatic activity, we propose it as the first protein known to repurpose the nitroreductase fold solely for protein-protein interaction. Using small angle x-ray scattering, we reveal the MMACHC-MMADHC complex as a 1:1 heterodimer and provide a structural model of this interaction, where the interaction region overlaps with the MMACHC-Cbl binding site. Together, our findings provide novel structural evidence and mechanistic insight into an essential biological process, whereby an intracellular “trafficking chaperone” highly specific for a trace element cofactor functions via protein-protein interaction, which is disrupted by inherited disease mutations. PMID:26483544

  11. Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking.

    PubMed

    Froese, D Sean; Kopec, Jolanta; Fitzpatrick, Fiona; Schuller, Marion; McCorvie, Thomas J; Chalk, Rod; Plessl, Tanja; Fettelschoss, Victoria; Fowler, Brian; Baumgartner, Matthias R; Yue, Wyatt W

    2015-12-01

    Conversion of vitamin B12 (cobalamin, Cbl) into the cofactor forms methyl-Cbl (MeCbl) and adenosyl-Cbl (AdoCbl) is required for the function of two crucial enzymes, mitochondrial methylmalonyl-CoA mutase and cytosolic methionine synthase, respectively. The intracellular proteins MMACHC and MMADHC play important roles in processing and targeting the Cbl cofactor to its destination enzymes, and recent evidence suggests that they may interact while performing these essential trafficking functions. To better understand the molecular basis of this interaction, we have mapped the crucial protein regions required, indicate that Cbl is likely processed by MMACHC prior to interaction with MMADHC, and identify patient mutations on both proteins that interfere with complex formation, via different mechanisms. We further report the crystal structure of the MMADHC C-terminal region at 2.2 Å resolution, revealing a modified nitroreductase fold with surprising homology to MMACHC despite their poor sequence conservation. Because MMADHC demonstrates no known enzymatic activity, we propose it as the first protein known to repurpose the nitroreductase fold solely for protein-protein interaction. Using small angle x-ray scattering, we reveal the MMACHC-MMADHC complex as a 1:1 heterodimer and provide a structural model of this interaction, where the interaction region overlaps with the MMACHC-Cbl binding site. Together, our findings provide novel structural evidence and mechanistic insight into an essential biological process, whereby an intracellular "trafficking chaperone" highly specific for a trace element cofactor functions via protein-protein interaction, which is disrupted by inherited disease mutations. PMID:26483544

  12. Role of vitamin B12 on methylmalonyl-CoA mutase activity.

    PubMed

    Takahashi-Iiguez, Tshiko; Garca-Hernandez, Enrique; Arregun-Espinosa, Roberto; Flores, Mara Elena

    2012-06-01

    Vitamin B(12) is an organometallic compound with important metabolic derivatives that act as cofactors of certain enzymes, which have been grouped into three subfamilies depending on their cofactors. Among them, methylmalonyl-CoA mutase (MCM) has been extensively studied. This enzyme catalyzes the reversible isomerization of L-methylmalonyl-CoA to succinyl-CoA using adenosylcobalamin (AdoCbl) as a cofactor participating in the generation of radicals that allow isomerization of the substrate. The crystal structure of MCM determined in Propionibacterium freudenreichii var. shermanii has helped to elucidate the role of this cofactor AdoCbl in the reaction to specify the mechanism by which radicals are generated from the coenzyme and to clarify the interactions between the enzyme, coenzyme, and substrate. The existence of human methylmalonic acidemia (MMA) due to the presence of mutations in MCM shows the importance of its role in metabolism. The recent crystallization of the human MCM has shown that despite being similar to the bacterial protein, there are significant differences in the structural organization of the two proteins. Recent studies have identified the involvement of an accessory protein called MMAA, which interacts with MCM to prevent MCM's inactivation or acts as a chaperone to promote regeneration of inactivated enzyme. The interdisciplinary studies using this protein as a model in different organisms have helped to elucidate the mechanism of action of this isomerase, the impact of mutations at a functional level and their repercussion in the development and progression of MMA in humans. It is still necessary to study the mechanisms involved in more detail using new methods. PMID:22661206

  13. Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part I--Folate, Vitamin B12, Vitamin B6.

    PubMed

    Simpson, Joe Leigh; Bailey, Lynn B; Pietrzik, Klaus; Shane, Barry; Holzgreve, Wolfgang

    2010-12-01

    This two-part review highlights micronutrients for which either public health policy has been established or for which new evidence provides guidance as to recommended intakes during pregnancy. One pivotal micronutrient is folate, the generic name for different forms of a water-soluble vitamin essential for the synthesis of thymidylate and purines and, hence, DNA. For non-pregnant adult women the recommended intake is 400 ?g/day dietary folate equivalent. For women capable of becoming pregnant an additional 400 ?g/day of synthetic folic acid from supplements or fortified foods is recommended to reduce the risk of neural tube defects (NTD). The average amount of folic acid received through food fortification (grains) in the US is only 128 ?g/day, emphasising the need for the supplemental vitamin for women of reproductive age. Vitamin B12 (cobalamin) is a cofactor required for enzyme reactions, including generation of methionine and tetrahydrofolate. B12 is found almost exclusively in foods of animal origin (meats, dairy products); therefore, vegetarians are at greatest risk for dietary vitamin B12 deficiency and should be supplemented. Vitamin B6 is required for many reactions, primarily in amino acid metabolism. Meat, fish and poultry are good dietary sources. Supplementation beyond routine prenatal vitamins is not recommended. PMID:20373888

  14. Contribution of Food Sources to the Vitamin B12 Status of South Indian Children from a Birth Cohort Recruited in the City of Mysore

    PubMed Central

    2014-01-01

    Objective There is evidence that sub-clinical vitamin B12 (B12) deficiency is common in India. Vegetarianism is prevalent and therefore meat consumption is low. Our objective was to explore the contribution of B12 source-foods and maternal B12 status during pregnancy to plasma B12 concentrations. Design Maternal plasma B12 concentrations were measured during pregnancy. Childrens dietary intakes and plasma B12 concentrations were measured at age 9.5 years; B12 and total energy intakes were calculated using food composition databases. We used linear regression to examine associations between maternal B12 status and childrens intakes of B12 and B12 source-foods, and childrens plasma B12 concentrations. Setting South Indian city of Mysore and surrounding rural areas. Subjects Children from the Mysore Parthenon Birth Cohort (n=512, 47.1% male). Results Three percent of children were B12 deficient (<150 pmol/l). A further 14% had marginal B12 concentrations (150-221 pmol/l). Childrens total daily B12 intake and consumption frequency of meat and fish, and micronutrient-enriched beverages were positively associated with plasma B12 concentrations (p=0.006, p=0.01 and p=0.04, adjusted for socio-economic indicators and maternal B12 status). Maternal pregnancy plasma B12 was associated with childrens plasma B12 concentrations, independent of current B12 intakes (p<0.001). Milk and curd (yoghurt) intakes were unrelated to B12 status. Conclusions Meat and fish are important B12 sources in this population. Micronutrient-enriched beverages appear to be important sources in our cohort, but their high sugar content necessitates care in their recommendation. Improving maternal B12 status in pregnancy may improve Indian childrens status. PMID:24866058

  15. Simultaneous determination of cobalt and nickel in vitamin B12 samples using high-resolution continuum source atomic absorption spectrometry.

    PubMed

    Adolfo, Franciele Rovasi; do Nascimento, Paulo Ccero; Bohrer, Denise; de Carvalho, Leandro Machado; Viana, Carine; Guarda, Ananda; Nunes Colim, Alexsandro; Mattiazzi, Patricia

    2016-01-15

    Nickel and cobalt were simultaneously assayed in vitamin B12 formulations by using atomic spectrometry. The proposed method is based on a compromise between the proximity of specific Ni and Co spectral lines and the relative abundances of the analytes in the samples. The analytes were found in concentrations ranging from 9.48 to 26.20gL(-1) (Ni) and from 156.90 to 279.25mgL(-1) (Co) in the commercial samples of vitamin B12. The limits of detection and quantification were 1.21 and 3.64mgL(-1) for Co and 0.39 and 1.19gL(-1) for Ni. Sample cleanup was not necessary for the determinations, and the interferences were discussed. PMID:26592602

  16. Anchoring Secreted Proteins in Endoplasmic Reticulum by Plant Oleosin: The Example of Vitamin B12 Cellular Sequestration by Transcobalamin

    PubMed Central

    Alberto, Jean-Marc; Arango-Rodriguez, Martha Ligia; Dumas, Dominique; Martinez-Fong, Daniel; Freund, Jean-Noel; Gueant, Jean-Louis

    2009-01-01

    Background Oleosin is a plant protein localized to lipid droplets and endoplasmic reticulum of plant cells. Our idea was to use it to target functional secretory proteins of interest to the cytosolic side of the endoplasmic reticulum of mammalian cells, through expressing oleosin-containing chimeras. We have designed this approach to create cellular models deficient in vitamin B12 (cobalamin) because of the known problematics associated to the obtainment of effective vitamin B12 deficient cell models. This was achieved by the overexpression of transcobalamin inside cells through anchoring to oleosin. Methodology chimera gene constructs including transcobalamin-oleosin (TC-O), green fluorescent protein-transcobalamin-oleosin (GFP-TC-O) and oleosin-transcobalamin (O-TC) were inserted into pAcSG2 and pCDNA3 vectors for expression in sf9 insect cells, Caco2 (colon carcinoma), NIE-115 (mouse neuroblastoma), HEK (human embryonic kidney), COS-7 (Green Monkey SV40-transfected kidney fibroblasts) and CHO (Chinese hamster ovary cells). The subcellular localization, the changes in vitamin B12 binding activity and the metabolic consequences were investigated in both Caco2 and NIE-115 cells. Principal findings vitamin B12 binding was dramatically higher in TC-O than that in O-TC and wild type (WT). The expression of GFP-TC-O was observed in all cell lines and found to be co-localized with an ER-targeted red fluorescent protein and calreticulin of the endoplasmic reticulum in Caco2 and COS-7 cells. The overexpression of TC-O led to B12 deficiency, evidenced by impaired conversion of cyano-cobalamin to ado-cobalamin and methyl-cobalamin, decreased methionine synthase activity and reduced S-adenosyl methionine to S-adenosyl homocysteine ratio, as well as increases in homocysteine and methylmalonic acid concentration. Conclusions/Significance the heterologous expression of TC-O in mammalian cells can be used as an effective strategy for investigating the cellular consequences of vitamin B12 deficiency. More generally, expression of oleosin-anchored proteins could be an interesting tool in cell engineering for studying proteins of pharmacological interest. PMID:19623264

  17. A case-control nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression.

    PubMed

    Ragasudha, Preethi N; Thulaseedharan, Jissa V; Wesley, Ramani; Jayaprakash, P G; Lalitha, Prema; Pillai, M Radhakrishna

    2012-01-01

    The present study was designed to identify the role of folate, B12, homocysteine, and polymorphisms of methylene tetrahydrofolatereductase (MTHFR) gene in cervical carcinogenesis among 322 women from Kerala, South India. Serum folate, vitamin B12 (chemiluminescence assay), and homocysteine (EIA) along with genetic polymorphisms of MTHFR gene (polymerase chain reaction/restriction fragment length polymorphism) were analyzed for 136 control subjects, 92 low-grade squamous intraepithelial lesions (LSIL) subjects, and 94 invasive cervical cancer cases (ICC). Statistically significant associations between MTHFR polymorphisms, serum homocysteine, and folate levels with cervical carcinogenesis were not evident, but we found that these parameters acted as effect modifiers of serum vitamin B12. The risk estimates observed for B12 became prominent only when there was a deficiency in serum folate levels [LSIL-odds ratio (OR): 14.9 (95% CI: 2.65 to 84.4); ICC-OR = 8.72 (95% CI = 1.55 to 48.8)] or when MTHFR A1298C polymorphic variant was present [LSIL-OR = 9.8 (95% CI = 2.61 to 36.7); ICC-OR = 10.0 (95%CI = 2.5 to 39.3)]. The statistical significance of this effect modification was further studied using an interaction model, where only folate was observed to have an influence on B12 levels as suggested by the odds ratio of 7.11 (95% CI = 0.45 to 111.9) obtained for ICC group, implicating a synergistic role of these 2 vitamins in invasive cervical cancer. PMID:22519865

  18. Homocysteine and vitamin B12 status and iron deficiency anemia in female university students from Gaza Strip, Palestine

    PubMed Central

    Sirdah, Mahmoud Mohammed; Yassin, Maged M.; El Shekhi, Sabreen; Lubbad, Abdel Monem

    2014-01-01

    Objective Nutritional deficiencies are very significant to the overall health of humans at all ages and for both genders, yet in infants, children and women of childbearing age these deficiencies can seriously affect growth and development. The present work is aimed to assess homocysteine and vitamin B12 status in females with iron deficiency anemia from the Gaza Strip. Methods Venous blood samples were randomly collected from 240 female university students (1822 years old) and parameters of the complete blood count, serum ferritin, homocysteine and vitamin B12 were measured. Statistical analysis included the t-test and analysis of variance (ANOVA) using the IBM SPSS software (version 18). Statistical significance was set for p-values <0.05. Results The results revealed that 20.4% of the students have iron deficiency anemia. The mean serum vitamin B12 level in females with iron deficiency anemia (212.962.8pg/mL) was significantly lower than in normal controls (286.957.1pg/mL) and subjects with microcytic anemia and normal ferritin (256.771.1pg/mL). Significantly higher serum homocysteine levels were reported in the iron deficiency anemia group (27.04.6?mol/L) compared to normal controls (15.52.9?mol/L) and in subjects with microcytic anemia and normal ferritin (18.12.7?mol/L). Statistically significant negative correlations were reported for serum homocysteine with serum ferritin, vitamin B12, hemoglobin, and hematocrit levels. Conclusion Important associations were found between serum homocysteine and markers of iron deficiency. Monitoring homocysteine levels might be essential to understand the development of different clinical conditions including anemia. It seems necessary to conduct prospective trials to determine whether treating anemia ameliorates homocysteine levels. PMID:25031061

  19. Maternal omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalizes angiogenic markers in the pup brain at birth.

    PubMed

    Rathod, Richa S; Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-06-01

    Vitamin B12 and omega-3 fatty acids are critical for normal brain development and function and their deficiencies during pregnancy could have adverse effects on cognitive performance in children. Our earlier studies indicate that both maternal vitamin B12 and omega-3 fatty acids influence brain development by regulating the levels of neurotrophins. Literature suggests that there exists a cross talk between neurotrophins like nerve growth factor (NGF) and angiogenic factors like vascular endothelial growth factor (VEGF). It remains to be established whether maternal nutrients like vitamin B12 and omega-3 fatty acids influence the levels of angiogenic markers like VEGF and NGF in the brain of the offspring. Therefore the present study examines the effect of maternal vitamin B12 and omega-3 fatty acids on protein and mRNA levels of VEGF, HIF-1 alpha (hypoxia inducible factor alpha) and NGF in the pup brain at birth. Pregnant Wistar rats were divided into five dietary groups (n=8 each): control, vitamin B12 deficient, vitamin B12 deficient+omega-3 fatty acid, vitamin B12 supplemented, vitamin B12 supplemented+omega-3 fatty acid. At birth the pups were dissected to collect the brain tissue. Maternal vitamin B12 deficiency showed lower (p<0.05) pup brain mRNA and protein levels (p<0.01) of VEGF, higher (p<0.01) HIF-1 alpha protein levels, lower (p<0.05) NGF protein levels while NGF mRNA levels were not altered. Omega-3 fatty acid supplementation to a vitamin B12 deficient group normalized the VEGF mRNA levels, NGF protein levels and HIF-1 alpha protein levels. Vitamin B12 supplementation showed similar protein and mRNA levels of VEGF and NGF as well as HIF-1 alpha protein levels as compared to control. Omega-3 fatty acid supplementation to the vitamin B12 supplemented group showed higher (p<0.01) protein and mRNA levels of NGF but the protein and mRNA levels of VEGF were comparable to control. In conclusion maternal vitamin B12 and omega-3 fatty acids both influence the levels and expression of neurotrophins and angiogenic factors in the offspring brain suggesting a possible benefit of combined maternal supplementation of these vital nutrients. PMID:25889224

  20. Identification and sequence analysis of genes involved in late steps in cobalamin (vitamin B12) synthesis in Rhodobacter capsulatus.

    PubMed Central

    Pollich, M; Klug, G

    1995-01-01

    A 6.4-kb region of a 6.8-kb BamHI fragment carrying Rhodobacter capsulatus genes involved in late steps of cobalamin synthesis has been sequenced. The nucleotide sequence and genetic analysis revealed that this fragment contains eight genes arranged in at least three operons. Five of these eight genes show homology to genes involved in the cobalamin synthesis of Pseudomonas denitrificans and Salmonella typhimurium. The arrangement of these homologous genes differs considerably in the three genera. Upstream of five overlapping genes (named bluFEDCB), a promoter activity could be detected by using lacZ fusions. This promoter shows no regulation by oxygen, vitamin B12 (cobalamin), or cobinamide. Disruption of the bluE gene by a Tn5 insertion (strain AH2) results in reduced expression of the puf and puc operons, which encode pigment-binding proteins of the photosynthetic apparatus. The mutant strain AH2 can be corrected to a wild-type-like phenotype by addition of vitamin B12 or cobinamide dicyanide. Disruption of the bluB gene by an interposon (strain BB1) also disturbs the formation of the photosynthetic apparatus. The mutation of strain BB1 can be corrected by vitamin B12 but not by cobinamide. We propose that a lack of cobalamin results in deregulation and a decreased formation of the photosynthetic apparatus. PMID:7635831

  1. Identification and sequence analysis of genes involved in late steps in cobalamin (vitamin B12) synthesis in Rhodobacter capsulatus.

    PubMed

    Pollich, M; Klug, G

    1995-08-01

    A 6.4-kb region of a 6.8-kb BamHI fragment carrying Rhodobacter capsulatus genes involved in late steps of cobalamin synthesis has been sequenced. The nucleotide sequence and genetic analysis revealed that this fragment contains eight genes arranged in at least three operons. Five of these eight genes show homology to genes involved in the cobalamin synthesis of Pseudomonas denitrificans and Salmonella typhimurium. The arrangement of these homologous genes differs considerably in the three genera. Upstream of five overlapping genes (named bluFEDCB), a promoter activity could be detected by using lacZ fusions. This promoter shows no regulation by oxygen, vitamin B12 (cobalamin), or cobinamide. Disruption of the bluE gene by a Tn5 insertion (strain AH2) results in reduced expression of the puf and puc operons, which encode pigment-binding proteins of the photosynthetic apparatus. The mutant strain AH2 can be corrected to a wild-type-like phenotype by addition of vitamin B12 or cobinamide dicyanide. Disruption of the bluB gene by an interposon (strain BB1) also disturbs the formation of the photosynthetic apparatus. The mutation of strain BB1 can be corrected by vitamin B12 but not by cobinamide. We propose that a lack of cobalamin results in deregulation and a decreased formation of the photosynthetic apparatus. PMID:7635831

  2. Association between dietary intake of folate, vitamin B6, B12 & MTHFR, MTR Genotype and breast cancer risk

    PubMed Central

    Weiwei, Zheng; Liping, Chen; Dequan, Li

    2014-01-01

    Objective: we conducted a case-control study to investigate the association between dietary folate, vitamin B6 and vitamin B12 intake, MTHFR and MTR genotype, and breast cancer risk. Methods: Genotyping for MTHFR C677T and A1298C and MTR A2756G polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) method. The intake of folate, vitamin B6 and vitamin B12 were calculated by each food item from questionnaire. Results: Subjects with breast cancer tended to have more first-degree relatives (?2=30.77, P<0.001) and have high intake of folate (t=2.42, P=0.008) and Vitamin B6 (t=2.94, P=0.002). Compared to the reference group, women with MTHFR 677 TT genotype and T allele had a significantly increased risk of breast cancer, with ORs (95%CI) of 1.8(1.08-2.27) and 1.39(1.02-1.92), respectively. For those who had folate intake?450 ug/day, MTHFR 667TT genotype was associated with a higher risk of breast cancer (OR=2.45, 95% CI=1.09-5.82, P=0.02). Similarly, subjects with Vitamin B6 intake?0.84 mg/day and MTHFR 667T allele genotype was correlated with a marginally increased risk of breast cancer. A significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer (P for interaction was 0.025). Conclusion: This case-control study found a significant association between MTHFR C667T polymorphism, folate intake and vitamin B6 and breast cancer risk, and a significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer. PMID:24639841

  3. Folate, vitamin B6, vitamin B12 and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case-control study.

    PubMed

    Zeng, Fang-Fang; Liu, Yuan-Ting; Lin, Xiao-Ling; Fan, Yu-Ying; Zhang, Xing-Lan; Xu, Chun-Hua; Chen, Yu-Ming

    2016-01-01

    Many studies have suggested that folate-related one-carbon metabolism-related nutrients may play a role in certain cancer risks, but few studies have assessed their associations with the risk for nasopharyngeal carcinoma (NPC). In this study, we investigated the association between four folate-related one-carbon metabolism-related nutrients (folate, vitamin B6, vitamin B12 and methionine) and NPC risk in Chinese adults. A total of 600 patients newly diagnosed (within 3 months) with NPC were individually matched with 600 hospital-based controls by age, sex and household type (urban v. rural). Folate, vitamin B6, vitamin B12 and methionine intakes were measured using a validated seventy-eight-item FFQ. A higher dietary folate or vitamin B6 intake was associated with a lower NPC risk after adjusting for potential confounders. The adjusted OR of NPC for quartiles 2-4 (v. 1) were 066 (95 % CI 048, 091), 052 (95 % CI 037, 074) and 034 (95 % CI 023, 050) (P trend<0001) for folate and 072 (95 % CI 052, 100), 055 (95 % CI 039, 078) and 044 (95 % CI 030, 063) (P trend<0001) for vitamin B6. No significant association with NPC risk was observed for dietary vitamin B12 or methionine intake. The risk for NPC with dietary folate intake was more evident in the participants who were not exposed to toxic substances than in those who were exposed (P interaction=0014). This study suggests that dietary folate and vitamin B6 may be protective for NPC in a high-risk population. PMID:26515433

  4. Establishing safe and potentially efficacious fortification contents for folic acid and vitamin B12.

    PubMed

    Dary, Omar

    2008-06-01

    Determining the micronutrient contents infortified foods depends not only on the health goal (additional intake to complement the diet), but also on ensuring that fortification does not raise micronutrient intakes beyond the Tolerable Upper Intake Level (UL), i.e., the safe limit. Technological incompatibility and cost may also restrict the fortification contents. For folic acid, the limiting factor is safety, while for vitamin B12, it is cost. However, adequate fortification contents that are both safe and efficacious can be estimated for both nutrients. In order to obtain the maximum benefit from the fortification programs, three different formulas responding to three categories of consumption, as specified by the median and 95th percentile of consumption, are proposed. The model presented is based on the estimation of a Feasible Fortification Level (FFL), which then is used to determine the average, minimum, and maximum contents of the nutrients during production, taking into consideration the acceptable variation of the fortification process. Finally, the regulatory parameters, which support standards and enforcement, are calculated by reducing the proportion of the nutrient that is degraded during the usual marketing process of the fortified food. It is expected that this model will establish a common standard for food fortification, and improve the reliability and enforcement procedures of these programs. The model was applied to flours as vehicles for folic acid in the United States, Guatemala, and Chile. Analysis of the data revealed that, with the exception of Chile, where wheat flour consumption is very high and probably within a narrow range, supplementation with folic acid is still needed to cover individuals at the low end of consumption. This is especially true when the difference in flour consumption is too wide, as in the case of Guatemala, where the proportional difference between consumption at the 95th percentile of the nonpoor group is as high as 100 times the consumption at the 5th percentile of the extremely poor group. Adoption of fortification content for staple foods near the safe limit brings together the need of restricting the voluntary addition of the specific nutrient to other foods and to dietary supplements. PMID:18709896

  5. Cerebral venous sinus thrombosis associated with hyperhomocysteinemia due to combined deficiencies of folate and vitamin B12.

    PubMed

    Kanaya, Yuhei; Neshige, Shuichiro; Takemaru, Makoto; Shiga, Yuji; Takeshima, Shinichi; Kuriyama, Masaru

    2016-03-01

    A 63-year-old man was admitted to our hospital because of convulsive seizures. Radiological examinations revealed cerebral venous sinus thrombosis in the anterior part of the superior sagittal sinus. He had marked hyperhomocysteinemia (93.5 nmol/ml) due to combined deficiencies of folate and vitamin B12. He was T/T homozygous for methylene tetrahydrofolate reductase C677T polymorphism. He received a supplement therapy of vitamins. First, he was administered folate orally. After 3 months, the serum level of homocysteine decreased to 22.6 nmol/ml (an 86% reduction), but was still above the normal level. Next, an additional supplement therapy of vitamin B12 lowered the homocysteine level to normal (12.3 nmol/ml) after 4 months. These results showed that the increase of homocysteine levels in this patient was mainly caused by the deficiency of folate. Additionally, acquired risk factors like vitamin deficiencies increased the level of serum homocysteine to almost 100 nmol/ml. PMID:26797484

  6. Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice.

    PubMed

    Ghosh, Shampa; Sinha, Jitendra Kumar; Putcha, Uday Kumar; Raghunath, Manchala

    2016-01-01

    Vitamin B12 deficiency is widely prevalent in women of childbearing age, especially in developing countries. In the present study, through dietary restriction, we have established mouse models of severe and moderate vitamin B12 deficiencies to elucidate the impact on body composition, biochemical parameters, and reproductive performance. Female weanling C57BL/6 mice were fed for 4?weeks: (a) control AIN-76A diet, (b) vitamin B12-restricted AIN-76A diet with pectin as dietary fiber (severe deficiency group, as pectin inhibits vitamin B12 absorption), or (c) vitamin B12-restricted AIN-76A diet with cellulose as dietary fiber (moderate deficiency group as cellulose does not interfere with vitamin B12 absorption). After confirming deficiency, the mice were mated with male colony mice and maintained on their respective diets throughout pregnancy, lactation, and thereafter till 12?weeks. Severe vitamin B12 deficiency increased body fat% significantly, induced adiposity and altered lipid profile. Pregnant dams of both the deficient groups developed anemia. Severe vitamin B12 deficiency decreased the percentage of conception and litter size, pups were small-for-gestational-age and had significantly lower body weight at birth as well as weaning. Most of the offspring born to severely deficient dams died within 24?h of birth. Stress markers and adipocytokines were elevated in severe deficiency with concomitant decrease in antioxidant defense. The results show that severe but not moderate vitamin B12 restriction had profound impact on the physiology of C57BL/6 mice. Oxidative and corticosteroid stress, inflammation and poor antioxidant defense seem to be the probable underlying mechanisms mediating the deleterious effects. PMID:26835453

  7. Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice

    PubMed Central

    Ghosh, Shampa; Sinha, Jitendra Kumar; Putcha, Uday Kumar; Raghunath, Manchala

    2016-01-01

    Vitamin B12 deficiency is widely prevalent in women of childbearing age, especially in developing countries. In the present study, through dietary restriction, we have established mouse models of severe and moderate vitamin B12 deficiencies to elucidate the impact on body composition, biochemical parameters, and reproductive performance. Female weanling C57BL/6 mice were fed for 4 weeks: (a) control AIN-76A diet, (b) vitamin B12-restricted AIN-76A diet with pectin as dietary fiber (severe deficiency group, as pectin inhibits vitamin B12 absorption), or (c) vitamin B12-restricted AIN-76A diet with cellulose as dietary fiber (moderate deficiency group as cellulose does not interfere with vitamin B12 absorption). After confirming deficiency, the mice were mated with male colony mice and maintained on their respective diets throughout pregnancy, lactation, and thereafter till 12 weeks. Severe vitamin B12 deficiency increased body fat% significantly, induced adiposity and altered lipid profile. Pregnant dams of both the deficient groups developed anemia. Severe vitamin B12 deficiency decreased the percentage of conception and litter size, pups were small-for-gestational-age and had significantly lower body weight at birth as well as weaning. Most of the offspring born to severely deficient dams died within 24 h of birth. Stress markers and adipocytokines were elevated in severe deficiency with concomitant decrease in antioxidant defense. The results show that severe but not moderate vitamin B12 restriction had profound impact on the physiology of C57BL/6 mice. Oxidative and corticosteroid stress, inflammation and poor antioxidant defense seem to be the probable underlying mechanisms mediating the deleterious effects. PMID:26835453

  8. Ultra-high performance liquid chromatographic and mass spectrometric analysis of active vitamin B12 in cells of Propionibacterium and fermented cereal matrices.

    PubMed

    Chamlagain, Bhawani; Edelmann, Minnamari; Kariluoto, Susanna; Ollilainen, Velimatti; Piironen, Vieno

    2015-01-01

    A sensitive and selective method is needed to analyse in situ produced vitamin B12 in plant-based materials, potential new dietary sources of vitamin B12. A UHPLC/UV method was developed and validated for the determination of human active vitamin B12 in cell extracts of Propionibacterium freudenreichii subsp. shermanii and after immunoaffinity purification in extracts of cereal matrices fermented by P. freudenreichii. An Acquity HSS T3 C18 column resulted in a baseline separation, a calibration curve of excellent linearity and a low limit of detection (0.075 ng/5 ?L injection). As confirmed by UHPLC-MS, the active vitamin B12 could be separated from pseudovitamin B12. The recovery of vitamin B12 from purified spiked cereal matrices was good (>90%; RSD<5%). A nutritionally relevant amount of active vitamin B12 was produced by P. freudenreichii in cereal malt matrices (up to 1.9 ?g/100 g) in 24h at 28 C. PMID:25053103

  9. Low Maternal Vitamin B12 Status Is Associated with Lower Cord Blood HDL Cholesterol in White Caucasians Living in the UK

    PubMed Central

    Adaikalakoteswari, Antonysunil; Vatish, Manu; Lawson, Alexander; Wood, Catherine; Sivakumar, Kavitha; McTernan, Philip G.; Webster, Craig; Anderson, Neil; Yajnik, Chittaranjan S.; Tripathi, Gyanendra; Saravanan, Ponnusamy

    2015-01-01

    Background and Aims: Studies in South Asian population show that low maternal vitamin B12 associates with insulin resistance and small for gestational age in the offspring. Low vitamin B12 status is attributed to vegetarianism in these populations. It is not known whether low B12 status is associated with metabolic risk of the offspring in whites, where the childhood metabolic disorders are increasing rapidly. Here, we studied whether maternal B12 levels associate with metabolic risk of the offspring at birth. Methods: This is a cross-sectional study of 91 mother-infant pairs (n = 182), of white Caucasian origin living in the UK. Blood samples were collected from white pregnant women at delivery and their newborns (cord blood). Serum vitamin B12, folate, homocysteine as well as the relevant metabolic risk factors were measured. Results: The prevalence of low serum vitamin B12 (<191 ng/L) and folate (<4.6 μg/L) were 40% and 11%, respectively. Maternal B12 was inversely associated with offspring’s Homeostasis Model Assessment 2-Insulin Resistance (HOMA-IR), triglycerides, homocysteine and positively with HDL-cholesterol after adjusting for age and BMI. In regression analysis, after adjusting for likely confounders, maternal B12 is independently associated with neonatal HDL-cholesterol and homocysteine but not triglycerides or HOMA-IR. Conclusions: Our study shows that low B12 status is common in white women and is independently associated with adverse cord blood cholesterol. PMID:25849948

  10. Human gut microbes use multiple transporters to distinguish vitamin B12 analogs and compete in the gut

    PubMed Central

    Degnan, Patrick H.; Barry, Natasha A.; Mok, Kenny C.; Taga, Michiko E.; Goodman, Andrew L.

    2014-01-01

    Summary Genomic and metagenomic sequencing efforts, including human microbiome projects, reveal that microbes often encode multiple systems that appear to accomplish the same task. Whether these predictions reflect actual functional redundancies is unclear. We report that the prominent human gut symbiont Bacteroides thetaiotaomicron employs three functional, homologous vitamin B12 transporters that in at least two cases confer a competitive advantage in the presence of distinct B12 analogs (corrinoids). In the mammalian gut, microbial fitness can be determined by the presence or absence of a single transporter. The total number of distinct corrinoid transporter families in the human gut microbiome likely exceeds those observed in B. thetaiotaomicron by an order of magnitude. These results demonstrate that human gut microbes use elaborate mechanisms to capture and differentiate corrinoids in vivo and that apparent redundancies observed in these genomes can instead reflect hidden specificities that determine whether a microbe will colonize its host. PMID:24439897

  11. Folate, vitamin B12, and vitamin B6 status of a group of high socioeconomic status women in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort.

    PubMed

    Fayyaz, Faiqa; Wang, Flora; Jacobs, René L; O'Connor, Deborah L; Bell, Rhonda C; Field, Catherine J

    2014-12-01

    Folic acid supplementation and food fortification policies have improved folate status in North American women of child bearing age. Recent studies have reported the possible inadequacy of vitamin B12 and B6 in the etiology of neural tube defects in folate-fortified populations. The aims of this study were to describe folate status and its relationship to supplementation and to assess vitamin B12 and B6 status in a cohort of pregnant women. Supplement intake data were collected in each trimester from the first cohort (n = 599) of the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Red blood cell folate (RBCF) and plasma folate, holotranscobalamin, and pyridoxal 5-phosphate were measured. Overt folate deficiency was rare (3%) but 24% of women in their first trimester had suboptimal RBCF concentration (<906 nmol·L(-1)). The proportion of the cohort in this category declined substantially in second (9%) and third (7%) trimesters. High RBCF (>1360 nmol·L(-1)) was observed in approximately half of the women during each pregnancy trimester. Vitamin B12 and B6 deficiencies were rare (<1% of the cohort). Women consuming folic acid supplements above the upper level had significantly higher RBCF and plasma folate concentrations. In conclusion, the prevalence of vitamin B12 and B6 deficiency was very low. A quarter of the women had suboptimal folate status in the first trimester of pregnancy and over half the women had abnormally high RBCF, suggesting that supplementation during pregnancy is not appropriate in a cohort of women considered to be healthy and a low risk for nutritional deficiencies. PMID:25386981

  12. Determination of Vitamin B12 in Infant, Adult, and Pediatric Formulas by HPLC-UV and Column Switching: Collaborative Study, Final Action 2011.10.

    PubMed

    Butler-Thompson, Linda D; Jacobs, Wesley A; Schimpf, Karen J

    2015-01-01

    AOAC First Action Method 2011.10, Vitamin B12 in Infant and Pediatric Formulas and Adult Nutritionals, was collaboratively studied. This method uses a pH 4.5 sodium acetate buffer and potassium cyanide at 105°C to extract and convert all biologically active forms of vitamin B12 present to cyanocobalamin; octylsilyl (C8) or C18 SPE cartridges to purify and concentrate cyanocobalamin; a combination of size-exclusion and RPLC to isolate cyanocobalamin; and visible absorbance at 550 nm to detect and quantitate cyanocobalamin in infant, pediatric, and adult nutritionals with vitamin B12 concentrations greater than 0.025 μg/100 g ready-to-feed (RTF) liquid. During this collaborative study, nine to 11 laboratories from eight different countries analyzed blind duplicates of 12 infant, pediatric, and adult nutritional formulas. Per the AOAC Expert Review Panel (ERP) on Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) Nutrient Methods the method demonstrated acceptable repeatability and reproducibility and met SPIFAN Standard Method Performance Requirements (SMPRs®) for the majority of product matrixes analyzed. Vitamin B12 SPIFAN SMPRs for repeatability were ≤15% RSD at vitamin B12 concentrations of 0.01 μg/100 g RTF liquid and ≤7% RSD at vitamin B12 concentrations of 0.2-5.0 μg/100 g RTF liquid. Vitamin B12 SPIFAN SMPRs for reproducibility were ≤11% RSD in products with vitamin B12 concentrations ranging from 0.3 to 5.0 μg/100 g RTF liquid. During this collaborative study, the RSDr ranged from 2.98 to 9.77%, and the RSDR ranged from 3.54 to 19.5%. During previous single-laboratory validation studies, the method LOQ was estimated to be 0.025 μg/100 g RTF liquid. PMID:26651579

  13. Maternal Folate and Vitamin B12 Status and Neural Tube Defects in Northern Iran: A Case Control Study

    PubMed Central

    Mobasheri, Elahm; Keshtkar, Abbasali; Golalipour, Mohammad-Jafar

    2010-01-01

    Objective This study was conducted to determine the serum level of folic acid and vitamin B12 in neural tube defects pregnancies (NTD) and healthy controls in Northern Iran. Methods This case-control study was performed on women with neural tube defects pregnancies and controls with unaffected pregnancies in Northern Iran during 2006. Twenty three pregnant women whose pregnancies were diagnosed as NTD by a second-trimester ultrasonographic examination were recruited as cases. The control group (n=23) consisted of women who were selected among socio-economic status (SES) matched women who had a normal targeted ultrasound during the second trimester with documented normal fet al outcome. Fetal NTD was suspected with targeted second-trimester ultrasound during the 16th week of gestation and confirmed with high maternal serum ?-fetoprotein levels. Folate, vitamin B12, homocysteine and alpha fetoprotein were evaluated after target ultrasonography. Findings Serum alpha fetoprotein level (meanSD) in cases and controls was 120.264.1 and 5033.5 iu/ml, respectively (P<0.05). The meanSD folate in cases and controls was 8.44.2 versus 9.34.2 ng/ml, respectively. This difference was not significant. Folate deficiency was found in 30.4% of the cases and 13% of the controls (OR=2.9, 95%: 0.5419.8). Vitamin B12 deficiency was found in 13% of cases and 17.7% of the controls (OR=0.7, 95%: 0.1-4.9). Conclusion This study showed that the probability of having a newborn with NTDs in maternal folate deficiency is three times higher than with normal folate in Northern Iran. PMID:23056699

  14. A Stability-Indicating HPLC Method for the Determination of Nitrosylcobalamin (NO-Cbl), a Novel Vitamin B12 Analog.

    PubMed

    Dunphy, Michael J; Sysel, Annette M; Lupica, Joseph A; Griffith, Kristie; Sherrod, Taylor; Bauer, Joseph A

    2014-04-01

    Nitrosylcobalamin (NO-Cbl), a novel vitamin B12 analog and anti-tumor agent, functions as a biologic 'Trojan horse', utilizing the vitamin B12 transcobalamin II transport protein and cell surface receptor to specifically target cancer cells. a stability-indicating HPLC method was developed for the detection of NO-Cbl during forced degradation studies. This method utilized an ascentis(®) RP-amide (150 mm × 4.6 mm, 5 μm) column at 35 °C with a mobile phase (1.0 mL min(-1)) combining a gradient of methanol and an acetate buffer at pH 6.0. Detection wavelengths of 450 and 254 nm were used to detect corrin and non-corrin-based products, respectively. NO-Cbl, synthesized from hydroxocobalamin and pure nitric oxide gas, was subjected to degradative stress conditions including oxidation, hydrolysis and thermal and radiant energy challenge. The method was validated by assessing linearity, accuracy, precision, detection and quantitation limits and robustness. The method was applied successfully for purity assessment of synthesized NO-Cbl and for the determination of NO-Cbl during kinetic studies in aqueous solution and in solid-state degradation assessments. This HPLC method is suitable for the separation of cobalamins in aqueous and methanolic solutions, for routine detection of NO-Cbl and for purity assessment of synthesized NO-Cbl. additionally, this method has potential application in identification and monitoring of diseases involving altered nitric oxide homeostasis where vitamin B12 therapy is utilized to scavenge excess nitric oxide, subsequently resulting in the in vivo production of NO-Cbl. PMID:24855323

  15. A Stability-Indicating HPLC Method for the Determination of Nitrosylcobalamin (NO-Cbl), a Novel Vitamin B12 Analog

    PubMed Central

    Dunphy, Michael J.; Sysel, Annette M.; Lupica, Joseph A.; Griffith, Kristie; Sherrod, Taylor

    2014-01-01

    Nitrosylcobalamin (NO-Cbl), a novel vitamin B12 analog and anti-tumor agent, functions as a biologic Trojan horse, utilizing the vitamin B12 transcobalamin II transport protein and cell surface receptor to specifically target cancer cells. a stability-indicating HPLC method was developed for the detection of NO-Cbl during forced degradation studies. This method utilized an ascentis RP-amide (150 mm 4.6 mm, 5 ?m) column at 35 C with a mobile phase (1.0 mL min?1) combining a gradient of methanol and an acetate buffer at pH 6.0. Detection wavelengths of 450 and 254 nm were used to detect corrin and non-corrin-based products, respectively. NO-Cbl, synthesized from hydroxocobalamin and pure nitric oxide gas, was subjected to degradative stress conditions including oxidation, hydrolysis and thermal and radiant energy challenge. The method was validated by assessing linearity, accuracy, precision, detection and quantitation limits and robustness. The method was applied successfully for purity assessment of synthesized NO-Cbl and for the determination of NO-Cbl during kinetic studies in aqueous solution and in solid-state degradation assessments. This HPLC method is suitable for the separation of cobalamins in aqueous and methanolic solutions, for routine detection of NO-Cbl and for purity assessment of synthesized NO-Cbl. additionally, this method has potential application in identification and monitoring of diseases involving altered nitric oxide homeostasis where vitamin B12 therapy is utilized to scavenge excess nitric oxide, subsequently resulting in the in vivo production of NO-Cbl. PMID:24855323

  16. Multiple vascular abnormalities and a paradoxical combination of vitamin B12 deficiency and thrombocytosis in a case with POEMS syndrome.

    PubMed

    Lewerenz, J; Gocht, A; Hoeger, P H; von den Driesch, P; Eckert, B; Lamszus, K; Stuerenburg, H-J; Methner, A

    2003-12-01

    POEMS/Crow-Fukase syndrome is a rare multisystem disorder associated with elevated vascular endothelial growth factor (VEGF), which clinically presents with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. We report a case of POEMS syndrome due to a gammopathy of undetermined significance with thrombocytosis, vitamin B(12) deficiency, highly elevated VEGF and in addition to glomeruloid angiomas two previously undescribed proliferative vascular lesions: a spinal arteriovenous fistula and a plexogenic pulmonary arteriopathy, which ultimately resulted in lethal pulmonary hypertension. We assume that the high VEGF levels caused the vascular abnormalities observed in our patient. PMID:14673584

  17. Industrial vitamin B12 production by Pseudomonas denitrificans using maltose syrup and corn steep liquor as the cost-effective fermentation substrates.

    PubMed

    Xia, Wei; Chen, Wei; Peng, Wei-Fu; Li, Kun-Tai

    2015-06-01

    The aerobic Pseudomonas denitrificans is widely used for industrial and commercial vitamin B12 fermentation, due to its higher productivity compared to the anaerobic vitamin B12-producing microorganisms. This paper aimed to develop a cost-effective fermentation medium for industrial vitamin B12 production by P. denitrificans in 120,000-l fermenter. It was found that maltose syrup (a low-cost syrup from corn starch by means of enzymatic or acid hydrolysis) and corn steep liquor (CSL, a by-product of starch industry) were greatly applicable to vitamin B12 production by P. denitrificans. Under the optimal fermentation medium performed by response surface methodology, 198.27 ± 4.60 mg/l of vitamin B12 yield was obtained in 120,000-l fermenter, which was close to the fermentation with the refined sucrose (198.80 mg/l) and was obviously higher than that obtained under beet molasses utilization (181.75 mg/l). Therefore, maltose syrups and CSL were the efficient and economical substrates for industrial vitamin B12 fermentation by P. denitrificans. PMID:25561346

  18. Effect of Folic Acid, Betaine, Vitamin B6, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine

    PubMed Central

    Rajdl, Daniel; Racek, Jaroslav; Trefil, Ladislav; Stehlik, Pavel; Dobra, Jana; Babuska, Vaclav

    2016-01-01

    Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. Methods: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B12 or B6). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B12 and vitamin B6 supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration. PMID:26771632

  19. The entropic contributions in vitamin B12 enzymes still reflect the electrostatic paradigm

    PubMed Central

    Schopf, Patrick; Mills, Matthew J. L.; Warshel, Arieh

    2015-01-01

    The catalytic power of enzymes containing coenzyme B12 has been, in some respects, the last bastion for the strain hypothesis. Our previous study of this system established by a careful sampling that the major part of the catalytic effect is due to the electrostatic interaction between the ribose of the ado group and the protein and that the strain contribution is very small. This finding has not been sufficiently appreciated due to misunderstandings of the power of the empirical valence bond (EVB) calculations and the need of sufficient sampling. Furthermore, some interesting new experiments point toward entropic effects as the source of the catalytic power, casting doubt on the validity of the electrostatic idea, at least, in the case of B12 enzymes. Here, we focus on the observation of the entropic effects and on analyzing their origin. We clarify that our EVB approach evaluates free energies rather than enthalpies and demonstrate by using the restraint release (RR) approach that the observed entropic contribution to the activation barrier is of electrostatic origin. Our study illustrates the power of the RR approach by evaluating the entropic contributions to catalysis and provides further support to our paradigm for the origin of the catalytic power of B12 enzymes. Overall, our study provides major support to our electrostatic preorganization idea and also highlights the basic requirements from ab initio quantum mechanics/molecular mechanics calculations of activation free energies of enzymatic reactions. PMID:25805820

  20. The entropic contributions in vitamin B12 enzymes still reflect the electrostatic paradigm.

    PubMed

    Schopf, Patrick; Mills, Matthew J L; Warshel, Arieh

    2015-04-01

    The catalytic power of enzymes containing coenzyme B12 has been, in some respects, the "last bastion" for the strain hypothesis. Our previous study of this system established by a careful sampling that the major part of the catalytic effect is due to the electrostatic interaction between the ribose of the ado group and the protein and that the strain contribution is very small. This finding has not been sufficiently appreciated due to misunderstandings of the power of the empirical valence bond (EVB) calculations and the need of sufficient sampling. Furthermore, some interesting new experiments point toward entropic effects as the source of the catalytic power, casting doubt on the validity of the electrostatic idea, at least, in the case of B12 enzymes. Here, we focus on the observation of the entropic effects and on analyzing their origin. We clarify that our EVB approach evaluates free energies rather than enthalpies and demonstrate by using the restraint release (RR) approach that the observed entropic contribution to the activation barrier is of electrostatic origin. Our study illustrates the power of the RR approach by evaluating the entropic contributions to catalysis and provides further support to our paradigm for the origin of the catalytic power of B12 enzymes. Overall, our study provides major support to our electrostatic preorganization idea and also highlights the basic requirements from ab initio quantum mechanics/molecular mechanics calculations of activation free energies of enzymatic reactions. PMID:25805820

  1. Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and risk of childhood brain tumors.

    PubMed

    Greenop, Kathryn R; Miller, Margaret; de Klerk, Nicholas H; Scott, Rodney J; Attia, John; Ashton, Lesley J; Dalla-Pozza, Luciano; Bower, Carol; Armstrong, Bruce K; Milne, Elizabeth

    2014-01-01

    Childhood brain tumors (CBT) are the second most common childhood cancers, yet their etiology is largely unknown. We investigated whether maternal gestational intake of folate and vitamins B6 and B12 was associated with CBT risk in a nationwide case-control study conducted 2005-2010. Case children 0-14 years were recruited from all 10 Australian pediatric oncology centers. Control children were recruited by national random digit dialing, frequency matched to cases on age, sex, and state of residence. Dietary intake was ascertained using food frequency questionnaires and adjusted for total energy intake. Data from 293 case and 726 control mothers were analyzed using unconditional logistic regression. The odds ratio (OR) for the highest versus lowest tertile of folate intake was 0.70 [95% confidence interval (CI): 0.48, 1.02]. The ORs appeared lower in mothers who drank alcohol during pregnancy (OR = 0.45, 95% CI: 0.22, 0.93), mothers who took folic acid (OR = 0.67, 95% CI: 0.42, 1.06) or B6/B12 supplements (OR = 0.51, 95% CI: 0.25, 1.06) and in children younger than 5 years (OR = 0.50, 95% CI: 0.27, 0.93). These findings are consistent with folate's crucial role in maintenance of genomic integrity and DNA methylation. Dietary intake of B6 and B12 was not associated with risk of CBT. PMID:24897174

  2. Effects of folate and vitamin B12 on cognitive function in adult and elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related neurocognitive disorders, primarily Alzheimer’s disease (AD) and Parkinson’s disease (PD), have a major impact on health and well-being. Separate lines of evidence have suggested that B vitamin status may be associated with risk and progression of AD and PD. This report summarizes the ev...

  3. The influence of vitamin B12 supplementation on the level of white blood cells and lymphocytes phenotype in rats fed a low-protein diet

    PubMed Central

    Lewicka, Aneta; Kalicki, Boles?aw; K?os, Anna; Bertrandt, Jerzy; Zdanowski, Robert

    2014-01-01

    Protein malnutrition has a negative effect on body composition and some blood parameters, especially in the young growing organism. One of nutritional factors which could protect against negative consequences of protein deficiency may be B group vitamins. The aim of the study was to investigate the effect of vitamin B12 supplementation on the immune system in rats fed a standard and a low-protein diet. Rats were fed a control (20% of energy from protein) or a protein-deficient diet (4.5% of energy from protein). Half of animals in each group were additionally supplemented with vitamin B12 (300% of the daily intake). The white blood cells analysis and lymphocytes immunophenotyping (number and percentage) were performed. Low-protein diets caused disturbances in WBC and lymphocyte subpopulations in both short- (30-day) as well as long-term periods (90-day). Vitamin B12 supplementation significantly reduced the negative impact of protein malnutrition after 30 days, however had no effect on long-term malnutrition. Furthermore, vitamin B12 addition in rats fed a control diet did not affect the studied parameters. This observation opens the promise of use of vitamin B12 supplementation to improve immune system parameters in protein malnourished organisms. PMID:26155157

  4. Higher prevalence of metformin-induced vitamin B12 deficiency in sulfonylurea combination compared with insulin combination in patients with type 2 diabetes: a cross-sectional study.

    PubMed

    Kang, Donghoon; Yun, Jae-Seung; Ko, Sun-Hye; Lim, Tae-Seok; Ahn, Yu-Bae; Park, Yong-Moon; Ko, Seung-Hyun

    2014-01-01

    Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes. We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period. A total of 394 patients with type 2 diabetes treated with metformin and sulfonylurea (S+M group, n = 299) or metformin and insulin (I+M group, n = 95) were consecutively recruited. The vitamin B12 and folate levels were quantified using the chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12≤300 pg/mL without folate deficiency (folate>4 ng/mL). The mean age of and duration of diabetes in the subjects were 59.4±10.5 years and 12.2±6.7 years, respectively. The mean vitamin B12 level of the total population was 638.0±279.6 pg/mL. The mean serum B12 levels were significantly lower in the S+M group compared with the I+M group (600.0±266.5 vs. 757.7±287.6 pg/mL, P<0.001). The prevalence of vitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001). After adjustment for various factors, such as age, sex, diabetic duration, duration or daily dose of metformin, diabetic complications, and presence of anemia, sulfonylurea use was a significant independent risk factor for B12 deficiency (OR = 4.74, 95% CI 1.41-15.99, P = 0.012). In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels. PMID:25299054

  5. Vitamin B12-Impaired Metabolism Produces Apoptosis and Parkinson Phenotype in Rats Expressing the Transcobalamin-Oleosin Chimera in Substantia Nigra

    PubMed Central

    Orozco-Barrios, Carlos Enrique; Battaglia-Hsu, Shyue-Fang; Arango-Rodriguez, Martha Ligia; Ayala-Davila, Jose; Chery, Celine; Alberto, Jean-Marc; Schroeder, Henry; Daval, Jean-Luc

    2009-01-01

    Background Vitamin B12 is indispensable for proper brain functioning and cytosolic synthesis of S-adenosylmethionine. Whether its deficiency produces effects on viability and apoptosis of neurons remains unknown. There is a particular interest in investigating these effects in Parkinson disease where Levodopa treatment is known to increase the consumption of S-adenosylmethionine. To cause deprivation of vitamin B12, we have recently developed a cell model that produces decreased synthesis of S-adenosylmethionine by anchoring transcobalamin (TCII) to the reticulum through its fusion with Oleosin (OLEO). Methodology Gene constructs including transcobalamin-oleosin (TCII-OLEO) and control constructs, green fluorescent protein-transcobalamin-oleosin (GFP-TCII-OLEO), oleosin-transcobalamin (OLEO-TCII), TCII and OLEO were used for expression in N1E-115 cells (mouse neuroblastoma) and in substantia nigra of adult rats, using a targeted transfection with a Neurotensin polyplex system. We studied the viability and the apoptosis in the transfected cells and targeted tissue. The turning behavior was evaluated in the rats transfected with the different plasmids. Principal Findings The transfection of N1E-115 cells by the TCII-OLEO-expressing plasmid significantly affected cell viability and increased immunoreactivity of cleaved Caspase-3. No change in propidium iodide uptake (used as a necrosis marker) was observed. The transfected rats lost neurons immunoreactive to tyrosine hydroxylase. The expression of TCII-OLEO was observed in cells immunoreactive to tyrosine hydroxylase of the substantia nigra, with a superimposed expression of cleaved Caspase-3. These cellular and tissular effects were not observed with the control plasmids. Rats transfected with TCII-OLEO expressing plasmid presented with a significantly higher number of turns, compared with those transfected with the other plasmids. Conclusions/Significance In conclusion, the TCII-OLEO transfection was responsible for apoptosis in N1E-115 cells and rat substantia nigra and for Parkinson-like phenotype. This suggests evaluating whether vitamin B12 deficit could aggravate the PD in patients under Levodopa therapy by impairing S-adenosylmethionine synthesis in substantia nigra. PMID:20027219

  6. Leukocyte Telomere Length is Associated With Serum Vitamin B12 and Homocysteine Levels in Older Adults With the Presence of Systemic Inflammation

    PubMed Central

    2016-01-01

    Folate, vitamin B12, and homocysteine (HCY) are involved in the metabolism of nucleic acid precursors and it has been hypothesized that they also influence telomere length, a biomarker of aging. However, previous studies have reported inconsistent findings, and data for older adults are limited. Our study aimed to evaluate associations between leukocyte telomere length (LTL) and serum folate, vitamin B12, and HCY levels among adults aged 55 years and over. In a cross-sectional study in 798 men and women aged 55-79 years, serum folate, vitamin B12, and HCY levels were measured using chemiluminescent immunometric assays, and relative LTL was assessed using quantitative real-time polymerase chain reaction. To evaluate associations between LTL and serum folate, vitamin B12, and HCY levels, multiple linear regression models were used. In multiple models adjusted for age, sex, serum high sensitive C-reactive protein (hs-CRP) levels, and other potential confounding factors, we found no association between LTL and serum folate, vitamin B12, and HCY levels. However, we did find a significant inverse association between HCY levels and LTL in participants with serum hs-CRP levels of ≥ 2 mg/L (p < 0.05). Moreover, there was a trend toward an association between HCY and vitamin B12 levels in these individuals (p = 0.08). In those with serum hs-CRP levels of < 2 mg/L, HCY was inversely associated with vitamin B12 levels (p < 0.001) and had no association with LTL. Our findings suggest that increased serum HCY levels, when combined with the presence of systemic inflammation, may play a role in accelerating biological aging. PMID:26839872

  7. Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial

    PubMed Central

    Kvestad, Ingrid; Taneja, Sunita; Kumar, Tivendra; Hysing, Mari; Refsum, Helga; Yajnik, Chittaranjan S.; Bhandari, Nita; Strand, Tor A.

    2015-01-01

    Objectives Deficiencies of vitamin B12 and folate are associated with delayed development and neurological manifestations. The objective of this study was to measure the effect of daily supplementation of vitamin B12 and/or folic acid on development in young North Indian children. Methods In a randomized, double blind trial, children aged six to 30 months, received supplement with placebo or vitamin B12 and/or folic acid for six months. Children were allocated in a 1:1:1:1 ratio in a factorial design and in blocks of 16. We measured development in 422 children by the Ages and Stages Questionnaire 3rd ed. at the end of the intervention. Results Compared to placebo, children who received both vitamin B12 and folic acid had 0.45 (95% CI 0.19, 0.73) and 0.28 (95% CI 0.02, 0.54) higher SD-units in the domains of gross motor and problem solving functioning, respectively. The effect was highest in susceptible subgroups consisting of stunted children, those with high plasma homocysteine (> 10 μmol/L) or in those who were younger than 24 at end study. With the exception of a significant improvement on gross motor scores by vitamin B12 alone, supplementation of either vitamin alone had no effect on any of the outcomes. Conclusion Our findings suggest that supplementation of vitamin B12 and folic acid benefit development in North Indian Children. Trial Registration ClinicalTrials.gov NCT00717730 PMID:26098427

  8. Conformational Cycle of the Vitamin B12 ABC Importer in Liposomes Detected by Double Electron-Electron Resonance (DEER)*

    PubMed Central

    Joseph, Benesh; Korkhov, Vladimir M.; Yulikov, Maxim; Jeschke, Gunnar; Bordignon, Enrica

    2014-01-01

    Double electron-electron resonance is used here to investigate intermediates of the transport cycle of the Escherichia coli vitamin B12 ATP-binding cassette importer BtuCD-F. Previously, we showed the ATP-induced opening of the cytoplasmic gate I in TM5 helices, later confirmed by the AMP-PNP-bound BtuCD-F crystal structure. Here, other key residues are analyzed in TM10 helices (positions 307 and 322) and in the cytoplasmic gate II, i.e. the loop between TM2 and TM3 (positions 82 and 85). Without BtuF, binding of ATP induces detectable changes at positions 307 and 85 in BtuCD in liposomes. Together with BtuF, ATP triggers the closure of the cytoplasmic gate II in liposomes (reported by both positions 82 and 85). This forms a sealed cavity in the translocation channel in agreement with the AMP-PNPBtuCD-F x-ray structure. When vitamin B12 and AMP-PNP are simultaneously present, the extent of complex formation is reduced, but the short 8282 interspin distance detected indicates that the substrate does not affect the closed conformation of this gate. The existence of the BtuCD-F complex under these conditions is verified with spectroscopically orthogonal nitroxide and Gd(III)-based labels. The cytoplasmic gate II remains closed also in the vanadate-trapped state, but it reopens in the ADP-bound state of the complex. Therefore, we suggest that the substrate likely trapped in ATPBtuCD-F can be released after ATP hydrolysis but before the occluded ADP-bound conformation is reached. PMID:24362024

  9. MTHFR polymorphisms involved in vitamin B12 deficiency associated with atrophic gastritis.

    PubMed

    Palladino, Mariangela; Chiusolo, Patrizia; Reddiconto, Giovanni; Marietti, Sara; De Ritis, Daniela; Leone, Giuseppe; Sica, Simona

    2009-10-01

    Genetic polymorphisms affecting methylentetrahydrofolate reductase (MTHFR) activity may influence hematological and neurological dysfunction in cobalamin-deficient patients. We studied the prevalence of C677T and A1298C polymorphisms by analyzing genomic DNA in 30 cobalamin-deficient patients. No significant difference was found in 677 and 1298 genotype distribution with respect to hematological parameters, B12 and folate levels, and neurological symptoms. The two MTHFR polymorphisms were not protective against anemia or neurological dysfunction in patients with cobalamin deficiency; however, we found evidence of a significant increase in atrophic gastritis in the 677TT group (P = 0.009) but not for the 1298CC genotype. Based on observations that inadequate cobalamin intake and reduced MTHFR activity might be significant risk factors for gastric cancer, and the increased risk of gastric cancer shown in patients affected by atrophic gastritis, we speculate that concomitant atrophic gastritis and impaired MTHFR function could have a role in the development of gastric cancer. PMID:19521764

  10. Lower Risk of Cervical Intraepithelial Neoplasia in Women with High Plasma Folate and Sufficient Vitamin B12 in the Post-Folic Acid Fortification Era

    PubMed Central

    Piyathilake, Chandrika J.; Macaluso, Maurizio; Alvarez, Ronald D.; Bell, Walter C.; Heimburger, Douglas C.; Partridge, Edward E.

    2016-01-01

    The purpose of this study was to determine the influence of plasma folate and vitamin B12 concentrations on cervical cancer risk in the U.S. after the folic acid fortification era. The study included 376 premenopausal women of childbearing age who tested positive for infections with high-risk (HR) human papillomaviruses (HPVs) and were diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN 2+, cases) or ≤CIN 1 (noncases). CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified plasma folate concentrations combined with plasma B12 concentrations as the independent predictors of primary interest, adjusting for age, race, education, smoking, parity, number of lifetime male sexual partners, use of contraceptives, waist circumference, physical activity, healthy eating index, and circulating concentrations of vitamins A, C, tocopherol, and total carotene. Women with supraphysiologic concentrations of plasma folate (>19.8 ng/mL) who also had sufficient plasma vitamin B12 (≥200.6 pg/mL) had 70% lower odds of being diagnosed with CIN 2+ (P = 0.04) when compared with women with plasma folate of ≤19.8 ng/mL and plasma vitamin B12 of <200.6 pg/mL. Our results do not corroborate the concern that supraphysiologic plasma folate concentrations seen in the post-U.S. folic acid fortification era increase the risk of CIN in premenopausal women of childbearing age. In fact, higher folate is associated with significantly lower risk of CIN, especially when vitamin B12 is sufficient, demonstrating the importance of vitamin B12 in the high-folate environment created by the folic acid fortification program. PMID:19542191

  11. Analytical Determination of Vitamin B12 Content in Infant and Toddler Milk Formulas by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

    PubMed Central

    Lee, Jung-Hoon; Shin, Jin-Ho; Park, Jung-Min; Kim, Ha-Jung; Ahn, Jang-Hyuk; Kwak, Byung-Man; Kim, Jin-Man

    2015-01-01

    The development of a sample preparation method and optimization of the analytical instrumentation conditions were performed for the determination of the vitamin B12 content in emulsified baby foods sold on the Korea market. After removal of the milk protein and fats by chloroform extraction and centrifugation, the vitamin B12 was water extracted from the sample. Following filtration of the solution through a nylon filter, the water-soluble extract was purified by solid-phase extraction using a Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). The solution eluted from the cartridge was dried under a stream of nitrogen gas and reconstituted with 1 mL of water. The sample solution was injected into an LC-MS/MS system after optimizing the mobile phase for vitamin B12 detection. The calibration curve showed good linearity with the coefficient of correlation (r2) value of 0.9999. The limit of detection was 0.03 µg/L and the limit of quantitation was 0.1 µg/L. The method of detection limit was 0.02 µg/kg. The vitamin B12 recovery from a spiking test was 99.62% for infant formula and 99.46% for cereal-based baby food. The sample preparation method developed in this study would be appropriate for the rapid determination of the vitamin B12 content in infant formula and baby foods with emulsified milk characteristics. The ability to obtain stable results more quickly and efficiently would also allow governments to exercise a more extensive quality control inspection and monitoring of products expected to contain vitamin B12. This method could be implemented in laboratories that require time and labor saving. PMID:26877636

  12. Maternal dietary intake of folate, vitamin B12 and MTHFR 677C>T genotype: their impact on newborn's anthropometric parameters.

    PubMed

    Torres-Snchez, Luisa; Lpez-Carrillo, Lizbeth; Blanco-Muoz, Julia; Chen, Jia

    2014-09-01

    In this study, we evaluated the effects of dietary intake of vitamin B12 and folate during pregnancy and their interactions with maternal polymorphism of MTHFR (677C>T; 1298A>C) on intrauterine development. Anthropometric parameters were obtained from 231 newborns that belong to a prospective birth cohort in Morelos, Mexico. Maternal dietary intake of vitamin B12 and folate was assessed using a semi-quantitative questionnaire administered during the first and third trimesters of the pregnancy. Maternal MTHFR 677C>T and 1298 A>C genotypes were determined by PCR-RFLP. The associations between deficient dietary intake of vitamin B12 (<2.0?g/d) and folate (<400?g/d) in the first and third trimesters and maternal polymorphisms of MTHFR on anthropometric parameters at birth were estimated using a multivariate linear regression model. During pregnancy, the deficient dietary intake was roughly 60% for folate and 19% for vitamin B12. Allelic frequencies of 677T and 1298C were 59 and 10%, respectively. After adjusting for confounders, deficiency in maternal dietary intake of vitamin B12 (<2.0?g/d) was associated with a significant reduction in length (?~-2.4; 95% CI -4.3; -0.6) and length-for-age at birth (?~-1.2; 95% CI -2.3; -0.1) among infants whose mothers were carriers of the 677TT genotype (p for interaction=0.02). In contrast, no association was observed between deficiency in maternal dietary intake of folate (<400?g/d) and any anthropometric parameter of newborns. These results suggest that supplementation with vitamin B12 during pregnancy could have a favorable impact on intrauterine fetal development mainly in populations that are genetically susceptible. PMID:25173112

  13. Direct exchange of vitamin B12 is demonstrated by modelling the growth dynamics of algalbacterial cocultures

    PubMed Central

    Grant, Matthew AA; Kazamia, Elena; Cicuta, Pietro; Smith, Alison G

    2014-01-01

    The growth dynamics of populations of interacting species in the aquatic environment is of great importance, both for understanding natural ecosystems and in efforts to cultivate these organisms for industrial purposes. Here we consider a simple two-species system wherein the bacterium Mesorhizobium loti supplies vitamin B12 (cobalamin) to the freshwater green alga Lobomonas rostrata, which requires this organic micronutrient for growth. In return, the bacterium receives photosynthate from the alga. Mathematical models are developed that describe minimally the interdependence between the two organisms, and that fit the experimental observations of the consortium. These models enable us to distinguish between different mechanisms of nutrient exchange between the organisms, and provide strong evidence that, rather than undergoing simple lysis and release of nutrients into the medium, M. loti regulates the levels of cobalamin it produces, resulting in a true mutualism with L. rostrata. Over half of all microalgae are dependent on an exogenous source of cobalamin for growth, and this vitamin is synthesised only by bacteria; it is very likely that similar symbiotic interactions underpin algal productivity more generally. PMID:24522262

  14. Vitamin B12 status in older adults living in Ontario long-term care homes: prevalence and incidence of deficiency with supplementation as a protective factor.

    PubMed

    Pfisterer, Kaylen J; Sharratt, Mike T; Heckman, George G; Keller, Heather H

    2016-02-01

    Vitamin B12 (B12) deficiency, although treatable, impacts up to 43% of community-living older adults; long-term care (LTC) residents may be at greater risk. Recommendations for screening require further evidence on prevalence and incidence in LTC. Small, ungeneralizable samples provide a limited perspective on these issues. The purposes of this study were to report prevalence of B12 deficiency at admission to LTC, incidence 1 year post-admission, and identify subgroups with differential risk. This multi-site (8), retrospective prevalence study used random proportionate sampling of resident charts (n = 412). Data at admission extracted included demographics, B12 status, B12 supplementation, medications, diagnoses, functional independence, cognitive performance, and nutrition. Prevalence at admission of B12 deficiency (<156 pmol/L) was 13.8%; 47.6% had normal B12 (>300 pmol/L). One year post-admission incidence was 4%. Better B12 status was significantly associated with supplementation use prior to LTC admission. Other characteristics were not associated with status. This work provides a better estimate of B12 deficiency prevalence than previously available for LTC, upon which to base protocols and policy. Prospective studies are needed to establish treatment efficacy and effect on health related outcomes. PMID:26781161

  15. Anemia - B12 deficiency

    MedlinePLUS

    ... vitamin B12. They include: Chronic alcoholism Crohn disease, celiac disease, infection with the fish tapeworm, or other problems ... may no longer be needed after Crohn disease, celiac disease, or alcoholism is properly treated. Your doctor or ...

  16. Neuropathological and neuroprotective features of vitamin B12 on the dorsal spinal ganglion of rats after the experimental crush of sciatic nerve: an experimental study

    PubMed Central

    2013-01-01

    Background Spinal motoneuron neuroprotection by vitaminB12 was previously reported; the present study was carried out to evaluate neuroprotectivity in the dorsal root ganglion sensory neuron. Methods In present study thirty-six Wister-Albino rats (aged 89 weeks and weighing 200250 g) were tested. The animals were randomly divided into 6 groups which every group contained 6 rats. Group A: received normal saline (for 42 days); Group B: vitamin B12 was administered (0.5 mg/kg/day for 21 days); Group C: received vitamin B12 (1 mg/kg/day for 21days); Group D: received vitamin B12 (0.5 mg/kg/day for 42 days); Group E; received vitamin B12 (1 mg/kg/day for 42 days); Group F; received no treatment. The L5 Dorsal Root Ganglion (DRG) neurons count compared to the number of left and right neurons .Furthermore, DRG sensory neurons for regeneration were evaluated 21 or 42 days after injury (each group was analyzed by One-Way ANOVA test). Results (1): The comparison of left crushed neurons (LCN) number with right non-crushed neurons in all experimental groups (B, C, D and C), indicating a significant decline in their neurons enumeration (p<0/05). (2): The comparison of test groups LCN with the control groups LCN revealed a significant rise in the number of experimental group neurons (p<0/05). (3): Moreover, comparing the number of right neurons in experimental groups with the number of neurons in crushed neurons indicated that the average number of right neurons showed a significant increase in experimental groups (p<0/05). Conclusion Consequently, the probability of nerve regeneration will be increased by the increment of the administered drug dosage and duration. On the other hand, the regeneration and healing in Dorsal Spinal Ganglion will be improved by increase of administration time and vitamin B12 dose, indicating that such vitamin was able to progress recovery process of peripheral nerves damage in experimental rats. Finally, our results have important implications for elucidating the mechanisms of nerve regeneration. Moreover, the results showed that vitaminB12 had a proliferative effect on the dorsal root ganglion sensory neuron. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7395141841009256 PMID:23902646

  17. Genetic Associations with Plasma B12, B6, and Folate Levels in an Ischemic Stroke Population from the Vitamin Intervention for Stroke Prevention (VISP) Trial

    PubMed Central

    Keene, Keith L.; Chen, Wei-Min; Chen, Fang; Williams, Stephen R.; Elkhatib, Stacey D.; Hsu, Fang-Chi; Mychaleckyj, Josyf C.; Doheny, Kimberly F.; Pugh, Elizabeth W.; Ling, Hua; Laurie, Cathy C.; Gogarten, Stephanie M.; Madden, Ebony B.; Worrall, Bradford B.; Sale, Michele M.

    2014-01-01

    Background: B vitamins play an important role in homocysteine metabolism, with vitamin deficiencies resulting in increased levels of homocysteine and increased risk for stroke. We performed a genome-wide association study (GWAS) in 2,100 stroke patients from the Vitamin Intervention for Stroke Prevention (VISP) trial, a clinical trial designed to determine whether the daily intake of high-dose folic acid, vitamins B6, and B12 reduce recurrent cerebral infarction. Methods: Extensive quality control (QC) measures resulted in a total of 737,081 SNPs for analysis. Genome-wide association analyses for baseline quantitative measures of folate, Vitamins B12, and B6 were completed using linear regression approaches, implemented in PLINK. Results: Six associations met or exceeded genome-wide significance (P ≤ 5 × 10−08). For baseline Vitamin B12, the strongest association was observed with a non-synonymous SNP (nsSNP) located in the CUBN gene (P = 1.76 × 10−13). Two additional CUBN intronic SNPs demonstrated strong associations with B12 (P = 2.92 × 10−10 and 4.11 × 10−10), while a second nsSNP, located in the TCN1 gene, also reached genome-wide significance (P = 5.14 × 10−11). For baseline measures of Vitamin B6, we identified genome-wide significant associations for SNPs at the ALPL locus (rs1697421; P = 7.06 × 10−10 and rs1780316; P = 2.25 × 10−08). In addition to the six genome-wide significant associations, nine SNPs (two for Vitamin B6, six for Vitamin B12, and one for folate measures) provided suggestive evidence for association (P ≤ 10−07). Conclusion: Our GWAS study has identified six genome-wide significant associations, nine suggestive associations, and successfully replicated 5 of 16 SNPs previously reported to be associated with measures of B vitamins. The six genome-wide significant associations are located in gene regions that have shown previous associations with measures of B vitamins; however, four of the nine suggestive associations represent novel finding and warrant further investigation in additional populations. PMID:25147783

  18. Reply to Lawrence R. Solomon: Negative interaction of high folate status with biochemical and neurological response to vitamin B-12 treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We thank Dr. Lawrence Solomon for his observations and comments regarding our recent article on biochemical and neurological responses to vitamin B-12 treatment in asymptomatic Chilean elderly (1). Our article highlighted the most important effects of treatment; in our response to Dr. Solomon’s ques...

  19. In vitamin B12 deficiency, higher serum folate is assoicated with increased total homocysteine (tHcy) and methlmalonic acid (MMA) concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In a recent study of older participants (age >/= 60 y) in the 1999-2002 National Health and Nutrition Examination Survey (NHANES), we showed that a combination of high serum folate and low vitamin B-12 status was associated with higher prevalence of cognitive impairment and anemia than other combina...

  20. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Historic data on folic acid treatment of pernicious anemia suggested that high-level fortification would delay diagnosis or exacerbate effects of vitamin B12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive and experime...

  1. Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: An analysis of data from the National Health and Nutrition Examination Survey indicated that in older adults exposed to folic acid fortification, the combination of low serum vitamin B-12 and elevated folate is associated with higher concentrations of homocysteine and methylmalonic acid ...

  2. Vitamin B12 conjugation of peptide-YY(3-36) decreases food intake compared to native peptide-YY(3-36) upon subcutaneous administration in male rats.

    PubMed

    Henry, Kelly E; Elfers, Clinton T; Burke, Rachael M; Chepurny, Oleg G; Holz, George G; Blevins, James E; Roth, Christian L; Doyle, Robert P

    2015-05-01

    Challenges to peptide-based therapies include rapid clearance, ready degradation by hydrolysis/proteolysis, and poor intestinal uptake and/or a need for blood brain barrier transport. This work evaluates the efficacy of conjugation of vitamin B12 (B12) on sc administered peptide tyrosine tyrosine (PYY)(3-36) function. In the current experiments, a B12-PYY(3-36) conjugate was tested against native PYY(3-36), and an inactive conjugate B12-PYYC36 (null control) in vitro and in vivo. In vitro experiments demonstrated similar agonism for the neuropeptide Y2 receptor by the B12-PYY(3-36) conjugate (EC50 26.5 nM) compared with native PYY(3-36) (EC50 16.0 nM), with the null control having an EC50 of 1.8 ?M. In vivo experiments were performed in young adult male Sprague Dawley rats (9 wk). Daily treatments were delivered sc in five 1-hour pulses, each pulse delivering 5-10 nmol/kg, by implanted microinfusion pumps. Increases in hindbrain Fos expression were comparable 90 minutes after B12-PYY(3-36) or PYY3-36 injection relative to saline or B12-PYYC36. Food intake was reduced during a 5-day treatment for both B12-PYY(3-36)- (24%, P = .001) and PYY(3-36)-(13%, P = .008) treated groups relative to baseline. In addition, reduction of food intake after the three dark cycle treatment pulses was more consistent with B12-PYY(3-36) treatment (-26%, -29%, -27%) compared with the PYY(3-36) treatment (-3%, -21%, -16%), and B12-PYY(3-36) generated a significantly longer inhibition of food intake vs. PYY(3-36) treatment after the first two pulses (P = .041 and P = .036, respectively). These findings demonstrate a stronger, more consistent, and longer inhibition of food intake after the pulses of B12-PYY(3-36) conjugate compared with the native PYY(3-36). PMID:25658456

  3. Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

    PubMed Central

    Scambi, Cinzia; De Franceschi, Lucia; Guarini, Patrizia; Poli, Fabio; Siciliano, Angela; Pattini, Patrizia; Biondani, Andrea; La Verde, Valentina; Bortolami, Oscar; Turrini, Francesco; Carta, Franco; D'Orazio, Ciro; Assael, Baroukh M.; Faccini, Giovanni; Bambara, Lisa M.

    2009-01-01

    Background Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis. Methodology and Principal Findings A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K+ content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association. Conclusion and Significance 5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF. Trial Registration ClinicalTrials.gov NCT00730509 PMID:19277125

  4. A Combined Supplementation of Omega-3 Fatty Acids and Micronutrients (Folic Acid, Vitamin B12) Reduces Oxidative Stress Markers in a Rat Model of Pregnancy Induced Hypertension

    PubMed Central

    Kemse, Nisha G.; Kale, Anvita A.; Joshi, Sadhana R.

    2014-01-01

    Objectives Our earlier studies have highlighted that an altered one carbon metabolism (vitamin B12, folic acid, and docosahexaenoic acid) is associated with preeclampsia. Preeclampsia is also known to be associated with oxidative stress and inflammation. The current study examines whether maternal folic acid, vitamin B12 and omega-3 fatty acid supplementation given either individually or in combination can ameliorate the oxidative stress markers in a rat model of pregnancy induced hypertension (PIH). Materials and Methods Pregnant Wistar rats were assigned to control and five treatment groups: PIH; PIH + vitamin B12; PIH + folic acid; PIH + Omega-3 fatty acids and PIH + combined micronutrient supplementation (vitamin B12 + folic acid + omega-3 fatty acids). L-Nitroarginine methylester (L-NAME; 50 mg/kg body weight/day) was used to induce hypertension during pregnancy. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d20 of gestation. Results Animals from the PIH group demonstrated higher (p<0.01 for both) systolic and diastolic BP; lower (p<0.01) pup weight; higher dam plasma homocysteine (p<0.05) and dam and offspring malondialdehyde (MDA) (p<0.01), lower (p<0.05) placental and offspring liver DHA and higher (p<0.01) tumor necrosis factoralpha (TNF?) levels as compared to control. Individual micronutrient supplementation did not offer much benefit. In contrast, combined supplementation lowered systolic BP, homocysteine, MDA and placental TNF-? levels in dams and liver MDA and protein carbonyl in the offspring as compared to PIH group. Conclusion Key constituents of one carbon cycle (folic acid, vitamin B12 and DHA) may play a role in reducing oxidative stress and inflammation in preeclampsia. PMID:25405347

  5. Comparison of directly compressed vitamin B12 tablets prepared from micronized rotary-spun microfibers and cast films.

    PubMed

    Sebe, Istvn; Bodai, Zsolt; Eke, Zsuzsanna; Kllai-Szab, Barnabs; Szab, Pter; Zelk, Romna

    2015-01-01

    Fiber-based dosage forms are potential alternatives of conventional dosage forms from the point of the improved extent and rate of drug dissolution. Rotary-spun polymer fibers and cast films were prepared and micronized in order to direct compress after homogenization with tabletting excipients. Particle size distribution of powder mixtures of micronized fibers and films homogenized with tabletting excipients were determined by laser scattering particle size distribution analyzer. Powder rheological behavior of the mixtures containing micronized fibers and cast films was also compared. Positron annihilation lifetime spectroscopy was applied for the microstructural characterization of micronized fibers and films. The water-soluble vitamin B12 release from the compressed tablets was determined. It was confirmed that the rotary spinning method resulted in homogeneous supramolecularly ordered powder mixture, which was successfully compressed after homogenization with conventional tabletting excipients. The obtained directly compressed tablets showed uniform drug release of low variations. The results highlight the novel application of micronized rotary-spun fibers as intermediate for further processing reserving the original favorable powder characteristics of fibrous systems. PMID:25190153

  6. Progressive hyperpigmentation in a Taiwanese child due to an inborn error of vitamin B12 metabolism (cblJ).

    PubMed

    Takeichi, T; Hsu, C-K; Yang, H-S; Chen, H-Y; Wong, T-W; Tsai, W-L; Chao, S-C; Lee, J Y-Y; Akiyama, M; Simpson, M A; McGrath, J A

    2015-04-01

    The physiology of human skin pigmentation is varied and complex, with an extensive melanogenic paracrine network involving mesenchymal and epithelial cells, contributing to the regulation of melanocyte survival and proliferation and melanogenesis. Mutations in several genes, involving predominantly the KIT ligand/c-Kit and Ras/mitogen-activated protein kinase signalling pathways, have been implicated in a spectrum of diseases in which there is hyperpigmentation, hypopigmentation or both. Here, we report on a 12-year-old girl from Taiwan with a 6-year history of diffuse progressive skin hyperpigmentation resulting from a different aetiology: an inborn metabolic disorder of vitamin B12 (cobalamin), designated cblJ. Using whole-exome sequencing we identified a homozygous mutation in ABCD4 (c.423C>G; p.Asn141Lys), which encodes an ATP-binding cassette transporter with a role in the intracellular processing of cobalamin. The patient had biochemical and haematological evidence of cobalamin deficiency but no other clinical abnormalities apart from a slight lightening of her previously black hair. Of note, she had no neurological symptoms or signs. Treatment with oral cobalamin (3mg daily) led to metabolic correction and some reduction in the skin hyperpigmentation at the 3-month follow-up. This case demonstrates that defects or deficiencies of cobalamin should be remembered in the differential diagnosis of diffuse hyperpigmentary skin disorders. PMID:25234635

  7. In-situ biochemical remediation of chlorinated organic compounds present as DNAPL using vitamin B12 and reduced titanium

    SciTech Connect

    Lesage, S.; Sorel, D.; Cherry, J.A.

    1995-12-31

    The feasibility of using a biochemical treatment for the cleanup of DNAPL solvents in the saturated zone was tested using an in-situ large vertical column. Laboratory column studies have shown that a mixture of vitamin B12 and titanium citrate pumped through a column containing 100 {mu}L of tetrachloroethene can completely dissolve and degrade the residual to ethene in a few days. A vertical test column, 80 cm in diameter was installed within a sheet-pile cell isolating a portion of aquifer at CFB Borden. An equimolar mixture of tetrachloroethene and 1,1,1-trichloroethane was injected below the water table to form a residual DNAPL. The injection withdrawal system was operated in an upward flow mode over a 2 m height. In order for the reaction to be proceed, the in-situ pH must be greater than 7 and the Eh lower than -480 mV. The redox of the aquifer and the formation of reaction products was monitored on site, through 8 side pods equipped with stainless steel tubing terminated with 40 {mu}m porous cups, installed at different heights in the test column. The volatile products at the withdrawal well were monitored on-line by dynamic headspace analysis/gas chromatography.

  8. Selective intestinal malabsorption of vitamin B12 displays recessive Mendelian inheritance: Assignment of a locus to chromosome 10 by linkage

    SciTech Connect

    Aminoff, M.; Tahvanainen, E.; Chapelle, A. de la

    1995-10-01

    Juvenile megaloblastic anemia caused by selective intestinal malabsorption of vitamin B12 has been considered a distinct condition displaying autosomal recessive inheritance. It appears to have a worldwide distribution, and comparatively high incidences were reported 30 years ago in Finland and Norway. More recently, the Mendelian inheritance of the condition has been questioned because almost no new cases have occurred in these populations. Here we report linkage studies assigning a recessive-gene locus for the disease to chromosome 10 in previously diagnosed multiplex families from Finland and Norway, proving the Mendelian mode of inheritance. The locus is tentatively assigned to the 6-cM interval between markers D10S548 and D10S466, with a multipoint maximum lod score (Z{sub max}) of 5.36 near marker D10S1477. By haplotype analysis, the healthy sibs in these families did not appear to constitute any examples of nonpenetrance. We hypothesize that the paucity of new cases in these populations is due either to a dietary effect on the gene penetrance that has changed with time, or to a drop in the birth rate in subpopulations showing enrichment of the mutation, or to both of these causes. 38 refs., 4 figs., 2 tabs.

  9. Folic Acid and Vitamins D and B12 Correlate With Homocysteine in Chinese Patients With Type-2 Diabetes Mellitus, Hypertension, or Cardiovascular Disease

    PubMed Central

    Mao, Xudong; Xing, Xubin; Xu, Rong; Gong, Qing; He, Yue; Li, Shuijun; Wang, Hongfu; Liu, Cong; Ding, Xin; Na, Rishu; Liu, Zhiwen; Qu, Yi

    2016-01-01

    Abstract Elevated serum homocysteine has been shown to be a risk factor for hypertension, cardiovascular disease (CVD), and type-2 diabetes mellitus (T2DM). We characterized the relationships between the serum levels of homocysteine, folic acid, and vitamins D2, D3, and B12 in patients with T2DM, CVD, and hypertension in Shanghai, China. The levels of these serum biochemical markers were determined for 9311 Chinese patients (mean age: 79.50 ± 13.26 years) with T2DM (N = 839), hypertension (N = 490), or CVD (N = 7925). The demographic and serum biochemical data were compared using an analysis of variance. We performed stratified analyses using Pearson linear regression to investigate correlations between the different variables in the T2DM, CVD, and hypertension groups and in patients aged < 50, 50 to 64, 65 to 80, and ≥80 years. A subgroup analysis was also performed to identify correlations between the serum biochemical markers. Stratified chi-squared analyses were performed based on the levels of folic acid and total vitamin D. In all 3 patient groups, elevated levels of vitamin D2 and homocysteine were observed, whereas the levels of folic acid and vitamins D3 and B12 were lower than the reference range for each serum marker (P < 0.05 for all). The linear regression and stratified analyses showed that the highest levels of folic acid and vitamins D2 and D3 correlated with the lowest level of homocysteine in T2DM, CVD, and hypertension patients (P < 0.05 for all), whereas the highest level of vitamin B12 correlated with a lowest level of homocysteine in CVD patients only (P < 0.05). Our results indicate that the contributions of both vitamin D2 and vitamin D3 should be considered in investigations of the effects of vitamin D supplements in T2DM, CVD, and hypertension patients. Our findings warrant future studies of the benefits of vitamin D and folic acid supplements for reducing the risk of T2DM, CVD, and hypertension in elderly Chinese people, as well as the benefits of vitamin B12 supplements for reducing the risk of CVD alone. PMID:26871790

  10. Folic Acid and Vitamins D and B12 Correlate With Homocysteine in Chinese Patients With Type-2 Diabetes Mellitus, Hypertension, or Cardiovascular Disease.

    PubMed

    Mao, Xudong; Xing, Xubin; Xu, Rong; Gong, Qing; He, Yue; Li, Shuijun; Wang, Hongfu; Liu, Cong; Ding, Xin; Na, Rishu; Liu, Zhiwen; Qu, Yi

    2016-02-01

    Elevated serum homocysteine has been shown to be a risk factor for hypertension, cardiovascular disease (CVD), and type-2 diabetes mellitus (T2DM).We characterized the relationships between the serum levels of homocysteine, folic acid, and vitamins D2, D3, and B12 in patients with T2DM, CVD, and hypertension in Shanghai, China. The levels of these serum biochemical markers were determined for 9311 Chinese patients (mean age: 79.50??13.26 years) with T2DM (N?=?839), hypertension (N?=?490), or CVD (N?=?7925). The demographic and serum biochemical data were compared using an analysis of variance. We performed stratified analyses using Pearson linear regression to investigate correlations between the different variables in the T2DM, CVD, and hypertension groups and in patients aged?vitamin D.In all 3 patient groups, elevated levels of vitamin D2 and homocysteine were observed, whereas the levels of folic acid and vitamins D3 and B12 were lower than the reference range for each serum marker (P?vitamins D2 and D3 correlated with the lowest level of homocysteine in T2DM, CVD, and hypertension patients (P?vitamin B12 correlated with a lowest level of homocysteine in CVD patients only (P?vitamin D2 and vitamin D3 should be considered in investigations of the effects of vitamin D supplements in T2DM, CVD, and hypertension patients. Our findings warrant future studies of the benefits of vitamin D and folic acid supplements for reducing the risk of T2DM, CVD, and hypertension in elderly Chinese people, as well as the benefits of vitamin B12 supplements for reducing the risk of CVD alone. PMID:26871790

  11. Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: A common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues. Methods: TC genotype and its associations with i...

  12. Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older hispanics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: A common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues. Methods: TC genotype and its associations with i...

  13. Vitamin B12

    MedlinePLUS

    Skip navigation links U.S. Department of Health & Human Services HHS.gov National Institutes of Health NIH.gov Font Size Decrease Font Size Increase Font Size Strengthening Knowledge and Understanding of Dietary ...

  14. Determination of vitamin B12 in infant formula and adult nutritionals by surface plasmon resonance: First Action 2011.16 (test kit method).

    PubMed

    Vyas, Pathik; O'Kane, Anthony A; Dowell, Dawn

    2012-01-01

    At the "Standards Development and International Harmonization: AOAC INTERNATIONAL Mid-Year Meeting" on June 29, 2011, an Expert Review Panel (ERP) agreed to further examine AOAC Official Method 2011.01, "Determination of Vitamin B12 by Surface Plasmon Resonance," for use with infant formula and adult nutritionals. The original collaborative study was conducted using the Biacore Q biosensor instrument and the Biacore Q Qflex Kit Vitamin B12 PI. Samples included in the study were infant formula, cereals, premixes, vitamin tablets, dietary supplements, and baby food. Eleven laboratories participated in the collaborative study. The results demonstrated a repeatability RSD (RSDr) of 1.59-27.8 and HorRat values for reproducibility of 0.34-1.89 in samples with levels ranging from ppm to ppb. The assay studied is a label-free protein binding-based assay that uses the principle of surface plasmon resonance to measure the interaction between vitamin B12 and a specific binding protein by passing a portion of the prepared sample extract combined with binding protein solution across a functionalized sensor chip. The response from the functionalized sensor chip is given as free-binding protein, as the mixture binds to the prepared surface of the chip. The ready-to-use Qflex Kit Vitamin B12 PI provides the reagents and accessories necessary to perform this assay. AOAC Method 2011.01 was approved by the AOAC Method Committee on Food Nutrition for Official First Action status, applicable to a wide range of food products, dietary supplements, and multivitamin premixes. After evaluation of the validation data available, an ERP agreed in June 2011 that the method meets standard method performance requirements, as articulated by the Stakeholder Panel on Infant Formula and Adult Nutritionals. The ERP granted the method First Action status, applicable to infant formula and adult/pediatric nutritional formula. PMID:22649915

  15. Association study between genome-wide significant variants of vitamin B12 metabolism and gastric cancer in a han Chinese population.

    PubMed

    Zhao, Lei; Wei, Yucai; Song, Ailing; Li, Yumin

    2016-04-01

    Gastric cancer is one of the leading causes of cancer mortality worldwide. Accumulating evidence suggests that vitamin B12 plays an important role in the development of gastric cancer. Genome-wide association studies on metabolites in the one-carbon metabolism pathway identified several vitamin B12-related polymorphisms. Therefore, we investigated the association between variants within vitamin B12-related genes and gastric cancer in a Han Chinese population. Eight variants within the genome were significant vitamin B12-related genes, and they were selected for analysis in this case-control study. This study used a total of 492 gastric cancer patients and 550 noncancer controls. The variant rs526934 from the TCN1 gene was associated with an increased risk of developing gastric cancer. Increased risks of gastric cancer occurrence were observed in the minor G allele (OR = 1.25, 95% CI = 1.03-1.52, P = 0.031) and GG genotype (OR = 2.06, 95% CI = 1.24-3.42, P = 0.0043) compared with the wild-type A allele and AA-GA genotype, respectively. In the haplotypic analysis, we found that the CUBN haplotypes were associated with an altered gastric cancer risk. The rs1801222T/rs11254363A (OR = 1.40, 95% CI = 1.05-1.86, P = 0.021) and rs1801222C/rs11254363G (OR = 4.39, 95% CI = 2.32-8.30, P < 0.0001) haplotypes exhibited an increased gastric cancer risk, while rs1801222T/rs11254363G showed protective effects against gastric cancer (OR = 0.43, 95% CI = 0.25-0.73, P = 0.002) compared with the wild-type rs1801222C/rs11254363A haplotype. The circulating vitamin B12 concentration-related variants were associated with the occurrence of gastric cancer. This finding shed light on the unexpected role of vitamin B12 metabolism genes in gastric carcinogenesis and highlighted the interplay of diet, genetics, and human cancers. © 2016 IUBMB Life, 68(4):303-310, 2016. PMID:26959381

  16. Positive predictive value of the diagnosis coding for vitamin B12 deficiency anemia in the Danish National Patient Register

    PubMed Central

    Ben Ghezala, Inès; Arendt, Johan Frederik Berg; Erichsen, Rune; Zalfani, Jihen; Gammelager, Henrik; Frøslev, Trine; Olsen, Morten

    2012-01-01

    Purpose The aim of this validation study was to assess the positive predictive value (PPV) of the International Classification of Diseases, 10th revision (ICD-10) diagnosis of vitamin B12 (cobalamin [Cbl]) deficiency anemia in the Danish National Patient Register (DNPR). Patients and methods We identified all patients above 18 years of age recorded in the DNPR with a diagnosis of Cbl deficiency anemia (ICD-10 code: D51) admitted to two Danish university hospitals and one Danish regional hospital from 2000 through 2009. We assessed the PPV using biochemical parameters on Cbl deficiency with or without anemia as reference standards. These data were obtained from the Laboratory Information Systems Database. Data on prescriptions with Cbl supplementation drugs were obtained from the Aarhus University Prescription Database. Results We identified 1089 patients coded with a Cbl deficiency anemia diagnosis in the DNPR. The PPV was 31.5% (95% confidence interval [CI]: 28.8%–34.3%) and 36.8% (95% CI: 34.0%–39.7%) depending on definitions of Cbl deficiency with anemia. When using Cbl deficiency without anemia as a reference standard, the PPV was 51.3% (95% CI: 48.4%–54.3%). The PPV for Cbl supplemented patients was 22.2% (95% CI: 18.0%–26.9%) and for non-Cbl supplemented patients 63.9% (95% CI: 60.5%–67.3%). Conclusion The PPVs of the ICD-10 diagnosis coding for Cbl deficiency anemia were generally low in the DNPR. Therefore, this register should be used with caution to study patients with Cbl deficiency anemia. PMID:23271924

  17. The vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model

    PubMed Central

    BRENNER, M.; BENAVIDES, S.; MAHON, S. B.; LEE, J.; YOON, D.; MUKAI, D.; VISEROI, M.; CHAN, A.; JIANG, J.; NARULA, N.; AZER, S. M.; ALEXANDER, C.; BOSS, G. R.

    2014-01-01

    Background and purpose Hydrogen sulfide (H2S) is a highly toxic gas for which no effective antidotes exist. It acts, at least in part, by binding to cytochrome c oxidase, causing cellular asphyxiation and anoxia. We investigated the effects of three different ligand forms of cobinamide, a vitamin B12 analog, to reverse sulfide (NaHS) toxicity. Methods New Zealand white rabbits received a continuous intravenous (IV) infusion of NaHS (3 mg/min) until expiration or a maximum 270 mg dose. Animals received six different treatments, administered at the time when they developed signs of severe toxicity: Group 1saline (placebo group, N = 9); Group 2IV hydroxocobalamin (N = 7); Group 3IV aquohydroxocobinamide (N = 6); Group 4IV sulfitocobinamide (N = 6); Group 5intramuscular (IM) sulfitocobinamide (N = 6); and Group 6IM dinitrocobinamide (N = 8). Blood was sampled intermittently, and systemic blood pressure and deoxygenated and oxygenated hemoglobin were measured continuously in peripheral muscle and over the brain region; the latter were measured by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS). Results Compared with the saline controls, all cobinamide derivatives significantly increased survival time and the amount of NaHS that was tolerated. Aquohydroxocobinamide was most effective (261.5 2.4 mg NaHS tolerated vs. 93.8 6.2 mg in controls, p < 0.0001). Dinitrocobinamide was more effective than sulfitocobinamide. Hydroxocobalamin was not significantly more effective than the saline control. Conclusions Cobinamide is an effective agent for inhibiting lethal sulfide exposure in this rabbit model. Further studies are needed to determine the optimal dose and form of cobinamide and route of administration. PMID:24716792

  18. Beneficial effects of omega-3 fatty acids and vitamin B12 supplementation on brain docosahexaenoic acid, brain derived neurotrophic factor, and cognitive performance in the second-generation Wistar rats.

    PubMed

    Rathod, Richa S; Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-01-01

    In vegetarian population, vitamin B12 deficiency coexists with suboptimal levels of omega-3 fatty acids. Studies indicate a need for supplementation/fortification of vitamin B12 and omega-3 fatty acids to reduce the risk of brain disorders. We have described the effects of vitamin B12 and omega-3 fatty acid supplementation on brain development in F1 generation animals. The current study investigates the effects of vitamin B12 and omega-3 fatty acids supplementation on brain function and cognition. Pregnant Wistar rats were assigned the following groups: control, vitamin B12 deficient (BD), vitamin B12 deficient + omega-3 fatty acid (BDO), vitamin B12 supplemented (BS), vitamin B12 supplemented + omega-3 fatty acid (BSO). The same diets were continued for two generations. BDO group showed higher (P < 0.05) levels of BDNF (brain derived neurotrophic factor) and DHA (docosahexaenoic acid) in the cortex and hippocampus as compared with the BD group. The cognitive performance was also normalized in this group. BS showed comparable levels of DHA, BDNF (protein and mRNA), and CREB mRNA (cAMP response element-binding protein) to that of control group while Tropomyosin receptor kinase mRNA levels were higher. The combined vitamin B12 and omega-3 fatty acid supplementation further enhanced the levels of DHA (P < 0.05) and BDNF (P < 0.05) in the hippocampus and CREB mRNA (P < 0.01) in the cortex as compared with BS group. The cognitive performance of these animals was higher (P < 0.05) as compared with BS group. Our data indicates the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation across two generations on brain development and function. PMID:26249019

  19. Human Vitamin B12 Absorption and Metabolism are Measured by Accelerator Mass Spectrometry Using Specifically Labeled 14C-Cobalamin

    SciTech Connect

    Carkeet, C; Dueker, S R; Lango, J; Buchholz, B A; Miller, J W; Green, R; Hammock, B D; Roth, J R; Anderson, P J

    2006-01-26

    There is need for an improved test of human ability to assimilate dietary vitamin B{sub 12}. Assaying and understanding absorption and uptake of B{sub 12} is important because defects can lead to hematological and neurological complications. Accelerator mass spectrometry (AMS) is uniquely suited for assessing absorption and kinetics of {sup 14}C-labeled substances after oral ingestion because it is more sensitive than decay counting and can measure levels of carbon-14 ({sup 14}C) in microliter volumes of biological samples, with negligible exposure of subjects to radioactivity. The test we describe employs amounts of B{sub 12} in the range of normal dietary intake. The B{sub 12} used was quantitatively labeled with {sup 14}C at one particular atom of the DMB moiety by exploiting idiosyncrasies of Salmonellametabolism. In order to grow aerobically on ethanolamine, S. entericamust be provided with either pre-formed B{sub 12} or two of its precursors: cobinamide and dimethylbenzimidazole (DMB). When provided with {sup 14}C-DMB specifically labeled in the C2 position, cells produced {sup 14}C-B{sub 12} of high specific activity (2.1 GBq/mmol, 58 mCi/mmol) and no detectable dilution of label from endogenous DMB synthesis. In a human kinetic study, a physiological dose (1.5 mg, 2.2 KBq/59 nCi) of purified {sup 14}C-B{sub 12} was administered and showed plasma appearance and clearance curves consistent with the predicted behavior of the pure vitamin. This method opens new avenues for study of B{sub 12} assimilation.

  20. Development and validation of PCR, PLS, and TLC densitometric methods for the simultaneous determination of vitamins B(1), B(6) AND B(12) in pharmaceutical formulations.

    PubMed

    Elzanfaly, Eman S; Nebsen, Marianne; Ramadan, Nesreen K

    2010-10-01

    This work represents the simultaneous determination of thiamine hydrochloride (B(1)), pyridoxine hydrochloride (B(6)) and cyanocobalamine (B(12)) by two different methods namely spectrophotometry multivariate calibration and densitometry. The spectrophotometric numerical method depends on the use of spectrophotometric data coupled to PLS and PCR multivariate calibration methods for the simultaneous determination of (B(1)) and (B(6)) in the presence of (B(12)) in laboratory prepared mixtures and commercial tablets. A calibration set was prepared, where the three vitamins were modeled using a full factorial 23 with three center points experimental design. This calibration set was used to build the PLS and PCR models. The models were validated by testing their predictive ability on a validation set where low RMSEP, RSEP % were obtained for both models. Figures of merit were determined using the net analyte signal concept. The proposed models were applied successfully to simultaneous determination of B1 and B6 in presence of a low concentration of B12 in pharmaceutical dosage forms that contain simple excipients. The TLC densitometric method was based on the use of a developing system of chloroform: ethanol: water: acetic acid solution (2: 8: 2: 0.5 v/v) to separate the three vitamins. The separated spots were scanned at 242nm, 291nm and 360nm for B(1), B(6) and B(12) respectively. The proposed method was applied successfully to simultaneous determination of the three vitamins in their pure powder form in the range 0.1-1.5 (g/spot), 0.5-3.5 (g/spot), 0.1-1.5 (g/spot) for B(1), B(6), and B(12) respectively and in their pharmaceutical formulations. PMID:20884455

  1. Determination of vitamin B12 in infant formula and adult nutritionals by liquid chromatography/UV detection with immunoaffinity extraction: First Action 2011.08.

    PubMed

    Campos-Gimnez, Esther; Fontannaz, Patric; Trisconi, Marie-Jos; Kilinc, Tamara; Gimenez, Catherine; Andrieux, Pierre; Nelson, Maria

    2012-01-01

    At the "Standards Development and International Harmonization: AOAC INTERNATIONAL Mid-Year Meeting," on June 29, 2011, an Expert Review Panel agreed that the method "Determination of Vitamin B12 in Infant Formulas and Adult Nutritionals by Liquid Chromatography/UV Detection with Immunoaffinity Extraction" be adopted AOAC Official First Action status. The method is applicable for the determination of vitamin B12, which includes added cyanocobalamin and natural forms, making it applicable to both fortified and nonfortified products. Vitamin B12 is extracted from the sample in sodium acetate buffer in the presence of sodium cyanide (100 degrees C, 30 min). After purification and concentration with an immunoaffinity column, vitamin B12 is determined by LC with UV detection (361 nm). A single-laboratory validation study was conducted on a range of products, including milk- and soy-based infant formulas, cereals, cocoa beverages, health care products, and polyvitamin premixes. The method demonstrated linear response over a large range of concentrations, recovery rates of 100.8 +/- 7.5% (average +/- SD), repeatability RSD (RSDr) of 2.1%, and intermediate reproducibility (RSD(iR)) of 4.3%. LOD and LOQ values were 0.10 and 0.30 microg/100 g, respectively, and correlation with the reference microbiological assay was good (R2 = 0.9442). The results of the study were published in J. AOAC Int. 91, 786-793 (2008). The performance characteristics of the method met the standard method performance requirements set forth by the Stakeholder Panel on Infant Formula and Adult Nutritionals; thus, the method was determined to be appropriate for First Action status. PMID:22649911

  2. Structure of AMP-PNP-bound BtuCD and mechanism of ATP-powered vitamin B12 transport by BtuCD-F.

    PubMed

    Korkhov, Vladimir M; Mireku, Samantha A; Veprintsev, Dmitry B; Locher, Kaspar P

    2014-12-01

    The reaction mechanism of BtuCD-F-catalyzed vitamin B12 transport into Escherichia coli is currently unclear. Here we present the structure of the last missing state in the form of AMP-PNP-bound BtuCD, trapped by a disulfide cross-link. Our structural and biochemical data allow a consistent mechanism to be formulated, thus rationalizing the roles of substrate, ATP and substrate-binding protein. PMID:25402482

  3. Red colored IgG4 caused by vitamin B12 from cell culture media combined with disulfide reduction at harvest.

    PubMed

    Derfus, Gayle E; Dizon-Maspat, Jemelle; Broddrick, Jared T; Velayo, Arleene C; Toschi, Josh D; Santuray, Rodell T; Hsu, Stephen K; Winter, Charles M; Krishnan, Rajesh; Amanullah, Ashraf

    2014-01-01

    While many antibody therapeutics are formulated at low concentration (~10-20 mg/mL) for intravenous administration, high concentration (> 100 mg/mL) formulations may be required for subcutaneous delivery in certain clinical indications. For such high concentration formulations, product color is more apparent due to the higher molecular density across a given path-length. Color is therefore a product quality attribute that must be well-understood and controlled, to demonstrate process consistency and enable clinical trial blinding. Upon concentration of an IgG4 product at the 2000 L manufacturing scale, variability in product color, ranging from yellow to red, was observed. A small-scale experimental model was developed to assess the effect of processing conditions (medium composition and harvest conditions) on final bulk drug substance (BDS) color. The model was used to demonstrate that, for two distinct IgG4 products, red coloration occurred only in the presence of disulfide reduction-mediated antibody dissociation. The red color-causing component was identified as vitamin B 12, in the hydroxocobalamin form, and the extent of red color was correlated with the cobalt (vitamin B 12) concentration in the final pools. The intensity of redness in the final BDS was modulated by changing the concentration of vitamin B 12 in the cell culture media. PMID:24552690

  4. Novel in situ product removal technique for simultaneous production of propionic acid and vitamin B12 by expanded bed adsorption bioreactor.

    PubMed

    Wang, Peng; Wang, Yunshan; Liu, Yongdong; Shi, Hong; Su, Zhiguo

    2012-01-01

    A new type of in situ product removal (ISPR) technique of expanded bed adsorption (EBA) bioreactor was studied to simultaneously produce extracellular propionic acid and intracellular vitamin B12 by Propionibacterium freudenreichii CICC 10019. Resin screening experiments showed that the ZGA330 resin have the best biocompatibility and highest adsorption for propionic acid. Through the EBA bioreactor, propionic acid could be recovered efficiently by semi-continuous recirculation of the unfiltered broth, which eliminated the feedback inhibition of propionic acid. Fed-batch fermentation was carried out using the EBA system, resulting in a propionic acid concentration of 52.5 g L(-1) and vitamin B12 concentration of 43.04 mg L(-1) at 160 h, which correspond to product yields of 0.66 g g(-1) and 0.54 mg g(-1), respectively. The present study suggests that the EBA bioreactor can be utilized for the simple and economical production of propionic acid and vitamin B12 in a single fermentation process. PMID:22082511

  5. Determining the Effect of Gutkha on Serum Levels of Vitamin B12 and Folic Acid as Compared to Smoking among Chronic Periodontitis Subjects : A Cross-Sectional Study

    PubMed Central

    Warad, Shivaraj; Kalburgi, Nagaraj B; Kalburgi, Veena C; Koregol, Arati C; Patanashetti, Jyoti; Rao, Subramaniam; Kokatnur, M. Vijayalaxmi

    2014-01-01

    Background: Periodontitis, being a common inflammatory disease has a multifactorial origin , with smoking and gutkha as few of the causative entities. The role of smoking as a risk factor for periodontitis is been well documented in literature. Cigarette smoke also affects vitamin B12 and folic acid mechanisms. Nutritionally derived vitamin B12 occurs mainly as either hydroxycobalamin or deoxyadenosycobalmin. Folic acid is also heat sensitive and water soluble, closely linked to vitamin B12 in its metabolism. However, effect of smokeless tobacco in form of gutkha on serum levels of vitamin B12 and folic acid is yet to be explored. Aims and Objectives: To estimate and correlate serum vitamin B12 (VB12) and folic acid (FA) levels among periodontally healthy subjects and Chronic Periodontitis (CP) subjects with habit of smoking and gutkha chewing. Materials and Methods: The study included 111 subjects ranging in age from 18 to 60 y. Participants were divided into four groups: 30 healthy subjects (Group I), 29 subjects with CP (Group II), 25 smokers with CP (Group III) and 27 gutkha chewers with CP (Group IV). Clinical parameters included pocket probing depth (PPD), clinical attachment level (CAL) & gingival index (GI) following which VB12 and FA levels were estimated through UV-spectrophotometry method and data was analysed using Statistical Package for Social Scientists software, Mann-Whitney U-test and Pearson correlation coefficient. p-values less than 0.05 were considered as significant. Results : Pairwise comparison by Mann-Whitney U-test showed an increase in the serum VB12 in Group IV when compared to Group I (p=0.01) and Group II (p=0.01). Although serum FA levels were found to be low in Group III (7.61 ug/ml) & Group IV (8.64 ug/ml), Group III was found to be statistically significant (P=0.046). The clinical parameters GI, PPD and CAL among the four groups of patients were also statistically significant (p < 0.05). Conclusion: The study results suggested that among the patients with periodontal disease, serum VB12 levels are directly related while serum FA levels are inversely related to inflammation and tissue destruction in periodontium as occurred in Group IV. PMID:25654040

  6. Effect of B Vitamin (Folate, B6, and B12) Supplementation on Osteoporotic Fracture and Bone Turnover Markers: A Meta-Analysis

    PubMed Central

    Ruan, Jianwei; Gong, Xiaokang; Kong, Jinsong; Wang, Haibao; Zheng, Xin; Chen, Tao

    2015-01-01

    Background B vitamins (including folate, B6, and B12) supplementation can effectively and easily modify high plasma homocysteine (Hcy). However, the role of Hcy in the pathogenesis of osteoporotic fracture and bone turnover is still controversial. This meta-analysis aimed to assess the impact of B vitamin supplementation on occurrence of any osteoporotic fracture and bone turnover by pooling the results of previous studies. Material/Methods Relevant randomized controlled trials (RCTs) were searched in databases. Data integration and analysis were done by using Review Manager 5.3 (the Cochrane Collaboration). The risk ratio (RR) and corresponding 95% confidence intervals (CI) of fracture (intervention vs. control) were estimated. Changes in bone turnover indicators (continuous data), weighted mean difference (WMD), and corresponding 95% (CI) were pooled for estimation. Results Based on the results of 4 RCTs, this meta-analysis failed to identify a risk-reducing effect of daily supplementation of B vitamins on osteoporotic fracture in patients with vascular disease and with relatively normal plasma Hcy. In addition, we also did not find any positive effects of B vitamin supplementation on bone turnover. Conclusions B vitamin supplementation might not be effective in preventing fracture and improving bone turnover. However, the possible benefits in selective populations, such as populations with very high plasma Hcy and from regions without B vitamin fortification should be explored in the future. PMID:25805360

  7. Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia.

    PubMed

    van Dijk, Suzanne C; Enneman, Anke W; Swart, Karin Ma; van Wijngaarden, Janneke P; Ham, Annelies C; de Jonge, R; Blom, Henk J; Feskens, Edith J; Geleijnse, Johanna Marianne; van Schoor, Natasja M; Dhonukshe-Rutten, Rosalie Am; de Jongh, Renate T; Lips, Paul; de Groot, Lisette Cpgm; Uitterlinden, Andre G; van den Meiracker, Ton H; Mattace-Raso, Francesco Us; van der Velde, Nathalie; Smulders, Yvo M

    2016-04-01

    B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (-1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. CLINICALTRIALSGOV IDENTIFIER NCT00696514. PMID:26774115

  8. The changing of serum vitamin B12 and homocysteine levels after gastrectomy in patients with gastric cancer: do they associate with clinicopathological factors?

    PubMed

    Bilici, Ahmet; Sonkaya, Alper; Ercan, Serif; Ustaalioglu, Bala Basak Oven; Seker, Mesut; Aliustaoglu, Mehmet; Orcun, Asuman; Gumus, Mahmut

    2015-02-01

    After total (TG) or distal subtotal gastrectomy (DG), patients are at high risk of vitamin B12 (vit-B12) deficiency, which results in elevation of homocysteine levels. The changing of serum vit-B12 and homocysteine levels in patients with gastric cancer is not well known. Seventy-two patients with gastric cancer who had undergone currative gastrectomy and 50 healthy controls were included. Serum vit-B12 and homocysteine levels were analyzed in gastric cancer patients. In addition, these parameters were compared with those of healthy control subjects. While serum vit-B12 levels in gastrectomized patients were significantly lower than that of healthy controls (221.8 ± 125.6 pg/mL vs. 309.9 ± 174.3 pg/mL, p = 0.002), homocysteine levels were significantly higher in patients with gastric cancer (14.2 ± 6.7 μmol/L vs. 12.5 ± 6.1 μmol/L, p = 0.016). Mean serum folate level was found to be high in healthy controls (7.3 ng/mL) compared to patients (9.2 ng/mL, p = 0.027). Out of 72 patients, 40 patients (55.6 %) with gastric cancer developed vit-B12 deficiency after gastrectomy. Vit-B12 deficiency was found to be related with gastrectomy type (p = 0.02) and homocysteine levels (p = 0.014). In patients who underwent TG, the incidence of vit-B12 deficiency was significantly higher compared with those with DG (67.5 vs. 32.5 %). In addition, serum vit-B12 level in patients with DG was significantly higher than that of patients with TG (248.3 ± 122.0 pg/mL vs. 200.8 ± 126.7 pg/mL, p = 0.041), whereas homocysteine levels were significantly lower in DG group compared with TG group (12.1 ± 6.1 μmol/L vs. 15.8 ± 6.9 μmol/L, p = 0.014). A logistic regression analysis showed that the extent of gastrectomy was found to be an independent factor for predicting the occurrence of vit-B12 deficiency (p < 0.001, odds ratio 1.38). Our results showed that cumulative vit-B12 deficiency rate was significantly higher after TG compared with that after DG, while homocysteine levels were significantly higher in TG group compared with DG group. The extent of gastrectomy was found to be an independent factor for predicting the occurrence of vit-B12 deficiency. Vit-B12 deficiency and hyperhomocysteinemia are imperious clinical situation for patients with gastric cancer after surgery. Hence, both preoperative and regular postoperative monitoring of vit-B12 and homocysteine levels for all gastrectomized patients with gastric cancer are important and necessary for early detection and prevention of vit-B12 deficiency and hyperhomocysteinemia as a risk factor for cardiovascular diseases. PMID:25296737

  9. Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12.

    PubMed

    Acharyya, Nirmallya; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit

    2015-11-01

    Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0?g, respectively/100g b.w. of rat for 28days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages. PMID:25850544

  10. Interactions between plasma concentrations of folate and markers of vitamin B(12) status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study.

    PubMed

    Doets, Esmée L; Ueland, Per M; Tell, Grethe S; Vollset, Stein Emil; Nygård, Ottar K; Van't Veer, Pieter; de Groot, Lisette C P G M; Nurk, Eha; Refsum, Helga; Smith, A David; Eussen, Simone J P M

    2014-03-28

    A combination of high folate with low vitamin B12 plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12 markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72-74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12 markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-ɛ4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12 in relation to cognitive performance. Plasma vitamin B12 concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12 concentrations in the lower range, the association between plasma folate and cognitive performance was strongest. PMID:24229560

  11. Vitamin B12 deficiency reduces proliferation and promotes differentiation of neuroblastoma cells and up-regulates PP2A, proNGF, and TACE.

    PubMed

    Battaglia-Hsu, Shyue-fang; Akchiche, Nassila; Noel, Nicole; Alberto, Jean-Marc; Jeannesson, Elise; Orozco-Barrios, Carlos Enrique; Martinez-Fong, Daniel; Daval, Jean-Luc; Guéant, Jean-Louis

    2009-12-22

    Vitamin B12 (cobalamin, Cbl) is indispensable for proper brain development and functioning, suggesting that it has neurotrophic effects beside its well-known importance in metabolism. The molecular basis of these effects remains hypothetical, one of the reasons being that no efficient cell model has been made available for investigating the consequences of B12 cellular deficiency in neuronal cells. Here, we designed an approach by stable transfection of NIE115 neuroblastoma cells to impose the anchorage of a chimeric B12-binding protein, transcobalamin-oleosin (TO) to the intracellular membrane. This model produced an intracellular sequestration of B12 evidenced by decreased methyl-Cbl and S-adenosylmethionine and increased homocysteine and methylmalonic acid concentrations. B12 deficiency affected the proliferation of NIE115 cells through an overall increase in catalytic protein phosphatase 2A (PP2A), despite its demethylation. It promoted cellular differentiation by improving initial outgrowth of neurites and, at the molecular level, by augmenting the levels of proNGF and p75(NTR). The up-regulation of PP2A and pro-nerve growth factor (NGF) triggered changes in ERK1/2 and Akt, two signaling pathways that influence the balance between proliferation and neurite outgrowth. Compared with control cells, a 2-fold increase of p75(NTR)-regulated intramembraneous proteolysis (RIP) was observed in proliferating TO cells (P < 0.0001) that was associated with an increased expression of two tumor necrosis factor (TNF)-alpha converting enzyme (TACE) secretase enzymes, Adam 10 and Adam 17. In conclusion, our data show that B12 cellular deficiency produces a slower proliferation and a speedier differentiation of neuroblastoma cells through interacting signaling pathways that are related with increased expression of PP2A, proNGF, and TACE. PMID:19959661

  12. Vitamin B12 regulates photosystem gene expression via the CrtJ antirepressor AerR in Rhodobacter capsulatus

    PubMed Central

    Cheng, Zhuo; Li, Keran; Hammad, Loubna A.; Karty, Jonathan A.; Bauer, Carl E.

    2014-01-01

    Summary The tetrapyrroles heme, bacteriochlorophyll and cobalamin (B12) exhibit a complex interrelationship regarding their synthesis. In this study, we demonstrate that AerR functions as an antirepressor of the tetrapyrrole regulator CrtJ. We show that purified AerR contains B12 that is bound to a conserved histidine (His145) in AerR. The interaction of AerR to CrtJ was further demonstrated in vitro by pull down experiments using AerR as bait and quantified using microscale thermophoresis. DNase I DNA footprint assays show that AerR containing B12 inhibits CrtJ binding to the bchC promoter. We further show that bchC expression is greatly repressed in a B12 auxotroph of Rhodobacter capsulatus and that B12 regulation of gene expression is mediated by AerR’s ability to function as an antirepressor of CrtJ. This study thus provides a mechanism for how the essential tetrapyrrole, cobalamin controls the synthesis of bacteriochlorophyll, an essential component of the photosystem. PMID:24329562

  13. Improvement of fine motoric movement control by elevated dosages of vitamin B1, B6, and B12 in target shooting.

    PubMed

    Bonke, D; Nickel, B

    1989-01-01

    Oral application of elevated dosages of vitamin B1, B6 and B12 have been found to improve target shooting in marksmen, recruited from a local pentathlon association, in two different studies. Study 1 was performed in an open controlled design, whereas in study 2 the group treated with B-vitamins was compared in a double-blind fashion with a placebo control group including 8 by 8 volunteers and 10 by 9 volunteers, respectively. The volunteers were randomly assigned to the groups. Performance quality was followed in both studies over a period of 8 weeks, while participants were continuously supplied with a combination of vitamins B1, B6 and B12 (Neurobion or Neurobion forte; E. Merck, Darmstadt, and Cascan, Wiesbaden, Germany). In both studies, marksmen in the vitamin-treated groups showed statistically significant, considerably improved firing accuracy as measured by the number of points achieved within a series of 20 shots at each examination. In study 2 the degree of improvement was linearly dependent on the duration of vitamin treatment, whereas the placebo-treated group, similar to the untreated control group in study 1, did not show any prominent change. Performance quality in marksmenship closely correlates with the magnitude of physiological tremor. Tremor can also be involved in the regulation quality of sensory-motor control systems. Thus, an improvement in firing accuracy as found in both studies is by the same token an improvement of fine motor control of slow movements, involving, for example, basal ganglia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2507698

  14. Short communication: Folates and vitamin B12 in colostrum and milk from dairy cows fed different energy levels during the dry period.

    PubMed

    Duplessis, M; Mann, S; Nydam, D V; Girard, C L; Pellerin, D; Overton, T R

    2015-08-01

    This study was undertaken to evaluate folate and vitamin B12 concentrations of colostrum and milk in early lactation of dairy cows fed different levels of energy during the dry period. A total of 84 multiparous Holstein cows were assigned to one of the following dietary treatments fed as a total mixed ration 57 d before the expected calving date: (1) high-energy one-group dry cow diet [1.35 Mcal of net energy for maintenance/kg of dry matter (DM); 56% corn silage, 12% wheat straw, and 32% concentrate mix on a daily DM basis]; (2) controlled-energy one-group dry cow diet (1.14 Mcal of net energy for maintenance/kg of DM; 29% corn silage, 36% wheat straw, and 35% concentrate mix on a daily DM basis); or (3) an intermediate step-up diet (controlled-energy diet from dry off until 29 d before the expected calving date and then switching to a diet representing a 50:50 blend of the controlled- and high-energy diets from 28 d before expected calving date until parturition; 1.24 Mcal of net energy for maintenance/kg of DM). After calving, all cows were fed the same diet served as a total mixed ration (44% corn silage, 14% grass silage, and 42% concentrate mix on a daily DM basis) until 42 d in milk (DIM). Colostrum samples were taken at the first milking after parturition and milk samples were taken during the morning milking at 11 and 392 DIM. Colostrum from the first milking and milk yields were weighed on the day of sampling. Colostrum yield from the first milking postpartum and milk yields at 11 and 39 DIM were unaffected by treatments. Colostrum yield averaged 6.80.7mg at the first milking postpartum, whereas milk yields at 11 and 39 DIM were, on average, 40.31.5 and 48.91.3mg/d, respectively. Folate concentrations in colostrum and milk were not different among treatments. Folate concentration of colostrum (440.318.8ng/mL) was higher than folate concentration in milk at 11 (93.73.0ng/mL) and at 39 DIM (78.42.6ng/mL). Vitamin B12 concentration in colostrum was higher for controlled-energy cows (31.71.4ng/mL) than intermediate cows (23.51.4ng/mL), whereas no treatment effect was noted for vitamin B12 concentration in milk. At 11 and 39 DIM, milk concentrations of vitamin B12 averaged 3.8 and 3.21.4ng/mL, respectively. In summary, results suggest that dietary change during the dry period could modify vitamin B12 concentration in colostrum, but had no effect on milk concentration of folates and vitamin B12 during early lactation. PMID:26094219

  15. Dynamic behaviour of the B12 riboswitch

    NASA Astrophysics Data System (ADS)

    Santilln, Moiss; Mackey, Michael C.

    2005-03-01

    Riboswitches are RNA segments that serve as ligand-responsive genetic control elements. They modulate the expression of certain genes in response to changing concentrations of metabolites. In this paper, we study the dynamic behaviour of the B12 riboswitch in E. coliperhaps the most widely studied and best known of all riboswitchesthrough a mathematical model of its regulatory pathway. To carry this out, we simulate dynamic experiments in which the bacterial B12 uptake capacity is measured after being depleted of this vitamin for a long time. The results of these simulations compare favourably with reported experimental data. The model also predicts that an overshoot of intracellular B12 should be observed if the replenishment experiments were to be carried out for longer times. This behaviour is discussed in terms of a possible evolutionary advantage for E. coli, together with the fact that regulation at the transcriptional and translational levels is almost equivalent dynamically.

  16. Pseudo-HELLP syndrome par carence en folates et/ou en vitamine B12: propos d'un cas

    PubMed Central

    Benali, Mechaal; Bouassida, Mahdi; Dhouib, Firas; Bouzeidi, Kaled

    2014-01-01

    Plusieurs pathologies mdicales peuvent interfrer avec la grossesse et mimer le tableau biologique de HELLP syndrome. Lvolution naturelle de ce syndrome est d'une particulire gravit pour la mre et le ftus, il convient dliminer rapidement les autres diagnostics afin dviter une extraction ftale prmature injustifie. Nous rapportons le cas d'une parturiente qui s'est prsente avec un tableau vocateur d'un HELLP syndrome, rapport finalement une carence en folates et en vitamine B12. PMID:25404961

  17. Pyrolysis of Animal Bones with Vitamin B12: A Facile Route to Efficient Transition Metal-Nitrogen-Carbon (TM-N-C) Electrocatalysts for Oxygen Reduction.

    PubMed

    Dou, Meiling; He, Duanpeng; Shao, Wenhao; Liu, Haijing; Wang, Feng; Dai, Liming

    2016-02-01

    By pyrolyzing cattle bones, hierarchical porous carbon (HPC) networks with a high surface area (2520?m(2) ?g(-1) ) and connected pores were prepared at a low cost and large scale. Subsequent co-pyrolysis of HPC with vitamin B12 resulted in the formation of three-dimensional (3D) hierarchically structured porous cobalt-nitrogen-carbon (Co-N-HPC) electrocatalysts with a surface area as high as 859?m(2) ?g(-1) as well as a higher oxygen reduction reaction (ORR) electrocatalytic activity, better operation stability, and higher tolerance to methanol than the commercial Pt/C catalyst in alkaline electrolyte. PMID:26712415

  18. Serum levels of homocysteine, folate and vitamin B12 in patients with vitiligo before and after treatment with narrow band ultraviolet B phototherapy and in a group of controls.

    PubMed

    Ata?, Hatice; Cemil, Beng evirgen; Gnl, Mzeyyen; Ba?trk, Eda; iek, Emel

    2015-07-01

    The association between vitamin B12, folate, homocysteine and vitiligo were studied in several studies, but the results are contradictory. Narrow-band ultraviolet B (NBUVB) phototherapy is now considered as a gold standard for the treatment of diffuse vitiligo. The effects of NBUVB phototherapy on both vitamin B12, folate and homocysteine levels have not been studied in vitiligo patients yet. Serum levels of vitamin B12, folate and homocysteine were measured in vitiligo patients and control group and also both before and after NBUVB phototherapy in vitiligo patients. While levels of homocysteine in patients with vitiligo were significantly higher than controls (16.98.4 vs. 10. 93.4 ?mol/L; p<0,001) vitamin B12 and folate levels were not different (p>0.05). NBUVB phototherapy led to a 33.721.9% (0-75%) response in patients with vitiligo after 80 seccions. Treatment with NBUVB improved vitiligo and decreased serum levels of vitamin B12 (375151 vs. 346119 pg/ml, p=0.024), while serum levels of folate and homocysteine did not change significantly after treatment (p=0.914, p=0.127). Further studies are needed to clarify the influence of NBUVB phototherapy on folate, vitamin B12 and homocysteine levels in patients with vitiligo. Furthermore, studies with the analysis of skin levels of homocysteine rather than circulating levels may be useful to elucidate the effects of phototherapy on homocysteine levels. PMID:25941975

  19. Vitamin B12 loaded polycaprolactone nanofibers: a novel transdermal route for the water soluble energy supplement delivery.

    PubMed

    Madhaiyan, Kalaipriya; Sridhar, Radhakrishnan; Sundarrajan, Subramanian; Venugopal, Jayarama Reddy; Ramakrishna, Seeram

    2013-02-28

    Biocompatible PCL polymer nanofiber mediated sustained release of hydrophilic drug and applicability as transdermal delivery system is attempted. This new attempt to investigate water soluble vitamin delivery with hydrophobic polymer nanofiber sustained the release of the vitamin and the method is suited for the transdermal patch applications. The drug loaded fibers were characterized with SEM for morphology, porometer for pore size measurements, mechanical strength calculation and FT-IR for drug load characterization. The contact angle measurement showed surface wettability and controlled release of drug was quantified with UV absorption measurements. To further enhance the release of vitamin, the polymer fiber was plasma treated at different time intervals and made hydrophilic gradually. Since the increased surface area and drug encapsulation in nano-reservoirs can able to release drug in small quantities and in a sustained manner we attempted the release of the energy supplement with nanofibrous delivery mode. PMID:23370432

  20. Effectiveness of the National Program of Complementary Feeding for older adults in Chile on vitamin B12 status in older adults; secondary outcome analysis from the CENEX Study (ISRCTN48153354)

    PubMed Central

    2013-01-01

    Background Older people are at increased risk of vitamin B12 deficiency and the provision of fortified foods may be an effective way to ensure good vitamin B12 status in later life. Aim To evaluate the effectiveness of a vitamin B12 fortified food provided by a national program of complementary food for older people on plasma vitamin B12 levels. Subjects and methods A random sub-sample of 351 subjects aged 65-67y from a large cluster randomised controlled trial provided blood samples at baseline and after 24 months of intervention. The intervention arm (10 clusters 186 participants) received a vitamin B12 fortified food designed to deliver 1.4 μg/day, while the control arm did not receive complementary food (10 clusters, 165 participants). Serum vitamin B12 and folate levels determined by radioimmunoassay were used to estimate the effect of intervention on vitamin B12 levels, adjusting for baseline levels and sex. Results Attrition at 24 months was 16.7% and 23.6% in the intervention and control arms respectively (p = 0.07). Over 24 months of intervention, mean (95% CI) serum vitamin B12 decreased from 392 (359–425) pmol/dL to 357 (300–414) pmol/dL (p < 0.07) in the intervention arm and from 395 (350–440) pmol/dL to 351 (308–395) pmol/dL in the control arm. There was no significant effect of the intervention on folate status. Discussion Our findings suggest that foods fortified with 1.4 μg/daily vitamin B12 as provided by Chile’s national programme for older people are insufficient to ensure adequate vitamin B12 levels in this population. Chile has a long and successful experience with nutrition intervention programs; however, the country’s changing demographic and nutritional profiles require a constant adjustment of the programs. PMID:24016218

  1. Immunohistochemical Quantification of the Vitamin B12 Transport Protein (TCII), Cell Surface Receptor (TCII-R) and Ki-67 in Human Tumor Xenografts

    PubMed Central

    Sysel, Annette M.; Valli, Victor E.; Nagle, Ray B.; Bauer, Joseph A.

    2014-01-01

    Background/Aim Cancer cells have an essential demand for vitamin B12 (cobalamin) to enable cellular replication. The present pilot study quantified the immunohistochemical expression of vitamin B12 transport protein (Transcobalamin II; TCII), cell surface receptor (Transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in human tumor xenografts. Materials and Methods Tissue microarray slides containing 34 xenograft tumor tissues were immunohistochemically stained using TCN2 (anti-TCII), CD320 (anti-TCII-R) and MIB-1 (anti-Ki-67) antibodies. Representatively stained areas of all slides were digitally imaged and protein expression was quantified using ImageJ software plugins. Results All xenograft tumor tissues stained positively for TCII, TCII-R and Ki-67 proteins; expression varied both within and between tumor types. Correlation between TCII/TCII-R and Ki-67 expression was not significant in xenograft tissues. Conclusion Proliferating cancer cells express measurable levels of TCII and TCII-R. Immunohistochemical quantification of these markers may be useful as a tool for detection of tumors, tailored selection of anti-tumor therapies and surveillance for evidence of recurrent disease. PMID:24122983

  2. Improved AOAC First Action 2011.08 for the Analysis of Vitamin B12 in Infant Formula and Adult/Pediatric Formulas: First Action 2014.02.

    PubMed

    Gimnez, Esther Campos

    2014-01-01

    This report documents improvement and single-laboratory validation performed on AOAC First Action Method 2011.08 for vitamin B12 in infant formula and adult/pediatric nutritional formula. The original validation study included a range of fortified products, from infant formulas to breakfast cereals or beverages. Extended validation data, including additional infant formulas and adult/pediatric nutritionals, has now been produced. In addition, the method has been modified to use ultra-HPLC and the calibration range extended in a multilevel calibration curve. Detection and quantification limits were also improved by increasing the sample weight used for analysis and the reconstitution rate adapted to the requirements. The Stakeholder Panel on Infant Formula and Adult Nutritionals Test Material Kit, designed to represent a large range of products within the category (infant formula and adult nutritionals made from any combination of milk, soy, rice, whey, hydrolyzed protein, starch, and amino acids, with and without intact protein), was used to determine performance characteristics of the method. The modifications included allow now full compliance with standard method performance requirements established for vitamin B12 (SMPR 2011.005). LOQ was ?0.01 ?g/100 g, working range between 0.01 and 5.0 ?g/100 g, repeatability ?7%, and recovery in the range 90-110%. The method was granted AOAC First Action status 2014.02. PMID:25902990

  3. THE DEVELOPMENT OF VALUES FOR VITAMINS E AND B12 FOR FORTIFIED FOODS IN THE UNITED STATES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrient data from the USDA National Nutrient Database for Standard Reference (SR) form the foundation of the Food and Nutrient Database for Dietary Surveys (FNDDS). Of the 7,000 foods in SR about 2,700 foods are used in the FNDDS. Complete nutrient profiles for >60 nutrients, including vitamins E a...

  4. Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status, and recommendations for revised cut-points

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: We propose a novel approach to diagnose B12 status by combining four blood markers: total B12 (B12), holo-transcobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy). Combined B12 status is expressed as cB12=log10[(holoTCB12)/(MMAHcy)](reference, age function). Her...

  5. Control of prostate cancer associated with withdrawal of a supplement containing folic acid, L-methyltetrahydrofolate and vitamin B12: a case report

    PubMed Central

    2011-01-01

    Introduction This is the first report of possible direct stimulation of hormone-resistant prostate cancer or interference of docetaxel cytotoxicity of prostate cancer in a patient with biochemical relapse of prostatic-specific antigen. This observation is of clinical and metabolic importance, especially at a time when more than 80 countries have fortified food supplies with folic acid and some contemplate further fortification with vitamin B12. Case presentation Our patient is a 71-year-old Caucasian man who had been diagnosed in 1997 with prostate cancer, stage T1c, and Gleason score 3+4 = 7. His primary treatment included intermittent androgen deprivation therapy including leuprolide + bicalutamide + deutasteride, ketoconazole + hydrocortisone, nilandrone and flutamide to resistance defined as biochemical relapse of PSA. While undergoing docetaxel therapy to treat a continually increasing prostate-specific antigen level, withdrawal of 10 daily doses of a supplement containing 500 ?g of vitamin B12 as cyanocobalamin, as well as 400 ?g of folic acid as pteroylglutamic acid and 400 ?g of L-5-methyltetrahydrofolate for a combined total of 800 ?g of mixed folates, was associated with a return to a normal serum prostatic-specific antigen level. Conclusion This case report illustrates the importance of the effects of supplements containing large amounts of folic acid, L-5-methyltetrahydrofolate, and cyanocobalamin on the metabolism of prostate cancer cells directly and/or B vitamin interference with docetaxel efficacy. Physicians caring for patients with prostate cancer undergoing watchful waiting, hormone therapy, and/or chemotherapy should consider the possible acceleration of tumor growth and/or metastasis and the development of drug resistance associated with supplement ingestion. We describe several pathways of metabolic and epigenetic interactions that could affect the observed changes in serum levels of prostate-specific antigen. PMID:21867542

  6. Relationship between vitamin B12, folate and homocysteine levels and H. Pylori infection in patients with functional dyspepsia: A cross-section study

    PubMed Central

    2012-01-01

    Background H. pylori infection has been associated with many micronutrient deficiencies. There is a dearth of data from communities with nutritional deficiencies and high prevalence of H. pylori infection. The aim of this study was to determine the impact of H. pylori infection on serum levels of vitamin B12, folate and homocysteine in patients with functional dyspepsia (FD). Methods One hundred and thirty-two patients with FD undergoing gastroscopy were enrolled. The serum was analyzed for B12, folate and homocysteine levels before gastroscopy. H. pylori infection was diagnosed by histopathological examination of gastric biopsies and urea breath test. An independent sample t-test and the MannWhitney test were used to compare mean serum concentrations of biomarkers between H. pylori-positive and H. pylori-negative groups of patients. A Chi-square test was performed to assess the differences among proportions, while Spearmans rho was used for correlation analysis between levels of B12 and homocysteine. Results The mean age of the group was 40.3??11.5 (1972) years. Folate deficiency was seen in 43 (34.6%), B12 deficiency in 30 (23.1%) and hyperhomocysteinemia in 60 (46.2%) patients. H. pylori was present in 80 (61.5%) patients with FD while it was absent in 50 (38.5%). Mean serum levels of B12, folate and homocysteine in the H. pylori-positive group of patients were not significantly different from the levels in the H. pylori-negative group (357??170 vs. 313??136?pg/mL; p?=?0.13), (4.35??1.89 vs. 4.42??1.93?ng/mL; p?=?0.84); (15.88??8.97 vs. 16.62??7.82??mol/L; p?=?0.24); respectively. B12 deficiency (?200?pg/mL) was 23.8% in the H. pylori-positive patients versus 22.0% in the H. pylori-negative patients. Folate deficiency (?3.5?ng/mL) was 33.8% in the H. pylori-positive group versus 36% in the H. pylori-negative group. Hyperhomocysteinemia (>15??mol/L) was present in 46.2% of H. pylori-positive patients compared to 44% in the H. pylori-negative group. Correlation analysis indicated that serum B12 levels were inversely associated with serum levels of homocysteine in patients with FD (rho?=??0.192; p?=?0.028). Conclusions This study demonstrated an inverse relationship between serum levels of B12 and homocysteine in patients with FD. Moreover, no impact of the presence of H. pylori was found on B12, folate and homocysteine levels in such patients. PMID:22546014

  7. Vitamin B12 Deficiency and Hemoglobin H Disease Early Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Series of Unfortunate Events

    PubMed Central

    Andreadis, Panagiotis; Theodoridou, Stamatia; Pasakiotou, Marily; Arapoglou, Stergios; Gigi, Eleni; Vetsiou, Evaggelia; Vlachaki, Efthymia

    2015-01-01

    We herein would like to report an interesting case of a patient who presented with anemia and thrombocytopenia combined with high serum Lactic Dehydrogenase where Thrombotic Thrombocytopenic Purpura was originally considered. As indicated a central venous catheter was inserted in his subclavian vein which led to mediastinal hematoma and finally intubation and Intensive Care Unit (ICU) hospitalization. After further examination patient was finally diagnosed with B12 deficiency in a setting of H hemoglobinopathy. There have been previous reports where pernicious anemia was originally diagnosed and treated as Thrombotic Thrombocytopenic Purpura but there has been none to our knowledge that was implicated with hemothorax and ICU hospitalization or correlated with thalassemia and we discuss the significance of accurate diagnosis in order to avoid adverse reactions and therapy implications. PMID:26609455

  8. In vitro release studies of vitamin B 12 from poly N-vinyl pyrrolidone/starch hydrogels grafted with acrylic acid synthesized by gamma radiation

    NASA Astrophysics Data System (ADS)

    Eid, M.

    2008-12-01

    Co-polymeric hydrogels containing N-vinyl pyrrolidone and starch grafted with acrylic acid were synthesized by gamma radiation to be used as drug delivery system. Their gel contents, grafting swelling and thermal gravimetric analysis were evaluated. The gel content increases by increasing the irradiation dose up to 50 kGy, then decreases. The grafting percent increases by the increasing of acrylic acid. The thermal stability and the rate of the thermal decomposition changed according to the different compositions. The maximum rate of the thermal decomposition decreases by increasing the irradiation dose from 20 to 30 kGy and increases by increasing the irradiation dose from 30 to 70 kGy. The hydrogels loaded with vitamin B 12 demonstrated a decrease release in acidic medium than the neutral one.

  9. Drug release profiles and microstructural characterization of cast and freeze dried vitamin B12 buccal films by positron annihilation lifetime spectroscopy.

    PubMed

    Szab, Barnabs; Kllai, Nikolett; Tth, Gerg?; Hetnyi, Gergely; Zelk, Romna

    2014-02-01

    Solvent cast and freeze dried films, containing the water-soluble vitamin B12 as model drug were prepared from two polymers, sodium alginate (SA), and Carbopol 71G (CP). The proportion of the CP was changed in the films. The microstructural characterization of various samples was carried out by positron annihilation lifetime spectroscopy (PALS). The drug release kinetics of untreated and stored samples was evaluated by the conventionally applied semi-empirical power law. Correlation was found between the changes of the characteristic parameters of the drug release and the ortho-positronium (o-Ps) lifetime values of polymer samples. The results indicated that the increase of CP concentration, the freeze-drying process and the storage at 75% R.H. decreased the rate of drug release. The PALS method enabled the distinction between the micro- and macrostructural factors influencing the drug release profile of polymer films. PMID:24269613

  10. Conformational Motions and Functionally Key Residues for Vitamin B12 Transporter BtuCD-BtuF Revealed by Elastic Network Model with a Function-Related Internal Coordinate.

    PubMed

    Su, Ji-Guo; Zhang, Xiao; Zhao, Shu-Xin; Li, Xing-Yuan; Hou, Yan-Xue; Wu, Yi-Dong; Zhu, Jian-Zhuo; An, Hai-Long

    2015-01-01

    BtuCD-BtuF from Escherichia coli is a binding protein-dependent adenosine triphosphate (ATP)-binding cassette (ABC) transporter system that uses the energy of ATP hydrolysis to transmit vitamin B12 across cellular membranes. Experimental studies have showed that during the transport cycle, the transporter undergoes conformational transitions between the "inward-facing" and "outward-facing" states, which results in the open-closed motions of the cytoplasmic gate of the transport channel. The opening-closing of the channel gate play critical roles for the function of the transporter, which enables the substrate vitamin B12 to be translocated into the cell. In the present work, the extent of opening of the cytoplasmic gate was chosen as a function-related internal coordinate. Then the mean-square fluctuation of the internal coordinate, as well as the cross-correlation between the displacement of the internal coordinate and the movement of each residue in the protein, were calculated based on the normal mode analysis of the elastic network model to analyze the function-related motions encoded in the structure of the system. In addition, the key residues important for the functional motions of the transporter were predicted by using a perturbation method. In order to facilitate the calculations, the internal coordinate was introduced as one of the axes of the coordinate space and the conventional Cartesian coordinate space was transformed into the internal/Cartesian space with linear approximation. All the calculations were carried out in this internal/Cartesian space. Our method can successfully identify the functional motions and key residues for the transporter BtuCD-BtuF, which are well consistent with the experimental observations. PMID:26247943

  11. Conformational Motions and Functionally Key Residues for Vitamin B12 Transporter BtuCD–BtuF Revealed by Elastic Network Model with a Function-Related Internal Coordinate

    PubMed Central

    Su, Ji-Guo; Zhang, Xiao; Zhao, Shu-Xin; Li, Xing-Yuan; Hou, Yan-Xue; Wu, Yi-Dong; Zhu, Jian-Zhuo; An, Hai-Long

    2015-01-01

    BtuCD–BtuF from Escherichia coli is a binding protein-dependent adenosine triphosphate (ATP)-binding cassette (ABC) transporter system that uses the energy of ATP hydrolysis to transmit vitamin B12 across cellular membranes. Experimental studies have showed that during the transport cycle, the transporter undergoes conformational transitions between the “inward-facing” and “outward-facing” states, which results in the open–closed motions of the cytoplasmic gate of the transport channel. The opening–closing of the channel gate play critical roles for the function of the transporter, which enables the substrate vitamin B12 to be translocated into the cell. In the present work, the extent of opening of the cytoplasmic gate was chosen as a function-related internal coordinate. Then the mean-square fluctuation of the internal coordinate, as well as the cross-correlation between the displacement of the internal coordinate and the movement of each residue in the protein, were calculated based on the normal mode analysis of the elastic network model to analyze the function-related motions encoded in the structure of the system. In addition, the key residues important for the functional motions of the transporter were predicted by using a perturbation method. In order to facilitate the calculations, the internal coordinate was introduced as one of the axes of the coordinate space and the conventional Cartesian coordinate space was transformed into the internal/Cartesian space with linear approximation. All the calculations were carried out in this internal/Cartesian space. Our method can successfully identify the functional motions and key residues for the transporter BtuCD–BtuF, which are well consistent with the experimental observations. PMID:26247943

  12. Erythrocyte fatty acid profiles and plasma homocysteine, folate and vitamin B6 and B12 in recurrent depression: Implications for co-morbidity with cardiovascular disease.

    PubMed

    Assies, Johanna; Mocking, Roel J T; Lok, Anja; Koeter, Maarten W J; Bockting, Claudi L H; Visser, Ieke; Pouwer, Franois; Ruh, Henricus G; Schene, Aart H

    2015-10-30

    Oxidative stress induced interactions between fatty acid (FA) and one-carbon metabolism may be involved in co-occurrence of major depressive disorder (MDD) and cardiovascular disease (CVD), which have been scarcely studied together. In 137 recurrent MDD-patients vs. 73 age- and sex-matched healthy controls, we simultaneously measured key components of one-carbon metabolism in plasma (homocysteine, folate, vitamins B6 and B12), and of FA-metabolism in red blood cell membranes [main polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) and structural FA-indices (chain length, unsaturation, peroxidation)]. Results show significant positive associations of folate with EPA, DHA, and the peroxidation index, which were similar in patients and controls. After correction for confounders, these associations were lost except for EPA. Associations between B-vitamins and FA-parameters were non-significant, but also similar in patients and controls. Homocysteine and DHA were significantly less negatively associated in patients than in controls. In conclusion, these data indicate similarities but also differences in associations between parameters of one-carbon and FA-metabolism in recurrent MDD patients vs. controls, which may reflect differences in handling of oxidative stress. Further research should test the consequences of these differences, particularly the premature development of CVD in MDD. PMID:26260568

  13. Neoproterozoic Oxygenation of Earth Surface Environments Reflected in the Late Evolution of the O2-Dependent Vitamin B12 Biosynthesis Pathway

    NASA Astrophysics Data System (ADS)

    Saito, M. A.; Bertrand, E. M.; Anbar, A.

    2008-12-01

    There are multiple lines of evidence for a significant rise of O2 in the Earth's atmosphere ~2.4 Ga. A second oxygenation event in the Neoproterozoic is not as well constrained. These changes in environmental redox affected the abundances of bioessential elements. Trace elements such as Co, Fe, and Ni were likely favored in the early evolution of metalloenzymes, prior to the first oxidation event. Consistent with this expectation, vitamin B12 is a Co-containing biomolecule whose biosynthesis is thought to have evolved prior to the origin of oxygenic photosynthesis and the first rise in O2. However, biochemical characterization of the many enzymes involved in B12 biosynthesis has revealed two distinct pathways: an O2-independent pathway and an O2-dependant pathway. The major difference between these pathways involves the timing of the insertion of Co. We examined the amino acid sequences of enzymes in the B12 biosynthesis pathway from a set of 100 phylogenetically diverse microbial genomes, focusing on enzymes exclusive to each pathway as well as enzymes shared by both. Molecular clock and phylogenetic analyses were performed on alignments of the sequences obtained from these study genomes. This approach focused on functional genes rather than the phylogeny of microbes in an attempt to understand the evolution of the pathway itself, rather than its presence in individual phylogenetic groups. Clear differences in age are apparent between representatives of each pathway. The O2-independent pathway and enzymes shared in both pathways show the most ancient last common ancestors. In contrast, the enzymes associated exclusively with the O2-dependent pathway diverged from a common ancestor less than a billion years ago. Phylogenetic analysis suggests that these enzymes were recruited from other biochemical pathways. From these results it seems likely that the evolution of the O2-dependent pathway occurred long after the initial evolution of the B12 biosynthesis. This conclusion provides evidence independent of the geological record as to the timing and existence of a second great oxidation event in Earth history.

  14. Navigating the B12 Road: Assimilation, Delivery, and Disorders of Cobalamin*

    PubMed Central

    Gherasim, Carmen; Lofgren, Michael; Banerjee, Ruma

    2013-01-01

    The reactivity of the cobalt-carbon bond in cobalamins is the key to their chemical versatility, supporting both methyl transfer and isomerization reactions. During evolution of higher eukaryotes that utilize vitamin B12, the high reactivity of the cofactor coupled with its low abundance pressured development of an efficient system for uptake, assimilation, and delivery of the cofactor to client B12-dependent enzymes. Although most proteins suspected to be involved in B12 trafficking were discovered by 2009, the recent identification of a new protein reveals that the quest for elucidating the intracellular B12 highway is still far from complete. Herein, we review the biochemistry of cobalamin trafficking. PMID:23539619

  15. Pulse radiolysis and ultra-high-performance liquid chromatography/high-resolution mass spectrometry studies on the reactions of the carbonate radical with vitamin B12 derivatives.

    PubMed

    Dassanayake, Rohan S; Shelley, Jacob T; Cabelli, Diane E; Brasch, Nicola E

    2015-04-20

    The reactions of the carbonate radical anion (CO3 (.) (-) ) with vitamin B12 derivatives were studied by pulse radiolysis. The carbonate radical anion directly oxidizes the metal center of cob(II)alamin quantitively to give hydroxycobalamin, with a bimolecular rate constant of 2.010(9) M(-1) s(-1) . The reaction of CO3 (.) (-) with hydroxycobalamin proceeds in two steps. The second-order rate constant for the first reaction is 4.310(8) M(-1) s(-1) . The rate of the second reaction is independent of the hydroxycobalamin concentration and is approximately 3.010(3) s(-1) . Evidence for formation of corrinoid complexes differing from cobalamin by the abstraction of two or four hydrogen atoms from the corrin macrocycle and lactone ring formation has been obtained by ultra-high-performance liquid chromatography/high-resolution mass spectrometry (UHPLC/HRMS). A mechanism is proposed in which abstraction of a hydrogen atom by CO3 (.) (-) from a carbon atom not involved in the ? conjugation system of the corrin occurs in the first step, resulting in formation of a Co(III) C-centered radical that undergoes rapid intramolecular electron transfer to form the corresponding Co(II) carbocation complex for about 50 % of these complexes. Subsequent competing pathways lead to formation of corrinoid complexes with two fewer hydrogen atoms and lactone derivatives of B12 . Our results demonstrate the potential of UHPLC combined with HRMS in the separation and identification of tetrapyrrole macrocycles with minor modifications from their parent molecule. PMID:25760981

  16. Reliability of a new technique for the determination of vitamin B12 absorption in children: single stool sample test--a double isotope technique

    SciTech Connect

    Hjelt, K.

    1986-03-01

    The fractional vitamin B12 absorption (FAB12) was determined in 39 patients with various gastrointestinal diseases by a double-isotope technique, employing a single stool sample test (SSST), as well as a complete stool collection. The age of the patients ranged from 2.5 months to 16.2 years (mean 5.0 years). The test dose was administered orally and consisted of 0.5-4.5 micrograms of /sup 57/CoB12 (approximately 0.05 microCi), carmine powder, and 2 mg /sup 51/CrCl/sub 3/ (approximately 1.25 microCi) as the inabsorbable tracer. The wholebody radiation to a 1-year-old child averaged only 20 mrad. The stool and napkin was collected and homogenized by addition of 300 ml chromium sulfuric acid. A 300-ml sample of the homogenized stool and napkin, as well as 300 ml chromium sulfuric acid (75% v/v) containing the standards, were counted in a broad-based well counter. The FAB12 determined by SSST employing the stool with the highest content of /sup 51/Cr (which corresponded to the most carmine-colored stool) correlated closely to the FAB12 based on complete stool collection (r = 0.98, n = 39, p less than 0.001). The reproducibility of FAB12 determined by SSST was assessed from double assays in 19 patients. For a mean value of 12%, the SD was 3%, which corresponded to a coefficient of variation (CV) of 25%. The excretion of /sup 57/Co and /sup 51/Cr in the urine was examined in six patients with moderate to severe mucosal damage and was found to be low.

  17. Enantioselective excited-state quenching of racemic Tb (III) and Eu (III) Tris (pyridine-2,6-dicarboxylate) by vitamin B 12 derivatives

    NASA Astrophysics Data System (ADS)

    Meskers, Stefan C. J.; Dekkers, Harry P. J. M.

    1999-08-01

    Enantioselectivity in the dynamic quenching of the luminescence of the ? and ? enantiomers of racemic Tb(III)(pyridine-2,6-dicarboxylate=DPA) 33- and Eu(DPA) 33- by a series of corrinoids is demonstrated by time resolved luminescence and circular-polarization-of-luminescence (CPL) spectroscopy. Studied are cyanocobalamin (vitamin B 12), aquacobalamin (B 12a) and its conjugated base hydroxocobalamin (HOCbl), dicyanocobinamide ((CN) 2Cbi) and the heptamethyl ester of dicyanocobyrinic acid ((CN) 2Cby(OMe) 7). For this set of quenchers (Q), the diastereomeric quenching rate constants ( kq? and kq?) are reported together with the degree of enantioselectivity Eq=( kq?- kq?)/( kq?+ kq?). In the systems with Tb, values of the average rate constant kqavg(=( kq?+ kq?)/2) are 1.0, 2.9 and 0.53 10 8 M -1 s -1 for CNCbl, (CN) 2Cbi, (CN) 2Cby(OMe) 7 with Eq=-0.24, -0.20, +0.01 (standard error of Eq is 0.01). The quenching by B 12a is strongly dependent on pH and ionic strength ( I); when I=12 mM we find kqavg=5.3, Eq=-0.23 at pH 6.7 and kqavg=1.3, Eq=-0.27 at pH 8.9. Corresponding rates for Eu are 0.41, 27, 3.4 10 7 M -1 s -1 and for B 12a, 7.3 and 1.2 10 7 M -1 s -1, corresponding values for Eq -0.27, -0.29, +0.02, -0.21 and -0.29. The quenching reaction is modeled as a pre-equilibrium involving the formation of an encounter complex (association constant K) followed by the actual electronic energy transfer step (rate ket). By relating the quenching data with molecular structure it is argued that the binding in the encounter complex involves two hydrogen bonds between the uncoordinated carboxylate oxygen atom of two DPA ligands of Ln(DPA) 33- and two amide groups of the corrinoid, presumably involving the a and g, the a and b, or the b and g side chains. For some corrinoid/Ln(DPA) 33- complexes the association constants and enantioselectivities in the ground state are known (Spectrochimica Acta 55A (1999) 1837-1855), which allows for an estimate of the average rate of energy transfer, ketavg (i.e. ( ket?+ ket?)/2). The enantioselectivity in the quenching reaction is lower than in the ground state association which is interpreted in terms of different values of ket in the two diastereomeric Ln-corrinoid complexes; for both Tb and Eu we find ket?/ ket?0.3 with CNCbl, B 12a at pH 6.7 and (CN) 2Cbi. These data imply that the chiral discrimination in the energy transfer is considerable and counteracts that in the binding but does not dominate it.

  18. Comparison of two modes of vitamin B12 supplementation on neuroconduction and cognitive function among older people living in Sandiago, Chile: A cluster randomized controlled trial. A study protocol(ISRCTN 02694183)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Older people have a high risk of vitamin B12 deficiency; this can lead to varying degrees of cognitive and neurological impairment. CBL deficiency may present as macrocytic anemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older peo...

  19. Expression of genes encoding enzymes involved in the one carbon cycle in rat placenta is determined by maternal micronutrients (folic acid, vitamin B12) and omega-3 fatty acids.

    PubMed

    Khot, Vinita; Kale, Anvita; Joshi, Asmita; Chavan-Gautam, Preeti; Joshi, Sadhana

    2014-01-01

    We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels. Vitamin B12 deficient groups were supplemented with omega-3 fatty acid. Placental mRNA levels of enzymes, levels of phospholipids, and glutathione were determined. Results suggest that maternal micronutrient imbalance (excess folic acid with vitamin B12 deficiency) leads to lower mRNA levels of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase , but higher cystathionine b-synthase (CBS) and Phosphatidylethanolamine-N-methyltransferase (PEMT) as compared to control. Omega-3 supplementation normalized CBS and MTHFR mRNA levels. Increased placental phosphatidylethanolamine (PE), phosphatidylcholine (PC), in the same group was also observed. Our data suggests that adverse effects of a maternal micronutrient imbalanced diet may be due to differential regulation of key genes encoding enzymes in one carbon cycle and omega-3 supplementation may ameliorate most of these changes. PMID:25003120

  20. Expression of Genes Encoding Enzymes Involved in the One Carbon Cycle in Rat Placenta is Determined by Maternal Micronutrients (Folic Acid, Vitamin B12) and Omega-3 Fatty Acids

    PubMed Central

    Khot, Vinita; Kale, Anvita; Joshi, Asmita; Chavan-Gautam, Preeti; Joshi, Sadhana

    2014-01-01

    We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels. Vitamin B12 deficient groups were supplemented with omega-3 fatty acid. Placental mRNA levels of enzymes, levels of phospholipids, and glutathione were determined. Results suggest that maternal micronutrient imbalance (excess folic acid with vitamin B12 deficiency) leads to lower mRNA levels of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase , but higher cystathionine b-synthase (CBS) and Phosphatidylethanolamine-N-methyltransferase (PEMT) as compared to control. Omega-3 supplementation normalized CBS and MTHFR mRNA levels. Increased placental phosphatidylethanolamine (PE), phosphatidylcholine (PC), in the same group was also observed. Our data suggests that adverse effects of a maternal micronutrient imbalanced diet may be due to differential regulation of key genes encoding enzymes in one carbon cycle and omega-3 supplementation may ameliorate most of these changes. PMID:25003120

  1. Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional studies of vitamin B12 metabolism.

    PubMed

    Pupavac, Mihaela; Tian, Xia; Chu, Jordan; Wang, Guoli; Feng, Yanming; Chen, Stella; Fenter, Remington; Zhang, Victor W; Wang, Jing; Watkins, David; Wong, Lee-Jun; Rosenblatt, David S

    2016-03-01

    Next generation sequencing (NGS) based gene panel testing is increasingly available as a molecular diagnostic approach for inborn errors of metabolism. Over the past 40years patients have been referred to the Vitamin B12 Clinical Research Laboratory at McGill University for diagnosis of inborn errors of cobalamin metabolism by functional studies in cultured fibroblasts. DNA samples from patients in which no diagnosis was made by these studies were tested by a NGS gene panel to determine whether any molecular diagnoses could be made. 131 DNA samples from patients with elevated methylmalonic acid and no diagnosis following functional studies of cobalamin metabolism were analyzed using the 24 gene extended cobalamin metabolism NGS based panel developed by Baylor Miraca Genetics Laboratories. Gene panel testing identified two or more variants in a single gene in 16/131 patients. Eight patients had pathogenic findings, one had a finding of uncertain significance, and seven had benign findings. Of the patients with pathogenic findings, five had mutations in ACSF3, two in SUCLG1 and one in TCN2. Thus, the NGS gene panel allowed for the presumptive diagnosis of 8 additional patients for which a diagnosis was not made by the functional assays. PMID:26827111

  2. Enantioselective outer-sphere complexation of lanthanide(III) tris (pyridine-2,6-dicarboxylate) chelates with vitamin B 12 derivatives. An NMR and CD study

    NASA Astrophysics Data System (ADS)

    Meskers, Stefan C. J.; Dekkers, Harry P. J. M.

    1999-08-01

    The binding of three corrinoids, cyanocobalarnin (vitamin B 12, CNCbl), aquacobalamin (vitamin B 12a, H 2OCbl +) and dicyanocobinamide ((CN) 2Cbi), collectively denoted by Q, to the ?- and ?-enantiomer of Ln(DPA) 33- complexes (Ln=lanthanide, DPA=2,6-pyridine dicarboxylate) in aqueous solution at room temperature is investigated by NMR and Circular Dichroism (CD) spectroscopy. Tb(DPA) 33- induces shifts of the 1H-NMR resonances of Q. A formula, describing the dipolar interaction between the proton spin and the paramagnetic moment of the lanthanide complex, is fitted to the lanthanide induced shifts, yielding the position of Tb(DPA) 33- and the orientation of its magnetic axis with respect to the corrinoid. The magnitude of the shifts provide the value of Kavg, an average of the association constants of the two diastereomeric complexes {?-Tb(DPA) 33-Q) and {?-Tb(DPA) 33-Q}. We find Kavg=40.5 (B 12) and 0.80.2 M -1 ((CN) 2Cbi). The value for H 2OCbl + depends strongly on the solution's ionic strength I: Kavg=(71)10 1, 225 and 167 M -1 at I=0.007, 0.12 and 0.22 M, respectively. The addition of the corrinoids to a (racemic) solution of Nd(DPA) 33-, induces CD in the electronic Nd(III) transitions in the 700-800 nm region (ICD). This Pfeiffer effect is attributed to an excess of ?-Nd(DPA) 33- in the enantioselective, outer-sphere association with the corrinoids. From the magnitude of the ICD as a function of [Q], in conjunction with the (indirectly) determined CD effect of ?-Nd(DPA) 33-, values are determined for K?- K?. We find K?- K?=-242 M -1 for H 2OCbl + at pH 6.7 and I=0.12 M and -122 M -1 at I=0.22 M; -4.40.5 M -1 for CNCbl and -0.90.3 M -1 for (CN) 2Cbi. Adopting the view that in the lanthanide series Ln(DPA) 33- chelates are isostructural, the results of the NMR and CD experiments are combined to estimate the enantioselectivity in the binding Eb, defined as ( K?- K?)/2 Kavg. We find Eb=-0.50.2 for H 2OCbl +, -0.70.2 for CNCbl and -0.70.3 for (CN) 2Cbi. On the basis of the NMR data, a molecular structure is proposed for the two diastereomeric {Ln(DPA) 33-Q} complexes. The bonding involves hydrogen bonds between the amide proton on the a and g side chain of the corrinoid and the carboxylate oxygen of two DPA ligands.

  3. Cellular uptake of metallated cobalamins.

    PubMed

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry; Gammelgaard, Bente; Furger, Evelyne; Alberto, Roger

    2016-03-16

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives including [Cbl-OH2](+), [{Co}-CN-{cis-PtCl(NH3)2}](+), [{Re}-{Co}-CN-{cis-PtCl(NH3)2}](+), and [{Co}-CN-{trans-Pt(Cyt)(NH3)2}](2+) (Cyt = cytarabin) was high compared to neutral B12, which implied the existence of an additional internalization pathway for charged B12 vitamin analogs. The affinities of the charged B12 derivatives to the B12 transporters HC, IF and TC were similar to that of native vitamin B12. PMID:26739575

  4. Studies on Derivation of Transcobalamin III from Granulocytes ENHANCEMENT BY LITHIUM AND ELIMINATION BY FLUORIDE OF IN VITRO INCREMENTS IN VITAMIN B12-BINDING CAPACITY

    PubMed Central

    Scott, J. M.; Bloomfield, F. J.; Stebbins, R.; Herbert, V.

    1974-01-01

    Unsaturated vitamin B12-binding capacity (UBBC) of human serum is not reproducibly measurable because it increases variably in vitro in relation to time, temperature, and, in the case of plasma, anticoagulant present before removal of cells. This variable increase proved to be due to variable release in vitro of transcobalamin III (TC III) from granulocytes. UBBC increase was greatest (up to fourfold normal levels) in the presence of lithium, which is the heparin salt used in many laboratories doing UBBC studies. In vitro increase was least when blood was collected in EDTA at 0C and immediately centrifuges at 0C (T0 sample); results equivalent to T0 were obtained at room temperature even after several hours delay when 47 mM fluoride was present; either cold temperature or 47 mM fluoride appeared to prevent TC III release from granulocytes. The measured levels of the three transcobalamins with T0 methods of collection, which presumably reflect most closely the in vivo circulating levels, suggest that TC I and TC III in normal plasms are of the same order of magnitude and together normally comprise less than 10% of the UBBC. Approximately 90% of the UBBC content of sonicates of peripheral blood granulocytes and of bone marrow aspirates of normal individuals appears to be TC III, with the rest being TC I. Thus, normal myelocytes, like normal granulocytes, appear to contain mainly TC III. No TC II was present in any of the sonicates. The general practice in most laboratories has been to determine serum UBBC. Because in vitro increments of up to 119% were found to occur in serum, this practice should be replaced by collection using methods that prevent such increments. Blood collected in EDTA-47 mM NaF had a stable, reproducible UBBC with no significant in vitro increment with time. EDTA-NaF UBBC was 640168 (range 380-921 pg B12 bound/ml plasma) for 12 normal adult men and 809232 (range 505-1208) for normal adult women. It presumably approximates circulating UBBC and is substantially below the serum UBBC mean of 935262 (range 611-1506 for the same 12 men) and 1273355 (range 811-2306 for the same 10 women). PMID:4202670

  5. Rationale, design and baseline characteristics of a large, simple, randomized trial of combined folic acid and vitamins B6 and B12 in high-risk patients: The Heart Outcomes Prevention Evaluation (HOPE)-2 trial

    PubMed Central

    2006-01-01

    BACKGROUND Epidemiological studies suggest that mild to moderate elevation in plasma homocysteine concentration is associated with increased risk of atherothrombotic cardiovascular (CV) disease. Simple, inexpensive and nontoxic therapy with folic acid and vitamins B6 and B12 reduces plasma homocysteine levels by approximately 25% to 30% and may reduce CV events. Therefore, a large, randomized clinical trial the Heart Outcomes Prevention Evaluation (HOPE)-2 study is being conducted to evaluate this therapy in patients at high risk for CV events. OBJECTIVES To evaluate whether long-term therapy with folic acid and vitamins B6 and B12 reduces the risk of major CV events in a high-risk population. The primary study outcome is the composite of death from CV causes, myocardial infarction and stroke. METHODS A total of 5522 patients aged 55 years or older with pre-existing CV disease or with diabetes and additional risk factor(s) at 145 centres in 13 countries were randomly assigned to daily therapy with combined folic acid 2.5 mg, vitamin B6 50 mg and vitamin B12 1 mg, or to placebo. Follow-up will average five years, to be completed by the end of 2005. RESULTS The patients baseline characteristics confirmed their high-risk status. Baseline homocysteine levels varied between countries and regions. HOPE-2 is one of the largest trials of folate and vitamins B6 and B12 and is expected to significantly contribute to the evaluation of the role of homocysteine lowering in CV prevention. PMID:16450017

  6. Folate- and vitamin B12-deficient diet during gestation and lactation alters cerebellar synapsin expression via impaired influence of estrogen nuclear receptor α.

    PubMed

    Pourié, Grégory; Martin, Nicolas; Bossenmeyer-Pourié, Carine; Akchiche, Nassila; Guéant-Rodriguez, Rosa Maria; Geoffroy, Andréa; Jeannesson, Elise; El Hajj Chehadeh, Sarah; Mimoun, Khalid; Brachet, Patrick; Koziel, Violette; Alberto, Jean-Marc; Helle, Deborah; Debard, Renée; Leininger, Brigitte; Daval, Jean-Luc; Guéant, Jean-Louis

    2015-09-01

    Deficiency in the methyl donors vitamin B12 and folate during pregnancy and postnatal life impairs proper brain development. We studied the consequences of this combined deficiency on cerebellum plasticity in offspring from rat mothers subjected to deficient diet during gestation and lactation and in rat neuroprogenitor cells expressing cerebellum markers. The major proteomic change in cerebellum of 21-d-old deprived females was a 2.2-fold lower expression of synapsins, which was confirmed in neuroprogenitors cultivated in the deficient condition. A pathway analysis suggested that these proteomic changes were related to estrogen receptor α (ER-α)/Src tyrosine kinase. The influence of impaired ER-α pathway was confirmed by abnormal negative geotaxis test at d 19-20 and decreased phsophorylation of synapsins in deprived females treated by ER-α antagonist 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP). This effect was consistent with 2-fold decreased expression and methylation of ER-α and subsequent decreased ER-α/PPAR-γ coactivator 1 α (PGC-1α) interaction in deficiency condition. The impaired ER-α pathway led to decreased expression of synapsins through 2-fold decreased EGR-1/Zif-268 transcription factor and to 1.7-fold reduced Src-dependent phosphorylation of synapsins. The treatment of neuroprogenitors with either MPP or PP1 (4-(4'-phenoxyanilino)-6,7-dimethoxyquinazoline, 6,7-dimethoxy-N-(4-phenoxyphenyl)-4-quinazolinamine, SKI-1, Src-l1) Src inhibitor produced similar effects. In conclusion, the deficiency during pregnancy and lactation impairs the expression of synapsins through a deregulation of ER-α pathway. PMID:26018677

  7. Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death

    SciTech Connect

    Hemendinger, Richelle A. Armstrong, Edward J.; Brooks, Benjamin Rix

    2011-03-15

    Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC{sub 50} (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC{sub 50} (concentration at which 50% of maximal cell death is inhibited) of 0.6 {mu}M and 0.4 {mu}M, respectively. In contrast, MTHF (up to 10 {mu}M) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.

  8. Determination of hydroxyalkyl derivatives of cobalamin (vitamin B12) using reversed phase high performance liquid chromatography with electrospray tandem mass spectrometry and ultraviolet diode array detection.

    PubMed

    Alsberg, T; Minten, J; Haglund, J; Trnqvist, M

    2001-01-01

    Electrospray ionization tandem mass spectrometry (ESI-MS/MS) and ultraviolet diode array detection (UV-DAD), coupled on-line to reversed phase high performance liquid chromatography (HPLC), was used for the characterization of hydroxyalkyl derivatives of cob(I)alamin. The reduced form of vitamin B12, cob(I)alamin, denoted a supernucleophile due to its high nucleophilic strength, has shown promise as an analytical tool in studies of electrophilically reactive compounds in vitro and in vivo. A method for analysis of DNA-phosphate adducts was developed earlier utilizing the supernucleophilicity of cob(I)alamin to transfer alkyl groups from the phosphotriester configuration in DNA, with the formation of a Co-substituted alkyl-cobalamin (alkyl-Cbl) complex. For the purpose of identification and quantification of alkyl-Cbls at high sensitivity, an MS/MS method has been developed with application to a number of 2-hydroxyalkyl-cobalamins (OHalkyl-Cbls). The precursor oxiranes were reacted with cob(I)alamin, followed by clean-up and mass spectrometric analysis of the resulting OHalkyl-Cbls. It was found that ionization was highly dependent on solvent composition. By using acetonitrile/water/trifluoroacetic acid (TFA) (eluent I), the base peak was the doubly protonated molecule [M + 2H](2+), whereas acetonitrile/water/1-methylpiperidine (eluent II) yielded the singly protonated molecule [M + H](+) as the base peak. Excellent separation was obtained with eluent II, with good separation between stereoisomers, thus enabling the characterization of these by means of UV spectra. Limits of quantitation for 2-hydroxypropyl-cobalamin (OHPr-Cbl) were 0.2 and 2 pg/microL (or 0.1 and 1 fmol/microL) using selected ion recording (SIR) with eluent I and II, respectively. The obtained detection level should be sufficient for analysis of alkyl-Cbls from a wide range of toxicological applications. PMID:11746915

  9. A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study.

    PubMed

    Swart, Karin M A; Ham, Annelies C; van Wijngaarden, Janneke P; Enneman, Anke W; van Dijk, Suzanne C; Sohl, Evelien; Brouwer-Brolsma, Elske M; van der Zwaluw, Nikita L; Zillikens, M Carola; Dhonukshe-Rutten, Rosalie A M; van der Velde, Nathalie; Brug, Johannes; Uitterlinden, Andr G; de Groot, Lisette C P G M; Lips, Paul; van Schoor, Natasja M

    2016-01-01

    Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ?65years with elevated plasma homocysteine concentrations [12-50mol/L (n=2919)] were randomly assigned to daily supplementation of 500g vitamin B12, 400g folic acid, and 600IU vitamin D3, or to placebo with 600IU vitamin D3. Physical performance (range 0-12) and handgrip strength (kg) were measured at baseline and after 2years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95% CI 0.9-1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95% CI 1.1-1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80years. These effects should be further tested in future studies. PMID:26412463

  10. A novel spectral resolution and simultaneous determination of multicomponent mixture of Vitamins B1, B6, B12, Benfotiamine and Diclofenac in tablets and capsules by derivative and MCR-ALS

    NASA Astrophysics Data System (ADS)

    Hegazy, Maha A.; Abdelwahab, Nada S.; Fayed, Ahmed S.

    2015-04-01

    A novel method was developed for spectral resolution and further determination of five-component mixture including Vitamin B complex (B1, B6, B12 and Benfotiamine) along with the commonly co-formulated Diclofenac. The method is simple, sensitive, precise and could efficiently determine the five components by a complementary application of two different techniques. The first is univariate second derivative method that was successfully applied for determination of Vitamin B12. The second is Multivariate Curve Resolution using the Alternating Least Squares method (MCR-ALS) by which an efficient resolution and quantitation of the quaternary spectrally overlapped Vitamin B1, Vitamin B6, Benfotiamine and Diclofenac sodium were achieved. The effect of different constraints was studied and the correlation between the true spectra and the estimated spectral profiles were found to be 0.9998, 0.9983, 0.9993 and 0.9933 for B1, B6, Benfotiamine and Diclofenac, respectively. All components were successfully determined in tablets and capsules and the results were compared to HPLC methods and they were found to be statistically non-significant.

  11. Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial.

    PubMed

    Enneman, Anke W; Swart, Karin M A; van Wijngaarden, Janneke P; van Dijk, Suzanne C; Ham, Annelies C; Brouwer-Brolsma, Elske M; van der Zwaluw, Nikita L; Dhonukshe-Rutten, Rosalie A M; van der Cammen, Tischa J M; de Groot, Lisette C P G M; van Meurs, Joyce; Lips, Paul; Uitterlinden, André G; Zillikens, M Carola; van Schoor, Natasja M; van der Velde, Nathalie

    2015-05-01

    High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged ≥65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p < 0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement. PMID:25712255

  12. Oxygen-Controlled Catalysis by Vitamin B12 -TiO2 : Formation of Esters and Amides from Trichlorinated Organic Compounds by Photoirradiation.

    PubMed

    Shimakoshi, Hisashi; Hisaeda, Yoshio

    2015-12-14

    An oxygen switch in catalysis of the cobalamin derivative (B12 )-TiO2 hybrid catalyst for the dechlorination of trichlorinated organic compounds has been developed. The covalently bound B12 on the TiO2 surface transformed trichlorinated organic compounds into an ester and amide by UV light irradiation under mild conditions (in air at room temperature), while dichlorostilbenes (E and Z forms) were formed in nitrogen from benzotrichloride. A benzoyl chloride was formed as an intermediate of the ester and amide, which was detected by GC-MS. The substrate scope of the synthetic strategy is demonstrated with a range of various trichlorinated organic compounds. A photo-duet reaction utilizing the hole and conduction band electron of TiO2 in B12 -TiO2 for the amide formation was also developed. PMID:26526962

  13. Lipid, Oxidative and Inflammatory Profile and Alterations in the Enzymes Paraoxonase and Butyrylcholinesterase in Plasma of Patients with Homocystinuria Due CBS Deficiency: The Vitamin B12 and Folic Acid Importance.

    PubMed

    Vanzin, Camila Simioni; Mescka, Caroline Paula; Donida, Bruna; Hammerschimidt, Tatiane Grazieli; Ribas, Graziela S; Kolling, Janana; Scherer, Emilene B; Vilarinho, Laura; Nogueira, Clia; Coitinho, Adriana Simon; Wajner, Moacir; Wyse, Angela T S; Vargas, Carmen Regla

    2015-08-01

    Cystathionine-?-synthase (CBS) deficiency is the main cause of homocystinuria. Homocysteine (Hcy), methionine, and other metabolites of Hcy accumulate in the body of affected patients. Despite the fact that thromboembolism represents the major cause of morbidity in CBS-deficient patients, the mechanisms of cardiovascular alterations found in homocystinuria remain unclear. In this work, we evaluated the lipid and inflammatory profile, oxidative protein damage, and the activities of the enzymes paraoxonase (PON1) and butyrylcholinesterase (BuChE) in plasma of CBS-deficient patients at diagnosis and during the treatment (protein-restricted diet supplemented with pyridoxine, folic acid, betaine, and vitamin B12). We also investigated the effect of folic acid and vitamin B12 on these parameters. We found a significant decrease in HDL cholesterol and apolipoprotein A1 (ApoA-1) levels, as well as in PON1 activity in both untreated and treated CBS-deficient patients when compared to controls. BuChE activity and IL-6 levels were significantly increased in not treated patients. Furthermore, significant positive correlations between PON1 activity and sulphydryl groups and between IL-6 levels and carbonyl content were verified. Moreover, vitamin B12 was positively correlated with PON1 and ApoA-1 levels, while folic acid was inversely correlated with total Hcy concentration, demonstrating the importance of this treatment. Our results also demonstrated that CBS-deficient patients presented important alterations in biochemical parameters, possibly caused by the metabolites of Hcy, as well as by oxidative stress, and that the adequate adherence to the treatment is essential to revert or prevent these alterations. PMID:25805165

  14. Evaluation of C677T polymorphism of the methylenetetra hydrofolate reductase gene and its association with levels of serum homocysteine, folate, and vitamin B12 as maternal risk factors for Down syndrome

    PubMed Central

    Mohanty, Pankaj K.; Kapoor, Seema; Dubey, Anand P.; Pandey, Sanjeev; Shah, Renuka; Nayak, Hemant K.; Polipalli, Sunil K.

    2012-01-01

    AIMS AND OBJECTIVE: Evaluation of C677T polymorphisms of the methylenetetra hydrofolate reductase (MTHFR) gene and its association with level of serum homocysteine, folate, and vitamin B12 as possible maternal risk factors for Down syndrome. DESIGN: This was a casecontrol study. MATERIAL AND METHODS Fifty-two mothers (mean age 27.6 years) with babies having free trisomy 21 of North Indian ethnicity and 52 control nonlactating mothers (mean age 24.9 years) of same ethnicity attending services of genetic lab for bloodletting for other causes were enrolled after informed written consent. Fasting blood was collected and was used for determination of plasma homocysteine, vitamin B12, and folate (serum and RBC), and for PCR amplification of the MTHFR gene. RESULTS: The prevalence of MTHFR C677T polymorphism in north Indian mothers of babies with trisomy 21 Down syndrome was 15.38% compared to 5.88 % in controls. The difference between two groups was not statistically significant (P = 0.124). Low serum folate was demonstrated in 34.62% of cases vs. 11.54% in controls, which was significant (P = 0.005). Low RBC folate was found in 30.7% of cases versus 11.53% in controls, which was not significant (P = 0.059), when analyzed independently. But on multiple regression analysis the difference was statistically significant. Low serum vitamin B12 was found in 42.31% of cases versus 34.62% in controls, which was not significant (P = 0.118). The mean serum homocysteine in cases was 10.35 0.68 while controls were 9.02 0.535. CONCLUSION: Serum levels of folate were low in cases. The RBC folate levels were comparable in both groups. However the combined serum folate and RBC folate were low in cases compared to control groups. Homocysteine levels in our study were higher in Down syndrome mothers compared to controls; however high-serum level of Homocysteine had no association with MTHFR polymorphism. No association of serum vitamin B12 with MTHFR polymorphism in occurrence of Down syndrome births was found. Peri- or preconceptional folate supplementation may therefore lead to a decline in DS births, if supported by larger studies. PMID:23716934

  15. Calcidiol and vitamin D binding protein uptake by LLC-PK/sub 1/ cells

    SciTech Connect

    Keenan, M.J.; Holmes, R.P.

    1986-03-01

    The process by which target cells take up vitamin D and its metabolites is not known. The authors studied the uptake of both /sup 3/H-calcidiol and /sup 125/I-Vitamin D Binding Protein (DBP) by LLC-PK/sub 1/ cells. Uptake was directly related to their extracellular concentrations. In the presence of 55 serum in the growth media cells previously incubated with 10 nM calcitriol for 4 hr had a greater uptake of calcidiol than those cells not incubated with calcitriol. This effect of calcitriol on calcidiol uptake was absent when cells were grown in hormone-supplemented, serum-free media, despite these cells having a cytosolic calcitriol receptor. Equal uptake of calcidiol occurred when DBP was absent and when DBP was present in a one to one molar ratio to calcidiol. With a 1:1 ratio of DBP to calcidiol and a measured K/sub D/ of 2 x 10/sup -8/M, the uptake of calcidiol could not be accounted for by uptake of the free ligand alone. A large excess of DBP (100:1) in relation to calcidiol suppressed uptake of calcidiol by approx. 90%. The authors have not been able to identify a saturable, specific uptake of either calcidiol or DBP despite DBP appearing to facilitate calcidiol uptake.

  16. Application of in vitro bioaccessibility and bioavailability methods for calcium, carotenoids, folate, iron, magnesium, polyphenols, zinc and vitamins B6, B12, D, and E

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A review of in vitro bioaccessibility and bioavailability methods for polyphenols and selected nutrients is presented. The review focuses on in vitro solubility, dialyzability, the dynamic gastrointestinal model (TIM), and Caco-2 cell models, the latter primarily for uptake and transport, and a disc...

  17. Superoxide-dependent uptake of vitamin C in human glioma cells.

    PubMed

    Rodrguez, Federico S; Salazar, Katterine A; Jara, Nery A; Garca-Robles, Mara A; Prez, Fernando; Ferrada, Luciano E; Martnez, Fernando; Nualart, Francisco J

    2013-12-01

    Glioblastomas are lethal brain tumors that resist current cytostatic therapies. Vitamin C may antagonize the effects of reactive oxygen species (ROS) generating therapies; however, it is often used to reduce therapy-related side effects despite its effects on therapy or tumor growth. Because the mechanisms of vitamin C uptake in gliomas are currently unknown, we evaluated the expression of the sodium-vitamin C cotransporter (SVCT) and facilitative hexose transporter (GLUT) families in human glioma cells. In addition, as microglial cells can greatly infiltrate high-grade gliomas (constituting up to 45% of cells in glioblastomas), the effect of TC620 glioma cell interactions with microglial-like HL60 cells on vitamin C uptake (Bystander effect) was determined. Although glioma cells expressed high levels of the SVCT isoform-2 (SVCT2), low functional activity, intracellular localization and the expression of the dominant-negative isoform (dnSVCT2) were observed. The increased glucose metabolic activity of glioma cells was evident by the high 2-Deoxy-d-glucose and dehydroascorbic acid (DHA) uptake rates through the GLUT isoform-1 (GLUT1), the main DHA transporter in glioblastoma. Co-culture of glioma cells and activated microglial-like HL60 cells resulted in extracellular ascorbic acid oxidation and high DHA uptake by glioma cells. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas. This study strongly suggests that the Bystander effect, that is, glioma cell interaction with oxidant-producing microglia, could be an important mechanism for glioma vitamin C loading in the absence of functional sodium-vitamin C cotransporter 2 (SVCT2) expression. The high cellular vitamin C load in glioma cells results from a high uptake of extracellular dehydroascorbic acid (DHA) generated by neighboring microglia. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas, considering that high-grade gliomas may be the only neoplasm where oxidant-producing microglia can almost equal the number of tumor cells. PMID:23859461

  18. Application of in vitro bioaccessibility and bioavailability methods for calcium, carotenoids, folate, iron, magnesium, polyphenols, zinc, and vitamins B6, B12, D, and E

    PubMed Central

    Etcheverry, Paz; Grusak, Michael A.; Fleige, Lisa E.

    2012-01-01

    A review of in vitro bioaccessibility and bioavailability methods for polyphenols and selected nutrients is presented. The review focuses on in vitro solubility, dialyzability, the dynamic gastrointestinal model (TIM)™, and Caco-2 cell models, the latter primarily for uptake and transport, and a discussion of how these methods have been applied to generate data for a range of nutrients, carotenoids, and polyphenols. Recommendations are given regarding which methods are most justified for answering bioaccessibility or bioavailability related questions for specific nutrients. The need for more validation studies in which in vivo results are compared to in vitro results is also discussed. PMID:22934067

  19. Different Neurologic Aspects of Nutritional B12 Deficiency in Infancy.

    PubMed

    Yilmaz, Sanem; Serdaroglu, Gul; Tekgul, Hasan; Gokben, Sarenur

    2016-04-01

    The objective of this study is to evaluate neurologic problems caused by nutritional vitamin B12 deficiency in infancy. Twenty-four cases between 2 and 18 months of age with neurologic symptoms and/or signs and diagnosed as nutritional vitamin B12 deficiency were analyzed. The most common symptoms were developmental retardation, afebrile seizures, and involuntary movements. The mean vitamin B12 levels were lower in patients with both neurologic and extraneurologic involvement when compared to those with only neurologic symptoms. All of the cases were treated with vitamin B12. In patients with severe deficiencies, involuntary movements were observed during vitamin B12 treatment using cyanocobalamin form. At the 1-year follow-up, all but 3 patients were considered neurodevelopmentally normal. The 3 patients that did not fully recover, on admission, had the lowest vitamin B12 levels. It is of great importance to prevent, diagnose, and treat vitamin B12 deficiency promptly to prevent the long-term neurologic problems. PMID:26310585

  20. Accurate measurement of the essential micronutrients methionine, homocysteine, vitamins B6, B12, B9 and their metabolites in plasma, brain and maternal milk of mice using LC/MS ion trap analysis.

    PubMed

    Oosterink, J Efraim; Naninck, Eva F G; Korosi, Aniko; Lucassen, Paul J; van Goudoever, Johannes B; Schierbeek, Henk

    2015-08-15

    Methionine, homocysteine, vitamins B6, B12, B9, and their metabolites are crucial co-factors and substrates for many basic biological pathways including one-carbon metabolism, and they are particularly important for brain function and development and epigenetic mechanisms. These are essential nutrients that cannot be synthesized endogenously and thus need to be taken in via diet. A novel method was developed that enables simultaneous assessment of the exact concentrations of these essential micronutrients in various matrices, including maternal milk, plasma, and brain of neonatal mice. The protocol for analysis of these components in the various matrices consists of a cleanup step (i.e. lipid extraction followed by protein precipitation) combined with a liquid chromatography mass spectrometry (LC/MS) ion trap method with high sensitivity and selectivity (SRM mode). This novel method enables the measurement of these essential nutrients with good recoveries (69-117%), and high intra-day (<10%) and high intra-day precision (defined as <15% for compounds with an isotopologue and <20% for compounds without an isotopologue as internal standard) in plasma, maternal milk, and brain of mice at low and high levels. In addition, lower limits of quantitation (LOQ) were determined for the various matrices in the range for methionine (700-2000nmol/L), homocysteine (280-460-nmol/L), vitamins B6 (5-230nmol/L), B12 (7-11nmol/L), B9 (20-30nmol/L). Degradation of vitamins and oxidation of homocysteine is limited to a minimum, and only small sample volumes (30?L plasma, 20mg brain and maternal milk) are needed for simultaneous measurement. This method can help to understand how these nutrients are transferred from mother to offspring via maternal milk, as well as how these nutrients are absorbed by the offspring and eventually taken up in various tissues amongst the brain in preclinical and clinical research settings. Therefore the method can help to explore critical periods in lactating mothers and developing offspring. PMID:26197436

  1. Vitamins

    MedlinePLUS

    ... are 13 vitamins your body needs. They are Vitamin A B vitamins (thiamine, riboflavin, niacin, pantothenic acid, biotin, ... anemic. Some vitamins may help prevent medical problems. Vitamin A prevents night blindness. The best way to get ...

  2. The 380 kb pCMU01 Plasmid Encodes Chloromethane Utilization Genes and Redundant Genes for Vitamin B12- and Tetrahydrofolate-Dependent Chloromethane Metabolism in Methylobacterium extorquens CM4: A Proteomic and Bioinformatics Study

    PubMed Central

    Roselli, Sandro; Nadalig, Thierry; Vuilleumier, Stphane; Bringel, Franoise

    2013-01-01

    Chloromethane (CH3Cl) is the most abundant volatile halocarbon in the atmosphere and contributes to the destruction of stratospheric ozone. The only known pathway for bacterial chloromethane utilization (cmu) was characterized in Methylobacterium extorquens CM4, a methylotrophic bacterium able to utilize compounds without carbon-carbon bonds such as methanol and chloromethane as the sole carbon source for growth. Previous work demonstrated that tetrahydrofolate and vitamin B12 are essential cofactors of cmuA- and cmuB-encoded methyltransferases of chloromethane dehalogenase, and that the pathway for chloromethane utilization is distinct from that for methanol. This work reports genomic and proteomic data demonstrating that cognate cmu genes are located on the 380 kb pCMU01 plasmid, which drives the previously defined pathway for tetrahydrofolate-mediated chloromethane dehalogenation. Comparison of complete genome sequences of strain CM4 and that of four other M. extorquens strains unable to grow with chloromethane showed that plasmid pCMU01 harbors unique genes without homologs in the compared genomes (bluB2, btuB, cobA, cbiD), as well as 13 duplicated genes with homologs of chromosome-borne genes involved in vitamin B12-associated biosynthesis and transport, or in tetrahydrofolate-dependent metabolism (folC2). In addition, the presence of both chromosomal and plasmid-borne genes for corrinoid salvaging pathways may ensure corrinoid coenzyme supply in challenging environments. Proteomes of M. extorquens CM4 grown with one-carbon substrates chloromethane and methanol were compared. Of the 49 proteins with differential abundance identified, only five (CmuA, CmuB, PurU, CobH2 and a PaaE-like uncharacterized putative oxidoreductase) are encoded by the pCMU01 plasmid. The mainly chromosome-encoded response to chloromethane involves gene clusters associated with oxidative stress, production of reducing equivalents (PntAA, Nuo complex), conversion of tetrahydrofolate-bound one-carbon units, and central metabolism. The mosaic organization of plasmid pCMU01 and the clustering of genes coding for dehalogenase enzymes and for biosynthesis of associated cofactors suggests a history of gene acquisition related to chloromethane utilization. PMID:23593113

  3. Status of Vitamins B-12 and B-6 but Not of Folate, Homocysteine, and the Methylenetetrahydrofolate Reductase C677T Polymorphism Are Associated with Impaired Cognition and Depression in Adults123

    PubMed Central

    Moorthy, Denish; Peter, Inga; Scott, Tammy M.; Parnell, Laurence D.; Lai, Chao-Qiang; Crott, Jimmy W.; Ordovás, José M.; Selhub, Jacob; Griffith, John; Rosenberg, Irwin H.; Tucker, Katherine L.; Troen, Aron M.

    2012-01-01

    The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene differs in frequency in various ethnic groups that have differing prevalence of age-related cognitive impairments. We used a series of neuro-psychological tests to examine the association of the MTHFR C677T polymorphism with cognition and depression and also to assess whether genotype modifies the association of folate and homocysteine with these outcomes. This study analyzed pooled cross-sectional data from 2 ethnically diverse cohorts of community-living adults: the Boston Puerto Rican Health Study (n = 939) and the Nutrition, Aging, and Memory in Elders study (n = 1017). Individuals in both cohorts underwent anthropometric and laboratory measurements and dietary and health assessments using validated questionnaires between the years 2003 and 2007. Cognitive outcomes included measures of global cognition [Mini-Mental Status Exam (MMSE)], depression (Center for Epidemiological Studies Depression Scale), and 3 factor scores for the domains of attention, executive function, and memory that were derived from a detailed set of neuropsychological tests. Low plasma vitamin B-12 concentrations were associated with poorer MMSE scores and higher depression scores, and low vitamin B-6 concentrations were associated with lower MMSE and worse attention and executive function in the multivariate analysis. In contrast, MTHFR genotype, folate, and homocysteine were not associated with cognition or depression in either ethnicity-pooled or stratified analysis. The current study did not find evidence of an association between the MTHFR C677T TT genotype and impaired cognition or depression in a population with adequate folate status and a high prevalence of cognitive impairment and depression. PMID:22739363

  4. B Vitamins

    MedlinePLUS

    ... get B vitamins from proteins such as fish, poultry, meat, eggs, and dairy products. Leafy green vegetables, beans, and peas also have B vitamins. Many cereals and some breads have added B vitamins. Not getting enough of certain B vitamins can cause diseases. A lack of B12 or B6 can cause ...

  5. Determination Co 2+ in vitamin B 12 based on enhancement of 2-(4-substituted-phenyl)-4,5-di(2-furyl) imidazole and H 2O 2 chemiluminescence reaction

    NASA Astrophysics Data System (ADS)

    Han, Lu; Zhang, Yumin; Kang, Jing; Tang, Jieli; Zhang, Yihua

    2011-11-01

    In this paper, three kinds of imidazole derivatives, 2-(4-methylphenyl)-4,5-di(2-furyl) imidazole (MDFI), 2-(4-nitrophenyl)-4,5-di(2-furyl) imidazole (NDFI), and 2-(4-tert-butylphenyl)-4,5-di(2-furyl) imidazole (t-BDFI) were synthesized. In an alkaline medium, the chemiluminescence (CL) reaction of imidazole derivatives with H 2O 2 has been investigated. It was also found that MDFI/H 2O 2 and t-BDFI/H 2O 2 systems gave strong CL. When Co 2+ was added into the two CL systems, the CL intensity was remarkably enhanced. In the optimum conditions, the CL intensity is linearly related to the logarithm of concentration of Co 2+. The linear ranges are 5 10 -9-2.5 10 -7 mol/L for MDFI/H 2O 2 system and 5 10 -9-2.5 10 -7 mol/L for t-BDFI/H 2O 2 system, and the corresponding detection limits are 1.2 10 -9 mol/L and 1.1 10 -9 mol/L, respectively. The method was applied to the determination of Co 2+ in vitamin B 12 injection. Furthermore, the CL mechanism was also discussed.

  6. Vitamin B12 and Folate Test

    MedlinePLUS

    ... include people with, for example, alcoholism , liver disease , gastric cancer, or individuals with malabsorption conditions such as celiac ... that removes part of the stomach, such as gastric bypass, or the intestines may ... People with cancer that has spread (metastasized) or with chronic hemolytic ...

  7. Vitamin B12 als biologisch aktive Modellsubstanz

    NASA Astrophysics Data System (ADS)

    Zagalak, Bolesław

    1982-02-01

    A critical review on corrinoid biochemistry and physiology is presented. This includes: chemical synthesis of biologically important organocorrinoids and the correlation between their structures and coenzymatic activity; forms, distribution and transport of physiologically active corrinoids; methylcobalamin- and adenosylcobalamin-dependent enzymatic reactions and their physiological functions; and steric course of the adenosylcobalamin-dependent enzymatic rearrangements. Special attention is paid to the mechanisms of adenosylcobalamin-dependent enzymatic reactions.

  8. UV-Stressed Daphnia pulex Increase Fitness through Uptake of Vitamin D3

    PubMed Central

    Walling, Kelly; Wilbert, Steven A.; Catlin, Diane M.; Monaghan, Cailin E.; Hlynchuk, Sofiya; Meehl, Pamela G.; Resch, Lauren N.; Carrera, J. Valerie; Bowles, Stephanie M.; Clark, Michael D.

    2015-01-01

    Ultraviolet radiation is known to be highly variable in aquatic ecosystems. It has been suggested that UV-exposed organisms may demonstrate enough phenotypic plasticity to maintain the relative fitness of natural populations. Our long-term objective is to determine the potential photoprotective effect of vitamin D3 on Daphnia pulex exposed to acute or chronic UV radiation. Herein we report our initial findings in this endeavor. D. pulex survival and reproduction (fitness) was monitored for 5 d as a proof of concept study. Significantly higher fitness was observed in the D. pulex with D3 than those without (most extreme effects observed were 0% survival in the absence of D3 and 100% with 10 ppm D3). Vitamin D3 was isolated from the culture media, the algal food (Pseudokirchneriella), and the D. pulex and quantified using high performance liquid chromatography (HPLC). Vitamin D3 was fluorescently labeled using a phenothiazinium dye and added to cultures of D. pulex. Images demonstrating the uptake of D3 into the tissues and carapace of the D. pulex were acquired. Our initial findings suggest a positive role for D3 in ecosystems as both UV-stressed algae and Daphnia sequester D3, and D. pulex demonstrate increased fitness in the presence of D3. PMID:26147286

  9. UV-Stressed Daphnia pulex Increase Fitness through Uptake of Vitamin D3.

    PubMed

    Connelly, Sandra J; Walling, Kelly; Wilbert, Steven A; Catlin, Diane M; Monaghan, Cailin E; Hlynchuk, Sofiya; Meehl, Pamela G; Resch, Lauren N; Carrera, J Valerie; Bowles, Stephanie M; Clark, Michael D; Tan, Loraine T; Cody, Jeremy A

    2015-01-01

    Ultraviolet radiation is known to be highly variable in aquatic ecosystems. It has been suggested that UV-exposed organisms may demonstrate enough phenotypic plasticity to maintain the relative fitness of natural populations. Our long-term objective is to determine the potential photoprotective effect of vitamin D3 on Daphnia pulex exposed to acute or chronic UV radiation. Herein we report our initial findings in this endeavor. D. pulex survival and reproduction (fitness) was monitored for 5 d as a proof of concept study. Significantly higher fitness was observed in the D. pulex with D3 than those without (most extreme effects observed were 0% survival in the absence of D3 and 100% with 10 ppm D3). Vitamin D3 was isolated from the culture media, the algal food (Pseudokirchneriella), and the D. pulex and quantified using high performance liquid chromatography (HPLC). Vitamin D3 was fluorescently labeled using a phenothiazinium dye and added to cultures of D. pulex. Images demonstrating the uptake of D3 into the tissues and carapace of the D. pulex were acquired. Our initial findings suggest a positive role for D3 in ecosystems as both UV-stressed algae and Daphnia sequester D3, and D. pulex demonstrate increased fitness in the presence of D3. PMID:26147286

  10. Mechanistic studies of the reactions of the reduced vitamin B12 derivatives with the HNO donor Piloty's acid: further evidence for oxidation of cob(i)alamin by (H)NO.

    PubMed

    Subedi, Harishchandra; Brasch, Nicola E

    2015-12-14

    There is accumulating evidence for the existence of HNO in biological systems. Compared with NO (˙NO), much less is known about the chemical and biochemical reactivity of HNO. Kinetic and mechanistic studies have been carried out on the reaction between the vitamin B12-derived radical complex cob(ii)alamin (Cbl(ii)˙, Cbl(ii)) with the widely used HNO donor Piloty's acid (PA). A stoichiometry of 1 : 2 Cbl(ii) : PA was obtained and PA decomposition to HNO and benzenesulfinate (C6H5SO2(-)) is the rate-determining step. No evidence was found for nitrite (Griess assay), ammonia (Nessler's test) or NH2OH (indooxine test) in the product solution, and it is likely that HNO is instead reduced to N2. A mechanism is proposed in which reduction of Cbl(ii) by (H)NO results in formation of cob(i)alamin (Cbl(i)(-)) and ˙NO. The Cbl(i)(-) intermediate is subsequently oxidized back to Cbl(ii) by a second (H)NO molecule, and Cbl(ii) reacts rapidly with ˙NO to form nitroxylcobalamin (NOCbl). Separate studies on the reaction between Cbl(i)(-) and PA shows that this system involves an additional step in which Cbl(i)(-) is first oxidized by (H)NO to Cbl(ii), which reacts further with (H)NO to form NOCbl, with an overall stoichiometry of 1 : 3 Cbl(i)(-) : PA. Experiments in the presence of nitrite for both systems support the involvement of a Cbl(i)(-) intermediate in the Cbl(ii)/PA reaction. These systems provide the second example of oxidation of cob(i)alamin by (H)NO. PMID:26618754

  11. Demonstration that CobG, the monooxygenase associated with the ring contraction process of the aerobic cobalamin (vitamin B12) biosynthetic pathway, contains an Fe-S center and a mononuclear non-heme iron center.

    PubMed

    Schroeder, Susanne; Lawrence, Andrew D; Biedendieck, Rebekka; Rose, Ruth-Sarah; Deery, Evelyne; Graham, Ross M; McLean, Kirsty J; Munro, Andrew W; Rigby, Stephen E J; Warren, Martin J

    2009-02-20

    The ring contraction process that occurs during cobalamin (vitamin B(12)) biosynthesis is mediated via the action of two enzymes, CobG and CobJ. The first of these generates a tertiary alcohol at the C-20 position of precorrin-3A by functioning as a monooxygenase, a reaction that also forms a gamma lactone with the acetic acid side chain on ring A. The product, precorrin-3B, is then acted upon by CobJ, which methylates at the C-17 position and promotes ring contraction of the macrocycle by catalyzing a masked pinacol rearrangement. Here, we report the characterization of CobG enzymes from Pseudomonas denitrificans and Brucella melitensis. We show that both contain a [4Fe-4S] center as well as a mononuclear non-heme iron. Although both enzymes are active in vivo, the P. denitrificans enzyme was found to be inactive in vitro. Further analysis of this enzyme revealed that the mononuclear non-heme iron was not reducible, and it was concluded that it is rapidly inactivated once it is released from the bacterial cell. In contrast, the B. melitensis enzyme was found to be fully active in vitro and the mononuclear non-heme iron was reducible by dithionite. The reduced mononuclear non-heme was able to react with the oxygen analogue NO, but only in the presence of the substrate precorrin-3A. The cysteine residues responsible for binding the Fe-S center were identified by site-directed mutagenesis. A mechanism for CobG is presented. PMID:19068481

  12. Vitamins

    MedlinePLUS

    ... helps you see at night. Vitamin C in oranges helps your body heal if you get a ... vitamin A? milk fortified with vitamin A liver orange fruits and vegetables (like cantaloupe, carrots, sweet potatoes) ...

  13. Proteins involved in uptake, intracellular transport and basolateral secretion of fat-soluble vitamins and carotenoids by mammalian enterocytes.

    PubMed

    Reboul, Emmanuelle; Borel, Patrick

    2011-10-01

    Our understanding of the molecular mechanisms responsible for fat-soluble vitamin uptake and transport at the intestinal level has advanced considerably over the past decade. On one hand, it has long been considered that vitamin D and E as well as β-carotene (the main provitamin A carotenoid in human diet) were absorbed by a passive diffusion process, although this could not explain the broad inter-individual variability in the absorption efficiency of these molecules. On the other hand, it was assumed that preformed vitamin A (retinol) and vitamin K1 (phylloquinone) absorption occurred via energy-dependent processes, but the transporters involved have not yet been identified. The recent discovery of intestinal proteins able to facilitate vitamin E and carotenoid uptake and secretion by the enterocyte has spurred renewed interest in studying the fundamental mechanisms involved in the absorption of these micronutrients. The proteins identified so far are cholesterol transporters such as SR-BI (scavenger receptor class B type I), CD36 (cluster determinant 36), NPC1L1 (Niemann-Pick C1-like 1) or ABCA1 (ATP-Binding Cassette A1) displaying a broad substrate specificity, but it is likely that other membrane proteins are also involved. After overviewing the metabolism of fat-soluble vitamins and carotenoids in the human upper gastrointestinal lumen, we will focus on the putative or identified proteins participating in the intestinal uptake, intracellular transport and basolateral secretion of these fat-soluble vitamins and carotenoids, and outline the uncertainties that need to be explored in the future. Identifying the proteins involved in intestinal uptake and transport of fat-soluble vitamins and carotenoids across the enterocyte is of great importance, especially as some of them are already targets for the development of drugs able to slow cholesterol absorption. Indeed, these drugs may also interfere with lipid vitamin uptake. A better understanding of the molecular mechanisms involved in fat-soluble vitamin and carotenoid absorption is a priority to better optimize their bioavailability. PMID:21763723

  14. Genomic distribution of B-vitamin auxotrophy and uptake transporters in environmental bacteria from the Chloroflexi phylum

    SciTech Connect

    Rodionova, Irina A.; Li, Xiaoqing; Plymale, Andrew E.; Motamedchaboki, Khatereh; Konopka, Allan; Romine, Margaret F.; Fredrickson, Jim K.; Osterman, Andrei; Rodionov, Dmitry A.

    2015-04-01

    Bacteria from the Chloroflexi phylum are dominant members of phototrophic microbial mat communities in terrestrial thermal environments. Vitamins of B-group are key intermediates (precursors) in the biosynthesis of indispensable enzyme cofactors driving numerous metabolic processes in all forms of life. A genomics-based reconstruction and comparative analysis of respective biosynthetic and salvage pathways and riboswitch regulons in over 20 representative Chloroflexi genomes revealed a widespread auxotrophy for some of the vitamins. The most prominent predicted phenotypic signature, auxotrophy for vitamins B1 and B7 was experimentally confirmed for the best studied model organism Chloroflexus aurantiacus. These observations along with identified candidate genes for the respective uptake transporters pointed to B vitamin exchange as an important aspect of syntrophic metabolism in microbial communities. Inferred specificities of homologous substrate-binding components of ABC transporters for vitamins B1 (ThiY) and B2 (RibY) were verified by thermofluorescent shift approach. A functional activity of the thiamine-specific transporter ThiXYZ from C. aurantiacus was experimentally verified by genetic complementation in E. coli. Expanding the integrative approach, which was applied here for a comprehensive analysis of B-vitamin metabolism in Chloroflexi would allow reconstruction of metabolic interdependencies in microbial communities.

  15. Associations between vitamin D-binding protein isotypes, circulating 25(OH)D levels, and vitamin D metabolite uptake in colon cancer cells.

    PubMed

    Hibler, Elizabeth A; Jacobs, Elizabeth T; Stone, Angelika Dampf; Sardo, Christine L; Galligan, Michael A; Jurutka, Peter W

    2014-04-01

    Vitamin D metabolites have been extensively studied as cancer chemopreventive agents. Gc-globulin (GC) isotypes, based on rs7041 and rs4588 diplotypes, have varying affinities for 1?,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25(OH)D), which may affect circulating metabolite concentration as well as delivery at the cellular level. We evaluated associations between GC isotype and circulating vitamin D metabolite concentrations in 403 ursodeoxycholic acid (UDCA) clinical trial participants. Metabolite uptake was evaluated in human colon cancer (HCT-116) cells treated with ethanol vehicle, 1,25(OH)2D, or 25(OH)D, and with plasma from individuals with known GC isotype. Mammalian-2-hybrid and vitamin D-responsive element-based luciferase assays were used to measure the vitamin D receptor pathway activation as a marker for metabolite uptake. Regression analysis demonstrated significantly lower serum 25(OH)D concentration for clinical trial participants with 1F_2, 1S_2, or 2_2 isotypes (P < 0.01) compared with 1S_1S. Consistent with these in vivo observations, cellular data revealed that 25(OH)D uptake varied less by GC isotype only at the higher concentration tested (P = 0.05), while 1,25(OH)2D uptake differed markedly by GC isotype across concentration and assay (P < 0.01). The 1F_1S and 1F_2 isotypes produced the greatest reporter gene induction with 1,25(OH)2D treatment and, while activation varied less with 25(OH)D, the 2_2 isotype demonstrated increased induction at the lower concentration. These results suggest that vitamin D metabolite concentration and delivery to colon cells may vary not only by GC isotype, but also that certain isotypes may more effectively deliver 1,25(OH)2D versus 25(OH)D. Overall, these results may help identify populations at risk for cancer and potential recipients of targeted chemoprevention. PMID:24472850

  16. A comparative study of folate and vitamin B12 serum levels in preeclamptic versus normotensive pregnant women in correlation with uterine and umbilical artery Doppler findings and pregnancy outcome

    PubMed Central

    Mahmoud, Ahmed; Elkattan, Eman A.; Eldaly, Ashraf A.; Omran, Eman F.; Mandour, Iman

    2009-01-01

    Objective To detect the serum levels of folate and B12 in both preclamptic and normotensive pregnant women and to determine whether there is any relation between these levels with the uterine and umbilical artery Doppler indices as well as the pregnancy outcome. Material and Methods This case controlled study comprised 79 pregnant patients with preeclampsia and 113 healthy, normotensive pregnant women with singleton pregnancies at gestational ages ranging from 3440 weeks. Patients were not obese (BMI<30) and did not suffer from chronic hypertension, chronic renal or liver disease nor diabetes mellitus. Serum folate and B12 were detected in all cases. They were also subjected to a Doppler study of both the uterine and umbilical arteries. Serum folate and B12 blood levels as well as the Doppler study indices (RI and PI) were compared in both groups. Results The serum folate level was significantly lower in preeclamptic patients than normal pregnant women (p<0.001). It was significantly correlated to uterine artery Doppler indices (RI and PI) and negatively correlated to umbilical artery Doppler indices (RI and PI). Low serum folate was significantly correlated to poor maternal outcome. Low serum folate was also significantly correlated to poor perinatal outcome. Serum B12 level was not significantly different in preeclamptic patients from the control group (P value=0.14). Conclusion Serum folate was significantly lower in preeclamptic pregnant women with a significant correlation to increased uterine and umbilical RI, PI and poor maternal and neonatal outcome. PMID:24591859

  17. Nitric oxide negatively regulates AKT1-mediated potassium uptake through modulating vitamin B6 homeostasis in Arabidopsis.

    PubMed

    Xia, Jinchan; Kong, Dongdong; Xue, Shaowu; Tian, Wang; Li, Nan; Bao, Fang; Hu, Yong; Du, Jing; Wang, Yu; Pan, Xiaojun; Wang, Lei; Zhang, Xiaochen; Niu, Guoqi; Feng, Xue; Li, Legong; He, Yikun

    2014-11-11

    Nitric oxide (NO), an active signaling molecule in plants, is involved in numerous physiological processes and adaptive responses to environmental stresses. Under high-salt conditions, plants accumulate NO quickly, and reorganize Na(+) and K(+) contents. However, the molecular connection between NO and ion homeostasis is largely unknown. Here, we report that NO lowers K(+) channel AKT1-mediated plant K(+) uptake by modulating vitamin B6 biosynthesis. In a screen for Arabidopsis NO-hypersensitive mutants, we isolated sno1 (sensitive to nitric oxide 1), which is allelic to the previously noted mutant sos4 (salt overly sensitive 4) that has impaired Na(+) and K(+) contents and overproduces pyridoxal 5'-phosphate (PLP), an active form of vitamin B6. We showed that NO increased PLP and decreased K(+) levels in plant. NO induced SNO1 gene expression and enzyme activity, indicating that NO-triggered PLP accumulation mainly occurs through SNO1-mediated vitamin B6 salvage biosynthetic pathway. Furthermore, we demonstrated that PLP significantly repressed the activity of K(+) channel AKT1 in the Xenopus oocyte system and Arabidopsis root protoplasts. Together, our results suggest that NO decreases K(+) absorption by promoting the synthesis of vitamin B6 PLP, which further represses the activity of K(+) channel AKT1 in Arabidopsis. These findings reveal a previously unidentified pivotal role of NO in modulating the homeostasis of vitamin B6 and potassium nutrition in plants, and shed light on the mechanism of NO in plant acclimation to environmental changes. PMID:25355908

  18. Vitamins

    MedlinePLUS

    ... wheat and oats wheat germ leafy green vegetables vegetable oils like sunflower, canola, and olive egg yolks nuts ... foods are rich in vitamin K? leafy green vegetables dairy products, like milk and yogurt broccoli soybean oil When your body gets this vitamin and the ...

  19. Vitamins

    MedlinePLUS

    ... left navigation Fitness and Nutrition Nutrition basics Proteins Carbohydrates Fats Vitamins Minerals Water How to eat for ... and cheese. B 1 Helps your body use carbohydrates for energy Good for your nervous system Yeasts, ...

  20. Uptake of (/sup 3/H)vitamin D/sub 3/ from low and high density lipoproteins by cultured human fibroblasts

    SciTech Connect

    Shireman, R.B.; Williams, D.; Remsen, J.F.

    1986-03-01

    The plasma distribution and cellular uptake of (/sup 3/H)vitamin D/sub 3/ was studied in vitro using cultured human fibroblasts. Incubation of (/sup 3/H)vitamin D/sub 3/ (cholecalciferol) with plasma followed by sequential ultracentrifugal fractionation of the lipoproteins indicated that 2-4% of the radioactivity associated with the very low density lipoprotein (VLDL), 12% with low density lipoprotein (LDL), and approximately 60% with the high density lipoprotein (HDL). The remaining radioactivity, 25%, was associated with the sedimented plasma fractions. By comparison, an average of 86% of the radioactivity from (/sup 3/H) 1,25-dihydroxycholecalciferol associated with the sedimented plasma fractions. The uptake of (/sup 3/H)vitamin D/sub 3/ from plasma, LDL, or HDL was studied in cultured human cells; uptake by normal fibroblasts was greatest from LDL and least from plasma. The cellular association of vitamin D/sub 3/ was time, concentration, and temperature dependent. At a concentration of 50 ..mu..g LDL/ml of medium, the uptake of (/sup 3/H)vitamin D/sub 3/ from LDL at 37/sup 0/C was rapid and reached a maximum at approximately 4 hr; it was slower from HDL but continued to increase slowly up to 24 hr. The significance of these in vitro findings is uncertain since much of the vitamin D/sub 3/ absorbed from the intestine reportedly associates with chylomicrons and is rapidly taken up by the liver.

  1. 1,25 (OH) sub 2 vitamin D sub 3 -induced sup 45 Ca uptake in vascular myocytes cultured from spontaneously hypertensive and normotensive rats

    SciTech Connect

    Xue, Hong; McCarron, D.A.; Bukoski, R.D. )

    1991-01-01

    The effect of 1,25 (OH){sub 2} vitamin D{sub 3} on basal {sup 45}Ca uptake was examined in vasvular smooth muscle cells cultured from mesenteric arteries of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) normotensive rats. Basal uptake of {sup 45}Ca was significantly greater in myocytes of WKY than SHR at 5, 10, 30 and 60 min incubation with the isotope. Incubation with 1 ng/ml 1,25 (OH){sub 2} vitamin D{sub 3} for 48 hr increased basal {sup 45}Ca uptake between 1-10 min in SHR and between 5-10 min in WKY. The dose-response relationship indicated that cells from both strains are equally sensitive to the calciotropic effects of 1,25 (OH){sub 2} vitamin D{sub 3} with half-maximal stimulation occurring at approximately 0.3-0.4 ng/ml. In cells of both strains maximal stimulation of {sup 45}Ca uptake was achieved only after a 12-24 hr period of incubation with hormone and pretreatment with cycloheximide inhibited 1,24 (OH){sub 2} vitamin D{sub 3}-enhanced {sup 45}Ca uptake. Although {sup 45}Ca binding by extracellular matrix material was significantly greater in WKY than SHR, 1,25 (OH){sub 2} vitamin D{sub 3} had no effect on the amount of matrix {sup 45}Ca binding in either strain.

  2. Crystallographic studies on B12 binding proteins in eukaryotes and prokaryotes

    PubMed Central

    Sukumar, Narayanasami

    2013-01-01

    The x-ray crystal structures of several important vitamin B12 binding proteins that have been solved in recent years have enhanced our current understanding in the vitamin B12 field. These structurally diverse groups of B12 binding proteins perform various important biological activities, both by transporting B12 as well as catalyzing various biological reactions. An in-depth comparative analysis of these structures was carried out using PDB coordinates of a carefully chosen database of B12 binding proteins to correlate the overall folding of the molecule with phylogeny, the B12 interactions, and with their biological function. The structures of these proteins are discussed in the context of this comparative analysis. PMID:23395752

  3. A relationship between vitamin B sub 12 , folic acid, ascorbic acid, and mercury uptake and methylation

    SciTech Connect

    Zorn, N.E.; Smith, J.T. )

    1990-01-01

    Ingestion of megadoses of certain vitamins appears to influence the in vivo methylation of mercuric chloride in guinea pigs. The addition of megadoses of vitamin B{sub 12} fed either singularly or in combination with folic acid resulted in increased methylmercury concentrations in the liver. Moreover, percent methylmercury levels were significantly increased with B{sub 12} treatment in the liver (B{sub 12} only and B{sub 12}/folic acid) and brain (B{sub 12}/vitamin C). Incorporation of high levels of folic acid into the dietary regime also increased the methylmercury concentration particularly in the liver and hair tissues. The addition of vitamin C in the diet, particularly in combination with B{sub 12} (brain) or folic acid (muscle) resulted in increased methylmercury levels in these tissues and percent methylmercury values with B{sub 12} in the muscle and brain tissue.

  4. Hydrosoluble vitamins.

    PubMed

    Chawla, Jasvinder; Kvarnberg, David

    2014-01-01

    The hydrosoluble vitamins are a group of organic substances that are required by humans in small amounts to prevent disorders of metabolism. Significant progress has been made in our understanding of the biochemical, physiologic and nutritional aspects of the water-soluble vitamins. Deficiency of these particular vitamins, most commonly due to inadequate nutrition, can result in disorders of the nervous system. Many of these disorders have been successfully prevented in developed countries; however, they are still common in developing countries. Of the hydrosoluble vitamins, the nervous system depends the most on vitamins B and C (ascorbic acid) for proper functioning. The B group vitamins include thiamin (vitamin B1), riboflavin (vitamin B2), niacin or niacinamide (vitamin B3), pantothenic acid (vitamin B5), pyridoxine or pyridoxal (vitamin B6) and cobalamin (vitamin B12). Clinical findings depend upon the deficiency of the underlying vitamin; generally, deficiency symptoms are seen from a combination rather than an isolated vitamin deficiency. True hereditary metabolic disorders and serious deficiency-associated diseases are rare and in general limited to particular geographic regions and high-risk groups. Their recognition is truly important as that determines the appropriate therapeutic management. The general availability of vitamins to practically everyone and several national health programs have saved many lives and prevented complications. However, there has been some apprehension for several decades about how harmless generous dosages of these vitamins are. Overt overdosages can cause vitamin toxicity affecting various body systems including the nervous system. Systemically, vitamin toxicity is associated with nonspecific symptoms, such as nausea, vomiting, diarrhea, and skin rash which are common with any acute or chronic vitamin overdose. At a national level, recommended daily allowances for vitamins become policy statements. Nutrition policy has far reaching implications in the food industry, in agriculture, and in food provision programs. Overall, water-soluble vitamins are complex molecular structures and even today, many areas of vitamin biochemistry still need to be explored. Many readers might be of the opinion that the classic forms of nutritional deficiency diseases have faded into the background of interesting history. This has caused their diverse symptoms to be neglected by most modern physicians since vitamin enrichment of many foods automatically erases them from their consideration in differential diagnosis. Vitamin B12 and folic acid deficiencies are discussed in other chapters. PMID:24365359

  5. Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin) Uptake by Pancreatic Acinar Cells

    PubMed Central

    Srinivasan, Padmanabhan; Thrower, Edwin C.; Loganathan, Gopalakrishnan; Balamurugan, A. N.; Subramanian, Veedamali S.; Gorelick, Fred S.; Said, Hamid M.

    2015-01-01

    Thiamin (vitamin B1), a member of the water-soluble family of vitamins, is essential for normal cellular functions; its deficiency results in oxidative stress and mitochondrial dysfunction. Pancreatic acinar cells (PAC) obtain thiamin from the circulation using a specific carrier-mediated process mediated by both thiamin transporters -1 and -2 (THTR-1 and THTR-2; encoded by the SLC19A2 and SLC19A3 genes, respectively). The aim of the current study was to examine the effect of chronic exposure of mouse PAC in vivo and human PAC in vitro to nicotine (a major component of cigarette smoke that has been implicated in pancreatic diseases) on thiamin uptake and to delineate the mechanism involved. The results showed that chronic exposure of mice to nicotine significantly inhibits thiamin uptake in murine PAC, and that this inhibition is associated with a marked decrease in expression of THTR-1 and THTR-2 at the protein, mRNA and hnRNAs level. Furthermore, expression of the important thiamin-metabolizing enzyme, thiamin pyrophosphokinase (TPKase), was significantly reduced in PAC of mice exposed to nicotine. Similarly, chronic exposure of cultured human PAC to nicotine (0.5 μM, 48 h) significantly inhibited thiamin uptake, which was also associated with a decrease in expression of THTR-1 and TH