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      B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin

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          Abstract

          Background

          Neurotropic B vitamins play crucial roles as coenzymes and beyond in the nervous system. Particularly vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) contribute essentially to the maintenance of a healthy nervous system. Their importance is highlighted by many neurological diseases related to deficiencies in one or more of these vitamins, but they can improve certain neurological conditions even without a (proven) deficiency.

          Aim

          This review focuses on the most important biochemical mechanisms, how they are linked with neurological functions and what deficits arise from malfunctioning of these pathways.

          Discussion

          We discussed the main role of B Vitamins on several functions in the peripheral and central nervous system (PNS and CNS) including cellular energetic processes, antioxidative and neuroprotective effects, and both myelin and neurotransmitter synthesis. We also provide an overview of possible biochemical synergies between thiamine, pyridoxine, and cobalamin and discuss by which major roles each of them may contribute to the synergy and how these functions are inter‐related and complement each other.

          Conclusion

          Taking into account the current knowledge on the neurotropic vitamins B1, B6, and B12, we conclude that a biochemical synergy becomes apparent in many different pathways in the nervous system, particularly in the PNS as exemplified by their combined use in the treatment of peripheral neuropathy.

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          Most cited references52

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          Vitamin B12 (cobalamin) deficiency in elderly patients.

          Vitamin B12 or cobalamin deficiency occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%-20% of all cases), insufficient dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.
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            Vitamin B 6 and Its Role in Cell Metabolism and Physiology

            Vitamin B6 is one of the most central molecules in cells of living organisms. It is a critical co-factor for a diverse range of biochemical reactions that regulate basic cellular metabolism, which impact overall physiology. In the last several years, major progress has been accomplished on various aspects of vitamin B6 biology. Consequently, this review goes beyond the classical role of vitamin B6 as a cofactor to highlight new structural and regulatory information that further defines how the vitamin is synthesized and controlled in the cell. We also discuss broader applications of the vitamin related to human health, pathogen resistance, and abiotic stress tolerance. Overall, the information assembled shall provide helpful insight on top of what is currently known about the vitamin, along with addressing currently open questions in the field to highlight possible approaches vitamin B6 research may take in the future.
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              How I treat cobalamin (vitamin B12) deficiency.

              The challenges in medical management of cobalamin deficiency lie in attention to the unique pathophysiology that underlies cobalamin deficiency, more than in the mechanics of therapy. The central physiologic principles are that clinically important deficiency is more likely to occur (and progress) when intrinsic factor-driven absorption fails than when diet is poor and that most causes take years to produce clinically obvious deficiency. Transient defects have little clinical impact. The key management principle is the importance of follow-up, which also requires knowing how the deficiency arose. The virtues of these principles are not always fully appreciated. Recent developments have made diagnosis and management more difficult by diminishing the ability to determine cobalamin absorption status. Clinicians must also grapple with premature medicalization of isolated, mild biochemical changes that added many asymptomatic cases of still undetermined medical relevance to their caseload, often expanded by inflated cobalamin level criteria. The potential for misattribution of cobalamin-unrelated presentations to nongermane cobalamin and metabolite abnormalities has grown. Pathophysiologically based management requires systematic attention to each of its individual components: correctly diagnosing cobalamin deficiency, reversing it, defining its underlying cause, preventing relapse, managing the underlying disorder and its complications, and educating the patient.
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                Author and article information

                Contributors
                mauricio.nava@urosario.edu.co , monavam@usal.es
                Journal
                CNS Neurosci Ther
                CNS Neurosci Ther
                10.1111/(ISSN)1755-5949
                CNS
                CNS Neuroscience & Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                1755-5930
                1755-5949
                06 September 2019
                January 2020
                : 26
                : 1 ( doiID: 10.1111/cns.v26.1 )
                : 5-13
                Affiliations
                [ 1 ] Center for Research in Genetics and Genomics (CIGGUR), GENIUROS Research Group, School of Medicine and Health Sciences Universidad del Rosario Bogotá Colombia
                [ 2 ] Neuroscience Research Group (NEUROS), School of Medicine and Health Sciences Universidad del Rosario Bogotá Colombia
                Author notes
                [*] [* ] Correspondence

                Mauricio Orlando Nava Mesa, Neuroscience Research Group (NEUROS), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.

                Emails: mauricio.nava@ 123456urosario.edu.co ; monavam@ 123456usal.es

                Author information
                https://orcid.org/0000-0001-8458-7862
                Article
                CNS13207
                10.1111/cns.13207
                6930825
                31490017
                fb97cc8c-2bfc-4e3e-805e-b2f69f15340c
                © 2019 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 April 2019
                : 22 July 2019
                : 26 July 2019
                Page count
                Figures: 3, Tables: 1, Pages: 9, Words: 6639
                Funding
                Funded by: Merck Selbstmedikation GmbH, Darmstadt, Germany, a legal entity of Procter & Gamble Health
                Categories
                Review Article
                Review Article
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.3 mode:remove_FC converted:25.12.2019

                Neurosciences
                b vitamins,biochemical action mechanism,neuropathy,pyridoxine,thiamine,vitamin b12
                Neurosciences
                b vitamins, biochemical action mechanism, neuropathy, pyridoxine, thiamine, vitamin b12

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