Vitamin B12 Deficiency, Demyelination, and Multiple Sclerosis

Reynolds, E. H.; Linnell, J. C.

doi:10.1016/s0140-6736(87)91411-5

Cited by 31 publications

(13 citation statements)

References 2 publications

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“…18 We identified 125 citations on the role of vitamin B 12 levels in MS. We excluded 114 references for the following reasons: they were reviews or case reports, dealt with other topics, or vitamin B 12 was measured in CSF. Of the remaining 11 references, three were excluded because they were letters to the editor, 34 did not provide control group data, 35 or were duplicated studies. 21 Eight studies were selected for analysis.…”

Section: Identified Studiesmentioning

confidence: 99%

Meta-analysis of the relationship between homocysteine, vitamin B12, folate, and multiple sclerosis

Zhu

Liu

2011

Journal of Clinical Neuroscience

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Section: Identified Studiesmentioning

confidence: 99%

Meta-analysis of the relationship between homocysteine, vitamin B12, folate, and multiple sclerosis

Zhu

Liu

2011

Journal of Clinical Neuroscience

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“…Given the high frequency of MS in the population, it seems most likely that more than one factor is involved. For example, geographical epidemiology and animal models clearly reveal important roles for vitamin D signaling [58], while deficiencies of vitamin B12 [59-61] or sadenosylmethionine [62, 63] can directly cause demyelination. Meanwhile recurrent reactivation of a latent herpes infection resembles relapsing-remitting MS and is commonly found in the CNS, where its potential role in MS pathogenesis is difficult to resolve owing to its nearly ubiquitous presence [64].…”

Section: Clinical Multiple Sclerosis and Animal Modelsmentioning

confidence: 99%

The Importance of NAD in Multiple Sclerosis

Penberthy¹,

Tsunoda²

2009

CPD

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The etiology of multiple sclerosis (MS) is unknown but it manifests as a chronic inflammatory demyelinating disease in the central nervous system (CNS). During chronic CNS inflammation, nicotinamide adenine dinucleotide (NAD) concentrations are altered by (T helper) Th1-derived cytokines through the coordinated induction of both indoleamine 2,3-dioxygenase (IDO) and the ADP cyclase CD38 in pathogenic microglia and lymphocytes. While IDO activation may keep autoreactive T cells in check, hyper-activation of IDO can leave neuronal CNS cells starving for extracellular sources of NAD. Existing data indicate that glia may serve critical functions as an essential supplier of NAD to neurons during times of stress. Administration of pharmacological doses of non-tryptophan NAD precursors ameliorates pathogenesis in animal models of MS. Animal models of MS involve artificially stimulated autoimmune attack of myelin by experimental autoimmune encephalomyelitis (EAE) or by viral-mediated demyelination using Thieler's murine encephalomyelitis virus (TMEV). The Wld S mouse dramatically resists razor axotomy mediated axonal degeneration. This resistance is due to increased efficiency of NAD biosynthesis that delays stress-induced depletion of axonal NAD and ATP. Although the Wld S genotype protects against EAE pathogenesis, TMEV-mediated pathogenesis is exacerbated. In this review, we contrast the role of NAD in EAE versus TMEV demyelinating pathogenesis to increase our understanding of the pharmacotherapeutic potential of NAD signal transduction pathways. We speculate on the importance of increased SIRT1 activity in both PARP-1 inhibition and the potentially integral role of neuronal CD200 interactions through glial CD200R with induction of IDO in MS pathogenesis. A comprehensive review of immunomodulatory control of NAD biosynthesis and degradation in MS pathogenesis is presented. Distinctive pharmacological approaches designed for NADcomplementation or targeting NAD-centric proteins (SIRT1, SIRT2, PARP-1, GPR109a, and CD38) are outlined towards determining which approach may work best in the context of clinical application.

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“…2 The cause of the macrocytosis is unknown, but some observations have suggested a possible disturbance in vitamin B 12 metabolism, binding or transport. 4 We have compared haematological records of patients with definite MS with those of an individually matched neurological control group.…”

mentioning

confidence: 99%