Posted by KaraS on December 31, 2004, at 0:55:16
In reply to Niacinamide....Wonder drug?, posted by Larry Hoover on December 30, 2004, at 14:47:55
> I posted this hours ago, and i don't see it....
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> :-/
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> At the risk of perhaps duplicating the info, here goes, again.
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> I was doing a little Pubmed crawling, not really trying hard to find stuff at all, when I came across a bunch of different abstracts reporting on the beneficial effects of niacinamide.
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> It is a potent neuroprotective compound, an anti-inflammatory, an immunomodulator, and has mitochondrial energy enhancing effects. This is in addition to its anti-allergic and anti-asthmatic activities, and its potentiation of GABA receptor function.
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> Pretty cool, for a simple vitamin.
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> Lar
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> Front Biosci. 2004 Sep 01;9:2500-20.
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> Navigating novel mechanisms of cellular plasticity with the NAD+ precursor and nutrient nicotinamide.
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> Li F, Chong ZZ, Maiese K.
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> Division of Cellular and Molecular Cerebral Ischemia, Institute of Environmental Health Sciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
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> Interest in neuroprotectants for the central nervous system continues to garner significant attention. Nicotinamide, the amide form of niacin (vitamin B3), is the precursor for the coenzyme beta-nicotinamide adenine dinucleotide (NAD+) and is considered to be necessary for cellular function and metabolism. However, recent work has focused on the development of nicotinamide as a novel agent that is critical for modulating cellular plasticity, longevity, and inflammatory microglial function. The ability of nicotinamide to preserve both neuronal and vascular cell populations in the brain during injury is intriguing, but further knowledge of the specific cellular mechanisms that determine protection by this agent is required. The capacity of nicotinamide to govern not only intrinsic cellular integrity, but also extrinsic cellular inflammation rests with the modulation of a host of cellular targets that involve protein kinase B, glycogen synthase kinase-3 beta (GSK-3 beta), Forkhead transcription factors, mitochondrial dysfunction, poly(ADP-ribose) polymerase, cysteine proteases, and microglial activation. Intimately tied to the cytoprotection of nicotinamide is the modulation of an early and late phase of apoptotic injury that is triggered by the loss of membrane asymmetry. Identifying robust cytoprotective agents as nicotinamide in conjunction with the elucidation of the cellular mechanisms responsible for cell survival will continue to solidify the development of therapeutic strategies against neurodegenerative diseases.
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> Trends Pharmacol Sci. 2003 May;24(5):228-32.
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> Nicotinamide: necessary nutrient emerges as a novel cytoprotectant for the brain.
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> Maiese K, Chong ZZ.
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> Division of Cellular and Molecular Cerebral Ischemia, Wayne State University, School of Medicine Detroit, St Antoine, MI 48201, USA. kmaiese@med.wayne.edu
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> Although usually identified as an essential cellular nutrient for cellular growth and maintenance, nicotinamide is under development as a novel cytoprotectant for acute and chronic neurodegenerative disorders. Here, we outline support for the premise that nicotinamide both prevents and reverses neuronal and vascular cell injury. Nicotinamide fosters DNA integrity and maintains phosphatidylserine membrane asymmetry to prevent cellular inflammation, cellular phagocytosis and vascular thrombosis. The downstream cellular and molecular cascades are considered vital for the cytoprotection offered by nicotinamide. These pathways encompass the modulation of Akt, the forkhead transcription factor FKHRL1, mitochondrial membrane potential, caspase activities and cellular energy metabolism, but remain independent of intracellular pH and mitogen-activated protein kinases. As both a therapeutic agent and an investigational tool, nicotinamide offers new therapeutic strategies for degenerative disorders of the CNS.
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> J Med Food. 2001 Spring;4(1):27-38.
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> Nicotinamide: A Nutritional Supplement that Provides Protection Against Neuronal and Vascular Injury.
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> Lin SH, Chong ZZ, Maiese K.
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> Division of Cellular and Molecular Cerebral Ischemia, Center for Molecular Medicine and Genetics, Center for Molecular and Cellular Toxicology, Wayne State University School of Medicine, Detroit, MI 48201.
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> In addition to functioning as an essential nutrient for cellular growth and maintenance, nicotinamide also may be an attractive therapeutic agent with efficacy demonstrated against free radical ischemic programmed cell death (PCD). Yet, the cellular mechanisms that mediate cellular PCD, as well as protection by nicotinamide, are considered to require further definition. In primary rat hippocampal neurons and rat cerebrovascular endothelial cells (ECs), cellular injury was determined through trypan blue dye exclusion, externalization of membrane phosphatidylserine (PS) residues, and activation of the mitogen-activated protein kinase p38 through Western blot analysis. Nicotinamide was without cellular toxicity at concentrations lower than 50 mM in both neuronal and EC populations. Exposure to either anoxia or the nitric oxide (NO) donors sodium nitroprusside and NOC-9 significantly decreased neuronal and EC survival from approximately 85% to 38% and increased membrane PS exposure from approximately 10% to 80% over a 24-hour period. Pretreatment with nicotinamide (12.5 mM) prevented anoxic and NO cytodegeneration by significantly increasing survival and decreasing membrane PS expression. Protection by nicotinamide in both neurons and ECs appeared to be independent and downstream from p38 activation. Further investigations that define the cellular and molecular mechanisms employed by the nutrient nicotinamide may provide greater insight into the potential therapeutic targets that determine neuronal and vascular injury.
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> FASEB J. 2003 Aug;17(11):1377-9.
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> Nicotinamide: a potential addition to the anti-psoriatic weaponry.
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> Namazi MR.
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> Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran. namazi_mr@yahoo.com
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> Psoriasis is an inflammatory disorder characterized by a T helper type 1 cell cytokine pattern. Increased expression of adhesion molecules, prominent neutrophil accumulation, and increased production of nitric oxide are characteristics of this disorder. Moreover, histamine and proteases are supposed to participate in the pathogenesis of psoriasis. Nicotinamide is an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1) that, through enhancement of nuclear kappa B-mediated transcription, plays a pivotal role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators. Through interaction with CD38 and inhibition of IL-1, IL-12, and TNF-alpha production, nicotinamide produces a mild TH2 bias. Nicotinamide is a potent phosphodiesterase inhibitor and suppresses neutrophil chemotaxis and mast cell histamine release. It inhibits nitric oxide synthase mRNA induction and suppresses antigen-induced lymphocyte transformation. Nicotinamide increases the biosynthesis of ceramides, which upon degradation produce sphingosine. Sphingosine inhibits protein kinase C (PKC) and decreases basal cell proliferation dependent on PKC. Taken together, it can be reasoned that nicotinamide could be a useful addition to anti-psoriatic armamentarium. The combination of nicotinamide and thalidomide or methotrexate provided a powerful synergistic inhibition of murine collagen-induced arthritis. Nicotinamide decreased the methotrexate-induced hepatotoxicity. The above combinations may prove to have a powerful anti-psoriatic effect as well. As PARP inhibitors could exert anti-retroviral effect, nicotinamide could also be of special value in the treatment of HIV-infected psoriatics.
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> Clin Exp Immunol. 2003 Jan;131(1):48-52.
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> Nicotinamide is a potent inhibitor of proinflammatory cytokines.
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> Ungerstedt JS, Blomback M, Soderstrom T.
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> Coagulation Research, Department of Surgical Sciences, Karolinska Institutet, Stockholm, Sweden. johanna.ungerstedt@ks.se
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> The present study investigates the modulating effects of nicotinamide on the cytokine response to endotoxin. In an in vitro model of endotoxaemia, human whole blood was stimulated for two hours with endotoxin at 1 ng/ml, achieving high levels of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF alpha. When coincubating whole blood, endotoxin and the vitamin B3 derivative nicotinamide, all four cytokines measured were inhibited in a dose dependent manner. Inhibition was observed already at a nicotinamide concentration of 2 mmol/l. At a concentration of 40 mmol/l, the IL-1 beta, IL-6 and TNF alpha responses were reduced by more than 95% and the IL-8 levels reduced by 85%. Endotoxin stimulation activates poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair enzyme. It has been hypothesized that the anti-inflammatory properties of nicotinamide are due to PARP inhibition. In the present study, the endotoxin induced PARP activation was dose dependently decreased with 4-40 mmol/l nicotinamide or 4-100 micro mol/l 6(5H) phenanthridinone, a specific PARP inhibitor. 6(5H)phenanthridinone however, failed to inhibit the proinflammatory cytokines. Thus, the mechanism behind the cytokine inhibition in our model seems not to be due to PARP inhibition. In conclusion, the present study could not only confirm previous reports of a down-regulatory effect on TNFalpha, but demonstrates that nicotinamide is a potent modulator of several proinflammatory cytokines. These findings demonstrate that nicotinamide has a potent immunomodulatory effect in vitro, and may have great potential for treatment of human inflammatory disease.
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> Ann Neurol. 2003;53 Suppl 3:S39-47; discussion S47-8.
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> Bioenergetic approaches for neuroprotection in Parkinson's disease.
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> Beal MF.
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> Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, USA. fbeal@mail.med.cornell.edu
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> There is considerable evidence suggesting that mitochondrial dysfunction and oxidative damage may play a role in the pathogenesis of Parkinson's disease (PD). This possibility has been strengthened by recent studies in animal models, which have shown that a selective inhibitor of complex I of the electron transport gene can produce an animal model that closely mimics both the biochemical and histopathological findings of PD. Several agents are available that can modulate cellular energy metabolism and that may exert antioxidative effects. There is substantial evidence that mitochondria are a major source of free radicals within the cell. These appear to be produced at both the iron-sulfur clusters of complex I as well as the ubiquinone site. Agents that have shown to be beneficial in animal models of PD include creatine, coenzyme Q(10), Ginkgo biloba, nicotinamide, and acetyl-L-carnitine. Creatine has been shown to be effective in several animal models of neurodegenerative diseases and currently is being evaluated in early stage trials in PD. Similarly, coenzyme Q(10) is also effective in animal models and has shown promising effects both in clinical trials of PD as well as in clinical trials in Huntington's disease and Friedreich's ataxia. Many other agents show good human tolerability. These agents therefore are promising candidates for further study as neuroprotective agents in PD.
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Wow, I'm sold! Maybe it is a long-term solution (assuming no tolerance). Probably a lot better for asthmatics than Singulair... I can't wait to give the good news to my friend with PD.Thanks, Lar
Kara
K
poster:KaraS
thread:435754
URL: http://www.dr-bob.org/babble/alter/20041212/msgs/435902.html