Vitamin B3 Abstracts

© 2010

Niacinamide. Monograph

            (2002) Download

Final report of the safety assessment of niacinamide and niacin

            (2005) Download

NAD+ metabolism in health and disease

            (Belenky, Bogan et al. 2007) Download

Nicotinamide adenine dinucleotide (NAD(+)) is both a coenzyme for hydride-transfer enzymes and a substrate for NAD(+)-consuming enzymes, which include ADP-ribose transferases, poly(ADP-ribose) polymerases, cADP-ribose synthases and sirtuins. Recent results establish protective roles for NAD(+) that might be applicable therapeutically to prevent neurodegenerative conditions and to fight Candida glabrata infection. In addition, the contribution that NAD(+) metabolism makes to lifespan extension in model systems indicates that therapies to boost NAD(+) might promote some of the beneficial effects of calorie restriction. Nicotinamide riboside, the recently discovered nucleoside precursor of NAD(+) in eukaryotic systems, might have advantages as a therapy to elevate NAD(+) without inhibiting sirtuins, which is associated with high-dose nicotinamide, or incurring the unpleasant side-effects of high-dose nicotinic acid.

Nicotinic acid: a new look at an old drug

            (Farmer 2009) Download

Dyslipidemia is central to the process of atherosclerosis. Modification of the lipid profile by diet, exercise, or pharmacologic therapy has been demonstrated to reduce the risk from atherosclerosis in clinical studies in primary and secondary prevention. Nicotinic acid has been in clinical use for over 50 years. The administration of nicotinic acid has been demonstrated to reduce apolipoprotein B-containing lipoproteins (very low-density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and lipoprotein (a)). Nicotinic acid also exerts significant effects on high-density lipoprotein. In addition to improving dyslipidemia, nicotinic acid has been demonstrated to induce a number of nonlipid or pleiotropic effects. The recent discovery of the nicotinic acid receptor has improved knowledge relative to the mechanism of action and the adverse effect profile of nicotinic acid. Clinical trials utilizing clinical or angiographic end points demonstrated efficacy for the use of nicotinic acid in monotherapy or in combination with bile acid resins or statins.

The nicotinamide phosphoribosyltransferase: a molecular link between metabolism, inflammation, and cancer

            (Galli, Van Gool et al. 2009) Download

Beyond its well-described role in cellular metabolism, intracellular nicotinamide adenine dinucleotide (NAD) levels have been shown to affect the enzymatic activity of a series of NAD-dependent enzymes, influencing biological responses such as cell survival and inflammation. Nicotinamide phosphoribosyl transferase activity has been shown to be essential for maintaining adequate intracellular NAD levels, suggesting that this enzyme may in fact play a central role in modulating the activity of a wide range of NAD-dependent enzymes. Several recent observations concur with this hypothesis and suggest that by regulating NAD availability, Nampt is able to control both cell viability and the inflammatory response. Nampt may thus represent a novel pharmacological target with valuable anti-inflammatory and antitumor properties.

Nampt: linking NAD biology, metabolism and cancer

            (Garten, Petzold et al. 2009) Download

Nicotinamide phosphoribosyltransferase (Nampt) converts nicotinamide to nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD) intermediate. Previously identified as a cytokine pre-B-cell colony-enhancing factor and controversially claimed as an insulin-mimetic hormone visfatin, Nampt has recently drawn much attention in several fields, including NAD biology, metabolism and inflammation. As a NAD biosynthetic enzyme, Nampt regulates the activity of NAD-consuming enzymes such as sirtuins and influences a variety of metabolic and stress responses. Nampt also plays an important part in regulating insulin secretion in pancreatic beta-cells. Nampt seems to have another function as an immunomodulatory cytokine and, therefore, has a role in inflammation. This review summarizes these various functional aspects of Nampt and discusses its potential roles in diseases, including type 2 diabetes and cancer.

Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau

            (Green, Steffan et al. 2008) Download

Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD(+)-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated alpha-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability.

Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models

            (Kaneko, Wang et al. 2006) Download

Axonal damage is a major morphological alteration in the CNS of patients with multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanism for the axonal damage associated with MS/EAE and its contribution to the clinical symptoms remain unclear. The expression of a fusion protein, named "Wallerian degeneration slow" (Wld(S)), can protect axons from degeneration, likely through a beta-nicotinamide adenine dinucleotide (NAD)-dependent mechanism. In this study, we find that, when induced with EAE, Wld(S) mice showed a modest attenuation of behavioral deficits and axon loss, suggesting that EAE-associated axon damage may occur by a mechanism similar to Wallerian degeneration. Furthermore, nicotinamide (NAm), an NAD biosynthesis precursor, profoundly prevents the degeneration of demyelinated axons and improves the behavioral deficits in EAE models. Finally, we demonstrate that delayed NAm treatment is also beneficial to EAE models, pointing to the therapeutic potential of NAm as a protective agent for EAE and perhaps MS patients.

Niacin status, NAD distribution and ADP-ribose metabolism

            (Kirkland 2009) Download

Dietary niacin deficiency, and pharmacological excesses of nicotinic acid or nicotinamide, have dramatic effects on cellular NAD pools, ADP-ribose metabolism, tissue function and health. ADP-ribose metabolism is providing new targets for pharmacological intervention, and it is important to consider how the supply of vitamin B3 may directly influence ADP-ribosylation reactions, or create interactions with other drugs designed to influence these pathways. In addition to its redox roles, NAD+ is used as a substrate for mono-, poly- and cyclic ADP-ribose formation. During niacin deficiency, not all of these processes can be maintained, and dramatic changes in tissue function and clinical condition take place. Conversely, these reactions may be differentially enhanced by pharmacological intakes of vitamin B3, and potentially by changing expression of specific NAD generating enzymes. A wide range of metabolic changes can take place following pharmacological supplementation of nicotinic acid or nicotinamide. As niacin status decreases towards a deficient state, the function of other types of pharmaceutical agents may be modified, including those that target ADP-ribosylation reactions, apoptosis and inflammation. This article will explore what is known and yet to be learned about the response of tissues, cells and subcellular compartments to excessive and limiting supplies of niacin, and will discuss the etiology of the resulting pathologies.

Safety of high-dose nicotinamide: a review

            (Knip, Douek et al. 2000) Download

Nicotinamide, the amide derivative of nicotinic acid, has over the past forty years been given at high doses for a variety of therapeutic applications. It is currently in trial as a potential means of preventing the onset of Type I (insulin-dependent) diabetes mellitus in high-risk, first-degree relatives. Nicotinamide is for regulatory purposes classed as a food additive rather than a drug and has not therefore required the formal safety evaluation normally expected of a new therapy. Because the safety of treatment with megadoses of vitamins cannot be assumed, a full literature review has been undertaken. The therapeutic index of nicotinamide is wide but at very high doses reversible hepatotoxicity has been reported in animals and humans. Minor abnormalities of liver enzymes can infrequently occur at the doses used for diabetes prevention. There is no evidence of teratogenicity from animal studies and nicotinamide is not in itself oncogenic; at very high doses it does however potentiate islet tumour formation in rats treated with streptozotocin or alloxan. There is no evidence of oncogenicity in man. Growth inhibition can occur in rats but growth in children is unaffected. Studies of its effects on glucose kinetics and insulin sensitivity are inconsistent but minor degrees of insulin resistance have been reported. The drug is well tolerated, especially in recent studies which have used relatively pure preparations of the vitamin. Experience to date therefore suggests that the ratio of risk to benefit of long-term nicotinamide treatment would be highly favourable, should the drug prove efficacious in diabetes prevention. High-dose nicotinamide should still, however, be considered as a drug with toxic potential at adult doses in excess of 3 gm/day and unsupervised use should be discouraged.

Nicotinic acid therapy of multiple sclerosis.

            (Kuberski and Kuklinska 1954) Download

Cell Life versus cell longevity: the mysteries surrounding the NAD+ precursor nicotinamide

            (Li, Chong et al. 2006) Download

Nicotinamide, the amide form of niacin (vitamin B(3)), is the precursor for the coenzyme beta-nicotinamide adenine dinucleotide (NAD(+)) and plays a significant role during the enhancement of cell survival as well as cell longevity. Yet, these abilities of nicotinamide appear to be diametrically opposed. Here we describe the development of nicotinamide as a novel agent that is critical for modulating cellular metabolism, plasticity, longevity, and inflammatory microglial function as well as for influencing cellular life span. 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 mitochondrial membrane potential, poly(ADP-ribose) polymerase, protein kinase B (Akt), Forkhead transcription factors, Bad, caspases, and microglial activation. Further knowledge acquired in regards to the ability of nicotinamide to foster cellular survival and regulate cellular lifespan should significantly promote the development of therapies against a host of disorders, such as aging, Alzheimer's disease, diabetes, cerebral ischemia, Parkinson's disease, and cancer.

Nicotinamide adenine dinucleotide: beyond a redox coenzyme

            (Lin 2007) Download

ADP-ribosylation using nicotinamide adenine dinucleotide (NAD+) is an important type of enzymatic reaction that affects many biological processes. A brief introductory review is given here to various ADP-ribosyltransferases, including poly(ADP-ribose) polymerase (PARPs), mono(ADP-ribosyl)-transferases (ARTs), NAD(+)-dependent deacetylases (sirtuins), tRNA 2'-phosphotransferases, and ADP-ribosyl cyclases (CD38 and CD157). Focus is given to the enzymatic reactions, mechanisms, structures, and biological functions.

The vitamin nicotinamide: translating nutrition into clinical care

            (Maiese, Chong et al. 2009) Download

Nicotinamide, the amide form of vitamin B(3) (niacin), is changed to its mononucleotide compound with the enzyme nicotinic acide/nicotinamide adenylyltransferase, and participates in the cellular energy metabolism that directly impacts normal physiology. However, nicotinamide also influences oxidative stress and modulates multiple pathways tied to both cellular survival and death. During disorders that include immune system dysfunction, diabetes, and aging-related diseases, nicotinamide is a robust cytoprotectant that blocks cellular inflammatory cell activation, early apoptotic phosphatidylserine exposure, and late nuclear DNA degradation. Nicotinamide relies upon unique cellular pathways that involve forkhead transcription factors, sirtuins, protein kinase B (Akt), Bad, caspases, and poly (ADP-ribose) polymerase that may offer a fine line with determining cellular longevity, cell survival, and unwanted cancer progression. If one is cognizant of the these considerations, it becomes evident that nicotinamide holds great potential for multiple disease entities, but the development of new therapeutic strategies rests heavily upon the elucidation of the novel cellular pathways that nicotinamide closely governs.

Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline

            (Morris, Evans et al. 2004) Download

BACKGROUND: Dementia can be caused by severe niacin insufficiency, but it is unknown whether variation in intake of niacin in the usual diet is linked to neurodegenerative decline. We examined whether dietary intake of niacin was associated with incident Alzheimer's disease (AD) and cognitive decline in a large, prospective study. METHODS: This study was conducted in 1993-2002 in a geographically defined Chicago community of 6158 residents aged 65 years and older. Nutrient intake was determined by food frequency questionnaire. Four cognitive tests were administered to all study participants at 3 year intervals in a 6 year follow up. A total of 3718 participants had dietary data and at least two cognitive assessments for analyses of cognitive change over a median 5.5 years. Clinical evaluations were performed on a stratified random sample of 815 participants initially unaffected by AD, and 131 participants were diagnosed with 4 year incident AD by standardised criteria. RESULTS: Energy adjusted niacin intake had a protective effect on development of AD and cognitive decline. In a logistic regression model, relative risks (95% confidence intervals) for incident AD from lowest to highest quintiles of total niacin intake were: 1.0 (referent) 0.3 (0.1 to 0.6), 0.3 (0.1 to 0.7), 0.6 (0.3 to 1.3), and 0.3 (0.1 to 0.7) adjusted for age, sex, race, education, and ApoE e4 status. Niacin intake from foods was also inversely associated with AD (p for linear trend = 0.002 in the adjusted model). In an adjusted random effects model, higher food intake of niacin was associated with a slower annual rate of cognitive decline, by 0.019 standardised units (SU) per natural log increase in intake (mg) (p = 0.05). Stronger associations were observed in analyses that excluded participants with a history of cardiovascular disease (beta = 0.028 SU/year; p = 0.008), those with low baseline cognitive scores (beta = 0.023 SU/year; p = 0.02), or those with fewer than 12 years' education (beta = 0.035 SU/year; p = 0.002) CONCLUSION: Dietary niacin may protect against AD and age related cognitive decline.

Pharmacological targeting of IDO-mediated tolerance for treating autoimmune disease

            (Penberthy 2007) Download

Cells at the maternal-fetal interface express indoleamine 2,3 dioxygenase (IDO) to consume all local tryptophan for the express purpose of starving adjacent maternal T cells of this most limiting and essential amino acid. This stops local T cell proliferation to ultimately result in the most dramatic example of immune tolerance, acceptance of the fetus. By contrast, inhibition of IDO using 1-methyl-tryptophan causes a sudden catastrophic rejection of the mammalian fetus. Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells. Thus it makes sense to consider IDO induction towards tolerance for autoimmune diseases in general. Approaches to cell specific therapeutic IDO induction with NAD precursor supplementation to prevent the collateral non-T cell pathogenesis due to chronic TNFalpha-IDO activated tryptophan depletion in autoimmune diseases are reviewed. Tryptophan is an essential amino acid most immediately because it is the only precursor for the endogenous biosynthesis of nicotinamide adenine dinucleotide (NAD). Both autoimmune disease and the NAD deficiency disease pellagra occur in women at greater than twice the frequency of occurrence in men. The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2. Loss of function leads to psychotic symptoms rapidly progressing to presenile dementia likely due to unchecked increases in microglial IDO expression, which depletes neurons of tryptophan causing neurodegeneration. Administration of NAD precursors rescued entire mental hospitals of dementia patients literally overnight in the 1930's and NAD precursors should help Nasu-Hakola patients as well. NAD depletion mediated by peroxynitrate PARP1 activation is one of the few established mechanisms of necrosis. Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD. Pharmacological doses of NAD precursors repeatedly provide dramatic therapeutic benefit for rheumatoid arthritis, type 1 diabetes, multiple sclerosis, colitis, other autoimmune diseases, and schizophrenia in either the clinic or animal models. Collectively these observations support the idea that autoimmune disease may in part be considered as localized pellagra manifesting symptoms particular to the inflamed target tissues. Thus pharmacological doses of NAD precursors (nicotinic acid/niacin, nicotinamide/niacinamide, or nicotinamide riboside) should be considered as potentially essential to the therapeutic success of any IDO-inducing regimen for treating autoimmune diseases. Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic prostaglandins PGE(2) and PGD(2). Next, PGD(2) is converted to the anti-inflammatory prostaglandin, 15d-PGJ(2). These prostaglandins exert potent anti-inflammatory activities through endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma respectively. Nicotinamide prevents type 1 diabetes and ameliorates multiple sclerosis in animal models, while nothing is known about the therapeutic potential of nicotinamide riboside. Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration.

Nicotinamide adenine dinucleotide biology and disease

            (Penberthy 2009) Download

Nicotinic Acid-Mediated Activation of Both Membrane and Nuclear Receptors towards Therapeutic Glucocorticoid Mimetics for Treating Multiple Sclerosis

            (Penberthy 2009) Download

The importance of NAD in multiple sclerosis

            (Penberthy and Tsunoda 2009) Download

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 auto-reactive 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 NAD-complementation 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.

No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide (NADH) in dementia

            (Rainer, Kraxberger et al. 2000) Download

Reduced nicotinamide adenine dinucleotide (NADH) is advertised as an over-the-counter product or dietary supplement to treat Alzheimer's disease. We performed a 3-month open-label study with oral 10 mg/day NADH with 25 patients with mild to moderate dementia of the Alzheimer, vascular, and fronto-temporal types in addition to their current cholinomimetic drug medication. In 19 patients who completed the study, we found no evidence for any cognitive effect as defined by established psychometric tests. We conclude that NADH is unlikely to achieve cognitive improvements in an extent reported earlier, and present theoretical arguments against an effectiveness of this compound in dementia disorders.

NAD+ and vitamin B3: from metabolism to therapies

            (Sauve 2008) Download

The role of NAD(+) metabolism in health and disease is of increased interest as the use of niacin (nicotinic acid) has emerged as a major therapy for treatment of hyperlipidemias and with the recognition that nicotinamide can protect tissues and NAD(+) metabolism in a variety of disease states, including ischemia/reperfusion. In addition, a growing body of evidence supports the view that NAD(+) metabolism regulates important biological effects, including lifespan. NAD(+) exerts potent effects through the poly(ADP-ribose) polymerases, mono-ADP-ribosyltransferases, and the recently characterized sirtuin enzymes. These enzymes catalyze protein modifications, such as ADP-ribosylation and deacetylation, leading to changes in protein function. These enzymes regulate apoptosis, DNA repair, stress resistance, metabolism, and endocrine signaling, suggesting that these enzymes and/or NAD(+) metabolism could be targeted for therapeutic benefit. This review considers current knowledge of NAD(+) metabolism in humans and microbes, including new insights into mechanisms that regulate NAD(+) biosynthetic pathways, current use of nicotinamide and nicotinic acid as pharmacological agents, and opportunities for drug design that are directed at modulation of NAD(+) biosynthesis for treatment of human disorders and infections.

Vitamin B3, the nicotinamide adenine dinucleotides and aging

            (Xu and Sauve 2010) Download

Organism aging is a process of time and maturation culminating in senescence and death. The molecular details that define and determine aging have been intensely investigated. It has become appreciated that the process is partly an accumulation of random yet inevitable changes, but it can be strongly affected by genes that alter lifespan. In this review, we consider how NAD(+) metabolism plays important roles in the random patterns of aging, and also in the more programmatic aspects. The derivatives of NAD(+), such as reduced and oxidized forms of NAD(P)(+), play important roles in maintaining and regulating cellular redox state, Ca(2+) stores, DNA damage and repair, stress responses, cell cycle timing and lipid and energy metabolism. NAD(+) is also a substrate for signaling enzymes like the sirtuins and poly-ADP-ribosylpolymerases, members of a broad family of protein deacetylases and ADP-ribosyltransferases that regulate fundamental cellular processes such as transcription, recombination, cell division, proliferation, genome maintenance, apoptosis, stress resistance and senescence. NAD(+)-dependent enzymes are increasingly appreciated to regulate the timing of changes that lead to aging phenotypes. We consider how metabolism, specifically connected with Vitamin B3 and the nicotinamide adenine dinucleotides and their derivatives, occupies a central place in the aging processes of mammals.

The effect of oral niacinamide on plasma phosphorus levels in peritoneal dialysis patients

            (Young, Cheng et al. 2009) Download

BACKGROUND: Hyperphosphatemia remains a significant problem for patients requiring dialysis and is associated with increased mortality. Current treatment options include dietary restriction, dialysis, and phosphate binders. Treatment using the latter is frequently limited by cost, tolerability, and calcium loading. One open-label trial found niacinamide to be effective at decreasing serum phosphorus values in hemodialysis patients. Niacinamide may effectively reduce phosphorus levels in peritoneal dialysis (PD) patients already receiving standard phosphorus-lowering therapies. METHODS: An 8 week, randomized, double blind, placebo-controlled trial to evaluate the effectiveness of niacinamide to reduce plasma phosphorus levels in PD patients. Patients had to demonstrate a baseline phosphorus value > 4.9 mg/dL. Patients were randomized to niacinamide or placebo and prescribed 250 mg twice daily, with titration to 750 mg twice daily, as long as safety parameters were not violated. Phosphate binders, active vitamin D, and cinacalcet were kept constant during the study. The primary end point was change in plasma phosphorus. Secondary end points included changes in lipid parameters. RESULTS: 15 patients started on the study drug (8 niacinamide, 7 placebo) and 7 in each arm had at least one on-study phosphorus measurement. The niacinamide treatment group experienced an average 0.7 +/- 0.9 mg/dL decrease in plasma phosphorus and the placebo-treated group experienced an average 0.4 +/- 0.8 mg/dL increase. The treatment effect difference (1.1 mg/dL) was significant (p = 0.037). No significant changes in high- or low-density lipoproteins or triglycerides were demonstrated. Two of the 8 patients randomized to the niacinamide treatment arm had to withdraw from the study due to drug-related adverse effects. Adverse effects may limit the use of niacinamide in PD patients. CONCLUSION: Niacinamide, when added to standard phosphorus-lowering therapies, resulted in a modest yet statistically significant reduction in plasma phosphorus levels at 8 weeks. [ClinicalTrials.gov number NCT00508885].


References

(2002). "Niacinamide. Monograph." Altern Med Rev 7(6): 525-9.

(2005). "Final report of the safety assessment of niacinamide and niacin." Int J Toxicol 24 Suppl 5: 1-31.

Belenky, P., K. L. Bogan, et al. (2007). "NAD+ metabolism in health and disease." Trends Biochem Sci 32(1): 12-9.

Farmer, J. A. (2009). "Nicotinic acid: a new look at an old drug." Curr Atheroscler Rep 11(2): 87-92.

Galli, M., F. Van Gool, et al. (2009). "The nicotinamide phosphoribosyltransferase: a molecular link between metabolism, inflammation, and cancer." Cancer Res 70(1): 8-11.

Garten, A., S. Petzold, et al. (2009). "Nampt: linking NAD biology, metabolism and cancer." Trends Endocrinol Metab 20(3): 130-8.

Green, K. N., J. S. Steffan, et al. (2008). "Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau." J Neurosci 28(45): 11500-10.

Kaneko, S., J. Wang, et al. (2006). "Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models." J Neurosci 26(38): 9794-804.

Kirkland, J. B. (2009). "Niacin status, NAD distribution and ADP-ribose metabolism." Curr Pharm Des 15(1): 3-11.

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Kuberski, Z. and Z. Kuklinska (1954). "[Nicotinic acid therapy of multiple sclerosis.]." Neurol Neurochir Psychiatr Pol 4(2): 145-52.

Li, F., Z. Z. Chong, et al. (2006). "Cell Life versus cell longevity: the mysteries surrounding the NAD+ precursor nicotinamide." Curr Med Chem 13(8): 883-95.

Lin, H. (2007). "Nicotinamide adenine dinucleotide: beyond a redox coenzyme." Org Biomol Chem 5(16): 2541-54.

Maiese, K., Z. Z. Chong, et al. (2009). "The vitamin nicotinamide: translating nutrition into clinical care." Molecules 14(9): 3446-85.

Morris, M. C., D. A. Evans, et al. (2004). "Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline." J Neurol Neurosurg Psychiatry 75(8): 1093-9.

Penberthy, W. T. (2007). "Pharmacological targeting of IDO-mediated tolerance for treating autoimmune disease." Curr Drug Metab 8(3): 245-66.

Penberthy, W. T. (2009). "Nicotinamide adenine dinucleotide biology and disease." Curr Pharm Des 15(1): 1-2.

Penberthy, W. T. (2009). "Nicotinic Acid-Mediated Activation of Both Membrane and Nuclear Receptors towards Therapeutic Glucocorticoid Mimetics for Treating Multiple Sclerosis." PPAR Res 2009: 853707.

Penberthy, W. T. and I. Tsunoda (2009). "The importance of NAD in multiple sclerosis." Curr Pharm Des 15(1): 64-99.

Rainer, M., E. Kraxberger, et al. (2000). "No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide (NADH) in dementia." J Neural Transm 107(12): 1475-81.

Sauve, A. A. (2008). "NAD+ and vitamin B3: from metabolism to therapies." J Pharmacol Exp Ther 324(3): 883-93.

Xu, P. and A. A. Sauve (2010). "Vitamin B3, the nicotinamide adenine dinucleotides and aging." Mech Ageing Dev 131(4): 287-98.

Young, D. O., S. C. Cheng, et al. (2009). "The effect of oral niacinamide on plasma phosphorus levels in peritoneal dialysis patients." Perit Dial Int 29(5): 562-7.