|1||Aging||Massudi et al.||2012|
Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue
|human pelvic tissue ||aging ||none||n/a|
- DNA damage correlated strongly with age
- lipid oxidation (MDA) levels increased with age in males but not females
- PARP activity significantly increased with age in males and inversely correlated with tissue NAD+ levels. These associations were less evident in females.
- a strong negative correlation was observed between NAD+ levels and age in both males and females
- SIRT1 activity also negatively correlated with age in males but not in females.
- strong positive correlations were also observed between lipid peroxidation and DNA damage, and PARP activity and NAD+ levels in post-pubescent males.
|2||Autoimmune arthritis||Busso et al.||2008|
Pharmacological Inhibition of Nicotinamide Phosphoribosyltransferase/Visfatin Enzymatic Activity Identifies a New Inflammatory Pathway Linked to NAD
|mouse||inflammatory arthritis model||FK866||10 mg/kg|
- reduced NAD+ concentrations in inflammatory cells
- reduced arthritic severity similar to etanercept
- lowered the levels of cytokine release in affected joints
|3||Blood||Vannini et al.||2019|
The NAD-booster nicotinamide riboside potently stimulates hematopoiesis through increased mitochondrial clearance
|female mice 8-12 wk old||HPSC||NR||7.57 mg/day|
- NR results in an enlarged pool of progenitors without concurrent HSC exhaustion
- improves survival by 80%
- accelerates blood recovery after murine lethal irradiation
- increases the production of WBC in immune-deficient mice
- induces autophagy and NAD generation gene expression
|4||Blood||Weidele et al. ||2010|
Ex vivo supplementation with nicotinic acid enhances cellular poly(ADP-ribosyl)ation and improves cell viability in human peripheral blood mononuclear cells
- increased cellular NAD+ levels
- boosts the cellular poly(ADP-ribosyl)ation response to genotoxic treatment
- protects from DNA-damage-induced cell death
|5||Cancer||Hong et al.||2019|
Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level
|mice + human CRC cells||colorectal cancer progression||NMN||n/a|
- showed that the NAD(H) pool size and NAD+ /NADH ratio both increased during colorectal cancer(CRC) progression due to activation of the NAD+ salvage pathway mediated by nicotinamide phosphoribosyltransferase (NAMPT).
- increases in the NAD(H) pool inhibited the accumulation of excessive reactive oxygen species (ROS) levels
- FK866 decreased the CRC nodule size by increasing ROS levels in AOM/DSS mice.
- NMN rescued the effects of FK866
|6||Cancer||van Horssen et al.||2012|
Intracellular NAD(H) levels control motility and invasion of glioma cells
|in vitro glioma cells||glioma||NAD+||10–50 μM|
- fluctuation in intracellular [NAD(H)] differentially affects cell growth and morphodynamics, with motility/invasion capacity showing the highest sensitivity to [NAD(H)] decrease
- extracellular supplementation of NAD+ or re-expression of NAMPT abolished the effects
|7||Cancer||Gujar et al.||2016||An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma||in vitro||glioblastoma stem-like cells||FK866||n/a|
- nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs).
- high NAMPT expression in tumors correlates with decreased patient survival.
- pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs.
- NAMPT mediates GSC radiation resistance.
|8||Cancer||Zhao et al.||2011|
NAD+ treatment decreases tumor cell survival by inducing oxidative stress.
|C6 Glioma, Neuro-2a, MKN-45, MCF-7 tumor cells||in vitro||NAD+, NMN, NAM||10uM-1mM for 24 or 48 hours|
- NAD+ at concentrations from 10 microMole to 1 mMole can significantly decrease the survival of various types of tumor cells
- NAD+ treatment did not impair the survival of primary astrocyte cultures
- oxidative stress mediates the effects of NAD+ on the survival of tumor cells, and P2X7 receptors and altered calcium homeostasis are involved in the effects of NAD+ on cell survival.
- NAM did not affect the survival of tumor cells
|9||Cancer ||Nacarelli et al. ||2019|
NAD+ metabolism governs the proinflammatory senescence-associated secretome
|mice||model of pancreatic cancer (PIN)||NAM, NMN, FK866, NA||FK866 25 mg ; NMN 500 mg/kg/day for 13 days, intraperitoneal injection ;NAM: 500 mg/kg/day every other day for 17 days|
- enhances the inflammatory environments in the pancreas to accelerate pancreatic cancer progression
- HMGA proteins and NAMPT promote the proinflammatory SASP through NAD+-mediated suppression of AMPK kinase, which suppresses the p53-mediated inhibition of p38 MAPK to enhance NF-κB activity
- NAD+ metabolism governs the proinflammatory SASP
|10||CNS||Wang et al.||2014|
The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity
|mouse cortical neuronal cultures||in vitro||NAD+||15 mM|
- NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preservation of mitochondrial biogenesis and integrity
|11||CNS||Johnson et al.||2018|
CA1 Nampt knockdown recapitulates hippocampal cognitive phenotypes in old mice which nicotinamide mononucleotide improves
|mice 2-20 months||hippocampal||NMN||300 mg/kg/day for 3 weeks|
- NAD+ levels declined in the hippocampus with age
- problem with sensory processing that was partially ameliorated with NMN supplementation
|12||CNS||Roh et al.||2018|
Effects of Chronic NAD supplementation on Energy Metabolism and Diurnal Rhythm in Obese Mice
|mice||hippocampal||NAD+||1 mg/kg for 4 weeks intraperitoneal injection;|
- significantly attenuated weight gain and recovered the suppressed rhythms
- exogenous NAD+ rescued cellular depletion expression of PER1 as well as blunted daily fluctuations of PER1 expression in obese mice
|13||CNS||Roh et al.||2018|
Exogenous nicotinamide adenine dinucleotide regulates energy metabolism via hypothalamic Connexin 43
|male mice 8-10 weeks old||hippocampal||NAD+||1 mg/kg|
- central and peripheral NAD administration suppressed fasting-induced hyperphagia and weight gain in mice.
|14||CNS||Sasaki et al.||2018|
Dysregulation of NAD+ Metabolism Induces a Schwann Cell Dedifferentiation Program
- rescues NAD+ decline
- reverses the SC maturation defect and the development of peripheral neuropathy
|15||CNS||Hou et al.||2018|
NAD+ supplementation normalizes key Alzheimer's features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency
|16-18-month-old mice||brain||NR||0.5mM for 3 months|
- lessened pTau pathology but had no impact on amyloid β peptide (Aβ) accumulation
- exhibited reduced DNA damage, neuroinflammation, and apoptosis of hippocampal neurons and increased activity of SIRT3 in the brain.
- improved cognitive function in multiple behavioral tests and restored hippocampal synaptic plasticity
|16||CNS||Liu et al.||2018|
Pharmacological bypass of NAD+ salvage pathway protects neurons from chemotherapy-induced degeneration
- bypassing NMN production protects neurons from degeneration
|17||CNS||Xie et al.||2019|
Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer's disease model mice
|16 female 14 months; 6 3 months; 16 male Alzheimer 3 months old; 10 male control 3 months||brain||NR||400-460 mg/kg/ day|
- NR improved short term spatial memory of aged mice and contextual fear memory of AD mice
- inhibited the activation of astrocytes and the elevation of serum NAMPT of aged mice;
- inhibited the accumulation of AB and the migration of astrocyte to AB
- inhibited the weight gain of both types of mice
|18||CNS||Caito et al.||2016|
NAD+ Supplementation Attenuates Methylmercury Dopaminergic and Mitochondrial Toxicity in Caenorhabditis Elegans
|Caenorhabditis elegans||neuro||NAD +||1 mM|
- NAD + supplementation also prevented DAergic neurodegeneration and deficits in DAergic-dependent behavior upon MeHg exposure.
|19||CNS||Lehmann et al.||2016|
Parp mutations protect against mitochondrial dysfunction and neurodegeneration in a PARKIN model of Parkinson's disease
|Drosophila||Parkin gene mutation||NAM||5 mM|
- rescues mitochondrial function and is neuroprotective
|20||CNS||Harlan et al.||2016|
Enhancing NAD+ Salvage Pathway Reverts the Toxicity of Primary Astrocytes Expressing Amyotrophic Lateral Sclerosis-linked Mutant Superoxide Dismutase 1 (SOD1)*
|in vitro ||ALS||NMN, NR,||5 mM|
- increasing total and mitochondrial NAD+ content in ALS astrocytes increases oxidative stress resistance and reverts their toxicity toward co-cultured motor neurons.
|21||CNS||Xie et al.||2017|
Protective effect of nicotinamide adenine dinucleotide (NAD+) against spinal cord ischemia-reperfusion injury via reducing oxidative stress-induced neuronal apoptosis
|rats||spinal cord ischemia-reperfusion injury||NAD+||50-100 mg/kg|
- decreased the oxidative stress level and neuronal apoptosis in the spinal cord of ischemia-reperfusion rats compared with saline
- restrained the neuronal apoptosis after ischemia injury while improving the neurological and motor function
|22||CNS||Gong et al.||2013|
Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models
|mice||Alzheimer||NR||250 mg/kg/day for 3 months|
- attenuates cognitive deterioration in and coincides with an increase in the steady-state levels of NAD+ in the cerebral cortex
- abolishes the deficits in long-term potentiation recorded in the CA1 region
- promotes PGC-1α expression in the brain and the reduction of Aβ production
|23||CNS||Stein et al.||2014|
Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging
|mice||hippocampal||NMN||500 mg/kg/day i.p. injection|
|24||CNS||Naia et al.||2017|
Comparative Mitochondrial-Based Protective Effects of Resveratrol and Nicotinamide in Huntington’s Disease Models
|murine; primary cortical and striatal cultures; human lymphoblastoid cell lines||Huntington's disease model||NAM||0.1 to 1 mM|
- high concentrations of NAM blocked mitochondrial-related transcription, worsening motor phenotype
- increased NAD+ levels
|25||CNS||Jia et al.||2008|
High doses of nicotinamide prevent oxidative mitochondrial dysfunction in a cellular model and improve motor deficit in a Drosophila model of Parkinson's disease
|Drosophila||model of Parkinsons's||NAM||15 and 30 mg/100 g diet s|
- significantly improved climbing ability
|26||CNS||Tarantini et al.||2019|
NMN supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice
|3 and 24-month old mice, in vivo, in vitro||aging model; vascular dementia||NMN||500 mg/kg injection 14 days|
- rescued NVC responses by increasing endothelial NO-mediated vasodilation, which was associated with significantly improved spatial working memory and gait coordination
|27||CNS||Di Stefano et al.||2015|
A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration
|cells, mice, zebrafish||axons, in vitro, ex vivo (mice), in vivo (zebrafish)||NMN||0.025-1mM|
- elevation of NMN promotes axon degeneration
- exogenous NMN (25uM-50mM) overcame protective effects of FK866
- the likely mechanism of uptake of NMN by cells is conversion to NR
- NR and NAD also abolished the protective effects of FK866 likely because both pass through the intermediate NMN
- NA, NaMN, NAAD do not abolish the protective effect of FK866 because they go through another pathway and NMN doesn't accumulate
- accumulation of NMN has also been shown to promote axon degeneration without physical injury (Vincristine-model of peripheral neuropathy)
- in mice, NMN levels rose 2.5 fold (4 nmol/g), approximately the concentration required to kill axons
|28||CNS||Klaidman et al.||2003|
Nicotinamide Offers Multiple Protective Mechanisms in Stroke as a Precursor for NAD+, as a PARP Inhibitor and by Partial Restoration of Mitochondrial Function
|mice ischemia-reperfusion model ||ischemia-reperfusion model ||NAM||500 mg/kg i.p. |
- using a global ischemia-reperfusion mouse model, ATP was depleted by 50% in the brain
- NAM provided a large reserve of brain NAD+, which restored ATP levels to 61% of control levels
- NAM as a PARP inhibitor restored ATP levels up to 72%
- pretreatment with NAM resulted in a large reserve of NAD+ in the brain and treatment just before reperfusion resulting in PARP inhibition proved to be additive, restoring ATP to 85% of control levels
|29||CNS||Di Stefano et al. ||2017|
NMN Deamidase Delays Wallerian Degeneration and Rescues Axonal Defects Caused by NMNAT2 Deficiency In Vivo
|mice and zebrafish||axons||NMN deamidase||n/a|
- NMN deamidase can delay axon degeneration in zebrafish larvae and in transgenic mice
- NMN deamidase reduces NMN accumulation in injured mouse sciatic nerves and preserves some axons for up to three weeks, even when expressed at a low level.
- NMN deamidase also rescues axonal outgrowth and perinatal lethality in a dose-dependent manner in mice lacking NMNAT2
- data support a pro-degenerative effect of accumulating NMN in axons in vivo
|30||CNS||Yao et al.||2017|
Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease
|mice||in vivo||NMN||100 mg/kg s.c. every other day for 28 days|
- NMN rescues cognitive impairment
- NMN suppresses JNK phosphorylation
- NMN decreases the level of AB and deposition
- NMN changes the processing of APP
- improves inflammation parameters (TNF, IL-1, IL-6)
|31||CNS||Rex et al.||2004||Treatment with reduced nicotinamide adenine dinucleotide (NADH) improves water maze performance in old Wistar rats||3 and 22-month old rats||learning||NADH||i.p. + i.v. 10-100 mg/kg |
- previous own experiments revealed an increased NADH level in the rat brain following peripheral application of NADH (10–100 mg/kg, i.p.+ i.v.)
- analyzed the effect of repeated i.p. injection of NADH on the performance of 3-month-old and 22-month-old Wistar rats in the Morris water maze and in the rota-rod test of motor coordination.
- repeated administration of NADH improved the performance of old rats in the acquisition phase (place version) and the spatial probe of the Morris water maze
|32||CNS||Ying et al.||2007|
Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia.
|rat||transient focal ischemia||NAD+||10 mg/kg NAD intranasal 2 hours after ischemic onset|
- intranasal NAD+ delivery significantly increased NAD+ contents in the brains.
- profoundly decreased infarct formation when assessed either at 24 or 72 hours after ischemia.
- NAD+ administration also significantly attenuated ischemia-induced neurological deficits.
- intranasal administration with 10 mg/kg NAM did not decrease ischemic brain damage.
|33||CNS||Park et al.||2016||Nicotinamide mononucleotide inhibits post-ischemic NAD+ degradation and dramatically ameliorates brain damage following global cerebral ischemia||male mice||global cerebral ischemia||NMN|
31.25 - 500 mg/kg
at ischemic onset or 30m after
- protection increased by lowering the doses
- most effective treatment was 62.5 mg/kg
- no signs of toxicity or mortality
- at doses higher than 62.5 mg/kg there was less survival of. CA1 hippocampal neurons
- this is in contrast to earlier studies where NAM showed the greatest effectiveness at 500 mg/kg
- significantly improved the neurologic outcome
|34||CNS||Mokudai et al.||2000||Delayed Treatment With Nicotinamide (Vitamin B3) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats||48 male rats||focal cerebral ischemia||NAM||500 mg/kg 2 hours after onset|
- transient focal cerebral ischemia was induced by MCAo for 2 hours, followed by reperfusion for either 3 or 7 days.
- treatment with NAM (500 mg/kg IP) 2 hours after the onset of transient focal cerebral ischemia in Wistar rats significantly improved sensory (38%, P,0.005) and motor (42%, P,0.05) neurological behavior and weight gain (7%, P,0.05) up to 7 days after MCAo.
- cerebral infarct volumes were also reduced by 46% (P,0.05) at 3 days and 35% (P50.09) at 7 days after MCAo.
|35||CNS||Wang et al.||2017||Nicotinamide Administration Improves Remyelination after Stroke||mice||stroke model||NAM||200 mg/kg daily for 14d starting 1h after stroke induction|
- NAM-treated mice showed significantly lower infarct area 7 d after stroke induction and significantly higher fractional anisotropy (FA) in the ipsilesional internal capsule (IC) 14 d after stroke induction than the other groups.
- higher levels of NAD+, BDNF, and remyelination markers were observed in the NAM-treated group.
- lesser functional deficits were observed in the NAM treated group than in the control group.
|36||CNS||Bi et al.||2012||PBEF exerts a neuronal protection through its enzymatic activity and the reduction of mitochondrial dysfunction in in vitro ischemic models||in vitro||mouse neurons||NAD+, NAM||15mM |
- pretreatment with high concentrations of NAD+ and NAM remarkably attenuated cell death at 24 hours after oxygen-glucose deprivation and glutamate toxicity
- surprisingly, NAM also restored NAD+ levels in the presence of FK866- either the enzyme is not completely inhibited, or some NAM is converted via the de novo pathway
- replenishment of NAD+ levels prevented ATP depletion caused by OGD
- NAD+ and NAM suppressed OGD-induced mitochondrial loss
|37||CNS||Zhao et al.||2015||Regenerative Neurogenesis After Ischemic Stroke Promoted by Nicotinamide Phosphoribosyltransferase–Nicotinamide Adenine Dinucleotide Cascade||10-week old male mice||brain||NAD+, NMN|
30 min, 12 hr, up to 7 days after ischemia
- NAD+ promotes neural stem cell activation and neurogenesis after ischemic stroke
- overexpression of NAMPT accelerates postischemic neurological function recovery and body weight gain
- early NMN administration at 30 min post-infarct decreased infarction and neurological deficit, enhanced animal survival and accelerated body weight recovery
- administration of NMN 12 hours after infarct was not neuroprotective but did reduce cell death and improved neuronal recovery and increased neurogenesis
|38||CNS||Wei et al.||2017||NAD replenishment with nicotinamide mononucleotide protects blood-brain barrier integrity and attenuates delayed tissue plasminogen activator-induced haemorrhagic transformation after cerebral ischaemia||8-week old male mice||ischemic stroke model||NMN||300 mg/kg/day|
- NMN prevents delayed tPA treatment-induced brain damage
- NMN restrains delayed tPA treatment-induced cerebral hemorrhage
- NMN inhibits delayed tPA treatment-induced neural apoptosis
- administration of NMN suppresses tPA treatment-induced neuroinflammation
- protection of BBB integrity contributes to the beneficial effects of NMN aginst tPA-induced hemorrhagic transformation
- NMN protects BBB integrity by suppressing tPA-induced activation of MMPs
|39||CNS||Zheng et al.||2012||NAD+ administration decreases ischemic brain damage partially by blocking autophagy in a mouse model of brain ischemia||adult male mice||transient ischemic stroke model||NAD+||50 mg/kg immediately after 90 min of ischemia|
- infarct size and brain swelling were significantly reduced in NAD+ treated mice
- NAD+ prevented autophagy in the ischemic brain
|40||CNS||Alano et al.||2004||Poly(ADP-ribose) Polymerase-1-mediated Cell Death in Astrocytes Requires NAD Depletion and Mitochondrial Permeability Transition||in vitro||cultured mouse astrocytes||NAD+||10 MM|
- in astrocytes, extracellular NAD can raise intracellular NAD concentrations.
- restoration of NAD enabled the recovery of mitochondrial membrane potential and blocked both MPT and cell death.
|41||CNS||Han et al.||2011||NAD+ Treatment Induces Delayed Autophagy in Neuro2a Cells Partially by Increasing Oxidative Stress|
|mouse neuroblastoma cell line||NAD+, NAM||1-10 mM for 48 hr|
- NAD+ increased the expression of a protein that indicates autophagy by nearly 10-fold
- NAM failed to cause the same increase
- NAD+ resulted in a decreased survival of cancer cells
|42||CNS||Xie et al.||2017||Nicotinamide Adenine Dinucleotide Protects against Spinal Cord Ischemia Reperfusion Injury-Induced Apoptosis by Blocking Autophagy||male rats||I/R injury model||NAD+||10 or 75 mg/kg i.p. injection|
- 75 mg/kg NAD+ inhibits autophagy activation after ischemia-reperfusion injury
- NAD+ ameliorates deteriorated neurological functions after autophagy activation after I/R injury
- NAD+ can alleviate cell apoptosis via inhibition of autophagy in I/R injury
|43||CNS||Long et al.||2015||Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model||mice + neuroblastoma cell line in vitro||Alzheimer model||NMN||100 mg/kg s.c. every other day for 28 days|
- NMN reverses deficient oxygen consumption rate in vitro and in vivo
- NMN reduced levels of full-length mutant APP
- NMN increased mitochondrial length and decreased fragmentation
- SIRT1 activity was increased in transgenic mice and NMN reduced this potentially preserving NAD+ for energetic metabolism
|44||CNS||Fang et al.||2016||NAD+ replenishment improves lifespan and healthspan in Ataxia telangiectasia models via mitophagy and DNA repair||worms, mice||ataxia telangiectasia model||NR/NMN||12 mM in drinking water|
- treatments that replenish intracellular NAD+ reduce the severity of AT neuropathology, normalize neuromuscular function, delay memory loss and extend lifespan in both animal models.
- treatments that increase intracellular NAD+ also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy.
|45||CNS||Wang et al.||2008||Cellular NAD Replenishment Confers Marked Neuroprotection Against Ischemic Cell Death Role of Enhanced DNA Repair||rat primary neuronal cultures||oxygen-glucose deprivation||NAD+||0.3-15mmol/L|
- direct NAD+ repletion in neurons either before or after OGD markedly reduced cell death and OGD-induced accumulation of DNA damage (AP sites, single and double strand breaks) in a concentration- and time-dependent manner.
- NAD+ repletion restored DNA repair activity by inhibiting serine-specific phosphorylation of the essential BER enzymes AP endonuclease and DNA polymerase-β.
|46||CNS||Kiss et al.||2019||Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells: a potential mechanism for the prevention of vascular cognitive impairment||rat cerebromicrovascular endothelial cells||age-related impairment in vasodilation||NMN||0.5 mM|
- NMN treatment in aged CMVECs significantly improved angiogenic processes and attenuated H2O2 production
- pre-treatment with a pharmacological inhibitor of SIRT1 prevented NMNmediated restoration of angiogenic processes in aged CMVECs
- normal cellular NAD+ levels are essential for normal endothelial angiogenic processes, suggesting that age-related cellular NAD+ depletion and consequential SIRT1 dysregulation may be a potentially reversible mechanism underlying impaired angiogenesis and cerebromicrovascular rarefaction in aging
|47||CNS||Liu et al.||2009|
Nicotinamide prevents NAD+ depletion and protects neurons against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neurons.
|cultured neurons and mouse model |
excitotoxic neuronal death in vitro
focal ischemic stroke in vivo
|NAM||200 mg/kg, i.p. injection|
- NAM inhibited SIRT1 deacetylase activity without affecting SIRT1 protein levels
- NAD+ levels were preserved and PAR accumulation and neuronal death induced by excitotoxic insults were attenuated in NAM-treated cells.
- treatment of neurons with the SIRT1 activator resveratrol did not protect them from glutamate/NMDA-induced NAD+ depletion and death.
- administration of NAM up to 1 h after the onset of ischemia elevated brain NAD+ levels and reduced ischemic infarct size.
|48||CNS||Huang et al.||2017||Combination of NAD+ and NADPH Offers Greater Neuroprotection in Ischemic Stroke Models by Relieving Metabolic Stress||primary mouse neurons; male mice||in vitro OGD; in vivo ischemic stroke model||NAD+ and NADPH|
50 mg/kg NAD+
2.5 or 7.5 mg/kg NADPH
- NAD+ was effective in protecting neurons against oxygen-glucose deprivation/reoxygenation (OGD/R) injury when given during the early time period of reoxygenation.
- in vivo studies in mice also suggested that NAD+ was effective for ameliorating ischemic brain damage when administered within 2 h after reperfusion
- combination of NADPH and NAD+ provided not only greater beneficial effects but also a larger therapeutic window in both cellular and animal models of stroke.
- combination of NADPH and NAD+ significantly increased the levels of adenosine triphosphate (ATP) and reduced the levels of reactive oxygen species (ROS) and oxidative damage of macromolecules
- combined medication significantly reduced long-term mortality, improved the functional recovery, and inhibited signaling pathways involved in apoptosis and necroptosis after ischemic stroke
|49||CNS||Hoane et al.||2006||Nicotinamide reduces acute cortical neuronal death and edema in the traumatically injured brain||rats||contusion injuries||NAM|
15 min after injury
- administration of NAM following TBI significantly reduced the number of FJ+ neurons in the injured cortex compared to saline-treated animals.
- NAM significantly attenuated the amount of water compared to saline-treated animals in the injured cortex.
- NAM administration significantly reduced neuronal death and attenuated cerebral edema following injury
|50||CNS||Ying et al.||2003||NAD+ repletion prevents PARP-1-induced glycolytic blockade and cell death in cultured mouse astrocytes||in vitro||mouse astrocytes||NAD+||10 mM|
- cultures incubated in high (10 mM) extracellular concentrations of NADþ after MNNG exposure showed normalization of intracellular NADþ concentrations.
- repletion of intracellular NADþ in this manner completely restored glycolytic capacity and prevented cell death
- suggests that NADþ depletion is the cause of glycolytic failure after PARP-1 activation
|51||CNS||Liu et al.||2013||Nicotinamide Forestalls Pathology and Cognitive Decline in Alzheimer Mice: Evidence for Improved Neuronal Bioenergetics and Autophagy Procession||mice||Alzheimer model||NAM||8 months|
- NAM preserved mitochondrial integrity and autophagy function, and reduced neuronal vulnerability to oxidative/metabolic insults and Aβ toxicity.
- NAD+ biosynthesis, autophagy, and PI3K signaling were required for the neuroprotective action of NAM
- improved cognitive performance, and reduced Aβ and p-Tau pathologies in the hippocampus and cerebral cortex.
- NAM treatment preserved mitochondrial integrity and improved autophagy-lysosome procession
- elevated levels of activated neuroplasticity-related kinases and the transcription factor cyclic AMP response element-binding protein in the hippocampus and cerebral cortex
|52||CNS||Green et al.||2008|
Nicotinamide restores cognition in AD transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau
|mice ||transgenic Alzheimer ||NAM||200 mg/kg/day in drinking water beginning at 4 months of. age|
- NAM selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1.
- NAM also dramatically increased acetylated-α-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability.
- these effects were limited to animals with mild-moderate pathology
- preclinical findings suggest that oral NAM may represent a safe treatment for AD and other tauopathies and that phosphorylation of tau at Thr231 may regulate tau stability.
|53||CNS||Sun et al.||2012||Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives||humans ||19 normotensive and 27 hypertensive||NAM||100 mg |
- hypertensives had higher baseline (fasting) levels of plasma NAM, Hcy and norepinephrine, but lower levels of plasma normetanephrine, a methylated norepinephrine derivative.
- NAM loading induced a significant increase in the levels of plasma MeNAM and norepinephrine, and a significant decrease in the levels of O-methylated epinephrine (metanephrine) and betaine, a major methyl donor, in both hypertensives and normotensives
- NAM-loading significantly increased plasma Hcy levels but decreased plasma normetanephrine levels in normotensives
- post-NAM loading levels of plasma epinephrine in hypertensives were higher than those of normotensives.
- high NAM intake may be involved in the pathogenesis of Hcy-related cardiovascular disease
|54||CNS||Hamity et al.||2017||Nicotinamide riboside, a form of vitamin B3 and NAD1 precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats||Female Sprague-Dawley rats||3 intravenous injections of 6.6 mg/kg paclitaxel over 5 days||NR||Daily oral administration of 200 mg/kg beginning 7 days before paclitaxel treatment and continuing for another 24 days|
- NR prevented the development of tactile hypersensitivity and blunted place escape-avoidance behaviors.
- effects were sustained after a 2-week washout period.
- NR increased blood levels of NAD1 by 50%, did not interfere with the myelosuppressive effects of paclitaxel, and did not produce adverse locomotor effects.
- NR for 3 weeks after paclitaxel reversed the well-established tactile hypersensitivity in a subset of rats and blunted escape-avoidance behaviors
|55||CVS||Su et al.||2007||Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion||male rats||isolated perfused rat lung||NAM||100 mg/kg 30 min after I/R|
- I/R increased the lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, pulmonary arterial pressure and capillary permeability, increased nitrate/ nitrite, methyl guanidine, tumour necrosis factor-a and interleukin-1b in lung perfusate, while it decreased adenosine triphosphate content with an increase in PARP activity in lung tissue.
- most of the I/R-induced changes were abrogated by post-treatment
- increase in pulmonary arterial pressure was enhanced by NAM post-treatment.
- NAM reduced the iNOS expression.
- results suggest that NAM exerted a protective effect on the acute lung injury caused by ischemia/reperfusion.
|56||CVS||Wu et al.||2017||Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats||male rats||isolated perfused rat lung model||FK866||n/a|
- FK866 significantly attenuated the increases in lung edema, pulmonary arterial pressure, lung injury scores, and TNF-α, CINC-1, and IL-6 concentrations in bronchoalveolar lavage fluid in the I/R group.
- malondialdehyde levels, carbonyl contents and MPO-positive cells in lung tissue were also significantly reduced by FK866
- FK866 mitigated I/R-stimulated degradation of IκB-α, nuclear translocation of NF-κB, Akt phosphorylation, activation of mitogen-activated protein kinase, and downregulated MKP-1 activity in the injured lung tissue.
- FK866 increased Bcl-2 and decreased caspase-3 activity in the I/R rat lungs.
- FK866 inhibited IL-8 production and NF-κB activation in human alveolar epithelial cells exposed to H/R.
|57||CVS||de Picciotto et al.||2016|
Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice
|4-8 month and 26-28 month male mice||arteries||NMN||300 mg/kg/day for 8 weeks|
- restored EDD and NO-mediated EDD
- reduced aPWV and EM
- normalized O2 production
- decreased nitrotyrosine,
- increased elastin, and restored vascular SIRT1 activity
- acute NMN incubation in isolated aortas increased NAD+ threefold
|58||CVS||Liu et al. ||2014|
Exogenous NAD+ supplementation protects H9c2 cardiac myoblasts against hypoxia/ reoxygenation injury via Sirt1-p53 pathway
|rat cardiomyocytes||in vitro||NAD+||various: 0-5000 uM|
- elevates intracellular NAD+ level and provides protection against HR injury in both time and concentration-dependent manners.
- attenuates HR-induced cell apoptosis, which is at least partly mediated by restoring Sirt1 activity and subsequently inhibiting p53 activity
|59||CVS||Cox et al.||2002|
Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats
|rats||model of chronic volume overload ||NAM||0.67 mg/ml in drinking water, 2 days pre-surgery and 4 wk post-surgery|
- preservation of cardiac function
- prevention of adverse remodeling
|60||CVS||Pillai et al.||2010|
Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway
|mice||angiotensin-II-induced mouse model of cardiac hypertrophy||NAD+||1 mg/kg/day for 2 wks |
- preservation of cardiac function
- prevention of adverse remodeling
|61||CVS||Lee et al.||2016|
Normalization of NAD+ Redox Balance as a Therapy for Heart Failure
|mice||pressure overload mouse model of hypertrophy: transverse aortic constriction||NMN||500 mg/kg i.p. every 3 days, 5 days before and until 4 wk postsurgery|
- preservation of cardiac function
- prevention of adverse remodeling
|62||CVS||Gero et al.||2015|
Salvage of nicotinamide adenine dinucleotide plays a critical role in the bioenergetic recovery of post-hypoxic cardiomyocytes
|rat cardiomyocyte cell line ||in vitro||NAD||n/a|
- salvage of NAD+ via nicotinamide phosphoribosyltransferase was essential for bioenergetic recovery in cardiomyocytes
- blockade of nicotinamide phosphoribosyltransferase prevented the restoration of the cellular ATP pool following oxygen-glucose deprivation injury by inhibiting both the aerobic and anaerobic metabolism in the cardiomyocytes
- NAD+ consumption by PARP-1 also undermined the recovery processes, and PARP inhibition significantly improved the metabolism and increased cellular ATP levels in cardiomyocytes.
|63||CVS||Diguet et al.||2017|
Nicotinamide riboside preserves cardiac function in a mouse model of dilated cardiomyopathy
|mice||dilated cardiomyopathy||NR||NR-enriched diet with a target dose of 400 mg/kg/day (starting 2 days postsurgery)|
- preservation of cardiac function
- prevention of adverse remodeling
|64||CVS||Martin et al.||2017|
Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich's ataxia cardiomyopathy model
|mice||Mouse model of Friedreich's ataxia cardiomyopathy||NMN|
500 mg/kg i.p., 2 times weekly for 4–5 w
- restored cardiac function
- improvement of cardiac and extracardiac metabolic bioenergetics
|65||CVS||Zhang et al.||2017|
Short-term administration of nicotinamide mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure
|mice||Mouse model of mitochondrial dysfunction (cardiac-specific KLF4−/− mice) with pressure overload cardiomyopathy||NMN||500 mg·kg−1·day−1 i.p., every day (starting 1 day presurgery to 3–5 days postsurgery)|
- restored cardiac contractility
- reduction in cardiac cell death
- decreased expression of inflammatory markers
|66||CVS||Yamamoto et al.||2014|
Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion
|mice||Mouse model of I/R injury||NMN||500 mg/kg i.p. 30 min before ischemia|
- reduced infarct size
- improved cardiac function
|67||CVS||Guan et al.||2016|
CD38 deficiency protects the heart from ischemia/reperfusion injury through activating SIRT1/FOXOs-mediated antioxidative stress pathway
|mice||Mouse model of I/R injury||NAD+||200 mg/kg i.p.|
|68||CVS||Zhu et al.||2016|
Nicotinamide restores tissue NAD+ and improves outcomes in a murine model of cardiac arrest
|mice||Mouse model of cardiac arrest||NAM||500 mg/kg iv postcardiac arrest protocol|
- increased sudden cardiac arrest survival
|69||CVS||Zhang et al.||2016|
Exogenous NAD+administration significantly protects against myocardial ischemia/reperfusion injury in rat model
|rat||rat model of I/R injury||NAD+||10–20 mg/kg iv before ischemia|
- reduced infarct size
- improved cardiac function
|70||CVS||Liu et al.||2009|
Cardiac Na+ current regulation by pyridine nucleotides
|ex vivo||mouse model of Brugada Syndrome||NAD+||100 µM perfusion, 20 min|
- reduction in arrhythmic susceptibility
|71||CVS||Liu et al.||2013|
Mitochondrial dysfunction causing cardiac sodium channel downregulation in cardiomyopathy
|mice and ex vivo human hearts||nonischemic cardiomyopathic mouse model: ||NAD+||100 mg/kg, 2 injections before euthanasia (24 h, 1 h)|
- improved the sodium channel conduction velocity in isolated cardiomyocytes
- failing human hearts showed a reduction in conduction velocity that improved with NAD+ via reduction of. mitochondrial ROS
|72||CVS||Tong et al.||2012||Nicotinamide Pretreatment Protects Cardiomyocytes against Hypoxia-Induced Cell Death by Improving Mitochondrial Stress||in vitro rat||cardiomyocytes||NAM||2.5-20 mmol/l |
- NAM reduces cell death of cardiomyocytes under normoxic conditions
- NAM pretreatment protects cardiomyocytes from hypoxia-induced cell death
- NAM pretreatment promotes energy synthesis and activated mitochondrial protection
|73||Ears||Brown et al.||2014|
Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing loss
|mice||ear||NR||1000 mg/kg 2 times per day for 5 days|
- increased NAD+, activation SIRT3
- administration of NR, even after noise exposure, prevents noise-induced hearing loss (NIHL) and spiral ganglia neurite degeneration
|74||Eyes||Lin et al.||2016||NAMPT-mediated NAD+ biosynthesis is essential for vision in mice||mice||model of retinal degeneration||NMN||300 mg/kg; 10 injections |
- rod or cone photoreceptor-specific deletion of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the major NAD+ biosynthetic pathway beginning with NAM, caused retinal degeneration.
- we could rescue vision with NMN
- retinal NAD+ deficiency was an early feature of multiple mouse models of retinal dysfunction, including light-induced degeneration, streptozotocin-induced diabetic retinopathy, and age-associated dysfunction.
- NAD+ deficiency caused metabolic dysfunction and consequent photoreceptor death.
- SIRT3/SIRT5 play important roles in retinal homeostasis and NAD+ deficiency causes SIRT3 dysfunction.
|75||Eyes||Williams et al.||2017|
Glaucoma as a metabolic optic neuropathy: making the case for nicotinamide treatment in glaucoma
- ~10-fold decrease in the risk of developing glaucoma.
|76||Immune ||Van Gool et al.||2009||Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner.||mice in vivo, mouse macrophage cells||endotoxic shock in vivo, in vitro||NAM||500 mg/kg|
- protected mice against a lethal high dose of LPS even when injected 2 hours following endotoxin
- Exogenous NAM inhibits TNF-α secretion through modulation of mRNA translation efficiency.
- capacity to produce TNF-α appears to be directly correlated with intracellular NAD levels
- similarly to NAM, structurally unrelated sirtuin inhibitors downregulate TNF-α secretion with minimal effect on TNF-α gene transcription.
- identified SIRT6 as a sirtuin member able to upregulate TNF-α synthesis in vitro
|77||Immune||Petin et al.||2019||NAD metabolites interfere with proliferation and functional properties of THP-1 cells||monocytic leukemia cell line THP-1||in vitro||NAM, NR,MeNAM|
8mM NAM, NR
3.2 mM MeNAM
- concentrations above the ones used strongly reduced the viability of cells
- treatment with NAM, NR, and MNA resulted in growth retardation accompanied by enrichment of cells in the G0/G1-phase independent of p21 and p53.
- NAM and NR caused an increase in intracellular NAD concentrations and SIRT1 and PARP1 mRNA expression was found to be enhanced.
- compounds failed to up-regulate the expression of the cell surface differentiation markers CD38, CD11b and CD14.
- modulated the reactive oxygen species production and primed the cells to respond less effectively to the LPS induced TNF-a production
|78||Immune||Liu et al.||2001||Extracellular nicotinamide adenine dinucleotide induces t cell apoptosis in vivo and in vitro.||mouse spleen, liver, bone marrow||in vitro||NAD+||1mM for 24 hours|
- contact of T cells with NAD causes cell death.
- naive T cells, when incubated with NAD and adoptively transferred into semiallogeneic mice, fail to cause graft-vs-host disease, and when injected into syngeneic, T cell-deficient recipients do not reconstitute these mice
- they accumulate in the liver, leading to an increase of apoptotic lymphocytes in this organ
- injection of NAD causes a dramatic increase of apoptotic CD3, CD4, and CD8 cells in the liver
- in vitro incubation of naive T cells with NAD is shown to induce apoptosis
- no cell death is demonstrable when T cells are activated before incubation with NAD.
Niacin ameliorates oxidative stress, inflammation, proteinuria, and hypertension in rats with chronic renal failure
|male rat||chronic kidney disease||Niacin||50 mg/kg/day in drinking water for 12 weeks|
- ameliorated hypertension, proteinuria, glomerulosclerosis, and tubulointerstitial injury.
|80||Kidney||Guan et al.||2017||Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1–Dependent Manner||3 and 20-month-old mice ||kidney||NMN||500 mg/kg for 4 days|
- restored renal SIRT1 activity and NAD+ content
- significantly protected mice in both age groups from cisplatin-induced AKI.
|81||Kidney||Tran et al.||2016||PGC1α-dependent NAD biosynthesis links oxidative metabolism to renal protection||mice||kidney||NAM||400 mg/kg/day in saline i.p. injection; 4 days|
- reversed established ischemic AKI and also prevented AKI in an unrelated toxic model.
|82||Kidney||Zheng||2018||Nicotinamide reduces renal interstitial fibrosis by suppressing tubular injury and inflammation||male mice||unilateral urethral obstruction||NAM||200-800 mg/kg/day i.p. injection|
- NAM inhibited unilateral urethral obstruction (UUO) induced renal interstitial fibrosis
- NAM suppressed tubular atrophy and apoptosis
- NAM suppressed UUO‐associated T cell and macrophage infiltration and induction of pro‐inflammatory cytokines, such as TNF‐α and IL‐1β.
- In cultured mouse proximal tubule cells, NAM blocked TGF–β‐induced expression of fibrotic proteins, while it marginally suppressed the morphological changes induced by TGF‐β
- NAM also suppressed the expression of pro‐inflammatory cytokines (eg MCP‐1 and IL‐1β) during TGF‐β treatment of these cells.
- no dose-response effect at these doses - the maximum effect was reached already at 200 mg/kg
|83||Liver||Pham et al.||2019|
Nicotinamide riboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis
|mice||liver fibrosis||NR||400 mg/kg/day for 20 weeks|
NR supplementation significantly reduced the body weight of mice after 7 weeks
- did not improve glucose tolerance
did not attenuate serum alanine aminotransferase levels, liver steatosis, or liver inflammation
NR markedly reduced collagen accumulation in the liver.
RNA-Seq analysis suggested that the expression of genes involved in NAD+ metabolism is altered in activated hepatic stellate cells (HSCs) compared to quiescent HSCs.
NR inhibited the activation of HSCs in primary mouse and human HSCs
NR increased energy expenditure, likely by upregulation of β-oxidation in skeletal muscle and brown adipose tissue.
|84||Metabolism||Zhou et al.||2009||Nicotinamide overload may play a role in the development of type 2 diabetes||humans/ rats||diabetes||NAM||100 mg humans; 2 g/kg rats|
- diabetic subjects had significantly higher plasma MeNAM levels 5 h after a 100-mg NAM load than the non-diabetic subjects (0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P < 0.001)
- cumulative doses of NAM (2 g/kg) significantly increased rat plasma MeNAM concentrations associated with severe insulin resistance, which was mimicked by MeNAM
- cumulative exposure to MeNAM (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio and increased plasma H2O2 levels.
- a decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to MeNAM in vitro.
- sweating eliminated excessive NAM (5.3-fold increase in sweat NAM concentration 1 h after a 100-mg NAM load).
- skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed MeNAM clearance.
|85||Metabolism||Crisol et al.||2018|
Nicotinamide riboside induces a thermogenic response in lean mice
|8-week old male mice||metabolism||NR||400 mg/kg/day for 5 weeks|
- negative correlation between genes of NAD+ synthesis (NAMPT and Nmnat1) and body weight and fat mass
- NR reduced the abdominal visceral fat deposits, slightly increased O2 consumption and increased body temp.
|86||Metabolism||Zhou et al.||2016|
Hepatic NAD+ deficiency as a therapeutic target for non-alcoholic fatty liver disease in aging
|male mice middle and old age||liver||NR||200 mg/kg/day for 4 weeks|
- humans: 70% NAD levels in >60 yrs compared to middle age
- salvage pathway but not the biosynthesis pathway was compromised in both mice and humans
- NR completely corrected NAFLD
- SIRT1 overexpression only partially rescued these phenotypes.
|87||Metabolism||Uddin et al.||2017|
Nicotinamide mononucleotide supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise
|Female offspring weaned onto HFD||hepatic||NMN||treadmill exercise for 9 weeks, or NMN injection daily for 18 days|
- both interventions improved adiposity, glucose status, and mitochondrial function
|88||Metabolism||Mardinoglu et al.||2017|
Personal model‐assisted identification of NAD+ and glutathione metabolism as intervention target in NAFLD
|mice||hepatic||NR + serine + NAC||400 mg/kg/day|
- 50% reduction in hepatic TGs
- tendency towards a decrease in the level of cholesterol esters and ceramides, and
- tendency towards an increase in sphingomyelin
- no significant changes in the level of phosphatidylethanolamine.
|89||Metabolism||Melo et al.||2000|
Lipid Peroxidation in Nicotinamide-Deficient and Nicotinamide-Supplemented Rats
|young rats||hepatic||NAM||500 mg/kg diet|
- lipid peroxidation was significantly increased in the liver
|90||Metabolism||Huang et al.||2018|
PARP Inhibitor PJ34 Attenuated Hepatic Triglyceride Accumulation in Alcoholic Fatty Liver Disease in Mice
|male mice||liver||NR||10 mg/kg|
- alleviated hepatic TG accumulation in alcohol-fed mice and elevated hepatic NAD+ content
|91||Metabolism||Bushehri et al.||1998|
Oral reduced B-nicotinamide adenine dinucleotide (NADH) affects blood pressure, lipid peroxidation, and lipid profile in hypertensive rats (SHR)
- systolic BP decreased and stayed markedly lower for the remainder of the study
- no significant differences were seen in blood levels of glucose, insulin, triglyceride, and HDL levels
- lowered total cholesterol and LDL.
|92||Metabolism||Yoshino et al.||2011|
Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice
|young HFD 3-6 months; old with diabetes||metabolism||NMN||500 mg/kg body weight/day|
- ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice.
- enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation.
|93||Metabolism||Li et al.||2014|
Dietary nicotinic acid supplementation ameliorates chronic alcohol-induced fatty liver in rats
- not worsened by dietary NA deficiency, but was ameliorated by dietary NA supplementation
- liver total NAD, NAD+, and NADH levels were remarkably higher
- NA supplementation increased the protein levels of hepatic cytochrome P450 4A1 (CYP4A1) and acyl-Coenzyme A oxidase 1 without affecting their mRNA levels.
- NA supplementation reduced the ubiquitination level of CYP4A1.
- hepatic fatty acid synthase expression was reduced, while the serum β-hydroxybutyrate and adiponectin concentrations were significantly elevated by dietary NA supplementation.
- modulated EtOH-perturbed liver and serum metabolite profiles
|94||Metabolism||Cantó et al.||2012||The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity||male mice||mitochondria and metabolism high-fat diet||NR, NA, NMN||400 mg/kg/day|
- NR and NMN do not cause flushing
- only NR and NA increased NAD+ levels in muscle
- all increased NAD+ levels in the liver
- NR increases SIRT1 activity by increasing NAD+ bioavailability
- HFD induced weight gain was significantly reduced by NR
- NR-fed mice ate more and moved the same amount
- NR-fed mice showed greater insulin sensitivity
- NR prevented the HFD rise in LDL and total cholesterol
- muscle isolated from NR-fed mouse gastrocnemius showed a better oxidative profile and more endurance
- chronic NR supplementation increased NAD+ in liver and muscle but not in brain or white adipose tissue
- NADH and NAM levels were largely diminished in NR-fed muscles
- NMN must be converted to NR for uptake by some cell types
- NR is a naturally occurring component of the diet
- NMN might be a precursor for the mitochondria
|95||Metabolism||Ramsey et al.||2008||Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1- overexpressing (BESTO) mice||mice||insulin secretion||NMN||500 mg/kg|
- NAD+ biosynthetic capacity of the islets does not alter during aging
- plasma levels of NMN were lower in older mice
- NMN ameliorates the defects in glucose-stimulated insulin secretion
- NMN slightly impaired glucose tolerance in female mice
|96||Metabolism||Caton et al.||2011||Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediated impairment of mouse islet function||male mice||fructose-rich diet||NMN||500 mg/kg|
- FRD-fed mice displayed markedly lower levels of circulating eNAMPT, with impaired insulin secretion and raised islet expression of Il1b.
- NMN administration lowered Il1b expression and restored suppressed insulin secretion in FRD-fed mice.
- NMN also restored insulin secretion in islets cultured with pro-inflammatory cytokines.
- anti-inflammatory effects of NMN were partially blocked by inhibition of sirtuin 1.
|97||Metabolism||Gariani et al.||2016||Eliciting the Mitochondrial Unfolded Protein Response by Nicotinamide Adenine Dinucleotide Repletion Reverses Fatty Liver Disease in Mice||mice||NAFLD||NR ||500 mg/kg/day|
- a high-fat high-sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic NAM adenine dinucleotide (NAD1) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation
- NR, a precursor of NAD1 biosynthesis, was added to the HFHS diet, either as a preventive strategy or as a therapeutic intervention.
- NR prevents and reverts NAFLD by inducing a sirtuin (SIRT)1- and SIRT3-dependent mitochondrial unfolded protein response, triggering an adaptive mitohormetic pathway to increase hepatic b-oxidation and mitochondrial complex content and activity.
|98||Metabolism||Tummala et al.||2014||Inhibition of De Novo NAD+ Synthesis by Oncogenic URI Causes Liver Tumorigenesis through DNA Damage||mice||oncogene-induced hepatocellular carcinoma||NR||500 mg/kg|
- increased hepatic NAD+ concentration
- reduced fibrosis, p53 abundance, ALT levels, and prevented tumor development
- also showed significant tumor regression in established tumors over a 48 week period
|99||Metabolism||Shi et al. ||2017||Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet||Nine-week-old male C57BL/6JRcc mice||mildly obesogenic diet||NR|| 5, 15, 30, 180, or 900 mg/kg diet for 15 weeks.|
- maximum delta respiratory exchange ratio when switching from CHO to FAO and when switching from FAO to CHO were largest in 30 mg NR per kg diet (30NR).
- in eWAT, the gene expression of Ppar, a master regulator of adipogenesis, and of Sod2 and Prdx3, two antioxidant genes, were significantly upregulated in 30NR compared to 5NR.
- 30NR is most beneficial for metabolic health, in terms of metabolic flexibility and eWAT gene expression, of mice on an obesogenic diet.
|100||Metabolism||Alenzi||2009||Effect of Nicotinamide on Experimental Induced Diabetes||rats||diabetes model||NAM||1g/kg/day orally for 3 days followed by (i.p.) STZ (55 mg/kg) with the NAM treatment continuing for an additional 14 days. |
- NAM treatment prevented STZ-induced diabetes
- it also antagonized an increase in NO and inhibited β-cell apoptosis.
- fasting blood glucose, serum insulin and serum C-peptide were all within the normal range in the NAM group.
- NAM protection of β-cells may be facilitated via inhibition of apoptosis and nitric oxide generation.
|Trammell et al.||2016||Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice||male mice||high-fat diet induced to develop diabetes ||NR||3g/kg of chow|
- NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy.
- in T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain, and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone.
- quantitative metabolomics established that hepatic NADP+ and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR.
|102||Metabolites||Li et al.||2009||Nicotinamide supplementation induces detrimental metabolic and epigenetic changes in developing rats||male rats||NAM long term exposure||NAM||1 or 4 g/kg chow for 8 weeks|
- low dose NAM exposure increased weight gain, but high-dose did not.
- NAM-treated rats had higher hepatic and renal levels of 8-hydroxy-20 -deoxyguanosine, a marker of DNA damage, and impaired glucose tolerance and insulin sensitivity when compared with the control rats.
- NAM supplementation increased the plasma levels of NAM, MeNAM, and choline and decreased the levels of betaine, which is associated with a decrease in global hepatic DNA methylation and uracil content in DNA.
- NAM had gene-specific effects on the methylation of CpG sites within the promoters and the expression of hepatic genes tested that are responsible for methyl transfer reactions, for homocysteine metabolism and for oxidative defense
- NAM-induced oxidative tissue injury, insulin resistance, and disturbed methyl metabolism can lead to epigenetic changes
- long-term high NAM intake (e.g. induced by niacin fortification) may be a risk factor for methylation- and insulin resistance-related metabolic abnormalities
|103||Metabolites||Li et al.||2012||Excessive nicotinic acid increases methyl consumption and hydrogen peroxide generation in rats||rats||cumulative dosing of NA||NA||2 g/kg|
- Cumulative doses of nicotinic acid produced a dose-dependent increase in the plasma levels of MeNAM and hydrogen peroxide, which was associated with a decrease in liver and skeletal muscle glycogen levels.
- in comparison with NAM, NA was weaker in raising plasma MeNAM levels but stronger in increasing plasma hydrogen peroxide levels
- NAM, unlike NA, did not reduce liver glycogen levels.
- excessive NA, like NAM, might induce methyl consumption, oxidative stress, and insulin resistance
- long-term consumption of high niacin may increase the risk of type 2 diabetes.
|104||Metabolites||Mori et al.||2012|
Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese
|Mouse CD1 brain striatum neuronal cells||toxicity of MENAM||MeNAM, NAM||10 mM|
- cell survival rate dropped significantly when the cells were cultivated with MeNAM
- a tendency for the survival rate to fall following the addition of 10 mM NAM
|105||Metabolites||Harrison et al.||2018|
The histone deacetylase inhibitor nicotinamide exacerbates neurodegeneration in the lactacystin rat model of Parkinson's disease
|rat||Parkinson model||NAM||250 or 500 mg/kg/day for 28 days intraperitoneal injection|
- exacerbated neurodegeneration of dopaminergic neurons, behavioral deficits and structural brain changes in the lactacystin‐lesioned rat
- induced histone hyperacetylation and over‐expression of numerous neurotrophic and anti‐apoptotic factors in the brain yet failed to result in neuroprotection
Effects of exogenous vitamins A, C, and E and NADH supplementation on proliferation, cytokines release, and cell redox status of lymphocytes from healthy aged subjects
|in vitro||Peripheral blood lymphocytes||NADH||500 uM|
- NADH significantly improved lymphocyte proliferation and mitigated cellular oxidative stress
|107||Mito/Immune||Li et al.||2015|
Nicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling pathway
|rabbits||immune system||NA||0.4% NA/ kg food|
- C-reactive protein (CRP) and monocyte chemotactic protein-1 (MCP-1) was significantly suppressed
- decreased the expression of cluster of differentiation 40 (CD40) and CD40 ligand (CD40L), but up-regulated SIRT1 expression
|108||Mito/Immune||Venter et al.||2014|
NAMPT-Mediated Salvage Synthesis of NAD+ Controls Morphofunctional Changes of Macrophages
|murine monocyte||blood cell||NAD+, NMN NADP+|
- restoration of NAD+ levels by NAD+, NMN, or NADP+ supplementation reversed the inhibitory effects of FK866. We conclude that direct coupling to local, actin-based, cytoskeletal dynamics is an important aspect of NAD+’s cytosolic role in the regulation of morphofunctional characteristics of macrophages.
|109||Mito/Immune||Sims et al. ||2018|
Nicotinamide mononucleotide preserves mitochondrial function and increases survival in hemorrhagic shock
|rats||in vivo||NMN||400 mg/kg/d |
- NMN significantly reduced lactic acidosis and serum IL-6 levels, two strong predictors of mortality in human patients
- in both livers and kidneys, NMN increased NAD levels and prevented mitochondrial dysfunction
- NMN preserved mitochondrial function in isolated hepatocytes cocultured with proinflammatory cytokines, indicating a cell-autonomous protective effect that is independent of the reduction in circulating IL-6
- in kidneys, but not in livers, NMN was sufficient to prevent ATP loss following shock and resuscitation
- NMN increased the time animals could sustain severe shock before requiring resuscitation by nearly 25% and significantly improved survival after resuscitation whether NMN was given as a pretreatment or only as an adjunct during resuscitation
- NMN substantially mitigates inflammation, improves cellular metabolism, and promotes survival following hemorrhagic shock
|110||Mito/Immune||Felici et al.||2015|
Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I–Mutant Fibroblasts
|human fibroblasts||in vitro||NR||0.1–10 mM|
- NR supplementation increased intracellular NAD content in human fibroblasts
- PARP-1 inhibitors increased transcription of mitochondrial transcription factor A and mitochondrial DNA–encoded respiratory complexes
- both NR and PARP-1 inhibitors restored mitochondrial membrane potential and increased organelle content as well as oxidative activity fibroblasts.
|111||Mito/Immune||Peek et al.||2013|
Circadian Clock NAD+ Cycle Drives Mitochondrial Oxidative Metabolism in Mice
|mouse||circadian mutant mice||NMN||250 for acute, 500 mg/kg for chronic treatment for 10 days|
- NAD+ supplementation restored protein deacetylation and enhanced oxygen consumption in circadian mutant mice
|112||Mito/Immune||Pittelli et al.||2011||Pharmacological Effects of Exogenous NAD on Mitochondrial Bioenergetics, DNA Repair, and Apoptosis||human HeLa, RAW HepG2||in vitro||NAD+||1uM-1mM|
- intracellular NAD contents increased upon exposure of cell lines or primary cultures to exogenous NAD (eNAD).
- NAD precursors could not reproduce the effects of eNAD, and they were not found in the incubating medium containing eNAD, thereby suggesting direct cellular eNAD uptake.
- in mitochondria of cells exposed to eNAD, NAD and NADH, as well as oxygen consumption and ATP production, were increased.
- DNA repair, a well known NADdependent process, was unaltered upon eNAD exposure.
- eNAD conferred significant cytoprotection from apoptosis triggered by staurosporine, C2-ceramide, or N-methyl-N- nitro-N-nitrosoguanidine.
- strengthen the hypothesis that eNAD crosses the plasma membrane intact and, on the other hand, provide evidence that increased NAD contents significantly affects mitochondrial bioenergetics and sensitivity to apoptosis.
|113||Mito/Immune||Klimova et al.||2019||Nicotinamide mononucleotide alters mitochondrial dynamics by SIRT3‐dependent mechanism in male mice||male mice||oxidative stress||NMN||62.5 mg/kg|
- single dose (62.5 mg/kg) of NMN, administered to male mice, increases hippocampal mitochondria NAD+ pools for up to 24 hr posttreatment and drives a sirtuin 3 (SIRT3)‐ mediated global decrease in mitochondrial protein acetylation.
- reduction of hippocampal reactive oxygen species levels via SIRT3‐driven deacetylation of mitochondrial manganese superoxide dismutase.
- mitochondria in neurons become less fragmented due to lower interaction of phosphorylated fission protein, dynamin‐related protein 1 (pDrp1 [S616]), with mitochondria.
|114||Muscle||Ryu et al.||2016|
NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation
|mice||skeletal muscle||NR||400 mg/kg/day|
- improved muscle function
- effects of NAD+ repletion relied on the improvement in mitochondrial function and structural protein expression and on the reductions in general poly(ADP)-ribosylation, inflammation, and fibrosis
|115||Muscle||Goody et al.||2012|
NAD+ Biosynthesis Ameliorates a Zebrafish Model of Muscular Dystrophy
|zebrafish||muscular dystrophy||NR, NAD+||0.1 mM|
- reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos
|116||Muscle||Oakey et al.||2018|
Metabolic tracing reveals novel adaptations to skeletal muscle cell energy production pathways in response to NAD+ depletion
|in vitro ||murine skeletal muscle||NR||.5 mM|
- no effect on ATP or NADP levels in normal cells
- no effect on carbon metabolism
- restores NADP-levels in depleted cells
- 9 fold increase in NAM
- MeNAM increased
|117||Muscle||Frederick et al.||2016|
Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle
|Nampt transgenic mice; 5.5 months old||skeletal muscle||NR, NAM||400 mg/kg/day|
- >60% decline in ATP in knockout mice
- young mice fatigued at the same rate but as they aged they fatigued faster
- no change in the ability to generate single force but the tetanic contraction was affected
- no difference in bone mineral density in young mice,
- rapidly ameliorated functional deficits and restored muscle mass despite having only a modest effect on the intramuscular NAD pool.
|118||Muscle||Pajk et al.||2017|
Exogenous nicotinamide supplementation and moderate physical exercise can attenuate the aging process in skeletal muscle of rats
|4 month and 28-month-old rats||effect on skeletal muscle aging||NAM||(1–0.5% in drinking|
water) was supplemented for 5 weeks
- activity of SIRT1 increased in both age groups
- increased PGC-1a and pCREB/CREB ratio in the gastrocnemius muscle of old but not young animals.
- attenuated the aging process in skeletal muscle of rats, but NAM administration together with exercise training might be too great a challenge to cope with in older animals since it leads to decreased levels of SIRT1.
|119||Muscle||Kourtzidis et al.||2018|
Nicotinamide riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance
|healthy rats||mechanisms of decreased exercise performance||NR||21 days of supplementation with 300 mg (kg body weight)−1 of|
- increased the levels of NADPH in the liver
- increased the levels of F2‐isoprostanes in plasma
- decreased the activity of glutathione peroxidase, glutathione reductase and catalase in erythrocytes,
- increased the level of glycogen in the liver
- decreased the concentration of glucose and maximal lactate accumulation in plasma
|120||Muscle||Kourtzidis et al.||2016|
The NAD+ precursor nicotinamide riboside decreases exercise performance in rats
|rats 4 months old||exercise performance||NR||300 mg/kg body weight/day for 21 days gavage|
- NR group showed a tendency towards worse physical performance by 35 % compared to the control group
|121||Muscle||Cerruti et al.||2014|
NAD+-Dependent Activation of Sirt1 Corrects the Phenotype in a Mouse Model of Mitochondrial Disease
|mouse||skeletal muscle||NR||400 mg/Kg)|
- marked improvement of the respiratory chain defect and exercise intolerance
|122||Muscle||Khan et al.||2014||Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3||male mice||model of myopathy||NR||400 mg/kg/day|
- NR delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation.
- NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease.
|123||Pharmacokinetic||Nikiforov et al.||2011||Pathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells ||in vitro||NAD pathways in human cells||all precursors||100 uM|
- results demonstrate that, besides NAM and NA, only the corresponding nucleosides readily enter the cells.
- nucleotides (e.g. NAD and NMN) undergo extracellular degradation resulting in the formation of permeable precursors.
- precursors can all be converted to cytosolic and mitochondrial NAD.
- for mitochondrial NAD synthesis, precursors are converted to NMN in the cytosol. When taken up into the organelles, NMN (together with ATP) serves as a substrate of NMNAT3 to form NAD
|124||Rejuvenation||Igarashi et al.||2016|
NAD+ supplementation rejuvenates aged gut adult stem cells
|aged male mice (>24 months)||intestinal crypts||NR||500 mg/kg/day in drinking water for 6 weeks ; 1000 mg/kg/day on day 5|
- NR restores colony formation, ISC number
- rescues functional defects in the gut
- treatment with rapamycin blocked rescue by NR
|125||Rejuvenation||Mills et al.||2016|
Long-term administration of nicotinamide mononucleotide mitigates the age-associated physiological decline in mice
- mitigates the age-associated physiological decline in mice
- suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity, and plasma lipid profile, and ameliorated eye function and other pathophysiologies
- prevented age-associated gene expression changes in key metabolic organs and enhanced mitochondrial oxidative metabolism
|126||Rejuvenation||Mitchell et al.||2018|
Nicotinamide improves aspects of healthspan but not lifespan in mice
|one-year-old mice for the remainder of life||liver||NAM||0.5-1 mg/kg|
- chronic NAM supplementation improves healthspan measures in mice without extending the lifespan
- metabolite profiling revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet
|127||Rejuvenation||Mouchiroud et al.||2013||The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling||worms, in vitro mouse hepatocytes||lifespan and mitochondrial function||NR, NAM||500 uM NR, 200 uM NAM|
- feeding worms with PARP inhibitors from birth until death resulted in a 15-23% lifespan extension
- supplementation with NR and NAM also resulted in lifespan extension
- using both compounds together was not synergistic at optimal concentrations but at suboptimal concentrations, was
- improved mobility of worms in old age
- increased mitochondrial function in worms
|128||Rejuvenation||Fang et al.||2014||Defective Mitophagy in XPA via PARP1 Hyperactivation and NAD +/SIRT1 Reduction||worms, mice||cerebellum, mitochondria||NR, NMN, PARP inhibition||500 mg/kg/day s.c. injections in the mice for 14 days|
- increased SIRT1 activation in worms
- improved function of the mitochondria
- NR and NMN rescued low NAD+ in very old worms to some extent
- PARP inhibition, NR and NMN all extended the lifespan in worms with a model of mitochondrial disease
|129||Rejuvenation||Scheibye-Knudsen et al.||2014||A High Fat Diet and NAD+ Rescue Premature Aging in Cockayne Syndrome||mice||premature aging||NR||not reported|
- old mice had decreased NAD+ and ATP levels before treatment
- one week of treatment with NR completely normalized levels
- NR rescued defects in cerebellar mitochondria
|130||Rejuvenation||Bitterman et al.||2002||Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1*||Yeast||in vitro||NAM||5 mM|
- NAM strongly inhibits yeast silencing, increases rDNA recombination, and shortens replicative life span to that of a sir2 mutant.
- NAM abolishes silencing and leads to an eventual delocalization of Sir2 even in G1-arrested cells, demonstrating that silent heterochromatin requires continual Sir2 activity
- physiological concentrations of NAM noncompetitively inhibit both Sir2 and SIRT1 in vitro. The degree of inhibition by NAM (IC50 < 50 M) is equal to or better than the most effective known synthetic inhibitors of this class of proteins.
|131||Rejuvenation||Batra et al.||2014|
Mitigation of gamma-radiation-induced abasic sites in genomic DNA by dietary nicotinamide supplementation: Metabolic up-regulation of NAD+ biosynthesis
|male mice||irradiation||NAM |
- dietary NAM supplementation restores DNA excision repair activity
|132||Rejuvenation||Mukherjee et al.||2017|
Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration
|10-14 week male mice||liver||NR||3 mg/mL dissolved in water; 500 mg/kg 1 day before partial hepatectomy|
- 48% increase in mitotic activity, increased DNA synthesis
- mass restoration in the liver
- ameliorated the steatosis that normally accompanies regeneration
|133||Rejuvenation||Schmeisser et al.||2013||Role of Sirtuins in Lifespan Regulation is Linked to Methylation of Nicotinamide||nematodes||lifespan||NAM, MeNAM||100uM, 1 uM|
- NAM and its metabolite, MeNAM, extend C. elegans lifespan, even in the absence of sir-2.1.
- MeNAM serves as a substrate for a newly identified aldehyde oxidase, GAD-3, to generate hydrogen peroxide acting as a mitohormetic ROS signal to promote C. elegans longevity.
- sirtuin-mediated lifespan extension depends on methylation of NAM
|134||Rejuvenation||Son et al.||2013|
Nicotinamide overcomes pluripotency deficits and reprogramming barriers.
|in vitro||human pluripotent |
|NAD+, NAM, NA||0.1-1 mM|
- NAD+ depletion by FK866 was fatal in hPSCs, particularly when deriving pluripotent cells from somatic cells and maintaining pluripotency.
- NAD+ and its precursors NAM and NA fully replenished the NAD+ depletion by FK866 in hPSCs.
- only NAM effectively enhanced the reprogramming efficiency and kinetics of hiPSC generation and was also significantly advantageous for the maintenance of undifferentiated hPSCs.
- NAM lowers the barriers to reprogramming by accelerating cell proliferation and protecting cells from apoptosis and senescence by alleviating oxidative stress, reactive oxygen species accumulation, and subsequent mitochondrial membrane potential collapse.
- the positive effects of NAM (occurring at concentrations well above the physiological range) on pluripotency control are molecularly associated with the repression of p53, p21, and p16.
- adequate intracellular NAD+ content is crucial for pluripotency; the distinct effects of NAM on pluripotency may be dependent not only on its metabolic advantage as an NAD+ precursor but also on the ability of NAM to enhance resistance to cellular stress
|135||Rejuvenation||Collins et al.||1991||The effects of nicotinamide and hyperbaric oxygen on skin flap survival ||male rats||skin flap||NAM||400 mg i.p. 15 days|
- NAM increased flap survival from 45% to 85%
|136||Reproduction||Ear et al.||2019|
Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring
|mice||development||NR||3 g/kg chow|
- increases lactation and nursing behaviors and stimulates the maternal transmission of macronutrients, micronutrients, and BDNF into milk
- increased postpartum weight loss
- advantaged in glycemic control, size at weaning, and synaptic pruning.
- retain advantages in physical performance, anti-anxiety, spatial memory, delayed onset of behavioral immobility, and promotion of adult hippocampal neurogenesis
|137||Reproduction||Shi et al.||2017|
NAD Deficiency, Congenital Malformations, and Niacin Supplementation
- prevented congenital malformations in mice
|138||Reproduction||Wu et al.||2019|
NMNAT-2-mediated NAD+ generation is essential for quality control of aged oocytes
|4-5 week old female mice and 42-45 wk old female mice||in vitro oocyte||NA||50 uM NA culture|
- improved quality of aged oocytes
|139||Skin||Gensler et al.||1999|
Oral Niacin Prevents Photocarcinogenesis and Photoimmunosuppression in Mice
|female mice||UV radiation||Niacin||0.1-1.0% 26 weeks|
- reduced the incidence of skin cancer from 68% to 28%
- elevated skin NAD content
Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide
|mice||UVB radiation||NAM||topical 40uM twice per week |
- decreased immunosuppression
- reduced tumor incidence from 75% to 48%
|141||Skin||Park et al.||2010|
Nicotinamide Prevents Ultraviolet Radiation-induced Cellular Energy Loss
|human keratinocytes||in vitro||NAM||50 uM|
- NAM prevented UV-induced cellular ATP loss and protected against UV-induced glycolytic blockade.
- NAM had no effect on ROS formation, and at the low UV doses used in these studies, equivalent to ambient daily sun exposure, there was no evidence of apoptosis.
- NAM appears to exert its UV protective effects on the skin via its role in cellular energy pathways
|142||Skin||Surjana et al.||2013||Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin||human keratinocytes and ex vivo skin||low dose UV ||NAM||50 uM for 24 hrs|
- NAM increased both the proportion of cells undergoing excision repair and the repair rate in each cell.
- NAM reduced CPDs cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8oxoG) formation
- reduction appeared to be due to the enhancement of DNA repair.
|143||Skin||Monfrecola et al.||2013||Nicotinamide downregulates gene expression of interleukin-6, interleukin-10, monocyte chemoattractant protein-1, and tumour necrosis factor-a gene expression in HaCaT keratinocytes after ultraviolet B irradiation||human keratinocytes||UVB radiation||NAM||100 uM and 5mM |
- NAM has antioxidant, immunomodulating and anti-inflammatory properties
- NAM is able to modulate UVB-induced expression of IL-1b, IL-6, IL-8, IL-10, MCP-1 and TNFa in HaCaT keratinocytes
- NCT downregulation of UVB-induced IL-10 overexpression may represent an additional explanation of its anti-immunosuppressive mechanism, supporting the recently proposed use of NCT as a preventive treatment for skin cancer
|144||Skin||Rovito & Oblong||2014||Nicotinamide preferentially protects glycolysis in dermal fibroblasts under oxidative stress conditions||dermal fibroblasts||oxidative stress||NAM||0.1-1 mmol/L |
- NAM was found to protect dose-dependently as well as restore glycolytic rates concurrent with restoring ATP to control levels.
- NAM had an effective dose-response range between 0.1 and 1.0 mmol/L, with maximal effects attained at 0.5 mmol/L
- FK866, a known NAM phosphoribosyltransferase inhibitor, was found to inhibit the protective effects of NAM significantly, suggesting part of the NAM mechanism of action involves NAD+ synthesis
|145||Skin||Tanno et al.||2000||Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier||human keratinocytes||in vitro||NAM||1-30 uM/L for 6 days|
- rate of ceramide biosynthesis was increased dose-dependently by 4.1±5.5-fold on the sixth day compared with control.
- NAM also increased the synthesis of glucosylceramide (7.4-fold) and sphingomyelin (3.1-fold) in the same concentration range effective for ceramide synthesis.
- activity of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis, was increased in NAM-treated cells.
- NAM increased the levels of human LCB1 and LCB2 mRNA, both of which encode subunits of SPT.
- NAM increased not only ceramide synthesis but also free fatty acid (2´3-fold) and cholesterol synthesis (1´5-fold).
- topical application of NAM increased ceramide and free fatty acid levels in the stratum corneum and decreased transepidermal water loss in dry skin