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Feb 6, 2023

Metabolism - Heart / Vascular - NMN - Obesity

Journal of Clinical Endocrinology & Metabolism

Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study

Pencina, Karol Mateusz


NMN administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure.

Feb 1, 2023

Liver - Fibrosis - Chronic Liver Disease - NMN


NAMPT Inhibition and Increased NAD-Bioavailability Atenuate Liver Damage in CCI4-Induced Mice Liver Fibrosis

Suarez-Cuenca, J.


This study shows that NAMPT inhibition concomitant to NAD restoration significantly attenuate experimental liver damage.

Oct 11, 2022

NMN - Metabolism - Gut Microbiota - Bioavailability


Nicotinamide mononucleotide (NMN) deamidation by host-microbiome interactions

Kim, Lynn-Jee


Ablation of the microbiome by antibiotic treatment increases the uptake and conversion of orally delivered NMN into the NAD metabolome, and that isotope labelled NMN overwhelmingly presents in intestinal tissue in the form of NR. Contrary to the assumption that exogenous NMN treatment raises NAD+ levels solely through its direct incorporation into the NAD metabolome, we show that treatment with isotope labelled NMN increases the levels of endogenous, unlabelled NAD metabolites....Given this evidence for the decomposition of NMN into free Nam prior to its uptake, a key question for the field is why downstream precursors in NAD+ synthesis such as NMN and NR lead to different outcomes compared to Nam alone...

May 1, 2022

Muscle - NMN - Aging

NPJ Aging

Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

Igarashi, Masaki


NMN oral supplementation at 250 mg/day in healthy older men for 12 weeks was safe and well-tolerated and significantly increased the levels of NAD + and NAD +-related metabolites in whole blood. Furthermore, NMN administration partly improved muscle performance, evaluated using gait speed and grip strength, in healthy older men...NMN did not affect the skeletal muscle mass of participants in our study...Thus, the chronic oral administration of NMN could be a therapeutic strategy for aging-related disorders in humans, such as sarcopenia.

Apr 11, 2022

NMN - Metabolism

Frontiers in Nutrition

Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects

Okabe, Keisuke


...Previous mouse models showed that NMN administration can increase NAD+ in various organs and ameliorate aging-related diseases, such as obesity, diabetes, heart failure, stroke, kidney failure, and Alzheimer’s disease through NAD+-mediated pathways. However, evidence of its effect on humans is still scarce. In this study, we conducted a placebo-controlled, randomized, double blind, parallel-group trial to investigate the safety of orally administered NMN and its efficacy to increase NAD+ levels in thirty healthy subjects...Oral supplementation of NMN for 12 weeks caused no abnormalities in physiological and laboratory tests, and no obvious adverse effects were observed. NAD+ levels in whole blood were significantly increased after NMN administration. We also observed the significant rise in nicotinic acid mononucleotide (NAMN) levels, but not in NMN...These results suggest that oral administration of NMN is a safe and practical strategy to boost NAD+ levels in humans.

Jun 11, 2021

NMN - Diabetes


Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

Yoshino, Mihoko


In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction(1–8). Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling (phosphorylation of AKT and mTOR) increased after NMN supplementation, but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate NMN increases muscle insulin sensitivity, insulin signaling and remodeling in women with prediabetes who are overweight or obese.

Jun 1, 2021

Diabetes - Neurons - Kidney - NMN

Journal of the American Society of Nephrology

Could NAD+ Precursor Supplements Induce a Legacy of Protection against Diabetic Nephropathy?

Hyndman, Kelly A.


Diabetic nephropathy (DN) is a complex disease with microvascular complications, profound changes in metabolism, inflammation, and redox status, leading to structural and functional changes that can culminate in End Stage Kidney Disease (ESKD)...500NMN mice had lower mortality and significantly improved urinary albumin-creatinine ratios even at 20 weeks post-treatment compared with the db/db mice. ...Therapeutic protocols leading to legacy effects by epigenetic reprogramming of the salvage pathway to sustain or even increase kidney NAD+ show promise for slowing the development of DN.

Mar 2, 2021

Neurons - Neurodegeneration - NMN


SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration

Figley, Matthew D.


SARM1 is a metabolic sensor activated by an increase in the NMN/NAD+ ratio…Upon the loss of NAD+ biosynthesis, [SARM1] initiates a positive feedback loop, ultimately resulting in catastrophic NAD+ depletion and axon self-destruction…

Apr 28, 2020


Frontiers in Cell and Developmental Biology

Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism

Hong, Weigi


NAD+, a co-enzyme involved in a great deal of biochemical reactions, has been found to be a network node of diverse biological processes. In mammalian cells, NAD+ is synthetized, predominantly through NMN, to replenish the consumption by NADase participating in physiologic processes including DNA repair, metabolism, and cell death. Correspondingly, aberrant NAD+ metabolism is observed in many diseases. In this review, we discuss how the homeostasis of NAD+ is maintained in healthy condition and provide several age-related pathological examples related with NAD+ unbalance...The NAD+ production and consumption pathways including NMN are essential for more precise understanding and therapy of age-related pathological processes such as diabetes, ischemia–reperfusion injury, heart failure, Alzheimer’s disease, and retinal degeneration.

Feb 1, 2020

Aging - NMN

Integrative Medicine

The Science Behind NMN–A Stable, Reliable NAD+Activator and Anti-Aging Molecule

Shade, Christopher


By middle age, our NAD+ levels have plummeted to half that of our youth. Numerous studies have demonstrated that boosting NAD+ levels increases insulin sensitivity, reverses mitochondrial dysfunction, and extends lifespan....NMN can be converted by the body to NR, which then enters cells, and is converted back to NMN by an enzyme called nicotinamide riboside kinase (NRK).

Jul 12, 2019

NMN Transporter - Bioavailability

Nature Metabolism

Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter

Schmidt, Mark


Despite genetic, pharmacological and kinetic evidence validated by a quantitative assay showing that nicotinamide mononucleotide (NMN) is dephosphorylated to nicotinamide riboside before cellular internalization1 , solute carrier family 12 member 8 (Slc12a8), which is widely expressed and annotated as a Na+/K+ Cl− transporter, has been nominated to be an NMN transporter. The analytical methods, transport data and interpretation underlying this assignment are not sound and do not support transport of NMN by Slc12a8.

Feb 28, 2019

Leigh Syndrome - Neurons - Mitochondria - NMN

Scientific Reports

Targeting NAD+ Metabolism as Interventions for Mitochondrial Disease

Lee, Chi Fung


We found that supplementation of the NAD+ precursor, nicotinamide mononucleotide (NMN), extended the lifespan of Ndufs4-KO [Leigh Syndrome] mice.

Mar 22, 2018

Heart ⎼ Vascular Aging (NMN)


Impairment of an endothelial NAD+‐H2S signaling network is a reversible cause of vascular aging

Das, Abhirup


A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1–SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a dietary restriction mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.

Mar 2, 2017

Neurons - NMN

Current Biology

NMN Deamidase Delays Wallerian Degeneration and Rescues Axonal Defects Caused by NMNAT2 Deficiency In Vivo

Di Stephano, Michelle


Our data strongly support an in vivo role for NMN accumulation in triggering axon degeneration both after injury and when NMNAT2 is constitutively depleted, with axon protection by WLDs /NMNATs and NMN deamidase in both situations at least partially relying on their ability to limit NMN accumulation.

Oct 27, 2016

Aging - NMN

Cell Metabolism

Long-Term Administration of Nicotinamide
Mononucleotide Mitigates Age-Associated
Physiological Decline in Mice

Mills, Kathryn F.


We found that a 12-month-long NMN administration (1) is well-tolerated without any obvious deleterious effects, (2) suppresses age-associated body weight gain, (3) enhances food intake, oxygen consumption, energy expenditure, and physical activity, (4) improves insulin sensitivity and plasma lipid profile, independent of its effect on body weight, and (5) improves eye function, bone density, and myeloid-lymphoid composition. NMN administration was also able to prevent age-associated gene expression changes in a tissue-dependent manner and enhance mitochondrial respiratory capability in skeletal muscle.

Oct 11, 2016

Bioavailability - NMN

Nature Communications

NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells

Ratajczak, Joanna


NAD+ is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD+ synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD+ synthesis from other NAD+ precursors, such as nicotinamide or nicotinic acid, is dispensable. Using stable isotope-labelled compounds, we confirm NMN is metabolized extracellularly to NR that is then taken up by the cell and converted into NAD+. Our results indicate that mammalian cells require conversion of extracellular NMN to NR for cellular uptake and NAD+ synthesis, explaining the overlapping metabolic effects observed with the two compounds.

Apr 24, 2015

Neurons - NMN


SARM1 activation triggers axon degeneration locally via NAD+ destruction

Gerdts, Josiah


Together these data implicate NAD+ loss as a critical step in SARM1-mediated axon destruction...axon degeneration and cell death were blocked by supplementation with the cell-permeable NAD+ precursor Nicotinamide Riboside (NR)...Cells undergo regulated self-destruction during development and in response to stresses...these data implicate NAD+ loss as a critical step in SARM1-mediated axon destruction...Rapid NAD+ depletion is sufficient to cause rapid axon loss...

Oct 17, 2014

Neurons - NMN

Cell Death and Differentiation

A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration

Di Stefano, M


...Here we show that the nucleotide precursor of NAD, nicotinamide mononucleotide (NMN), accumulates after nerve injury and promotes axon degeneration. Inhibitors of NMN-synthesising enzyme NAMPT confer robust morphological and functional protection of injured axons and synapses despite lowering NAD. Exogenous NMN abolishes this protection, suggesting that NMN accumulation within axons after NMNAT2 degradation could promote degeneration...These data indicate that the mechanism by which NMNAT and the related WldS protein promote axon survival is by limiting NMN accumulation. They indicate a novel physiological function for NMN in mammals and reveal an unexpected link between new strategies for cancer chemotherapy and the treatment of axonopathies.

Mar 26, 2010

Neurons - NMN

Annual Review of Neuroscience

Wallerian Degeneration, WldS, and Nmnat

Coleman, Michael P.


Despite the importance of extra-axonal support for long-term survival, axons are now thought to initiate their own degeneration when these systems fail. Moreover, the trigger is not a general lack of nutrients. Injured axons appear to self-destruct through a regulatable or active process that is distinct from apoptosis

NAD Research - NMN

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