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Research

Clinical Trials

Results from First Human Clinical Study Demonstrate ChromaDex’s NIAGEN(R) Nicotinamide Riboside Effectively Increases the Co-enzyme NAD+ and is Safe

Findings: NR supplementation was shown to effectively and safely increase NAD+ in humans

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans

Findings: Human blood NAD+can rise as much as 2.7-fold with a single oral dose of NR. Single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD+metabolome in the first clinical trial of NR pharmacokinetics in humans

Study to Evaluate the Effect of Nicotinamide Riboside on Immunity

Findings:  A study showed that fasting has a good effect on immune cell health in healthy people. And when immune cells were exposed to NR they had a similar positive response as with fasting. Researchers want to see if healthy people have the same effects from NR and fasting, and if those effects last. (Note this study is still ongoing)

Mitochondrial Function

Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging

Findings: During aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits (Oxidative Phosphorylation). Raising NAD+ levels in old mice reverses metabolic dysfunction and restores mitochondrial function to that of young mice.

NAD+ in aging, metabolism, and neurodegeneration

Findings: Cellular NAD+concentrations change during aging, and modulation of NAD+ usage or production can prolong both health span and life span.

NAD+ and sirtuins in aging and disease

Findings: Restoring NAD+ by supplementing NAD+ intermediates can dramatically ameliorate age-associated functional defects and counteract many disease of aging. The combination of sirtuin activation and NAD+ intermediate supplementation may be an effective antiaging intervention.

Partial reversal of skeletal muscle aging by restoration of normal NAD+ levels

Findings: Restoring NAD+ levels may be beneficial throughout the organism (shown in mice). Intervention in mitochondrial aging may be possible using appropriate NAD+ precursors such as NR.

Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans

Findings: NAD+ is essential for life in all organisms, and plays a role in slowing aging in experimental systems. Nicotinamide riboside is suggested to be a useful compound for elevation of NAD+ levels in humans.

NAD+-dependent activation of Sirt1 corrects the phenotype in a mouse model of mitochondrial disease

Findings: NR supplementation leads to marked improvement of respiratory chain defect and exercise intolerance, with the potential as a therapy for mitochondrial disorders in humans.

The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity

Findings: NR can be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.

Cancer

Inhibition of De Novo NAD+ Synthesis by Oncogenic URI Causes Liver Tumorigenesis through DNA Damage

Findings: Restoring NAD+ pools with NR prevents DNA damage and tumor formation. Boosting NAD+ can be prophylactic or therapeutic in hepatocellular carcinoma.

Neuopathies

Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy

Findings: Stimulation of NAD+ biosynthetic pathways may be useful in preventing or delaying axonal degeneration, which occurs in many neurodegenerative disease and after traumatic injury.

Activation of SIRT3 by the NAD+ Precursor Nicotinamide Riboside Protects from Noise-Induced Hearing Loss

Findings: NAD+ exhibits axon-protective effects in cultured neurons. Administration of NR, even after noise exposure, prevents noise-induced hearing loss and spiral ganglia neurite degeneration.

Boosting NAD to Spare Hearing

Findings: Cochlear NAD is diminished by deafening noise but protected by NR. Hearing protection by NR depends on Sirt3.

Myopathies

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3

Findings: NR effectively delayed early- and late-stage mitochondrial myopathy progression by robustly inducing mitochondrial biogenesis, preventing structure abnormalities and mtDNA deletions. These results indicate that NR and strategies boosting NAD+ levels are a promising treatment for mitochondrial myopathy.

Metabolism

Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes

Finings: NR lowered the total cholesterol concentration and rescued the disrupted cellular integrity f the mitochondria and nucleus in the livers of obese and diabetic mice.  NR significantly improved hepatic proinflammatory markers.

Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet-and age-induced diabetes in mice

Findings: Boosting NAD+ may enhance insulin sensitivity, glucose intolerance, and lipid profiles in age-induced Type-2 diabetic mice.

Eliciting the mitochondrial unfolded protein response via NAD+ repletion reverses fatty liver disease

Findings: NR prevents and reverts non-alcoholic fatty liver disease.

NAD+ Biosynthesis

Enzymology of mammalian NAD metabolism in health and disease.

Findings: NAD homeostasis is related to the free radicals-mediated production of reactive oxygen species responsible for irreversible cellular damage in infectious disease, diabetes, inflammatory syndromes, neurodegeneration and caner.  Degradation of NAD likely contributes to the mechanisms underlying the pathogenesis of these disease.

Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae

Findings: NR has been shown to ameliorate NAD+ deficiencies that effect various biological processes including calorie restriction-mediated life span extension.

Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+

Findings: Exogenous nicotinamide riboside promotes Sir2-depedent repression of recombination, improves gene silencing, and extends lifespan without calorie restriction.

The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling

Findings: Restoration of NAD+ prevents age-associated metabolic decline and promores longevity in worms.

NAD+ as a signaling molecule modulating metabolism

Findings: NAD+ levels play a pivotal role in whole-body metabolic homeostasis.

Reviews & News

Human clinical trial supports bioavailability, safety of nicotinamide riboside

Findings: A single dose of nicotinamide riboside (NR) may significantly increases levels of NAD+, which is key to cellular energy metabolism and mitochondrial function, says data from studies with mice and humans

The First Human Clinical Study for NMN has started in Japan

Findings: Recently (October 2016), an international collaborative team between Keio University School of Medicine in Tokyo and Washington University School of Medicine in St Louis has started the phase I human clinical study for NMN

ChromaDex Clinical Trial Studying NIAGEN® Well Underway, With Eight Additional Collaborative Human Studies Active

Findings: New research seems to be publishing on almost a weekly basis, further building the body of evidence around the effectiveness of NR and the importance of boosting NAD+.

Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection

Findings: NR in models of Alzheimer’s disease indicate bioavailability to brain and protective effects, likely by stimulation of brain NAD synthesis. NR has properties that are insulin sensitizing, enhancing to exercise, resisting to negative effects of high-fat diet and neuroprotecting.

Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition

Findings: NR may be the only vitamin precursor that supports neuronal NAD+ synthesis. Substantially greater rates of NAD+ synthesis may be beneficial to protect against neurological degeneration, Candida glabrata infection, and possibly to enhance reverse cholesterol transport.

NAD+ and vitamin B3: from metabolism to therapies

Findings: NAD+ metabolism regulates important biological effects, including lifespan. NAD+ metabolism could be targeted for therapeutic benefit with opportunities for drug design that are directed at modulation of NAD+ biosynthesis for treatment of human disorders and infections.

NAD+ metabolism in health and disease

Findings: NAD+ might be applicable therapeutically to prevent neurodegenerative conditions and to fight Candida glabrata infection. NAD+ metabolism contributes to lifespan extension in model systems. NR may elevate NAD+ without inhibiting sirtuins or incurring unpleasant side-effects.

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