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Cell Metabolism Mar 2018Research on the biology of NAD has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In... (Review)
Review
Research on the biology of NAD has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NAD intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions. Although the pharmacokinetics and metabolic fates of NMN and NR are still under intensive investigation, these NAD intermediates can exhibit distinct behavior, and their fates appear to depend on the tissue distribution and expression levels of NAD biosynthetic enzymes, nucleotidases, and presumptive transporters for each. A comprehensive concept that connects NAD metabolism to the control of aging and longevity in mammals has been proposed, and the stage is now set to test whether these exciting preclinical results can be translated to improve human health.
Topics: Aging; Animals; Humans; NAD; Niacinamide; Nicotinamide Mononucleotide; Pyridinium Compounds
PubMed: 29249689
DOI: 10.1016/j.cmet.2017.11.002 -
Skin Therapy Letter Nov 2020Nicotinamide (or niacinamide), a form of vitamin B3 that is often confused with its precursor nicotinic acid (or niacin), is a low-cost, evidence-based oral treatment...
Nicotinamide (or niacinamide), a form of vitamin B3 that is often confused with its precursor nicotinic acid (or niacin), is a low-cost, evidence-based oral treatment option for actinic keratosis, squamous cell carcinomas, basal cell carcinomas, and bullous pemphigoid. Despite its favorable safety profile and affordability, the integration of nicotinamide into clinical practice is an ongoing process, and like many over-the-counter supplements it has faced some barriers. The purpose of this article is to address some of those barriers by reviewing its efficacy, safety profile, and emphasizing the difference between nicotinamide and niacin. Lastly, we offer practical guidance around recommendations and the availability of nicotinamide, which can be hard to find for patients and providers alike.
Topics: Administration, Oral; Dietary Supplements; Humans; Niacinamide; Skin Neoplasms; Vitamin B Complex
PubMed: 33196157
DOI: No ID Found -
Nutrients May 2020Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD) precursors, due to its numerous potential health benefits... (Review)
Review
Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD) precursors, due to its numerous potential health benefits mediated via elevated NAD content in the body. NAD is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD precursors.
Topics: Aging; Animals; Betacoronavirus; Biological Availability; COVID-19; Cardiovascular Diseases; Coronavirus Infections; Dietary Supplements; Humans; Longevity; Metabolism; Neurodegenerative Diseases; Niacinamide; Pandemics; Pneumonia, Viral; Pyridinium Compounds; SARS-CoV-2
PubMed: 32486488
DOI: 10.3390/nu12061616 -
Current Nutrition Reports Sep 2023NAD+ is a vital molecule that takes part as a redox cofactor in several metabolic reactions besides being used as a substrate in important cellular signaling in... (Review)
Review
PURPOSE OF REVIEW
NAD+ is a vital molecule that takes part as a redox cofactor in several metabolic reactions besides being used as a substrate in important cellular signaling in regulation pathways for energetic, genotoxic, and infectious stress. In stress conditions, NAD+ biosynthesis and levels decrease as well as the activity of consuming enzymes rises. Dietary precursors can promote NAD+ biosynthesis and increase intracellular levels, being a potential strategy for reversing physiological decline and preventing diseases. In this review, we will show the biochemistry and metabolism of NAD+ precursors NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide), the latest findings on their beneficial physiological effects, their interplay with gut microbiota, and the future perspectives for research in nutrition and food science fields.
RECENT FINDINGS
NMN and NR demonstrated protect against diabetes, Alzheimer disease, endothelial dysfunction, and inflammation. They also reverse gut dysbiosis and promote beneficial effects at intestinal and extraintestinal levels. NR and NMN have been found in vegetables, meat, and milk, and microorganisms in fermented beverages can also produce them. NMN and NR can be obtained through the diet either in their free form or as metabolites derivate from the digestion of NAD+. The prospection of NR and NMN to find potential food sources and their dietary contribution in increasing NAD+ levels are still an unexplored field of research. Moreover, it could enable the development of new functional foods and processing strategies to maintain and enhance their physiological benefits, besides the studies of new raw materials for extraction and biotechnological development.
Topics: Humans; Nicotinamide Mononucleotide; NAD; Niacinamide; Diet
PubMed: 37273100
DOI: 10.1007/s13668-023-00475-y -
Science Advances Jul 2023Nicotinamide riboside is a precursor to the important cofactor nicotinamide adenine dinucleotide and has elicited metabolic benefits in multiple preclinical studies. In... (Review)
Review
Nicotinamide riboside is a precursor to the important cofactor nicotinamide adenine dinucleotide and has elicited metabolic benefits in multiple preclinical studies. In 2016, the first clinical trial of nicotinamide riboside was conducted to test the safety and efficacy of human supplementation. Many trials have since been conducted aiming to delineate benefits to metabolic health and severe diseases in humans. This review endeavors to summarize and critically assess the 25 currently published research articles on human nicotinamide riboside supplementation to identify any poorly founded claims and assist the field in elucidating the actual future potential for nicotinamide riboside. Collectively, oral nicotinamide riboside supplementation has displayed few clinically relevant effects, and there is an unfortunate tendency in the literature to exaggerate the importance and robustness of reported effects. Even so, nicotinamide riboside may play a role in the reduction of inflammatory states and has shown some potential in the treatment of diverse severe diseases.
Topics: Humans; Niacinamide; NAD; Pyridinium Compounds; Dietary Supplements
PubMed: 37478182
DOI: 10.1126/sciadv.adi4862 -
Indian Journal of Dermatology,... 2018
Review
Topics: Administration, Oral; Administration, Topical; Animals; Dermatology; Humans; Niacinamide; Skin Diseases; Skin Lightening Preparations; Skin Neoplasms; Vitamin B Complex
PubMed: 29405129
DOI: 10.4103/ijdvl.IJDVL_286_17 -
JAMA Ophthalmology Jan 2022Open-angle glaucoma may continue to progress despite significant lowering of intraocular pressure (IOP). Preclinical research has suggested that enhancing mitochondrial...
IMPORTANCE
Open-angle glaucoma may continue to progress despite significant lowering of intraocular pressure (IOP). Preclinical research has suggested that enhancing mitochondrial function and energy production may enhance retinal ganglion cell survival in animal models of glaucoma, but there is scant information on its effectiveness in a clinical setting.
OBJECTIVE
To test the hypothesis that a combination of nicotinamide and pyruvate can improve retinal ganglion cell function in human glaucoma as measured with standard automated perimetry.
DESIGN, SETTING, AND PARTICIPANTS
In this phase 2, randomized, double-blind, placebo-controlled clinical trial at a single academic institution, 197 patients were assessed for eligibility. Of these, 42 patients with treated open-angle glaucoma and moderate visual field loss in at least 1 eye were selected for inclusion and randomized. A total of 32 completed the study and were included in the final analysis. The mean (SD) age was 64.6 (9.8) years. Twenty-one participants (66%) were female. Participant race and ethnicity data were collected via self-report to ensure the distribution reflected that observed in clinical practice in the US but are not reported here to protect patient privacy. Recruitment took place in April 2019 and patients were monitored through December 2020. Data were analyzed from January to May 2021.
INTERVENTIONS
Ascending oral doses of nicotinamide (1000 to 3000 mg) and pyruvate (1500 to 3000 mg) vs placebo (2:1 randomization).
MAIN OUTCOMES AND MEASURES
Number of visual field test locations improving beyond normal variability in the study eye. Secondary end points were the rates of change of visual field global indices (mean deviation [MD], pattern standard deviation [PSD], and visual field index [VFI]).
RESULTS
Twenty-two of 29 participants (76%) randomized to the intervention group and 12 of 13 participants (92%) randomized to placebo received their allocation, and 32 participants (32 eyes; ratio 21:11) completed the study (21 from the intervention group and 11 from the placebo group). Median (IQR) follow-up time was 2.2 (2.0-2.4) months. No serious adverse events were reported during the study. The number of improving test locations was significantly higher in the treatment group than in the placebo group (median [IQR], 15 [6-25] vs 7 [6-11]; P = .005). Rates of change of PSD suggested improvement with treatment compared with placebo (median, -0.06 vs 0.02 dB per week; 95% CI, 0.02 to 0.24; P = .02) but not MD (0.04 vs -0.002 dB per week; 95% CI, -0.27 to 0.09; P = .35) or VFI (0.09 vs -0.02% per week; 95% CI, -0.53 to 0.36; P = .71).
CONCLUSIONS AND RELEVANCE
A combination of nicotinamide and pyruvate yielded significant short-term improvement in visual function, supporting prior experimental research suggesting a role for these agents in neuroprotection for individuals with glaucoma and confirming the need for long-term studies to establish their usefulness in slowing progression.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03797469.
Topics: Animals; Double-Blind Method; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Niacinamide; Pyruvic Acid
PubMed: 34792559
DOI: 10.1001/jamaophthalmol.2021.4576 -
Cellular and Molecular Life Sciences :... Aug 2022Alterations in cellular nicotinamide adenine dinucleotide (NAD) levels have been observed in multiple lifestyle and age-related medical conditions. This has led to the... (Review)
Review
Alterations in cellular nicotinamide adenine dinucleotide (NAD) levels have been observed in multiple lifestyle and age-related medical conditions. This has led to the hypothesis that dietary supplementation with NAD precursors, or vitamin B3s, could exert health benefits. Among the different molecules that can act as NAD precursors, Nicotinamide Riboside (NR) has gained most attention due to its success in alleviating and treating disease conditions at the pre-clinical level. However, the clinical outcomes for NR supplementation strategies have not yet met the expectations generated in mouse models. In this review we aim to provide a comprehensive view on NAD biology, what causes NAD deficits and the journey of NR from its discovery to its clinical development. We also discuss what are the current limitations in NR-based therapies and potential ways to overcome them. Overall, this review will not only provide tools to understand NAD biology and assess its changes in disease situations, but also to decide which NAD precursor could have the best therapeutic potential.
Topics: Animals; Disease Models, Animal; Mice; NAD; Niacinamide; Pyridinium Compounds
PubMed: 35918544
DOI: 10.1007/s00018-022-04499-5 -
Nature Communications Oct 2016Nicotinamide riboside (NR) is in wide use as an NAD precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD metabolism in humans. We...
Nicotinamide riboside (NR) is in wide use as an NAD precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD metabolism in humans. We report that human blood NAD can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that 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. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD, is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD repletion.
Topics: Administration, Oral; Animals; Biological Availability; Biomarkers; Humans; Leukocytes, Mononuclear; Liver; Male; Metabolome; Mice, Inbred C57BL; Middle Aged; NAD; Niacinamide; Pyridinium Compounds; Vitamins
PubMed: 27721479
DOI: 10.1038/ncomms12948 -
Mechanisms of Ageing and Development Oct 2021NAD is a fundamental molecule in human life and health as it participates in energy metabolism, cell signalling, mitochondrial homeostasis, and in dictating cell... (Review)
Review
NAD is a fundamental molecule in human life and health as it participates in energy metabolism, cell signalling, mitochondrial homeostasis, and in dictating cell survival or death. Emerging evidence from preclinical and human studies indicates an age-dependent reduction of cellular NAD, possibly due to reduced synthesis and increased consumption. In preclinical models, NAD repletion extends healthspan and / or lifespan and mitigates several conditions, such as premature ageing diseases and neurodegenerative diseases. These findings suggest that NAD replenishment through NAD precursors has great potential as a therapeutic target for ageing and age-predisposed diseases, such as Alzheimer's disease. Here, we provide an updated review on the biological activity, safety, and possible side effects of NAD precursors in preclinical and clinical studies. Major NAD precursors focused on by this review are nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and the new discovered dihydronicotinamide riboside (NRH). In summary, NAD precursors have an exciting therapeutic potential for ageing, metabolic and neurodegenerative diseases.
Topics: Aging; Alzheimer Disease; Cell Survival; Drug Development; Energy Metabolism; Humans; NAD; Niacinamide; Nicotinamide Mononucleotide; Pyridinium Compounds; Signal Transduction
PubMed: 34517020
DOI: 10.1016/j.mad.2021.111567