
Science of NAD
How are your NAD levels today?


Feb 10, 2023
Liver - NAFLD
Cells
Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice
Wang, Dao-Xin
SUMMARY:
Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis....Taken together, our results show that hepatic Nampt deficiency aggravates dyslipidemia and liver damage in HFD fed mice. Hepatocyte Nampt can be a protective target against dyslipidemia and fatty liver.
Feb 9, 2023
Bone - Osteoporosis
Preprint
Nicotinamide enhances osteoblast differentiation through the activation of mitochondrial antioxidant defense system
Ryoo, Hyun-Mo
Feb 6, 2023
Muscle - Diabetes - Obesity
Preprint
Loss of NAMPT and SIRT2 but not SIRT1 Attenuate GLO1 Expression and Activity: Potential Mechanism for Obesity-Mediated GLO1 Attenuation in Human Muscle
Miranda, Edwin
SUMMARY:
Glyoxolase 1 (GLO1) [a rate-limiting enzyme for detoxification of methylglyoxal, which has been implicated in Type 2 diabetes (T2D) and other age-related disorders] is decreased in muscle from individuals with obesity prior to the development of T2D. In vitro modeling of this molecular milieu via GLO1 KD in human immortalized myotubes suggest that muscle lacking GLO1 is characterized by inflammation, stress, fibrosis, and muscle dysfunction. Mechanistic experiments in human myotubes and implicate SIRT2, NAMPT, and NAD+ as potential regulators of GLO1 protein and activity and suggest that NR or other NAD precursors may be able to augment GLO1....The findings presented here demonstrating that nicotinamide riboside NR can promote GLO1 transcripts, and activity, as well as NRF2 are perhaps the most exciting data which warrant further exploration of NR as a potential therapy for the prevention and treatment of metabolic dysfunction.
Feb 6, 2023
Muscle - Muscular Dystrophy
Preprint
The vitamin B3 analogue nicotinamide riboside has only very minor effects on reducing muscle damage in mdx mice
Stan, Tiberiu Loredan
SUMMARY:
Our data showed a trend for increase in NAD+-levels in blood; only in the D2-mdx NR-treated mice the NAD+-levels were slightly increased. These markers were elevated in mdx models compared to controls, but not affected by the NR treatment. Histological analysis of muscle tissues indicated a mild treatment effect in D2-mdx mice. Based on our results, testing NR treatment in clinical trials in DMD patients is not warranted.
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
Feb 6, 2023
Neurons - Brain - Parkinson's
Brain Sciences
Could Vitamins Have a Positive Impact on the Treatment of Parkinson’s Disease?
Sandeep
SUMMARY:
"...Vitamin B3 supplementation has been shown to alleviate various symptoms associated with PD...Mechanistically, vitamin B3 promotes the biosynthesis of the classical enzyme cofactor nicotinamide adenine dinucleotide (NAD) and mediates the release of nicotinamide by poly-ADP ribosylation. This generates an anti-inflammatory response, which alleviates DA-ergic neurodegeneration caused by neuroinflammation. These findings suggest that dietary supplementation with vitamin B3 may ameliorates oxidative stress and neuroinflammation, which would therefore prevent the death of DA-ergic neurons..."
Feb 4, 2023
Heart / Vascular - Aging
Antioxidants
NAD+ Homeostasis and NAD+-Consuming Enzymes: Implications for Vascular Health
Campagna, Roberto
SUMMARY:
Although future studies are required to better clarify the potential of targeting NAD+ homeostasis, the strategies based on administering NAD+ precursors or inhibiting NAD+-dependent enzymes seem to be an attractive approach for reducing chronic low-grade inflammation, enhancing mitochondrial biogenesis, and improving oxidative metabolism in vascular cells.
Feb 3, 2023
Aging - Metabolism
International Journal of Molecular Sciences
The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation
Poljsak, Borut
Feb 1, 2023
Liver - Fibrosis - Chronic Liver Disease - NMN
Preprint
NAMPT Inhibition and Increased NAD-Bioavailability Atenuate Liver Damage in CCI4-Induced Mice Liver Fibrosis
Suarez-Cuenca, J.
Jan 26, 2023
Brain - Alzheimer's Disease
Translational Neurodegeneration
Combined Metabolic Activators Improves Cognitive Functions in Alzheimer’s Disease
Yulug, Burak
SUMMARY:
We designed a randomized, double-blinded, placebo-controlled human phase 2 clinical trial and showed that the administration of CMAs improves cognitive functions in AD patients...We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.
Jan 23, 2023
Cancer - Breast
Oncogene
NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling
Jiang, Yi
SUMMARY:
Here, we show that NAD+ supplement suppresses tumor metastasis in a Triple Negative Breast Cancer Model...Overall, we demonstrate that NAD+ supplementation executes its anti-tumor function via activating the SIRT1-p66Shc axis, which highlights the preventive and therapeutic potential of SIRT1 activators as effective interventions for TNBC.
Jan 22, 2023
Liver - NAFLD - CD38
International Journal of Medical Sciences
Mechanism of CD38 via NAD+ in the Development of Non-alcoholic Fatty Liver Disease
Dong, Min
SUMMARY:
NAFLD is the most common form of liver disease, but there are no licensed medications available for its treatment. The progression of NAFLD is closely related to chronic inflammation, insulin resistance, and lipid accumulation. NAD+ is currently considered as a potential therapeutic target for NAFLD. As the critical NAD+ degrading enzyme in mammals, inhibiting of CD38 can significantly increase NAD+ levels and prevent NAFLD progression. These ideas have been confirmed in animal studies, but clinical trials still need to be verified.
Jan 22, 2023
Vision - Glaucoma
Acta Neuropathologica Communications
NAD salvage pathway machinery expression in normal and glaucomatous retina and optic nerve
Tribble, James R.
SUMMARY:
NAD production is an ideal target for neuroprotection in glaucoma and other age-related ophthalmic diseases...While the retina favors the NAD-salvage pathway, the anterior chamber favors the Preiss-Handler pathway and nicotinamide riboside as an alternative substrate to the NAD-salvage pathway...
Jan 19, 2023
Neurons - Spinal Cord Injury
Preprint
Elevation of NAD+ by nicotinamide riboside spares spinal cord tissue from injury and promotes locomotor recovery
Metcalfe, Mariajose
SUMMARY:
Administration of the NAD+ precursor, NR, to elevate NAD+ within the injured spinal cord mitigates the tissue damage and functional decline that occurs following spinal cord injury….administration of NR enhances NAD+ levels within the injured rat spinal cord, reduces tissue damage, and improves locomotor recovery after a thoracic spinal cord contusion injury in rats. Collectively, the results show that NR is a safe and effective bioavailable agent that can mitigate spinal cord damage.
Jan 13, 2023
Sepsis - Reproduction
Eurasian Journal of Medicine
Nicotinamide Riboside Preserves Ovarian Injury in Experimental Sepsis Model in Rats
Selli, Jale
SUMMARY:
Our findings indicated that nicotinamide riboside diminished ovarian injury in sepsis via inhibition of tissue infiltration and incresing of endogenous antioxidant capacity. Nicotinamide Riboside administration may represent a new treatment approach for the prevention of sepsis induced ovarian injury.
Jan 13, 2023
Neurons - Neurodegeneration - Parkinsons - Alzheimer's - Huntington's Disease - ALS
International Journal of Molecular Sciences
A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation
Tyagi, Alpna
Dec 31, 2022
Kidney - Heart / Vascular
Journal of Molecular and Cellular Cardiology
Nicotinamide riboside improves MI-induced acute kidney injury through increasing nicotinamide phosphorybosil transferase and NAD renal levels
Habeichi, Nada
Dec 30, 2022
Intestinal Barrier Dysfunction
Nutrients
NAD Supplement Alleviates Intestinal Barrier Injury Induced by Ethanol Via Protecting Epithelial Mitochondrial Function
Li, Wenli
SUMMARY:
Boosting NAD by Nicotinamide Riboside (NR) prevents ethanol-induced intestinal dysfunction by activation of epithelial mitochondrial function. The protective effects of NAD on intestinal barrier depend on the activation of SirT1 to a considerable extent. NR acts as a good NAD precursor without side effects and is able to regulate mitochondrial function via activating the SirT1 signaling pathway, maintain intestinal epithelial tight junctions stability and ultimately reverse ethanol-induced damage to the intestinal epithelial barrier.
Dec 28, 2022
Liver - NAFLD
Biomedical and Biophysical Research Communications
Metabolomic analysis shows dysregulation in amino acid and NAD+ metabolism in palmitate treated hepatocytes and plasma of non-alcoholic fatty liver disease spectrum
Aggarwal, Savera
Dec 27, 2022
Cancer - Chemotherapy
Cells
Nicotinamide Mononucleotide Administration Prevents Doxorubicin-Induced Cardiotoxicity and Loss in Physical Activity in Mice
Margier, Marielle
SUMMARY:
NMN significantly increased tissue levels of NAD+ and its metabolites and improved survival and bodyweight loss in both experimental models. In addition, NMN protected against Doxo-induced cardiotoxicity and loss of physical function in acute and chronic studies, respectively. In the heart, NMN prevented Doxo-induced transcriptomic changes related to mitochondrial function, apoptosis, oxidative stress, inflammation and p53, and promyelocytic leukemia nuclear body pathways. Overall, our results suggest that NMN could prevent Doxo-induced toxicity in heart and skeletal muscle.
Dec 26, 2022
Neurons - Neurodegeneration - Alzheimer's Disease - Parkinson's Disease
Life Sciences
Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases
Turkez, Hasan
SUMMARY:
We showed that combined metabolic activators [including nicotinamide riboside] administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the Alzheimer's Disease and Parkinson's Disease animal models and is a promising treatment for improving the metabolic parameters and brain functions in neurodegenerative diseases.
Dec 26, 2022
Reproduction - Fertility
Free Radical Biology and Medicine
Intermittent fasting reverses the declining quality of aged oocytes
Li, Chan
SUMMARY:
Just one month of every-other-day fasting was sufficient to improve oocyte quality [in mice]...Positive impact of intermittent fasting on aged oocytes was mediated by restoration of the nicotinamide adenine dinucleotide (NAD+)/Sirt1-mediated antioxidant defense system, which eliminated excessive accumulated ROS to suppress DNA damage and apoptosis.
Dec 14, 2022
Brain - Neurons - Neurodegeneration - Inflammation - Alzheimer's
Aging Cell
Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin
Vreones, Michael
SUMMARY:
We report the first study examining [extracellular vesicles enriched for neuronal origin or "NEV"] NEV biomarkers in response to oral NR supplementation. Our primary analysis of NAD+ and NADH in NEVs suggests an increase in neuronal NAD+ concentration in response to oral NR supplementation....We demonstrate that oral NR supplementation [in humans] increases NAD+ levels in NEVs ...These findings support the ability of orally administered NR to augment neuronal NAD+ levels and modify biomarkers related to neurodegenerative pathology in humans.
Dec 8, 2022
Liver - Bioavailability
Nature Communications
The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction
Hu, Guanlan
SUMMARY:
We demonstrate supplementing with nicotinamide (NAM) and related components of this pathway improve mitochondrial and overall hepatic metabolic dysfunction. We find that the effects of modulating the TRP-NAD+ pathway are mediated through SIRT1...NAM treatment can either reduce mitochondria degradation or increase its biogenesis in our model of severe malnutrition...NAM was shown to increase SIRT1 levels. The effect was not specific to NAM, as Nicotinamide Riboside (NR) and Tryptophan (TRP) demonstrated a similar effect...In our study, NAM treatment did not significantly restore NAD+ levels whereas NR did...
Dec 2, 2022
Cancer - Chemotherapy
Preprint
The CD73 immune checkpoint promotes tumor cell metabolic fitness
Allard, David
SUMMARY:
We demonstrated that CD73 promote tumor growth in a cancer-cell autonomous manner by increasing metabolic fitness. This in turn favors cancer cell adaptation to nutrient-deprived microenvironments and cytotoxic stress by increasing OXPHOS, aspartate biosynthesis and DNA repair. Our study highlights new therapeutic opportunities that may be exploited in novel combination anti-cancer strategies.
Nov 29, 2022
Obesity
International Journal of Molecular Sciences
Reduction of Obesity and Insulin Resistance through Dual Targeting of VAT and BAT by a Novel Combination of Metabolic Cofactors
Quesada-Vazquez, Sergio
SUMMARY:
Supplementation with a metabolic cocktail including nicotinamide riboside promotes the amelioration of adipose tissue dysfunction observed in the diet-induced obese mouse model...Altogether, this study suggests that the supplements ameliorate adipose tissue dysfunction acting in different pathways affected by obesity, and can be an effective treatment for reducing the incidence of obesity-related metabolic disorders.
Nov 28, 2022
Diabetes - Aging
International Journal of Molecular Sciences
Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study
Akasaka, Hiroshi
Nov 23, 2022
Vision - AMD
Mechanisms of Ageing and Development
The role of NAD+ metabolism in macrophages in age-related macular degeneration
Lin, Ruoyi
Nov 17, 2022
Brain - Alzheimer's - Neuroinflammation - Metabolism - Diabetes
Scientific Reports
Sirt3 deficiency induced down regulation of insulin degrading enzyme in comorbid Alzheimer’s disease with metabolic syndrome
Tyagi, Alpna
SUMMARY:
Mitochondrial dysfunction, insulin resistance, metabolic dysregulation and neuroinflammation that contribute to cognitive decline in Alzheimer's Disease...The findings of this study suggest that SIRT3 is a potential therapeutic target for the treatment of AD. Sirtuins, including SIRT3, require NAD+ as a cosubstrate. Administration of NR, a precursor of NAD+, leads to increase in the cellular level of NAD+. In this study, we demonstrate that NR increases the levels of IDE as well as neprilysin and decreases the levels of BACE1 in vivo. Interestingly, NR also increases the levels of SIRT3, probably by autoregulation. NR has been reported to reverse insulin resistance and glucose intolerance in a mouse model for type 2 diabetes. NR has been shown to be effective in reducing neuroinflammation and improve cognition in Alzheimer’s mouse models. Therefore, NR-based treatment can be considered for the treatment of AD with comorbidities.
Nov 14, 2022
Obesity - Diabetes - Inflammation
Food & Function
Nicotinamide riboside ameliorates high-fructose-induced lipid metabolism disorder in mice via improving FGF21 resistance in the liver and white adipose tissue
Zhao, Hui
Nov 8, 2022
Liver - Gut Microbiome - NAFLD - Intestinal Barrier Dysfunction
International Journal of Molecular Sciences
Microbiota Dysbiosis and Gut Barrier Dysfunction Associated with Non-Alcoholic Fatty Liver Disease Are Modulated by a Specific Metabolic Cofactors’ Combination
Quesada-Vazquez, Sergio
Oct 28, 2022
Cancer - Chemotherapy
Reproduction
Intravenous Nicotinamide Riboside Administration Has a Cardioprotective Effect in Chronic Doxorubicin-Induced Cardiomyopathy
Podyacheva, Ekaterina
SUMMARY:
We demonstrated that NR intravenous administration decreases cardiac-muscle fibrous-tissue formation in chronic doxorubicin-induced cardiotoxicity development...Moreover, a pronounced protective effect of NR on the cardiovascular system was demonstrated...Simultaneously, the preventive NR administration had a more significant protective effect on the animal’s body as a whole.
Oct 26, 2022
Aging
Life Medicine
A comparative study of metformin and nicotinamide riboside in alleviating tissue aging in rats
Geng, Lingling
SUMMARY:
Here, we showed that Metformin (MET) and Nicotinamide Riboside (NR) exhibited a geroprotective effect on aged human stem cells and various tissues in aged rats. Both MET and NR repressed systemic inflammation and inhibited aging markers across multiple tissues in aged rats. MET and NR treatment attenuated aging-associated gene expression across tissues, with the most protective effects in adipose and aortic tissues. We found that that both MET and NR alleviated the aging-associated phenotypes, especially systemic inflammation, tissue fibrosis, and aggresome formation in aged rat tissues. We further showed that both MET and NR partially rescued aging Differentially Expressed Genes in several tissues, and the most remarkable effects were found in adipose and aortic tissues
Oct 22, 2022
Viral Infection - COVID
Nature Metabolism
Innate metabolic responses against viral infections
Palmer, Clovis S.
SUMMARY:
Metabolic disorders may increase the vulnerability of individuals to SARS-CoV-2 and worsen disease prognosis...Low levels of circulating NAD+ are reported in severe COVID-19...Coronavirus infection can deplete cellular NAD+ levels, and boosting NAD+ with NAD precursors has been shown to enhance the antiviral activities of PARP isozymes...NAD+ is also essential for critical host antioxidant and anti-inflammatory responses. Thus, therapeutic reinforcement of the NAD+ system has been proposed as a potential prophylaxis approach against viruses such as SARS-CoV-2 infection...Ultimately, the outcome of this ‘tug-of-war’ [between the virus and the immune system both drawing down NAD] is likely to be influenced by the nutritional status of the host....
Oct 21, 2022
Kidney - Reproduction - Pregnancy
Cells
Low Nephron Number Induced by Maternal Protein Restriction Is Prevented by Nicotinamide Riboside Supplementation Depending on Sirtuin 3 Activation
Pezzotta, Anna
SUMMARY:
Evidence that has accumulated over the last three decades suggests that renal diseases start in utero...Low nephron number is one of the main contributors to chronic kidney disease (CKD) susceptibility in adulthood...Here, we show that a nephron number deficit and impaired renal architecture of mice born to mothers fed a low protein diet can be restored by NR supplementation during pregnancy through the induction of SIRT3 expression and activity...These findings have huge potential for clinical translation, given that inadequate nephrons at birth increase the risk in adulthood of hypertension and renal diseases. Chronic kidney disease affects over 10% of the adult population worldwide, with rising overall morbidity and mortality rates. In view of this, it is evident that prenatal kidney care is an important global health challenge.
Oct 20, 2022
Brain - Neurodegeneration - Mitochondria - Parkinsons - Alzheimers - ALS
International Journal of Molecular Sciences
Mitochondrial Dysfunction and Neurodegenerative Disorders: Role of Nutritional Supplementation
Mantle, David
SUMMARY:
We have selected a number of neurodegenerative disorders that are known to involve mitochondrial dysfunction in their pathogenesis. We have further selected a number of nutrients that have a key role in mitochondrial function. We then correlated data on the deficiency (Table 1) and supplementation of these nutrients (Table 2) in the said neurodegenerative disorders. In this review, we have therefore provided a rationale for a combination of CoQ10, B-vitamins/NADH, l-carnitine, vitamin D, and alpha-lipoic acid to support the future treatment of these neurodegenerative disorders.
Oct 19, 2022
Muscle - Stem Cells
Frontiers in Cell Development Biology
Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration
Sonntag, Tanja
SUMMARY:
During regeneration, muscle stem cells (MuSCs) from [mice with both NRK1 and NRK2 knocked out] hyper-proliferate but fail to differentiate. Double NRK Knockout also alters the recovery of NAD+ during muscle regeneration as well as mitochondrial adaptations and ECM remodeling required for tissue repair. These metabolic perturbations result in a transient delay of muscle regeneration which normalizes during myofiber maturation at late stages of regeneration via over-compensation of anabolic IGF1-Akt signaling.
Oct 17, 2022
Kidney - Inflammation - Diabetes
Preprint
NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease
Myakala, Komuraiah
Oct 12, 2022
Aging - Progeria - Bioavailability
Frontiers in Aging
The use of progeroid DNA repair-deficient mice for assessing anti-aging compounds, illustrating the benefits of nicotinamide riboside
Birkisdóttir, María B.
SUMMARY:
Interestingly, mice supplemented with NA revealed a significant delay in the onset of imbalance, whereas NR supplementation showed a trend towards delaying the median age of onset of tremors. Furthermore, NR significantly extended median lifespan by approximately 25% or 5 weeks, while animals receiving NA lived about as long as control-fed animals.
Oct 11, 2022
NMN - Metabolism - Gut Microbiota - Bioavailability
Preprint
Nicotinamide mononucleotide (NMN) deamidation by host-microbiome interactions
Kim, Lynn-Jee
SUMMARY:
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...
Oct 11, 2022
Circadian Rhythm - Aging - Heart
American Journal of Physiology - Cell Physiology
Circadian cardiac NAD+ metabolism, from transcriptional regulation to healthy aging
Carpenter, Bryce J.
SUMMARY:
...Recent studies have expanded on the role of circadian rhythms and the core clock factors that maintain them in the regulation of NAD+ levels in the heart. This has revealed that NAD+ pools and their use are tightly linked to cardiac function, but also heart failure. The convergence of these fields, namely, clock regulation, heart disease, and NAD+ metabolism present a complex network ripe with potential scientific and clinical discoveries, given the growing number of animal models, recently developed technology, and opportunity for safe and accessible precursor supplementation...
Oct 10, 2022
Muscle - Aging - Stem Cells
JCI Insight
A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals
Jensen, Jonas
SUMMARY:
...The objective of this study was to investigate if supplementation with nicotinamide riboside and pterostilbene (NRPT) promotes skeletal muscle regeneration after muscle injury in elderly individuals by improved recruitment of MuSCs...Daily supplementation with 1,000 mg NR and 200 mg PT is safe but does not improve recruitment of the MuSC pool or other measures of muscle recovery in response to injury or subsequent regeneration in elderly individuals.
Oct 1, 2022
Cancer - Breast
Biosensors and Bioelectronics
A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism
Maric, Tamara
SUMMARY:
Our results demonstrate that NR supplementation results in a significant increase in cancer prevalence and metastases of TNBC to the brain. These results outline the important role of powerful nutraceuticals like NR in cancer metabolism and the need to personalize their use in certain patient populations.
Oct 1, 2022
Reproduction - Fertility
Reproduction
Nicotinamide Riboside supplementation ameliorated postovulatory oocyte quality decline
Li, Hui
SUMMARY:
NR treatment not only restored MII oocyte quality but also enhanced early embryonic development potential of postovulatory oocytes via alleviating mitochondrial dysfunction and maintaining normal spindle/chromosome structure. ...NR supplementation increases the oocyte quality and early embryonic development potential in post-ovulatory oocytes which could potentially increase the successful rate in assisted reproductive technology.
Oct 1, 2022
Cancer - Skin
Journal of Drugs in Dermatology
A Narrative Review of Nicotinamide Adenine Dinucleotide (NAD)+ Intermediates Nicotinamide Riboside and Nicotinamide Mononucleotide for Keratinocyte Carcinoma Risk Reduction
Kahn, Benjamin
SUMMARY:
Oral nicotinamide (NAM) supplementation has been shown to decrease the incidence of keratinocyte carcinoma (KC) in high-risk skin cancer patients. NAM is a nicotinamide adenine dinucleotide (NAD+) intermediate and thus directly leads to increased NAD+. This increase in NAD+ is believed to be responsible for NAM’s impact on keratinocyte carcinoma risk. NAD+ has protective cellular effects and is a necessary cofactor for DNA repair, helping to prevent potentially oncogenic mutations. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are NAD+ intermediates like NAM...
Oct 1, 2022
Heart / Vascular - Mitochondrial Disorder
Molecular Metabolism
Nicotinamide riboside alleviates exercise intolerance in ANT1-deficient mice
Schaefer, Patrick
Sep 28, 2022
Skin - Aging
Plastic and Reconstructive Surgery
The Role of NAD+ in Regenerative Medicine
Conlon, Nichola
SUMMARY:
Addressing aging at the cellular level is now critically important. Many surgical procedures rely on the healing and regenerative capacity of the skin which is known to decline with age, leading to disappointing results or negative postsurgery outcomes. Improving health and resilience at the cellular level with NAD+ restoration could be harnessed as a way to ensure consistent results and recovery irrespective of patient age. It should also be noted that the efficacy of many nonsurgical aesthetic procedures such as microneedling and laser technologies ultimately rely on the activation of cellular stress pathways to trigger the clearance of damaged cells and stimulate the production of new collagen. Many of these pathways require adequate NAD+ levels for optimal function, meaning NAD+ restoration before treatment could be a strategy to ensure the underlying cells are in an optimal condition to respond to the treatment.
Sep 26, 2022
Aging - Longevity - Sirtuins
Archives of Gerontology and Geriatrics
A Science-Based Review of the World’s Best-Selling Book on Aging
Brenner, Charles
SUMMARY:
Lifespan, a book by Harvard scientist David Sinclair, has become an influential source of misinformation on longevity, featuring counterfactual claims about longevity genes being conserved between yeast and humans, the existence of supposed activators of these genes, and claimed successful age reversal in mice based on partial reprogramming. The book has popularized a stack of drugs and supplements with significant potential to harm the general public.The reviewer suggests that scientists and physicians emphasize to the general public that aging is known to be a highly polygenic developmental process and that the most important things that people can do to age better are to maintain high physical and mental activity.
Sep 22, 2022
Aging - Longevity - Sirtuins
Life Metabolism
Sirtuins are Not Conserved Longevity Genes
Brenner, Charles
SUMMARY:
While sirtuins carry out interesting biochemical reactions and perform important functions for organisms, their degree of regulation is modest compared to most other enzymes that function in the NAD system. In addition, the degree of hype, framing, and nonreproducibility in the sirtuin literature is persistently misleading. Dispassionate analysis of their functions does not support assignment as longevity enzymes or as principal mediators of the effects of NAD repletion.
Sep 20, 2022
Metabolism
Nutrients
Emerging Role of Nicotinamide Riboside in Health and Diseases
Sharma, Chiranjeev
Sep 20, 2022
Pancreas - Aging
Molecular Metabolism
Nicotinamide Riboside Kinase 1 protects against diet and age-induced pancreatic β-cell failure
Circillieux, Angelique
SUMMARY:
Disturbances in NAD+ metabolism have been described as a hallmark for multiple metabolic and age-related diseases, including type 2 diabetes. While alterations in pancreatic β-cell function are critical determinants of whole-body glucose homeostasis, the role of NAD+ metabolism in the endocrine pancreas remains poorly explored. Here, we aimed to evaluate the role of nicotinamide riboside (NR) metabolism in maintaining NAD+ levels and pancreatic β-cell function in pathophysiological conditions...
Sep 14, 2022
Heart / Vascular - Aging
Journal of Cardiovascular Aging
Metabolic targets in cardiac aging and rejuvenation
Liu, Chang
SUMMARY:
NAD+ repletion can delay several hallmarks of aging and suppress the deterioration of age-related diseases[95]. This suggests a significant potential for the treatment of cardiac diseases in the elderly population with supplementation of NAD+ precursors. Indeed, the dietary intake of NAM could reduce cardiac hypertrophy and diastolic dysfunction in aged mice
Sep 14, 2022
Heart / Vascular
JACC: Basic to Translational Science
Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction
O'Brien, Kevin
SUMMARY:
The mitochondrial dysfunction characteristic of heart failure (HF) is associated with changes in intracellular nicotinamide adenine dinucleotide (NAD+) and NADH levels. Raising NAD+ levels with the NAD+ precursor, nicotinamide riboside (NR), may represent a novel HF treatment. In this 30-participant trial of patients with clinically stable HF with reduced ejection fraction, NR, at a dose of 1,000 mg twice daily, appeared to be safe and well tolerated, and approximately doubled whole blood NAD+ levels...
Sep 9, 2022
Liver - NAFLD
Hepatology
NRPT reduces markers of hepatic inflammation in non-alcoholic fatty liver disease: a double-blind, placebo-controlled clinical trial
Dellinger, Ryan
SUMMARY:
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing globally on a path to becoming the most frequent cause of chronic liver disease. Novel strategies for the prevention and treatment of NAFLD are urgently needed. A 6-month prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to assess the efficacy of daily NRPT (commercially known as Basis; a combination of nicotinamide riboside and pterostilbene) supplementation in 111 adults with NAFLD...This study demonstrates that NRPT at the recommended dose is safe and may hold promise in lowering markers of hepatic inflammation in patients with NAFLD.
Sep 4, 2022
Reproduction - Fertility
Biomedicines
Methods for Assessing Oocyte Quality: A Review of Literature
Lemseffer, Yassir
SUMMARY:
The rate of infertility continues to rise in the world for several reasons, including the age of conception and current lifestyle. We list in this paper potential non-invasive and invasive techniques to assess oocyte quality. We searched the database PubMed using the terms “oocytes AND quality AND evaluation”. In the first part, we study the morphological criteria, compartment by compartment, to then focus in a second part on more objective techniques such as genetics, molecular, apoptosis, or human follicular fluid that contain biologically active molecules. The main criteria used to assess oocyte quality are morphological; however, several other techniques have been studied in women to improve oocyte quality assessment, but most of them are invasive and not usable in routine.
Aug 30, 2022
Leigh Syndrome
Clinical and Translational Discovery
How to mitigate neurological and cardiac decompensation in Leigh syndrome: Can nicotinamide riboside be an answer?
Prigione, Allesandro
SUMMARY:
Leigh syndrome is the most common form of mitochondrial disease in children. The mechanisms underlying its pathogenesis are not fully understood and no therapies are approved for the treatment of patients with LS. In a new study, Yoon and colleagues1 shed light on the pathophysiological mechanisms of cardio-encephalomyopathy in LS and demonstrates that nicotiname riboside (NR) provides significant amelioration in disease models of LS
Aug 26, 2022
Hearing - Aging
Preprint
Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice
Okur, Mustafa
SUMMARY:
Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer’s and Parkinson’s Disease. It has also been beneficial against noise induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL...
Aug 22, 2022
Fat Metabolism
Frontiers in Cell and Developmental Biology
Nicotinamide-riboside shifts the differentiation of human primary white adipocytes to beige adipocytes impacting substrate preference and uncoupling respiration through SIRT1 activation and mitochondria-derived reactive species productio
Bai, Peter
Aug 15, 2022
Circadian Rhythm - Metabolism
Preprint
Time-of-day defines the efficacy of NAD+ to treat diet-induced metabolic disease by adjusting oscillations of the hepatic circadian clock
Escalante-Covarrubias, Q
SUMMARY:
The circadian clock is a time-tracking endogenous system which anticipates and coordinates adaptation to daily environmental fluctuations. Circadian misalignment leads to obesity, which is accompanied by reduced levels of the clock-controlled metabolite NAD+. Concomitantly, increasing NAD+ levels is emerging as a therapy for diet-induced obesity and type 2 diabetes; however, the impact of daily fluctuations of NAD+ on these therapies remains unknown. Here, we demonstrate that time-of-day determines the efficacy of NAD+ as a therapy for diet-induced metabolic disease in mice...
Aug 7, 2022
Brain - Aging - Cognitive Decline - Alzheimers - Stroke
Nutrients
Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts
Campbell, Jared
Aug 2, 2022
Metabolism - Bioavailability
Cellular and Molecular Life Sciences
Balancing NAD+ deficits with nicotinamide riboside: therapeutic possibilities and limitations
Circillieux, Angelique
SUMMARY:
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...
Jul 25, 2022
Neurons - Leigh Syndrome - Mitochondrial Dysfunction
Clinical and Translational Medicine
Metabolic rescue ameliorates mitochondrial encephalo-cardiomyopathy in murine and human iPSC models of Leigh syndrome
Yoon, Jin-Young
SUMMARY:
Our study reveals direct mechanistic explanations of the observed cardiac bradyarrhythmia, diastolic dysfunction and neuronal apoptosis in mouse and human induced pluripotent stem cells (iPSC) models of Leigh Syndrome….Metabolic rescue by nicotinamide riboside (NR) supplementation increased intracellular NAD+/ NADH, restored metabolic derangement, reversed protein hyperacetylation through NAD+‐dependent Sirtuin deacetylase, and ameliorated cardiomyopathic phenotypes...NR also attenuated neuronal apoptosis and microglial activation...
Jul 22, 2022
Brain - Cancer - NRH
Cancers (Basel)
Overcoming Temozolomide Resistance in Glioblastoma via Enhanced NAD+ Bioavailability and Inhibition of Poly-ADP-Ribose Glycohydrolase
Li, Jianfeng
Jul 18, 2022
Vision - AMD
Oxidative Medicine and Cellular Longevity
Nicotinamide Mononucleotide Ameliorates Cellular Senescence and Inflammation Caused by Sodium Iodate in RPE
Ren, Chengda
SUMMARY:
The antioxidant N-acetylcysteine (NAC) could alleviate cellular senescence only by a minimal degree, whereas supplementation with nicotinamide mononucleotide (NMN) strongly ameliorated RPE senescence through the alleviation of DNA damage and the maintenance of mitochondrial function. The protective effects of NMN were demonstrated to rely on undisturbed Sirt1 signaling. Moreover, both the expression of senescence markers of RPE and subretinal inflammatory cell infiltration were decreased by NMN treatment in vivo. Our results indicate that RPE senescence induced by NaIO3 acquired several key features of AMD. More importantly, NMN may potentially be used to treat RPE senescence and senescence-associated pre-AMD changes by restoring the NAD+ levels in cells and tissues.
Jul 18, 2022
Brain - Ataxia
Neuropediatrics
Nicotinamide Riboside for Ataxia Telangiectasia: Report of an Early Treated Individual
Steinbruecker, Katja
Jul 15, 2022
Metabolism - Cancer - Niacin
Pharmaceuticals
Structure-Based Identification and Biological Characterization of New NAPRT Inhibitors
Franco, Jorge
Jul 9, 2022
Metabolism - Bioavailability
Metabolites
NAD+ Precursors: A Questionable Redundancy
Canto, Carles
SUMMARY:
The last decade has seen a strong proliferation of therapeutic strategies for the treatment of metabolic and age-related diseases based on increasing cellular NAD+ bioavailability. Among them, the dietary supplementation with NAD+ precursors—classically known as vitamin B3—has received most of the attention. Multiple molecules can act as NAD+ precursors through independent biosynthetic routes. Interestingly, eukaryote organisms have conserved a remarkable ability to utilize all of these different molecules, even if some of them are scarcely found in nature. Here, we discuss the possibility that the conservation of all of these biosynthetic pathways through evolution occurred because the different NAD+ precursors might serve specialized purposes.
Jul 7, 2022
Brain - Oxytocin - Autism
Frontiers in Neuroscience
Oxytocin Dynamics in the Body and Brain Regulated by the Receptor for Advanced Glycation End-Products, CD38, CD157, and Nicotinamide Riboside
Higashida, Harohiro
SUMMARY:
...It has recently been found that gavage application of a precursor of nicotinamide adenine dinucleotide, nicotinamide riboside, for 12 days can increase brain Oxytocin (OT) in mice. Here, we review the evaluation of the new concept that RAGE is involved in the regulation of OT dynamics at the interface between the brain, blood, and intestine in the living body...
Jul 1, 2022
Metabolism - Bioavailability - NRH - NARH
Nutrients
Nicotinamide Riboside and Dihydronicotinic Acid Riboside Synergistically Increase Intracellular NAD+ by Generating Dihydronicotinamide Riboside
Ciarlo, Eleonora
SUMMARY:
This work demonstrates for the first time that NARH can act as a NAD+ precursor in mammalian cells and how different NAD+ precursors can interact and influence each other when co-administered...NARH achieved synergistic effects with NR in increasing NAD+ levels, but not with any of the other NAD+ precursors tested...The effect was remarkable, given the fact that NR or NARH had limited effects on NAD+ levels in these two cell lines when used as single treatments...The synergistic action of NR and NARH could be confirmed in vivo...NR degradation to NAM was not a critical step, as NAM and NARH did not lead to cooperative increases in NAD+ levels...The vigorous increase in NAD+ levels observed when combining NR and NARH was reminiscent of the effects of NRH...The simplest explanation for this would be that the combination of NR and NARH led to the production of NRH...The results showed that, when used together, NR and NARH increased the intracellular levels of NRH...Simply adding the two molecules to a vial of water at room temperature was enough to generate NRH
Jun 27, 2022
Neurons - Neuropathy - Cancer - Chemotherapy
Neuro-Oncology Advances
Nicotinamide riboside alleviates cisplatin-induced peripheral neuropathy via SIRT2 activation
Acklin, Scarlett
SUMMARY:
We show that NR, an NAD+ precursor and pharmacologic activator of SIRT2, effectively prevents and alleviates CIPN in mice. We present in vitro and in vivo genetic evidence to illustrate the specific dependence on SIRT2 of NR-mediated CIPN mitigation. Importantly, we demonstrate that NAD+ mediates SIRT2-dependent neuroprotection without inhibiting cisplatin cytotoxic activity against cancer cells. NAD+ may, in fact, further sensitize certain cancer cell types to cisplatin.
Jun 21, 2022
Addiction
Current Psychiatry Research and Reviews
Nicotinamide Adenine Dinucleotide (NAD+) and Enkephalinase Inhibition (IV1114589NAD) Infusions Significantly Attenuate Psychiatric Burden Sequalae in Substance Use Disorder (SUD) in Fifty Cases
Blum, Kenneth
Jun 14, 2022
Inflammation
Current Developments in Nutrition
The Clinical Effects of Nicotinamide Riboside on Inflammatory Parameters
Kwon, Jun
SUMMARY:
The objective of this study was to investigate the clinical evidence of NR's mitigation of inflammation in humans. We identified 5 clinical trials of oral NR supplementation that measured inflammation. There was substantial heterogeneity in inflammatory endpoints evaluated. NR dose and treatment duration ranged from 1–2 g/day and 5-d– 6-wks, respectively. Participants varied in age (18–78 years) and health status. In one study, NR was given as part of a nutritional cocktail, while NR was the sole intervention in the remaining studies. Of the 3 studies assessing circulating inflammatory markers, two investigated IL-6 and reported significant reductions in its levels with NR treatment, while effects on MCP-1 and TNF-α were inconsistent. NR significantly lowered gene expression of IL-6 and IL-18, but not NLRP3 or IL-1B in peripheral blood mononuclear cells in one study...Preliminary evidence suggests that NR may improve some inflammatory measures, with potential for more robust effects among populations with compromised NAD + and higher inflammation status, e.g., elderly or diseased...
Jun 1, 2022
Circadian Rhythm
Seminars and Cell and Development Biology
Circadian NAD(P)(H) cycles in cell metabolism
Levine, Daniel
May 28, 2022
Reproduction - Muscle - Postpartum
Nutrients
Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood
Serrano, Alba
SUMMARY:
...Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. ...These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.
May 25, 2022
Obesity - Liver - Inflammation
Journal of Nutritional Biochemistry
Nicotinamide riboside supplementation exerts an anti-obesity effect and prevents inflammation and fibrosis in white adipose tissue of female diet-induced obesity mice
Kim, Mi-Bo
SUMMARY:
...We previously reported that NR supplementation prevented the development of liver fibrosis in male mice. However, whether NR exerts a similar effect in females is unknown. Therefore, we determined whether NR supplementation can prevent obesity-induced inflammation and fibrosis in the liver and white adipose tissue (WAT) by providing NAD+ in obese female mice...Our results indicated that NR supplementation exerted an anti-obesity effect and prevented the development of inflammation and fibrosis in the white adipose tissue of old, but not young, female mice with diet-induced obesity.
May 23, 2022
NAM - Cancer - Prostate
Frontiers in Molecular Biosciences
CD38-Induced Apoptosis and Mitochondrial Damage is Restored by Nicotinamide in Prostate Cancer
Kanayama, Mayuko
SUMMARY:
...CD38 expression is consistently silenced by methylation in prostate cancer and progressively downregulated in advanced castration-resistant prostate cancer, suggesting a connection between NAD+ and prostate carcinogenesis as well as prostate cancer progression. ...In this study, we...demonstrate that CD38 overexpression resulted in growth suppression and apoptosis accompanied by cleavage of poly (ADP-ribose) polymerase 1 (PARP1). CD38 overexpression also dramatically reduced intracellular NAD+ levels and decreased mitochondrial respiration as measured by oxygen consumption rate. We further show that some but not all of these CD38-induced phenotypes could be rescued by exogenous NAM. Treatment of cells with NAM rescued CD38-induced apoptosis and mitochondrial stress but did not restore intracellular NAD+ levels. We also found that NAM demonstrated biphasic effect on mitochondria function, a finding that can be explained by the dual role of NAM as both a precursor of NAD+ and also as a suppressor of a number of NAD+-dependent enzymes...
May 22, 2022
NAM - Metabolism
Nutrients
A Combination of Nicotinamide and D-Ribose (RiaGev) Is Safe and Effective to Increase NAD+ Metabolome in Healthy Middle-Aged Adults: A Randomized, Triple-Blind, Placebo-Controlled, Cross-Over Pilot Clinical Trial
Xue, Yongquan
May 9, 2022
Heart - Vascular - Circadian Rhythm - Aging
Frontiers in Molecular Medicine
Nicotinamide Riboside Improves Cardiac Function and Prolongs Survival After Disruption of the Cardiomyocyte Clock
Dierickx, Pieterjan
SUMMARY:
Here, we show that supplementation with the NAD+ precursor NR as a dietary supplement improves heart function and extends the lifespan of female mice lacking cardiac REV-ERBs. Thus, boosting NAD+ levels can improve cardiac function in a setting of heart failure caused by disruption of circadian clock factors, providing new insights into the links between the circadian clock, energy metabolism, and cardiac function.
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
SUMMARY:
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 28, 2022
Diabetes - Neuropathy - Neurons
International Journal of Molecular Sciences
NAD+ Precursors Repair Mitochondrial Function in Diabetes and Prevent Experimental Diabetic Neuropathy
Chandrasekaran, Krish
SUMMARY:
Diabetic peripheral neuropathy (DPN) is a common neurological complication of diabetes. Currently, there is no therapy that permanently prevents or reverses neuropathy. ...Correction of NAD+ depletion [with dietary NR] in dorsal root ganglion neurons may be sufficient to prevent diabetic peripheral neuropathy, but does not significantly affect glucose tolerance, insulin levels, or insulin resistance.
Apr 28, 2022
Muscle - Gut Microbiota - Stem Cells - Mitochondria - Obesity
Science Advances
Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation and gut microbiota composition in a twin study
Lapatto, Helena
SUMMARY:
We aimed to determine whether long-term nicotinamide riboside (NR) supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twins from 22 BMI-discordant monozygotic pairs were supplemented with an escalating dose of NR (250-1000 mg/day) for 5 months (clinicaltrials.gov entry NCT03951285). NR improved blood and tissue NAD+ metabolism, muscle mitochondrial number, myoblast differentiation and gut microbiota composition independent of BMI. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD+ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.