NAD+ increase AND supplements

NAD+ boosting via nicotinamide riboside (NR) confers anti-inflammatory effects. However, its underlying mechanisms and therapeutic potential remain incompletely defined. Here, we showed that NR increased the expression of CC-chemokine receptor 7 (CCR7) in human M1 macrophages by flow cytometric analysis of cell surface receptors. Consequently, chemokine ligand 19 (CCL19, ligand for CCR7)-induced macrophage migration was enhanced following NR administration. Metabolomics analysis revealed that prostaglandin E2 (PGE2) was increased by NR in human monocytes and in human serum following in vivo NR supplementation...

Prior studies showed that polyQ-expanded AR is aberrantly acetylated and that deacetylation of the mutant AR by overexpression of NAD+-dependent sirtuin 1 (SIRT1) is protective in cell models of spinal and bulbar muscular atrophy (SBMA). Based on these observations and reduced NAD+ in muscles of SBMA mouse models, we tested the therapeutic potential of NAD+ restoration in vivo by treating post-symptomatic transgenic SBMA mice with the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide riboside (NR)...

Pseudomonas aeruginosa is a versatile opportunistic pathogen which causes a variety of acute and chronic human infections, some of which are associated with the biofilm phenotype of the pathogen. We hypothesize that defining the intracellular metabolome of biofilm cells, compared to that of planktonic cells, will elucidate the metabolic pathways and biomarkers indicative of biofilm inception. Disc-shaped stainless-steel coupons (12.7 mm diameter) were employed as a surface for static biofilm establishment. Each disc was immersed in a well, of a 24-well microtiter plate, containing a 1-mL Lysogeny broth (LB) suspension of P...

Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40-65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement...

Bladder cancer (BLCA) is one of the most prevalent malignancies worldwide with a high mortality rate and poor response to immunotherapy in patients expressing lower programmed death ligand 1 (PD-L1) levels. Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme responsible for the biosynthesis of nicotinamide adenine dinucleotide (NAD+ ) from nicotinamide was reported to be overexpressed in various cancers; however, the role of NAMPT in BLCA is obscure. Immunohistochemistry of tissue microarrays, a real-time polymerase chain reaction, Western blotting, proliferation assay, NAD+ quantification, transwell-migration assay, and colony-formation assay were performed to measure NAMPT and PD-L1 expression levels in patients and the effect of NAMPT inhibition on T24 cells...

BACKGROUND: Chronic overconsumption of lipids followed by their excessive accumulation in the heart leads to cardiomyopathy. The cause of lipid-induced cardiomyopathy involves a pivotal role for the proton-pump vacuolar-type H+ -ATPase (v-ATPase), which acidifies endosomes, and for lipid-transporter CD36, which is stored in acidified endosomes. During lipid overexposure, an increased influx of lipids into cardiomyocytes is sensed by v-ATPase, which then disassembles, causing endosomal de-acidification and expulsion of stored CD36 from the endosomes toward the sarcolemma...

Vascular ageing is associated with increased arterial stiffness and cardiovascular mortality that might be linked to altered vascular energy metabolism. The aim of this study was to establish a Seahorse XFe96 Analyzer-based methodology for the reliable, functional assessment of mitochondrial respiration and glycolysis in single murine aortic rings and to validate this functional assay by characterising alterations in vascular energy metabolism in aged mice. Healthy young and old C57BL/6 mice were used for the analyses...

INTRODUCTION: Sarcopenia is the age-associated loss of muscle mass and strength. Nicotinamide adenine dinucleotide (NAD) plays a central role in both mitochondrial function and cellular ageing processes implicated in sarcopenia. NAD concentrations are low in older people with sarcopenia, and increasing skeletal muscle NAD concentrations may offer a novel therapy for this condition. Acipimox is a licensed lipid-lowering agent known to act as an NAD precursor. This open-label, uncontrolled, before-and-after proof-of-concept experimental medicine study will test whether daily supplementation with acipimox improves skeletal muscle NAD concentrations...

The essential role of nicotinamide adenine dinucleotide+ (NAD+ ) in redox reactions during oxidative respiration is well known, yet the coenzyme and regulator functions of NAD+ in diverse and important processes are still being discovered. Maintaining NAD+ levels through diet is essential for health. In fact, the United States requires supplementation of the NAD+ precursor niacin into the food chain for these reasons. A large body of research also indicates that elevating NAD+ levels is beneficial for numerous conditions, including cancer, cardiovascular health, inflammatory response, and longevity...

Trimethylamine N-oxide (TMAO) has attracted interest because of its association with cardiovascular disease and diabetes, and evidence for the beneficial effects of TMAO is accumulating. This study investigates the role of TMAO in improving exercise performance and elucidates the underlying molecular mechanisms. Using C2C12 cells, we established an oxidative stress model and administered TMAO treatment. Our results indicate that TMAO significantly protects myoblasts from oxidative stress-induced damage by increasing the expression of Nrf2, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (NQO1), and catalase (CAT)...

The present study assessed the protective effects and underlying mechanisms of mulberry leaf polysaccharides (MLPs) against hydrogen peroxide (H2 O2 )-induced oxidative stress injury in the peripheral blood leukocytes (PBLs) of Megalobrama amblycephala . Five treatment groups were established in vitro: the NC group (PBLs incubated in an RPMI-1640 complete medium for 4 h), the HP group (PBLs incubated in an RPMI-1640 complete medium for 3 h, and then stimulated with 100 μM of H2 O2 for 1 h), and the 50/100/200-MLP pre-treatment groups (PBLs were pre-treated with MLPs (50, 100, and 200 μg/mL) for 3 h, and then stimulated with 100 μM of H2 O2 for 1 h)...

INTRODUCTION: Nicotinamide adenine dinucleotide (NAD+) participates in various processes that are dysregulated in cardiovascular diseases. Supplementation with NAD+ may be cardioprotective. However, whether the protective effect exerted by NAD+ in heart failure (HF) is more effective before acute myocardial infarction (MI) or after remains unclear. The left anterior descending arteries of male Sprague Dawley rats and beagles that developed HF following MI were ligated for 1 week, following which the animals were treated for 4 weeks with low, medium, and high doses of NAD+ and LCZ696...

A subset of patients experiences persistent fatigue symptoms after COVID-19, and patients may develop long COVID, which is characterized by lasting systemic symptoms. No treatments for this condition have been validated and are urgently warranted. In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19...

Nicotinamide adenine dinucleotide (NAD+ ) is the fundamental molecule that performs numerous biological reactions and is crucial for maintaining cellular homeostasis. Studies have found that NAD+ decreases with age in certain tissues, and age-related NAD+ depletion affects physiological functions and contributes to various aging-related diseases. Supplementation of NAD+ precursor significantly elevates NAD+ levels in murine tissues, effectively mitigates metabolic syndrome, enhances cardiovascular health, protects against neurodegeneration, and boosts muscular strength...

C-peptide, a byproduct of insulin synthesis believed to be biologically inert, is emerging as a multifunctional molecule. C-peptide serves an anti-inflammatory and anti-atherogenic role in type 1 diabetes mellitus (T1DM) and early T2DM. C-peptide protects endothelial cells by activating AMP-activated protein kinase α, thus suppressing the activity of NAD(P)H oxidase activity and reducing reactive oxygen species (ROS) generation. It also prevents apoptosis by regulating hyperglycemia-induced p53 upregulation and mitochondrial adaptor p66shc overactivation, as well as reducing caspase-3 activity and promoting expression of B-cell lymphoma-2...

Reversal or mitigation against an age-related decline in NAD+ has likely benefits, and this premise has driven academic and commercial endeavour to develop dietary supplements that achieve this outcome. We used a systems-based approach to improve on current supplements by targeting multiple points in the NAD+ salvage pathway. In a double-blind, randomised, crossover trial, the supplement - Nuchido TIME+® (NT) - increased NAD+ concentration in whole blood. This was associated with an increase in SIRT1 and an increase in nicotinamide phosphoribosyltransferase (NAMPT) in peripheral blood mononucleocytes, lower concentrations of pro-inflammatory cytokines in plasma, including a reduction in interleukin 2 (IL2), a reduction in glycated serum protein and a shift in the glycosylation profile of immunoglobulin G (IgG) toward a younger biological age, all of which are likely to promote a healthier ageing trajectory...

Nicotinamide adenine dinucleotide (NAD) coenzymes are carriers of high energy electrons in metabolism and also play critical roles in numerous signaling pathways. NAD metabolism is decreased in various cardiovascular diseases. Importantly, stimulation of NAD biosynthesis protects against heart disease under different pathological conditions. In this review, we describe pathways for both generation and catabolism of NAD coenzymes and the respective changes of these pathways in the heart under cardiac diseases, including pressure overload, myocardial infarction, cardiometabolic disease, cancer treatment cardiotoxicity, and heart failure...

Abnormal NAD+ signaling has been implicated in axonal degeneration in diabetic peripheral neuropathy (DPN). We hypothesized that supplementing NAD+ precursors could alleviate DPN symptoms through increasing the NAD+ levels and activating the sirtuin-1 (SIRT1) protein. To test this, we exposed cultured Dorsal Root Ganglion neurons (DRGs) to Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN), which increased the levels of NAD+ , the SIRT1 protein, and the deacetylation activity that is associated with increased neurite growth...

BACKGROUND: In heart failure (HF), mitochondrial dysfunction and metabolic remodeling lead to a reduction in energy productivity and aggravate cardiomyocyte injury. Supplementation with α-ketoglutarate (AKG) alleviated myocardial hypertrophy and fibrosis in mice with HF and improved cardiac insufficiency. However, the myocardial protective mechanism of AKG remains unclear. We verified the hypothesis that AKG improves mitochondrial function by upregulating NAD+ levels and activating silent information regulator 2 homolog 1 (SIRT1) in cardiomyocytes...

Aging in mammals is accompanied by an imbalance of intestinal homeostasis and accumulation of mitochondrial DNA (mtDNA) mutations. However, little is known about how accumulated mtDNA mutations modulate intestinal homeostasis. We observe the accumulation of mtDNA mutations in the small intestine of aged male mice, suggesting an association with physiological intestinal aging. Using polymerase gamma (POLG) mutator mice and wild-type mice, we generate male mice with progressive mtDNA mutation burdens. Investigation utilizing organoid technology and in vivo intestinal stem cell labeling reveals decreased colony formation efficiency of intestinal crypts and LGR5-expressing intestinal stem cells in response to a threshold mtDNA mutation burden...