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Acute, short-term inflammation is essential to the body's healing process. Chronic, long-term inflammation is actually harmful. Some human clinical studies show that replenishing NAD levels reduces inflammation.

ARTICLE: Can NAD Reduce Chronic Inflammation?


Here are the studies:

Sep 19, 2023

Skin - Inflammation - Psoriasis - Immunity

Cell Reports Medicine

Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects

Han, Kim


NR supplementation blunts Th1 and Th17 immune responsiveness in healthy volunteers and in psoriasis...This study has expanded our understanding of NAD+ boosting in the adaptive immune system with the focus on NR blunting Th17 immune activity...The finding from this study that NR blunts Th1 and Th17 immune responsiveness in an ex vivo study supports that the utilization of NAD+ boosting could potentially be employed as a supplemental therapy in this disease. The concept is now being explored in vivo, where mild to moderate psoriasis patients are being investigated in a placebo-controlled study...

Aug 17, 2023

Neurons - Inflammation

Frontiers in Cellular Neuroscience

Nicotinamide enhances myelin production after demyelination through reduction of astrogliosis and microgliosis

Kaplanis, Stefanos loannis


Overall, we show that the increased myelin production that follows NAM treatment in vivo is accompanied by a decrease in both astrocyte and microglia accumulation at the lesion site. Our data indicate that NAM influences astrocytes and microglia directly, in favor of the remyelination process by promoting a less inflammatory environment.

Aug 14, 2023

Stem cells - Inflammation - Liver - Digestion - IBD

Cellular & Molecular Immunology

NAD+ salvage governs the immunosuppressive capacity of mesenchymal stem cells

Fang, Jiankai


This study demonstrated that...NAD+ metabolism governs the anti-inflammatory function of mesenchymal stem cells during inflammation.

Aug 1, 2023

Inflammation - Diabetes - Kidney

Journal of Biological Chemistry

NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease

Myakala, Komuraiah


Diabetes mellitus is the leading cause of cardiovascular and renal disease in the United States...Overall, these data show that NR supplementation boosted NAD metabolism to augment mitochondrial function, reducing inflammation and thereby preventing the progression of diabetic kidney disease.

Jul 24, 2023

Bone - Arthritis - Mitochondria - Inflammation

Molecular and Cellular Biochemistry

The role and intervention of mitochondrial metabolism in osteoarthritis

Qi, Zhanhai


Recent studies have revealed the significant contribution of mitochondrial dysfunction and disrupted energy metabolism to the pathogenesis of osteoarthritis. Impaired mitochondrial function leads to the accumulation of reactive oxygens species, which contribute to cartilage degradation and chondrocyte apoptosis...Compounds capable of modulating mitochondrial metabolism and improving mitochondrial function, such as nicotinamide riboside and pyrroloquinoline quinone, have also been investigated in the context of osteoarthritis. These compounds promote mitochondrial biogenesis, enhance mitochondrial respiration, and reduce oxidative stress and inflammation in chondrocytes, ultimately preserving the integrity of the cartilage matrix...

Jul 9, 2023

Diabetes - Inflammation - Neurons


Nicotinamide Prevents Diabetic Brain Inflammation via NAD+-Dependent Deacetylation Mechanisms

Torres-Méndez, Jeimy Katherine


NAM supplementation prevented brain inflammation and microglial activation inthe brains of diabetic mice.

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


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.

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


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


...We found that NR supplementation could ameliorate high-fructose-induced lipid metabolism disorder by improving FGF21 resistance in the liver and WAT, which may be related to the regulation of inflammation mediated by the SIRT1/NF-κB signaling pathway.

Oct 17, 2022

Kidney - Inflammation - Diabetes

Journal of Biological Chemistry

NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease

Myakala, Komuraiah


Our data showed that NR supplementation boosted the NAD metabolism to modulate inflammation and mitochondrial function and prevent progression of diabetic kidney disease.

Jun 14, 2022


Current Developments in Nutrition

The Clinical Effects of Nicotinamide Riboside on Inflammatory Parameters

Kwon, Jun


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...

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


...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.

Mar 1, 2022

Immunity - Lupus - Inflammation

Journal of Clinical Investigation

Boosting NAD+ Blunts Toll-Like Receptor-4 Induced Type-I Interferon in Control and Systemic Lupus Erythematosus Monocytes

Wu, Jing


Fasting and NAD+-boosting compounds, including NAD+ precursor nicotinamide riboside (NR), confer antiinflammatory effects. However, the underlying mechanisms and therapeutic potential are incompletely defined. We explored the underlying biology in myeloid cells from healthy volunteers following in vivo placebo or NR administration and subsequently tested the findings in vitro in monocytes extracted from patients with systemic lupus erythematosus (SLE)...We conclude that NR, in an NAD+-dependent manner and in part via inosine signaling, mediated suppression of autophagy and attenuated type I IFN in myeloid cells, and we identified NR as a potential adjunct for systemic lupus erythematosus management.

Sep 21, 2021

Aging - Brain - Ataxia - Stem Cells - Bone Marrow - Inflammation

Aging Cell

NAD+ augmentation with nicotinamide riboside improves lymphoid potential of Atm−/− and old mice HSCs

Zong, Le


Our data suggest that NR administration in compromised hematopoietic systems (NAD+ depleted system) drives cell-intrinsic changes of the HSC compartment together with an overall reduction in circulating inflammatory cytokines. However, once the aged system has been exposed to NR, the effects of removing the supplementation may have undesirable consequences. Thus, once a deficient system is exposed to NAD+ supplementation, to maintain the benefits we have demonstrated, the regimen may need to be sustained long-term...Our results showed significant alterations in lineage commitment of HSCs after NR treatment, with enhanced lymphoid potential. This correlated with changes in inflammatory cytokines and transcriptional alterations of the HSCs. While transplantation of aged NR-treated HSCs reproduced the enhanced lymphoid output seen in the transcriptional profiles, the changes in potential are not sustained after NR withdrawal in the aged mice, and the rebound phenotype appear to exacerbate aging phenotypes. Our results highlight the importance of the duration of NR exposure and the timing of initial exposure to derive robust, balanced lineage outputs from HSCs.

May 9, 2021

Brain - Neuroinflammation

Journal of Neurochemistry

Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide-induced microglial and astrocytic neuroinflammation by increasing NAD+

Roboon, Jureepon


Neuroinflammation is initiated by activation of the brain’s innate immune system in response to an inflammatory challenge. Insufficient control of neuroinflammation leads to enhanced or prolonged pathology in various neurological conditions including multiple sclerosis and Alzheimer’s disease. Nicotinamide adenine dinucleotide (NAD+) plays critical roles in cellular energy metabolism and calcium homeostasis. Our previous study demonstrated that deletion of CD38, which consumes NAD+, suppressed cuprizone-induced demyelination, neuroinflammation and glial activation. However, it is still unknown whether CD38 directly affects neuroinflammation through regulating brain NAD+ level...These results suggest that CD38-mediated neuroinflammation is linked to NAD+ consumption and that boosting NAD+ by CD38 inhibition and NR supplementation directly suppress neuroinflammation in the brain.

Nov 16, 2020

Inflammation - Aging

Nature Metabolism

Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages

Covarrubias, Anthony J.


These results link the accumulation of senescent cells with age to the age-related NAD decline…Our study demonstrates that increased expression of CD38 in macrophages is an important source of increased NADase activity during ageing.

Oct 12, 2020

Heart / Vascular - Inflammation

Journal of Clinical Investigation

Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure

Zhou, Bo


While mitochondria play an important role in innate immunity, the relationship between mitochondrial dysfunction and inflammation in heart failure is poorly understood. In this study we aimed to investigate the mechanistic link between mitochondrial dysfunction and inflammatory activation in peripheral blood mononuclear cells (PBMCs), and the potential antiinflammatory effect of boosting the NAD level. ...Oral nicotinamide riboside (NR) administration enhanced PBMC respiration and reduced proinflammatory cytokine gene expression in 4 subjects with heart failure. These findings suggest that systemic inflammation in patients with heart failure is causally linked to mitochondrial function of the PBMCs. Increasing NAD levels may have the potential to improve mitochondrial respiration and attenuate proinflammatory activation of PBMCs in heart failure.

Mar 19, 2020

Inflammation - Metabolism - Bioavailability

Frontiers in Oncology

NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

Audrito, Valentina


Extracellular NAD is degraded by three main classes of specific ectoenzymes: CD38 and CD157, ARTs, ENPP1 and CD73. NADase, ENPP1 and CD73 can lead to the formation of adenosine (ADO), a potent immunosuppressant factor, independently of the activity of CD39. Beside generating ADO, eNAD can be degraded to nicotinamide mononucleotide (NMN) by CD38, generating Nam which can cross plasma membranes and be re-converted to NAD through NAMPT and NMN adenylyltransferase (NMNAT)...

Sep 11, 2019

Immunity - Inflammation

Nature Communications

Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation

Manago, Antonella


Damage-associated molecular patterns (DAMPs) are molecules that can be actively or passively released by injured tissues and that activate the immune system. Here we show that nicotinate phosphoribosyltransferase (NAPRT), detected by antibody-mediated assays and mass spectrometry, is an extracellular ligand for Toll-like receptor 4 (TLR4) and a critical mediator of inflammation, acting as a DAMP. Exposure of human and mouse macrophages to NAPRT activates the inflammasome and NF-κB for secretion of inflammatory cytokines. Furthermore, NAPRT enhances monocyte differentiation into macrophages by inducing macrophage colony-stimulating factor. These NAPRT-induced effects are independent of NAD-biosynthetic activity, but rely on NAPRT binding to TLR4. In line with our finding that NAPRT mediates endotoxin tolerance in vitro and in vivo, sera from patients with sepsis contain the highest levels of NAPRT, compared to patients with other chronic inflammatory conditions. Together, these data identify NAPRT as a endogenous ligand for TLR4 and a mediator of inflammation.

Aug 13, 2019

Muscle - Inflammation

Cell Reports

Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD(+) Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures

Elhassan, Yasir


...We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome and if it can alter muscle mitochondrial bioenergetics...Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR.

NAD Research - Inflammation

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