Niagen (nicotinamide riboside) / ChromaDex - LARVOL DELTA

N-DOSE AD: A Dose Optimization Trial of Nicotinamide Riboside in Alzheimer's Disease (clinicaltrials.gov) - P2 | N=80 | Completed | Sponsor: Haukeland University Hospital | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Jun 2025

Trial completion • Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

NAD+ depletion drives age-related monocyte hyperinflammation after stroke and is reversed by nicotinamide riboside. (PubMed, J Neuroinflammation) - No abstract available

Journal • Cardiovascular • Inflammation • Inflammatory Bowel Disease

Preventive and Protective Effects of Nicotinamide Adenine Dinucleotide Boosters in Aging and Retinal Diseases. (PubMed, Int J Mol Sci) - "This review summarizes substantial evidence of therapeutic NAD+ boosters, including nicotinamide, nicotinamide mononucleotide, or nicotinamide riboside...Furthermore, natural products may work together to boost their therapeutic effects against retinal damage. Together, our review article highlights NAD+ metabolism as a potential therapeutic target for addressing retinal degeneration and maintaining vision in aging, neurologic disorders, and various metabolic diseases, including diabetes."

Journal • Review • Age-related Macular Degeneration • CNS Disorders • Diabetes • Diabetic Retinopathy • Inflammation • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders

Randomized, Open-label, Safety Study of Subcutaneous and Intramuscular Injections of Niagen® Plus (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: ChromaDex, Inc.

New P1 trial • Fatigue

Effects of a Gain-of-Function Mutation in the Voltage-Gated Sodium Channel Gene, and of Dietary α-Linolenic Acid Supplementation, on Whole-Body Metabolism in Drosophila. (PubMed, Res Sq) - "Critically, levels of nicotinamide riboside and its derivative nicotinic acid adenine dinucleotide were decreased...Overall, our data indicate that sodium-channel hyperexcitability elicits coordinated metabolic reprogramming that links mitochondrial dysfunction with redox imbalance and interactions between microbiota and immune pathways, and that dietary ALA lessen these changes. The affected pathways represent testable targets for mechanism-based epilepsy interventions."

Journal • CNS Disorders • Epilepsy • Metabolic Disorders

Nicotinamide riboside supplementation restores microglial health and improves cognition in aged male mice. (PubMed, Geroscience) - "This was supported by immunostaining, which showed reduced lipoprotein lipase (LPL), a DAM marker, in the cortex and hippocampus. Overall, NR appeared to mitigate age-related cognitive decline by shifting microglial gene expression and metabolism toward a younger phenotype, suggesting potential therapeutic relevance for healthy brain aging."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • Inflammation • GFAP • LPL

A pilot study of nicotinamide riboside supplementation in allogeneic bone marrow transplantation (ASH 2025) - P1 | "In the human umbilical cord blood setting, nicotinamide-based cell expansiontechnology (NiCord) has been used ex-vivo to expand the number of donor cells, while maintaining theirfunction. We conclude that NR supplementation is safe and well tolerated in alloBMT with dose dependentincreases in NAD+/NADPH levels that preliminarily are associated with more rapid PE and shorter LOS. These findings may have implications for improved resource utilization and cost-effectiveness in alloBMT,which will be further assessed as the trial proceeds to cohort 4."

Clinical • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Pneumonia • Respiratory Diseases • Transplantation • TINCR

Defective mitophagy of CD4+T cells in ITP via NAD+/SIRT1 reduction (ASH 2025) - "Nicotinamide riboside (NR) and a SIRT1 agonist (SRT1720) were administered to ITPCD4+ T cells in vitro to reveal the role of the NAD+/SIRT1 axis in mitophagy deficiency. GSEA revealed that the expression oftype I interferon in ITP CD4+ T cells and the pathways positively regulated by type 1 interferon weresignificantly upregulated, suggesting that mitophagy deficiency may promote the production of type Iinterferons by CD4+ T cells in ITP, thereby participating in the immune imbalance in ITP.ConclusionDefects in the NAD+/SIRT1 axis lead to mitophagy deficiency in ITP CD4+ T cells, resulting in an immuneimbalance in ITP. Targeted correction of the NAD+/SIRT1 axis can regulate CD4+ T-cell differentiationthrough the correction of mitophagy in ITP CD4+ T cells, providing new therapeutic ideas and targets forthe clinical treatment of ITP."

Genetic Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Inflammation • Metabolic Disorders • Thrombocytopenia • Thrombocytopenic Purpura • BST1 • CD4 • PINK1 • SIRT1

Results of the observational program CITOTREK (use of the drug CITOflavin in Tablets) in patients with tension headaches against the backgRound of asthenic syndromE taKing into account comorbidity (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "The results of the study allow us to consider the drug Cytoflavin in the treatment regimens for comorbid patients with TTH in asthenic disorders."

Clinical • Journal • Cardiovascular • CNS Disorders • Depression • Hypertension • Mood Disorders • Pain • Psychiatry • Pulmonary Arterial Hypertension • Sleep Disorder

AGK2 and nicotinamide riboside reveal SIRT2's protective role in a diabetic-dietary rat model of NASH via deacetylation of NLRP3, LKB1, and FOXO3a and restoration of AMPK-ACC/PGC-1α-Nrf2 signaling. (PubMed, Int Immunopharmacol) - "Collectively, these findings identify SIRT2 as an integrative regulator of metabolism and inflammation in NASH, with NLRP3 deacetylation and AMPK-ACC/PGC-1α-Nrf2 restoration as pivotal therapeutic nodes. As no selective activators of SIRT2 are currently available, our results highlight the urgent need to develop such agents for metabolic liver disease."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Diabetes • Dyslipidemia • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus • FOXO3 • IL18 • IL1B • NLRP3 • STK11

Nicotinamide Riboside is Protective in a Mouse Model of Heart Failure with Reduced Ejection Fraction (AHA 2025) - "Similarly, morphometric data showed that NR prevented hypertrophy of the LVPW compared with saline treatment (p=0.008), which was consistent with HW/BW significantly (p=0.007) decreased in TAC/MI+NR compared to TAC/MI mice. TGF-β2, a prototypic pro-fibrotic cytokine central to fibrotic remodeling was overtly elevated in TAC/MI (p<0.001) than TAC/MI+NR mice (p= 0.17) compared to the Sham mice.Our data show for the first time that boosting the NAD+ pool with NR protects mice against systolic dysfunction and hypertrophy in TAC/MI mice, thus necessitating further studies to elucidate underlying mechanisms and facilitate translational potentials."

Preclinical • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Fibrosis • Heart Failure • Hypertension • Metabolic Disorders • Myocardial Infarction • TGFB1

Bendamustine Is Less Toxic Than Fludarabine-Cyclophosphamide-Based Lymphodepletion before CD28-Costimulated CART19 through Reduced Inflammatory Cytokines (ASH 2023) - "We previously demonstrated that bendamustine (Benda) LD is as effective as standard fludarabine and cyclophosphamide (Flu/Cy) LD prior to 4-1BB-costimulated tisagenlecleucel but is characterized by significantly reduced cytokine-release syndrome (CRS), neurotoxicity (ICANS), and hematological toxicities...Both LD regimens induced profound lymphopenia by the time of axi-cel infusion...We also found that NADH and nicotinamide riboside, critical elements for cellular redox balance, were reduced in pts exposed to Flu/Cy LD... In this retrospective comparison, Benda LD is a safer alternative to Flu/Cy for CART19 immunotherapy with similar efficacy and significantly reduced toxicities. Our data can serve as guidance to clinicians for the selection of the best regimen for lymphodepletion. Our conclusions are supported by our mechanistic studies showing reduced inflammatory cytokines after Benda LD."

B Cell Lymphoma • Febrile Neutropenia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • CXCL8 • IL15 • IL2 • IL7

Mitochondrial Transcriptional-Translational Conflict Contributes to Defective Erythropoiesis and Disease Progression in Splicing Factor Mutant Myelodysplastic Syndromes (ASH 2024) - "We screened ROS scavengers (N-acetylcysteine), NAD+ precursor (Nicotinamide Riboside), integrated stress response inhibitor or ESR inhibitor (ISRIB, 4-Phenylbutyric acid), NADPH oxidase inhibitor (Setanaxib), tropomyosin receptor kinase (TRK) inhibitor (Larotrectinib), and translation-associated drugs (A-484954, 4EGI-1) to test whether they can rescue anemia, but unfortunately all of these drugs failed to improve erythropoiesis of mutated cells. In summary, our findings provide insights into the critical role of mitochondrial transcription and translation in governing erythropoiesis via the mTOR signaling pathway. We propose that SF3B1 mutation cause dysfunctional mitochondria and elevated ESR, leading to aberrant mitochondrial translation and impaired protein synthesis, and suggest rapamycin as a potential therapeutic strategy for MDS patients with SF3B1 mutation to alleviate anemia by inhibiting stress-induced mTOR activation."

Acute Myelogenous Leukemia • Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ATF4 • CD34 • SF3B1

Mitochondrial tRNA Pseudouridylation Regulates Erythropoiesis Via the mTOR Signaling Pathway: Implications for Mlasa and Treatment Strategies (ASH 2023) - "Screening of mitochondrial supplements, which could boost mitochondrial function or modulating protein synthesis, revealed that nicotinamide ribose (NR) and mitoquinone (MitoQ) improved mitochondrial function but failed to promote erythroid differentiation in MLASA-iPSCs. In MLASA disease states (right), PUS1 deficiency causes the loss of pseudouridine modifications of specific tRNAs and thus affects the amount of PUS1 targeted tRNAs and its corresponding mitochondrial protein products, leading to mitochondrial dysfunction. The defects resulted in aberrant activation of the mTOR signaling pathway and accelerated global translation rate, ultimately leading to a blockage in erythroid differentiation, which could be relieved with rapamycin treatment."

Anemia • Hematological Disorders • Metabolic Disorders • Myositis

Enzyme Architecture: Activation of Phosphite Dehydrogenase-Catalyzed Hydride Transfer by NAD+ Cofactor Fragments. (PubMed, Biochemistry) - "The ADP and AMP fragments of NAD+ activate PTDH for catalysis of hydride transfer from phosphite to nicotinamide riboside (NR)...By comparison, the activation of formate dehydrogenase- and glycerol phosphate dehydrogenase-catalyzed hydride transfer by ADP is from enzyme interactions with the α-phosphate of ADP, with little or no contribution from the β-phosphate. These results show a diversity in the evolution of enzyme-activating conformational changes for dehydrogenase-catalyzed hydride transfer reactions."

Journal

Low Regimen Therapeutic Strategies to Mitigate TET2 Mutant Clonal Hematopoiesis (ASH 2024) - "In this study, we screened three nontoxic and well tolerated anti-inflammatory molecules (Nicotinamide riboside (NR), Danazol, and Ibuprofen) along with TETi76, a known TET inhibitor that restricts the evolution of TET2MT by inhibiting residual TET-dioxygenase activity. A complete to partial restoration of normal hematopoiesis was observed by TETi76. Our results indicated this low regimen, non-toxic treatment could be a potential option for preventing TET2MT CHIP."

Bone Marrow Transplantation • Hematological Malignancies • Oncology • Respiratory Diseases • ITGAM • PTPRC • TET2

The Effect of Exercise and Nicotinamide Riboside Muscle Health and Insulin Resistance in Survivors of Childhood Cancer (clinicaltrials.gov) - P=N/A | N=20 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Oct 2025 ➔ Sep 2026 | Trial primary completion date: Oct 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Metabolic Disorders • Oncology • Solid Tumor • Type 2 Diabetes Mellitus

Emerald-NRAD: Passive Sensor Identification of Digital Biomarkers to Assess Effects of Orally Administered Nicotinamide Riboside (clinicaltrials.gov) - P=N/A | N=40 | Recruiting | Sponsor: Mclean Hospital | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2025 ➔ May 2026 | Trial primary completion date: Apr 2025 ➔ May 2026

Biomarker • Enrollment open • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Mental Retardation • Psychiatry • APOE

Altered nicotinamide adenine dinucleotide metabolism drives cartilage degeneration and osteoarthritis. (PubMed, Clin Transl Med) - "PARP14 is upregulated in OA cartilage and contributes to NAD⁺ depletion. PARP14 silencing restores NAD⁺ levels and represses OA-related metabolic and matrix-degrading changes. NAD⁺ precursor treatment and NMNAT1 overexpression protect against cartilage degeneration in aging and post-traumatic OA models."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • NAMPT • PARP1

Zn-NR-001: Zinc and Nicotinamide Riboside for Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Cedars-Sinai Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Monocyte-derived mitochondria-containing extracellular vesicles drive inflammation in heart failure (AHA 2025) - "Given the known role of NAD+ in preserving mitochondrial health, we tested nicotinamide riboside (an NAD+ precursor) supplementation in cultured monocytes and in HFrEF patients. These findings identify EV-Mito as a mechanistically distinct and targetable mediator of inflammation in HF. By preventing their release, NAD+ augmentation offers a clinically feasible anti-inflammatory strategy with potential to improve outcomes in HF patients."

IO biomarker • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation • Metabolic Disorders • CD14 • IL1B • TLR9 • TNFA

A Suspected Case of Drug Induced Liver Injury Due to Tongkat Ali (Eurycoma longifolia) (ACG 2025) - "The patient had been taking numerous HDS products since April 2023: resveratrol, niagen (NAD+), L-Tyrosine, creatine, magnesium L-Threonate, Vitamin D3, Vitamin K, inositol, glycine, and tongkat ali (Table 1)...A: Graph demonstrating the downward trend of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (AP) over time. (B): Graph demonstrating the downward trend of total bilirubin levels (mg/dL) over time."

Clinical • Autoimmune Hepatitis • Erectile Dysfunction • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Psychiatry

From Bench to Clinic: The 2024 FASEB Scientific Research Conference on NAD Metabolism and Signaling. (PubMed, Mol Med) - "Given the broad and reaching impact of NAD+ on health, there is significant interest in NAD+ pathway modulation, including through precursors such as nicotinic acid, nicotinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). There is also growing research regarding the heterogeneity among individuals, as well as differences and similarities among the NAD+ precursors, specifically in relation to dosing, timing, and their impact on various health conditions."

Journal

Effects of Nicotinamide Riboside on Bioenergetics and Oxidative Stress in Mild Cognitive Impairment/Alzheimer's Dementia (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Mclean Hospital | Trial completion date: Apr 2025 ➔ Jan 2026 | Trial primary completion date: Apr 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APOE • Aβ42

AN OBSERVATIONAL STUDY OF THE EFFICACY OF A COMBINATION OF INOSINE, NICOTINAMIDE, RIBOFLAVIN, AND SUCCINIC ACID IN PATIENTS WITH ISCHEMIC STROKE NOT TREATED WITH REPERFUSION (WSC 2025) - "Interim analysis supported continuation without changes. Final superiority testing will proceed as planned at α=0.0235. Currently, 24 centers in 7 countries are participating."

Clinical • Observational data • Cardiovascular • Ischemic stroke