Niagen (nicotinamide riboside) / ChromaDex - LARVOL DELTA

Differential mitochondrial function drives sex differences in T cell exhaustion (IMMUNOLOGY 2025) - "Treatment with antioxidant (N-acetylcysteine) or mitophagy inducer (nicotinamide riboside) mitigated the sex differences in exhausted phenotype in T cells, suggesting that differences in mitochondria function may be a driver of sex differences in T cell exhaustion. Furthermore, combining anti-PD1 and 4-1BB agonist antibodies, which enhance mitochondrial function in T cells, improved survival of both male and female pre-clinical GBM models. These findings suggest that differential mitochondrial dysfunction drives sex differences in T cell exhaustion, offering a target for sex-specific therapies."

IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Metabolic Disorders • Oncology • Solid Tumor

Comparative analysis of NAD+ boosters reveals the role of liver-nerve axis in metabolic health (EASL 2025) - "In a diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), we compared the metabolic benefits of inhibiting PARP and SARM1 to the benchmark treatment of supplementing the NAD+ precursor nicotinamide riboside (NR). C57BL/6J mice were fed a western-style diet (WD) or chow at thermoneutrality (30°C) for 23 weeks with therapeutic treatment of NR (500 mg/kg/day), SARM1i (60 mg/kg/day), or olaparib (50 mg/kg/day) during the final 14 weeks... These findings suggest that increasing NAD+ levels through SARM1 inhibition alone can lead to comparable or greater metabolic benefits than NR, highlighting the importance of preserving nerve health for these effects. Furthermore, NR supplementation in vitro protects against nerve degeneration. Thus, preserving nerve health, including the function of the hepatic sympathetic nervous system, which is impaired in MASH, is central to the metabolic benefits of NAD+ elevation."

Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Metabolic Impact of Extended Continuous Positive Airway Pressure in Stable Preterm Infants: A Secondary Analysis of a Randomized Controlled Trial (PAS 2025) - "Biochemicals with higher levels (mean 1.67-fold) at p< 0.001 in dCPAP infants included 3 bilirubin metabolites, 3 acylcarnitines, dihydroorotate, spermidine, creatine and deoxycarnitine, and those with lower levels (mean 1.72-fold) included 2-aminoheptanonate (homonorleucine), glucuronate, pregnanediol sulfate, nicotinamide riboside, N1-methyladenosine and N-acetyltheanine... The 33 eCPAP and 31 dCPAP infants had similar GA, birth weight, postnatal age at randomization, sex, race/ethnicity, caloric intake and FRC at day 0, but the increases (%) at day 14 in both FRC (2.1-fold, p=0.005) and weight (1.13-fold, p=0.03) were greater in eCPAP infants (Table). For all infants, levels of 46% of 1101 named blood metabolites differed (p < 0.05) by postnatal age at blood collection, which was adjusted for in the analysis. Levels of 72 metabolites (6.5%) were higher in dCPAP than eCPAP infants and 78 metabolites (7.1%) were lower at p< 0.05."

Clinical • Prematurity • Retinopathy of Prematurity

Novel Molecules Targeting Metabolism and Mitochondrial Function in Cardiac Diseases. (PubMed, Curr Cardiol Rev) - "And finally, we highlight the evidence from in vitro, in vivo, and clinical studies of the cardioprotective effects of drugs that preserve mitochondrial function in CVD. It is hoped that this review may provide new insights into the need to discover new pharmacological targets with direct actions on mitochondria that may provide combined therapeutic strategies to optimally treat these pathologies."

Journal • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Reperfusion Injury • Respiratory Diseases

A Randomized Controlled Trial of Nicotinamide Riboside Supplementation in Early Parkinson's Disease (clinicaltrials.gov) - P3 | N=400 | Active, not recruiting | Sponsor: Haukeland University Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

Study of Nicotinamide Riboside Supplementation in Allogeneic Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Case Comprehensive Cancer Center | Trial completion date: Apr 2026 ➔ Sep 2026 | Trial primary completion date: Apr 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Transplantation

NICO: Effect of Oral NAD+ Precursors Administration on Blood NAD+ Concentration in Healthy Adults (clinicaltrials.gov) - P=N/A | N=68 | Completed | Sponsor: Société des Produits Nestlé (SPN) | Active, not recruiting ➔ Completed

Trial completion

Berberine partially ameliorates cardiolipotoxicity in diabetic cardiomyopathy by modulating SIRT3-mediated lipophagy to remodel lipid droplets homeostasis. (PubMed, Br J Pharmacol) - "Collectively, SIRT3 could moderate cardiac lipotoxicity in DCM by promoting lipophagy, suggesting that the regulation of SIRT3-mediated lipophagy may be a promising strategy for treating DCM. The findings indicate that the therapeutic potential of berberine for DCM is associated with lipophagy."

Journal • Cardiomyopathy • Cardiovascular • Diabetes • Metabolic Disorders • SIRT3

E1231/SR647 Protects Against Unilateral Renal Ischemia-Reperfusion Injury by Modulating SIRT1/FOXO3 Interactions with Nrf2 and NFκB Pathways. (PubMed, Eur J Pharm Sci) - "Furthermore, E1231/SR647 reduced the inflammatory response by inhibiting NFκB activity. In conclusion, E1231/SR647 is a promising therapy that may protect renal function during ischemic events through the modulation of SIRT1/FOXO3 control over Nrf2 and NFκB pathways."

Journal • Acute Kidney Injury • Cardiovascular • Inflammation • Nephrology • Renal Disease • Reperfusion Injury • CST3 • FOXO3 • KIM1 • NQO1 • SIRT1

NAD+ boosting increases atherosclerotic plaques and inflammation in Apoe knockout mice. (PubMed, Atherosclerosis) - "High-dose NR supplementation in mice did not decrease but increase both aortic plaque lesions and systemic inflammation. These effects may be mediated by increased CD38 expression in macrophages, with NAD+ metabolism shifted from sirtuins towards CD38 and PARP1 pathways. Caution should be applied with presumed NAD+ boosters in patients with atherosclerosis."

IO biomarker • Journal • Preclinical • Atherosclerosis • Cardiovascular • Inflammation • Metabolic Disorders • APOE • CD86 • IL6 • SIRT1 • TNFA

Absorption and Tolerability of Injectable Administration of Niagen®+, as Compared to NAD+ (clinicaltrials.gov) - P=N/A | N=70 | Recruiting | Sponsor: Nutraceuticals Research Institute

New trial

Adjuvant pharmacological modulation with Cytoflavin in rehabilitation at stages 2-3 in patients with acute cerebral insufficiency and post-intensive care syndrome (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "To further evaluate the efficacy of Cytoflavin (Inosine+Nicotinamide+Riboflavin+Succinic Acid) in post-intensive care syndrome (PICS) in patients who have suffered ischemic stroke and to present the design of a new prospective study on the rehabilitation of PIC syndrome in patients with acute cerebral insufficiency (ACI). The study is scheduled to be conducted from May 2024 to October 2025. The results of the planned prospective study will clarify the feasibility of including Cytoflavin in clinical recommendations for the treatment of PICS at the stages of rehabilitation treatment."

Journal • Cardiovascular • Critical care • Ischemic stroke

Nicotinamide Riboside Mitigates Retinal Degeneration by Suppressing Damaged DNA-Stimulated Microglial Activation and STING-Mediated Pyroptosis. (PubMed, Invest Ophthalmol Vis Sci) - "These findings suggest that NR confers neuroprotection by attenuating damaged DNA-triggered STING-mediated microglial activation and pyroptosis. Targeting the cGAS-STING pathway presents a promising therapeutic avenue for retinal degeneration."

Journal • Inflammation • Metabolic Disorders • Ophthalmology • STING

Niagen Bioscience Confirms Its Operations Remain Resilient Amid New Tariff Developments (Businesswire) - "Niagen Bioscience, Inc...reaffirms that the manufacturing of its Niagen ingredient (patented nicotinamide riboside or NR) and Tru Niagen and pharmaceutical-grade Niagen products remain resilient amid the recently enacted global tariffs....Manufactured in the U.S. by the Company’s partner, W.R. Grace, Niagen is rigorously tested, encapsulated, bottled, and packaged domestically as Tru Niagen using premium materials. With only a small percentage of materials sourced internationally, the cost to manufacture final Niagen products remains largely insulated from global price volatility."

Commercial • CNS Disorders

SUNRISE: Milk Volume Outcomes Following Oral Nicotinamide Riboside Supplementation in Mothers of Extremely Preterm Infants (clinicaltrials.gov) - P2/3 | N=32 | Recruiting | Sponsor: University of California, Davis | Not yet recruiting ➔ Recruiting

Enrollment open

Mitochondrial and Microtubule Defects in Exfoliation Glaucoma. (PubMed, Free Radic Biol Med) - "Treatment of XFG TFs with a mitophagy inducer, Urolithin A, and a mitochondrial biogenesis inducer, Nicotinamide Ribose, improved mitochondrial bioenergetics and reduced ROS accumulation. Our results demonstrate that XFG TFs have abnormal mitochondria and suggest that mitophagy inducers may represent a potential class of therapeutics for reversing mitochondrial dysfunction in XFG patients."

Journal • CNS Disorders • Glaucoma • Metabolic Disorders • Ophthalmology • Targeted Protein Degradation

Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation. (PubMed, Aging (Albany NY)) - "In line with this, NAD+ augmentation, via supplementation with nicotinamide riboside, reduces senescence and improves mitochondrial metabolic profiles in MSCs with WRN knockout (WRN-/-) and in primary fibroblasts derived from WS patients compared to controls...However, restoration of mitochondrial or cellular NAD+ is not sufficient to reinstall cellular proliferation in immortalized cells with siRNA-mediated knockdown of WRN, highlighting an indispensable role of WRN in proliferation even in an NAD+ affluent environment. Further cell and animal studies are needed to deepen our understanding of the underlying mechanisms, facilitating related drug development."

Journal • Metabolic Disorders • NAMPT • WRN

COMBINING D-BETA -HYDROXYBUTYRATE (DBHB) AND NICOTINAMIDE RIBOSIDE (NR) WITH EXERCISE IMPROVES BRAIN ENERGETICS IN PARKINSON'S (PD) DISEASE: RESULTS OF A PILOT STUDY (ADPD 2025) - P=N/A | "This pilot study provides three novel features of brain energy metabolism in PD: (i) a possible improvement in energy metabolism by the Substantia Nigra, (ii) increased ketone uptake on DBHB+NR alone, (iii) 50% higher plasma ketones and brain ketone uptake with DBHB+NR+Ex vs. DBHB+NR alone."

Clinical • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Beneficial effects of mitophagy enhancers on amyloid beta-induced mitochondrial and synaptic toxicities in Alzheimer's disease. (PubMed, Mitochondrion) - "This study determined the optimal doses of four mitophagy enhancers-Urolithin A (UA), actinonin, tomatidine, and nicotinamide riboside (NR)-using immortalized mouse hippocampal (HT22) neurons...Notably, UA demonstrated the most robust mitigating effects. These findings underscore the therapeutic potential of mitophagy enhancers, particularly UA, as promising candidates to treat mitochondrial and synaptic dysfunctions in AD."

Journal • Alzheimer's Disease • CNS Disorders • Metabolic Disorders • APP

NRII: Mechanistic Studies of Nicotinamide Riboside in Human Heart Failure (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: University of Washington | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2025 ➔ Nov 2024

Enrollment closed • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders

N-DOSE AD: a Dose Optimization Trial of Nicotinamide Riboside in Alzheimer's Disease (clinicaltrials.gov) - P2 | N=80 | Active, not recruiting | Sponsor: Haukeland University Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2025 ➔ Oct 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

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

Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice. (PubMed, Pharmaceuticals (Basel)) - " NMN and NR improve dyslipidemia and fatty liver but promote atherosclerosis in ApoE-/- mice. These findings emphasize the safe dosage for the clinical trials of NMN."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • APOE

Establishing a novel pathway for the biosynthesis of nicotinamide mononucleotide. (PubMed, Enzyme Microb Technol) - "An optimized in vitro multi-enzyme cascade (XapA/PNP/NRK, PPM, NRK) identified NRK as the most efficient catalyst for NMN biosynthesis from D-ribose and niacinamide. In Escherichia coli, overexpression of this cascade, knockout of competing pathways, and secretion enhancement via a pelB signal peptide-fused PnuC transporter achieved an NMN titer of 62.0 mg L-¹ .This work provides a viable alternative for the biosynthesis of NMN."

Journal

Niagen Bioscience Secures U.S. Patent for the Composition of Matter for Nicotinamide Riboside (NR) Salt Forms (Businesswire) - "Niagen Bioscience, Inc...today announced the broadening of its NAD+ precursor intellectual property (IP) portfolio with the newly granted U.S. Patent 12,252,506, which covers the composition of matter for nicotinamide riboside (NR) salt forms, including NR Malate and NR Tartrate, and other NR derivatives. This is part of a family of patents covering methods of making NR and related derivatives, some of the most efficient NAD+ precursors available, which Niagen Bioscience has through an exclusive license from Queen’s University Belfast (QUB)....This patent will provide Niagen Bioscience protection for various NR and NR triacetate salt forms until 2034. U.S. Patent 12,252,506..."

Patent • Immunology

Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD+ synthesis via enterohepatic circulation. (PubMed, Sci Adv) - "Thus, enterohepatic circulated NA is preferentially used in the liver. These findings showed that NMN and NR are indirectly converted to NAD+ via unexpected metabolic pathways."

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