ArticlePloS one2020
Dihydronicotinamide riboside promotes cell-specific cytotoxicity by tipping the balance between metabolic regulation and oxidative stress.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Therapeutic potential of dihydronicotinamide riboside (NRH) on obesity and glucose intolerance in mice.Nature communications · 2026Article
- Reduced Versus Oxidized NADFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- NAD+ Boosting Through NRH Supplementation Enhances Treatment Efficacy in EOC In Vitro.International journal of molecular sciences · 2025Article
- Article
- Supplementation with NAD+ and its precursors: A rescue of female reproductive diseases.Biochemistry and biophysics reports · 2024Review
- Nicotinamide Mononucleotide Supplementation: Understanding Metabolic Variability and Clinical Implications.Metabolites · 2024Review
- A tipping point in dihydroxyacetone exposure: mitochondrial stress and metabolic reprogramming alter survival in rat cardiomyocytes H9c2 cells.Chemico-biological interactions · 2024Article
- Synthesis, Detection, and Metabolism of Pyridone Ribosides, Products of NAD Overoxidation.Chemical research in toxicology · 2024Article
- Targeting NAD Metabolism for the Therapy of Age-Related Neurodegenerative Diseases.Neuroscience bulletin · 2024Review
- Specific quinone reductase 2 inhibitors reduce metabolic burden and reverse Alzheimer's disease phenotype in mice.The Journal of clinical investigation · 2023Article
- Defining NAD(P)(H) Catabolism.Nutrients · 2023Review
- Balancing NADCellular and molecular life sciences : CMLS · 2022Review
- Synthesis of Mixed Dinucleotides by Mechanochemistry.Molecules (Basel, Switzerland) · 2022Article
- Measurement of NQO2 Catalytic Activity and of Its Inhibition by Melatonin.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Dihydronicotinamide Riboside Is a Potent NADFrontiers in immunology · 2022Article
- Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells.PloS one · 2022Article
- Nicotinamide adenine dinucleotide and the sirtuins caution: Pro-cancer functions.Aging medicine (Milton (N.S.W)) · 2021Review
- Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NADCell reports · 2021Article
- Evolving concepts in NADCell metabolism · 2021Review
- Chemical and Biochemical Reactivity of the Reduced Forms of Nicotinamide Riboside.ACS chemical biology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Nicotinamide adenine dinucleotide (NAD+), the essential cofactor derived from vitamin B3, is both a coenzyme in redox enzymatic processes and substrate in non-redox events; processes that are intimately implicated in all essential bioenergetics. A decrease in intracellular NAD+ levels is known to cause multiple metabolic complications and age-related disorders. One NAD+ precursor is dihydronicotinamide riboside (NRH), which increases NAD+ levels more potently in both cultured cells and mice than current supplementation strategies with nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) or vitamin B3 (nicotinamide and niacin). However, the consequences of extreme boosts in NAD+ levels are not fully understood. Here, we demonstrate the cell-specific effects of acute NRH exposure in mammalian cells. Hepatocellular carcinoma (HepG3) cells show dose-dependent cytotoxicity when supplemented with 100-1000 μM NRH. Cytotoxicity was not observed in human embryonic kidney (HEK293T) cells over the same dose range of NRH. PUMA and BAX mediate the cell-specific cytotoxicity of NRH in HepG3. When supplementing HepG3 with 100 μM NRH, a significant increase in ROS was observed concurrent with changes in the NAD(P)H and GSH/GSSG pools. NRH altered mitochondrial membrane potential, increased mitochondrial superoxide formation, and induced mitochondrial DNA damage in those cells. NRH also caused metabolic dysregulation, altering mitochondrial respiration. Altogether, we demonstrated the detrimental consequences of an extreme boost of the total NAD (NAD+ + NADH) pool through NRH supplementation in HepG3. The cell-specific effects are likely mediated through the different metabolic fate of NRH in these cells, which warrants further study in other systemic models.
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