Significance: Nicotinamide adenine dinucleotide (NADH) represents the reduced form of NAD+, and together they constitute the two forms of the nicotinamide adenine dinucleotide whose balance is named as the NAD+/NADH ratio. NAD+/NADH ratio is mainly involved in redox reactions since both the molecules are responsible forcarrying electrons to maintain redox homeostasis. Recent Advances: NADH acts as a reducing agent, and one of the most known processes exploiting NADH function is energy metabolism. The two main pathways generating energy and involving NADH are glycolysis and oxidative phosphorylation, occurring in cell cytosol and in the mitochondrial matrix, respectively. Critical Issues: Although NADH is primarily produced through the reduction of NAD+ and consumed by its own oxidation, several are the biosynthetic and consumption pathways, reflecting the NADH role in multiple cellular processes. This review gathers all the main current data referring to NADH incorrelation with metabolic and cellular pathways, such as its coenzyme activity, effect in cell death, and on modulating redox and calcium homeostasis. Future Directions: Gene expression control, as well as the potential impact on neurodegenerative, cardiac disorders and infections, suggest NADH application in clinical settings.Thorough clinical trials and continued investigation into the long-term impacts of NADH are crucial to validate its effectiveness and safety, thereby facilitating its wider acceptance as a therapeutic option in medical practice.
Keywords: NAD+/NADH ratio; NADH; aging; metabolism; redox.