RESUMEN
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.
RESUMEN
Ketone bodies are small compounds derived from fatty acids that behave as an alternative mitochondrial energy source when insulin levels are low, such as during fasting or strenuous exercise. In addition to the metabolic function of ketone bodies, they also have several signaling functions separate from energy production. In this perspective, we review the main current data referring to ketone bodies in correlation with nutrition and metabolic pathways as well as to the signaling functions and the potential impact on clinical conditions. Data were selected following eligibility criteria accordingly to the reviewed topic. We used a set of electronic databases (Medline/PubMed, Scopus, Web of Sciences (WOS), Cochrane Library) for a systematic search until July 2022 using MeSH keywords/terms (i.e., ketone bodies, BHB, acetoacetate, inflammation, antioxidant, etc.). The literature data reported in this review need confirmation with consistent clinical trials that might validate the results obtained in in vitro and in vivo in animal models. However, the data on exogenous ketone consumption and the effect on the ketone bodies' brain uptake and metabolism might spur the research to define the acute and chronic effects of ketone bodies in humans and pursue the possible implication in the prevention and treatment of human diseases. Therefore, additional studies are required to examine the potential systemic and metabolic consequences of ketone bodies.