Combined application of NADH and nicotinamide riboside
Nicotinamide adenine dinucleotide (NAD+) is a central cofactor in cells, playing a key role in energy metabolism and the regulation of numerous life processes. NADH, the reduced counterpart of the oxidized form of NAD+, directly drives ATP production via the electron transport chain in mitochondria. The cellular NAD+/NADH ratio determines the cell's redox state and influences the efficiency of metabolic pathways, DNA repair mechanisms, and mitochondrial function. During aging, NAD+ levels gradually decrease in the body, which can be linked to age-related energy deficiency, increased inflammation, and cellular damage. In recent years, there has been significant scientific interest in so-called NAD+ booster molecules—such as nicotinamide riboside (NR) and NADH—as they could potentially slow down the aging process and support the extension of a healthy lifespan by restoring NAD+ levels. This summary reviews the importance of NAD+ in cellular function, the mechanisms of action of NADH and NR separately and in combination, the consequences of age-related NAD+ decline, and the latest research on these compounds in terms of longevity and healthspan. Finally, we discuss practical application methods, dosages, bioavailability, the benefits of combination, and potential risks.
The role of NAD+ in energy metabolism, DNA repair, and sirtuin activity
Energy production:
NAD+ is an essential cofactor for cellular respiration, accepting electrons in glycolysis and the mitochondrial citric acid cycle (reducing to NADH), and then contributing to ATP production by releasing electrons as NADH in the respiratory chain. In mitochondria, NAD+ levels can be a limiting factor: if NAD+ is low, the efficiency of oxidative phosphorylation decreases, and ATP production is reduced. Both NAD+ and mitochondrial concentrations are particularly high in energy-demanding tissues (e.g., brain, muscle).
DNA repair and genomic stability:
NAD+ is a necessary cofactor for the function of DNA repair enzymes, such as poly(ADP-ribose) polymerases (PARPs). PARPs utilize NAD+ to build ADP-ribose chains onto target proteins when DNA breaks are detected and repaired. At low NAD+ levels, PARP activity may decrease, hindering efficient DNA repair and contributing to genomic instability, a fundamental hallmark of aging. Additionally, NAD+ is essential for the function of the sirtuin protein family: sirtuins hydrolyze NAD+ to remove acetyl groups from histones and other proteins, modifying gene expression and supporting stress responses. Particularly, SIRT1 in the nucleus and SIRT3 in the mitochondria are important in anti-aging protective mechanisms—their activity increases with NAD+ levels and influences numerous lifespan-regulating processes (e.g., metabolic regulation, anti-inflammation).
