Abstract
Recent years have seen a surge in research focused on NAD+ decline and potential interventions, and despite significant progress, new discoveries continue to highlight the complexity of NAD+ biology. Nicotinamide mononucleotide (NMN), a well-established NAD+ precursor, has garnered considerable interest due to its capacity to elevate NAD+ levels and induce promising health benefits in preclinical models. Clinical trials investigating NMN supplementation have yielded variable outcomes while shedding light on the intricacies of NMN metabolism and revealing the critical roles played by gut microbiota and specific cellular uptake pathways. Individual variability in factors such as lifestyle, health conditions, genetics, and gut microbiome composition likely contributes to the observed discrepancies in clinical trial results. Preliminary evidence suggests that NMN's effects may be context-dependent, varying based on a person's physiological state. Understanding these nuances is critical for definitively assessing the impact of manipulating NAD+ levels through NMN supplementation. Here, we review NMN metabolism, focusing on current knowledge, pinpointing key areas where further research is needed, and outlining future directions to advance our understanding of its potential clinical significance.