Nicotinamide Mononucleotide (NMN): Difference between revisions

NMN is often advertiezed, e.g. by NMN suppliers, that NMN is a direct precursor to NAD+ that thus be more effective compared to other precursors like '''Nicotinamide Riboside (NR)'''. However, NMN's role as a direct precursor is effective only when it is '''inside the cell'''. This raises questions about how NMN, when ingested or administered externally, enters the cell to contribute to NAD+ synthesis. The central controversy surrounding NMN as a precursor to NAD+ lies in its mechanism of cellular entry. While NMN is a direct precursor of NAD+ within the cell, the debate focuses on whether NMN can be directly absorbed by cells or if it must first be converted to NR. In that case, NR would hold an edge over NMN because NR would need on conversion less compared to NMN.  

One hypothesis is that NMN can directly enter cells through specific transporters. The ''Slc12a8'' transporter in the aged mouse ileum is an example, suggested to facilitate NMN's direct absorption{{pmid|31131364}}. However, this notion has faced challenges due to conflicting research findings{{pmid|32694648}}{{pmid|27725675}}, and the functionality of ''Slc12a8'' in humans is yet to be conclusively determined.

An alternative and currently more widely accepted theory proposes that NMN is not directly used by cells. Instead, it is first converted to '''Nicotinamide Riboside (NR)''' through dephosphorylation before cellular absorption. This conversion is mediated by ectonucleotidases like CD73. Upon entry into the cell as NR via equilibrative nucleoside transporters (ENT1, ENT2, and ENT4), it is phosphorylated into NMN{{pmid|27725675}}{{pmid|32389638}}. Studies, such as those by Kim et al., indicate that orally ingested NMN is predominantly converted to NR in intestinal tissue before absorption, challenging the direct precursor role of NMN{{pmid|37463842}}.