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Nicotinamide Mononucleotide (NMN): Difference between revisions
Nicotinamide Mononucleotide (NMN) (view source)
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While various methods to enhance NMN’s bioavailability are being explored, conclusive evidence on the most effective form or administration method is still emerging. Current research is focused on understanding how different formulations affect NMN's absorption and utilization in the body. Future studies are expected to provide more insights and possibly lead to more effective NMN supplementation strategies. | While various methods to enhance NMN’s bioavailability are being explored, conclusive evidence on the most effective form or administration method is still emerging. Current research is focused on understanding how different formulations affect NMN's absorption and utilization in the body. Future studies are expected to provide more insights and possibly lead to more effective NMN supplementation strategies. | ||
== Controversy about NMN as Direct Precursor == | |||
The primary issue is that 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 '''Nicotinamide Riboside (NR)'''. In that case, NR would hold an edge over NMN because NR would need on conversion less compared to NMN. | |||
=== Direct Transport Mechanism === | |||
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<ref name="ref160">[Source 160]</ref>. However, this notion has faced challenges due to conflicting research findings<ref name="ref161">[Source 161]</ref><ref name="ref162">[Source 162]</ref>, and the functionality of ''Slc12a8'' in humans is yet to be conclusively determined. | |||
=== Dephosphorylation to NR as a Precursor === | |||
An alternative and 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<ref name="ref162">[Source 162]</ref><ref name="ref163">[Source 163]</ref>. 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}}<ref name="ref168">[Source 168]</ref>. | |||
==Potential Benefits== | ==Potential Benefits== | ||