Reduced Nicotinamide Mononucleotide (NMNH): Difference between revisions

Revision as of 20:58, 1 November 2023

Reduced Nicotinamide Mononucleotide (NMNH) represents a novel NAD+ precursors, offering a promising alternative to the more commonly known compounds such as Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR). Unlike these precursors, NMNH exhibits a remarkable ability to elevate NAD+ levels in cells more effectively and at a faster rate in mice. NMNH operates via a unique metabolic pathway that is independent of the enzymes NRK (Nicotinamide Riboside Kinase) and NAMPT (Nicotinamide Phosphoribosyltransferase). This distinct mechanism not only sets NMNH apart from other NAD+ precursors but also contributes to its heightened efficacy in boosting NAD+ levels within cells. When administered to mice, NMNH has shown a rapid and sustained increase in NAD+ levels across a variety of tissues including the liver, kidney, muscle, brain, brown adipose tissue, and heart. Interestingly, this effect was not observed in white adipose tissue. This broad-spectrum increase in NAD+ levels underscores the potential of NMNH as a robust and efficient NAD+ precursor, offering new possibilities for its application in health and longevity research. ^[1]

References

↑ Zapata-Pérez R et al.: Reduced nicotinamide mononucleotide is a new and potent NAD⁺ precursor in mammalian cells and mice. FASEB J 2021. (PMID 33724555) [PubMed] [DOI] Abstract
Nicotinamide adenine dinucleotide (NAD+ ) homeostasis is constantly compromised due to degradation by NAD+ -dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.

[pmid33724555-1] Zapata-Pérez R et al.: Reduced nicotinamide mononucleotide is a new and potent NAD⁺ precursor in mammalian cells and mice. FASEB J 2021. (PMID 33724555) [PubMed] [DOI] Abstract
Nicotinamide adenine dinucleotide (NAD+ ) homeostasis is constantly compromised due to degradation by NAD+ -dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.

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 == References ==
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 [[Category:Orally Consumable Longevity Molecules]]