Reduced Nicotinamide Mononucleotide (NMNH)

Reduced Nicotinamide Mononucleotide (NMNH) represents a breakthrough in the field of 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. ^[1]

NMNH is synthesized through a specialized method, and it 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.

The potential therapeutic applications of NMNH are extensive, with studies demonstrating its efficacy in reducing cellular damage and expediting repair processes, particularly in renal tubular epithelial cells following hypoxia/reoxygenation injury. This indicates a promising role for NMNH in the treatment of acute kidney injury, showcasing its capacity to contribute positively to cellular health and recovery.

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.

In summary, NMNH emerges as a novel and potent NAD+ precursor, with a unique metabolic pathway and promising therapeutic potential. Its ability to rapidly and significantly increase NAD+ levels across multiple tissues positions it as an exciting new compound in the realm of cellular health and longevity research.

↑ 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] 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] 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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