NAD+ ⇒ A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+

[daviddean]

A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor

Molecular Metabolism - Volume 30, December 2019, Pages 192-202
Judith Giroud-Gerbetant, Magali Joffraud, Maria PilarGiner et al.

Highlights
• A reduced form of nicotinamide riboside (NRH) is a potent NAD+ precursor in cultured cells and mouse tissues.

• NRH leads to NAD+ synthesis through a new, independent path to that of NR.

• NRH is orally bioavailable and not degraded in plasma.

• NRH alleviates cisplatin-induced acute kidney injury.

A decay in intracellular NAD+ levels is one of the hallmarks of physiological decline in normal tissue functions. Accordingly, dietary supplementation with NAD+ precursors can prevent, alleviate, or even reverse multiple metabolic complications and age-related disorders in diverse model organisms. Within the constellation of NAD+ precursors, nicotinamide riboside (NR) has gained attention due to its potent NAD+ biosynthetic effects in vivo while lacking adverse clinical effects. Nevertheless, NR is not stable in circulation, and its utilization is rate-limited by the expression of nicotinamide riboside kinases (NRKs). Therefore, there is a strong interest in identifying new effective NAD+ precursors that can overcome these limitations.

Methods
Through a combination of metabolomics and pharmacological approaches, we describe how NRH, a reduced form of NR, serves as a potent NAD+ precursor in mammalian cells and mice.

Results
NRH acts as a more potent and faster NAD+ precursor than NR in mammalian cells and tissues. Despite the minor structural difference, we found that NRH uses different steps and enzymes to synthesize NAD+, thus revealing a new NRK1-independent pathway for NAD+ synthesis. Finally, we provide evidence that NRH is orally bioavailable in mice and prevents cisplatin-induced acute kidney injury.

Conclusions
Our data identify a new pathway for NAD+ synthesis and classify NRH as a promising new therapeutic strategy to enhance NAD+ levels.

Link to the study (pdf available)
https://www.sciencedirect.com/science/a ... 7819309160

[Fred]

Thank you Daviddean. Perhaps you can move this to the "NR"-section of the forum since it involves nicotinamide riboside (NR), albeit in the reduced form?

It will be easier to find for those using the search function in the future. Thanks.

EDIT: nevermind. AlbertY already posted it in the NR section.

[daviddean]

Thank you Fred, I didn't see it before. This Forum is growing faster and is difficult to check all posts.
David

[Fred]

Thank you Fred, I didn't see it before. This Forum is growing faster and is difficult to check all posts.
David

I understand, it's the same for me. Double-posts will be unavoidable but posting in the right section helps everyone in any case. Thanks.