NAD+ Forums

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.

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.

https://www.sciencedirect.com/science/a ... 7819309160

I was just going to post this ^^. Great find.

Here is the previous study on NRH:

"Dihydronicotinamide riboside is a potent NAD+
concentration enhancer in vitro and in vivo"

"NR and NMN require large dosages for effect. Herein we describe synthesis of dihydronicotinamide riboside (NRH) and the discovery that NRH is a potent NAD+ concentration enhancing agent, which acts within as little as 1 hr after administration to mammalian cells to increase NAD+ concentrations by 2.5-10 fold over control values.

Comparisons to NR and NMN show that in every instance NRH provides greater NAD+ increases at equivalent concentrations. NRH also provides substantial NAD+ increases in tissues when administered by intraperitoneal injection to C57BL/6J mice.

NRH substantially increases NAD+/NADH ratio in cultured cells and in liver, and no induction of apoptotic markers or significant increases in lactate levels in cells. Cells treated with NRH are resistant to cell death caused by NAD+-depleting genotoxins such as hydrogen peroxide and methylmethane sulfonate.

Studies to identify its biochemical mechanism of action showed that it does not inhibit NAD+ consumption suggesting it acts as a biochemical precursor to NAD+. Cell lysates possess an ATP-dependent kinase activity which efficiently converts NRH to the compound NMNH, but independent of Nrk1 or Nrk2.

These studies identify a putative new metabolic pathway to NAD+, and a potent pharmacologic agent for NAD+ concentration enhancement in cells and tissues."

http://www.jbc.org/content/early/2019/0 ... 2.full.pdf