Nicotinamide Riboside and Dihydronicotinic Acid Riboside Synergistically Increase Intracellular NAD+ by Generating Dihydronicotinamide Riboside

Abstract

Through evolution, eukaryote organisms have developed the ability to use different molecules as independent precursors to generate nicotinamide adenine dinucleotide (NAD+), an essential molecule for life. However, whether these different precursors act in an additive or complementary manner is not truly well understood. Here, we have evaluated how combinations of different NAD+ precursors influence intracellular NAD+ levels. We identified dihydronicotinic acid riboside (NARH) as a new NAD+ precursor in hepatic cells. Second, we demonstrate how NARH, but not any other NAD+ precursor, can act synergistically with nicotinamide riboside (NR) to increase NAD+ levels in cultured cells and in mice. Finally, we demonstrate that the large increase in NAD+ prompted by the combination of these two precursors is due to their chemical interaction and conversion to dihydronicotinamide riboside (NRH). Altogether, this work demonstrates for the first time that NARH can act as a NAD+ precursor in mammalian cells and how different NAD+ precursors can interact and influence each other when co-administered.

An Axis between the Long Non-Coding RNA HOXA11-AS and NQOs Enhances Metastatic Ability in Oral Squamous Cell Carcinoma

“…NQO2 differs from NQO1 in that it requires NRH as a coenzyme [10]. NRH is a precursor of NAD [37] and increases intracellular NAD levels [38,39]. Our experiments showed that an increase in NQO2 following HOXA11-AS knockdown resulted in a decrease in NAD concentration.…”

NAD+ Metabolism and Interventions in Premature Renal Aging and Chronic Kidney Disease

“…NAD + is present in the kidney at concentrations ranging from 0.3 to 1 mmol/kg of tissue, which is comparable to concentrations found in liver and muscle [22,26,27]. In this section, we detail the NAD + biosynthetic pathways from different precursors in PTECs, and describe its cellular roles in renal tissue, before explaining the alterations in NAD + homeostasis occurring during premature renal aging and CKD.…”

“…NMNH has also been shown to increase NAD + levels after a dephosphorylation step to NRH prior to its incorporation into the intracellular space [54]. A final reduced precursor, dihydronicotinic acid riboside (NARH) can act synergistically with nicotinamide riboside (NR) to increase NAD + through their conversion to NRH [26]. The greater effectiveness of NRH compared to NR as an NAD + booster could be based on both the higher enzymatic phosphorylation rate of AK compared to NRK1, and the fact that NRH is not or less degraded to NAM in plasma, which is the case for NR [27].…”

Supplementation with NAD+ and its precursors: A rescue of female reproductive diseases

“…NRH is a reduced form of NR, a new and very efficient fifth pathway for NAD + synthesis. Unlike NR, which is phosphorylated to NMN by Nrk, NRH is phosphorylated by adenosine kinase (AK) and converted to NMNH and subsequently to NADH and NAD + [ 26 , 27 ]. NRH can improve mitochondrial function and regulate oxidative stress [ 28 ].…”