Nicotinamide Riboside-The Current State of Research and Therapeutic Uses

Mario Mehmel, Nina Jovanović, Urs Spitz, Mario Mehmel, Nina Jovanović, Urs Spitz

Abstract

Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD+) precursors, due to its numerous potential health benefits mediated via elevated NAD+ content in the body. NAD+ is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD+ precursors.

Keywords: COVID-19; age-associated diseases; bioavailability; metabolic disorders; nicotinamide adenine dinucleotide; nicotinamide riboside; safety; supplementation.

Conflict of interest statement

The authors declare the following competing financial interest(s): M.M and U.S. are employees of the Biosynth Carbosynth group, a corporation that sells various nicotinamide riboside derivatives. U.S. acknowledges that he has intellectual property related to methods to produce NR salts and possible uses thereof. Royalties on sales of NR are expected to accrue to U.S. as inventor. No further conflicts of interest are declared.

Figures

Figure 1
Figure 1
NAD+ synthesis pathways. The figure depicts NAD+ de novo pathway from tryptophan (Trp) through quinolinic acid (QA), Preiss–Handler pathway from nicotinic acid (NA) via nicotinic acid adenine dinucleotide (NAAD) and NAD synthetase (NADS), and “salvage pathways” from nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) via purine nucleoside phosphorylase (NP) and nicotinamide phosphoribosyltransferase (NAMPT) enzymes or nicotinamide ribose kinases (NRK) and NMN/NaMN adenylyltransferases (NMNAT), respectively.
Figure 2
Figure 2
Activation of the NMRK2 pathway represent a common adaptive mechanism in the failing heart where NAD+ levels are low. NAD+ synthesis from NR through the NMRK2 pathway may be favored, as the NMN synthesis from NR by NMRK enzymes requires only one ATP molecule while synthesis from NAM by NAMPT requires at least three ATP equivalents.

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