NAD+ Precursors Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR): Potential Dietary Contribution to Health

Abstract

Purpose of review: NAD+ is a vital molecule that takes part as a redox cofactor in several metabolic reactions besides being used as a substrate in important cellular signaling in regulation pathways for energetic, genotoxic, and infectious stress. In stress conditions, NAD+ biosynthesis and levels decrease as well as the activity of consuming enzymes rises. Dietary precursors can promote NAD+ biosynthesis and increase intracellular levels, being a potential strategy for reversing physiological decline and preventing diseases. In this review, we will show the biochemistry and metabolism of NAD+ precursors NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide), the latest findings on their beneficial physiological effects, their interplay with gut microbiota, and the future perspectives for research in nutrition and food science fields.

Recent findings: NMN and NR demonstrated protect against diabetes, Alzheimer disease, endothelial dysfunction, and inflammation. They also reverse gut dysbiosis and promote beneficial effects at intestinal and extraintestinal levels. NR and NMN have been found in vegetables, meat, and milk, and microorganisms in fermented beverages can also produce them. NMN and NR can be obtained through the diet either in their free form or as metabolites derivate from the digestion of NAD+. The prospection of NR and NMN to find potential food sources and their dietary contribution in increasing NAD+ levels are still an unexplored field of research. Moreover, it could enable the development of new functional foods and processing strategies to maintain and enhance their physiological benefits, besides the studies of new raw materials for extraction and biotechnological development.

Keywords: NAD+ precursors; Nicotinamide mononucleotide; Nicotinamide riboside; Promoting health; Pyridine derivatives.

Fig. 1

Chemical structure and schematic illustration of the beneficial health effects of NAD+ precursors NMN and NR

Fig. 2

NAD biosynthesis pathways in humans (A) and plants (B). NMN could be uptake through CD73-mediated dephosphorylating to NR, or via a transporter encoded by gene SLC12A8. Arrows dotted indicate a putative pathway. Precursors/Metabolites: KYN: N-formylkynurenine; NMN (nicotinamide mononucleotide); NMNH (dihydronicotinamide mononucleotide); NR (nicotinamide riboside); NRH (dihydronicotinamide riboside); NAR (nicotinic acid riboside); NAM (nicotinamide); NA (nicotinic acid); NAMN (nicotinic acid mononucleotide); NAAD (nicotinic acid adenine dinucleotide), QA (quinolinic acid); TRYP (tryptophan). Enzymes: AK, adenosine kinase; CD73/CD38/CD157, ectoenzimas; IDO, indoleamine 2,3-dioxygenase; NADPPase (NAD pyrophosphatase); NADS (NAD synthase); NAMPT, nicotinamide phosphoribosyltransferase; NAPT (nicotinate phosphoribosyltransferase); NARK (nicotinic acid ribose kinase); NIC (nicotinamidase); NMNAT (nicotinamide/nicotinic acid mononucleotide adenylyltransferase); NRase (nicotinamide riboside nucleosidase); NRD (nicotinamide riboside deaminase); NRK1/2: nicotinamide riboside kinases; NUDase (5′- nucleotidase); PARPs, poli-ADPR polymerases; PNP, purine nucleoside phosphorylase; QPRTase: QA-phosphoribosyltransferase; SIRTs, sirtuins, TDO, tryptophan 2,3-dioxygenase. Image created with https://www.biorender.com/