What is really known about the effects of nicotinamide riboside supplementation in humans

Abstract

Nicotinamide riboside is a precursor to the important cofactor nicotinamide adenine dinucleotide and has elicited metabolic benefits in multiple preclinical studies. In 2016, the first clinical trial of nicotinamide riboside was conducted to test the safety and efficacy of human supplementation. Many trials have since been conducted aiming to delineate benefits to metabolic health and severe diseases in humans. This review endeavors to summarize and critically assess the 25 currently published research articles on human nicotinamide riboside supplementation to identify any poorly founded claims and assist the field in elucidating the actual future potential for nicotinamide riboside. Collectively, oral nicotinamide riboside supplementation has displayed few clinically relevant effects, and there is an unfortunate tendency in the literature to exaggerate the importance and robustness of reported effects. Even so, nicotinamide riboside may play a role in the reduction of inflammatory states and has shown some potential in the treatment of diverse severe diseases.

Fig. 1.. Pathways of mammalian NAD⁺ biosynthesis and metabolism.

Metabolites are shown in green, and enzymes are shown in blue. Major NAD⁺-consuming enzymes are in red, and CD157 degrades both NAD⁺ and NR. Abbreviations: TRP, tryptophan; ACMS, 2-amino-3-carboxymuconate semialdehyde; QA, quinolinic acid; NAMN, nicotinic acid mononucleotide; NAR, nicotinic acid riboside; NA, nicotinic acid; NAAD, nicotinic acid adenine dinucleotide; NAD⁺, nicotinamide adenine dinucleotide; NAM, nicotinamide; NAMOX, nicotinamide N-oxide; MeNAM, methyl-nicotinamide; Me2PY: N-methyl-2-pyridone-5-carboxamide; Me4PY, N-methyl-4-pyridone-5-carboxamide; NR, nicotinamide riboside; NMN, nicotinamide mononucleotide; TDO, tryptophan-2,3-dioxygenase; IDO, indoleamine-2,3-dioxygenase; QRPT, quinolinic acid phosphoribosyl-transferase; NRK, nicotinamide riboside kinase (1 and 2); NAPRT, nicotinic acid phosphoribosyltransferase; NMNAT, nicotinamide mononucleotide adenylyltransferase (1, 2, and 3); NADS, nicotinamide adenine dinucleotide synthase; CYP2E1, cytochrome P450 2E1; NNMT, nicotinamide N-methyltransferase; AOX1, aldehyde oxidase 1; PNP, purine nucleoside phosphorylase; NAMPT, nicotinamide phosphoribosyltransferase; PRPP, phosphoribosyl pyrophosphate; PPi, inorganic pyrophosphate; ATP, adenosine triphosphate.