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.

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation‐induced premature aging mice

“…Therefore, we assume that the NR acts mainly in MPP, not HSCs. A recent review assesses the currently published research articles on human NR supplementation and claims that oral NR supplementation has displayed few clinically relevant effects (Damgaard & Treebak, 2023), which is consistent with our results. Specialized BM microenvironments, termed HSC niches, maintain HSC numbers and function through cellular interactions and secreted factors that can be damaged by IR (Morrison & Scadden, 2014).…”

Chronically low NMNAT2 expression causes sub-lethal SARM1 activation and altered response to nicotinamide riboside in axons

“…Our study has also shown that the NAD precursor supplement NR lowers NAD instead of increasing it in neurites expressing sub-heterozygous levels of NMNAT2. While NR supplementation is likely to be harmless and potentially beneficial in the majority of the population, (with no toxicity being reported so far in human studies [30]), our findings suggest that NR and possibly other NAD precursors could be problematic in a subset. As well as the known human cases with mutations in NMNAT2 , there are other conditions where the levels, activity, or transport of the protein could be compromised.…”

Personalized Porous Gelatin Methacryloyl Sustained‐Release Nicotinamide Protects Against Noise‐Induced Hearing Loss

“…[ 18 , 28 ] However, its short stability in the circulation and NRK‐expression–limited utilization has restricted its clinical application. [ 48 , 49 ] NMN has been shown to exert beneficial effects on age‐ and diet‐induced diabetes, acute heart failure, renal injury and neurodegeneration; it also protects against cisplatin‐induced ototoxicity. [ 27 , 50 ] NMN appears to have good bioavailability, given its rapid absorption and conversion to NAD + in various organs (e.g., skeletal muscle, kidney and live), but how it is transported into cells remains unclear.…”