Therapeutic potential of dihydronicotinamide riboside (NRH) on obesity and glucose intolerance in mice

NAD⁺ is a crucial metabolic cofactor whose intracellular levels can influence the progression of multiple metabolic and age-related complications. There is therefore a strong interest in using NAD⁺ precursors (vitamin B3s) as therapeutic tools, but most current precursors exhibit either poor bioavailability or adverse effects. This study examines the metabolic impact of chronic dietary supplementation with a newly described NAD⁺ precursor, dihydronicotinamide riboside (NRH), in mice using a comprehensive approach including phenotyping tests, RNA sequencing in different tissues and microbiome analyses. We show that chronic NRH administration at 100 mg/(kg*day) is well tolerated, yet has minimal metabolic effects in mice on a regular diet. However, NRH mitigates high-fat diet-induced metabolic complications when used as a preventive or as a treatment strategy, including improvements in glucose tolerance, increased hepatic expression of lipid catabolism genes and fat redistribution. These results highlight the potential of NRH as a therapeutic agent, although further studies are needed to optimize its use, as higher doses reveal signs of toxicity.