Nicotinamide Riboside Attenuates NASH Progression: Preclinical Findings

Synopsis

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease driven by oxidative stress and inflammation. This study investigated whether increasing NADPH, a key molecule that fuels the body’s antioxidant defenses, could protect against NASH. Researchers used two approaches: nicotinamide riboside (NR) supplementation—a vitamin B3–derived NAD+ precursor that elevates NADPH levels—and genetically modified mice overexpressing G6PD, an enzyme that produces NADPH. In a mouse model of NASH induced by a methionine-choline-deficient diet, both strategies increased liver NADPH levels and reduced oxidative stress, but the benefits occurred only in female mice. NR-treated females showed lower liver fat (steatosis), reduced inflammation, and decreased liver injury markers, while both treatments enhanced antioxidant gene activity and reduced lipid peroxidation. The G6PD modification and NR treatment also reduced inflammatory immune cells, including macrophages and natural killer cells. These results indicate that boosting NADPH through NR supplementation strengthens the liver’s antioxidant capacity, limits oxidative damage, and slows NASH progression, particularly in females.

Journal

Free Radical Biology and Medicine