Comparative Evaluation of Four NAD+ Precursors in Preventing High-Glucose-Induced Hepatocyte Damage: Preclinical Findings

Synopsis

Boosting NAD+ levels is known to protect the liver from metabolic stress, but the effectiveness of different NAD+ precursors—nicotinic acid (NA), niacinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN)—had not been directly compared. Using a fish liver cell model exposed to high glucose (to mimic hyperglycemia-induced liver injury), researchers found that all four compounds increased cell survival, but NR had the strongest protective effect. NR most effectively restored NAD+ levels, activated SIRT1 and SIRT3, and reduced oxidative stress, inflammation, and cell death. It also improved glucose metabolism by enhancing glucose transport, glycolysis, and glycogen synthesis, while suppressing glucose overproduction (gluconeogenesis). In live fish, oral NR supplementation produced the greatest increase in hepatic NAD+ content and the NAD+/NADH ratio compared to other precursors. These results demonstrate that NR is the most potent NAD+ booster for improving liver metabolism and resilience under high-glucose stress, highlighting its therapeutic potential for metabolic and liver disorders.

Journal

Antioxidants