NMN and NR Improve Lipid Metabolism but Promote Atherosclerosis in ApoE-Knockout Mice: Preclinical Findings

Synopsis

Supplementation with nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) raised NAD+ levels and produced clear metabolic benefits in mice, including reduced body weight, lower serum lipids, and less fatty liver. However, in ApoE⁻/⁻ mice, a standard model of atherosclerosis, long-term NMN and NR supplementation consistently worsened plaque formation, regardless of supplier, dose, or administration route. Higher NMN doses (≈300 mg/kg) aggravated atherosclerosis most strongly, while lower doses (~100 mg/kg) had minimal harmful effects. These results indicate that although NMN and NR correct metabolic dysfunction, they may promote atherosclerosis under hyperlipidemic conditions, underscoring the importance of dose safety and careful monitoring in clinical applications.

Journal

Pharmaceuticals