Reduced Nicotinamide Mononucleotide (NMNH) Potently Enhances NAD⁺, Suppresses Glycolysis, TCA Cycle and Cell Growth

Abstract

In the present study, we developed a chemical method to produce dihydro nicotinamide mononucleotide (NMNH), which is the reduced-form of nicotinamide mononucleotide (NMN). We demonstrated that NMNH was a better NAD⁺ enhancer compared to NMN both in vitro and in vivo mediated by NMNAT. Additionally, NMNH increased the reduced NAD (NADH) levels in cells and in mouse liver. Metabolomic analysis revealed that NMNH inhibited glycolysis and TCA cycle. In vitro experiments demonstrated that NMNH induced cell cycle arrest and suppressed cell growth. Nevertheless, NMNH treatment did not cause observable difference in mice. Taken together, our work demonstrates that NMNH is a potent NAD⁺ enhancer, and suppresses glycolysis, TCA cycle and cell growth.