Preliminary exploration of acute limit toxicity testing for nicotinamide mononucleotide in the neonatal population

This study investigated the potential toxicity of nicotinamide mononucleotide (NMN) during the neonatal period, a critical and vulnerable developmental window. While NMN, a precursor of NAD⁺, has demonstrated safety and therapeutic potential in adults, its toxicological effects on newborns remain unclear.

We conducted an acute limit toxicity test to evaluate the impact of NMN on vital organs (liver, kidney, and central nervous system) in neonatal mice.

Under these experimental conditions, no significant acute toxicity was observed, with no histopathological damage or serum biochemical abnormalities detected in the major organs. However, high-throughput transcriptome sequencing revealed subtle yet specific gene expression perturbations, involving liver proliferation signal regulation, kidney adaptation to excretory load, and brain suppression of neuroinflammation alongside coordinated growth and metabolism.

Despite the absence of overt histopathological or clinical toxicity, transcriptomic analysis revealed that a single high-dose NMN exposure may induce early molecular-level stress and compensatory adjustments in neonates. These findings provide crucial preliminary experimental evidence and transcriptomic insights for assessing NMN safety in early life, highlighting the need for future studies on long-term, subchronic, and chronic effects, while noting that the results cannot be directly extrapolated to human infants.