Nicotinamide Riboside Protects Bones via Mitochondrial Support: Preclinical Findings

Synopsis

This study uncovered how gut microbiota imbalances contribute to osteoporosis through the overproduction of trimethylamine-N-oxide (TMAO), a metabolite formed from L-carnitine by intestinal bacteria. Elevated TMAO disrupted bone formation, leading to reduced bone mass by impairing osteoblast function, the cells responsible for building bone. Mechanistically, TMAO caused stress in both the endoplasmic reticulum and mitochondria, blocking protein folding and energy production in bone cells. Importantly, nicotinamide riboside (NR), a vitamin B3–derived NAD+ booster, restored mitochondrial unfolded protein response (UPRmt), improved oxidative phosphorylation, and promoted healthy bone matrix formation, protecting against TMAO-induced bone loss. The study also found that transplanting healthy gut microbiota reduced TMAO levels and prevented osteoporosis in mice. Together, these findings reveal a gut–bone connection and suggest that NR supplementation and microbiome therapies could help maintain bone health and prevent osteoporosis.

Journal

Cellular and Molecular Life Sciences