Vitamin supplements that boost a key metabolite in the body can slow the advance of muscle wasting, according to a new investigation in mice. The study supports further investigation of the potential benefits of this compound in patients with muscular dystrophy. Duchenne muscular dystrophy (DMD) and other muscle disorders have been associated with dysfunction of the mitochondria (the powerhouse of the cell), which weakens muscles over time, and often leads to heart and respiratory failure. Despite recent advances in DMD treatment approaches, effective and safe therapies are still lacking. Here, Dongryeol Ryu and colleagues offer new insights, now linking the disease to low levels of NAD+, a molecule that plays a central role in mitochondrial function. The authors analyzed skeletal muscle from DMD patients, finding increased expression of enzymes that used up NAD+. In healthy mice, the expression of genes involved in mitochondrial formation were closely correlated with NAD+ synthesis, while mouse and nematode models of DMD showed reduced levels of NAD+ in muscles. Further, both animals given dietary supplements of nicotinamide riboside, a NAD+ precursor, demonstrated improved mobility and reduced muscle fibrosis and inflammation. Treated mice also showed greater grip strength and were less prone to muscle damage. These observations suggest that replenishing NAD+ may offer a unique therapeutic strategy for neuromuscular diseases and injuries.