Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are characteristic of skeletal muscle aging and sarcopenia, but it is unclear whether these defects result from local changes or are mediated by systemic or dietary influences. This study reports a functional relationship between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid, NAD+ levels, and muscle health in various species.