Emerging potential benefits of modulating NAD⁺metabolism in cardiovascular disease

Nicotinamide adenine dinucleotide (NAD + ) and related metabolites are central mediators of fuel oxidation and bioenergetics within cardiomyocytes. Additionally, NAD + is required for the activity of multifunctional enzymes, including sirtuins and poly(ADP-ribose) polymerases that regulate posttranslational modifications, DNA damage responses, and Ca 2+ signaling. Recent research has indicated that NAD + participates in a multitude of processes dysregulated in cardiovascular diseases. Therefore, supplementation of NAD + precursors, including nicotinamide riboside that boosts or repletes the NAD + metabolome, may be cardioprotective. This review examines the molecular physiology and preclinical data with respect to NAD + precursors in heart failure-related cardiac remodeling, ischemic-reperfusion injury, and arrhythmias. In addition, alternative NAD + -boosting strategies and potential systemic effects of NAD + supplementation with implications on cardiovascular health and disease are surveyed.