Ketone Bodies as Regulators of Cardiac Energy Metabolism and Cardiovascular Signaling

Ketone Bodies as Regulators of Cardiac Energy Metabolism and Cardiovascular Signaling

Alvin Sherman Library

The heart has a high and continuous energy demand and depends on metabolic flexibility to maintain function under both physiological and pathological conditions. Ketone bodies, particularly β-hydroxybutyrate, have emerged as important alternative fuels for the myocardium and as biologically active signaling molecules. This review examines how ketone bodies support cardiac energy metabolism and regulate vascular and myocardial biology through intracellular signaling pathways. A narrative synthesis of peer-reviewed literature was conducted, focusing on ketone utilization in healthy and diseased hearts, metabolic remodeling in heart failure, and the non-energetic signaling roles of ketone bodies in cardiovascular tissues. Evidence indicates that ketone bodies provide an efficient supplemental energy source for the myocardium, especially in energy-deficient states such as heart failure where mitochondrial oxidative capacity is reduced. Increased ketone oxidation partially compensates for impaired glucose and fatty acid metabolism, contributing to improved cardiac efficiency. Beyond their role as fuels, ketones influence signaling pathways involved in inflammation, oxidative stress, endothelial function, and gene transcription. In vascular smooth muscle and endothelial cells, ketone-mediated signaling supports cell proliferation and vascular integrity, potentially limiting capillary rarefaction. Together, these metabolic and signaling actions position ketone bodies as active regulators of cardiovascular homeostasis rather than passive metabolic byproducts. Understanding these mechanisms provides a foundation for developing metabolic-based strategies to support cardiovascular health.