Several ongoing clinical trials are evaluating whether ketone bodies—substances we produce during fasting or from limited carbohydrate consumption—can help against heart disease.

In a paper published online on July 5 in the Journal of the American College of Cardiology (JACC): Basic to Translational Science, Gaetano Santulli, M.D., Ph.D., and colleagues looked at how ketone bodies might work at the molecular level to heal ischemic heart disease (i.e., heart muscle damaged by a cutoff in oxygen and nutrients as occurs in heart attacks). Their study involved cardiac specimens from heart failure patients who’d suffered heart attacks, healthy controls, a mouse model of post-ischemic heart failure, and experiments on cardiac cells. In all cases, the researchers observed that ischemic injury triggered chromatin remodeling that repressed the protein PCG1alpha—the master regulator of mitochondrial biogenesis—leading to mitochondrial dysfunction and death of cardiac cells. Treatment with beta-hydroxybutyrate (BHB)—the most abundant ketone body in humans—greatly reduced maladaptive chromatin remodeling, preserving mitochondrial function, and preventing the death of heart tissue. The findings bolster the case for ketone bodies as a possible treatment for ischemic heart disease and reveal for the first time the molecular mechanism underlying their beneficial effects.

Dr. Santulli is an associate professor of medicine and of molecular pharmacology at Einstein.