Therapeutic Ketosis for Heart Failure: A State-of-the-Art Review

Heart failure is characterized by an energy-deprived heart, and in recent years it has been found that the failing heart increases ketone body oxidation to meet its energy demands. Accumulating evidence suggests that this metabolic adaptation is cardioprotective, suggesting that interventions that boost blood ketone levels could aid the failing heart. Indeed, multiple small clinical trials with short-term follow up have demonstrated that supplying the failing heart with exogenous ketone bodies may improve myocardial function across various manifestations of heart failure. As such, therapeutic ketosis, which is a metabolic state in which blood ketone levels are mildly elevated, could have great potential to ameliorate heart failure. Therapeutic ketosis can be achieved endogenously via exercise or dietary practices, exogenously via supplementation with ketone bodies, or pharmacologically via treatment with a sodium-glucose cotransporter-2 inhibitor. Although ketosis-inducing practices cannot be routinely recommended to patients with heart failure at this time due to a lack of robust data regarding the long-term benefits and risks, anecdotal evidence suggests that some patients have begun to adopt ketosis-inducing practices, so it is important for clinicians to be aware of how to manage patients optimally when they are in therapeutic ketosis. In this review, we discuss myocardial ketone metabolism in heart failure, the current evidence for therapeutic ketosis in patients with heart failure, a framework to distinguish between therapeutic ketosis and the pathologic state of ketoacidosis, and practical considerations for managing patients adhering to ketosis-inducing practices.