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January 02 2025
“The pharmacological targeting of ketone body metabolism has emerged as a novel therapeutic approach to improve cardiac efficiency, reduce energy defi...
“The pharmacological targeting of ketone body metabolism has emerged as a novel therapeutic approach to improve cardiac efficiency, reduce energy deficiency, and enhance cardiac function in failing hearts.”
So states a paper published recently in Frontiers in Pharmacology, which presented the evidence for ketotherapy as a treatment for heart failure. The review covered the ketogenic diet and use of exogenous ketones (salts or esters taken orally, and infusions) as ways of elevating serum ketone levels, noting that ketones are an efficient fuel for cardiac muscle.
As noted in the paper, the most obvious rationale for elevating ketones in individuals with heart failure is that “myocardial cells utilize energy produced by ketone oxidation more efficiently than fatty acid and glucose oxidation. Therefore, when the efficiency of fatty acid and glucose oxidation in myocardial cells decreases, ketones can serve as a ‘super fuel’ to promptly replenish energy.”
The paper goes beyond ketones as a cardiac fuel source and explores other mechanisms by which ketones may be therapeutic for heart failure. Among these are reduced generation of reactive oxygen species (ROS) in a ketogenic metabolism and the fact that beta-hydroxybutyrate may act directly as an antioxidant. Ketone administration to human subjects with heart failure was also shown to increase vasodilation and blood flow, thereby alleviating symptoms.
While exogenous ketone administration may induce helpful effects, a ketogenic diet may go even further and lead to improvements in other issues associated with heart failure, such as improved blood glucose regulation, weight loss, and lower blood pressure. The authors noted that ketogenic diets have the drawback of potentially increased LDL-cholesterol and increased risk for non-alcoholic fatty liver disease, but a growing body of research suggests that an increase in LDL-C on a ketogenic diet is not automatically harmful, and keto diets are actually effective for reversing NAFLD.
Decades ago, it was thought that very-low-carb ketogenic diets were harmful for cardiovascular health, but as we covered in a previous Research Forum, the tide is turning and keto is increasingly recognized for its beneficial effects on cardiovascular health. The authors of this recent paper concluded, “…ketone bodies have the potential to become an important new field for the treatment of heart failure.”
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