Ketogenic Diet and Cardiac Substrate Metabolism

Abstract

The ketogenic diet (KD) entails a high intake of fat, moderate intake of protein, and a very limited intake of carbohydrates. Ketogenic dieting has been proposed as an effective intervention for type 2 diabetes and obesity since glycemic control is improved and sustained weight loss can be achieved. Interestingly, hyperketonemia is also associated with beneficial cardiovascular effects, possibly caused by improved cardiac energetics and reduced oxygen use. Therefore, the KD has the potential to both treat and prevent cardiovascular disease. However, the KD has some adverse effects that could counteract the beneficial cardiovascular properties. Of these, hyperlipidemia with elevation of triglycerides and LDL cholesterol levels are the most important. In addition, poor diet adherence and lack of knowledge regarding long-term effects may also reduce the broader applicability of the KD. The objective of this narrative review is to provide insights into the KD and its effects on myocardial ketone body utilization and, consequently, cardiovascular health.

Keywords: diabetic cardiomyopathy; heart; heart failure; ketogenic diet; ketone bodies; metabolism.

Figure 1

Postabsorptive myocardial substrate metabolism. In the healthy heart, the majority of energy expenditure arises from oxidation of fatty acids from FFA and circulating lipoproteins. In individuals with heart failure, oxidation of ketone bodies (3-hydroxybutyrate, acetoacetate) is upregulated at the expense of fatty acid oxidation. The estimates in the figure were extracted from the recent paper by Murashige et al. [22]. FFA: free fatty acids; LpFA: fatty acids from circulating lipoproteins; LVEF: left ventricle ejection fraction, ATP: adenosine triphosphate, TCA: tricarboxylic acid cycle, AcetylCoA: acetyl coenzyme A, TG: triglycerides.