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Therefore, future research can investigate the protective effects of a ketone ester diet on heart failure. However, long-term studies on the effects of ketone esters on heart failure are still lacking and require further exploration. Currently, ketone ester trials are mainly conducted in healthy individuals (Selvaraj et al., 2022), with limited research on heart failure patients. A study on heart failure mice revealed that ketones can restore ATP levels in damaged hearts and ameliorate heart failure symptoms (Yurista et al., 2021a), indicating that ketones alleviate impaired cardiac function by providing energy to the failing heart. A ketogenic diet is currently emerging as a trend for weight loss, but it is not suitable for long-term use due to poor patient compliance. The classical ketogenic diet focuses on increased intake of long-chain fats, which may lead to obesity. A KD stimulates endogenous ketone production by adjusting the dietary structure and has protective effects on damaged hearts. These methods mildly elevate ketone levels in the body, thereby improving heart failure symptoms (Figure 5). These results reveal the multilevel and complex regulatory effects of ketone bodies on the energy metabolism network of the body and suggest that more rigorous research is needed to evaluate the effects of ketone bodies on failing hearts. Clinically, the administration of ketones to patients has been shown to increase vasodilation and blood flow, thereby alleviating symptoms of heart failure (Nielsen et al., 2019). However, although relevant studies have demonstrated that ketone metabolism can regulate physiological processes through PTMs, there is currently no direct evidence of its impact on heart disease, and further research is needed in this area. Wang et al. (2008) found that cardiac systolic function in mice with myocardial ischemia did not improve and may even be worsened by ketogenic diets. Although the protective effects of ketone oxidation on the heart have been supported by several studies, the specific mechanisms involved have not been fully elucidated. However, in a heart failure mouse model, prolonged elevation of circulating ketone body levels alleviated NLRP3 inflammasome-mediated myocardial inflammation and improved cardiac function (Byrne et al., 2020; Youm et al., 2015). Additionally, ketogenic diets can significantly extend the lifespan of mice with genetic lethal cardiomyopathy because they help maintain the integrity of cardiomyocytic mitochondrial structures and improve oxidative phosphorylation (Krebs et al., 2011). Recently, studies have reported that ketone bodies play a role in maintaining mitochondrial integrity in heart disease (Huynh, 2016). 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