Why the study?
Heart failure remains the leading cause of morbidity and mortality in the developed world, highlighting the urgent need for novel, effective therapeutics.
Do ketone bodies and short-chain fatty acids offer therapeutic benefits in patients with HFrEF and HFpEF?
Do ketone bodies and short-chain fatty acids offer therapeutic benefits in patients with HFrEF and HFpEF?
Ketone bodies and short-chain fatty acids offer potential therapeutic benefits in heart failure through both metabolic and nonmetabolic mechanisms.
May support SCFA metabolic modulation in HF; leaves open clinical benefit pending prospective trials.
Heart failure (HF) remains the leading cause of morbidity and mortality in the developed world, highlighting the urgent need for novel, effective therapeutics. Recent studies support the proposition that improved myocardial energetics as a result of ketone body (KB) oxidation may account for the intriguing beneficial effects of sodium-glucose cotransporter-2 inhibitors in patients with HF. Similar small molecules, short-chain fatty acids (SCFAs) are now realized to be preferentially oxidized over KBs in failing hearts, contradicting the notion of KBs as a rescue "superfuel." In addition to KBs and SCFAs being alternative fuels, both exert a wide array of nonmetabolic functions, including molecular signaling and epigenetics and as effectors of inflammation and immunity, blood pressure regulation, and oxidative stress. In this review, the authors present a perspective supported by new evidence that the metabolic and unique nonmetabolic activities of KBs and SCFAs hold promise for treatment of patients with HF with reduced ejection fraction and those with HF with preserved ejection fraction.
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Challa et al. (2022) studied this question.
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