The Present and Future
JACC State-of-the-Art Review
Therapeutic Potential of Ketone Bodies for Patients With Cardiovascular Disease: JACC State-of-the-Art Review

https://doi.org/10.1016/j.jacc.2020.12.065Get rights and content
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Highlights

  • Data from experimental and human studies suggest that ketone bodies exert protective effects in patients with CVD.

  • Administration of exogenous ketones may become an alternative to a ketogenic diet as a means of elevating ketone bodies.

  • Future studies should assess the clinical impact of increasing ketone utilization in patients with or at risk of developing CVD.

Abstract

Metabolic perturbations underlie a variety of cardiovascular disease states; yet, metabolic interventions to prevent or treat these disorders are sparse. Ketones carry a negative clinical stigma as they are involved in diabetic ketoacidosis. However, evidence from both experimental and clinical research has uncovered a protective role for ketones in cardiovascular disease. Although ketones may provide supplemental fuel for the energy-starved heart, their cardiovascular effects appear to extend far beyond cardiac energetics. Indeed, ketone bodies have been shown to influence a variety of cellular processes including gene transcription, inflammation and oxidative stress, endothelial function, cardiac remodeling, and cardiovascular risk factors. This paper reviews the bioenergetic and pleiotropic effects of ketone bodies that could potentially contribute to its cardiovascular benefits based on evidence from animal and human studies.

Key Words

cardiovascular disease
heart failure
ketones
pleiotropic effects

Abbreviations and Acronyms

BDH
beta-hydroxybutyrate dehydrogenases
CVD
cardiovascular disease
HF
heart failure
KD
ketogenic diet
KE
ketone ester
KS
ketone salts
MCT
medium-chain triglycerides
βOHB
beta-hydroxybutyrate

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Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.

Subodh Verma, MD, PhD, served as Guest Associate Editor for this paper. Javed Butler, MD, MPH, MBA, served as Guest Editor-in-Chief for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.