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New Findings: What is the topic of this review? The integrative physiological response to exogenous ketone supplementation. What advances does it highlight? The physiological effects and therapeutic potential of exogenous ketones on metabolic health, cardiovascular function, cognitive processing, and modulation of inflammatory pathways and immune function. Also highlighted are current challenges and future directions of the field.
Abstract: Exogenous oral ketone supplements, primarily in form of ketone salts or esters, have emerged as a useful research tool for manipulating metabolism with potential therapeutic application targeting various aspects of several common chronic diseases. Recent literature has investigated the effects of exogenously induced ketosis on metabolic health, cardiovascular function, cognitive processing, and modulation of inflammatory pathways and immune function. This narrative review provides an overview of the integrative physiological effects of exogenous ketone supplementation and highlights current challenges and future research directions. Much of the existing research on therapeutic applications - particularly mechanistic studies - has involved pre-clinical rodent and/or cellular models, requiring further validation in human clinical studies. Existing human studies report that exogenous ketones can lower blood glucose and improve some aspects of cognitive function, highlighting the potential therapeutic application of exogenous ketones for type 2 diabetes and neurological diseases. There is also support for the ability of exogenous ketosis to improve cardiac metabolism in rodent models of heart failure with supporting human studies emerging; long-terms effects of exogenous ketone supplementation on the human cardiovascular system and lipid profiles are needed. An important avenue for future work is provided by research accelerating technologies that enable continuous ketone monitoring and/or the development of more palatable ketone mixtures that optimize plasma ketone kinetics to enable sustained ketosis. Lastly, research exploring the physiological interactions between exogenous ketones and varying metabolic states (e.g., exercise, fasting, metabolic disease) should yield important insights that can be used to maximize the health benefits of exogenous ketosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103874 | PMC |
http://dx.doi.org/10.1113/EP090430 | DOI Listing |
Background: Oral treatment with the exogenous ketone body 3-hydroxybutyrate improves cardiac function in patients with heart failure with reduced ejection fraction, but ketosis is limited to 3 to 4 hours. Treatment with (R)-1,3-butanediol (BD) provides prolonged ketosis in healthy controls, but the hemodynamic and metabolic profile is unexplored in patients with heart failure with reduced ejection fraction.
Methods And Results: This was a randomized, single-blind, placebo-controlled, crossover study.
J Clin Med
December 2024
Department of Medicine, Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, NY 10461, USA.
Ketone bodies are molecules produced from fatty acids in the liver that act as energy carriers to peripheral tissues when glucose levels are low. Carbohydrate- and calorie-restricted diets, known to increase the levels of circulating ketone bodies, have attracted significant attention in recent years due to their potential health benefits in several diseases. Specifically, increasing ketones through dietary modulation has been reported to be beneficial for cardiovascular health and to improve glucose homeostasis and insulin resistance.
View Article and Find Full Text PDFMolecules
December 2024
Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Biology, Pharmaceutical Biology, Staudtstraße 5, 91058 Erlangen, Germany.
Enzymes capable of processing a variety of compounds enable plants to adapt to diverse environmental conditions. PRISEs (progesterone-5β-reductase/iridoid synthase-like enzymes), examples of such substrate-promiscuous enzymes, are involved in iridoid and cardenolide pathways and demonstrate notable substrate promiscuity by reducing the activated C=C double bonds of plant-borne and exogenous 1,4-enones. In this study, we identified PRISE genes in () and (), and the corresponding enzymes were determined to share a sequence identity of 95%.
View Article and Find Full Text PDFExerc Sport Sci Rev
December 2024
Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Leuven, Belgium.
A high-fat, low-carbohydrate, ketogenic diet has already appealed to athletes for a long time due to its purported ability to improve exercise performance and post-exercise recovery. The availability of ketone supplements has further sparked such interest. The review therefore focuses on the potential beneficial impact of exogenous and endogenous ketosis in the context of ultra-endurance exercise.
View Article and Find Full Text PDFJ Clin Invest
December 2024
Division of Nutritional Science and Obesity Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Despite the impressive clinical benefits and widespread adoption of sodium glucose cotransporter 2 inhibitors (SGLT2i) to treat all classes of heart failure, their cardiovascular mechanisms of action are poorly understood. Proposed mechanisms range broadly and include enhanced ketogenesis, where the mild ketosis associated with SGLT2i use is presumed to be beneficial. However, in this issue of the JCI, carefully conducted metabolic flux studies by Goedeke et al.
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