Exogenous Ketones in Cardiovascular Disease and Diabetes

Recent breakthroughs in ketone metabolism reveal that these compounds are more than just energy sources—they are potent signaling molecules with the potential to transform treatments for cardiovascular disease and diabetes. Once misunderstood and feared due to their association with diabetic ketoacidosis, ketones have now emerged as promising therapeutic agents, capable of reducing inflammation, improving heart function, and stabilizing blood sugar levels. This article explores the science behind exogenous ketones, particularly β-hydroxybutyrate (BHB), and their role in revolutionizing care for two of the most pressing global health challenges.

Author: Dr. Andreia Torres
Andreia Torres

Dr. Andreia Torres

Clinical nutritionist with a doctorate in health education. International expert in ketogenic nutrition.
Andreia Torres
Review: Dr. Natalia Drabińska
Dr Natalia Drabinska

Dr. Natalia Drabińska

Scientist specialising in nutrition, food research and the ketogenic diet. She is conducting pioneering global research into the effects of the keto diet on the human body.
Dr Natalia Drabinska
exogenous ketones juicy peach 150g

What will you learn from the article?

Exogenous Ketones in Cardiovascular Disease and Diabetes

In recent years, interest in ketone metabolism has increased as it has been discovered that ketone bodies are not only vital sources of energy, but also powerful signaling molecules that influence cell metabolism, inflammation and bioenergetics in various organs. This has led to ketones being researched as potential therapeutic agents for a range of diseases including cancer, diabetes, heart disease and neurodegenerative disorders. In the past, ketones were feared by doctors because they were associated with diabetic ketoacidosis. However, research has changed this view and revealed their role as important metabolic intermediates, especially in times of starvation or carbohydrate deprivation.

What Are Ketone Bodies?

The three main ketone bodies produced during ketogenesis are β-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone. BHB is the most abundant ketone body and has gained particular attention for its ability to influence metabolic and signaling pathways rapidly. Amino acids like lysine and leucine also contribute to ketone body synthesis, providing key substrates in the liver.

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The Promise of Ketones in Therapeutic Interventions in Cardiovascular disease

Exogenous ketones, particularly BHB, have shown potential as adjuncts to traditional pharmacological therapies, especially in the management of cardiovascular diseases and diabetes. Research suggests that ketone bodies could be used to preserve heart function and improve metabolic health, acting in synergy with existing treatments. 

Research involving exogenous BHB has shown beneficial effects on cardiac function. In healthy volunteers, BHB supplementation improved cardiac performance, reduced vascular resistance, and increased myocardial blood flow. This suggests that BHB can enhance heart function and may be beneficial in heart disease treatment (1).

A small study of patients with heart failure with reduced ejection fraction (HFrEF) confirmed these findings. Patients who received intravenous BHB showed improved cardiac output, stroke volume, and oxygen consumption. Importantly, these effects were achieved without compromising myocardial efficiency, a critical factor in heart failure prognosis (2).

Another study with patients suffering from non-diabetic HFrEF showed that 14 days of oral BHB supplementation improved stroke volume, left ventricular ejection fraction (LVEF), and vascular resistance (3).

More robust trials, like the KETO-SHOCK1 study, demonstrated that intravenous ketone ester improved cardiac function in patients with acute myocardial infarction. These findings support BHB as a potential drug candidate for heart failure treatment (4).

Ketones and Diabetes: A Glimpse into Promising Therapeutic Benefits

Human studies have also pointed to the therapeutic potential of BHB in diabetes. For example, a meta-analysis with 327 data points from 30 studies indicated that exogenous ketones, like BHB, reduced blood glucose levels in individuals with obesity and prediabetes (5). Another study showed that ketone supplementation could lower blood glucose without increasing insulin levels—an exciting finding for managing type 2 diabetes (6).

In addition to glucose-lowering effects, ketones have been shown to reduce inflammation. Inflammation is a major contributor to the development of T2D and its complications. A study on individuals at risk for T2D showed that BHB supplementation suppressed pro-inflammatory cytokines, which are often elevated in those with diabetes (7).

BHB’s impact extends beyond metabolism—it functions as an inhibitor of several NAD+-independent histone deacetylases (HDACs), which could directly influence glucose regulation, oxidative stress, and mitochondrial health. This opens up exciting possibilities for BHB in treating various metabolic diseases. A graphical summary illustrating BHB’s protective effects on heart and pancreatic beta cells is provided by Kansawar et al., 2024:

image

Conclusion

In conclusion, ketone bodies, particularly exogenous BHB, hold promise not just as metabolic fuels but as modulators of health, from immune function to heart health. BeKeto™ is the first brand in the UK and Europe fully dedicated to the ketogenic and low-carbohydrate (low-carb) diet. Our mission is to help as many people as possible achieve a state of ketosis and optimal health by following the healthiest low-carbohydrate lifestyle possible.

We’ve spent thousands of hours bringing you the highest quality ketogenic products, such as Exogenous Ketones in different flavours. Whether you’re already keto or just starting your amazing journey, BeKeto™ is the perfect fit. 

Be well, BeKeto!

Bilbiography

1 – Oneglia AP, Young BE, Cipher DJ, Zaha V, Nelson MD. Acute effects of β-hydroxybutyrate on left ventricular function in young, healthy adults. J Appl Physiol (1985). 2023 Dec 1;135(6):1440-1445. doi: 10.1152/japplphysiol.00630.2023. Epub 2023 Oct 26. PMID: 37881851; PMCID: PMC10979827.

2 – Nielsen R, Møller N, Gormsen LC, Tolbod LP, Hansson NH, Sorensen J, Harms HJ, Frøkiær J, Eiskjaer H, Jespersen NR, Mellemkjaer S, Lassen TR, Pryds K, Bøtker HE, Wiggers H. Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients. Circulation. 2019 Apr 30;139(18):2129-2141. doi: 10.1161/CIRCULATIONAHA.118.036459. PMID: 30884964; PMCID: PMC6493702.

3 – Berg-Hansen, K., Gopalasingam, N., Christensen, K. H., Ladefoged, B., Andersen, M. J., Poulsen, S. H., Borlaug, B. A., Nielsen, R., Møller, N., & Wiggers, H. (2024). Cardiovascular Effects of Oral Ketone Ester Treatment in Patients with Heart Failure with Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial. Circulation, 149(19), 1474-1489. https://doi.org/10.1161/CIRCULATIONAHA.123.067971

4 – Berg-Hansen K, Christensen KH, Gopalasingam N, Nielsen R, Eiskjær H, Møller N, Birkelund T, Christensen S, Wiggers H. Beneficial Effects of Ketone Ester in Patients With Cardiogenic Shock: A Randomized, Controlled, Double-Blind Trial. JACC Heart Fail. 2023 Oct;11(10):1337-1347. doi: 10.1016/j.jchf.2023.05.029. Epub 2023 Jul 12. PMID: 37452805.

5 – Yu Q, Falkenhain K, Little JP, Wong KK, Nie J, Shi Q, Kong Z. Effects of ketone supplements on blood β-hydroxybutyrate, glucose and insulin: A systematic review and three-level meta-analysis. Complement Ther Clin Pract. 2023 Aug;52:101774. doi: 10.1016/j.ctcp.2023.101774. Epub 2023 Jun 10. PMID: 37327753.

6 – Myette-Côté É, Neudorf H, Rafiei H, Clarke K, Little JP. Prior ingestion of exogenous ketone monoester attenuates the glycaemic response to an oral glucose tolerance test in healthy young individuals. J Physiol. 2018 Apr 15;596(8):1385-1395. doi: 10.1113/JP275709. Epub 2018 Mar 2. Erratum in: J Physiol. 2019 Nov;597(22):5515. doi: 10.1113/JP279035. Abstract corrected. PMID: 29446830; PMCID: PMC5899975.

7- Helena Neudorf, Hashim Islam, Kaja Falkenhain, Barbara Oliveira, Garett S Jackson, Alfonso Moreno-Cabañas, Kenneth Madden, Joel Singer, Jeremy J Walsh, Jonathan P Little, Effect of the ketone beta-hydroxybutyrate on markers of inflammation and immune function in adults with type 2 diabetes, Clinical and Experimental Immunology, Volume 216, Issue 1, April 2024, Pages 89–103, https://doi.org/10.1093/cei/uxad138

8 – Kansakar U, Nieves Garcia C, Santulli G, Gambardella J, Mone P, Jankauskas SS, Lombardi A. Exogenous Ketones in Cardiovascular Disease and Diabetes: From Bench to Bedside. J Clin Med. 2024 Dec 4;13(23):7391. doi: 10.3390/jcm13237391. PMID: 39685849; PMCID: PMC11642481.

Dr Andreia Torres
Dr Andreia Torres

Clinical dietitian, with a PhD in Health Education. For over 20 years, Andreia has coached medical professionals, patients, and families interested in the use of metabolic therapies, such as low-carb and keto diets for the treatment of conditions such as obesity, diabetes, Alzheimer's, bipolar disorder, and certain types of cancer

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