Key Points of Ketone Esters Article

  • 25 grams of ketone esters (KE) taken after exercise and before bed was found to stimulate muscle skeletal muscle capillarization. KE increased the number of capillary contacts and the capillary-to-fiber perimeter exchange index by 44% and 42%, respectively.
  • Ketone esters also increased blood EPO levels. Serum erythropoietin concentration was also increased by 26%.
  • The data indicate that exogenous ketosis supplementation may evolve as a potent nutritional strategy to facilitate recovery from strenuous endurance exercise, stimulating beneficial muscular adaptations.


Exogenous ketones are becoming a hot topic in sports and fitness. Studying exogenous ketones and their impact on endurance training is rapidly evolving. Recent research has shed light on the potential of exogenous ketones to enhance muscular adaptations, particularly during periods of intense endurance training.

Endurance training is critical for athletes and fitness enthusiasts aiming to improve performance and stamina. However, excessive training can sometimes negatively affect the body’s ability to adapt and recover. A groundbreaking new study, “Exogenous Ketosis Elevates Circulating Erythropoietin and Stimulates Muscular Angiogenesis During Endurance Training Overload” published in The Journal of Physiology, has shed light on the potential benefits of exogenous ketone supplementation. (Poffé et al., 2023) This article delves into the study’s key findings and explores the implications for endurance athletes.

Exogenous Ketones: What Are They?

Ketones are molecules the liver produces during low carbohydrate intake or fasting periods. They serve as an alternative fuel source for the body, particularly for the brain and muscles, when glucose availability is limited.

The three main types of ketones produced are beta-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone. The body can use ketones as an energy source, and their production can be increased through dietary interventions such as consuming a ketogenic diet or using exogenous ketone supplements.

Exogenous ketones are supplements that provide the body with an external source of ketones, typically in the form of ketone esters or salts. The body utilizes these compounds as an energy source, particularly during periods of low carbohydrate availability. Research has shown that exogenous ketones can enhance endurance performance by providing a more efficient muscle fuel source during exercise. (Costa et al., 2020)

Exogenous ketones, specifically (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE), have been shown to have a significant impact on training adaptations. Recent studies have demonstrated that KE ingestion during a 3-week endurance training overload period markedly blunted the development of overreaching symptoms.(Poffé et al., 2019). However, not all studies have found KE to be beneficial for performance. (Costa et al., 2020)(Brooks et al., 2022; Dearlove et al., 2020; Poffé et al., 2020) This discovery opens new doors in understanding the role of exogenous ketones benefits in endurance performance.

The Impact of Ketones on Endurance Performance

exogenous ketones benefitsketone esters angiogenesis exogenous keto supplements exogenous ketonesKetones have been found to influence endurance performance by altering how the body utilizes energy. A 2021 review of the existing evidence on the role of ketones in post-exercise recovery identified potential mechanisms that drive improved recovery. They suggested exogenous ketones benefits may enhance recovery and cumulative impact over subsequent exercise performance. (Mansor & Woo, 2021)

The mechanisms underlying the potential effects of exogenous ketones on muscular adaptations are still not fully understood. It is hypothesized that exogenous ketones may act as hormone-like signaling molecules, influencing various physiological processes. (Egan, 2018) Additionally, exogenous ketones may affect energy metabolism, oxidative stress, inflammation, and gene expression, which could contribute to their potential benefits in muscular adaptations.(Stubbs et al., 2020)

By providing an alternative to glucose, ketones can help preserve glycogen stores, reduce lactate production, and enhance fat oxidation, which may provide performance adaptations. Several studies have demonstrated the positive effects of exogenous ketones on endurance performance, including improved time-trial performance and increased exercise capacity.

Ketones have been found to influence various aspects of endurance performance. A recent study showed that KE resulted in a 15% higher training load in the final week of a 3-week intervention(Poffé et al., 2019).

Muscle Capillarization and its Importance for Endurance Performance

Muscle capillarization refers to the density of capillaries within muscle tissue. This is vital for delivering oxygen and nutrients to muscles during exercise. Increased muscle capillarization has been linked to enhanced endurance performance, allowing for more efficient oxygen delivery and waste removal. Training adaptations that increase capillarization can lead to significant improvements in endurance capacity.

Muscle capillarization plays a pivotal role in endurance performance and metabolic health. However, overload training or overreaching can impair the normal angiogenic response (i.e., muscle capillarization) to endurance exercise. A recent meta-analysis indicated that skeletal muscle capillarization increases within only 2 weeks of endurance training in untrained subjects, but overload training may hinder this response. (Liu et al., 2022) The role of exogenous ketones in modifying these effects is an area of ongoing exploration.

The Significance of VEGF and EPO Production for Cardiovascular Training and Adaptations

exogenous ketones benefitsketone esters angiogenesis exogenous keto supplements exogenous ketones

VEGF (vascular endothelial growth factor) and EPO (erythropoietin) play crucial roles in cardiovascular adaptations. VEGF promotes angiogenesis (i.e., muscle capillarization) and the formation of new blood vessels, while EPO stimulates red blood cell production. Both factors are essential for improving muscle oxygen delivery and have been linked to enhanced endurance performance. Various factors, including training intensity and nutritional interventions, can influence the production of VEGF and EPO.

VEGF (vascular endothelial growth factor) and EPO are key players in cardiovascular adaptations. The exercise-induced angiogenic response in KE was found to be mediated by VEGF.(Gliemann et al., 2015) Interestingly, KE increased serum EPO levels in response to the training period, and this elevation can persist for many hours after blood ketone levels have returned to baseline.(Gliemann et al., 2015) The pro-angiogenic effects of EPO on skeletal muscle under pathological conditions further underscore the significance of VEGF and EPO in cardiovascular training.

New 2023 Study: Exogenous Ketones and Training Overload

This new study investigated the effects of exogenous ketosis, a state where the body uses ketones as fuel instead of carbohydrates, on muscle adaptation during endurance training. The researchers wanted to understand if taking a ketone ester drink during training could enhance the growth of blood vessels in the muscles, a process called angiogenesis, which is important for improving endurance performance.

Training Program

The study involved 20 healthy male participants who underwent a 3-week cycling training program. Subjects underwent two training sessions per day, six days a week. The training sessions included high-intensity interval, intermittent, and constant-load endurance training sessions.

The training load was gradually increased over the three weeks, with a total training load that was similar between the ketone ester and control groups during the first two weeks. However, in the final training week, the training load was 15% higher in the KE group compared to the CON group. Each training session was performed in the laboratory on calibrated cycling ergometers under the supervision of the investigators.

Supplement Protocol

Half of the participants received a ketone ester drink, while the other half received a control drink. Muscle biopsies and blood samples were taken before and after the training to assess changes in muscle capillarization (the growth of blood vessels) and the levels of certain proteins involved in angiogenesis. Subjects from the ketone ester group received 25 g of ketone ester immediately following each training session and 30 min pre-sleep. The control group ingested an isocaloric control drink containing 16.4 g of pure medium-chain triglycerides.

The key findings include the following:

The results showed that the group receiving the ketone ester drink significantly increased muscle capillarization compared to the control group. This means that the ketone ester drink promoted the growth of new blood vessels in the muscles, which can improve oxygen and nutrient delivery during exercise. The ketone ester drink also increased vascular endothelial growth factor (VEGF) and erythropoietin (EPO), proteins that play a role in angiogenesis.

Increased Muscle Capillary Growth:

Participants who consumed exogenous ketone supplements showed increased muscle capillary growth compared to the control group. This finding suggests that exogenous ketosis may have practical applications in improving blood flow and oxygen delivery to muscles during exercise, potentially enhancing endurance performance.

Elevated EPO Levels:

The ketone group exhibited increased EPO levels compared to baseline, indicating enhanced red blood cell production. VEGF is known to play a crucial role in promoting angiogenesis, while EPO is involved in stimulating red blood cell production. These findings suggest that exogenous ketosis may have practical applications in enhancing the body’s natural mechanisms for tissue repair and adaptation to exercise.

Enhanced Angiogenesis:

During the last week of training overload, the ketone group experienced increases in angiogenesis (i.e., the formation of new blood vessels in skeletal muscle), a response typically blunted during periods of training overload. This finding suggests that exogenous ketosis may have practical applications in promoting tissue repair and recovery from strenuous exercise.

Potential for Improved Training Adaptation:

The study proves that exogenous ketosis may benefit endurance training-induced muscular adaptation. By stimulating angiogenesis and promoting tissue repair, exogenous ketosis may enhance the body’s ability to adapt to the demands of endurance exercise, potentially leading to improved performance and recovery.

The study’s key findings include the potential of exogenous ketosis to impact training adaptation and the role of KE in blunting over-reaching symptoms during endurance training overload. (Poffé et al., 2023). These findings contribute novel insights into the complex interplay between exogenous ketones, angiogenesis, and endurance performance.

Implications for Endurance Athletes: Ketone Esters as Recovery Supplements

exogenous ketones benefitsketone esters angiogenesis exogenous keto supplements exogenous ketones

The study’s findings have practical applications for endurance athletes. The observed increases in muscle capillarization and EPO levels suggest that ketone esters could be used as recovery supplements during intense training phases. This could lead to enhanced performance and reduced risk of overtraining. Other studies have also supported using ketone esters for recovery, highlighting their potential benefits in reducing inflammation and muscle damage.

The potential of exogenous ketones, particularly KE, as recovery supplements during high-volume endurance training, is a promising frontier. The observed effects on training load, EPO levels, and angiogenic response suggest that ketone esters could benefit endurance athletes. The most highlighted action of EPO is the stimulation of erythropoiesis, leading to the elevation of total circulating hemoglobin mass, a primary determinant of aerobic performance (Schmidt & Prommer, 2010). This adds another dimension to the potential applications of exogenous ketones in sports nutrition.


In conclusion, the use of ketone esters as a recovery supplement for endurance athletes shows promising results in enhancing endurance performance and promoting cardiovascular training adaptations. The increase in muscle capillarization and the production of VEGF and EPO are crucial factors that contribute to improved endurance capacity. The recent 2023 study further supports the positive impact of exogenous ketones on training overload and recovery. As an endurance athlete, incorporating ketone esters into your training regimen may prove to be a game-changer. However, it is important to consult with your healthcare professional or sports nutritionist before incorporating any new supplement into your routine. Stay ahead of the competition and take your endurance performance to new heights with the potential benefits of ketone esters.


Brooks, E., Lamothe, G., Nagpal, T. S., Imbeault, P., Adamo, K. B., Kara, J., & Doucet, É. (2022). Acute Ingestion of Ketone Monoesters and Precursors Do Not Enhance Endurance Exercise Performance: A Systematic Review and Meta-Analysis. International Journal of Sport Nutrition and Exercise Metabolism.

Costa, D. D., Banagalee, V., & Naidoo, R. (2020). Exogenous Ketone Supplement Ingestion and Submaximal Exercise Response in Trained, Male Cyclists: A Randomised, Double-Blind Study. Annals of Applied Sport Science.

Dearlove, D. J., Faull, O. K., Hodson, L., Jefferson, A., Clarke, K., & Cox, P. J. (2020). The Effect of Blood Ketone Concentration and Exercise Intensity on Exogenous Ketone Oxidation Rates in Athletes. Medicine & Science in Sports & Exercise.

Egan, B. (2018). The Glucose-Lowering Effects of Exogenous Ketones: Is There Therapeutic Potential? The Journal of Physiology.

Gliemann, L., Gunnarsson, T. P., Hellsten, Y., & Bangsbo, J. (2015). 10-20-30 training increases performance and lowers blood pressure and VEGF in runners. Scand J Med Sci Sports, 25(5), e479-489.

Liu, Y., Christensen, P. M., Hellsten, Y., & Gliemann, L. (2022). Effects of Exercise Training Intensity and Duration on Skeletal Muscle Capillarization in Healthy Subjects: A Meta-analysis. Med Sci Sports Exerc, 54(10), 1714-1728.

Mansor, L. S., & Woo, G. H. (2021). Ketones for Post-Exercise Recovery: Potential Applications and Mechanisms. Frontiers in Physiology.

Poffé, C., Ramaekers, M., Bogaerts, S., & Hespel, P. (2020). Exogenous Ketosis Impacts Neither Performance Nor Muscle Glycogen Breakdown in Prolonged Endurance Exercise. Journal of Applied Physiology.


Poffé, C., Ramaekers, M., Van Thienen, R., & Hespel, P. (2019). Ketone ester supplementation blunts overreaching symptoms during endurance training overload. J Physiol, 597(12), 3009-3027.

Poffé, C., Robberechts, R., Van Thienen, R., & Hespel, P. (2023). Exogenous ketosis elevates circulating erythropoietin and stimulates muscular angiogenesis during endurance training overload. J Physiol, 601(12), 2345-2358.

Schmidt, W., & Prommer, N. (2010). Impact of alterations in total hemoglobin mass on VO 2max. Exerc Sport Sci Rev, 38(2), 68-75.

Stubbs, B. J., Koutnik, A. P., Volek, J. S., & Newman, J. C. (2020). From Bedside to Battlefield: Intersection of Ketone Body Mechanisms in Geroscience With Military Resilience. GeroScience.

What are ketone esters and how do they work?

Ketone esters are a type of dietary supplement that provide the body with exogenous ketones, specifically beta-hydroxybutyrate (BHB). When consumed, these ketone esters increase blood ketone levels, which can enhance endurance performance by providing an alternative energy source for the muscles and brain.

Additional Information

The keto diet has taken the world by storm, promising rapid weight loss and numerous health benefits. Central to this diet is the concept of ketosis, a metabolic state where the body burns fat for fuel instead of carbs. But what if there was a way to achieve this state without strictly adhering to a low-carb diet? Enter exogenous ketones.

What are Exogenous Keto Supplements?

While endogenous ketones are produced by the body during ketogenesis, exogenous ketones are supplements that can elevate levels of ketones in the blood, mimicking a state of ketosis. They come in two main forms: ketone salts and ketone esters. For the purpose of this article, we’ll focus on ketone salts.

Exogenous Ketones Benefits

Appetite Suppression:

One of the primary benefits of exogenous ketones is appetite suppression. By elevating blood ketone levels, they can help reduce calories intake, making weight loss more achievable.

Boosting Metabolism:

Exogenous ketones can increase the rate at which the body burns body fat for energy, enhancing the effects of a low-carb or high-fat diet.

Health Benefits Beyond Weight Loss

Blood Sugar Regulation: Exogenous ketones can help stabilize blood glucose levels, reducing the need for insulin. This can be particularly beneficial for those with type 2 diabetes or obesity.

Epilepsy: The keto diet was originally developed to treat epilepsy. Exogenous ketones can offer similar benefits, reducing the frequency and severity of seizures.

Enhanced Athletic Performance: Some athletes, especially those participating in time trials, have found that exogenous ketones can improve performance by providing a quick source of energy in the form of ATP.

The Role of Minerals

Ketone salts are often bound to minerals like potassium, magnesium, and calcium. These minerals are essential for various bodily functions and can help alleviate symptoms of the keto flu, a common side effect when transitioning to a keto diet.

How Do They Work?

When consumed, exogenous ketones are rapidly absorbed into the bloodstream, leading to higher levels of ketones. This signals the body to start burning free fatty acids and adipose tissue (stored fat) for energy, especially in peripheral tissues. The result? Reduced reliance on carbs and a potential decrease in blood sugar levels.

When to Use Exogenous Ketones?

Transitioning to Keto: When starting a keto diet, it’s common to experience the keto flu. Exogenous ketones can help ease this transition, reducing symptoms like fatigue and irritability.

Fasted State: For those practicing intermittent fasting, exogenous ketones can provide an energy boost without breaking the fast.

After Consuming Carbs: If you’ve had a cheat day or consumed more carbs than usual, exogenous ketones can help return the body to a state of ketosis more quickly.

Potential Side Effects

While exogenous ketones are generally safe, some people might experience stomach discomfort, diarrhea, or nausea. It’s essential to start with a small dose and gradually increase.


Exogenous ketones supplements offer a promising way to harness the benefits of the keto diet without strict adherence. Whether you’re looking to lose weight, stabilize blood sugar, or enhance athletic performance, these supplements might be worth considering. However, as with any supplement, it’s essential to consult with a healthcare professional before starting.

About The Author

Leave a Reply