Ketone Esters for Endurance: Study Proves Cognitive Benefits Summary

  • The study investigated ketone esters for endurance performance and cognitive effect before, during, and after an ultra-marathon race.
  • Ketone esters did not affect performance, but they did inhibit the decline in mental alertness, helping to maintain cognitive function throughout the marathon. Secondly, keto ester supplements increase plasma dopamine levels, which can contribute to improved mental alertness and decision-making.
  • The Keto ester drink inhibiedt the infiltration of macrophages in skeletal muscles post-exercise and suppressed AMPK phosphorylation, indicating improved post-exercise recovery.

Endurance athletes are always on the lookout for ways to enhance their performance. One such method that has garnered attention is the use of ketone esters for endurance. Ketone esters have garnered significant attention in recent years, especially in the realm of endurance sports like the Tour de France. Staying focused during training or competition can make all the difference during a race.

There are two forms of ketone supplements: Ketone esters and salts. Studies have found ketone esters to be more effective at raising blood ketones and been shown to improve cognitive function in endurance athletes. Ketone salts, on the other hand, can supply smaller amounts of ketone bodies without causing gastro-intestinal distress. Staying focused during training or competition can make all the difference during a race.

One way to potentially improve your cognitive function during endurance exercise is by using ketone esters, which have been shown to increase the efficiency of mitochondrial metabolism. The latest study published in the Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology, titled “Exogenous ketosis increases circulating dopamine concentration and maintains mental alertness in ultra-endurance exercise” highlighted the potential benefits of ketone esters for endurance athletes, especially those participating in ultra-marathons.

Introduction: Dietary Induced Ketosis vs. Supplemental Ketosis

Ketosis, a metabolic state where the body burns fat for fuel in the absence of carbohydrates, can be achieved through two primary methods: dietary-induced ketosis and supplemental ketosis. (Cox et al., 2016) Dietary-induced ketosis is achieved by following a ketogenic diet, which is high in fats and low in carbohydrates.

Supplemental ketosis, on the other hand, is achieved by consuming exogenous keto ester supplements. (Cox & Clarke, 2014) Supplemental ketosis involves consuming exogenous ketones as ketone esters to increase blood ketone levels quickly and provide extra energy. For athletes, supplementing with ketone esters might be a more feasible option, offering the benefits of ketosis without the strict dietary restrictions.

Beyond sports, the beneficial effects of ketone esters extend to metabolic health. They’ve been shown to enhance insulin sensitivity, regulate blood glucose, and even modulate carbohydrate metabolism. In a fasted state, the body taps into adipose tissue, breaking down fatty acid to produce energy. Ketone esters, acting as an alternative energy source, can influence this process, potentially reducing the reliance on plasma glucose.

What are Supplemental Ketones and How Can They Enhance Performance?

ketone esters keto ester drink keto ester supplement ketone esters for enduranceKetones, specifically β-hydroxybutyrate (βHB) and acetoacetate (AcAc) are organic compounds produced by the liver when glucose is scarce. (Hargreaves & Spriet, 2020) They serve as an alternative fuel source for the brain and muscles, and have been shown to prevent oxidative stress in the myocardium. Recent studies have shown that ketone supplementation can alter substrate utilization during exercise, increasing fat utilization and decreasing carbohydrate oxidation. (Poffé et al., 2020) This makes them a promising option for enhancing performance and improving cognitive function in endurance athletes.

Literature Review: The Mixed Results on Ketones and Performance

Oral ketone supplements have gained popularity as a potential means to improve endurance exercise performance. Some studies have shown that acute ingestion of the ketone ester improved performance, while others have shown contrasting results. (Cox et al., 2016; Poffé & Hespel, 2020) Some have even observed a detrimental effect on high-intensity exercise performance. (Poffé et al., 2021)

Furthermore, while some research indicates that ketone bodies can facilitate certain aspects of post-exercise recovery (Vandoorne et al., 2017), others found no significant impact on muscle function or systemic markers of muscle damage. (Martin-Arrowsmith et al., 2020)

The Mental Benefits of Exogenous Ketones

Ketone esters for endurance athletes have been shown to boost cognitive function and reduce fatigue during exercise significantly. The human brain requires a constant supply of energy. While glucose is its primary fuel, during periods of low carbohydrate availability, the brain turns to ketones for energy.

This metabolic shift can improve cognitive function and prevent cognitive impairment, as ketones are more efficient and sustainable than glucose for prolonged, intense physical activity. In a previous article on Evidence Based Muscle, I covered how the military experimented with ketones on sleep-deprived soldiers.

ketone esters keto ester drink keto ester supplement ketone esters for enduranceStudies have shown that these ketone esters can significantly improve cognitive function and decrease fatigue during exercise. (Evans & Egan, 2018) In addition to enhancing athletic performance, exogenous ketones also hold promise for individuals with neurological conditions like Alzheimer’s and Parkinson’s disease. Alzheimer’s disease and other neurodegenerative diseases have been linked to disruptions in brain energy pathways, making the use of ketone esters as a potential neurotrophic factor for brain plasticity and cognitive function.

Oral Ketone Esters and Dopamine: The Neurotransmitter Connection

Dopamine, a neurotransmitter associated with pleasure, motivation, and cognitive alertness, plays a pivotal role in our mental well-being. (Rihet et al., 2002) This neurotransmitter, often associated with pleasure and motivation, may play a crucial role in the cognitive benefits that ketone esters provide.

A crucial component in ultra-endurance exercise performance is the gradual development of mental fatigue, which reduces resilience and impairs mental alertness and decision-making. (Cona et al., 2015) It has been the prevailing opinion for a long time that mental fatigue during prolonged exercise primarily results from increased brain serotonin and adrenaline activity.

However, more recent data indicate ketone esters may prevent suppression of dopamine activity and potentially play a pivotal role in improving cognitive function. (Mahajan et al., 2022) Therefore, it is reasonable to postulate that exogenous ketosis may be a potent strategy to impact dopamine signaling during ultra-endurance exercise beneficially and thereby counteract a decline in cognitive functioning and metabolic effects.

Exogenous Ketone Esters For Endurance Study

For endurance athletes, cognitive function is as crucial as physical stamina. A recent study highlighted the potential benefits of ketone esters for endurance athletes, especially those participating in ultra-marathons. The study aimed to find whether ingesting a ketone ester supplement could maintain mental alertness and increase dopamine levels during prolonged physical activity, compared to a placebo.

The researchers also sought to evaluate the safety and tolerability of the ketone ester supplement in this context; some studies have found that ketone esters can result in gastrointestinal stress. The study also examines the effect of exogenous ketosis on muscle repair and recovery post-event.

Study Protocol and Ketone Esters Supplement Protocol

The study involved 18 recreational runners who participated in a 100km trail run or ran to premature exhaustion. Subjects ran a 100 km off-road run in Beauvechain, Belgium. The run consisted of a 20 km loop with 657m vertical altitude meters per loop. Participants received ketone ester supplements or a non-caloric placebo.

Subjects were randomized to receive either a ketone ester drink (KE) or a control drink (CON) during the run and the day after. KE subjects received the pure (R)-βHB (R)1,3-butanediol ketone ester at regular intervals. The participants received the KE or placebo 30 minutes before the run (25 grams), every 30 minutes during the run (12.5 grams), and 5 additional times (25 grams each) in the ensuing 24 hours, specifically after the run, before sleep, before breakfast and lunch the next day, and before sleep the next day. The CON subjects received a taste-matched non-caloric placebo.


Poffé, C., Robberechts, R., Stalmans, M., Vanderroost, J., Bogaerts, S., & Hespel, P. (2023). Exogenous ketosis increases circulating dopamine concentration and maintains mental alertness in ultra-endurance exercise. J Appl Physiol (1985), 134(6), 1456-1469.


At the end of the ultramarathon, of the participants, 8 finished the full 100-km run: 5 from the KE group and 3 from the placebo. Both groups had comparable race distances, times, paces, and perceived exertion levels, scoring 18 out of 20.

During the race, the placebo group’s blood βHB levels stayed around 0.1–0.2 mM, while the KE group’s levels were at 2.0–2.5 mM. Blood sugar levels were steady at 6 mM in the placebo group but dropped to 5 mM in the KE group after 60 km.

ketone esters keto ester drink keto ester supplement ketone esters for endurance

Post Ultra Marathon Tests

Post-run, the KE group had almost double the plasma dopamine and noradrenaline levels immediately and 36 hours later compared to placebo. After the run, both groups showed increased muscle damage (i.e., creatine kinase levels). KE also inhibited muscular inflammation after exercise with a lower infiltration of macrophages.

Reaction times in the placebo group worsened by 20%–40%, and visual processing slowed by 12% post-run. In contrast, the KE group maintained their pre-run levels, resulting in faster post-run reaction and visual processing times compared to placebo.

Both groups experienced a decline in jump performance and increased muscle pain and stomach discomfort after the run. However, these areas had no significant difference between the KE and placebo groups. (Poffé et al., 2023)

An important note: the study didn’t regulate the participants’ food intake during the run, apart from the provided supplements. This led to the KE group consuming nearly 30% more calories than the placebo group (3,974 kcal vs. 2,921 kcal) due to the energy content of the KE supplements. Even though both groups had similar macronutrient consumption, the increased calorie intake in the KE group increase in calories may have influenced mental fatigue just by having more calories.

In conclusion, this study protocol and its results suggest ketone esters for endurance athletes may improve endurance athletes’ cognitive function. These findings pave the way for subsequent human studies that can further explore the benefits of ketone esters for endurance athletes in enhancing exercise performance and cognitive abilities. Continued research in this field will provide valuable insights into how ketone esters can be effectively utilized in sports nutrition and their potential applications beyond athletic performance.

Practical Applications

The study demonstrates the potential benefits of consistent exogenous ketosis during ultra-marathon running. These findings, along with the positive association between ketone esters for endurance athletes, sports performance, and cognitive capacity could be helpful for athletes and coaches in optimizing performance and endurance during long-distance events. However, it should be noted the small study size and difference in calories between the groups make it difficult to determine if ketone esters are genuinely beneficial. Further research is needed to determine if similar effects would be observed in different groups.


Cona, G., Cavazzana, A., Paoli, A., Marcolin, G., Grainer, A., & Bisiacchi, P. S. (2015). It’s a Matter of Mind! Cognitive Functioning Predicts the Athletic Performance in Ultra-Marathon Runners. PLoS One, 10(7), e0132943.

Cox, P. J., & Clarke, K. (2014). Acute nutritional ketosis: implications for exercise performance and metabolism. Extrem Physiol Med, 3, 17.

Cox, P. J., Kirk, T., Ashmore, T., Willerton, K., Evans, R., Smith, A., Murray, A. J., Stubbs, B., West, J., McLure, S. W., King, M. T., Dodd, M. S., Holloway, C., Neubauer, S., Drawer, S., Veech, R. L., Griffin, J. L., & Clarke, K. (2016). Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab, 24(2), 256-268.

Evans, M., & Egan, B. (2018). Intermittent Running and Cognitive Performance after Ketone Ester Ingestion. Med Sci Sports Exerc, 50(11), 2330-2338.

Hargreaves, M., & Spriet, L. L. (2020). Skeletal muscle energy metabolism during exercise. Nature Metabolism, 2(9), 817-828.

Mahajan, V. R., Nadel, J. A., King, M. T., Pawlosky, R. J., Davis, M. I., Veech, R. L., Lovinger, D. M., & Salinas, A. G. (2022). Ketone ester-enriched diet ameliorates motor and dopamine release deficits in MitoPark mice. bioRxiv, 2022.2011.2014.516368.

Martin-Arrowsmith, P. W., Lov, J., Dai, J., Morais, J. A., & Churchward-Venne, T. A. (2020). Ketone Monoester Supplementation Does Not Expedite the Recovery of Indices of Muscle Damage After Eccentric Exercise. Front Nutr, 7, 607299.

Poffé, C., & Hespel, P. (2020). Ketone bodies: beyond their role as a potential energy substrate in exercise. J Physiol, 598(21), 4749-4750.

Poffé, C., Ramaekers, M., Bogaerts, S., & Hespel, P. (2020). Exogenous ketosis impacts neither performance nor muscle glycogen breakdown in prolonged endurance exercise. J Appl Physiol (1985), 128(6), 1643-1653.


Poffé, C., Robberechts, R., Stalmans, M., Vanderroost, J., Bogaerts, S., & Hespel, P. (2023). Exogenous ketosis increases circulating dopamine concentration and maintains mental alertness in ultra-endurance exercise. J Appl Physiol (1985), 134(6), 1456-1469.

Poffé, C., Wyns, F., Ramaekers, M., & Hespel, P. (2021). Exogenous Ketosis Impairs 30-min Time-Trial Performance Independent of Bicarbonate Supplementation. Med Sci Sports Exerc, 53(5), 1068-1078.

Rihet, P., Possamaï, C. A., Micallef-Roll, J., Blin, O., & Hasbroucq, T. (2002). Dopamine and human information processing: a reaction-time analysis of the effect of levodopa in healthy subjects. Psychopharmacology (Berl), 163(1), 62-67.

Vandoorne, T., De Smet, S., Ramaekers, M., Van Thienen, R., De Bock, K., Clarke, K., & Hespel, P. (2017). Intake of a Ketone Ester Drink during Recovery from Exercise Promotes mTORC1 Signaling but Not Glycogen Resynthesis in Human Muscle. Front Physiol, 8, 310.

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