In the early 2000’, the agency responsible for research and innovation in the US military – DARPA – was looking for nutritional ways to enhance the performance of their elite forces. Fighters of these units work under extreme psychological and emotional stress. The compound DARPA was looking for should have improved both physical and mental performance.
Ketones seemed like a great fit for DARPA’s needs. The liver naturally produces ketones in times of food scarcity, which is the most significant physical and psychological stressor our body had to deal with throughout human evolution. Ketones helped our ancestors to remain mentally sharp and physically fit when they tried to obtain food after starving for several days1.
Indeed, raising ketone blood levels by starvation would not be a viable strategy for fighters. Therefore, DARPA collaborated with researchers from NIH and the University of Oxford to develop a ketone drink. The collaboration proved successful and led to the development of a ketone monoester drink. This drink can raise your blood beta-hydroxybutyrate (BHB; the primary type of ketones in humans) to 2-3 mM in only 20 minutes2. Such blood BHB levels are typically achieved after 2 days of fasting3.
Thanks to deltaG, the use of the ketone drink is not limited only to military usage. It is available to everyone. In this blog, we explain how ketones can improve your athletic performance. You can also have a look at our other posts, where we describe how ketones improve your metabolism, cognition and longevity.
The benefits of ketones in the world of endurance performance can be divided into two parts – improved mitochondrial efficiency and glycogen sparing. Let’s start with the former. If you are into endurance sports, you probably know that mitochondria are cellular organelles where energy is produced in the form of ATP. Fatty acids, glucose or ketones are oxidised (burned) in mitochondria, and the energy released during the oxidation is used in the mitochondria to generate ATP. The energy stored in ATP is then used to fuel various processes in our body. One of these processes is muscle contraction. A seminal paper from 1995 showed that ketone oxidation results in remarkably efficient ATP production4.
If you want to discover in more detail how our mitochondria produce energy and why oxidising ketones results in more efficient ATP production than oxidising fatty acids or glucose, you can read our article about cellular respiration here. You will also find out why our company is called deltaG.
The improved efficiency of mitochondrial ATP production induced by ketones enables working muscles to contract more powerfully with lower oxygen consumption. This was demonstrated in an experiment with a perfused rat heart. When the heart was fuelled by a mix of ketones and glucose, its efficacy increased by 28% compared to the heart fuelled by glucose alone4. To make an analogy, ketones are like fuel which can increase the range of a car because its combustion generates more energy than the combustion of conventional fuel, in this case, glucose.
Moreover, this study also showed that burning ketones for energy generates less oxidative stress, which can damage many cellular organelles5. In the car analogy, oxidative stress could be compared to the amount of air-polluting exhaust gases released into the atmosphere. To sum up, ketones make the heart muscle contract stronger, require less oxygen for its combustion and generate less oxidative stress in the process.
You might argue that exercising body is a much more complicated system than a perfused rat heart. You are right; the physiology of perfused rat heart is not the same as the physiology of a runner or cyclist. However, there is evidence that ketones improved mitochondrial efficiency in exercising humans as well6. Endurance-trained athletes performed 60 minutes of incremental cycling exercise at the intensity of 25%, 50% and 75% of their VO2max. Compared to the control condition, ingestion of deltaG improved mitochondrial efficiency by 7%. In other words, deltaG allowed athletes to do more work with less oxygen.
The other mechanism of ketone-mediated exercise enhancement is glycogen sparing. There is one thing that every endurance athlete is afraid of – hitting the wall. Many endurance athletes believe you hit the wall when your muscle fibres run out of glycogen. Coming back to our car analogy, you hit the wall when your fuel tank is empty. This is only half-right. A new study7 from July 2022 showed that muscle bioenergetics are more complicated than a car tank.
While car performance is the same if the fuel tank is full or 80% empty, this study showed that muscle works differently. The performance started to decrease significantly when glycogen was depleted only halfway. While it might seem strange that the body would work this way, it is important to realise that body cannot afford to run out of glycogen entirely because it could be fatal. Therefore, fatigue starts well before the glycogen stores are empty. This means that keeping your muscle glycogen high is crucial for endurance performance.
According to a 2016 study8, ketones help you to spare glycogen during endurance exercice. Endurance-trained athletes cycled for 2 hours at 70% VO2max intensity on two occasions – after drinking only a carbohydrate solution or after consuming carbohydrates with deltaG. Muscle biopsies were performed after the 2 hours of exercise to examine muscle glycogen levels. Significantly more glycogen was preserved after drinking the deltaG+carbohydrate mixture. Such results suggest that raising your blood ketones delays glycogen use in the initial stages of endurance activity. As a result, more glycogen is available towards the end of the race, which gives you an advantage over your competitors.
Now we know the molecular mechanisms by which ketones affect performance. However, your question probably is if there is evidence from randomised controlled trials (gold-standard method of research) which shows that ketone can actually make you faster. Yes, there is! Endurance-trained athletes cycled for one hour at 75% Wmax, followed by a 30-minute time trial8. They performed the exercise on two separate occasions, once with a carbohydrate drink only and then with a deltaG+carbohydrate drink which kept blood BHB levels over 2mM for most of the exercise. On average, athletes cycled 411 meters further after drinking deltaG, which translates into a 2% performance improvement. This study was conducted in 2016. Six years later, deltaG is used by world-class endurance athletes in competitions like Tour de France or IRONMAN.
The benefits of ketones are usually mentioned in the context of endurance exercise, but recent evidence from a 2022 study9 showed that ketones improve high-intensity exercise as well. This study developed a test which simulated the performance profile of rugby union. It consisted of carrying one 20kg tackle bag over a 9-meter distance, followed by carrying a second bag over the same distance, picking up a ball, and sprinting 14 m before completing an unanticipated rapid change in direction. Rugby players completed this high-intensity test 2.1% faster after deltaG consumption. Our drink is used by high-intensity athletes in leagues like NFL or NHL.
As mentioned in the beginning, ketones evolved to help us survive periods of starvation. Our body faces a wide variety of challenges during a fast, as we describe in this blog post. One of these challenges is the preservation of muscle. While the body can use protein as fuel during starvation, this process is not favourable as we would lose muscle mass rapidly. Ketones can prevent the breakdown of muscles and preserve muscle mass which increases the chances of survival. This ‘ancient’ role of ketones also makes them a great aid for post-exercise recovery.
The repeated contraction of muscle fibres impairs the structural integrity of many muscle proteins, which are crucial for supporting the structure of the muscle fibre9. Moreover, similarly to starvation, muscle protein can also be used as a source of energy during exercise. The muscle reacts to exercise-induced damage by increasing muscle protein synthesis after exercise. Therefore, protein shakes are a necessary tool for every athlete as they provide enough amino acids to repair damaged protein and build new muscle protein. Many athletes think that post-exercise protein intake is the sole factor that dictates the effectiveness of muscle protein synthesis after exercise. However, this is not the case.
A 2017 study10 recruited endurance-trained athletes who did an exhaustive glycogen-depleting exercise for 80 minutes. In the 4 hours after the exercise, athletes drank either a classical protein/carbohydrate post-exercise shake alone or together with deltaG. Researchers performed muscle biopsies 5 hours after the exercise was finished. Athletes whose post-exercise included deltaG showed higher expression of mTOR protein in their muscles. mTOR is the major regulator of muscle protein synthesis and stimulates growth. Adding BHB to a culture of muscle cells increased protein synthesis by 90% due to increased mTOR activity. Clearly, the rate of muscle protein synthesis does not depend only on your post-exercise protein shake and can be enhanced by BHB. The ability of BHB to preserve muscle makes it a promising therapeutic tool for inpatients at risk of cachexia11, the excessive loss of muscle during prolonged bed rest.
The value of any sports science study increases when the study manages to authentically replicate the real world. A study which fulfils such criteria was published in 201912. The study took 3 weeks and aimed to investigate if deltaG can prevent a decline in performance induced by overreaching. The recruited athletes were pushed to their limits. They trained 2 times a day, 6 days a week for 3 weeks, and the total training load increased every week. Training sessions included high-intensity interval training, intermittent endurance training and constant-load endurance training. Participants in the experimental group received deltaG and a standard carbohydrate+protein shake after each training session and
30 minutes before sleep. Those in the control group received only the carbohydrate+protein shakes.
Participants were advised to exercise at the highest sustainable levels during endurance training sessions. The workload in these sessions did not differ between groups in the first two weeks, but those who drank deltaG showed a 15% greater training load in the third week. Moreover, at the very end of the 3-week programme, participants did an endurance test. It consisted of moderate-intensity cycling for 90 minutes to induce fatigue, followed by an all-out 30-minute time trial. Remarkably, those in the deltaG group showed 15% higher power output during the 30-minute time trial. Based on these results, researchers concluded that deltaG prevents the performance decline associated with a prolonged heavy training load. Studies like this explain why deltaG is currently used by most of the peloton in the Tour de France, where cyclists race over 2000 miles in only 23 days.
Cognition in Sports
So far, we have covered the effects of ketones on the physical aspects of performance. The numerous split-second decisions required in sports like football, ice hockey or basketball make cognitive function critical for these sports. Similarly, staying focused at the final stages of a race is also essential for endurance performance.
Out of all the tissues in the body, the brain prefers ketones the most. Again, this is determined by the evolutionary role of ketones. Our brain is usually fuelled by glucose because carbohydrate intake blocks any production of ketones. However, things change when glucose becomes scarce during starvation. Glucose scarcity is not a problem for many tissues because they can substitute glucose with fatty acids as an energy substrate. However, the brain does not have this option because it cannot metabolise fatty acids. The body has a clever way around this. It sends fatty acids into the liver and converts them into ketones, which are released into the bloodstream and used as fuel by the brain. Therefore, ketones are the brain’s alternative fuel during starvation.
The intriguing part is that in conditions when both glucose and ketones are available to the brain, the intake of ketones into the brain will increase, and intake of glucose will decrease13. In a prolonged fast, ketones will become the dominant fuel source for the brain3. Such findings show that ketones are not only an alternative but also the preferred brain fuel.
The fact that the brain prefers ketones as a metabolic substrate is also supported by results of a recent study from October 202214, which showed that ketones improve cognition under mental fatigue, such as during and after exercise. Participants completed cognitive tests combined with exercise on two different occasions - with or without drinking deltaG. First, they underwent 40-minutes of computer-based tests, which induced mental fatigue. Then, participants did 45 minutes of high-intensity, intermittent exercise, which simulated a soccer match. Participants performed one session of the reaction test before the exercise started and 6 sessions during the exercise. As expected, exercise impaired the performance in the reaction test. However, the control group showed a 3.4% reduction in correct answers, while the performance of the deltaG group dropped only by 1.3%.
The enhancement of cognitive function is also an example of the major difference between ketone esters (deltaG) when compared to ketone salts. A study published in 202015 reported that ketone salts do not improve cognitive performance. However, a closer look into this study reveals that peak blood BHB levels after ketone salt consumption were only 0.8mM. For comparison, deltaG raised BHB levels to 1.6mM in the previously mentioned study, where ketones did improve cognitive performance. This shows that the capacity of ketone supplements to raise blood BHB over a certain threshold often decides whether it works or not. We described the major differences between ketone esters and ketone salts in this article.
As you can see, we do not make baseless claims about our product, we rely on science. We do in-house research, but we also gladly send our product to research labs worldwide, which produced many of the studies cited in this article. With all the information from this article, we will let you decide if we are justified to call ketones the natural super fuel. If you have more questions about deltaG and ketones, you can always schedule a 15-minute appointment with our ketone coach to get a bespoke protocol for using deltaG for your specific use case.
- Dilliraj, L.N., Schiuma, G., Lara, D., Strazzabosco, G., Clement, J., Giovannini, P., Trapella, C., Narducci, M. and Rizzo, R., 2022. The Evolution of Ketosis: Potential Impact on Clinical Conditions. Nutrients, 14(17), p.3613.
- Clarke, K., Tchabanenko, K., Pawlosky, R., Carter, E., King, M.T., Musa-Veloso, K., Ho, M., Roberts, A., Robertson, J., VanItallie, T.B. and Veech, R.L., 2012. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regulatory Toxicology and Pharmacology, 63(3), pp.401-408.
- Cahill Jr, G.F., 2006. Fuel metabolism in starvation. Annu. Rev. Nutr., 26, pp.1-22.
- Sato, K., Kashiwaya, Y., Keon, C.A., Tsuchiya, N., King, M.T., Radda, G.K., Chance, B., Clarke, K. and Veech, R.L., 1995. Insulin, ketone bodies, and mitochondrial energy transduction. The FASEB Journal, 9(8), pp.651-658.
- Sies, H., Berndt, C. and Jones, D.P., 2017. Oxidative stress. Annual review of biochemistry, 86, pp.715-748.
- Dearlove, D.J., Harrison, O.K., Hodson, L., Jefferson, A., Clarke, K. and Cox, P.J., 2021. The effect of blood ketone concentration and exercise intensity on exogenous ketone oxidation rates in athletes. Medicine and science in sports and exercise, 53(3), p.505.
- Vigh-Larsen, J.F., Ørtenblad, N., Nielsen, J., Andersen, O.E., Overgaard, K. and Mohr, M., 2022. The Role of Muscle Glycogen Content and Localization in High-Intensity Exercise Performance: A Placebo-Controlled Trial. Medicine and Science in Sports and Exercise.
- Cox, P.J., Kirk, T., Ashmore, T., Willerton, K., Evans, R., Smith, A., Murray, A.J., Stubbs, B., West, J., McLure, S.W. and King, M.T., 2016. Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell metabolism, 24(2), pp.256-268.
- Keefe, G. and Wright, C., 2016. An intricate balance of muscle damage and protein synthesis: the key players in skeletal muscle hypertrophy following resistance training. The Journal of Physiology, 594(24), p.7157.
- Vandoorne, T., De Smet, S., Ramaekers, M., Van Thienen, R., De Bock, K., Clarke, K. and Hespel, P., 2017. Intake of a ketone ester drink during recovery from exercise promotes mTORC1 signaling but not glycogen resynthesis in human muscle. Frontiers in physiology, 8, p.310.
- Koutnik, A.P., D’Agostino, D.P. and Egan, B., 2019. Anticatabolic effects of ketone bodies in skeletal muscle. Trends in Endocrinology & Metabolism, 30(4), pp.227-229.
- Poffé, C., Ramaekers, M., Van Thienen, R. and Hespel, P., 2019. Ketone ester supplementation blunts overreaching symptoms during endurance training overload. The Journal of physiology, 597(12), pp.3009-3027.
- Cunnane, S.C., Courchesne-Loyer, A., Vandenberghe, C., St-Pierre, V., Fortier, M., Hennebelle, M., Croteau, E., Bocti, C., Fulop, T. and Castellano, C.A., 2016. Can ketones help rescue brain fuel supply in later life? Implications for cognitive health during aging and the treatment of Alzheimer’s disease. Frontiers in molecular neuroscience, p.53.
- Quinones, M.D. and Lemon, P.W., 2022. Ketone Ester Supplementation Improves Some Aspects of Cognitive Function during a Simulated Soccer Match after Induced Mental Fatigue. Nutrients, 14(20), p.4376.
- Waldman, H.S., Shepherd, B.D., Egan, B. and McAllister, M.J., 2020. Exogenous ketone salts do not improve cognitive performance during a dual-stress challenge. International journal of sport nutrition and exercise metabolism, 30(2), pp.120-127.
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