Ketones have been touted as this magic supplement that results in extra-ordinary performances. Is it really a magic bullet or is it an expensive placebo. A new study investigated.
“It is possible that ketones, spare muscle glycogen and improve performance but it is also possible that ketones inhibit carbohydrate metabolism and reduce high intensity exercise performance. Neither of these theories has been tested”
Studies on ketone esters so far?
Ketone supplements have received a lot of attention recently and we discussed it in this previous blog. It is important to distinguish ketone salts and ketones esters. Ketone salts can supply smaller amounts of ketone bodies without causing gastro-intestinal distress. Ketone esters are tolerated much better but are more difficult to obtain in many parts of the world and are expensive. The effects of the intake of ketone bodies are still uncertain.
Improved performance with ketone esters
One study showed a small effect on time trial performance after 1h of steady state exercise (1). The researchers observed a 2% improvement in a 30 min time trial performance. It was shown that the ketone ester caused ketosis (high ketone body concentrations in the blood) and it was suggested that this might have resulted in glycogen sparing in the muscle. Essentially the ketone bodies are a type of fat, and when that is used as a fuel, there is no need to use the precious carbohydrate stores. Glycogen sparing during the first hour, would perhaps explain the performance benefit in the subsequent time trial.
No effect on performance with ketone esters
A follow-up study (2) found no effects of ketone esters on performance and suggested that the ketone esters may not stimulate fat metabolism but inhibit carbohydrate metabolism. This inhibiting effect on carbohydrate use (glycolytic rate) could be detrimental in some situations.
“Results of studies with ketone esters so far have been inconclusive”
The new study
A recent study from the University of Leuven in Belgium (3) tried to get some answers.
The researchers performed a double blind placebo controlled study for which they recruited 12 cyclists and triathletes. The participants performed 2 exercise trials. Both trials consisted of a 3 hours intermittent exercise, followed by a 15 min time trial and a sprint. In both conditions, cyclists received carbohydrate during exercise (60g/h), but in once condition they also received ketone esters. The ketone esters were ingested 60 min before , 20 min before and after 30 min during exercise (25g, 20g and 20g respectively). Muscle biopsies were collected to measure muscle glycogen and performance was measured in the time trial and sprint.
What did they find?
No difference in muscle glycogen breakdown or performance were observed between the ketone ester and control treatment. If anything, glycogen breakdown was more rapid in the ketone ester trial. This means that there were neither positive nor negative effects and the study did not support the theory that glycogen was spared but it also did not find evidence for inhibition of glycolysis and negative effects on high intensity exercise performance.
No difference in muscle glycogen breakdown or performance were observed between the ketone ester and control treatment.
Effect on buffering capacity?
In the paper the authors describe another observation they made. They observed a decrease in the blood pH and a decrease in blood bicarbonate. This would indicate the negative effect on buffering capacity. However, since there was no effect on performance we should question the importance of this.
The authors conclude: Ketone ester intake does not cause glycogen sparing, neither does it affect all out performance in the final stage of a simulated race.
This study shows that glycogen has little or no role to play in any potential ketone effects. Assumptions were made in this study that a potential effect of ketone ester ingestion was through glycogen glycogen and also that it should be avoided to take ketone ester later in exercise because it could potentially inhibit glycolytic rate. As a result in this study, blood ketone body concentrations returned to within the normal range towards the end of exercise. So, if ketone bodies would have another effect, that was dependent on ketosis and not related to glycogen, it is perhaps not surprising that no effects were seen in this study. After 3 hours of intermittent exercise, ketone body concentrations may not have been elevated enough. So his study has helped to establish that glycogen sparing is very unlikely to be an important mechanism, but there are still many questions about a possible role of ketone esters.
Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab 24: 256– 268, 2016.
Evans M, McSwiney FT, Brady AJ, Egan B. No benefit of ingestion of a ketone monoester supplement on 10-km running performance. Med Sci Sports Exerc 51: 2506–2515, 2019.
Poffé, C.,M. Ramaekers, S. Bogaerts, and P. Hespel. Exogenous ketosis impacts neither performance nor muscle glycogen breakdown in prolonged endurance exercise J Physiol 2020 https://doi.org/10.1152/japplphysiol.00092.2020