Exogenous Ketones and EPO boosting - Worth the Hype?

Exogenous ketones have generated considerable buzz in the endurance sports community over the past few years. Not to be confused with the ketones that circulate in the blood after adaptation to a very low carbohydrate, high-fat ketogenic diet, exogenous ketones are ingested in a supplement, much like carbohydrates in sports drinks. There are several types of exogenous ketones, with ketone monoesters receiving the most attention.

Initially, it was thought that, like carbohydrates in sports drinks, consuming exogenous ketones during exercise might provide an alternative fuel source to power prolonged exercise and reduce the use of our finite glycogen stores. Some evidence suggests that exogenous ketones do help us reduce glycogen use during exercise, although probably not through the direct burning of ketones for energy; the effect likely relates to some signaling response. In 2019, data emerged suggesting exogenous ketones might aid recovery from demanding exercise. Now, data suggest exogenous ketones may promote crucial cardiovascular adaptations to exercise training, via effects on the vital hormone erythropoietin, or EPO. We will focus on this data in this article.

Erythropoietin – EPO – what is it?

Erythropoietin, or EPO, is a hormone produced by the kidneys that plays a crucial role in the production of red blood cells. It signals the bone marrow to produce more red blood cells, responsible for carrying oxygen throughout the body. Increasing your overall red blood cell count is a key goal of endurance training, as more red blood cells mean enhanced ability to carry oxygen to the muscles to support aerobic metabolism. Increasing your red blood cell count and oxygen-carrying capacity will boost essential endurance-related variables like V̇O2max.

If you follow professional cycling, you may have heard of EPO. The use of artificial EPO was widespread as a performance-enhancing drug, particularly in the 1990s. Athletes injected EPO to stimulate red blood cell production and improve their performance. Research studies have shown that even small doses of EPO enhance endurance performance. Obviously, injecting artificial EPO to improve performance is both illegal and potentially dangerous; but the point I am making here is that stimulating EPO production naturally will likely improve performance in endurance events.

What did the new study show?

The exciting headline finding of the new study was that including a ketone monoester in post-exercise recovery nutrition stimulated greater EPO concentrations. The study, conducted by researchers from the University of Bath in the UK, had nine male participants undertake a one-hour cycling session involving high-intensity intervals interspersed with periods at lower intensities. The participants did this twice; once with ingestion of carbohydrate and protein during the recovery period, and once with ketones added to the carbohydrate and protein.

The researchers took blood samples during the four hours following the exercise and measured the concentration of EPO in those samples. In the control condition, i.e., without ketones, there was a small elevation in EPO, particularly in the 2-4-hour post-exercise period. When ketones were ingested, the increase in circulating EPO concentration was larger, with the peak EPO concentration about 20% higher than in the control condition. The overall exposure to EPO above resting values, known as the integrated area under the curve, was also about three-fold greater in the ketone condition.

Practical applications

These results are, as you can imagine, generating a fair bit of excitement in the sports nutrition world, as finding a safe, legal means of elevating EPO has the potential to stimulate red blood cell production and improve performance. The authors were, however, cautious to note that they only assessed the acute EPO response, and we should exercise some caution in interpreting these findings. We don't know if elevating EPO in this manner actually results in greater red blood cell production – it is likely, but we need longer-term trials to show this before we can be confident. Still, it's exciting!

So, what should we do? Well, the results do seem to add to the literature suggesting that ingesting ketones during recovery might be something we should consider as endurance athletes. The precise dosage we should take is still to be determined. That said, keep an eye on this space!

References

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4. Evans E, Walhin JP, Hengist A, Betrts JA, Dearlove DJ, Gonzalez JT. Ketone monoester ingestion increases postexercise serum erythropoietin concentrations in healthy men [Online]. Am J Physiol - Endocrinol Metab 324: E56–E61, 2023. https://www.who.int/news-room/fact-sheets/detail/autism-spectrum-disorders.
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