Ketone Supplements for Endurance Performance: Looking beyond the Physical Realm

Could alertness and dopamine underlie the ergogenic benefits of ketone esters?

Ketone esters have emerged as a novel addition to the realm of performance-enhancing supplements, yet the evidence for their efficacy has been less than compelling.

Initial studies investigating ketone esters for endurance performance demonstrated a modest improvement of approximately 2% in physical endurance during a 30-minute cycling time trial following a 1-hour submaximal cycling bout.

However, newer research has failed to replicate these findings, showing no performance enhancement in longer-duration endurance events with ketone esters and, in some cases, observing a negative impact on high-intensity exercise performance. These latter effects are usually attributed to gastrointestinal side effects that may occur due to the ingestion of exogenous ketones, or an increase in blood acidity (pH).

What are ketone esters, also referred to as exogenous ketones?

Exogenous ketones: a brief overview and physiological effects

Ketones are produced by our liver during periods of fasting, low-carbohydrate dieting, and prolonged exercise. When fat is broken down (“burned”), ketones are synthesized in the liver and shuttled to the brain, skeletal muscle, and other tissues where they can be used to produce energy in the form of ATP.

https://journals.physiology.org/doi/full/10.1152/ajpcell.00359.2023 

Exogenous ketones are ketones that you ingest in the form of a supplement (usually in liquid form) — allowing you to enter ketosis without fasting, dieting, or exercise. This is known as exogenous ketosis, in contrast to endogenous ketosis which occurs when your body is producing ketones.

For those looking to learn more, we’ve got an entire page dedicated to exogenous ketones on Examine.

The potential performance benefits of exogenous ketones may be attributed to a shift in "fuel preference" during exercise, marked by increased ketone body oxidation and reduced glycolysis. Ketones offer an alternative substrate for energy production in the brain, heart, and skeletal muscles, potentially conserving glucose and glycogen.

Notably, ketones appear to be advantageous only when exercise duration is sufficient to deplete muscle glycogen or lower blood glucose levels. That’s because high-intensity exercise relies on carbohydrate oxidation, making exogenous ketones less likely to provide benefits, whereas long-duration activities, such as ultramarathon running, may benefit from ketone supplementation due to depleted glycogen levels.

The potential cognitive boost associated with ketones also raises the question of whether they could positively impact the mental aspects of exercise. This becomes particularly important during (ultra)endurance events, where mental fatigue, a lack of focus, and reduced alertness could compromise performance. More on this later.

https://journals.physiology.org/doi/full/10.1152/ajpcell.00359.2023 

Limited literature on exogenous ketones and cognitive performance suggests that ingesting ketone esters may mitigate the decline in executive function after exhaustive high-intensity exercise. In non-exercise contexts, ketone ester supplementation has shown promise in improving cerebral blood flow and various cognitive aspects in adults with obesity. However, the effectiveness of ketones in cognition appears to be dependent on achieving a blood ketone level at or above 1.5 millimolar (mM).

Conversely, when blood ketone levels are below 1 mM, and ketone salts are used instead of esters, no cognitive improvement is observed during dual-stress challenges or following high-intensity exercise.

Ketones for exercise recovery

In addition to an interaction between exercise and cognitive performance, some studies even suggest that ketones might be beneficial in preventing overtraining symptoms and aiding exercise recovery by promoting muscle protein synthesis and restoring muscle energy balance, 

In fact, there’s a neat hypothesis that exogenous ketones may be useful as a strategy for exercise recovery.