Key Takeaway
Ketone ester supplementation during 12 hours of ultra-endurance cycling preserved mental alertness and increased circulating dopamine levels compared to placebo.
Summary
This randomized controlled trial investigated whether exogenous ketone ester supplementation could maintain cognitive function and mental alertness during ultra-endurance exercise. The study used a 12-hour cycling protocol designed to simulate the extreme demands of ultra-endurance competition, where cognitive decline from prolonged exertion is a real performance and safety concern.
Participants consumed ketone ester drinks alongside carbohydrate during the prolonged cycling bout. The researchers measured circulating neurotransmitter levels, subjective mental alertness, and cognitive performance at multiple time points throughout the 12-hour effort. The key finding was that exogenous ketosis significantly increased circulating dopamine concentrations and maintained mental alertness, while the placebo group experienced progressive cognitive decline.
The dopamine findings are particularly notable because central fatigue during ultra-endurance exercise is thought to be partly mediated by changes in brain neurotransmitter balance. By maintaining dopamine levels, ketone supplementation may address one of the mechanistic drivers of mental fatigue during prolonged exercise, offering a practical tool for ultra-endurance athletes where pacing decisions and hazard awareness depend on sustained cognitive function.
Methods
Randomized, placebo-controlled, crossover trial. Trained endurance athletes completed 12 hours of cycling on two occasions, receiving either ketone ester or placebo alongside matched carbohydrate intake. Blood samples were collected at regular intervals for analysis of BHB, dopamine, and other neurotransmitter metabolites. Cognitive performance and subjective mental alertness were assessed at multiple time points throughout the protocol.
Key Results
- Ketone ester supplementation significantly elevated blood BHB throughout the 12-hour exercise bout
- Circulating dopamine concentrations were significantly higher in the ketone condition compared to placebo
- Mental alertness was maintained in the ketone group while it progressively declined in placebo
- The cognitive protective effects became more pronounced in the later hours of exercise when fatigue was greatest
- Carbohydrate oxidation and overall energy expenditure were comparable between conditions
Limitations
- Small sample size typical of ultra-endurance research protocols
- Circulating dopamine may not directly reflect central (brain) dopamine levels
- The 12-hour lab-based cycling protocol, while demanding, may not fully replicate real-world ultra-endurance race conditions
- Single dose/formulation tested, so optimal dosing remains unclear
- Participants were trained athletes, so results may not generalize to recreational exercisers
- Taste differences between ketone ester and placebo may have partially unblinded participants