Exogenous Ketones Research

This 2025 systematic review examined the efficacy and safety of exogenous ketones for cognitive function in mild cognitive impairment and Alzheimer's disease. Improvements were observed across multiple cognitive domains, though heterogeneity limits firm conclusions.

This systematic review evaluated the effects of both ketogenic diets and exogenous ketone supplements on the aerobic performance of endurance runners. The review specifically focused on running as the exercise modality, distinguishing it from the broader ketone-and-exercise literature that predominantly uses cycling protocols.

The authors systematically searched for studies examining ketone interventions in runners, assessing outcomes including time trial performance, VO2max, running economy, substrate utilization, and perceived exertion. For exogenous ketone supplements specifically, the evidence showed no consistent performance improvements in running-specific outcomes. However, metabolic changes were observed, including shifts toward greater fat oxidation and potential glycogen sparing during prolonged efforts.

The review highlights important distinctions between ketogenic diets and exogenous ketone supplements as interventions, and between cycling and running as exercise modalities. The authors note that running may impose unique physiological demands (weight-bearing, thermoregulation, biomechanics) that could influence how ketone metabolism affects performance. The lack of consistent performance benefits suggests that any metabolic advantages from ketone availability may not translate into meaningful performance gains for runners under typical race conditions.

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.

This systematic review and meta-analysis examined whether acute ketone body supplementation enhances endurance performance. No significant ergogenic effect was found across studies, despite theoretical mechanisms suggesting potential benefits.

This comprehensive narrative review examines the current state of evidence on exogenous ketone supplements in athletic contexts. The authors trace the history of ketone research from early metabolic studies through to modern sport-specific applications, covering ketone salts, ketone esters, and medium-chain triglycerides (MCTs).

The review synthesizes findings across multiple domains including endurance performance, recovery, cognitive function during exercise, and body composition. While exogenous ketones reliably elevate circulating beta-hydroxybutyrate (BHB) levels, the translation to measurable performance improvements has been inconsistent across studies. The authors highlight that benefits may be context-dependent, with the most promising applications in glycogen sparing during prolonged exercise, post-exercise recovery, and maintenance of cognitive function during exhaustive efforts.

The paper also identifies key methodological challenges in the field, including variability in ketone supplement formulations, dosing protocols, and exercise testing conditions. The authors outline future research directions needed to clarify the conditions under which exogenous ketones may offer genuine athletic advantages.

This randomized, crossover trial examined whether acute ingestion of exogenous beta-hydroxybutyrate (BHB) could improve exercise economy and reduce perceived exertion during submaximal treadmill walking. Ten non-aerobically trained participants (3 male, 7 female) consumed either 1 ounce of BHB solution or a placebo 30 minutes before completing two stages of a modified Bruce treadmill protocol.

Blood BHB concentrations were significantly elevated at both pre-exercise and post-exercise time points in the ketone condition compared to placebo, confirming the supplement successfully raised circulating ketone levels. However, despite this elevation in blood ketones, there were no significant differences between conditions for oxygen consumption, respiratory exchange ratio, energy expenditure, or rating of perceived exertion.

The findings suggest that while exogenous BHB reliably increases blood ketone availability, this does not automatically translate to improved exercise efficiency or reduced effort perception in untrained individuals performing moderate-intensity exercise. The authors concluded there was no evidence of an ergogenic benefit from BHB supplementation in this healthy, non-athlete population.

Study examining the acute effects of exogenous ketone consumption on appetite hormones and subjective hunger.

This narrative review examined the emerging interest in ketone body supplementation for athletic performance enhancement, particularly amid media speculation that professional cyclists were using ketone supplements. The authors reviewed the scientific literature on ketone body metabolism, availability, utilization during exercise, and the potential ergogenic effects of exogenous supplementation.

The review found that while skeletal muscle can use ketone bodies as fuel, uptake appears to saturate at relatively low concentrations (0.8-1.7 mmol/L), even though ketone supplements can raise blood levels to 3-6 mmol/L within 1-2 hours. Dietary strategies to increase endogenous ketone availability (ketogenic diets) require 4+ days of high-fat, low-carbohydrate eating, which may impair high-intensity exercise performance by reducing carbohydrate utilization.

The authors concluded that current understanding of ketone body kinetics during exercise is insufficient to warrant their use as an ergogenic aid in any practical sports setting. They noted that no data were available to support the claim that ingesting ketone bodies during exercise improves performance under conditions where evidence-based nutritional strategies are already applied appropriately. Key concerns included gastrointestinal tolerance, potential negative effects on carbohydrate availability during high-intensity efforts, and the lack of studies in trained athletes under realistic competitive conditions.

The review served as an important early critical assessment of the ketone supplement hype, tempering enthusiasm with a careful examination of the limited evidence base available at the time.

Landmark study examining the effects of ketone ester supplementation on endurance exercise performance in elite athletes.