Ketone monoester ingestion and cognitive and physical performance during exercise-heat stress

What ketone monoester is

A drink that raises blood ketones directly, with no fasting and no cutting of carbohydrate. The body can burn the ketone beta hydroxybutyrate alongside glucose, and the brain takes it up as well.

Why they ran it

Hyperthermia degrades cognition partly through reduced cerebral blood flow and substrate delivery, with a reported eighteen percent global drop in cerebral blood flow during exercise heat stress, and glucose may become less available to the brain.

Ketones offer an alternative cerebral substrate and have protected cognition under hypoxia and after exhaustive exercise, but the authors state their efficacy during exercise heat stress remained unexplored.

Drawn from the paper's introduction, which states a purpose rather than a formal hypothesis.

Seventeen endurance trained men repeated the same session twice, a week or two apart. Each visit opened with a standard breakfast and caffeine at 4 mg per kg of body mass. Then came 90 minutes of treadmill walking at a 5 percent grade in 34 C and 45 percent humidity, wearing a vest at 20 percent of body mass, and a run to exhaustion at the end. The only difference between visits was a ketone monoester drink or an energy matched carbohydrate drink. Working memory, reaction time, blood ketones and glucose, heart rate and rectal core temperature were all tracked.

The run to exhaustion lasted 8.9 minutes after the ketone drink against 7.0 minutes after carbohydrate. On the easier 1-back working memory task, ketones held total accuracy 2.8 percent higher and target accuracy 8.9 percent higher across every time point, with better target discrimination too. Blood beta hydroxybutyrate ran 1.7 mmol/L higher mid exercise and 3.5 mmol/L higher afterwards, while blood glucose sat 14.7 and 27.6 mg/dL lower at those same points. Average heart rate and core temperature climbed with time in both conditions and never differed between them.

The wins were narrow. The harder 2-back task, Dynavision reaction time and the object hit and avoid task all came out level, and the authors are candid about why that is hard to read. Within subject variability was high on several measures, with baseline coefficients of variation reaching 37 percent for 2-back target accuracy. Both drinks were taken with caffeine, so nothing here separates a ketone effect from a caffeine effect.

The numbers

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Why this might happen

Proposed by the authors This is the explanation the authors offer in their discussion. This study did not test it.

Because ketone ingestion produced markedly elevated blood beta hydroxybutyrate, the authors suggest the increase in cerebral blood flow reported alongside raised beta hydroxybutyrate could underlie some of the cognitive effect, in regions associated with working memory and sustained attention.

They also raise the possibility that exogenous ketones supported central drive through greater energetic efficiency, preserving motivation and motor output despite hyperthermia.

They rule out the simplest alternative on their own data: core temperature and heart rate were the same in both conditions, so the differences were not mediated by reduced thermoregulatory or cardiovascular strain.

Drawn from the discussion sections on cognitive performance and on physiological responses.

What this does not show

This cannot tell you what the ketone monoester did on its own. Both arms received 4 mg per kg of caffeine, and the comparison was ketone versus carbohydrate on top of that. The authors note the independent effects of ketone, carbohydrate and caffeine were never tested here.
The endurance result was not something everyone got. Against a smallest worthwhile change of about 0.6 minutes, 9 of 17 participants improved, 4 got meaningfully worse on the ketone drink and 4 barely moved. The group standard deviation was 4.6 minutes on ketone against 2.1 on carbohydrate.
The flat cognitive results are not evidence that nothing happened. Reaction time and the object hit and avoid task carried high within subject variability, and the authors say the protocol may not have disturbed some measures enough for any effect to show.
None of this extends beyond young, very fit men. All 17 participants were males aged 18 to 35 who had to clear a VO2max of 55 ml/kg/min to enrol. Women, older adults and less trained people were not studied.

Where this leaves us

It is now more likely that ketone monoester taken alongside caffeine preserves accuracy on lower load working memory and stretches high intensity time to exhaustion after prolonged loaded exercise in the heat. The authors flag this as discordant with most existing literature, which has found exogenous ketones ergolytic for high intensity endurance.

Seventeen healthy endurance trained men aged 18 to 35 doing ninety minutes of loaded treadmill walking at 34 degrees Celsius in a weighted vest, with caffeine given in both conditions.

Trials that separate the independent effects of ketone monoester, carbohydrate and caffeine, with outcome measures of stronger test retest reliability, plus neuroimaging to link blood ketone concentration to cognition.

Caveats worth holding

The trial was built around a special operations use case, so the weight vest, the fixed walking pace and the heat chamber are not a normal training session for most athletes.
Ketone monoester has a strong distinctive taste. The team added a bittering agent to the carbohydrate drink and asked participants to guess which they had received, but taste based unblinding is hard to rule out in a study of this kind.
Most of the cognitive testing happened outside the heat chamber for practical reasons, with participants wrapped in a space blanket, so it did not capture thinking while genuinely hot.
The ketone monoester came from a commercial supplement maker.