The effects of acute ketone monoester supplementation on brain insulin responsiveness and cognitive performance: Results of a randomized, double-blind, placebo-controlled crossover trial in older men with overweight.
MetabolismJun 9, 2026 (epub)
Kevin M R Nijssen, Tanja C Adam, Ronald P Mensink et al.
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In 30 seconds
This randomized, double-blind, placebo-controlled crossover trial examined the effects of acute ketone monoester (KME) supplementation on brain insulin responsiveness and cognitive performance in 18 older men with overweight. KME significantly lowered insulin-induced cerebral blood flow responses in multiple brain regions and modestly improved attention and psychomotor speed, with a reaction time reduction of 9 ms (P = 0.029).
Key findings
- KME induced nutritional ketosis with a peak β-hydroxybutyrate of 2.9 ± 0.4 mmol/L (P < 0.001).
- KME lowered insulin-induced CBF responses in ten brain clusters (all P ≤ 0.05).
- Attention and psychomotor speed improved with KME, showing a reaction time reduction of 9 ms (P = 0.029).
- Resting whole-brain CBF decreased by 4.7 mL/100 g/min (P < 0.001) after KME ingestion.
Why it matters
Understanding how nutritional ketosis affects brain insulin responsiveness and cognitive performance could inform strategies to mitigate age-related cognitive decline, particularly in older adults with overweight.