Short-term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross-over trial.
Level 2 - randomized trial
Individual randomized crossover trial
PubMed 34605026 · doi:10.1113/JP281988
What was done
Fourteen adults with obesity (10 females, mean age 56 ± 12 years, BMI 33.8 ± 6.9 kg/m²) participated in a double-blind, placebo-controlled crossover trial. Participants consumed 30 mL (12 g) of a β-hydroxybutyrate (β-OHB) ketone monoester or placebo three times daily for 14 days. Extracranial blood flow and cerebrovascular conductance were assessed in the common carotid, internal carotid, and vertebral arteries via duplex ultrasound. Fasting serum and plasma brain-derived neurotrophic factor (BDNF) were measured by ELISA, and cognitive function was evaluated using digit-symbol substitution (DSST), Stroop, and task-switching tests.
What was found
Compared to placebo, 14 days of β-OHB supplementation led to significant increases in common carotid artery blood flow (+12%), vertebral artery blood flow (+11%), vertebral artery conductance (+12%), and vertebral artery shear rate (+10%). Performance on the DSST significantly improved (+2.7 correct responses) and this improvement correlated positively with the increases in carotid and vertebral blood flow and conductance. β-OHB supplementation did not significantly alter fasting serum or plasma BDNF concentrations.
Why it matters
These findings suggest that oral ketone ester supplementation can acutely enhance cerebral hemodynamics and processing speed in individuals with obesity who are at elevated risk for vascular and cognitive decline.
Limits
The study is limited by a very small sample size (n = 14) and a short 14-day intervention period. The abstract does not report specific quantitative outcomes for the Stroop or task-switching tests, and the clinical significance of these modest short-term vascular and cognitive changes over the long term remains unknown.
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- context Fasting and ketogenic diets increase adenosine levels in the brain, and fasting can acutely increase cerebral blood flow by 30%.