Canadian researchers, which used ketone supplements containing β-hydroxybutyrate (β-OHB), found improvements to aspects of cognition and increases cerebrovascular blood flow (CBF).
These supplements may also reduce postprandial hyperglycaemia, which may increase CBF and levels of brain-derived neurotrophic factor (BDNF) that protect against obesity-related cognitive dysfunction.
"Once validated with a larger group of people, we expect that these supplements can be used to protect and improve brain health in people with obesity," suggests Dr Jeremy Walsh, first author on the study.
Study method
The research team began the placebo-controlled double-blind, cross-over design, by enrolling 14 adults with obesity, who all consumed 30 millilitres (mL) of β-OHB or placebo thrice-daily for 14 days.
They measured cognitive function and brain blood flow, also taking blood samples to measure hormone levels that help neurons grow and improving cognitive function.
Following the 14 days of ketone supplementation, the team observed significant improvements in cerebrovascular outcomes.
The team also observed improvements in the digit-symbol substitution (DSST) cognition test used in the experiment.
Here participants are asked to match symbols with digits based on nine corresponding digit-symbol pairings. The primary endpoint of the DSST is the number of correct items processed in 90 seconds.
“DSST performance significantly improved following ketone supplementation (+2.7 correct responses) and improved DSST performance was positively associated improvements in cerebrovascular outcomes,” the team writes.
“β-OHB supplementation was well-tolerated and appears to be safe for cerebrovascular health, suggesting potential therapeutic benefits of β-OHB in a population at risk of neurocognitive impairment.”
Nutritional ketosis
β-OHB is an endogenous, alternative fuel source for the brain, heart and skeletal muscle during periods of starvation, and exerts pleiotropic effects as a signalling molecule.
Until recently, elevating circulating β-OHB levels was only achievable via prolonged fasting or severe carbohydrate restriction.
The recent advent of exogenous oral ketone supplements capable of inducing rapid, nutritional ketosis and attenuating hyperglycaemia may aid in protecting and improving brain health, especially in adults with obesity.
While studies have shown an infusion of β-OHB increases CBF by 30–40% in young and middle-to-older aged humans, mechanisms remain unclear and independent of changes in arterial pco2 (a measure of carbon dioxide within arterial blood) or pH.
Past suggestions include the influence of subtle alternations in neuronal redox potential, reductions in oxidative stress and/or direct effects vascular function.
However, these effects are described solely in terms acute β-OHB exposure (i.e. hours) and the impact of regular short-term (i.e. days) ketone supplementation on CBF is unknown.
β-OHB neuroprotective qualities
“The results of the present study provide support for the recently reported safety and tolerability of β-OHB supplementation with respect to cerebrovascular health,” the team concludes.
“β-OHB may also be neuroprotective by positively modulating cerebral monocytes via the hydroxy-carboxylic acid receptor 2.
“Indeed, 14 days of β-OHB supplementation lowers lipopolysaccharide-stimulated monocyte activation in humans; however, we are unable to assess cerebral immune cell function in vivo in humans.”
Source: The Journal of Physiology,
Published online: DOI: 10.1113/JP281988
“Short-term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross-over trial.”
Authors: Jeremy Walsh et al.
