Ketone supplements may promote better brain health in obese adults

Ketone supplements containing β-hydroxybutyrate (β-OHB) yield potential neurocognitive benefits in individuals with obesity, specifically bolstering cognitive function and increasing cerebral blood flow (CBF), as reported in a recent study.

“We show for the first time that 14 days of thrice-daily β-OHB supplementation improves aspects of cognition and increases cerebrovascular flow, conductance, and shear rate in the extracranial arteries of adults with obesity,” according to the first author of the study Dr Jeremy Walsh of McMaster University in Hamilton, Ontario, Canada.

Walsh also pointed out that their team found a significant positive relationship between elevated CBF and improved cognition following β-OHB supplementation.

Obesity may increase susceptibility to cerebrovascular disease and neurological impairment, partly because acute and chronic hyperglycaemia can reduce CBF and because reduced glucose tolerance contributes to poor cognitive performance and hippocampal atrophy. Impaired glucose tolerance and obesity are independently associated with reduced levels of circulating brain-derived neurotrophic factor (BDNF), which is critical for cognitive functioning. [J Biophotonics 2019;12:201900002; Tissue Cell 2018;54:139-143; Trends Endocrinol Metab 2014;25:89-98; Hippocampus 2009;19:973-980]

“We hypothesized that ketone supplementation, [which has been previously shown to reduce postprandial hyperglycaemia], would confer benefit on the cerebrovasculature via the direct effects of β-OHB on cerebral metabolism and CBF, as well as indirectly through its glucose-lowering effects,” Walsh said. [J Clin Endocrinol Metab 2021;106:e1738-e1754]

In the cross-over trial, 14 adults with obesity (mean age 56 years, 10 women, mean body mass index 33.8 kg/m²) were randomized to receive 30 mL (12 g) of β-OHB or placebo thrice-daily for 14 days. They were then switched to the alternative intervention for another 14-day period.

Walsh and colleagues used duplex ultrasound to measure blood flow (Q) and cerebrovascular conductance (CVC) in the common carotid (CCA), internal carotid (ICA), and vertebral (VA) arteries. They also quantified BDNF using an enzyme-linked immunosorbent assay.  

At the end of the intervention, ketone supplementation produced significantly better cerebrovascular outcomes than did placebo. There were improvements seen in Q_CCA (12 percent), Q_VA (11 percent), VA_CVC (12 percent), VA shear rate (10 percent), and digit-symbol substitution (DSST) performance (2.7 correct responses). Of note, DSST performance was positively correlated with improvements in Q_CCA, CCA_CVC, Q_VA and VA_CVC. [J Physiol 2021;doi:10.1113/JP281988]

However, β-OHB conferred no benefits for fasting serum and plasma BDNF.

“To the best of our knowledge, the present study is the first to characterize the effect of short-term ketone supplementation on multiple aspects of brain health in adults with obesity,” Walsh said.

“Given that the supplementation regimen was effective at lowering postprandial glucose and well-tolerated by participants, our trial provides a foundation for the potential nonpharmacological therapeutic application of ketone supplementation in patient groups at risk of hyperglycaemic cerebrovascular disease and cognitive dysfunction,” he added.