Acute administration of ketone beta-hydroxybutyrate downregulates 7T proton magnetic resonance spectroscopy-derived levels of anterior and posterior cingulate GABA and glutamate in healthy adults.
Level 3 - non-randomized controlled study
Controlled within-subject metabolic intervention study without explicit mention of randomization in the abstract
PubMed 35995971 · doi:10.1038/s41386-022-01364-8
What was done
Researchers investigated the neurochemical effects of acute d-beta-hydroxybutyrate (D-βHB) monoester administration in fasting healthy adults using 7 Tesla proton magnetic resonance spectroscopy (MRS). The investigation used two within-subject experiments: one assessing pre- and post-D-βHB changes in the anterior cingulate cortex (n = 16), and another assessing pre- and post-D-βHB changes in the posterior cingulate cortex compared to an active glucose control (n = 26). Associations with age and blood concentrations of D-βHB and glucose were also examined.
What was found
Levels of GABA and glutamate (Glu) decreased significantly in both the anterior and posterior cingulate cortices after D-βHB administration. This reduction occurred with D-βHB but was not observed following glucose administration. The magnitude of GABA and Glu reduction was significantly predicted by older age and by greater elevations in circulating blood D-βHB levels. No exact numerical concentrations, effect sizes, or confidence intervals were reported in the abstract.
Why it matters
This paper demonstrates that exogenous ketone administration acutely alters primary inhibitory and excitatory neurotransmitter levels in the human cortex differently than glucose, with stronger effects observed in older individuals.
Limits
The sample sizes were small across both cohorts. The abstract does not specify whether treatment order was randomized or blinded, tests only acute effects in fasting healthy adults rather than chronic clinical outcomes, and reports no numerical values or variance metrics.
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