Acute Supplementation of Beta‐Hydroxybutyrate Increases Visual Cortical Excitability in Humans: A Combined Electro‐EncephaloGraphy and Magnetic Resonance Spectroscopy Study

Abstract

Increasing plasma levels of ketone bodies via supplementation has been recently found to modulate the neurometabolic profile in the healthy human brain. Here, we aimed to explore the physiological consequences of these neurometabolic changes by assessing visual cortical function. Ten young adult human volunteers (mean age 27 years, range 23–34) were orally administered a single dose of a β‐hydroxybutyrate (βHB) ester (one of the main ketone bodies), and we measured neurometabolic change after supplementation. We used Electroencephalography (EEG) to assess cortical responsivity to visual stimuli and endogenous rhythms, and magnetic resonance spectroscopy (MRS) to quantify glutamate and GABA+ concentrations in the occipital cortex. βHB supplementation increased the amplitude of steady‐state visual evoked potentials and increased resting‐state EEG alpha power (8–13 Hz). These electrophysiological changes were paralleled by an increase in glutamate (but not GABA+) concentration in the occipital cortex. The glutamate increase was correlated with the increased steady‐state visual evoked potentials amplitude. This suggests that acute βHB supplementation increases the excitability of the brain cortex, as assessed neurometabolically and electrophysiologically. We discuss how these effects of acute supplementation may differ from the long‐term effects of chronic interventions in healthy or pathological brains.

Priming effects of ketone monoester supplementation on theta-burst stimulation-induced plasticity in the primary motor cortex: a randomized placebo-controlled crossover study

“…On the other hand, while extended ketogenic diets are a well-known antiepileptic intervention driven mainly by higher GABA/glutamate ratio (Pflanz et al, 2019; Qiao et al, 2024), such effects do not seem to extend to the acute nutritional ketosis induced by KME. In fact, MRS imaging showed a significant increase in glutamate (but not GABA) in the occipital cortex after acute KME supplementation (Steinwurzel et al, 2025). Other MRS studies revealed that acute KME supplementation significantly decreased both glutamate and GABA concentrations in the cingulate cortex (Hone-Blanchet et al, 2023; van Nieuwenhuizen et al, 2025).…”

Priming effects of ketone monoester supplementation on theta-burst stimulation-induced plasticity in the primary motor cortex: a randomized placebo-controlled crossover study

“…On the other hand, while extended ketogenic diets are a well-known antiepileptic intervention driven mainly by higher GABA/glutamate ratio (Pflanz et al, 2019; Qiao et al, 2024), such effects do not seem to extend to the acute nutritional ketosis induced by KME. In fact, MRS imaging showed a significant increase in glutamate (but not GABA) in the occipital cortex after acute KME supplementation (Steinwurzel et al, 2025). Other MRS studies revealed that acute KME supplementation significantly decreased both glutamate and GABA concentrations in the cingulate cortex (Hone-Blanchet et al, 2023; van Nieuwenhuizen et al, 2025).…”

Priming effects of ketone monoester supplementation on theta-burst stimulation-induced plasticity in the primary motor cortex: a randomized placebo-controlled crossover study

“…On the other hand, while extended ketogenic diets are a well-known antiepileptic intervention driven mainly by higher GABA/glutamate ratio (Pflanz et al, 2019; Qiao et al, 2024), such effects do not seem to extend to the acute nutritional ketosis induced by KME. In fact, MRS imaging showed a significant increase in glutamate (but not GABA) in the occipital cortex after acute KME supplementation (Steinwurzel et al, 2025). Other MRS studies revealed that acute KME supplementation significantly decreased both glutamate and GABA concentrations in the cingulate cortex (Hone-Blanchet et al, 2023; van Nieuwenhuizen et al, 2025).…”

Priming effects of ketone monoester supplementation on theta-burst stimulation-induced plasticity in the primary motor cortex: a randomized placebo-controlled crossover study

“…On the other hand, while extended ketogenic diets are a well-known antiepileptic intervention driven mainly by higher GABA/glutamate ratio (Pflanz et al, 2019; Qiao et al, 2024), such effects do not seem to extend to the acute nutritional ketosis induced by KME. In fact, MRS imaging showed a significant increase in glutamate (but not GABA) in the occipital cortex after acute KME supplementation (Steinwurzel et al, 2025). Other MRS studies revealed that acute KME supplementation significantly decreased both glutamate and GABA concentrations in the cingulate cortex (Hone-Blanchet et al, 2023; van Nieuwenhuizen et al, 2025).…”