Ketogenic Diet: Electrophysiological Effects on the Normal Human Cortex

Summary: Purpose: To explore the cortical electrophysiology of the ketogenic diet (KD) in the normal human. KD is effective against refractory epilepsy, but its precise mechanism is obscure. At the transmitter level, an enhancement of GABA inhibition has often been proposed. Methods: We studied eight healthy volunteers undergoing a “classic” KD for 2 weeks. We measured several biochemical variables at baseline (T0), after 1 week (T1) and 2 weeks (T2) of KD, then 3 months after the KD conclusion (T3). Ketosis was quantified as 24-h ketonuria. At the same time, we studied the motor cortical excitability by means of transcranial magnetic stimulation (TMS). We also quantitatively evaluated the EEG signal in search of frequency shifts over the rolandic areas. Results: Significant (p < 0.05) neurophysiological changes appeared at T2. These consisted of a strengthening of short-latency cortical inhibition (SICI), a TMS index which is thought to reflect GABA-A inhibition in the cortex. Then, there was an enhancement of the beta EEG band over the perirolandic region, similar to that following administration of GABA-A agonists. All changes disappeared at T3. Conclusions: A standard, short-term KD affected the cortical physiology of the normal human. The main changes were an augmented SICI and an increased perirolandic beta EEG activity, which are compatible with a lower level of neural excitation within the cortex.