Seizure tests distinguish intermittent fasting from the ketogenic diet

Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests.

Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ∼12 days, starting at 3-4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol.

The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz-induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol.

In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption.