Low glycaemic index diet reduces seizure susceptibility in a syndrome-specific mouse model of generalized epilepsy

• The low GI diet reduce the expression of generalized seizures by ∼30% in a mouse model.
• Under hypoglycaemic conditions the low GI diet was no longer effective.
• Fluctuating blood glucose levels may act as a seizure precipitant.
• A low GI diet may be an effective alternative dietary manipulation when more conventional diet options have failed.

SummaryPurposeClinical evidence suggests that low glycaemic index diets are effective at reducing seizure frequency potentially through the stabilization of blood glucose levels. Here we investigate if diets containing carbohydrates with varying glycaemic index (GI) can modulate seizure susceptibility in a mouse model of generalized epilepsy.MethodsElectrocortical recordings were made from mice harboring the GABAAγ2 (R43Q) epilepsy mutation after three weeks on a low-or high-GI diet. Standard rodent diet was used as a control. Occurrence and durations of spike-wave-discharges (SWDs) were measured. An insulin injection was used to reduce blood glucose to levels known to precipitate SWDs in the GABAAγ2 (R43Q) mouse on the low and high-GI diets.Key findingsSWD occurrence was reduced by approximately 35% in mice on the low-GI compared to high-GI diet. SWD occurrence was not different between high-GI diet and a standard diet suggesting that low-GI diet is protective. Weight gain of mice for all diet groups was identical suggesting that they were equally well tolerated. Under low blood glucose conditions SWD occurrence increased in the low and high-GI diets. Importantly, under low glucose conditions the low-GI diet no longer conferred protection against SWDs.SignificanceSWDs were reduced in mice on a low GI-diet suggesting it may be an effective and well tolerated therapy for generalized epilepsy. The lack of effect of low-GI diet when glucose levels are reduced suggests that seizure protection in the GABAAγ2 (R43Q) mouse model may be due to the diets ability to stabilize blood glucose levels.