What Diet Is Better for Seizure Reduction in Drug-Resistant Childhood Epilepsy?

Compared with the ketogenic diet, the modified Atkins diet may have better efficacy in seizure reduction and be more tolerable for the treatment of children with refractory epilepsy, according to study findings published in JAMA Pediatrics.

Researchers in India sought to assess the efficacy and safety of different dietary therapies used to treat drug-resistant childhood epilepsy. They conducted a systematic review and meta-analysis, searching for studies that focused on the ketogenic (including classic ketogenic and medium chain triglyceride) diet, the modified Atkins diet, and the low glycemic index diet.

The researchers identified 2158 possible journal articles published in PubMed, Embase, Ovid, and Cochrane from inception to April 2022. They included only 12 randomized control trials that included 907 patients (67% male) in their study. Of these 907 children, 664 were randomly assigned to one of these diets, while the remaining 243 received standard treatment.

The researchers determined treatment efficacy based on whether the diets reduced seizures by 50% or more, 90% or more, or 100% in the short-term (within 3 months or less). Additionally, they analyzed the safety of each diet by assessing adverse events causing withdrawal from the diet.

Within 3 months, approximately 36% of children treated with dietary therapies successfully achieved seizure reduction by 50% or more, 17% achieved seizure reduction by 90% or more, and 10% achieved complete seizure freedom.

Compared with standard care, the ketogenic diet (odds ratio [OR], 8.6; 95% CI, 3.7-20), the modified Atkins diet (OR, 11.3; 95% CI, 5.1-25.1), and the low glycemic index diet (OR, 24.7; 95% CI, 5.3-115.4) significantly reduced seizure frequency by 50% or higher. Indirectly, there was no significant difference between the 3 diets for this outcome.

Compared with standard care and the low glycemic index diet, only the ketogenic (OR, 6.5; 95% CI, 2.3-18.0) and modified Atkins (OR, 5.1; 95% CI, 2.2-12.0) diets resulted in a reduction of seizures by 90% or more. Similarly, only the ketogenic (OR, 5.0; 95% CI, 1.3-19.5) and modified Atkins (OR, 4.4; 95% CI, 1.3-14.5) diets resulted in complete seizure freedom. Indirectly, there was no significant difference between these 2 diets for these 2 outcomes, suggesting comparable efficacy.

Only 6 of the 12 studies evaluated safety of the dietary therapies. During the study periods, 44 children (7%) withdrew from the dietary therapies due to adverse events. Overall, in terms of discontinuation rates due to adverse events, children with refractory epilepsy tolerated the modified Atkins diet (OR, 6.5; 95% CI, 1.4-31.2) better than the ketogenic diet (OR, 8.6; 95% CI, 1.8-40.6).

The most commonly reported adverse events for those on the ketogenic diet included constipation, diarrhea, vomiting, hunger, fatigue, abdominal pain, hypercalciuria, and dyslipidemia. Adverse events for those on the modified Atkins diet included constipation, fatigue, vomiting, anorexia, dyslipidemia, and hypercalciuria.

“All dietary therapies (KD, [ketogenic diet], MAD [modified Atkins diet], and LGIT [low glycemic index diet]) are effective for 50% or higher seizure reduction in the short term compared with care as usual,” the researchers acknowledged.

“However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet,” they concluded.

Study limitations included clinical heterogeneity of the included studies, imprecision, and lack of strong evidence for indirect comparison between dietary therapies.