Low glycemic index therapy diet reduces seizure burden with fewer adverse events

The low glycemic index therapy diet provided a balance between reducing seizures and relatively fewer adverse events compared with the ketogenic diet and the modified Atkins diet, according to findings published in JAMA Pediatrics.

While neither the modified Atkins diet nor the low glycemic index therapy diet were noninferior to the ketogenic diet regarding seizure reduction at 24 weeks, the balance between fewer seizures and fewer adverse events with the low glycemic index therapy diet indicated that the risk-benefit decision between the three diets should be individualized for every patient, the researchers stated.

“Drug-resistant epilepsy responds poorly to pharmacologic management and frequently requires intervention via other modalities, including surgery, vagus nerve stimulation, and dietary therapy,” the researchers wrote. “The ketogenic diet has been used successfully to treat children with drug-resistant epilepsy. Data assessing the efficacy of the modified Atkins diet and low glycemic index therapy diet compared with the ketogenic diet are scarce.”

Vishal Sondhi, DM, of the Center of Excellence & Advanced Research on Childhood Neurodevelopmental Disorders in the division of child neurology, department of pediatrics, at All India Institute of Medical Sciences in New Delhi, and colleagues conducted a randomized trial to determine whether adding either the modified Atkins diet or the low glycemic therapy index diet to ongoing antiseizure drug therapy demonstrated noninferiority to the ketogenic diet regarding decreasing seizures. Percentage change in seizure frequency at 24 weeks served as the primary outcome.

Sondhi and colleagues randomly assigned 158 children to the ketogenic diet (n = 52), the modified Atkins diet (n = 52) or the low glycemic index therapy diet (n = 54). Eligibility criteria included age (1 to 15 years), seizure frequency (4 or more per month), response to prior therapy (no response to 2 or more antiseizure drugs) and diet history (no prior treatment with any of the diets investigated in the study). Enrollment took place between April 1, 2016 and Aug. 20, 2017, at a tertiary care referral center in India.

The median number of baseline daily seizures (ketogenic diet, 9; modified Atkins diet, 8.5; low glycemic index therapy diet, 9), number of patients with structural epilepsy (ketogenic diet, 33; modified Atkins diet, 41; low glycemic index diet, 41), and number of patients requiring four or more antiseizure drugs (ketogenic diet, 20; modified Atkins diet, 31; low glycemic index therapy diet, 31) were similar across study arms.

The researchers reported normal baseline clinical examinations in nine patients (16.4%) in the ketogenic diet arm compared with two patients (3.5%) in the low glycemic index therapy diet arm and two patients (3.4%) in the modified Atkins diet arm (P = .01). Patients in the low glycemic index therapy arm demonstrated significantly better dietary adherence (94.3%) compared with the ketogenic diet (91.4%) and modified Atkins diet (90.6%) arms, but all patients demonstrated greater than 80% adherence throughout the study.

After 24 weeks, the intention-to-treat analysis demonstrated a median interquartile range (IQR) change in seizure frequency that was similar across all groups (ketogenic diet: 66% [IQR, 85% to 38%]; modified Atkins diet: 45% [IQR, 91% to 7%]; and low glycemic index therapy diet: 54% [IQR, 92% to 19%]).

The median difference, according to the intention-to-treat analysis, in decreased seizure activity between the ketogenic diet and modified Atkins diet arms was 21 percentage points (95% CI, 29 to 3 percentage points) and 12 percentage points between the ketogenic diet and low glycemic index therapy diet arms (95% CI, 21 to 7 percentage points), with both breaching the noninferiority margin of 15 percentage points. Study findings showed similar rates of treatment-related adverse events between the ketogenic diet (31 of 55; 56.4%) and modified Atkins diet (33 of 58; 56.9%) arms and significantly fewer events in the low glycemic index therapy diet arm (19 of 57; 33.3%).

The results demonstrate that all three dietary regimens significantly decrease the seizure burden among children with drug resistant epilepsy, the researchers wrote, and support the use of all three dietary therapies. However, the results regarding the noninferiority of the modified Atkins and low glycemic index therapy diets remain inconclusive, according to Sondhi and colleagues.

“The risk profiling illustrates that the [low glycemic index therapy] diet is associated with the least number of and least severe adverse events, while the other [two] diets are more likely to be associated with serious and life-threatening events,” the researchers wrote. “It appears that each dietary intervention should be assessed in terms of the benefit in reducing seizure burden and the risk of adding adverse events before starting the [ketogenic diet], [modified Atkins diet], or [low glycemic therapy index] diet in children.”