Modified Atkins and Low Glycemic Index Diets Noninferior to Ketogenic Diet in Epilepsy

Sheffali Gulati, MD

A trial (NCT02708030) assessing the efficacy of the modified Atkins diet (MAD) and low glycemic index therapy (LGIT) diet to the standard ketogenic diet (KD) in children with drug-resistant epilepsy demonstrated that neither diet is noninferior to KD, and that risk-benefit decisions for all 3 options should be individualized.

In total, 158 children (age range, 1–15 years) who had ≥4 seizures per month and had not responded to 2 or more antiseizure drugs nor been treated previously with any of the 3 diets completed the trial. Sheffali Gulati, MD, professor of pediatrics and chief, Child Neurology Division, All Institute of Medical Sciences, and colleagues, used percent change in seizure frequency after 24 weeks of dietary therapy in the MAD cohort compared with the KD cohort and in the LGIT diet cohort compared with the KD cohort.

After 24 weeks of intervention, the median change in seizure frequency for those on KD (n = 52) was –66% (interquartile range [IQR], –85% to –38%) compared to –45% for MAD (n = 52; IQR, –91% to –7%) and –54% on LGIT diet (n = 54; IQR, –92% to –19%). All 3 diet interventions showed similar significant seizure reduction (P = .39), with neither the MAD nor the LGIT diet meeting the noninferiority criteria.

Gulati and colleagues did notice 1 significant difference between the diet groups, though. Treatment-related adverse events (TEAEs) were similar between the KD (31 of 55; 56.4%) and MAD (33 of 58; 56.9%) arms but were significantly less frequent in the LGIT diet arm (19 of 57; 33.3%). Vomiting was among the most common adverse event (AE), which was observed in 28 patients (50.9%) who were on KD, 26 patients (44.8%) on MAD, and 18 patients (31.6%) on the LGIT diet.

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The investigators went on to write that the findings imply that “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 KD, MAD, or LGIT diet in children.”

The median difference, per intention-to-treat analysis, in seizure reduction between the KD and MAD arms was –21 percentage points (95% CI, –29 to –3) and between the KD and LGIT arms was –12 percentage points (95% CI, –21 to 7). Both comparisons breached the noninferiority margin of –15 percentage points, which was predefined at the beginning of the trial.

Secondary analyses that looked at ≥50% seizure reduction at 24 weeks were comparable across all 3 arms. In total, 35 of 52 (67.3%) patients on KD, 27 of 52 (51.9%) on MAD, and 32 of 54 (59.3%) on LGIT diet experienced that reduction. Notably, the change in seizure frequency was no associated with urinary ketone levels.

The investigators of the trial also noted that there was a rapid seizure reduction over the initial 4 weeks of the study with the KD and MAD, while the decrease was gradual over 10 to 12 weeks with the LGIT diet.

Baseline characteristics between the 3 arms showed similar median daily seizures (KD, 9; MAD, 8.5; and LGIT diet, 9; P = .99), proportion of patients with structural epilepsy (KD, 33; MAD, 41; and LGIT diet, 41; P = .33), and proportion of patients requiring 4 or more antiseizure drugs (KD, 20; MAD, 31; LGIT diet, 31; P = .16).

Ketogenic diets have often been a standard of care to treat intractable seizures and decrease plasma glycine levels in patients with glycine encephalopathy. In a recent NeurologyLive interview, Elizabeth Felton, MD, PhD, assistant professor of neurology, University of Wisconsin, provided insight on the additional oversight required when caring for adult epilepsy patients who remain on the ketogenic diet. Watch that conversation below.

REFERENCE
Sondhi V, Agarwala A, Pandey RM, et al. Efficacy of ketogenic diet, modified atkins diet, and low glycemic index therapy diet among children with drug-resistant epilepsy. JAMA Pediatr. Published online August 3, 2020. doi: 10.1001/jamapediatrics.2020.2282