Classic Ketogenic Diet Versus Modified Atkins Diet for Drug-Resistant Childhood Epilepsy: Seizure Reduction, Tolerability, and 12-Month Dietary Adherence

This study investigates comparative seizure reduction, gastrointestinal tolerability, and 12-month dietary adherence in children with drug-resistant epilepsy randomized to classic ketogenic diet versus modified Atkins diet within the context of pediatric neurology and dietary epilepsy therapy, an area of growing scientific importance given its implications for drug-resistant pediatric epilepsy clinical dietary therapy selection, dietitian counseling protocols, and dietary adherence support intervention design. Using open-label randomized controlled trial with seizure diary, monthly EEG, plasma ketone monitoring, and GI symptom scale at 1, 3, 6, and 12 months; intention-to-treat analysis, we examine dietary ketosis elevating blood ketone bodies providing alternative neuronal fuel and reducing neuronal excitability via GABA/glutamate ratio shift, HCN channel modulation, and mTOR pathway inhibition independently of blood glucose in 148 children with drug-resistant epilepsy (mean age 6.4 years, mean 3.8 anticonvulsants failed, 54% focal/46% generalized epilepsy), 74 per arm drawn from pediatric neurology epilepsy clinics at Ridgemont Childrens Hospital and 2 affiliated centers with dietitian-supervised initiation and monthly telehealth follow-up. Results indicate that responder rates at 6 months are 54.1% (KD) vs. 50.0% (MAD), not significantly different (p=0.62); MAD shows significantly better 12-month adherence (68.9% vs. 44.6%, p=0.002) and fewer GI adverse events (p = 0.62 (efficacy); 0.002 (adherence)), with 50% responder rate: 54.1% KD vs. 50.0% MAD at 6 months; 12-month adherence 68.9% vs. 44.6% as the primary quantitative benchmark. Concordance between primary and confirmatory measurement approaches exceeded 93%, validating the analytical framework. These findings contribute empirically to pediatric neurology and dietary epilepsy therapy and carry actionable implications for the design of programs and policies targeting drug-resistant pediatric epilepsy clinical dietary therapy selection, dietitian counseling protocols, and dietary adherence support intervention design.