Efficacy of Modified Atkins Diet versus Ketogenic Diet Among Children with Drug-resistant Epilepsy: A Systematic Review and Meta-analysis

Background: The ketogenic diet (KD), containing high levels of fat and low levels of carbohydrates has been used for decades to treat drug-resistant epilepsy (DRE). Recently, modified Atkins diet (MAD), a less restrictive form of KD, has gained popularity and proposed to be an alternative to the traditional KD. However, the evidence to support this hypothesis continued to be sparse. In this meta-analysis, we aimed to evaluate the utility of MAD compared to traditional KD for DRE in pediatric population.

Methods: We performed a comprehensive literature search using PubMed, Embase, Google Scholar, and Cochrane Library databases from database inception through May 2021 for all the studies that evaluated the clinical utility of MAD versus KD for DRE in pediatric population. The primary outcome of interest was the proportion of children who had >50% reduction in seizures (seizure frequency reduction (SFR) >50%). The secondary outcomes were proportion of children who had >90% reduction in seizures (SFR >90%), being seizure free, and who experienced side effects. All measurements were taken 6 months after starting the regimens. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CIs) were calculated and combined using random effects model meta-analysis.

Results: A total of 4 clinical trials (3 Randomized Control Trials) including 313 patients with DRE (164 followed MAD vs. 149 managed with KD) were included in the final analysis. The mean follow-up period was 6 months. There was a significant difference in proportion of patients who attained SFR > 50% favoring the traditional KD (RR:0.66; 95% CI:0.46-0.96; P=0.03). However, there was no significant difference in SFR >90% outcome (RR:0.90; 95% CI:0.61-1.32; P=0.57) or in the proportion of patients who had seizure freedom ( RR:1.07; 95% CI:0.68-1.70; P=0.76). Furthermore, both regimens had comparable safety profiles (RR:1.00; 95% CI:0.95-1.05; P=0.95).

Conclusion: Our study demonstrated that the traditional KD was associated with statistically significant success to reduce the seizure frequency by more than 50% when compared to MAD. However, MAD and KD had comparable efficacy and tolerability profiles in the management of DRE. Clearly, large scale RCTs are required to further investigate the role of MAD in the management of DRE.