Low Carbohydrate Diet May Help Drug-Resistant Epilepsy

Safety, Efficacy, and Tolerability of the Modified Atkins Diet in Persons With Drug-Resistant Epilepsy

April 06, 2023

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Written by L. Carlos Mayor MD, FAES, FACNS
The modified Atkins diet has been found to be useful in some ways for patients with drug-resistant epilepsy (DRE). It is not easy to adapt to the Atkins diet because it usually represents a big change in food options. There are also concerns about safety in terms of increased levels of blood cholesterol and triglycerides as well as osteoporosis while on the diet.

In this article Manral et al describe the safety, efficacy, and tolerability of the modified Atkins diet in adolescents and adults with DRE. Between 2015 and 2019, the investigators conducted a prospective randomized study of patients attending an outpatient epilepsy clinic in India. Participants were drug-resistant, on at least three anti-seizure medications (ASM), and on no diet therapy for epilepsy for the past year. The patients continued on ASM only (control) or were randomized to ASM plus the modified Atkins diet. The target was a 50% reduction in seizures; secondary outcomes were improvement in quality of life, behavior, safety, and adverse events, and rate of ASM withdrawal at 6 months. Of the 160 patients included, 50% were adults and 50% were adolescents. At 6 months, there was a 26.2% seizure reduction in the Atkins group; 52.1% experienced an improvement in quality of life versus 42.5 % in the control group. Only 1 patient lost weight (an effect which can be useful in overweight patients) and 2 patients experienced diarrhea.

The results support the addition of a modified Atkins diet to the ASM schedule in people with DRE. The diet presents an opportunity for seizure reduction and improvement in quality of life for this group of patients who aren’t candidates for epilepsy surgery.


Abstract

BACKGROUND AND OBJECTIVES
Modified Atkins diet (MAD) has emerged as an adjuvant therapy in drug-resistant epilepsy (DRE). Most studies are in children; there is limited evidence for DRE in adults. This study aimed to investigate whether MAD along with standard drug therapy (SDT) was indeed more effective than SDT alone in reducing seizure frequency and improving psychological outcomes at 6 months in adolescents and adults with DRE (nonsurgical).

METHODS
A prospective randomized controlled trial was conducted at tertiary care referral center in India. Persons with DRE aged 10-55 years attending outpatient epilepsy clinics between August 2015 and April 2019, who had more than 2 seizures per month despite using at least 3 appropriate antiseizure medications (ASMs) at their maximum tolerated doses and had not been on any form of diet therapy for the past 1 year, were enrolled. Patients were assessed for the eligibility and randomly assigned to receive SDT plus MAD (intervention arm) or SDT alone (control arm). The primary outcome was >50% reduction in seizure frequency, and the secondary outcomes were quality of life (QOL), behavior, adverse events, and rate of withdrawal at 6 months. Intention-to-treat analysis was performed.

RESULTS
A total of 243 patients were screened for eligibility; 160 patients (80 adults and 80 adolescents) were randomized to either the intervention or control arm. Demographic and clinical characteristics in both groups were comparable at baseline. At 6 months, >50% seizure reduction was seen in 26.2% in the intervention group vs 2.5% in the control group (95% CI 13.5-33.9; p < 0.001). Improvement in QOL was 52.1 ± 17.6 in the intervention group vs 42.5 ± 16.4 in the control group (mean difference, 9.6; 95% CI 4.3 to 14.9, p < 0.001). However, behavior scores could be performed in 49 patients, and improvement was seen in the intervention vs control group (65.6 ± 7.9 vs 71.4 ± 8.1, p = 0.015) at the end of the study. One patient had weight loss; 2 patients had diarrhea.

DISCUSSION
The MAD group demonstrated improvement in all aspects (reduction in seizure frequency and behavioral problems) compared with the control group at the end of the study. MAD is an effective modality in controlling seizures; further research is required to assess its efficacy in terms of biomarkers along with descriptive metabolomics studies.

TRIAL REGISTRATION INFORMATION
The clinical trial registry of India: CTRI/2015/07/006048.

CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that the MAD increases the probability of seizure reduction in adolescents and adults with DRE.

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