Investigation of the low glutamate diet as an adjunct treatment for pediatric epilepsy: A pilot randomized controlled trial

Gabrielle L Sarlo; Amy Kao; Kathleen F Holton

doi:10.1016/j.seizure.2023.02.013

Investigation of the low glutamate diet as an adjunct treatment for pediatric epilepsy: A pilot randomized controlled trial

Seizure. 2023 Mar:106:138-147. doi: 10.1016/j.seizure.2023.02.013. Epub 2023 Feb 20.

Authors

Gabrielle L Sarlo¹, Amy Kao², Kathleen F Holton³

Affiliations

¹ Department of Neuroscience, Behavior, Cognition and Neuroscience Program, American University, Washington DC, United States; Children's National Research Institute, Center for Neuroscience, Washington, DC, United States.
² Division of Neurophysiology, Epilepsy, and Critical Care, Center for Neuroscience and Behavioral Medicine, Children's National Medical Center, Washington, DC, United States; Division of Neurology 2, Office of Neuroscience, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, United States.
³ Department of Health Studies, American University, Washington DC, United States; Department of Neuroscience, American University, Washington DC, United States; Center for Neuroscience and Behavior, American University, Washington DC, United States. Electronic address: holton@american.edu.

PMID: 36867910
DOI: 10.1016/j.seizure.2023.02.013

Abstract

Introduction: Current dietary therapies for epilepsy have side effects and are low in nutrients, which would make an alternative dietary treatment, which addresses these issues, advantageous. One potential option is the low glutamate diet (LGD). Glutamate is implicated in seizure activity. Blood brain barrier permeability in epilepsy could enable dietary glutamate to reach the brain and contribute to ictogenesis.

Objective: to assess the LGD as an adjunct treatment for pediatric epilepsy.

Methods: This study was a nonblinded, parallel, randomized clinical trial. The study was conducted virtually due to COVID-19 and registered on clinicaltrials.gov (NCT04545346). Participants were eligible if they were between the ages of 2 and 21 with ≥4 seizures per month. Baseline seizures were assessed for 1-month, then participants were allocated via block randomization to the intervention month (N=18), or a wait-listed control month followed by the intervention month (N=15). Outcome measures included seizure frequency, caregiver global impression of change (CGIC), non-seizure improvements, nutrient intake, and adverse events.

Results: Nutrient intake significantly increased during the intervention. No significant differences in seizure frequency were observed between intervention and control groups. However, efficacy was assessed at 1-month compared to the standard 3-months in diet research. Additionally, 21% of participants were observed to be clinical responders to the diet. Overall health (CGIC) significantly improved in 31%, 63% experienced ≥1 non-seizure improvements, and 53% experienced adverse events. Clinical response likelihood decreased with increasing age (0.71 [0.50-0.99], p=0.04), as did the likelihood of overall health improvement (0.71 [0.54-0.92], p=0.01).

Discussion: This study provides preliminary support for the LGD as an adjunct treatment before epilepsy becomes drug resistant, which is in contrast to the role of current dietary therapies in drug resistant epilepsy.

Keywords: diet; epilepsy; glutamate.

Publication types

Randomized Controlled Trial

MeSH terms

Adolescent
Adult
Anticonvulsants / therapeutic use
COVID-19*
Child
Child, Preschool
Diet
Drug Resistant Epilepsy* / drug therapy
Epilepsy* / drug therapy
Glutamic Acid / therapeutic use
Humans
Pilot Projects
Seizures / drug therapy
Young Adult

Substances

Glutamic Acid
Anticonvulsants

Associated data

ClinicalTrials.gov/NCT04545346