The low glutamate diet improves cognitive functioning in veterans with Gulf War Illness and resting-state EEG potentially predicts response

ABSTRACT

Objectives: Gulf War Illness (GWI) is a chronic, multi-symptom disorder with underlying central nervous system dysfunction and cognitive impairments. The objective of this study was to test the low glutamate diet as a novel treatment for cognitive dysfunction among those with GWI, and to explore if baseline resting-state electroencephalography (EEG) could predict cognitive outcomes.

Methods: Cognitive functioning was assessed at baseline, after one-month on the diet, and across a two-week double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG) relative to placebo.

Results: Significant improvements were seen after one-month on the diet in overall cognitive functioning, and in all other domains tested (FDR p < 0.05), except for memory. Challenge with MSG resulted in significant inter-individual response variability (p < 0.0001). Participants were clustered according to baseline resting-state EEG using k-means clustering to explore the inter-individual response variability. Three distinct EEG clusters were observed, and each corresponded with differential cognitive effects during challenge with MSG: cluster 1 had cognitive benefit (24% of participants), cluster 2 had cognitive detriment (42% of participants), and cluster 3 had mild/mixed effects (33% of participants).

Discussion: These findings suggest that the low glutamate diet may be a beneficial treatment for cognitive impairment in GWI. Future research is needed to understand the extent to which resting-state EEG can predict response to the low glutamate diet and to explore the mechanisms behind the varied response to acute glutamate challenge.

KEYWORDS:

• Gulf War Illness
• cognitive functioning
• electroencephalography (EEG)
• glutamate
• dietary intervention

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data is available upon request.

Additional information

Funding

This work is supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Gulf War Illness Research Program under Award No. W81XWH-17-1-0457. The U.S. Army Medical Research Acquisition Activity, 820 Chandler St, Fort Detrick MD 21702-5014, is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

Notes on contributors

Anna E. Kirkland

Drs. Anna E. Kirkland (previous graduate student) and Kathleen F. Holton (Associate Professor in the Health Studies Department) are part of the Nutritional Neuroscience Lab at American University, which studies the negative effects of food additives on glutamatergic neurotransmission, as well as the protective effects of certain micronutrients against excitotoxicity, with the aim of optimizing neurological function through dietary treatment.

Michael Baron

Dr. Michael Baron is a Professor in the Mathematics and Statistics department at American University, and his research interests include sequential analysis and optimal sequential designs; change-point estimation and on-line detection; multiple comparisons; Bayesian inference; and the application of statistics in epidemiology.

John W. VanMeter

Dr. John W. VanMeter is a Professor in the Department of Neurology and the Director of the Center for Functional and Molecular Imaging at Georgetown University, and his research focuses on the study of neurodevelopment and adolescent drug and alcohol use by employing longitudinal studies and the integration of different kinds of MRI data.

James N. Baraniuk

Dr. James N. Baraniuk is Professor in the Department of Medicine at Georgetown University, and his research focuses on improving lives through clinical sciences with an emphasis on Gulf War Illness and Chronic Fatigue Syndrome.