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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  &lt; 0.05), except for memory. Challenge with MSG resulted in significant inter-individual response variability ( p  &lt; 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.

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