(PTFS10-01-26) Confirmation That the Low Glutamate Diet Significantly Improves Cognitive Function in Veterans With Gulf War Illness

Objectives: Gulf War Illness (GWI) is a chronic multisymptom condition in veterans associated with cognitive impairment and other neurological symptoms. Prior research demonstrated that the low glutamate diet significantly improved cognition in veterans with GWI. A phase III clinical trial was conducted to confirm and expand on these prior findings.

Methods: Veterans with GWI were recruited from across the US. Subjects completed lab visits including blood draw, questionnaires, and a computerized cognitive assessment (CNSVS) (N=89). Subjects received a 2-hr dietary training via Zoom, were given detailed diet related materials, and then followed the diet for 1-month before returning for a post-diet visit. Dietary adherence was measured with an excitotoxin food frequency questionnaire. A subgroup then completed a double-blind placebo-controlled crossover challenge with MSG (n=55) and a 2-back working memory task (n= 50). Change scores were analyzed using paired t-tests/Wilcoxon signed-rank tests. Generalized linear mixed models were used to analyze the crossover challenge data. Cluster analysis was used to group participants based on MSG response, and blood measures were compared across clusters using one-way ANOVA/Kruskal-Wallis tests, with Tukey/Dunn’s post-hoc tests where applicable.

Results: Dietary adherence was high (p < 0.001). Following the diet, significant improvements were observed for overall cognitive function (96(14) to 103(11), p< 0.001). and working memory based on 2-Back accuracy (56% to 77%, p< 0.001). Significant inter-individual variability in cognitive response to MSG v. placebo was observed. Cluster analysis identified three patterns, improved (n=21), no response (n=7), and worsened (n=22), differing significantly across 8 cognitive domains (all p< 0.01). Significant differences between clusters were noted for RBC magnesium; kynurenic and quinolinic acid; plasma glutamine, proline, and asparagine levels.

Conclusions: The low glutamate diet was confirmed to significantly improve cognitive outcomes in veterans with GWI. Substantial heterogeneity in individual response to MSG was associated with mineral and metabolite variation, suggesting differential in how glutamate is being handled post dietary intervention.

Funding Sources: Department of Defense