Therapeutic Effects of the Low Glutamate Diet on PTSD Are Mediated by Reductions in Oxidative Stress

Objectives: Glutamate excitotoxicity causes oxidative stress, and both are implicated in post-traumatic stress disorder (PTSD). PTSD is caused by trauma and affects 16% of U.S. veterans. The low glutamate diet, which reduces dietary free glutamate and increases antioxidant intake, was previously shown to improve PTSD in veterans. The objective of this study is to examine whether the therapeutic effects of the low glutamate diet on PTSD are mediated by reducing oxidative stress, in veterans with Gulf War Illness. Methods: Preliminary data were analyzed from 17 veterans who completed participation in an ongoing clinical trial. Data were collected before and after 1-month on the low glutamate diet. Dietary adherence was assessed with an Excitotoxin FFQ. The Post-traumatic Checklist (PCL-5) measured PTSD severity. Blood and urine were collected to measure plasma glutamate and urinary lipid peroxides. Pre-post changes were assessed with paired t-tests/Wilcoxon Signed Rank tests, Pearson/Spearman correlations were assessed, and mediation was analyzed with the PROCESS macro model 4 in R. Mediation models examined whether reduction in lipid peroxides mediated the relationship between either dietary adherence or change in plasma glutamate, with PTSD score change. P-values ≤ 0.05 were considered significant, but marginally significant results are also reported given the small sample size. Results: PTSD symptoms were significantly reduced after the diet (p = 0.002). Excitotoxin FFQ scores showed strong dietary adherence (p = 0.0003), and plasma glutamate levels were marginally reduced (p = 0.06). Plasma glutamate reduction was related to reduction in lipid peroxides (a measure of oxidative stress) (r = 0.59, p = 0.02), and lipid peroxide reduction was marginally correlated with PTSD improvement (r = 0.46, p = 0.07). Mediation analyses showed that reduction in lipid peroxides mediated the relation of reduction in excitotoxin exposure with PTSD reduction, Bootstrap CI [0.01, 0.36], as well as the relation of reduced plasma glutamate and PTSD reduction, Bootstrap CI [0.14, 2.77]. Conclusions: These preliminary data suggest that the low glutamate diet effectively reduces PTSD symptoms, and this effect is partially due to reductions in oxidative stress. Findings will be updated as more data is collected.