Effects of a diet low in excitotoxins on PTSD symptoms and related biomarkers.

Post-traumatic stress disorder (PTSD) develops after trauma exposure and involves symptoms of avoidance, intrusive re-experiencing, mood and cognitive dysfunction, and hypervigilance. PTSD is often comorbid with Gulf War Illness (GWI), a neurological condition involving widespread pain, cognitive dysfunction, digestive problems, and other symptoms, in Gulf War veterans. PTSD tends to be more severe when comorbid with GWI. Low cortisol and elevated homocysteine levels have been found in PTSD, making them potential PTSD biomarkers. The low-glutamate diet, which aims to reduce excitotoxicity by eliminating the consumption of free glutamate and aspartate, has been shown to significantly reduce GWI and PTSD symptoms. This study examined whether changes in serum cortisol and homocysteine are associated with reduced PTSD severity in veterans with GWI after one month on the low-glutamate diet, and whether reducing the consumption of dietary excitotoxins was associated changes in PTSD and serum biomarkers. Data were analyzed for 33 veterans. No serum biomarkers significantly changed post-diet; however, cortisol increased as dietary excitotoxin consumption decreased, which held in a multivariable linear regression after adjustment for sex. Reduced dietary excitotoxin consumption was also associated with reduced hyperarousal symptoms, which held in a multivariable linear regression after adjustment for sex. Cortisol increase was associated with reduced avoidance symptoms after adjustment for change in BMI, and was marginally associated with overall PTSD reduction. Change in homocysteine was not significantly related to dietary adherence nor change in PTSD. Results suggest that reducing the consumption of dietary excitotoxins may normalize cortisol levels, which has been associated with alleviating PTSD.

Sex Hormones, Neurosteroids, and Glutamatergic Neurotransmission: A Review of the Literature.

Glutamatergic dysfunction has been implicated in the pathophysiology of multiple conditions including epilepsy, chronic pain, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD), raising interest in potential ways of modifying glutamate in the nervous system. Emerging research has suggested an interactive effect between sex hormones and glutamatergic neurotransmission. The objective of this paper was to review existing literature on the mechanism of interaction between sex hormones and glutamatergic neurotransmission, as well as to explore what is known about these interactions in various neurological and psychiatric conditions. This paper summarizes knowledge regarding mechanisms for these effects, and glutamatergic response to direct modulation of sex hormones. Research articles were identified via scholarly databases including PubMed, Google Scholar, and ProQuest. Articles were included if they were original research from peer-reviewed academic journals that dealt with glutamate, estrogen, progesterone, testosterone, neurosteroids, glutamate and sex hormone interactions, or the potential impact of glutamate and sex hormone interactions in the following conditions: chronic pain, epilepsy, PTSD, and PMDD. Current evidence suggests that sex hormones can directly modulate glutamatergic neurotransmission, with specific protective effects against excitotoxicity noted for estrogens. An effect of monosodium glutamate consumption on sex hormone levels has also been demonstrated, suggesting a possible bidirectional effect. Overall, there is a good deal of evidence suggesting a role for sex hormones, and specifically for estrogens, in the modulation of glutamatergic neurotransmission.

Post-traumatic stress disorder may set the neurobiological stage for eating disorders: A focus on glutamatergic dysfunction.

Post-traumatic stress disorder (PTSD) is a trauma and stress-related disorder which has been shown to be highly comorbid with, and commonly a precedent of, the eating disorders anorexia nervosa, bulimia nervosa, and binge eating disorder. The objective of this review is to discuss a potential overlapping neurobiological mechanism for this comorbidity. Alterations in glutamatergic neurotransmission have been observed in all four of the aforementioned disorders. Excessive excitation via glutamate contributes to excitotoxicity, and over-activation of the hypothalamic-pituitary-adrenal axis, both of which have implications for the deterioration of various brain structures. Prominent structures impacted include the hippocampus, hypothalamus, and prefrontal cortex, all of which are integral to the regulation of stress and eating. The current review suggests that altered glutamate function by trauma or extreme stress may facilitate PTSD and subsequent eating disorder onset, and that glutamatergic modulation may be a key treatment for individuals suffering from these conditions. This overlapping mechanism may help inform future research on individuals with comorbid PTSD and eating disorders, and it could also help inform ways to potentially prevent the onset of these conditions.

Effect of the low glutamate diet on inflammatory cytokines in veterans with Gulf War Illness (GWI): A pilot study.

AIM: To examine the effects of the low glutamate diet on inflammatory cytokines in veterans with Gulf War Illness (GWI). MAIN METHODS: Forty veterans with GWI were recruited from across the country. Anthropometric measurements and blood samples were collected at baseline and after one month on the low glutamate diet. Dietary adherence was measured with a glutamate food frequency questionnaire (FFQ). Inflammatory cytokines (IL-1ß, IL-6, IFN-γ, and TNF-α) were measured in pre- and post-diet serum (N = 34). Improvement was defined as being "much" or "very much" improved on the patient global impression of change scale (PGIC), or as having ≥30% of their symptoms remit. Correlations of the FFQ and the cytokines were calculated, followed by multivariable linear regression for significant findings. Mann Whitney U tests were used to compare cytokine levels according to improvement on the diet, and then logistic regression was used to estimate the association after adjustment for potential confounders. Classification trees were also produced to determine the ability of change in the inflammatory cytokines to predict improvement on the diet. KEY FINDINGS: Dietary adherence was significantly associated with reduction in TNF-α, and PGIC improvement was significantly associated with reduced IL-1ß, after adjustment for potential confounders. Classification trees demonstrated that IL-1ß, TNF-α, and IL-6 can predict improvement on the diet with 76.5% accuracy. SIGNIFICANCE: Findings suggest that the low glutamate diet may be able to reduce systemic inflammation in veterans with GWI.