Sustained military operations (SUSOPs) expose soldiers to a multitude of stressors, including sustained physical activity, caloric deficit, and sleep deprivation. Several studies have shown that the combination of these factors result in psychological stress, which often leads to significant cognitive impairment.~Psychological stress has been shown to result in activation of neuroendocrine pathways that signal into the periphery and relay information from the brain to the immune system. This process is generally characterized by elevations of several key pro-inflammatory cytokines, chemokines, secondary messengers and reactive oxygen species. Notably, peripheral classical monocytes are reported to undergo recruitment to the brain during periods of psychological stress following priming by cytokines secreted from activated microglia.~Carnosine, an endogenous dipeptide consisting of beta-alanine and L-histidine, has been shown to inhibit the synthesis of inflammatory and oxidative mediators in microglia in vitro. Beta-alanine, which is the rate limiting amino acid in carnosine formation has been shown to increase carnosine concentrations in various regions of the brain in rodents which been associated with biochemical changes that resulted in favorable improvements in resilience to stress exposure. However, data on the effects of beta-alanine supplementation on cognition in humans is less clear. Further, the effect of beta-alanine supplementation on systemic and cellular mediators of monocyte recruitment has not been examined.~Goals:~To investigate the effect of sustained-release beta-alanine on changes in psychological stress and cognition using Automated Neuropsychological Assessment Metric (ANAM) cognitive assessments during a 24-hour simulated military operation.~To examine the effect of sustained-release beta-alanine on monocyte chemoattractant protein-1 (MCP-1), interleukin-8, Lymphocyte function-associated antigen-1 (CD11a), macrophage-1-antigen (CD11b) expression and C-C chemokine receptor 2 (CCR2) expression on neutrophils and classical monocytes during a 24-hour simulated military operation.~To examine associations between MCP-1, interleukin-8, CD11a, CD11b, CCR2 and a composite measure of cognition derived from ANAM assessment scores during a 24-hour simulated military operation.~Method:~Double-blind placebo controlled trial compared the effect of supplementation with sustained release beta-alanine (12 grams per day) versus placebo (equivalent amount of rice powder) on cognition and monocyte responses during a 24-hour simulated military operation consisting of sleep-restriction, caloric restriction, and acute and sustained periods military specific physical activity.~Supplementation occurred over a period of 14 days prior to completion of the simulated military operation. ANAM tests were assessed and blood samples taken upon arrival to the lab for the 24 hour simulated operation (0 hours) and at 12, 18 and 24 hours during the SUSOP.
Sustained military operations (SUSOPs) result in psychological stress and cognitive dysfunction, which may be related to the recruitment of classical monocytes into the brain.~Goals:~To investigate the effect of sustained-release beta-alanine on changes in cognition and markers of immune cell recruitment during a 24-hour simulated military operation.~To examine associations between changes cognition and changes in markers mediating immune cell recruitment.