During the 1990-91 Gulf War (GW), military personnel were exposed to numerous chemical and environmental agents during deployment including spraying of pesticides, petroleum combustion products, and nerve gas. Exposure to these chemical and environmental agents can damage cell function and more specifically, mitochondrial function, which negatively affects energy production and can lead to oxidative stress and neuroinflammation. Animal models using similar exposures have documented this in the central nervous system (CNS) compartment. This disruption in mitochondrial function and energy production is likely tied to resulting symptoms of Gulf War Illness (GWI) including fatigue, headaches, joint and muscle pain, gastrointestinal and sleep disturbances, neurologic and neuropsychological symptoms, respiratory issues, and cardiovascular problems.~The Gulf War Illness Clinical Trials and Interventions Consortium (GWICTIC) plans to evaluate N-Acetyl Cysteine (NAC) as a promising approach to help the CNS recover from chronic oxidative stress and depletion of antioxidants. The Congressionally Directed Medical Research Program's (CDMRP's) two Gulf War Illness Consortiums (GWICs) and others have added to the growing evidence of the role of CNS oxidative stress and neuroinflammation in symptoms of GWI, yet there is little definitive work on the delivery of antioxidants to the CNS environment. In this mechanistic study, we aim to determine if NAC has the ability to target mitochondrial dysfunction and reverse oxidative stress in the CNS. Based on our early experiences with antioxidants in GWI and other complex disease states along with the proven record of NAC in reducing glutathione (GSH) deficits, it is possible that this antioxidant will help to restore mitochondrial function and provide a more targeted approach to improve outcomes in Veterans with GWI.
This mechanistic study will test if NAC affects chronic oxidative stress and depletion of antioxidants in GWI participants. Blood specimen collection and neuroimaging will be used to determine whether NAC affects serum glutathione (GSH) concentration and oxidative stress in the CNS when compared to placebo.