Alcohol abuse, oxidative stress, and zinc deficiency in lung disease

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DESCRIPTION (provided by applicant): Alcohol abuse is a major burden on society and even more of a problem in the veteran population. Chronic alcohol ingestion can have serious health consequences including pneumonia and acute lung injury, which can occur suddenly and without warning even in physically fit individuals, such as trained military personnel, even without apparent signs of alcohol dependence. Therefore, it is vital for the health of our veterans and indeed our entire population to identify effective treatments that can limit or even prevent these devastating consequences. The primary goal of this clinical research project is to determine if either dietary zinc or S-adenosylmethionine (SAM) supplements can augment lung immune defenses in otherwise healthy alcoholics and thereby decrease the risk of lung injury and infection. There is already strong evidence from our experimental animal models that moderate daily alcohol ingestion for as little as six weeks causes both redox stress and zinc deficiency in the lung. Regular alcohol consumption interferes with the body's ability to take in zinc from food and deliver it to the lung where it is essential for normal immune function and overall health of the lung. Research in the animal model suggests that oxidative stress and zinc deficiency in the lung result in dysfunction of the alveolar macrophage, which is the resident immune cell, and predisposes animals to the development of pneumonia. Importantly, in this same animal model, we found that adding either zinc or glutathione to the diet prevents these problems and preserves lung health even during daily alcohol ingestion. This CDA-2 project will translate basic findings in the animal model to the clinical setting and determine whether or not zinc or SAM supplements are effective in humans who pathologically consume alcohol. Parallel to the animal model data, our preliminary results from otherwise healthy alcoholic volunteers shows there exists both zinc deficiency and oxidative stress in the lung. This project will extend these findings and enroll veterans who are beginning alcohol treatment at the Atlanta Veterans Hospital in the Substance Abuse Treatment Program (SATP). Participants will be evaluated by undergoing a procedure to obtain samples of fluid from their lungs, measure zinc levels, redox potential, and assess how well their alveolar macrophages respond to bacteria (by determining phagocytic capacity). After completion of the initial evaluation, the participants will be randomized to receive standard treatment (placebo), zinc supplements, or dietary SAM for 14 days. All subjects will be evaluated for two weeks as they undergo treatment. At the end of this two week period, measurements of lung zinc, redox potential and macrophage function will be repeated and compared between the two groups. The hypothesis is that both dietary zinc and SAM supplements will improve alveolar macrophage immune function (as reflected by bacterial phagocytic capacity). If this project is successful, it will lead to larger scale clinical trials o determine if either dietary zinc or SAM supplements can be effective even in the acute clinical setting and improve outcomes in alcoholics who develop pneumonia or acute lung injury. Both zinc and SAM supplements are safe, simple, and inexpensive to provide, allowing these potential treatments to be easily implemented in the veteran population as well as society in general. Given the significant burden of unhealthy alcohol use, we desperately need to find ways to limit the physical consequences of alcohol abuse in this vulnerable population while we continue the efforts at public education and addiction treatment.