MONITORING GLUTATHIONE LEVELS AFTER THE INGESTION OF A LIPOSOMAL GLUTATHIONE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. An application as recently submitted to NIH for funding of a study of the potential health benefits of an oral liposomal glutathione preparation. The application was not funded but received many positive comments and Dr. Gardner and colleagues intend to resubmit. One particular suggestion from a reviewer was that preliminary pharmacokinetic data be gathered on just 2-3 people, and presented with the next submission. It is the intent of this GCRC application to generate that requested preliminary data. The abstract for the original NIH application is presented here, although it is not particularly relevant since our current proposal to the GCRC is simply to run the pharmacokinetics. BACKGROUND: A number of observational and experimental studies have shown that the recognized risk factors for atherosclerosis and cardiovascular disease promote an inflammatory oxidative environment in the vasculature that is conducive to pathologic changes in the endothelium. Considerable evidence now exists that endothelial dysfunction both precedes and accelerates atherosclerosis. Antioxidant nutrients may therefore be presumed likely to contribute to a decrease of endothelial dysfunction and to diminish the incidence of cardiovascular events. However, the previous use of antioxidant supplements in clinical trials (e.g., Vitamins E and C, beta-carotene) has yielded disappointing and controversial results. Despite the null findings from recent trials, the biological plausibility of potential benefits from antioxidants remains strong. Continued work is needed in testing various compounds with antioxidant properties, and identifying the specific antioxidants that are effective therapeutic agents. OBJECTIVE: This study will determine whether a dietary supplement containing glutathione will lower levels of inflammatory markers, and whether the presence or absence of supplemental arginine will add to the effectiveness of the glutathione therapy. DESIGN: This is a randomized, double blind, placebo-controlled, parallel-arm, feasibility study. Ninety adults with elevated risk factors for atherosclerosis and heart disease will be randomly assigned for 8 weeks to either: 1) glutathione (GSH, n=30), 2) glutathione + arginine (GSH+Arg, n=30) or placebo (Plac, n=30). Data will be collected at baseline, 2, 4, and 8 weeks. Primary study outcomes are serum markers of inflammation including c-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-a) and soluble intercellular adhesion molecule-1 (sICAM-1). Secondary outcomes include blood pressure, blood cholesterol, serum isoprostanes (a measure of oxidative stress) and s-nitrosyl glutathione (a stable, nitric oxide containing compound). IMPLICATIONS: If glutathione, +/- arginine, can effectively lower inflammatory markers, this would suggest a safe and relatively inexpensive therapy to reduce the risk of cardiovascular disease. Recent studies have shown that oxidative stress and the inflammation associated with it are very common in the general population, and so any beneficial therapies found in this area would have widespread benefits.