Our long-term goal is to understand the health-related effects of consuming polyphenols found in plant based foods and beverages. Eating a diet rich in fruits, vegetables, and plant-derived beverages may reduce the risk of diseases that have been linked to oxidative stress, including inflammatory bowel disease, cardiovascular disease and cancer. Plants are a source of nutritive antioxidants (vitamins) but may also be a source of non-nutritive antioxidants. Polyphenols are the most common group of plant secondary products, and are effective antioxidants in vitro. We believe that the specific class of polyphenols known as the polymeric polyphenols has unique attributes not shared by other non-nutritive antioxidants. Polymeric polyphenols bind proteins with high affinity, so that polyphenol-protein complexes are the major species in the gastrointestinal tract. We speculate that binding to protein alters the properties-such as lifetime and antioxidant activities of polymeric polyphenols, making them uniquely suited to alleviating inflammatory bowel disease. We hypothesize that polymeric polyphenol/protein adducts provide a pool of persistent, high capacity activity that is localized to the Gl tract and is thus able to alleviate oxidative damage and inflammation directly at the site of inflammatory bowel disease. There are thousands of plant polyphenols, in several distinct structural classes. Conducting in vivo tests of our hypothesis would be impossible because it is not clear which compounds might be most bioactive. We propose in vitro studies to examine the persistence of ten different polyphenols and their protein adducts under gastrointestinal conditions. We will then examine the antioxidant and anti-inflammatory activities of these polyphenols and their protein adducts. This should allow us to identify types of dietary polyphenols that are most likely to alleviate inflammatory bowel disease in vivo, and position us to continue with testing in animals in a future proposal.