2009 Annual Report 1a.Objectives (from AD-416) The current agreement seeks to utilize the research and development efforts of the Arkansas Children’s Nutrition Center (ACNC) and the Agriculture Research Service (ARS) within the USDA in conducting laboratory, animal and human studies related to the use of cranberry and cranberry products in the diet as related to diabetes/obesity and how specifically the Type A procyanidins in cranberry and other foods might augment or alter the action of insulin. The project will utilize ARS’ technology and expertise in analyzing high procyanidin and other high antioxidant foods to understand absorption of polyphenolics and polyphenolic metabolites and Decas Botanical Synergies’ expertise in formulation and manufacture of natural compound based dietary supplements. Together the parties hope to identify sources and formulations of the target foods which optimize Type A procyanidin uptake. Test a modified colorimetric method (DMAC) for the quantitation of proanthocyanidins in cranberries and cranberry products and organize validation tests in multiple laboratories, collect, collate and analyze all data and summarize in a manuscript that is to be submitted for publication. 1b.Approach (from AD-416) Perform appropriate animal studies using the rat as the experimental model to study the ability of Type A procyanidins from cranberry to affect insulin action, blood glucose absorption/disappearance and parameters of lipid metabolism and body fat/lean mass. Develop a dose response curve for Type A procyanidins and observed alterations related to diabetes, obesity, and insulin resistance. 3.Progress Report Three animal experiments have been completed as part of this agreement. The objective of the first experiment was to evaluate the effect of dietary consumption of a cranberry concentrate powder (CCP) on metabolic parameters in a high fructose fed rat model of metabolic syndrome. Male Sprague-Dawley rats were fed one of five purified diets:. 1)Control (starch-based modified AIN93 diet);. 2)Fructose-rich diet (AIN-based diet containing 53% by weight of fructose (HF), 0 kcal starch);. 3)Fructose-rich diet with low, 3.3 g CCP per kg diet (HF + LC);. 4)Fructose-rich diet with medium, 6.6 g CCP per kg diet (HF + MC); and. 5)Fructose-rich diet with high, 33 g CCP per kg diet (HF + HC). Responses in blood levels of triglycerides, cholesterol, glucose, and insulin were monitored during the course of the experiment. An oral glucose tolerance test was used to monitor insulin function. The data from the experiment were analyzed and results suggested that inclusion of CCP in the diet was effective in modulating certain, but not all, aspects of metabolic parameters associated with metabolic syndrome and obesity. The medium level of CCP in the diet produced a better response than the lower and higher levels. A second objective of this study was to identify and quantitate in the urine catechin, epicatechin, and 19 phenolic acids and their conjugates in rats fed three levels of the CCP. Dietary flavonoids found in CCP can be converted into phenolic acids by colonic microflora and be absorbed into the circulation and may contribute to the health-promoting effects of the parent compounds. In this study, several phenolic acid metabolites were identified that could be related directly to the cranberry consumed. From this work it was clear that studies of bioactivity and health effects of food phytochemicals need to consider more than just the compound(s) in the food, since they can be metabolized to other lower molecular weight compounds which in turn may also be methylated or conjugated in some form that may affect the perceived health effects. A progress report was given during a visit to Decas Botanicals by the principal investigator in August 2009. Three manuscripts have been drafted and submitted for publication based upon the data obtained under this agreement. An additional meeting was held to discuss developing methods of analysis of cranberry procyanidins, with the objective of proposing a standardized method or methods that could be used by the cranberry industry. In this meeting plans were made to conduct a multi-lab validation study of the method selected, which has been completed and a manuscript has been drafted and submitted for publication.