Progress 11/01/07 to 04/30/10
Outputs
Progress Report 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. 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. Cranberry procyanidins alter insulin sensitivity: Male rats were given a single intraperitoneal (ip) injection of freshly prepared streptozotocin (STZ) at a dose of 70 mg/kg in 50 mM citrate buffer and produced a hyperglycemia greater than 400 mg/dL on day 7 after STZ injection. Cranberry proanthocyanidins given orally plus a low dose of insulin given ip potentiated insulin action in lowering glucose equivalent comparable to a high dose of insulin in diabetic rats. Cranberry-derived procyanidins had an additive antihyperglycemic effect in the presence of a low insulin dose, but not in the absence of insulin. Effects of dietary consumption of cranberry on insulin and other metabolic parameters associated with metabolic syndrome in growing rats fed high fructose diets: The effect of dietary consumption of a cranberry powder (CP) containing increased amounts of procyanidins and other phytochemicals on metabolic parameters associated with metabolic syndrome was investigated in rats fed a high fructose diet. Dietary treatments were control (starch-based), high fructose (HF), and HF containing low/med/hi levels of CP. Fasting plasma glucose and triglycerides tended to be higher with HF feeding and were reduced by feeding CP. The area under the curve following an oral glucose tolerance test was 35-50% higher in animals fed a HF diet compared to the control diet and decreased to control levels in rats fed the low/medium level of CP in the diet. Feeding CP tended to lower fasting plasma insulin. Homeostatic models of insulin resistance and beta-cell function were lowest in rats fed the low/medium levels of CP diets. In the fed state, plasma triglyceride levels increased with high fructose diet, whereas plasma insulin levels were lower. Inclusion of the CP in the diet was effective in modulating some aspects of metabolic parameters associated with metabolic syndrome; the medium level of CP in the diet produced a better response than the lower and higher CP levels. Standardization of method for determining cranberry procyanidins: Our goal was to validate an improved 4-dimethylaminocinnamaldehyde (DMAC) colorimetric method using a commercially available standard (procyanidin A2), for the quantitation of proanthocyanidins (PACs) in CPs, to establish dosage guidelines for the uropathogenic bacterial anti-adhesion effect of cranberry. For comparative purposes, the commercially available cranberry samples were alternatively quantitated using weights of extracted PACs (gravimetric). The correlation coefficient between the two methods was 0.989. This improved DMAC method provides a simple, robust, and relatively specific spectrophotometric assay for total PACs in cranberry samples using commercially available procyanidin A2 dimer as a standard. DMAC is most useful within a given type of food such as cranberries, but may not be appropriate for comparing concentrations across different food types, particularly those where large differences exist among the relative amounts of each of the proanthocyanidin oligomers and polymers.
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Progress 10/01/08 to 09/30/09
Outputs
Progress Report 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. 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. Significant Activities that Support Special Target Populations 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.
Impacts
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Progress 10/01/07 to 09/30/08
Outputs
Progress Report 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. 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. Significant Activities that Support Special Target Populations A total of four experiments using animal models have been outlined and details worked out. We have had three conference calls and a face to face meeting to work out some of the details. Progress has been slowed due to the inability to hire appropriately qualified personnel to work on the project. Animals and diet have now been ordered for the first experiment which is to be started in mid-August. The objective of the initial experiment is to determine if the cranberry preparation provided by Decas Botanicals, when fed in the diet to rats, will alter the dyslipidemia observed with high fructose feeding. Three levels of the cranberry preparation in the diet will be tested. The second experiment is expected to be started within 5 weeks of starting the first experiment. An additional meeting is being planned in which USDA will meet with Decas scientists to discuss methods of analysis of cranberry procyanidins with the objective of proposing a standardized method or methods that could be used by the cranberry industry.
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