{ "METABOLOMICS WORKBENCH":{"VERSION":"1","CREATED_ON":"April 13, 2017, 1:32 pm"}, "PROJECT":{"PROJECT_TITLE":"Mayo Metabolomics Pilot and Feasibility Award: Effects of Curcumin Supplementation on the Plasma Metabolome of Older Adults: Relation to Vascular Function","PROJECT_SUMMARY":"Age is the major risk factor for cardiovascular diseases (CVD). Two key contributors to the increased risk of CVD in middle-aged and older (MA/O) adults are stiffening of the large elastic arteries and the development of vascular endothelial dysfunction, indicated by impaired nitric oxide (NO)-induced endothelium-dependent dilation (EDD). The mechanisms by which aging causes arterial dysfunction are incompletely understood, but involve reductions in NO bioavailability associated with the development of oxidative stress and inflammation. Thus, establishing novel strategies to reduce arterial stiffness and increase vascular endothelial function in MA/O adults by increasing NO bioavailability and reducing oxidative stress and inflammation are a high biomedical research priority. Curcumin is a naturally occurring phenol found in the Indian spice turmeric that improves physiological function in animal models of age-related diseases and is a promising nutraceutical for intervention for promoting healthy aging. Our preclinical results indicate that chow supplemented with curcumin reduces aortic pulse wave velocity (PWV), the most common and clinically important measure of large elastic artery stiffness, restores NO-mediated EDD and reduces arterial oxidative stress and inflammation in old C57/BL6 mice. Preliminary data from our recently funded NIH R21 pilot grant indicate that curcumin supplementation improves vascular function in humans. It is possible that changes in the circulating (plasma) metabolome with oral curcumin supplementation will provide insight into novel metabolic mechanisms by which curcumin may improve vascular function. The goal of this project is to identify key metabolic pathways that change with oral curcumin supplementation and to relate those changes with improvements in vascular function in MA/O adults with initial endothelial dysfunction. Metabolomic analysis of plasma samples at baseline also may produce unique molecular signatures that predict responsiveness (changes in vascular function) to curcumin supplementation among individuals.","INSTITUTE":"Mayo Clinic","LAST_NAME":"Seals","FIRST_NAME":"Douglas","ADDRESS":"Department of Integrative Physiology University of Colorado Boulder, CO 80309","EMAIL":"seals@colorado.edu","PHONE":"303-492-5305"}, "STUDY":{"STUDY_TITLE":"Large Scale C18 Profiling of the Effects of Curcumin Supplementation of Older Adults: Relation to Vascular Function","STUDY_SUMMARY":"Perform large scale profiling C18 metabolite analysis related to nitric oxide biology, oxidative stress and inflammation in plasma before and after 12 weeks of oral curcumin (2000 mg/d) or placebo (double-blind, randomized) in men and women aged 45-79 years who are free from clinical cardiovascular disease.","INSTITUTE":"Mayo Clinic","LAST_NAME":"Seals","FIRST_NAME":"Douglas","ADDRESS":"Department of Integrative Physiology University of Colorado Boulder, CO 80309","EMAIL":"seals@colorado.edu","PHONE":"303-492-5305"}, "SUBJECT":{"SUBJECT_TYPE":"Human","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606"}, "SUBJECT_SAMPLE_FACTORS":[ { "Subject ID":"1", "Sample ID":"04jun15_004-r001", "Factors":{"group":"young","Time point":"Baseline"}, "Additional sample data":{"ionmode":"NC18"} }, { "Subject ID":"1", "Sample ID":"04jun15_004-r002", "Factors":{"group":"young","Time point":"Baseline"}, "Additional sample data":{"ionmode":"NC18"} }, { "Subject ID":"2", "Sample ID":"04jun15_005-r001", "Factors":{"group":"Old-Curcumin","Time point":"Pre"}, "Additional sample data":{"ionmode":"NC18"} }, { "Subject ID":"2", "Sample ID":"04jun15_005-r002", "Factors":{"group":"Old-Curcumin","Time point":"Pre"}, "Additional sample data":{"ionmode":"NC18"} }, { "Subject ID":"2", "Sample ID":"04jun15_006-r001", "Factors":{"group":"Old-Curcumin","Time point":"Post"}, "Additional sample data":{"ionmode":"NC18"} }, { "Subject ID":"2", 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"Factors":{"group":"Old-Curcumin","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"17", "Sample ID":"01jun15_031-r002", "Factors":{"group":"Old-Curcumin","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"17", "Sample ID":"01jun15_032-r001", "Factors":{"group":"Old-Curcumin","Time point":"Post"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"17", "Sample ID":"01jun15_032-r002", "Factors":{"group":"Old-Curcumin","Time point":"Post"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"18", "Sample ID":"01jun15_033-r001", "Factors":{"group":"young","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"18", "Sample ID":"01jun15_033-r002", "Factors":{"group":"young","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"19", "Sample ID":"01jun15_034-r001", "Factors":{"group":"Old-Placebo","Time point":"Pre"}, "Additional sample 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"Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"40", "Sample ID":"26may15_035-r001", "Factors":{"group":"Old-Placebo","Time point":"Post"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"40", "Sample ID":"26may15_035-r002", "Factors":{"group":"Old-Placebo","Time point":"Post"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"41", "Sample ID":"26may15_036-r001", "Factors":{"group":"Old-Placebo","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"41", "Sample ID":"26may15_036-r002", "Factors":{"group":"Old-Placebo","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"41", "Sample ID":"26may15_037-r001", "Factors":{"group":"Old-Placebo","Time point":"Post"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"41", "Sample ID":"26may15_037-r002", "Factors":{"group":"Old-Placebo","Time point":"Post"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"42", "Sample ID":"26may15_038-r001", "Factors":{"group":"Old-Placebo","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"42", "Sample ID":"26may15_038-r002", "Factors":{"group":"Old-Placebo","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"42", "Sample ID":"26may15_039-r001", "Factors":{"group":"Old-Placebo","Time point":"Post"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"42", "Sample ID":"26may15_039-r002", "Factors":{"group":"Old-Placebo","Time point":"Post"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"43", "Sample ID":"26may15_040-r001", "Factors":{"group":"young","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} }, { "Subject ID":"43", "Sample ID":"26may15_040-r002", "Factors":{"group":"young","Time point":"Pre"}, "Additional sample data":{"ionmode":"PC18"} } ], "COLLECTION":{"COLLECTION_SUMMARY":"Healthy men & women aged 45-79 without clinical CVD, but with below normal baseline endothelial dysfunction (FMDBA < 7%)."}, "TREATMENT":{"TREATMENT_SUMMARY":"A 12-week randomized, double-blind, placebo controlled study will be conducted. After CTRC screening for inclusion/exclusion criteria, qualified subjects will be randomly assigned to 1 of 2 groups. The investigators involved in the acquisition and analysis of key outcomes will be blinded to the curcumin intake status of the subjects. With the assistance of dietary monitoring from the UC-Boulder CTRC bionutritionists, subjects will maintain their baseline diet with either unchanged (control) or enhanced curcumin intake delivered as capsules (Longvida®, Verdure Sciences): Group 1 = placebo (inert substances); Group 2 = curcumin (2000mg curcumin/day). Extensive published work has established that the curcumin dose of 2000 mg/day is well tolerated and safe. Sessions 1 & 2: Screening measurements. Session 3: Baseline measurements and blood draw. Sessions 4-8 (every other week to assess adherence and overall subject well-being): Body weight, BP, adherence, discuss any problems. Session 9: Identical to session 3 (stop intake of capsules after completion of post-testing)."}, "SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Venous blood sampling. All blood samples are handled in a similar time frame and immediately spun to extract plasma and stored in our -80 freezer until ready for analysis."}, "CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Waters Acquity","COLUMN_NAME":"Waters Acquity HSS C18 (150 x 2.1mm, 1.8um)"}, "ANALYSIS":{"ANALYSIS_TYPE":"MS"}, "MS":{"MS_COMMENTS":"-","INSTRUMENT_NAME":"Agilent 6550 QTOF","INSTRUMENT_TYPE":"QTOF","MS_TYPE":"ESI","ION_MODE":"NEGATIVE"}, "MS_METABOLITE_DATA":{ "Units":"intensity", 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