7751 - Antioxidant Vitamin Therapy: To 'E' or not to 'E'...

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Unformatted text preview: Antioxidant Vitamin Therapy: To 'E' or not to 'E' JoAnn E. Manson, MD, DrPH Chief, Division of Preventive Medicine Brigham and Women's Hospital Professor of Medicine Harvard Medical School State of the Art Lecture ROAD MAP Biological Mechanisms Animal Studies Human Observational Studies Randomized Clinical Trials Conclusions CAUSES OF DEATH IN THE UNITED STATES National Center for Health Statistics, 1998. Heart Disease 31.6% Cerebrovascular Disease 9.4% Other 27.5% Cancer 23.4% Respiratory Diseases 8.1% C a r d i o v s c u l D e 41% HYPOTHESIZED ANTIATHEROGENIC MECHANISMS OF ANTIOXIDANT VITAMINS Antioxidant vitamins can inhibit the oxidation and/or uptake of LDL cholesterol. Oxidized LDL is the particularly atherogenic form of cholesterol. ROLE OF OXIDIZED-LDL IN ATHEROSCLEROSIS Endothelial damage Monocyte/macrophage recruitment Increased uptake of LDL by foam cell Alteration in vascular tone Induction of growth factors Formation of autoantibodies to oxidized LDL HYPOTHESIZED ANTICANCER MECHANISMS OF ANTIOXIDANT VITAMINS Antioxidant vitamins may prevent tissue damage by trapping organic free radicals and deactivating excited oxygen molecules, a by-product of many metabolic processes. DEFENSE MECHANISMS AGAINST FREE RADICAL OXIDATION Compartmentalization of oxidative metabolism Transition metal binding by transport and storage proteins Intracellular enzymes Superoxide dismutase Glutathione peroxidase Catalase Dietary antioxidants Vitamin E Vitamin C Carotenoids DNA repair mechanisms STUDY OF PROBUCOL AND LOVASTATIN IN HYPERLIPIDEMIC RABBITS Extent of aortic lesions, % surface area involved Exp. group Total aorta Aortic arch Untreated (n = 6) 40.6 5.1 87.5 3.5 Lovastatin (n = 11) 27.5 4.6 65.0 4.9 Probucol (n = 11) 14.3 2.1 47.1 5.3 Source: Carew T, et al. Proc Natl Acad Sci 1987; 84:7725-29. ANIMAL STUDIES OF VITAMIN E AND PREVENTION OF ATHEROSCLEROSIS Species Dose Endpoint Restricted 1,000 mg/kg feed Decreased plasma an ovulatory hens peroxides and aortic intimal thickening Hypercholesterolemic 10 mg/kg body Decreased aortic mongrel rabbits weight thickening Monkeys fed 108 IU at entry or Decreased carotid atherogenic diet 12 months after ultrasound stenosis atherogenic diet PROSPECTIVE COHORT STUDIES OF ANTIOXIDANT VITAMINS AND CARDIOVASCULAR DISEASE Nurses Health Study Massachusetts Elderly Cohort Health Professionals Follow-up Study First National Health and Nutrition Examination Survey (NHANES I) Iowa Womens Health Study LIMITATIONS OF OBSERVATIONAL EVIDENCE Observational epidemiologic studies are unable to control for the potential effects of confounding variables not collected or not known to the investigators....
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This note was uploaded on 02/23/2012 for the course PHARM 290 taught by Professor Staff during the Fall '10 term at Rutgers.

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7751 - Antioxidant Vitamin Therapy: To 'E' or not to 'E'...

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