title: EDTA Chelation Therapy to Reduce Cardiovascular Events in Persons with Diabetes.
abstract: The Trial to Assess Chelation Therapy (TACT) was a randomized double-blind placebo-controlled trial enrolling patients age ≥50 years with prior myocardial infarction. TACT used a 2 × 2 factorial design to study ethylene diamine tetraacetic acid (EDTA) chelation and high-dose vitamin supplementation. Chelation provided a modest but significant reduction in cardiovascular endpoints. The benefit was stronger and significant among participants with diabetes but absent in those without diabetes. Mechanisms by which chelation might reduce cardiovascular risk in persons with diabetes include the effects of EDTA chelation on transition and toxic metals. Transition metals, particularly copper and iron, play important roles in oxidative stress pathways. Toxic metals, in particular cadmium and lead, are toxic for the cardiovascular system. This review discusses the epidemiologic evidence and animal and human studies supporting the role of these metals in the development of diabetes and ischemic heart disease and potential ways by which EDTA chelation could confer cardiovascular benefit.
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 301 Bldg St 2400, 4940 Eastern Ave, Baltimore, MD, 21224, USA. pouyang1@jhmi.edu.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ouyang
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, 301 Bldg St 2424, 4940 Eastern Ave, Baltimore, MD, 21224, USA. sgottli@jhmi.edu.
authors.forename: Sheldon H
authors.initials: SH
authors.lastname: Gottlieb
authors.affiliation: Division of Biochemistry and Molecular Biology, Johns Hopkins University School of Public Health, 615 N. Wolfe St, E7626, Baltimore, MD, 21205, USA. vculotta@jhsph.edu.
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Culotta
authors.affiliation: Division of Occupational and Environmental Health, Johns Hopkins University School of Public Health, 615 N. Wolfe St, W7513D, Baltimore, MD, 21205, USA. anavas@jhu.edu.
authors.forename: Ana
authors.initials: A
authors.lastname: Navas-Acien
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D002614:Chelating Agents / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000379:methods*; D048909:Diabetes Complications / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D004492:Edetic Acid / Q000627:therapeutic use*; D006801:Humans; D008670:Metals; D019216:Metals, Heavy / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic
chemical_list: D002614:Chelating Agents; D008670:Metals; D019216:Metals, Heavy; D004492:Edetic Acid
keywords: Cardiovascular disease; Chelation; Diabetes; Metals; Oxidative stress