Diving deep into chelation therapy for coronary artery disease: a review
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20195295Keywords:
Chelation therapy, EDTA, Cardiovascular disease, Coronary artery diseaseAbstract
Chelation therapy is still a mainstay therapy when it comes to dealing with heavy metal intoxication. The ability of various chelators to bind metal and other chemical molecules led to the idea whether chelation therapy can be used as an alternative therapy to enchain calcium element that is known to be present in the atherosclerotic plaque. Various studies have been conducted, one of which is a large trial to assess chelation therapy study to show in case ethylenediaminetetraacetic acid (EDTA) chelator can be proven by evidence-based in managing coronary heart disease. Despite the favorable results that were found in many literature studies, the results of the study are still under debate in various aspects. To address this issue, we conducted a review article to discuss comprehensively the general description of EDTA as chelation therapy, various mechanisms that can explain the use of EDTA in the management of coronary heart disease, the pharmacokinetic aspects of EDTA chelation therapy, as well as describing various existing studies with a good level of evidence to review the effectiveness of these therapies against coronary artery disease.
References
American Heart Association - Coronary Artery Disease. Available at: https://www.heart.org/ en/health-topics/consumer-healthcare/what-is-cardiovascular-disease/coronary-artery-disease. Accessed on 01 September 2019.
World Health Organization - Noncommunicable Disease (NCD) Country Profiles (Indonesia). Available at: https://www.who.int/nmh/countries/ idn_en.pdf. Accessed on 01 September 2019.
American Heart Association - Chelation Therapy: A New Look at an Old Treatment for Heart Disease, Particularly in Diabetics. Available at: https://www. ahajournals.org/doi/10.1161/CIRCULATIONAHA.114.010774. Accessed on 01 September 2019.
Deaths Associated with Hypocalcemia from Chelation Therapy --- Texas, Pennsylvania, and Oregon, 2003--2005. Available at: https://www.cdc. gov/mmwr/preview/mmwrhtml/mm5508a3.htm. Accessed on 01 September 2019.
Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL, et al. Design of the trial to assess chelation therapy (TACT). Am Heart J. 2012;163:7-12.
Flora SJS, Shrivastava R, Mittal M. Chemistry and pharmacological properties of some natural and synthetic antioxidants for heavy metal toxicity, Curr Med Chem. 2013;20:4540-74.
Drisko JA. Chapter 107: Chelation therapy: in Integrative medicine. USA; Philadelphia: Elsevier; 2018.
American College of Cardiology - Chelation Therapy for CAD. Available at: https://www.acc.org/latest-in-cardiology/articles/2016/02/26/09/34/chelation-therapy-for-cad. Accessed on 01 September 2019.
Waters RS, Bryden NA, Patterson KY, Veillon C, Anderson RA. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res. 2001;83:207-21.
Rekab K, Lepeytre C, Goettmann F, Dunand M, Guillard C, Hermann JM. Degradation of a cobalt(II)-EDTA complex by photocatalysis and H2O2/UV-C. Application to nuclear wastes containing 60Co. J Radioanal Nucl Chem. 2014;303:131-7.
Peguero JG, Arenas I, Lamas GA. Chelation therapy and cardiovascular disease: Connecting scientific silos to benefit cardiac patients. Trends Cardiovasc Med. 2014; 24:232-40.
National Center for Complementary and Integrative Health - Questions and Answers: The NIH Trials of EDTA Chelation Therapy for Coronary Heart Disease. Available at: https://nccih.nih.gov/ health/chelation/TACT-questions. Accessed on 01 September 2019.
Wu SY, Tsai HC, Peng S Chang LT. Calcium-activated gene transfection from DNA/poly(Amic acid-co-imide) complexes. Int J Nanomedicine. 2015;10:1-11.
Seely DMR, Wu P, Mills EJ. EDTA chelation therapy for cardiovascular disease: a systematic review. BMC Cardio Dis. 2005;5:32.
Roussel AM, Favier IH, Waters R, Osman M, Fernholz K, Anderson RA. EDTA chelation therapy, without added vitamin C, decreases oxidative DNA damage and lipid peroxidation. Altern Med Rev. 2009;14:56-61.
The Role of Lipids and Lipoproteins in Atherosclerosis. Available at: https://www.ncbi.nlm. nih.gov/books/NBK343489/#_ncbi_dlg_citbx_NBK343489. Accessed on 01 September 2019.
Escolar E, Lamas Gervasio A., Mark Daniel B., Boineau Robin, Goertz Christine, Rosenberg Yves, et al. The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Prior Myocardial Infarction in the Trial to Assess Chelation Therapy (TACT). Circ Cardiovasc Qual Outcomes. 2014;7:15-24.
Kraml P. The role of iron in pathogenesis of atherosclerosis. Physiol Res. 2017;66:S55-S67.
Synthesis of iron (III) EDTA complex Disease. Available at: https://www.stem.org.uk/resources/ elibrary/resource/35088/synthesis-ironiii-edta-complex-nafeedta3h2o. Accessed on 01 September 2019.
Green DJ, O’Driscoll JG, Maiorana A, Serimgeour NB, Weerasooriya R, Taylor RR. Effects of chelation with EDTA and vitamin B therapy on nitric oxide-related endothelial vasodilator function. Clin Exp Pharmacol P. 1999;26:853-856.
Flora SJS, Pachauri V. Chelation in metal intoxication, Int J Environ Res Public Health. 2010;7:2745-88.
Chisolm J. The use of chelating agents in the treatment of acute and chronic lead intoxication in childhood. J Pediatr. 1968;73:1-38.
AHFS Drug information 86. Bethesda, MD: American Society of Hospital Pharmacists, 1986.
Gilman AG, Rall TW, Nies AS, Taylor P. Goodman and Gilman's the pharmacological basis of therapeutics. New York: Pergamon Press; 1990.
Anderson TJ, Hubacek J, Wyse Dg, Knudtson ML. Effect of chelation therapy on endothelial function in patients with coronary artery disease: PATCH substudy. J Am Coll Cardiol N Y. 2003;41:420-5.
Dans AL, Tan FN, Villarruz-Sulit EC. Chelation therapy for atherosclerotic cardiovascular disease (Review). Cochrane. 2002: 1-37.
Olszewer E, Sabbag FC, Carter JP. A pilot double-blind study of sodium magnesium EDTA in peripheral vascular disease. J National Med Assoc. 1990;82:173-7.
Knudtson MI, Wyse DG, Galbraith PD, Brant R, Hildebrand K, Paterson D, et al. Chelation therapy for ischemic heart disease: A randomized controlled trial. JAMA. 2002;287:481-6.
Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL, et al. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. JAMA. 2013;309:1241-50.
Spruance SL, Reid JE, Grace M, Samore M. Hazard ratio in clinical trials. Antimicrob Agents Chemother. 2004;48:2787-92.
Ujueta F, Arenas IA, Escolar E, Diaz D, Boineau R, Mark DB, et al. The effect of EDTA-based chelation on patients with diabetes and peripheral artery disease in the Trial to Assess Chelation Therapy (TACT). J Diabetes Complications. 2019;33:490-4.
Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M, et al. EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy. Am Heart J. 2014;168:37-44.e5.
Issa OM, Roberts R, Mark DB, Boineau R, Goertz C, Rosenberg Y, et al. Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT). Am Heart J. 2018;195:70-7.
Mathew RO, Schulman-Marcus J, Nichols EL, Newman JD, Bangalore S, Farkouh M, et al. Chelation therapy as a cardiovascular therapeutic strategy: The rationale and the data in review. Cardiovasc Drugs Ther. 2017;31:619-25.
Trial to Assess Chelation Therapy 2 (TACT2). Available at: https://clinicaltrials.gov/ct2/ show/NCT02733185. Accessed on 01 September 2019.
