Chelation therapy for cardiovascular disease

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Chelation therapy for post-myocardial infarction, chelation therapy for diabetics

Overview

Chelation Therapy and CVD

The use of chelation therapy as a treatment for atherosclerosis dates back to the 1950’s as Clarke et al investigated the use of EDTA for the treatment of angina pectoris.[1] Opinions regarding the use of chelation therapy for CVD have long been controversial as there was not enough evidence on the benefits of their use.[2] Several studies investigated the use of chelation therapy for atherosclerotic diseases. According to a study, there was an association between chelation therapy and improvement of ischemic heart disease and peripheral vascular disease with EDTA chelation therapy.[3] Another study demonstrated that vitamin B supplemented EDTA and not EDTA alone was effective in improving forearm blood flow reflecting improved vasodilation.[4] A systematic review of four randomized clinical trial on chelation therapy and PAD revealed no benefit associated with chelation therapy.[5] In addition, a systematic review on the role of chelation therapy in coronary heart disease (CHD) revealed that the data on chelation therapy and CHD is insufficient and hence cannot be recommended yet.[6] In fact, according to the 2012 summary of clinical practice guidelines from the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons, it was recommended that chelation therapy should not be used for symptomatic treatment or cardiovascular risk reduction among patients with stable ischemic heart disease.[7]


In the light of the controversies regarding the benefits of chelation therapy and the absence of any previous large clinical trial investigating its use in the context of coronary artery disease, Trial to assess chelation therapy (TACT), a randomized, double blind, placebo controlled trial, investigated the effect of EDTA based infusions among 1708 stable post-myocardial infarction patients who are more than 50 years of age. The primary outcome of this trial was a composite of all-cause mortality, coronary revascularization, recurrence of myocardial infarction, stroke or angina requiring hospitalization. A follow up period of 55 months revealed a modest decrease in the adverse cardiovascular outcomes risks. In fact, 30% of post-MI patients who did not receive chelation therapy were reported to have the primary outcome compared to 26% of those who received the chelation therapy ( HR: 0.82; 95% CI: 0.69-0.99; p= 0.035). The association between chelation therapy and decrease in the risk of each of the components of the primary outcome was significant except for total mortality. Despite the moderate improvement in the cardiovascular outcomes, the findings of this study were not enough to promote chelation therapy as a treatment for stable post-myocardial infarct patients.[8]

Mechanism of Action

Ethylenediamine tetraacetic acid (EDTA), a type of chelation therapy, binds to metals and forms soluble complexes facilitating their subsequent excretion in the urine.[9] Hence, chelation therapy helps in the elimination of metals including lead, iron, copper and calcium from the blood. The chelation therapy consists of EDTA along with additives such as vitamin B, ascorbic acid and magnesium which are thought to have a protective effect on the endothelial cells.[10] Cardiovascular benefits of chelation therapy are thought to result from its antioxidant effect as it decreases the metal-dependent formation of reactive oxygen species and lipid peroxidation.[10] In addition, the removal of calcium from arterial wall by chelation therapy can possibly lead to a regression of the atherosclerotic plaques.[11][12]

Side Effects

Landmark Trials

References

  1. ↑ CLARKE CN, CLARKE NE, MOSHER RE (1956). "Treatment of angina pectoris with disodium ethylene diamine tetraacetic acid". Am J Med Sci. 232 (6): 654–66. PMID 13372537.
  2. ↑ Villarruz MV, Dans A, Tan F (2002). "Chelation therapy for atherosclerotic cardiovascular disease". Cochrane Database Syst Rev (4): CD002785. doi:10.1002/14651858.CD002785. PMID 12519577.
  3. ↑ Olszewer E, Carter JP (1988). "EDTA chelation therapy in chronic degenerative disease". Med Hypotheses. 27 (1): 41–9. PMID 3144646.
  4. ↑ Green DJ, O'Driscoll JG, Maiorana A, Scrimgeour NB, Weerasooriya R, Taylor RR (1999). "Effects of chelation with EDTA and vitamin B therapy on nitric oxide-related endothelial vasodilator function". Clin Exp Pharmacol Physiol. 26 (11): 853–6. PMID 10561804.
  5. ↑ Ernst E (1997). "Chelation therapy for peripheral arterial occlusive disease: a systematic review". Circulation. 96 (3): 1031–3. PMID 9264515.
  6. ↑ 6.0 6.1 Ernst E (2000). "Chelation therapy for coronary heart disease: An overview of all clinical investigations". Am Heart J. 140 (1): 139–41. doi:10.1067/mhj.2000.107548. PMID 10874275.
  7. ↑ Qaseem A, Fihn SD, Dallas P, Williams S, Owens DK, Shekelle P; et al. (2012). "Management of stable ischemic heart disease: summary of a clinical practice guideline from the American College of Physicians/American College of Cardiology Foundation/American Heart Association/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society of Thoracic Surgeons". Ann Intern Med. 157 (10): 735–43. doi:10.7326/0003-4819-157-10-201211200-00011. PMID 23165665.
  8. ↑ 8.0 8.1 Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL; et al. (2013). "Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial". JAMA. 309 (12): 1241–50. doi:10.1001/jama.2013.2107. PMID 23532240.
  9. ↑ WILDER LW, DE JODE LR, MILSTEIN SW, HOWARD JM (1962). "Mobilization of atherosclerotic plaque calcium with EDTA utilizing the isolation-perfusion principle". Surgery. 52: 793–5. PMID 14000694.
  10. ↑ 10.0 10.1 Lamas GA, Ackermann A (2000). "Clinical evaluation of chelation therapy: is there any wheat amidst the chaff?". Am Heart J. 140 (1): 4–5. doi:10.1067/mhj.2000.107549. PMID 10874253.
  11. ↑ CLARKE NE (1960). "Atherosclerosis, occlusive vascular disease and EDTA". Am J Cardiol. 6: 233–6. PMID 13810514.
  12. ↑ KITCHELL JR, PALMON F, AYTAN N, MELTZER LE (1963). "The treatment of coronary artery disease with disodium EDTA. A reappraisal". Am J Cardiol. 11: 501–6. PMID 14033183.


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