Chelation therapy involves the intravenous infusion of a chelating agent, usually ethylenediaminetetraacetic acid (EDTA), over a 2-3 hour period once or twice a week for 10-40 sessions. The total cost of a series of treatments can range from $3000-$5000. Despite the lack of convincing evidence showing benefit of chelation therapy for atherosclerotic disease, intravenous administration of chelating agents has become a popular and widely available alternative treatment, especially for peripheral vascular disease. Although the procedure is not reimbursed by insurance programs, numerous clinics that administer chelation therapy have been set up nationwide. Two medical associations, the American College for Advancement in Medicine in Laguna Hills, California, and the Great Lakes Association of Clinical Medicine in Chicago, train their physician members in the administration of chelation therapy and publish numerous pamphlets about all aspects of this procedure.
History of Chelation Therapy
Derived from the Greek "chele" or claw, chelation therapy has come to mean repeated intravenous administrations of EDTA. EDTA therapy has been successfully used for the treatment of lead and other heavy metal poisonings. An observation was made in the 1950s that patients receiving EDTA therapy for lead poisoning experienced a relief of angina pectoris. Subsequently, many uncontrolled studies have reported promising results, primarily in small groups of patients with severe claudication and peripheral vascular disease. A meta-analysis of primarily uncontrolled positive reports with data on more than 22,000 patients reported a high positive correlation between EDTA therapy and an improvement in vascular disease. The lack of negative reports or control subjects makes these claims suspect. Only recently have more carefully controlled trials of this therapy been attempted.
Biochemistry and Mechanism of Action
EDTA is a chelator-meaning that it binds ions in the blood. It is highly effective as a treatment of heavy metal poisoning (such as lead), for which it is currently approved for use. Other divalent ions, such as calcium, magnesium, and iron, are bound by EDTA as well.
Studies using fluoroscopy and, more recently, ultrafast CT scanning have shown a correlation between the degree of calcium in arteries and the extent of atherosclerotic disease. Investigators have been able to use the percent of calcium in coronary arteries to determine a probability of developing symptomatic coronary artery disease over a five-year period.
Chelation with EDTA is thought to remove calcium from atherosclerotic plaques, promoting their regression. How the removal of calcium leads to the reduction in the amount of cholesterol in a plaque is unclear. It has yet to be proven that chelation of calcium in the plasma promotes leaching of calcium from an atherosclerotic plaque.
Other biochemical effects of EDTA have been suggested. EDTA has been proposed to function as an antioxidant, inhibit the peroxidation of lipids, stabilize membranes, and possibly have calcium channel-blocking effects. Some advocates of chelation therapy have proposed that EDTA works by chelating iron or cooper, thereby preventing the formation of free radicals. Unfortunately, there are very few biochemical data published to prove these claims.
Clinical Studies
Numerous uncontrolled studies and reviews have been published regarding the efficacy of chelation therapy, primarily in peripheral vascular disease. Most of these reports consist of small numbers of patients without control groups comparing EDTA treatment with placebo.
A small pilot study with a control group was published in 1990 that claimed a benefit of chelation therapy. Ten infusions of EDTA were compared to distilled water injection in a total of 10 patients with peripheral vascular disease. An improvement in walking distance and in the ankle/arm blood pressure index was demonstrated after the 10 treatments. (The ankle/arm blood pressure index compares the blood pressure obtained in the brachial artery with the blood pressure in the leg, usually at the posterior tibial artery obtained by Doppler. Normally, the ratio is 1:1. A declining ratio indicates worsening severity of peripheral vascular disease.)
A multicenter trial published in 1992, however, found no significant difference in outcomes both immediately after treatment and at six months in a group of 153 individuals. Recently, a double-blind, randomized, controlled trial of 32 patients found no benefit in subjective and measured walking distances and ankle/arm indices in a treatment group compared with placebo. In addition, there were no differences found in other outcome measures, including lifestyle parameters, cardiac function, ECG, kidney function, hematologic studies, glucose, and lipid levels up to three months after therapy. Interestingly, almost 60% of the control group patients noted an improvement in walking distance, indicating either a profound placebo effect or the benefit that a walking program alone way give patients with peripheral vascular disease.
The publication of these studies prompted Ernst from the Department of Complementary Medicine in Exeter to review the effectiveness of chelation therapy for peripheral vascular disease. He reviewed four publications fitting the criteria of randomized, placebo-controlled, double-blind trials evaluating the efficacy and safety of chelation therapy for peripheral vascular disease. He concludes stating that chelation therapy "should now be considered obsolete."
Since many patients with claudication will experience improvement in leg pain by participating in a walking program, placebo-controlled studies must be performed to determine the efficacy of this therapy.
Formulation
EDTA chelation therapy for peripheral vascular disease is usually administered intravenously as magnesium chelate. Infusion periods of EDTA in normal saline 1.5-3 hours twice weekly over 15 weeks with a maximum of 36 g each time is a standard prescription. To prevent leaching of important ions from the blood, most protocols require the use of vitamin, mineral, and iron supplements in conjunction with the chelating agent. In contrast, 1g in 5% dextrose twice daily over 3-5 days is commonly used for adult lead poisoning to promote binding and excretion of the ion. Oral chelation therapy to lower cholesterol levels and treat atherosclerotic disease has been advocated but not evaluated to the same degree as intravenous EDTA administration.
Adverse Effects
Chelation therapy is associated with potentially severe side effects. Significant hypocalcemia and tetany may occur, which can be life threatening. There have been reports of severe kidney damage and death after chelation therapy.
Conclusion
Carefully performed studies in patients with peripheral vascular disease and claudication have failed to prove any benefit from chelation therapy. The therapy is costly, requires repeated administration, and it's potentially dangerous. Patients with claudication are better off quitting smoking and participating in a daily walking program to relieve symptoms and promote the growth of collateral circulation. Chelation therapy cannot be recommended as a treatment for atherosclerotic peripheral vascular disease.
Return to the Perry
Hookman, M.D., P.A. Home Page