Chelation Therapy

A chemical term and wartime antidotes

A toxicology review traces the word chelate to the Greek chele, the claw of a lobster, and states that the term was first applied by Gilbert T. Morgan and H. D. K. Drew in 1920. The same review reports that dimercaprol, also called British anti-Lewisite or BAL, was developed by British biochemists at Oxford during the Second World War as an antidote, and that it has been used clinically since 1949 for arsenic, cadmium and mercury poisoning.

The review describes calcium disodium EDTA as a mainstay of treatment for childhood lead poisoning since the 1950s, adopted after lead poisoning was observed among large numbers of navy personnel after the war. The authors of the TACT trial likewise state that treatment of lead toxicity with EDTA was first reported in the early 1950s. Later oral agents, such as succimer (DMSA), were studied over several decades in China, Japan and Russia, according to the review.

Extension to heart and blood-vessel disease

According to the TACT investigators, apparent success in reducing abnormal calcium deposits led a physician named Clarke to treat patients with angina using EDTA in 1956. Over the following decades, they write, chelation practitioners increased their use of EDTA for coronary and peripheral artery disease on the basis of favorable anecdotal and case-report experience, and the treatment came to consist of infusions of vitamins together with disodium EDTA.

The same paper cites a 2007 national health statistics report estimating that adult use of chelation therapy in the United States rose by 68 percent between 2002 and 2007, from about 66,000 to 111,000 adults. A Cochrane review describes chelation as promoted and practiced around the world as a form of alternative medicine for atherosclerotic cardiovascular disease.

Autism and detoxification uses

A 2006 report in the CDC's Morbidity and Mortality Weekly Report notes that some practitioners had given chelation to children with autism in the belief that mercury or other heavy metals produce the symptoms. A Cochrane review explains the underlying hypothesis as a proposed link between autism severity and stored toxic metals. A medical toxicology paper reports that chelator-provoked urine tests for metals remain in use and are recommended by some practitioners. The sources reviewed do not date when these uses began.

Chelate and chelating agent

In the toxicology literature, a chelating agent is a compound that binds toxic metal ions to form complex structures that the body can excrete more easily, removing the metal from inside or outside cells. A government consumer summary describes the process as a substance delivered through the veins to bind metals or minerals so that they can be removed in the urine. Chelation therapy is the clinical use of such agents, and the same word is used for both medical and alternative practice.

EDTA salts and similar drug names

EDTA stands for ethylenediaminetetraacetic acid. Two salts matter for safety. Disodium EDTA (Na2EDTA, edetate disodium) binds calcium and other cations; the TACT investigators describe it as a drug that binds divalent and some trivalent cations, including calcium. Calcium disodium EDTA (CaNa2EDTA, often written CaEDTA) is the form used for lead poisoning. The CDC report found that brand names for the two forms had been used interchangeably in medical records, which was likely to have contributed to a fatal medication error.

Provoked, challenge and mobilization tests

The terms urine mobilization test, challenge test and provoked urine test all describe giving a person a chelating agent before collecting urine to measure metals. A paper in the journal of the American College of Medical Toxicology notes that agents used include DMSA, DMPS and EDTA, and that there is no standard, validated version of the test. Practitioners who use these tests sometimes speak of a metal body burden, a concept the same paper examines.

Medical chelation for poisoning and overload

Reviews of metal intoxication describe several agents. DMSA and DMPS are available as oral capsules and are described as less toxic and more efficient than BAL for heavy-metal poisoning. Calcium disodium EDTA is poorly absorbed by mouth, under 5 percent, so it is given by injection or infusion. For copper overload, d-penicillamine is still widely used, and the thiol drugs are described as ineffective for iron.

For iron overload, a hematology review states that deferoxamine, deferiprone and deferasirox are approved for use in conditions such as myelodysplastic syndromes, sickle cell disease and thalassemia, where repeated transfusions or increased absorption load the body with iron. The review states that the decision to start chelation and which drug to use is made jointly by the clinician and the patient.

EDTA infusion courses in alternative practice

A government consumer summary states that a course of EDTA chelation for coronary heart disease can involve 20 to 40 weekly infusions lasting several hours each. In TACT, the active regimen was 40 infusions of a 500 mL solution containing 3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine and heparin, given weekly for 30 weeks and then 10 more at intervals of 2 to 8 weeks.

Provoked urine testing before treatment

Some practitioners give a chelating drug and then collect urine to look for metals, according to a medical toxicology paper. It reports that the agents, routes of administration, doses and urine collection methods vary, and that results are often compared with reference ranges that were set for unprovoked urine. In a 2003 case described by the CDC, a woman received intravenous EDTA from a naturopathic practitioner for what was recorded as heavy metal removal.

Established clinical indications

The medical uses described in the reviews are treatment of documented poisoning with lead, arsenic, mercury, cadmium and some other metals, removal of excess iron in transfusion-dependent and other iron-loading conditions, and treatment of copper overload. These uses belong to clinical toxicology and hematology. Evidence and experience from these settings does not by itself say anything about chelation for other purposes.

Heart and blood-vessel disease

Advocates have presented EDTA chelation as a safe, relatively inexpensive, non-surgical way to restore blood flow in narrowed arteries, according to the Cochrane review, which treats this as a claim to be tested. The TACT investigators note that chelation practitioners used it for coronary and peripheral artery disease after early reports of reduced calcium deposits. The sources reviewed do not set out a single agreed mechanism for these claims.

Autism and general detoxification

For autism, the claim reviewed by Cochrane was that removing heavy metals with pharmaceutical chelating agents would reduce symptoms. In detoxification settings, provoked urine results are used to describe a hidden body burden of metals and to justify chelation, according to the medical toxicology paper. The sources reviewed do not describe a standard protocol for either use.

Metal poisoning and iron overload

One toxicology review calls chelation the preferred medical treatment for reducing the toxic effects of metals. A hematology review states that iron chelators lower tissue iron, prevent complications of iron overload and improve event-free survival. Both are narrative reviews, and this page does not grade evidence for individual drugs.

The TACT trial

TACT was a double-blind, placebo-controlled factorial trial of 1708 people aged 50 or older who had had a heart attack at least 6 weeks earlier, recruited at 134 sites in the United States and Canada. Over a median follow-up of 55 months, the combined outcome of death, heart attack, stroke, coronary revascularization or hospitalization for angina occurred in 26 percent of the EDTA group and 30 percent of the placebo group (hazard ratio 0.82, 95% CI 0.69 to 0.99), just under the trial's significance threshold. There was no difference in total mortality.

The investigators concluded that the modest reduction, much of it in revascularization procedures, was enough to guide further research but not to support routine use after a heart attack. A government summary reports that participants with diabetes, about a third of the total, had a 41 percent lower risk of any cardiovascular event in a subgroup analysis.

TACT2 in people with diabetes

TACT2 tested whether the diabetes finding would replicate. Among 959 people aged 50 or older with diabetes and a previous heart attack who received at least one infusion at 88 sites, the primary outcome occurred in 35.6 percent of the chelation group and 35.7 percent of the placebo group (adjusted hazard ratio 0.93, 95% CI 0.76 to 1.16) over a median of 48 months. Chelation lowered median blood lead levels, but did not reduce cardiovascular events.

A companion report on the factorial vitamin arm found that high-dose oral multivitamins and minerals did not reduce events, and that the combination of active chelation and active vitamins did not differ significantly from double placebo (hazard ratio 0.91, 95% CI 0.67 to 1.23). The government summary states that TACT2 did not reproduce TACT and does not support chelation for this purpose.

Systematic review of atherosclerotic disease

A 2020 Cochrane review included five randomized trials of EDTA chelation against placebo with 1993 participants, three in peripheral vascular disease and two in coronary artery disease. It found no evidence of a difference in all-cause mortality, heart attack, angina, stroke, ankle-brachial index or walking distance, with certainty of evidence mostly low to very low. The authors concluded that evidence is insufficient to determine whether chelation is effective or ineffective for clinical outcomes. The review predates TACT2.

Autism spectrum disorder

A 2015 Cochrane review searched more than 20 databases and registers and found one eligible randomized trial. In its second phase, 49 children with autism classed as high metal excreters received repeated three-day courses of oral DMSA or placebo, with no effect on autism symptoms. The reviewers found no trial evidence that chelation is effective for autism.

Limits of the TACT findings

TACT had notable weaknesses that its own report describes. Some 17 percent of participants withdrew consent, more often in the placebo group (174) than the chelation group (115), and the result sat just under the adjusted significance threshold. Revascularization procedures, which depend partly on clinician decisions, made up a large share of events. About 60 percent of sites already offered chelation. The investigators reported that their sensitivity analyses did not change the result.

Validity of provoked urine tests

The medical toxicology paper reports that volunteer studies find mercury in the urine of most people without known exposure, that urinary mercury rises after a chelator is given regardless of exposure history, and that challenge testing fails to reveal a body burden from past exposure. It concludes that there are no reference ranges for provoked samples in healthy people and no reliable evidence of diagnostic value, and that the tests should not be used.

Hypocalcemia and deaths

The CDC report described three deaths from cardiac arrest associated with hypocalcemia during chelation between 2003 and 2005: a 2-year-old girl with lead poisoning who was given disodium EDTA in error instead of calcium disodium EDTA; a 5-year-old boy with autism treated with intravenous disodium EDTA in a physician's office; and a 53-year-old woman given intravenous EDTA by a naturopathic practitioner. The report advised that disodium EDTA should not be given to children.

The TACT investigators state that disodium EDTA can cause hypocalcemia and death, particularly when infused too rapidly. In their trial, low calcium before an infusion was recorded in 6.2 percent of chelation patients and 3.5 percent of placebo patients, and severe unexpected events possibly or definitely related to treatment occurred in two people in each group, including one death in each.

Kidney injury and other adverse effects

A government summary identifies hypocalcemia and kidney damage as the most important serious side effects of EDTA chelation. A toxicology review describes the risks of calcium disodium EDTA as substantial, including kidney failure; the kidney toxicity is described as dose-dependent and reversible on stopping, but doses above the stated maximum could be fatal. Prolonged use can deplete zinc, copper and manganese, and mobilized lead may redistribute to soft tissues such as the brain. BAL has a narrow safety margin.

The 2015 Cochrane review cites prior reports of hypocalcemia, kidney impairment and death, and judged that the risks of chelation for autism outweigh any benefit shown. The 2020 Cochrane review of atherosclerotic disease found no evidence of major or minor adverse events in its included trials, which were conducted under research protocols.

Specialist oversight and care boundaries

The CDC report advised clinicians unfamiliar with chelating agents to consult an expert in treating lead poisoning before using them. The medical toxicology paper notes potential harm from chelators given for provoked testing. The government summary advises people considering chelation for heart disease to discuss it first with their cardiologist or other provider. Chelation should not delay or replace established care for heart disease, autism or suspected poisoning. The sources reviewed do not describe a professional training standard for practitioners who offer chelation outside hospital medicine.