What does chelation therapy do?

What Chelation Therapy Does

Chelation therapy uses intravenous infusions of chelating agents (primarily disodium EDTA) that bind to polyvalent metal ions like calcium, lead, cadmium, and other heavy metals, forming soluble complexes that are then excreted from the body, primarily through the kidneys. 1

Mechanism of Action

Chelation works through a chemical process where a chelating agent (ligand) with lone pairs of electrons forms ring-like complex structures with metal ions, effectively trapping them for elimination. 2, 3

• EDTA specifically combines with polyvalent cations including calcium and cadmium (a constituent of cigarette smoke associated with cardiovascular risk) to form soluble complexes that can be excreted. 1
• The chelating agent acts as a donor molecule that binds the central metal atom/ion, with different metals requiring specific chelating agents based on their reactivity. 3
• This process removes metals from both intracellular and extracellular spaces, reducing their toxic effects on tissues and organs. 2

FDA-Approved Indications

Disodium EDTA is FDA-approved for specific conditions involving metal toxicity, NOT for cardiovascular disease. 1

The approved uses include:

• Iron overload (hemochromatosis and transfusion-related iron overload) 1
• Lead poisoning 1
• Wilson's disease (copper overload) - though penicillamine is the primary chelator used 4
• Cystinuria (when using penicillamine as the chelating agent) 4

Use in Iron Overload

For patients with myelodysplastic syndromes and transfusion-dependent iron overload:

• Chelation therapy should be initiated when serum ferritin reaches 1,000 ng/mL or when transfusion need is ≥2 units/month for >1 year. 1
• The goal is to preserve organ function and improve survival by preventing iron-related organ damage (particularly cardiac and hepatic). 1
• Therapy should continue as long as the patient requires transfusions and iron overload persists. 1

Controversial Use in Cardiovascular Disease

The usefulness of chelation therapy for cardiovascular disease remains highly questionable and uncertain. 1

Evidence Summary:

• The 2014 ACC/AHA guidelines upgraded chelation from Class III (No Benefit) to Class IIb (uncertain benefit) based on the TACT trial, but emphasized the usefulness remains "highly questionable." 1
• In the TACT trial, chelation showed a modest reduction in composite cardiovascular endpoints (HR 0.82,95% CI 0.69-0.99, p=0.035), but no individual endpoint differed significantly between groups. 1
• A subgroup of diabetic patients showed a 39% reduction in composite endpoints (HR 0.61,95% CI 0.45-0.83), but this finding requires confirmation. 1
• TACT2 did not confirm efficacy in reducing cardiovascular events in diabetic patients. 5

Critical Concerns:

• 50% more patients withdrew from chelation than placebo, raising concerns about unmasking of treatment assignments that could have influenced outcomes like revascularization or hospitalization. 1
• The proposed mechanism (improving blood flow in atherosclerotic vessels) lacks strong scientific basis. 1

Significant Safety Risks

Chelation therapy is not risk-free and can cause serious adverse effects, particularly when EDTA is infused too rapidly. 1

Major Complications:

• Hypocalcemia (from calcium binding) 1
• Acute renal failure 1
• Death (when administered improperly) 1
• Hepatotoxicity 6
• Depletion of essential metals like copper and zinc 6
• Potential redistribution of heavy metals to the brain, increasing neurotoxicity 6

Common Pitfalls to Avoid:

• Never use chelation therapy for cardiovascular disease outside of clinical trials, as it is not FDA-approved for this indication and evidence remains insufficient. 1
• Ensure proper infusion rates to minimize risk of hypocalcemia and renal failure. 1
• Monitor renal function closely during therapy. 1
• Do not confuse legitimate uses (metal poisoning, iron overload) with unproven cardiovascular applications. 1