EDTA Monograph

EDTA Monograph

EDTA
Also Known As:
Acide Éthylènediaminetétracétique, Calcium Disodium Edathamil, Calcium Disodium Edetate, Calcium Disodium EDTA, Calcium Disodium Versenate, Calcium Edetate, Calcium EDTA, Chelation Therapy, Disodium Edathamil, Disodium Edetate, Disodium EDTA, Disodium Tetraacetate, EDTA de Calcium Disodique, EDTA de Fer, Éthylènediaminetétraacétate de Calcium et de Disodium, Éthylène-Diamine-Tétracétate Disodique, Iron EDTA, Sodium Edetate, Traitement Chélateur.
Scientific Name:
Ethylenediamine tetraacetic acid; Disodium ethylenediamine tetraacetic acid; Trisodium ethylenediamine tetraacetic acid.
People Use This For:
Topically, EDTA has been used as an ointment for skin irritations produced by metals such as chromium, nickel and copper.
Intravenously and intramuscularly, EDTA is used for acute and chronic lead poisoning and lead encephalopathy. Intravenous EDTA is also used in the calcium EDTA mobilization test which is used to evaluate a patient’s response to chelation therapy for suspected lead poisoning. EDTA is also used intravenously to treat poisonings by radioactive products such as plutonium, thorium, uranium, and strontium. It is also used intravenously for removing copper in patients with Wilson’s disease, hypercalcemia, cardiac glycoside-induced arrhythmias, atherosclerotic vascular disease, scleroderma, porphyria, hypercholesterolemia, and in the diagnosis of hypoparathyroidism. EDTA has also been used intravenously to treat essential hypertension, Raynaud’s syndrome, intermittent claudication, gangrene, cancer, rheumatoid arthritis, osteoarthritis, decreased vision due to macular degeneration, diabetes, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, psoriasis, and angina.
Ophthalmically, EDTA is used for corneal calcium deposits in the eye.
In foods, EDTA is used as iron EDTA to fortify grain-based products such as breakfast cereals and cereal bars. EDTA is also used as calcium disodium EDTA and disodium EDTA as an additive to preserve food; and to promote the color, texture, and flavor of food.
In manufacturing, EDTA is used as disodium EDTA and trisodium EDTA to improve stability in pharmaceutical preparations, detergents, liquid soaps, shampoos, agricultural chemical sprays, oil emulsion devices, contact lens cleaners and cosmetics. It is also used in manufactured clinical laboratory evacuated blood collection tubes to anticoagulate blood specimens.
Safety:
LIKELY SAFE …when used orally in amounts commonly found in foods. EDTA has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912, 10266). …when used intravenously or intramuscularly and appropriately, short-term. Parenteral EDTA in the disodium and calcium disodium forms are FDA-approved prescription products (15).
POSSIBLY SAFE …when used ophthalmically and appropriately (5774). Solutions of 0.35-1.85% EDTA in the disodium form seem to be safe (5774).
LIKELY UNSAFE …when used intravenously or intramuscularly in excessive doses or long-term. Doses exceeding 50 mg/kg/day or greater than 3 grams per day, or used longer than 5-7 days per treatment course are associated with severe toxicity including nephrotoxicity (5733). …when used intravenously and infused at an excessive rate. Infusion of the disodium form of EDTA over less than 3 hours can cause severe, life-threatening adverse effects including hypocalcemia and death (5737).
PREGNANCY AND LACTATION: POSSIBLY SAFE …when used orally and appropriately in amounts commonly found in foods (7705, 10266). There is insufficient reliable information available for other forms of EDTA; avoid using.
Effectiveness:
EFFECTIVE

Lead toxicity. Administering EDTA intravenously and intramuscularly is effective for treating acute and chronic lead poisoning and lead encephalopathy (15, 5730, 5731, 5734, 5735, 5736). The calcium disodium form of EDTA is FDA approved for these uses (15). Calcium disodium EDTA is used when blood lead concentrations are 45 ug/dL or greater or when patients are symptomatic. Treatment of 3-5 days is usually required to lower blood lead levels below 40 ug/dL (15, 5730, 5733). A second treatment course can be required if blood lead concentrations rebound to 45 ug/dL or greater within 5-7 days after the initial treatment (15). Treatment with calcium disodium EDTA improves symptoms of lead poisoning such as abdominal pain, fatigue, constipation, and anorexia (5730). It also seems slow progression of renal dysfunction in patients who have had chronic lead poisoning (5732). Calcium disodium EDTA is preferred to disodium EDTA for lead poisoning because unlike calcium disodium EDTA, disodium EDTA can significantly lower serum calcium levels and cause hypocalcemia when used in doses necessary to treat lead poisoning (15). However, EDTA does not seem to be effective for diagnosing lead poisoning. Some clinicians use a diagnostic test known as the calcium EDTA mobilization test. Many experts consider the test obsolete due to technical inconsistencies in administering and interpreting the test (5733). Treatment of lead poisoning should not be delayed for performance of this test if blood lead levels are 45 mcg/dL or greater (15).

LIKELY EFFECTIVE

Cardiac glycoside-induced ventricular arrhythmias. Administering EDTA intravenously is effective for emergency treatment of cardiac glycoside-induced ventricular arrhythmias. The disodium form of EDTA is approved by the FDA for this use. Disodium EDTA works rapidly to control ventricular arrhythmias, but it is very short acting (15, 5761, 5762). Clinicians do not consider it the preferred treatment (15). Other agents such as lidocaine or phenytoin (Dilantin) (505) are typically used because they are safer and more effective (15).
Hypercalcemia. Administering EDTA intravenously is effective for emergency treatment of hypercalcemia. The disodium form of EDTA is approved by the FDA for this use (15). Disodium EDTA can temporarily lower serum calcium to safe levels (15). However, clinicians generally prefer other methods of treatment such as forced diuresis with saline or use of pamidronate (Aredia), calcitonin (Miacalcin, others), or glucocorticoids (5775). These treatments more effectively lower serum calcium concentrations over longer periods of time than would be achieved with disodium EDTA and are less likely to cause renal side effects (15).

POSSIBLY EFFECTIVE

Corneal calcium deposits. A single ophthalmic application of the disodium form of EDTA can clear corneal calcium deposits, and improve eyesight (5773, 5774). However, debridement of the corneal epithelium prior to application of EDTA is required (5773, 5774).

POSSIBLY INEFFECTIVE

Scleroderma. Administering EDTA intravenously doesn’t seem to be effective for treating localized and systemic scleroderma. Although there have been some anecdotal reports showing benefit (5757, 5760), clinical studies show no significant changes or improvements in the skin or joints of scleroderma patients treated with disodium EDTA (5757, 5758, 5759, 5760).

LIKELY INEFFECTIVE

Coronary heart disease. Administering EDTA intravenously isn’t effective for treating coronary heart disease or peripheral arterial occlusive disease. The effectiveness of EDTA in chelation therapy is highly debated (5738, 5739). Proponents often cite anecdotal reports or poorly controlled studies as evidence to support EDTA chelation therapy (5737, 5738, 5739, 5740, 5742, 5743, 5751, 5770), but well-designed research shows that EDTA offers no significant benefit for these conditions (5737, 5740, 5742, 5750, 5752, 5753, 5754).

Mechanism of Action:
Ethylenediaminetetraacetic acid (EDTA) is known as a chelating agent. It is a complex molecule with a claw-like structure, which binds and seizes divalent and trivalent metal ions such as calcium and aluminum to form a stable ring structure (5729, 5749). EDTA binds and chelates metal ions in the following decreasing order: chromium, iron (ferric ion), mercury, copper, aluminum, nickel, zinc, calcium, cobalt, iron (ferrous ion), manganese, calcium, and magnesium (5737). After intravenous administration, accessible metal ions are chelated forming stable soluble complexes, which are then excreted in the urine (505). EDTA is not metabolized, but elimination is decreased with renal dysfunction (5737). Calcium disodium EDTA and disodium EDTA are the two forms of EDTA available for clinical use (15). Calcium disodium EDTA is the form of EDTA used primarily for lead poisoning (5730, 5731, 5732, 5733, 5734, 5735, 5736). The calcium in calcium disodium EDTA is displaced by metal ions such as lead to form a soluble complex that is then excreted in the urine (15). Unlike disodium EDTA, calcium disodium EDTA can be administered in large quantities without causing substantial changes in serum or total body calcium concentrations (15). Radioactive isotopes such as uranium and plutonium can also be chelated to a limited extent by calcium disodium EDTA (15).
Disodium EDTA antagonizes the ventricular inotropic and chronotropic effects of cardiac glycosides on the heart by decreasing the amount of extracellular calcium in the blood (5761, 5762). Some researchers think that decreased extracellular calcium can increase potassium re-entry into myocardial cells which then counteracts with the intracellular potassium depletion caused by cardiac glycosides (5762).
Ophthalmically, disodium EDTA is used to dissolve corneal calcium deposits by binding with calcium in the eye (5774). EDTA can also disorganize the outer membrane of gram-negative bacteria, inhibit the coaggregation between pairs of microorganisms and is possibly an effective inhibitor of bacterial adhesins (5764).
Chelation therapy using disodium EDTA has been purported by many as being efficacious in the treatment of many disease conditions, including atherosclerosis (5738, 5739, 5743, 5751, 5768). Many biochemical mechanisms have been proposed to justify the use of disodium EDTA in the treatment of atherosclerotic vascular disease (5738, 5741, 5743). Mechanisms claimed include that EDTA chelation therapy can extract calcium out of atherosclerotic plaques and clear atherosclerotic arteries (5742, 5749) or that calcium removed by chelation is replaced by calcium from the bone, causing secretion of parathyroid hormone (PTH) which then promotes a transfer of calcium from hardened arterial tissue and plaque to bone (5749).
Other mechanisms claimed also include that EDTA blocks production of free radicals involved in reactions causing atherosclerosis by reducing iron loads (5738), by binding toxic metals released when blood clots in occluded arteries (5749), or that disodium EDTA prevents damage and mutation of arterial cells caused by free radicals (5749). None of these proposed mechanisms have been scientifically proven (5749, 5756), and controlled scientific clinical studies have been unable to confirm that EDTA can reverse peripheral arterial occlusive disease (5740, 5742) or atherosclerotic vascular disease (5746, 5750, 5752, 5753, 5754, 5769).
Severe nephrotoxicity is the major toxicity that can result when disodium EDTA and calcium disodium EDTA is used in excessively large doses (15). The degeneration of proximal tubular cells that results is proposed to be due to an interaction between EDTA and endogenous metals in the tubular cells (505). EDTA can also chelate and cause increased urinary excretion of magnesium (15), which may also result in decreased serum concentrations and increased excretion of potassium (15). Sudden decreases in calcium can occur if disodium EDTA is administered too rapidly, resulting in tetany, cardiac arrhythmias, and respiratory arrest (5763).
Disodium EDTA inhibits the growth of Candida albicans in vitro. EDTA binds the calcium that is required for growth of this fungal species (4621).
Adverse Reactions:
Intravenously, EDTA can commonly cause abdominal cramps, anorexia, nausea, vomiting, diarrhea, headache (15), hypotension (5737), exfoliative dermatitis (15), and a burning sensation and pain at the site of infusion (5744). EDTA can also sometimes cause fever, chills, fatigue, malaise, thirst, sneezing and nasal congestion (15), arrhythmias (5771, 5772), thrombophlebitis (15), anemia (15), prolonged prothrombin time (PT) (5737), transient bone marrow depression (5737, 5772), and urinary urgency and frequency (5772).
The calcium disodium form of EDTA can also cause zinc deficiency (5771, 5772), hypercalcemia (5771, 5772), mild elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and decreased alkaline phosphatase levels (15).
The disodium form of EDTA can occasionally cause muscle cramps, back pains, muscle weakness, tremors, tingling, myalgias, paresthesias (15), decreased magnesium and potassium serum concentrations (5771, 5772), and rarely cause histamine-like reactions and insulin shock (5737).
The most serious adverse effect of both forms of EDTA is nephrotoxicity (5772), which is dose dependent of greater than 3 grams per day (15). Both forms of EDTA can cause nocturia, hyperuricemia, polyuria, dysuria, oliguria, proteinuria, glycosuria, hematuria and distal tubule and glomeruli changes (15). Both forms of EDTA can also cause acute renal tubular necrosis, and renal insufficiency and failure (5772). Rapid infusion of disodium EDTA or when given in too concentrated a solution can cause hypocalcemia, tetany, convulsions, severe cardiac arrhythmias, respiratory arrest, and death (15). When used ophthalmically, disodium EDTA can cause transient chemosis and stromal edema (15). Inhalation of disodium EDTA contained in nebulizer solutions has been reported to cause dose-related bronchoconstriction (5765).
Interactions with Herbs & Supplements:
MAGNESIUM: EDTA can bind to and cause increased urinary excretion of magnesium (15).
TRACE MINERALS: EDTA can bind to and cause increased urinary excretion of trace minerals (15, 5733). Some trace minerals include boron, chromium, cobalt, copper, fluorine, iodine, iron, manganese, molybdenum, nickel, selenium, sulfur, and zinc.
Interactions with Drugs:

DIURETIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

EDTA can decrease serum potassium levels and increase excretion of potassium (15). There is some concern that people receiving EDTA along with potassium depleting diuretics might be at an increased risk for hypokalemia. Initiation of potassium supplementation or an increase in potassium supplement dose may be necessary for some patients. Some diuretics that can deplete potassium include chlorothiazide (Diuril), furosemide (Lasix), and hydrochlorothiazide (HCTZ, Hydrodiuril, Microzide).

INSULIN

Interaction Rating = Major Do not take this combination.

Severity = High • Occurrence = Probable • Level of Evidence = B

Concomitant use of disodium EDTA with insulin can cause severe decreases in blood glucose concentrations (5737, 5771). EDTA chelates zinc in insulin products (15)and might interfere with the designed onset and duration of activity of various insulin preparations.

WARFARIN (Coumadin)

Interaction Rating = Major Do not take this combination.

Severity = High • Occurrence = Probable • Level of Evidence = D

There is some concern that disodium EDTA can decrease the anticoagulant effects of warfarin. Disodium EDTA has been reported to decrease international normalized ratio (INR) in a patient taking warfarin (4611).

Interactions with Foods:
None known.
Interactions with Lab Tests:
ALANINE AMINOTRANSFERASE (ALT, SGPT): Calcium disodium EDTA can cause mild increases in serum ALT (15).
ALKALINE PHOSPHATASE: Disodium EDTA can decrease serum alkaline phosphatase concentrations (15, 3314). Disodium EDTA can cause low magnesium serum concentrations, which decreases the activity of alkaline phosphatase (15).
ASPARTATE AMINOTRANSFERASE (AST, SGOT): Calcium disodium EDTA can cause mild increases in AST (15).
CALCIUM: Calcium serum concentrations cannot be determined by colorimetric methods in patients receiving disodium EDTA due to chelation of a calcium disodium complex. Oxalate and other precipitation methods may also give falsely decreased levels when disodium EDTA is present (15).
PROTHROMBIN TIME (PT): Disodium EDTA can increase prothrombin time (PT) in some patients (5737).
Interactions with Diseases or Conditions:
ASTHMA: Nebulizer solutions containing disodium EDTA as a preservative can produce dose-related bronchoconstriction in some asthmatics (5765).
CARDIAC RHYTHM IRREGULARITIES: Calcium disodium EDTA can cause ECG changes such as T wave inversions (15). Disodium EDTA can have negative inotropic effects on the heart (15). Use with caution in patients with pre-existing cardiac rhythm irregularity conditions.
DIABETES: Use of disodium EDTA may result in poor control of glucose levels in diabetic patients due to disodium EDTA’s interactions with insulin preparations and serum glucose lowering effect (15).
HYPOCALCEMIA: Disodium EDTA can decrease serum calcium levels. Disodium EDTA may exacerbate hypocalcemia in patients with existing low calcium levels (15); avoid using.
HYPOKALEMIA: EDTA can increase urinary excretion of potassium and reduce serum potassium concentrations (15). EDTA might exacerbate hypokalemia in patients with existing potassium deficiency; avoid using.
HYPOMAGNESEMIA: EDTA can chelate magnesium and cause increased urinary excretion of magnesium resulting in depletion of serum magnesium concentrations (15). EDTA might exacerbate hypomagnesemia in patients with existing magnesium depletion; avoid using.
LIVER DYSFUNCTION AND HEPATITIS: Calcium disodium EDTA can cause mild increases in serum ALT (SGPT) and AST (SGOT) (15). Theoretically, EDTA might exacerbate liver dysfunction in patients with liver dysfunction or hepatitis; avoid using.
RENAL DYSFUNCTION: EDTA is nephrotoxic and might exacerbate existing renal disease. Avoid using in patients with severe renal disease and renal failure. EDTA doses should be reduced in patients with renal insufficiency (15).
SEIZURE DISORDERS: There is some concern that disodium EDTA might increase the risk of seizure in people with epilepsy or those prone to seizure (15). Disodium can cause severe decreases in serum calcium which can induce seizure (15).
TUBERCULOSIS: Use of disodium EDTA is contraindicated in people with active tuberculosis or healed calcified tubercular lesions (15). Theoretically, use of EDTA may cause the chelation of calcium from calcified tubercular lesions, resulting in possible reactivation of the tuberculosis disease process.
Dosage/Administration:
TOPICAL: For corneal calcium deposits, a 0.35% to 1.85% solution is prepared with sterile 0.9% sodium chloride and commercially available disodium EDTA preparations for injection (15). Debridement of the corneal epithelium must be done before application of the solution since EDTA does not penetrate the epithelium (5773, 5774). The solution is applied as a corneal bath one time for 15-20 minutes (15)followed by debridement of the calcium (5774), or a cellulose sponge is soaked in disodium EDTA solution and wiped over the deposits until the calcium is removed (5774). The eye should be irrigated with 0.9% sodium chloride following application of disodium EDTA solution (15).
INTRAVENOUS: For acute and chronic lead poisoning and lead encephalopathy, a dose of calcium disodium EDTA 50 mg per kilogram body weight to a maximum daily dose of 3 grams (15) is diluted with 5% dextrose or 9% sodium chloride to a concentration of 2-4 mg/mL and given as a single infusion over 8-24 hours for up to 5 days (15). A minimal 2-day waiting period is suggested before starting a second 5-day course of chelation therapy to further minimize development of nephrotoxicity (15). For blood lead levels greater than 70 mcg/dL, it is recommended that dimercaprol (BAL, British Anti-Lewisite) be used in conjunction with calcium disodium EDTA (5731). For people exposed long-term to low levels of lead and with decreased renal function, 1 gram of calcium disodium EDTA has been used and mixed with 200 mL of 5% dextrose and infused over 2 hours once weekly for 2 months (5732). For hypercalcemia, a dose of disodium EDTA 50 mg/kg body weight up to a maximum daily dosage of 3 grams is diluted with 5% dextrose or 0.9 % sodium chloride to a concentration of 2-4 mg/mL and infused over 3 hours or more (15). For cardiac glycoside-induced ventricular arrhythmias, disodium EDTA is given in a dose of 15 mg/kg per hour to a maximum of 60 mg/kg infused in 5% dextrose (15). For the treatment of atherosclerotic vascular disease, people have used disodium EDTA in a dose of 50 mg/kg up to a maximum of 5 grams diluted in 500-1000 mL of a 150-osmolar carrier (5737). Heparin, sodium ascorbate, elemental magnesium, lidocaine, pyridoxine, and sodium bicarbonate is often added to the infusion with optional additives of adrenal cortex extract, cyanocobalamin, niacin, pantothenic acid, and vitamin-B complex (5737). People usually eat before treatment and bring snacks to eat during a 3-hour infusion (5738).
INTRAMUSCULAR: For acute and chronic lead poisoning and lead encephalopathy, the dosage of calcium disodium EDTA is the same as intravenous administration in divided doses every 8-12 hours (15). When given in conjunction with dimercaprol, the daily dosage is given in equally divided doses every 4 hours. To decrease pain at the injection site, 1 mL of 1% lidocaine HCl or 1 mL of 1% procaine HCl is added to each mL of calcium disodium EDTA to obtain a final lidocaine or procaine HCl concentration of 5 mg/mL (15).
Editor’s Comments:
The American College for Advancement of Medicine (ACAM) strongly supports using EDTA chelation therapy for cardiovascular conditions. ACAM has a standard chelation therapy protocol and has trained more than 6000 practitioners to administer chelation treatments for various conditions (5768). However, the majority of the medical community does not support chelation therapy due to the lack of supporting evidence (5747, 5749, 5756).
An iron-EDTA chelate is also used for iron fortification of grain-based foods. The established acceptable daily intake (ADI) for iron EDTA is 2.5 mg/kg/day. Iron EDTA has Generally Recognized as Safe (GRAS) status in the US (5728).

This monograph was last reviewed on 05/04/2013 and last updated on 04/03/2012. Monographs are reviewed and/or updated multiple times per month and at least once per year. If you have comments or suggestions on something that should be reviewed or included, please tell the editors. For details about our evidence-based approach, see our Editorial Principles and Process.
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