Chelation therapy uses naturally occurring or chemically designed molecules to reduce potentially dangerous levels of heavy metal ions within the body. Chelation treatment is routinely performed for cases of iron overload, lead poisoning, copper toxicity, and other heavy metal conditions. The use of chelation therapy for non-overload indications continues to be investigated. This document addresses the medical necessity of chelation therapy. This document is not applicable to agents used for the treatment of drug overdose or toxicities.

Note: Please see the following related document for additional information:

• MED.00107 Medical and Other Non-Behavioral Health Related Treatments for Pervasive Developmental Disorders

Medically Necessary:

The administration of U.S. Food and Drug Administration (FDA) approved chelating agents is considered medically necessary treatment in any of the following conditions:

• Individuals with disorders of iron metabolism (e.g., primary or secondary hemochromatosis); or
• Lead overload in cases of acute or long-term lead exposure; or
• Individuals with disorders of copper metabolism (e.g., Wilson's disease); or
• Arsenic, mercury, iron, copper or gold poisoning when long-term exposure thereto and toxicity has been confirmed through lab results (i.e., blood, plasma, or urine results) or clinical findings (i.e., symptoms consistent with metal toxicity); or
• Aluminum overload in individuals on chronic hemodialysis; or
• Emergency treatment of hypercalcemia.

Investigational and Not Medically Necessary:

Chelation therapy is considered investigational and not medically necessary for the treatment of all other conditions, including but not limited to:

• Prevention and treatment of cardiovascular disease;
• Peripheral vascular disease;
• Chronic fatigue syndrome secondary to dental amalgam therapy;
• Treatment for Alzheimer's disease;
• Treatment of rheumatoid arthritis;
• Treatment of Parkinson's disease;
• Treatment of cadmium exposure.

Chelation therapy is considered an effective therapy for conditions where heavy metal overload is clearly pathogenic. For example, iron overload can result in kidney, liver and other internal organ damage, and the medical literature has shown chelation therapy to be a relatively safe and effective treatment of this condition. In individuals with heavy metal poisonings, chelation therapy has been established as a relatively safe and effective method of decreasing blood metal concentrations. Several studies published in peer-reviewed medical literature have shown chelation therapy is useful in binding toxic metal ions and allowing their excretion through the liver or kidneys. Several studies have shown the action of chelation agents in individuals with metal poisoning avoids complications such as organ damage and impaired neurological functioning.

The causal effect of heavy metal overload in other conditions has not been proven, and thus the role of chelation therapy remains investigational. For example, although chelation therapy has been investigated as a treatment of a wide variety of diseases and conditions, including Alzheimer's disease, Parkinson's, and rheumatoid arthritis, there has not been adequate scientific evidence to prove the effectiveness and safety of such methods. Further study is needed to ascertain the causal role of heavy metal overload in these conditions, followed by studies demonstrating the efficacy of chelation therapy.

Dental amalgams have been investigated as a cause of increased blood levels of mercury potentially associated with chronic fatigue syndrome or Alzheimer's disease. In 2009, the American Dental Association's Council on Scientific Affairs reviewed the scientific literature on amalgam and stated: "the scientific evidence supports the position that amalgam is a valuable, viable and safe choice for dental patients." The Journal of the American Dental Association (ADA) reported that researchers found "no significant association of Alzheimer's Disease with the number, surface area or history of having dental amalgam restorations" and "no statistically significant differences in brain mercury levels between subjects with Alzheimer's disease and control subjects." The ADA's position has been reaffirmed by the U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health in 2002, 2006 and 2009. The ADA's 2010 amalgam safety update cites that "studies continue to support the position that dental amalgam is a safe restorative option for both children and adults."

Chelation therapy has been proposed as a treatment of coronary artery disease, based in part on the hypothesis that chelation could remove atherosclerotic calcium deposits or provide an antioxidant benefit. One small placebo-controlled randomized study of 84 individuals with atherosclerotic heart disease did not report any advantage of chelation therapy, as measured by time to ischemia at 27 weeks of follow up (Anderson, 2003; Knudtson, 2002). The use of chelation therapy in lieu of established therapies, the lack of adequate prior research to verify its safety and effectiveness, and the overall impact of coronary artery disease had prompted the National Center for Complementary and Alternative Medicine (NCCAM) and the National Heart, Lung, and Blood Institute (NHLBI) to sponsor a large-scale study. The 5-year Trial to Assess Chelation Therapy (TACT) in coronary artery disease began recruiting individuals in March of 2003. This multicenter, randomized, double-blind study plans to enroll more than 1,600 participants aged 50 or older who have had a heart attack. The study will test whether chelation therapy or high-dose vitamin therapy is effective for the treatment of coronary artery disease (CAD). The primary study endpoint of this trial will be a composite of heart attack, stroke, hospitalization for angina, coronary revascularization, and death. The study will also evaluate cardiac deaths, nonfatal heart attacks, health-related quality of life, and cost effectiveness, among other factors. Results of TACT will provide either a significant positive result or an informative null result upon which rational clinical decision-making and health policy can be based. The study has completed enrollment, the participants will continue to be followed through 2011 with analysis of the results in 2012.

The American Heart Association (AHA, 2008) has updated a consensus position along with the American College of Cardiology (ACC), FDA and National Institutes for Health (NIH) concluding that there is inadequate scientific evidence to justify the application of chelation therapy for atherosclerosis at this time.

Chelation therapy involves the administration of drugs that bind heavy metal ions such as lead, arsenic, iron, and mercury in the blood stream preventing their interaction with vital organs, which include the nervous system and kidneys. Such drugs are known as chelating agents. The presence of heavy metals in the blood stream can be the result of several factors including environmental exposure, intake in water and food or in some instances such as lead, inhaling the metal from the air in a location where it is in excess. One frequent cause of lead exposure is through older buildings in which lead based paints were used. There are occupational settings where high levels of metals can occur as well. Additionally, many medical conditions may lead to excess iron in the blood stream that may cause health problems. Chelation therapy reduces the accumulation of essential heavy metals, such as iron and copper or nonessential metals, such as lead and aluminum. Chelators bind with heavy metal ions and enhance the urinary and fecal excretion of these toxic metals. 

Chelation therapy has been proposed as a treatment for the removal of heavy metal ions to reduce cellular oxidative damage caused by the production of hydroxyl radicals. This therapy is under investigation for the treatment of numerous non-overload conditions including, but not limited to, cardiovascular disease, reperfusion injury during coronary angioplasty or cardiopulmonary bypass surgery, anthracycline-associated cardiac damage, Alzheimer's disease, and rheumatoid arthritis.

Chelation agents, however, also have potential toxicity. Chelation agents have been known to bind elements in the body which are necessary for regular functioning, including zinc and calcium. Large doses of vitamins usually accompany the use of chelation agents to lessen these types of side effects. When there is life threatening heavy metal toxicity necessitating treatment with high doses of chelating agents, treatment in the hospital may be needed to monitor for possible side effects. Under less urgent circumstances, chelating agents may be administered on an outpatient basis. Different chelation agents are specific to certain kinds of poisonings.

Primary hemochromatosis: A rare genetic disease that results in the overabundance of iron in the liver, brain, heart and kidneys, causing liver dysfunction, diabetes, changes in skin pigmentation, heart problems, arthritis and testicular atrophy.

Secondary hemochromatosis: A type of hemochromatosis which is usually the result of another condition or disease that causes the overabundance of iron. This disease and condition may include anemias, chronic liver diseases, and the requirement of blood transfusions.

Sickle cell disease: An inherited genetic disorder that causes red blood cells to take on a characteristic crescent or sickle-like shape with decreased ability to carry oxygen.

Sideroblastic anemia: A condition in which there is excess iron in the bone cells.

Thalassemia intermedia: A genetic form of anemia in which there is an abnormality in the oxygen carrying portion of red blood cells.

Wilson's disease: An inherited (autosomal recessive) disorder where excessive quantities of copper build up in the body, particularly in the liver and central nervous system.

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Medically Necessary: 

When services may be Medically Necessary when criteria are met:
For the procedure codes listed above for the following diagnosis codes: 

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Future ICD-10 coding (effective 10/01/2013)
A draft of ICD-10 Coding related to this document, as it might look today, is available for reference and comments at: Appendix 1: Future ICD-10 coding

Peer Reviewed Publications:

1. Anderson TJ, Hubacek J, Wyse DG, et al. Effect of chelation therapy on endothelial function in patients with coronary artery disease: PATCH study. J Am Coll Cardiol. 2003; 41(3):420-425.
2. Bellinger DC, Trachtenberg F, Barregard L, et al. Neuropsychological and renal effects of dental amalgam in children: a randomized clinical trial. JAMA. 2006: 295(25): 1775-1783.
3. Cohen AR, Martin MB. Iron chelation therapy in sickle cell disease. Semin Hematol. 2001; 38(1Suppl1):69-72.
4. Franchini M, Gandini G, de Gironcoli M, et al. Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. Blood. 2000; 95(9):2776-2779.
5. Guha Mazumder DN, De BK, Santra A, et al. Randomized placebo-controlled trial of 2,3-dimercapto-1-propanesulfonate (DMPS) in therapy of chronic arsenicosis due to drinking arsenic-contaminated water. J Toxicol Clin Toxicol. 2001; 39(7):665-674.
6. Hoffbrand AV, AL-Refaie F, Davis B, et al. Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients. Blood. 1998; 91(1):295-300.
7. Knudtson ML, Wyse DG, Galbraith PD, et al. Chelation therapy for ischemic heart disease: A randomized controlled trial. JAMA. 2002; 287(4):481-486.
8. Lin JL, Ho HH, Yu CC. Chelation therapy for patients with elevated body lead burden and progressive renal insufficiency. A randomized, controlled trial. Ann Intern Med. 1999; 130(1):7-13. 
9. Rogan WJ. Safety and efficacy of succimer in toddlers with blood lead levels of 20-44microg/dL. Treatment of lead-exposed children (TLC) trial group. Pediatr Res. 2000; 48(5):593-599.
10. Rogan WJ, Dietrich KN, Ware JH, et al. The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead. N Engl J Med. 2001; 344(19):1421-1426.
11. Rombos Y, Tzanetea R, Konstantopoulos K, et al. Chelation therapy in patients with thalassemia using the orally active iron chelator deferiprone (L1). Haematologica. 2000; 85(2):115-117.
12. Shimizu N, Yamaguchi Y, Aoki T. Treatment and management of Wilson's disease. Pediatr Int. 1999; 41(4):419-422.
13. Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res. 2001; 83(3):207-221.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Agency for Health Care Policy and Research (AHCPR). Health Technology Assessment (HTA) Report. Hemoperfusion in conjunction with deferoxamine for the treatment of aluminum toxicity or iron overload in patients with end-stage renal disease. No. 8. Rockville, MD; U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. 1986; 8:1-20.
2. American Academy of Pediatrics. Policy Statement. Lead exposure in children: prevention, detection, and management. Pediatrics. 2005; 116(4): 1036-1046.
3. American Dental Association. Amalgam safety update. September 2010. Available at: http://www.ada.org/sections/professionalResources/pdfs/amalgam_literature_review_1009.pdf. Accessed on October 29, 2010.
4. American Dental Association. Statement on Dental Amalgam. ADA council on scientific affairs. Revised August 2009. Available at: http://www.ada.org/1741.aspx. Accessed on December 9, 2010.
5. American Heart Association. AHA Recommendation: Chelation therapy. March 11, 2008. Available at: http://www.americanheart.org/presenter.jhtml?identifier=4493. Accessed on October 27, 2010.
6. Centers for Medicare and Medicaid Services. Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd. Accessed on October 27, 2010.
   • National Coverage Determination: Chelation Therapy for Treatment of Atherosclerosis. NCD #20.21. Effective date not posted
   • National Coverage Determination: Ethylenediamine-Tetra-Acetic (EDTA) Chelation Therapy for Treatment of Atherosclerosis. NCD #20.22. Effective date not posted
7. Dans AL, Tan FN, Villarruz-Sulit EC. Chelation therapy for atherosclerotic cardiovascular disease. Cochrane Database Syst Rev. 2002 (4):CD002785.
8. Department of Health and Human Services. Iron overload and hemochromatosis: treatment. Last review September 2, 2010. Available at: http://www.cdc.gov/ncbddd/hemochromatosis/treatment.html. Accessed on October 29, 2010.
9. Sampson EL, Jenagaratnam L, McShane R. Metal protein attenuating compounds for the treatment of Alzheimer's disease. Cochrane Database Syst Rev. 2008 (1):CD005380.

1. National Heart, Lung, and Blood Institute. Disease and Conditions Index, Blood Diseases. Thalassemia. Revised August 2010. Available at: http://www.nhlbi.nih.gov/health/dci/Browse/Blood.html. Accessed on October 27, 2010.
2. U.S. Food and Drug Administration Center for Devices and Radiological Health (CDRH). CDRH consumer information. Dental amalgams. Updated July 28, 2009. Rockville, MD: FDA. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DentalProducts/DentalAmalgam/default.htm. Accessed on October 27, 2010.

BAL
Calcium disodium Versenate^®
Calcium EDTA
CaNa2-EDTA
Chemet^®
Cooley's anemia
Cuprimine^®
D-penicillamine
Deferasirox
Deferoxamine mesylate
Depen^®
Desferal^®
Desferrioxamine
Dimercaprol
Dimercaptosuccinic acid
Disodium EDTA
DMSA
Edathamil calcium disodium
Edathamil disodium
Edetate calcium disodium
Edetate disodium
Exjade^®
Hemochromatosis
Sodium calcium EDTA
Sodium edetate
Succimer
Wilson's Disease

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.