Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy
This review summarizes evidence from 2 lines of research previously thought to be unrelated: the unexpectedly positive results
of TACT (Trial to Assess Chelation Therapy), and a body of epidemiological data showing that accumulation of biologically
active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas
of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We
examine the history of chelation up through the report of TACT. We then describe work connecting higher metal levels in the
body with the future risk of cardiovascular disease. We conclude by presenting a brief overview of a newly planned National
Institutes of Health trial, TACT2, in which we will attempt to replicate the findings of TACT and to establish that removal of
toxic metal stores from the body is a plausible mechanistic explanation for the benefits of edetate disodium treatment.
History of Chelation
Metal ions that enter the body from the environment can bind to many of the molecules in body tissues, including proteins and polysaccharides. Furthermore, many of these metals are biologically active, participating in a variety of different physiological and pathophysiological reactions. Chelation, in the context of medical therapeutics, is a process in which the organic chelator molecules are introduced into the blood, where they bind the target metal ions with high affinity. The complex of chelator and metal ion remains in the blood compartment until filtered by the kidneys or excreted by the liver, thus removing the metal ions from the body. Edetate disodium, a synthetic chelating agent first synthesized in Germany in the 1930s, has up to 6 binding sites with which to hold and envelop metal ions. The medical utility of edetate disodium was only discovered after some trial and error. After World War II, the U.S. Navy discovered that edetate disodium was effective in treating lead poisoning in naval shipyard workers using lead-based paint.