The article by Voest and colleagues [1] provided a comprehensive summary of the pathophysiologic rationale and current indications for the use of chelation therapy in conditions unrelated to iron overload. One controversial area that was not mentioned was the use of ethylenediaminetetraacetic acid (EDTA) as therapy for atherosclerotic coronary artery and peripheral vascular disease, which evolved in the 1950s and 1960s. Advocates originally claimed that EDTA worked by chelating calcium from atherosclerotic plaques [2]. Greater knowledge of the mechanisms of atherosclerosis made this hypothesis untenable, and EDTA therapy fell into disfavor [3]. Nonetheless, chelation therapy with EDTA has quietly flourished, both in this country and abroad. More than 500 000 patients have reportedly received this form of treatment for atherosclerotic vascular disease in the United States alone [4]. Practitioners of chelation therapy now believe that EDTA works by chelating iron and copper, thus impairing the generation of free radicals and the propagation of lipid peroxidation [2, 4]. Unfortunately, both proponents and opponents of EDTA chelation therapy have, until now, used isolated case reports or poorly designed studies done in the 1950s and 1960s to support their respective views.

We could find only two randomized, placebo-controlled, double-blind studies assessing EDTA chelation therapy. A Danish multicenter study of 153 patients with peripheral vascular disease showed no significant symptomatic or angiographic improvement in the EDTA group compared with the placebo group [5]. A smaller Brazilian study, however, showed dramatic resolution of claudication and increased exercise tolerance in patients with peripheral vascular disease who were treated with EDTA [4]. Neither study examined patients with coronary artery disease. Given the explosion of information about free radicals and their role in atherosclerosis, as well as the widespread prevalence of what is still a questionable mode of therapy, it may be appropriate to conduct larger, scientifically rigorous studies to determine whether EDTA is indeed a safe and effective treatment for atherosclerosis.