John C. Pittman, M.D.
The word chelation means "claw" and refers to the chemical process of binding metals and other minerals in the body and removing them through the urine. Intravenous chelation therapy entails injecting the chelating agent EDTA into the bloodstream for the purpose of eliminating from the body undesirable substances such as heavy metals and fatty plaques found in the arteries and elsewhere in the circulatory system.
A variety of chelating agents have been developed since the 1930s, each having different chemical properties that made them useful for certain purposes. Three agents are now the most commonly used: DMSA, an oral chelator that binds to lead, mercury and other metals; DMPS, an intravenous or oral chelator that is especially good at removing mercury; and EDTA, an intravenous binder of lead and other metals.
Of these three chelators, EDTA has been the most studied for the treatment of atherosclerosis and diabetes due to its theoretical ability to bind to calcium in fatty plaque and thereby remove the plaque from artery walls. In principle, this would reduce the size of blockages while improving blood and oxygen flow.
The History of Chelation Therapy (back top)
First conceived by chemist Alfred Werner in the 1890s, it wasn’t until the 1930s that the first chelators were developed with the patent for Ethylene Diamine Tetra Acetic Acid, or EDTA, being first granted in Germany in 1935. EDTA was used by the textile industry to remove calcium from water so that dyes would adhere to fabric better. Shortly afterward, it was discovered that EDTA also had the ability to bind to lead and other toxic heavy metals, making them useful in World War II in the treatment of soldiers with nerve gas poisoning. After the war, there was greater interest in the medical uses for this compound, one discovery being as an anti-coagulant, used to this day in purple top laboratory tubes in which EDTA has been placed to prevent the blood from clotting. Health conditions in which individuals had elevated blood calcium were also being treated with EDTA leading to FDA approval by the late 1940s for the two forms of EDTA: Calcium EDTA for lead removal and Di-Sodium EDTA for lowering blood calcium.
By the 1950s, EDTA chelation was in common use as a treatment for lead poisoning. With the burgeoning automotive industry, there were increasing numbers of workers exposed to lead as they manufactured batteries for all the new cars the baby boomers were buying. During the treatment of a number of these men in Detroit, it was observed that those who had preexisting cardiovascular disease causing chest pain, shortness of breath, and leg pain with walking all experienced improvements of these symptoms. This sparked an interest in research to try to understand the biochemical mechanism of action of EDTA and ushered in the “Golden Age” of chelation when numerous researchers began publishing articles on a variety of benefits from chelation including cardiovascular disease and diabetes.
These early studies demonstrated that EDTA not only bound to lead and other metals, but also opened up blockages in atherosclerotic vessels, improving blood flow and oxygenation. Subsequent studies have demonstrated other mechanisms likely contributing to the effectiveness of EDTA, one being how the chelator will transiently lower blood calcium which causes a surge of parathyroid hormone to be released. This, in turn, results in calcium being removed from areas in the body where it isn’t supposed to be, such as in the walls of arteries and other tissues, moving it back where it should be, such as in the bones. These findings helped EDTA become part of mainstream medicine and began an era of public interest in this therapy for a condition, cardiovascular disease, which prior to that time had no effective treatment.
The tide began to turn in the mid 1960s, however, with the development of coronary artery bypass surgery, a procedure that could instantly fix a blocked artery. Now instead of doing a series of intravenous EDTA infusions to open blood vessels throughout the body, a single surgical procedure could save a person’s life. Nevertheless there was a downside, as the procedure only addressed the three or four major coronary arteries that typically are blocked and don’t do anything for the rest of the body. Nevertheless, this was a groundbreaking procedure and attracted much publicity for the hospitals and surgeons performing the operation. Further developments included the use of balloon angioplasties and stents, creating the highly profitable specialty of Interventional Cardiology, now considered the standard of care.
Because EDTA had never been FDA-approved for the treatment of cardiovascular disease, the final nail in the coffin was the expiration of Abbott Pharmaceutical’s patent in 1969. Since the cost to get a drug approved by the FDA can approach $1 billion in today’s dollars, there is no incentive for pharmaceutical companies to invest in this process unless they have the exclusive right to produce and sell the product by owning the drug patent. This allows them to be able to charge a very high price due to lack of competition and thus make back the money they spent to get the drug approved. The result of these events was that EDTA became an “orphaned drug”, a fate that has befallen many other promising medications resulting in their true potential never being adequately tested. EDTA was no longer on the radar for the conventional world and was soon forgotten by the mainstream medical establishment.
Nonetheless, many of the physicians who had worked with EDTA chelation up to that point were not deterred and continued to administer chelation infusions, publishing small but significant studies documenting its benefits. In 1973, the American Institute of Medical Preventics, later called the American College for the Advancement in Medicine (ACAM) was founded to promote and teach chelation therapy. The definitive Textbook of Chelation Therapy was published soon afterward, and has been regularly updated since. More and more physicians began providing this treatment, and the benefits were speaking for themselves, leading to greater public interest and demand.
The 1980s saw an even greater volume of publications including those showing improvements in patients with congestive heart failure, improved carotid blood flow, lung function and bone density. Studies were published showing no adverse effect on kidney function from EDTA chelation, a criticism left over from the 1950s when safe dosing guidelines had not yet been established. Public demand grew even more as our culture began evolving into a greater awareness of the need for less invasive and more natural approaches. The American Medical Association called for studies to assess the efficacy of chelation therapy. At the same time, conventional cardiologists who were obviously threatened by the popularity of chelation wrote several articles critical of the therapy; may were exposed as blatantly biased toward bypass surgery.
During this same decade, The American Board of Chelation Therapy was formed to certify doctors who provided the therapy, later changing its name to the American Board of Clinical Metal Toxicology.The first major randomized clinical trial to evaluate the effects of chelation therapy was started at Walter Reed Army Hospital in the late 1980s. Less than half the study had been carried out when it was suddenly discontinued, allegedly because the investigators were called to serve in the Gulf War and did not return to complete the study. Instead, a smaller cross-over clinical trial was undertaken, with its findings published in 1990 showing significantly favorable results in the treatment of peripheral vascular disease.
Throughout the 1990s, small studies continued to be published showing benefits from chelation while at the same time other articles were being published in conventional medical literature stating that there was too much heart surgery being done in the United States and that outcomes from non-surgical therapies were just as good if not better for many patients. This opened the door for the re-evaluation of chelation therapy within the conventional establishment with a landmark 100 page article published in 1998 by Steven Olmstead, a research cardiologist at the University of Washington Medical School explaining the mechanisms, chemistry and scientific evidence regarding chelation therapy. One of his conclusions was that the preponderance of evidence was in favor of the therapy for peripheral vascular disease.
Support for chelation continued to be documented with a 1993 study showing that 90% of patients scheduled for coronary artery bypass surgery or amputation due to poor circulation were able to cancel their surgery after undergoing a series of EDTA chelation treatments. Shortly afterward a comprehensive analysis of 19 studies on chelation therapy was carried out, evaluating the effectiveness of the treatment in 22,795 patients showed 90% effectiveness in measurable improvements in cardiovascular disease in patients undergoing chelation.
While not specifically looking at the effects of chelation, a study that led to further refinement of thinking as to the mechanism of action of chelation in the treatment of cardiovascular disease was published in 1999 in the Journal of the American College of Cardiology. This study evaluated the amount of lead and mercury in the heart muscle tissue of patients who died of heart disease and found that mercury levels were 22,000 times higher and lead levels were 18,000 times higher in the heart muscle of individuals dying of heart failure compared to people not dying of heart failure. This reinforced the concept that chelation does more than just act as a roto-rooter; that the removal of highly toxic heavy metals could likely also be helping improve heart function and improve symptoms of heart disease.
Despite this apparent Renaissance in the academic world’s appreciation for chelation, remember that without a patent, there is no interest by private, for-profit pharmaceutical companies in paying for research to prove safety and effectiveness. They have no ability to generate income from the sale of EDTA because any manufacturer can produce it. Competition drives down price so it is not possible to make enough profit to pay back their investment. The only way an orphaned drug has any chance of coming back in a new incarnation is for the research to be carried out by our tax-payer supported research institution, the National Institutes of Health (NIH).
EDTA Chelation Therapy: Mechanisms and Applications (back top)
EDTA was initially developed to pull calcium out of hard water for use in the textile industry, but was later discovered to be an antidote for nerve gas poisoning. After WWII, EDTA was shown to be effective in treating lead toxicity, pulling lead out of the body and removing it through the kidneys. Soon, researchers were taking note that EDTA had many other effects including the removal of radioactive substances in acute radiation poisoning, lowering blood cholesterol levels, beneficial effects in treating arthritis and other auto-immune disorders, improvement in the elasticity of blood vessels, and removal of excess iron. Among the more intriguing claims was that EDTA chelation could reduce chest pain in patients with heart disease. This purported benefit has led many patients to seek chelation therapy either as an alternative or complement to conventional pharmaceutical and surgical treatment.
Chelation therapy using EDTA has been employed in patients with cardiovascular disease based on the theory that binding of calcium by EDTA may stabilize or reduce atherosclerotic plaque containing calcium (Ibad et al. 2016). This theory derives in large part from the fact that EDTA is a powerful and nonspecific chelator of various cations, including calcium. Calcification is observed along the medial elastic layers that make arteries stiff, and EDTA effectively removes calcium from these calcified vascular tissues (Lei et al. 2013). In addition, intravenous injection of EDTA substantially reduced the extent of calcium deposits in the aortic wall (Cavallotti et al. 2004). Again, the general decalcifying mechanism of EDTA may derive from its affinity for this divalent cation mineral. A clinical study demonstrated that calcification in coronary artery disease could be reversed by EDTA–tetracycline long-term therapy (Maniscalco et al. 2004).
Moreover, the disodium salt form of EDTA has been shown to cause transient hypocalcemia, thus leading to the popular hypothesis that it might decalcify atherosclerotic plaque (Lamas et al. 2013). That EDTA binds to calcium is not in question. Researchers postulate that EDTA would pull calcium from the plaques and thereby reduce atherosclerotic plaques on arterial walls. Nevertheless, this mechanism alone may not be sufficient to account for EDTA’s therapeutic effects; other mechanisms may account for the improvements in cardiovascular outcomes demonstrated in the randomized trial by Lamas et al. (2013).
Other putative beneficial effects of EDTA chelation therapy for cardiovascular disease include “free radical scavenging, reduction of total body iron, cell membrane stabilization, arterial dilatation due to reduced calcium channel activity, improve arterial wall elasticity, increased production of nitric oxide, and reduction in lead and cadmium levels” (Obad et al. 2016; multiple citations provided in this review). The TACT study proposed that reduction of oxidative stress by chelation of toxic metals as a biologically plausible mechanism of action (Avila et al. 2014).
As discussed below, the TACT study showed a significant reduction in cardiovascular endpoints for people with diabetes. Mechanisms by which chelation therapy could reduce cardiovascular risk in diabetic individuals include the effects of EDTA chelation on transition and toxic metals. Transition metals, notably iron and copper, play key roles in oxidative stress pathways; on the other hand, toxic metals, notably lead and cadmium, are toxic to the cardiovascular system (Ouyang et al. 2015). Indeed, EDTA’s best documented use is in the chelation of lead, a metal that has been linked with the pathogenesis of hypertension and cardiovascular disease (Vaziri et al., 2008). Any one or combination of these mechanisms could account for the therapeutic benefits that have been reported with EDTA chelation therapy.
Could there be a larger role for chelation therapy in the common problem of excessive lead levels? Dramatic reductions in blood lead levels in the U.S. population over the past four decades have been attributed to phasing out lead as a gasoline additive and restricting the amount of lead permitted in paint. Nevertheless, many people continue to be exposed through lead found in the drinking water supply. The recent largescale lead poisoning debacle in Flint, Michigan, has brought the issue of lead-tainted water into the public eye. The scientific consensus is that there is no safe level of lead, particularly for children, who tend to have larger exposures and more vulnerable nervous systems. The reference blood lead concentration for children set by the U.S. Centers for Disease Control and Prevention, 5 μg per deciliter, is meaningful only for assessing risks within the population. Even lower blood levels have been associated with cognitive and neuromotor problems; however, clinical data are lacking as to whether chelation therapy would help children with excessive blood lead levels.
In the 1990s, researchers at Boston City Hospital (Boston, MA) conducted a decision analysis to compare the clinical impacts and cost-effectiveness of several management strategies for childhood lead poisoning, and to determine how effective chelation therapy would need to be in reducing neuropsychologic sequelae to warrant its use. Based on the modeling they used in this study, they offered the following conclusion: “Chelation of the 1.4% of United States preschoolers whose blood lead levels are 2.21 mumol/L (25 micrograms/dL) or higher could prevent more than 45,000 cases of reading disability, and save more than $900 million per year in overall costs when the costs of remedial education are considered.” (Glotzer et al. 1995)
Some research suggests that EDTA chelation, perhaps combined with DMSA, may be an effective strategy for lowering blood levels in children (Besunder et al. 1997). At this writing, however, no consensus exists regarding the preferred treatment strategy for children with lead poisoning, or how much of a reduction in blood levels would be needed to achieve beneficial measurable outcomes, such as improvements in cognitive and neuromotor functioning.
A controlled clinical trial at the University of Cincinnati Medical College, Cincinnati, OH, sought to evaluate the effects of chelation therapy on blood lead levels, and more importantly on cognitive and behavioral impairments that were attributable to blood lead levels greater than 20 mcg/dL (Dietrich et al. 2004). The chelating agent used in this study was succimer, an oral treatment taken in pill form. The study found that chelation therapy lowered average blood lead levels for approximately six months but without a significant benefit in terms of cognitive, behavioral, and neuromotor endpoints. Specifically, children (ages 5 to 7.5) with blood lead levels between 20 and 44 mcg/dL and treated with succimer chelation did not show better scores on cognitive, neuropsychological, or behavioral tests after 36 months of follow-up (McKay, 2013).
In their discussion of the findings, the researchers conceded that the study’s failure to demonstrate a difference in test scores may have been due to “the small difference in blood lead levels” that resulted following chelation. The succimer pills used had a terrible, sulfide smell, and could easily have been spit out or rejected by the chelation group. The bottom line is that blood lead levels may not have been reduced enough to see a significant improvement in cognitive, neuropsychological, or behavioral outcomes.
A more recent trial conducted by the same Cincinnati research group examined the impact of chelation therapy on lead-associated impairments of motor functions such as postural balance and locomotion or gait activities (Bhattacharya et al. 2007). This randomized, placebo-controlled, double blind clinical trial enrolled 161 children in Cincinnati with high blood lead levels and again employed succimer as the chelating agent. The main outcomes of interest were postural balance and functional locomotion or gait. When compared to the placebo group, the chelation group showed significant improvements in neuromotor functioning, as indicated by reduced postural sway (hence improved postural balance). The chelation group also showed significant improvements in functional tasks of obstacle crossing and normal walking. Thus, some beneficial neuromotor effects of chelation therapy were observed in this study, as reported in the May 2007 issue of Neurotoxicology.
The Trial to Assess Chelation Therapy (TACT) (back top)
Heart disease is the number one killer disease in the United States, and treatments for clogged arteries can have life-saving consequences. In 2000 Rep. Dan Burton, chairman of the Congressional Oversight Committee, held a hearing about chelation with testimony from researchers at the National Institutes of Health (NIH) and from experienced chelation physicians. This hearing was prompted by Rep. Burton’s experience with chelation as a therapy for his autistic grandson. The child’s condition had improved significantly following chelation therapy for heavy metal toxicity. The conclusion was that a large study was clearly indicated leading to the Trial to Assess Chelation Therapy (TACT) and a team of researchers, medical schools and experienced chelation physicians agreed to participate.
The principal investigator chosen to carry out the TACT was Gervasio Lamas, M.D., director of cardiovascular research and academic affairs at Mount Sinai Medical Center-Miami Heart Institute. He explained how chelation gathered momentum in the 1970s and 1980s as a treatment for cardiovascular disease but after a couple of small studies did not show particularly positive results, the therapy was discredited in conventional cardiology and it went into the realm of alternative medicine where it continued to grow. Anecdotal reports and case studies were published describing marked improvement in cardiovascular disease and better blood flow after chelation therapy. It was because there were hundreds of thousands of infusions of chelation each year in the United States that the NIH felt a clinical trial was needed.
The TACT study was approved in 2002 and was funded at $30 million. The study began in April 2003 with eligibility requirements including participants over 50 years of age, having a documented heart attack at least six months prior and having had no cardiac procedures for the prior six months. Such individuals are at high risk of a subsequent cardiac event so the goal was to find out if chelation therapy provided any benefit in terms of reduced or less severe cardiac events. The study was originally planned for 2372 patients but was reduced 1708 patients due to difficulty with recruitment.
TACT was a double-blind, placebo-controlled, multicenter randomized trial of post-myocardial infarction patients who were randomly assigned to receive 40 EDTA infusions versus placebo treatment. The study participants were evenly divided, with one half receiving 3 grams of EDTA or less based on kidneys function along with magnesium, B-vitamins and other components that are used in the standard protocol. The other half was given a placebo which was an infusion of sugar water. No oral supplementations were incorporated beyond a basic multi-vitamin.
Participants were given 30 weekly infusions, then 10 additional infusions every other month for a total of 40 infusions going through this process over approximately 24 months. Originally planned for only three years, the enrollment period was extended to five years with another two years of observation after the last treatments were completed. The final number of participants was 1708 with 55,222 infusions given in 134 sites in US and Canada.
Almost 60 years after the first discovery that EDTA chelation therapy could be effective in the treatment of heart and blood vessel diseases, results of the first large randomized double-blind trial were reported at the American Heart Association meeting in November 2012. The primary end point was an aggregate or composite of total mortality, myocardial infarction, stroke, coronary revascularization, or hospitalization for angina (chest pain).
The study showed that those patients undergoing EDTA infusions had a statistically significant 18% reduction in cardiac events when compared to patients who received the placebo. There were six fewer deaths in the EDTA group as well as 15 fewer heart attacks in comparisons to those receiving the placebo. The longer that patients were followed, the greater the difference better the treatment group and the placebo group suggesting the benefits held for the long term and were not just temporary.
The TACT trial also confirmed our clinic’s practice of combining chelation with an antioxidant supplement regimen. In the trial, the 1,708 post-myocardial infarction patients were randomly assigned to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitamin-multimineral supplement mixture or placebo.
The multivitamin supplement component did appear to improve the outcome, as there was a 26% reduction in mortality for the double active treatment (infusion plus multivitamin) compared with double placebo. The authors concluded that “in stable [post-myocardial infarction] patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance” (Lamas et al. 2014).
In the TACT trial, it is clear that the most remarkable benefit of chelation therapy was among participants with diabetes. Following chelation therapy, this high-risk population showed a 41% relative reduction in cardiovascular risk and a 43% reduction in total mortality (risk of dying from any cause). Thus the 322 patients undergoing EDTA experienced considerable benefits. A comprehensive review of chelation therapy by Peguero et al. (2014) concludes that the “magnitude of benefit [in the TACT trial] is such that it suggests urgency in replication and implementation, which could, due to the excellent safety record, occur simultaneously.” [Italics added for emphasis]
Nevertheless, given that this was the first well-powered clinical trial, the TACT data alone do not constitute sufficient evidence to warrant the routine use of chelation therapy for all post-myocardial infarction patients, particularly with diabetes. On the other hand, the findings are noteworthy and certainly strengthen the overall evidence base for chelation therapy. In the clinical research to date, 16 case series and three randomized controlled trials have shown a significant benefit with chelation therapy in terms of cardiovascular outcomes (Ibad et al. 2016). Given this overall body of research, EDTA chelation therapy may certainly be considered a treatment option (i.e., optional, a possible choice) for patients with cardiovascular disease.
Significance of Chelation for People with Diabetes (back top)
Diabetes is a growing epidemic in the United States with 21 million people being diagnosed with Type 1 or Type 2 diabetes in 2014. It is estimated that 8.1 million are undiagnosed and a huge 86 million are pre-diabetic. Diabetes is one of the most costly diseases as well with estimates at $245 billion annually in the US. Diabetes is the 7th leading cause of death in the US mostly due to the various complications that can occur when poorly treated. These secondary conditions include hypertension, hyperlipidemia, coronary artery disease, cerebral vascular accidents, chronic kidney disease, amputation, and neuropathy. The inability to maintain a stable a normal blood sugar can lead to damage to the microcirculation causing peripheral vascular disease and many other complications include vision loss (due to retinopathy) and stroke.
Type 2 diabetes is clearly linked to obesity so as obesity rates climb, so does the diagnosis. 80-90 percent of patients diagnosed with type 2 diabetes are classified as obese. The International Diabetes Foundation was quoted, “Diabetes and obesity are the biggest public health challenges of the 21st century”. The link here is clear; obesity drives insulin resistance and an inflammatory response. Prolonged insulin resistance puts an extreme amount of stress on the pancreas. When resistance is accompanied by dysfunction of the pancreatic islet b cells that is what ultimately leads to the disease.
As noted in the preceding section, while the overall results of the TACT study were very positive and encouraging of more research, it was the significant benefits observed among diabetic patients that attracted the greatest attention. Given the increase in diabetes in the American population and the younger age of onset for many victims, any treatment offering significant benefit should, in the best of possible worlds, be readily embraced. Most remarkable in the TACT study were the benefits observed by diabetics with severe peripheral vascular disease, losing the circulation in their extremities which in most cases leads to amputation. There were 24 such patients in each group. None of those who received real EDTA in their infusions had to undergo amputation while all but one in the placebo group did have to undergo amputation.
Nutritional support for people with diabetes is imperative. A dietary goal should be to minimize refined sugars and starches. Modern carbohydrate staples, like potatoes, breads, and cereals, have a high glycemic index and a very strong link to chronic disease. Foods low on the glycemic index scale like sweet potatoes, winter squash, and beans help to stabilize blood glucose levels. This can be achieved with whole structured foods and selection of less sugary carbohydrates. Clinical trials support low glycemic index diets with greater fat content are more effective than low fat diets in preventing complications associated with cardiovascular disease. Often a low fat diet contains the highest glycemic index carbs, which leads to increased insulin resistance. Low glycemic index diets improved whole body insulin sensitivity throughout the trials with no increase in LDL cholesterol.
While dietary management is the key to prevention, when complications of diabetes have already developed, chelation has a long history of clinical benefits. Reports of chelation improvements in diabetics have been published for over 50 years. Dozens of peer-reviewed scientific papers have documented significant improvements of vital importance to diabetics and nondiabetics alike: blood sugar, cholesterol, HDL cholesterol, triglycerides, kidney function and serum creatinine levels, artery blockage disease (even of the aorta), severe heart artery blockage, blockage of neck carotid arteries, hardening of the arteries, platelet clotting functions, fatigue, pulse rate and blood pressure, serum calcium and iron levels, trace element patterns in degenerative diseases, psychological status, and other clinical improvements in patients undergoing chelation therapy.
Negative Media Reporting About Chelation Therapy (back top)
Even as the TACT study was underway, negative publicity about chelation continued to be spotlighted in the media leading to confusion about its safety. This all stems from a single event in 2005 in Pennsylvania involving a medication error. The physician administering chelation therapy was blamed for giving the wrong medication. In fact, however, he had ordered Calcium EDTA, but his nurse misunderstood the order and gave Sodium EDTA instead. Calcium EDTA which is used solely as a binder of lead and has no known cardiovascular benefits can be administered quickly without any risk. Sodium EDTA exerts is clinical effects mainly through its ability to transiently lower blood calcium levels and must be infused slowly so as to not lower calcium too quickly. In this case, a medication error led to the infusion of Sodium EDTA at too quick a rate causing calcium levels to fall to a level that resulted in cardiac arrest – a tragic mistake.
By analogy, this same medication error occurs in hospitals on a daily basis, resulting in many adverse and even deadly reactions—as well as millions of dollars of malpractice payments. Clearly the problem is not with chelation itself, but with the use of the wrong form of EDTA which was administered incorrectly. In addition, physicians who do not provide antioxidant and essential mineral support to their patients run the risk of having adverse reactions occur following chelation treatment. It is essential that you receive chelation therapy from a physician who understands these issues. Chelation, like surgery, is a tool that must be wielded in a skillful and judicious manner by a well trained practitioner.
The Role of Heavy Metals in Chronic Illnesses (back top)
As noted above, studies have also linked heart disease to the presence of high levels of mercury and lead in heart tissues leading to the conclusion that the removal of these toxic metals is likely contributing to benefits observed when patients undergo chelation therapy. These metals along with many others have been linked to cancer and numerous degenerative conditions with there being no levels of these toxins in our body which is considered safe. Low dose exposures to lead and mercury have been found to have adverse effects on cognitive ability, particularly in the first few years of life. Any therapy that reduces the body burden of toxic metals could help combat or control these chronic diseases.
It is the small amounts of toxic metals that are the cause of the problems, not industrial exposure or poisoning. There are thousands of references in the medical literature linking small amounts of lead to hypertension. Studies have shown numerous links between cadmium exposures from fertilizer to cancer. Studies on rats have shown the toxic effects are synergistic not additive as chronic exposure is accumulative. Significant links between mercury and Alzheimer’s have been documented.
The future of chelation will likely result from the growing recognition that in spite of spending 5 times what other countries spend on healthcare we are 27th in the world in health quality and with 70% of all deaths being due to chronic disease, addressing the most likely underlying causes which include heavy metal burden should be considered in any preventive healthcare regimen. Understanding the synergy of metals is also important as we appreciate the dangers we face. When rats are fed lead containing water, you find that LD1 is the lethal dose that kills one, LD 25 is the lethal dose that will kill 25 out of 100. The LD100 is the dose that will kill all of them. If you take the LD1 for mercury and 1/20th of the LD 1 for lead and put both in the rat’s water, the result will be an LD100 effect – all 100 will be killed with just the tiniest amount of both toxic metals. This means that small amounts of several toxic metals matter more than you expect – synergism and inflammation.
The Carolina Center’s History with Chelation Therapy
Opening in October 1994, the Carolina Center is the Triangle’s oldest Integrative Medical practice. Dr. Pittman’s training in chelation began in 1995 with his certification by the American Board of Clinical Medical Toxicology being granted in 2000. Over the subsequent 15 years, the role of toxic metals has become even more apparent as numerous studies have continued to show connection between these environmental toxins and degenerative diseases. In the wake of the successes of the TACT Study, there is an even greater value to this procedure provided by the Carolina Center.
The Treatment Process: Preparation for Chelation (back top)
Prior to beginning chelation, it is important that a patient be in a strong nutritional state, especially in terms of minerals as chelators not only remove lead and other metals but also some important trace minerals such as zinc and selenium. Replacement of the minerals regularly while undergoing chelation is critical to avoid complications from treatment. We typically recommend that patients undergo two to three intravenous Mega Mineral infusions prior to starting chelation to be in the strongest place possible nutritionally. Periodic mineral testing and adjustment in supplement recommendations will be carried out to insure ongoing safety. The first chelation treatment incorporates the Urinary Chelation Challenge Test; a procedure is to assess the body’s toxic metal burden which accumulates over months and years. This is very different from procedures used to diagnosis acute or severe metal toxicity which is typically noted through elevation of metals in the blood or through non-challenged urine testing.
For most of us, metals accumulate gradually over years of mild exposure so they aren’t going to be seen in the blood, having been bound in tissues and locked deeply in the body. These stored metals when combined with other environmental toxins that have accumulated in the body, ultimately result in chronic oxidative stress overload along with inflammation and other forms of biological dysfunction. Having very high levels of metals following the challenge test can provide some indication as to the degree that toxic metals may be contributing to oxidative stress and compromising your health on an ongoing basis.
Challenge testing or the "provoked urine test" are terms used to describe the administration of a chelating agent to a person prior to collection of their urine to test for metals. Our approach to challenge testing entails the administration of two chelating agents, Calcium EDTA and DMPS, followed by a 6 hour urine collection which is then sent to the lab to determine the types and amount of metals being removed. While not a true picture of the metals stored in the body, this can give a fairly accurate representation of heavy metal burden. The more metals that can be shaken loose and come out, the more likely that there are more where that came from. The challenge test can then be done again periodically to assess the response to chelation in terms of observing a gradual reduction in the amount of metals being released.
A 2000 study assessed the potential for intravenous DMPS to reduce the body burden of various metals. They showed that the DMPS challenge test resulted in a significant increase in urinary excretion of mercury (3- to 107-fold), as well as 2- to 119-fold increase in copper excretion (Torres-Alanis et al. 2000). In a clinical study of humans exposed to mercurous chloride, DMPS significantly increased the urinary excretion of mercury; the authors concluded that “the DMPS/mercury challenge test is of value for a more realistic estimation of mobilizable mercury” (Maiorino et al. 1996). In another clinical study of mercury-exposed individuals, “DMPS treatment was effective in lowering the body burden of mercury and in decreasing the urinary mercury concentration to normal levels” (Gonzalez-Ramirez et al. 1998).
A study at the University of Arizona concluded that the DMSA “challenge test holds great promise as a diagnostic test for mercury exposure, especially for low level mercurialism. Urinary mercury after [DMSA] challenge may be a better biomarker of low level mercurialism than unchallenged urinary mercury excretion” (Aposhian et al. 1995). Multiple chelation therapy sessions, even without the supplemental use of antioxidant vitamins, have been shown to reduce oxidative stress in humans, as reflected by significant reductions in plasma peroxide levels and oxidative DNA damage (Roussel et al. 2009).
In summary, challenge testing is an important preliminary step before beginning chelation therapy. According to the American College of Medical Toxicologists, challenge testing is not a reliable means to diagnose metal poisoning. Nevertheless, much research has shown that the test is helpful for assessing a person’s overall body burden of metals. Gradual reduction in that body burden is reflected in the challenge testing results with serial measurements over time. Although we can show some level of toxic metal exposure based on red blood cell analysis, the optimal method for evaluating general body burden is the challenge test. This can help indicate potential concerns that might be missed by blood and urine testing. Having very high levels of metals in the urine following the challenge test can provide some indication as to the body burden of toxic metals; it may also indirectly indicate the degree to which toxic metals may be contributing to oxidative stress and compromising your health on an ongoing basis.
Chelation Treatment: A Comprehensive Approach (back top)
The chelation treatment itself consists of a 90 minute infusion of Sodium EDTA along with magnesium, various B vitamins and other nutrients. Treatment frequency depends on various factors but for the majority of patients, infusions are recommended on a weekly basis with the goal of completing 30 infusions after which infusions are done every month or other month for 10 additional treatments.
Further maintenance on a less frequent basis may be recommended beyond these 40 sessions depending on the underlying health issues and overall response to therapy. IV Mega Mineral infusions are interspersed after every fifth chelation to insure no mineral deficiency issues arise.
It is important to understand that Chelation Therapy is a comprehensive treatment protocol that incorporates more than just the IV infusion of Sodium EDTA. The key to therapeutic success is the combination of dietary, lifestyle and nutritional support incorporated during this process. Important oral supplements with minerals and antioxidants are needed between chelation treatments.
Research reported in the April 2007 issue of Cellular & Molecular Biology indicates that chelation therapy may be more effective and better tolerated when combined with specific antioxidant nutrients and herbals to support optimal detoxification. Other oral strategies may be used to accelerate toxic metal removal beyond what can be accomplished with chelation therapy alone.
Health-Related Benefits of Chelation Therapy (back top)
Because this is a non-specific treatment that removes toxins, redistributes calcium, and ultimately improves circulatory flow and oxygenation of all tissues, its benefits are far reaching. This is very different from the highly selective prescription drugs in use today. Most conventional physicians view this "one symptom, one drug" approach as standard medicine and look skeptically upon a therapy which can improve so many different conditions. However, understanding the basic mechanism of action (restoring oxygen to body tissues) allows one to see how EDTA chelation can be beneficial in treating a variety of conditions.
Preclinical, observational and case-series studies suggest potential benefits of chelation therapy for the following conditions, either in terms of reducing risk or complementing standard treatment: myocardial and coronary insufficiency, cerebral arteriosclerosis, Alzheimer's disease, senile dementia, schizophrenia, rheumatoid arthritis, osteoarthritis, gouty arthritis, calcific tendonitis, calcific bursitis, kidney stones, gallbladder stones, multiple sclerosis, lupus erythematosus, Parkinson's disease, Lou Gehrig's disease, cataracts, glaucoma, cancer, osteoporosis, varicose veins, hypertension, scleroderma, Raynaud's disease, digitalis intoxication, heart arrhythmias, hypercalcemia, heart valve calcification, peripheral vascular insufficiency, intermittent claudication, aortic calcinosis, aneurysm, cerebral ischemia, stroke, diabetes, diabetic ulcers, diabetic gangrene, diabetic retinopathy, macular degeneration, emphysema, leg ulcers, venomous snake bite, and any other condition where the problem is an interruption in blood flow because of atherosclerotic plaque, arterial spasm, due to excessive calcium ion concentration, a sluggishness of parathyroid glands in calcium metabolism, or a lack of collateral circulation.
Patients in our facility have reported being able to stop using nitroglycerin tablets for chest pain if they had heart disease, a reduction in the amount of insulin used if they are diabetics, stopping all leg pain on exertion if they have peripheral vascular disease, reduction in arthritic pain and swelling, and an overall improved sense of wellbeing. There are reports of increased energy levels, improved sleep, reduction in food cravings, improved ability to cope with stress, and a feeling of youthfulness and vitality. The more seriously advanced the illness, the more noticeable are the improvements.
Cost and Insurance Issues Around Chelation Therapy (back top)
Understanding the history of chelation therapy as reviewed above, it should come as no surprise that insurance and Medicare do not currently pay for this treatment. Only drugs that have gone through the full FDA approval process for a specific indication such as cardiovascular disease will be accepted as legitimate by the conventional medical establishment and be considered reimbursable by insurance companies. Also, there is tremendous pressure from the cardiac surgeons and cardiologists to suppress this therapy because it directly affects their very lucrative business. Cardiac by-pass surgery, stents and angioplasty account for tremendous revenue for these physicians as well as hospitals they use. We are in a different age now, post the TACT study, and with the second TACT study in the works, doors may eventually open that will allow coverage for this treatment but this is likely still a long way off.
For now, chelation therapy along with the supportive therapies and medical supervision that are integral to its success are not covered by insurance and therefore must be paid for out of pocket. These costs are not insignificant as regulations regarding the dispensing of EDTA and other components of the infusion have tightened in recent years, driving up the cost of supplies.
The cost for this program is divided between the initial and periodic office visits necessary for monitoring and assessing response to treatment and the costs for the actual IV infusions and other components of the treatment. The individual chelation therapy cost is $172 for each infusion with patients undergoing a series of 30 infusions given on a weekly or every other week basis after which treatments are reduced to every 1-2 months for a year then every 3-4 months for maintenance after that. While insurance will not reimburse for the IV chelation therapy itself, for individuals with certain insurance plans with good out of network coverage, the cost of office visits, labs and many other services may be covered at least partially.
Laboratory testing is generally covered for all patients, with Medicare being one of the best in terms of paying for a variety of specialty testing. We work with all patients to balance what is medically needed for each patients versus costs, both what insurance can cover as well as what the patient has to pay directly. We are where to do as much or as little as patients wish or are able.
Patient Decision Making (back top)
While the TACT study is clearly the best evidence available showing that chelation therapy might benefit those with vascular disease, new guidelines for addressing vascular problems call for the treating physician to have a conversation with his or her patients explaining the risks and potential benefits of all options of therapy meaning that chelation now must be offered to such patients as a treatment option. It is then imperative that the patient decides what mode of therapy sounds best to him or her. This is the new “gold standard” with the patient as the decision-maker, not the doctor. Chelation therapy should be discussed in light of the evidence of TACT. With the current status of evidence, chelation therapy may at least be offered to patients as a possible treatment option, particularly as an adjunct to standard care for patients with diabetes and vascular disease.
Physicians trained in providing intravenous chelation report better overall results than TACT. One reason that clinical practice might be better is that continued monthly maintenance is commonly offered after the basic course of treatment. TACT treated patients intravenously for 18-24 months then stopped treatment but followed them for 5 years, still finding that those treated with EDTA fared better than those who received the placebo.
Another reason physicians well-versed in the use of chelation therapy may see better results may relate to the fact that the TACT study did not follow patients using chelation challenge tests for heavy metals to assess how well the metals were coming out. A reaccumulation of toxic metals is not unlikely. Finally, other nutritional therapies are often added by integrative physicians. All of these measures contribute to the best care for each individual patient and would likely improve the overall results.
The Complete Program (back top)
As effective as chelation has been shown to be in clinical studies, in the real world, the greatest benefit in any health program is recognizing that many different components must integrate for optimum results. Chelation is not a magic bullet cure or a miracle drug. It is a tool to be used along with others for total health. At the very top of the list are dietary and lifestyle factors.
Proper nutrition and a complete reevaluation of dietary patterns are necessary for patients who have always eaten a typical American diet (and particularly a typical Southern diet). Lifestyle awareness including proper exercise, avoidance of toxic substances, and control of alcohol, tobacco, and drug use are also top priority issues. Very specific nutritional supplements must be included in one's daily routine to replenish any that are removed from the effects of the chelation. Also very important is the proper assessment of the function of each organ system of the body, including the digestive system, endocrine system (hormones), and organs of elimination.
The ultimate goal is to insure that the highest quality food is taken into the body, thoroughly digested and completely absorbed, and then efficiently transported to the cells where nutrients can be taken in and utilized by the cell for energy. Then, most importantly, the wastes products from the burning of this fuel must be removed from the cell, transported to the organs of elimination, and efficiently removed from the body. When this cycle is working properly through the use of these integrative therapies, every cell in the body will be working at peak efficiency and this will create a situation in which disease simply cannot exist. This is optimum health. When maintained, life can be lived to its fullest and sustained with great vitality.
Linda’s Success Story (back top)
Ever since the TACT study provided compelling evidence for the efficacy of EDTA chelation for diabetic patients with cardiovascular disease, cardiologists have begun referring some of their patients to the Carolina Center for chelation therapy. These are typically individuals for whom no effective conventional treatment options remain. One such patient is Linda, a 56-year-old woman we initially saw on January 2014 when she came to our clinic with extreme weakness, fatigue, and shortness of breath. Her medical history included juvenile onset diabetes, multiple heart attacks and kidney failure. Linda arrived for her initial visit accompanied with her elderly mother who was her full-time caretaker.
Linda was diagnosed with diabetes at age 3, being on injected insulin since. She began having complications of diabetes in her twenties, being hospitalized frequently for wide swings of blood sugar. At age 24 she was diagnosed with diabetic retinal damage in left eye, with significant vision loss. She continued to undergo regular hospitalizations for blood sugar complications.
At age 45, she suffered the first of several heart attacks and was told she had congestive heart failure from long-term damage of her heart due to an insufficient oxygen supply. She continued to have vascular complications of diabetes with the main blood vessels in her legs becoming blocked, thus requiring stent placement in both legs at age 47. Over the next few years, her health declined significantly, with ongoing fatigue, difficulty breathing and further vision loss. Her ability to care for herself was diminishing, and she eventually became unable to stand or walk without experiencing exhaustion.
At age 51 Linda had a second heart attack, then two more at age 53, and two more at age 54. The last heart attack occurred just a couple of weeks prior to her initial office visit in January 2014. At that time she was told that she had lost significant heart function and would need a heart transplant if she was to survive. Shortly before this, she was told that, due to her escalating kidney failure, she would need a kidney transplant and would soon have to start dialysis.
At her initial office visit, Linda had numerous complaints including worsening vision in her remaining eye, chronic chest pain, swelling of her extremities, being unable to lie flat in the bed, and shortness of breath with any exertion. She was retaining fluid, having just gotten out of the hospital a few weeks earlier. She had lost 17 lbs of water after treatment for heart failure.
Linda also had numerous GI complaints with chronic pain, indigestion, heartburn, nausea, bloating, alternating constipation and diarrhea. Her energy level was extremely low, feeling tired and groggy all day. Weakness was severe, being unable to type on a computer keyboard for more than a few minutes with her arms becoming weak. She often became easily exhausted. Due to this constant fatigue, she was unable to drive and thus unable to go shopping or to go out in public for extended periods of time without assistance.
Linda came to us expressing an interest in chelation therapy, as her cardiologist had suggested this treatment following the 2013 publication of the TACT study. She was aware that the study had shown a significant benefit for diabetic patients with cardiovascular disease. After Linda’s initial office visit, she underwent various tests to assess her overall health and various factors that might be contributing to her symptoms.
Linda began nutritional IV nutrient infusions with minerals and other basic vitamins to prepare her for chelation therapy. Chelation therapy can remove good minerals along with heavy metals and calcium therefore mineral supplementation is important for any individual undergoing this treatment.
Linda’s initial lab testing showed her kidney function to be declining, another common complication of diabetes, as noted by a rising creatinine. Kidneys function was severely impaired with a high creatinine of 3.55 (normal range is 0.50-1.10). She was found to have strong markers for chronic yeast infections, a finding that is common in diabetics.
She then began Sodium EDTA chelation treatments on a weekly basis. Before she had received only a few treatments, however, she had another heart attack—her seventh—in April 2014. The attack was considered “mild” relative to her previous attacks, and she was discharged from the hospital more quickly than usual, not having the typical complications.
She resumed sodium EDTA infusions on a weekly basis and by the summer of 2014 noticed a reduction of angina, no longer suffering from chest pain on a daily basis. Unfortunately she suffered her eighth heart attack in September 2014. This manifested mostly by shortness of breath rather than angina, as had been the case in the past. Although this was again considered to be a “mild” heart attack, she was told then that she was no longer a candidate for the kidney transplant due to the seriousness of her heart condition.
After this event, Linda continued chelation therapy. Over the next few months, it became apparent that something had changed. Previously she had been going to the ER with a cardiac event every eight or nine weeks, sometimes even monthly; however, she was now staying away from the ER much longer without any problems. Again, keep in mind that the issues that had occurred since starting chelation had been considered “mild” relative to her previous events. By late 2014, Linda was noting improved energy and greater ease in her breathing. She was able to participate in activities that had previously caused her to easily become exhausted. She was noting an overall sense of well being, something she hadn’t experienced in a long time. Her blood pressure was becoming lower, and her cardiologist was beginning to reduce the dose of some of her medications.
Unfortunately she then had her ninth heart attack in late January 2015 but was considered even milder than the previous ones, and it occurred four months after the previous heart attack—the longest she had gone thus far between events. Her kidney function was beginning to improve, her creatinine now being lower at 3.06 (normal range 0.50-1.10). To Linda’s great relief, her kidney specialist informed her that she no longer needed dialysis.
Linda continued regular chelation therapy through the winter and spring of 2015. In May 2015, however, she had increased shortness of breath and was admitted to the hospital again for a heart attack (her tenth). Again, the event was considered extremely mild. She was quickly released from the hospital and felt very well within a few days. Within a few weeks, she was feeling and functioning even better than before. She able to start doing housework, go shopping and be more social, as well as returning to church. In the past, such activities would leave her feeling exhausted for days afterward. In contrast, she was now only mildly tired after outings.
By the fall of 2015, Linda was doing extremely well, her blood sugar being very stable and consistently lower. After having gained weight following her initial office visit, she had begun losing weight, feeling satisfied with less food. At her latest office visit early 2016, Linda was feeling even better; having lost 12 pounds. Her blood sugar was more stable than in the past, and her kidney function was further improved.
Perhaps most impressively, Linda had experienced no further heart attacks since May 2015. This was the longest she had gone since starting treatment.. Moreover, she was able to do everything any normal person could do: drive her car, go shopping, work on the computer, clean her house and cook food, all without becoming exhausted within minutes as had been the case in the past. She had been seen by her other physicians recently, all of whom were amazed by her progress and the effectiveness of the treatment. She was deemed strong enough to begin a cardiac rehab exercise regimen.
As of her last visit to the Carolina Center, Linda had almost completed the full series of 30 chelation infusions. Based on her stability, the plan was to reduce the frequency of these infusions from every two weeks to every four to six weeks, and over time reduce this further to every three months for long-range maintenance. We have been thrilled to see the progress she has made and how wonderfully she demonstrates the power of chelation therapy.
Citations (back top)
Aposhian HV, Maiorino RM, Gonzalez-Ramirez D, Zuniga-Charles M, Xu Z, Hurlbut KM, Junco-Munoz P, Dart RC, Aposhian MM. Mobilization of heavy metals by newer, therapeutically useful chelating agents. Toxicology. 1995 Mar 31;97(1-3):23-38.
Avila MD, Escolar E, Lamas GA. Chelation therapy after the trial to assess chelation therapy: results of a unique trial. Current Opinion in Cardiology. 2014; 29(5):481-8.
Besunder JB, Super DM, Anderson RL. Comparison of dimercaptosuccinic acid and calcium disodium ethylenediaminetetraacetic acid versus dimercaptopropanol and ethylenediaminetetraacetic acid in children with lead poisoning. J Pediatr. 1997 Jun;130(6):966-71
Bhattacharya A, Shukla R, Auyang ED, Dietrich KN, Bornschein R. Effect of succimer chelation therapy on postural balance and gait outcomes in children with early exposure to environmental lead. Neurotoxicology. 2007 May;28(3):686-95.
Cavallotti CFMTL, Artico M. Experimental calcification of the aorta in rabbits: Effects of chelating agents and glucagon. Journal of Laboratory Animal Science. 2004;31:215–219
Dietrich KN, Ware JH, Salganik M, Radcliffe J, Rogan WJ, Rhoads GG, Fay ME, Davoli CT, Denckla MB, Bornschein RL, Schwarz D, Dockery DW, Adubato S, Jones RL; Treatment of Lead-Exposed Children Clinical Trial Group. Effect of chelation therapy on the neuropsychological and behavioral development of lead-exposed children after school entry. Pediatrics. 2004 Jul;114(1):19-26.
Escolar E, Lamas Ga, Mark DB, Boineau R, Goertz C, Rosenberg Y, Nahin RL, Ouyang P, Rozema T, Magaziner A, Nahas R, Lewis EF, Lindblad L, Lee KL. The effect of an EDTA-based chelation regimen on patients with diabetes mellitus and prior myocardial infarction in the Trial to Assess Chelation Therapy (TACT) Circ Cardiovasc Qual Outcomes. 2014 Jan;7(1):15–24.
Glotzer DE, Freedberg KA, Bauchner H.Management of childhood lead poisoning: clinical impact and cost-effectiveness. Med Decis Making. 1995 Jan-Mar;15(1):13-24.
Gonzalez-Ramirez D1, Zuniga-Charles M, Narro-Juarez A, Molina-Recio Y, Hurlbut KM, Dart RC, Aposhian HV. DMPS (2,3-dimercaptopropane-1-sulfonate, dimaval) decreases the body burden of mercury in humans exposed to mercurous chloride. J Pharmacol Exp Ther. 1998 Oct;287(1):8-12.
Ibad A, Khalid R, Thompson PD. Chelation therapy in the treatment of cardiovascular diseases. Journal of Clinical Lipidology. 2016; 10(1):58-62.
Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL, Lindblad L, Lewis EF, Drisko J, Lee KL; TACT Investigators.
Collaborators (329). Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. JAMA. 2013;309(12):1241-50
Lamas GA, Boineau R, Goertz C, Mark DB, Rosenberg Y, Stylianou M2, Rozema T, Nahin RL, Terry Chappell L, Lindblad L, Lewis EF, Drisko J, Lee KL. EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy. Am Heart J. 2014;168(1):37-44
Lei Y, Grover A, Sinha A, Vyavahare N. Efficacy of reversal of aortic calcification by chelating agents. Calcif Tissue Int. 2013; 93(5):426-35.
Maniscalco BS, Taylor KA. Calcification in coronary artery disease can be reversed by EDTA-tetracycline long-term chemotherapy. Pathophysiology. 2004;11(2):95-101.
Maiorino RM, Gonzalez-Ramirez D, Zuniga-Charles M, Xu Z, Hurlbut KM, Aposhian MM, Dart RC, Woods JS, Ostrosky-Wegman P, Gonsebatt ME, Aposhian HV. Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans. III. Urinary mercury after exposure to mercurous chloride. J Pharmacol Exp Ther. 1996;277(2):938-44.
McKay CA Jr. Role of chelation in the treatment of lead poisoning: discussion of the Treatment of Lead-Exposed Children Trial (TLC). J Med Toxicol. 2013 Dec;9(4):339-43.
Ouyang P1, Gottlieb SH2, Culotta VL3, Navas-Acien A4. EDTA Chelation Therapy to Reduce Cardiovascular Events in Persons with Diabetes. Curr Cardiol Rep. 2015;17(11):96. doi: 10.1007/s11886-015-0656-y.
Peguero JG, Arenas I, Lamas GA. Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients. Trends Cardiovasc Med. 2014;24(6):232-40.
Roussel AM, Hininger-Favier I, Waters RS, Osman M, Fernholz K, Anderson RA. EDTA chelation therapy, without added vitamin C, decreases oxidative DNA damage and lipid peroxidation. Altern Med Rev. 2009 Mar;14(1):56-61
Torres-Alanis O, Garza-Ocanas L, Bernal MA, Pineyro-Lopez A. Urinary excretion of trace elements in humans after sodium 2,3-dimercaptopropane-1-sulfonate challenge test. J Toxicol Clin Toxicol. 2000;38(7):697–700
Vaziri ND. Mechanisms of lead-induced hypertension and cardiovascular disease. Am J Physiol Heart Circ Physiol. 2008; 295(2):H454-65