A Textbook on EDTA Chelation Therapy: Second Edition

Introduction to the First Edition

Elmer M. Cranton, M.D.

Renewed research into the potential benefits of EDTA chelation therapy has sparked increasing interest from clinicians and scientists around the world. Physicians experienced in the use of EDTA are often asked for pertinent clinical data and for guidance on how to safely administer the therapy. This text is designed to provide a compilation of the most current and pertinent information on that subject.

While processing applications for research permits, the FDA has searched extensively for reports of adverse or poor results, including serious side effects, stemming from EDTA chelation therapy as it is now routinely administered. The FDA could find no such evidence. An official request was sent from the FDA to state health and regulatory agencies across the United States asking that any information relating to untoward results, poor results, or patient complaints about EDTA chelation therapy be forwarded to the FDA. No reports of that type were received by the FDA in response to their request.

The safety of properly administered intravenous EDTA is therefore not an issue with Food and Drug Administration (FDA) officials when Investigational New Drug (IND) license applications are reviewed. A large body of published research has been presented to the FDA showing that EDTA is safer than many other more widely accepted therapies.

Increasing Criticism of Bypass Surgery

Many medical authorities have become increasingly critical of bypass surgery. Thomas A. Preston, M.D., Professor of Medicine at the University of Washington School of Medicine and Chief of Cardiology at the Pacific Medical Center, Seattle, Washington, stated about coronary artery bypass surgery, As it is now practiced, its net effect on the patient's health is probably negative. The operation does not cure patients, it is scandalously overused and its high cost drains resources from other areas of need. He further says, A decade of scientific study has shown that except in certain well defined situations, bypass surgery does not save lives or even prevent heart attacks. Among patients who suffer from coronary artery disease, those who are treated without surgery enjoy the same survival rates as those who undergo open heart surgery. Yet many American physicians continue to prescribe surgery immediately upon the appearance of angina or chest pain.¹

In April 1987, results of a Veterans Administration Cooperative Study were published in the New England Journal of Medicine. That study included 486 victims of atherosclerotic heart disease of the most critical kind with unstable angina pectoris. Half were subjected to bypass surgery and the other half were treated without surgery. The overall two-year survival rate did not differ between surgically-treated patients and those who were treated without surgery, and the incidence of myocardial infarction was not significantly different.²

A small group of cardiac patients with severely reduced ejection fraction did show an improvement in death rate of approximately 10 percent after two years. Those results are very similar to the previously published CASS study.³,⁴ Both studies, however, were conducted prior to the use of calcium channel blockers, although beta blockers were administered to half of the CASS patients. Both types of prescription medicine have been shown to reduce the incidence of myocardial infarction, decrease death rate in coronary artery disease, and relieve angina without surgery. It is therefore not possible to conclude whether patients would not do equally as well or even better without surgery unless further research is done to compare bypass surgery with present-day medicines and chelation therapy.

Another report in the New England Journal of Medicine in 1987 showed that coronary blood vessels increase in size as plaques occur. When a plaque grows to approach 50 percent of the lumen of a coronary artery, the artery simultaneously enlarges to compensate. The diseased artery therefore continues to allow the same flow of blood as a healthy artery.⁵

Only when plaque blockage exceeds 50 percent does coronary blood flow begin to decrease. At that point, collateral circulation will often maintain an adequate supply of blood, even when a major vessel becomes totally blocked. With 75 percent blockage from plaque, compensatory enlargement causes overall blood flow to remain equal to that in a healthy artery with only a 50 percent blockage. Furthermore, animal experiments show that more than 50 percent blockage of a normal coronary artery is necessary to decrease heart function, even under maximum physical stress. More than 75 percent blockage of an artery, without time to compensate, is needed to impair cardiac function at rest. Nonetheless, bypass surgery is aggressively recommended in many instances with plaque blockage of 75 percent or less, despite adequate coronary blood flow.

An editorial in that same issue of the New England Journal of Medicine stated, Those…who perform coronary arteriography have made one serious mistake. It consists of the unfortunate adoption of a grading system for stenoses expressed as a percentage of the arterial lumen that is compromised. This grading system implies a degree of accuracy that coronary angiography cannot achieve. It is not possible to accurately predict the three-dimensional flow of blood in an artery from two-dimensional x-ray shadows. That editorial goes on to point out that 75 percent blockage of a diseased coronary vessel is therefore necessary to even begin to compromise the heart with maximum stress, and that considerably more than a 75 percent plaque blockage is necessary to reduce cardiac function without strenuous physical exertion.⁶

Conclusions in that report state, The preservation of a nearly normal lumen cross-sectional area, despite the presence of a large plaque, should be taken into account in evaluating atherosclerotic disease with the use of coronary angiography.⁵ That recommendation is most often ignored at medical centers dependent on financial income from bypass surgery.

Arterial spasm, best treated without surgery, can cause anginal pain and myocardial infarction, even without atherosclerotic plaque. Reversible spasm can also be triggered by irritation from contrast media and diminished oxygen transport during catheterization, which can closely mimic atherosclerotic plaque.

Why then are patients so often told they must have bypass surgery on the basis of arteriograms showing a 75 percent blockage, with little consideration for overall heart function and total coronary flow? Why is the heart not routinely evaluated with non-invasive technetium and thallium radioisotope imaging, before proceeding with surgery? Is it because isotope imaging will so often show efficient cardiac function and adequate coronary perfusion, despite the abnormal arteriograms? Is it possible that isotope studies are so seldom done because surgery might be canceled if results of noninvasive imaging did not agree with arteriography?

Arteriograms are a major marketing tool for bypass surgery and balloon (or now laser) angioplasty. Catheterization and arteriograms are too often used to frighten patients into accepting unnecessary, dangerous, and expensive surgery or angioplasty, when nonsurgical treatment would be equally as effective or more so, with less danger and expense. The risk of harm or death to the patient, even from the catheterization and arteriograms, is significant. Arteriograms should be used only after all else has failed, after a decision to consider surgery or angioplasty has been made, based on severity of symptoms and lack of response to nonsurgical treatments including chelation therapy.

Another reason to delay surgery whenever possible is a recent report of accelerated atherosclerosis in coronary arteries after they have been subjected to bypass. Plaques grow faster after surgery.⁷ When an artery is bypassed beyond a point of high-grade obstruction, a region of back-flow and stagnant flow is created between that partial obstruction and the site of the surgically implanted bypass. When a bypassed artery is only partially blocked, as is often the case, thrombosis and total occlusion of the bypassed segment, up to the point of bypass, can more easily occur, creating total dependence on a thin-walled and weaker vein graft. When that vein graft fails, the patient is worse off than before surgery.

The AMA has publicized in its Journal of the American Medical Association that 44 percent of all bypass surgery in the United States is done for inappropriate reasons. The Congress of the United States, Office of Technology Assessment, has criticized the unproven character of bypass surgery and many other commonly performed medical procedures.⁹ Balloon angioplasty was introduced in the early 1980s as a way to avoid costly and dangerous bypass surgery. Instead, the number of bypass operations has increased from 200,000 in 1984 to 230,000 in 1988, at a time when angioplasty procedures increased from 46,000 to 200,000 per year. Angioplasties often fail in less than a year, leading to repeated angioplasties or bypass surgery. Angioplasty can also damage an artery, exposing collagen to platelet aggregation and rapid clotting, making chelation therapy and other nonsurgical treatments less effective.

The Chelation Alternative

Patients are rarely told about chelation therapy before bypass surgery or angioplasty, although chelation is hundreds of times safer at a small fraction of the cost. If asked, cardiologists and bypass surgeons will usually criticize chelation therapy and press for the much more profitable catheterization and bypass surgery or angioplasty.

This text presents a compilation of data to support the clinical effectiveness of EDTA chelation therapy for the treatment of atherosclerotic cardiovascular disease. Results of clinical trials are published in this volume. All support this therapy.

Clinical research relating to EDTA chelation therapy came to a virtual standstill in the early 1960s, as bypass surgery first came into vogue. Even limited studies of chelation therapy were not resumed until the 1980s. Perhaps that timing was mere coincidence, but the fact remains that discontinuance of chelation research might historically be the greatest wind-fall to surgeons and hospitals since the discovery of general anesthesia.

The leading investigator of chelation therapy in the early 1960s, Dr. Kitchell, published data very favorable to EDTA chelation therapy in his final Reappraisal article. In contradiction to his data, Kitchell ended that report with a negative conclusion.¹⁰ That one article with its erroneous conclusion was primarily responsible for an end to chelation research lasting for decades. Kitchell's data were analyzed in detail by Cranton and Frackelton¹¹ and that analysis is published elsewhere in this text.

A careful search of the scientific literature in 1989 shows no negative data which refutes the usefulness of EDTA chelation therapy. Adverse reports have either been editorial in nature or totally anecdotal, with no supporting scientific evidence to contradict the growing body of evidence which supports the safety and clinical effectiveness of EDTA. Most criticisms of chelation therapy continue to originate from individuals with vested interests in competing therapies.

The American College for Advancement in Medicine maintains an extensive library of scientific literature relating to EDTA chelation therapy, including many of the articles listed as references to chapters throughout this book. Copies are available from ACAM:

References

1. Preston TA. Marketing an operation: Coronary artery bypass surgery. J Holistic Med 1985;7(1):8-15.

2. Luchi RJ, Scott SM, Deupree RH, et al. Comparison of medical and surgical treatment for unstable angina pectoris. N Engl J Med 1987;316(16):977-984.

3. CASS Principal Investigators and Their Associates: Coronary artery surgery study (CASS): A randomized trial of coronary artery bypass surgery. Circulation 1983; 68(5):951-960.

4. CASS Principal Investigators and Their Associates: Myocardial infarction and mortality in the coronary artery surgery study (CASS) randomized trial. N Engl J Med 1984;310(12):750-758.

5. Glagov S, Weisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316(22):1371-1375.

6. Paulin S. Assessing the severity of coronary lesions with angiography. N Engl J Med 1987;316(22):1405-1407.

7. Cashin LW, Sanmarco ME, Nessim SA, Blankenhorn DH. Accelerated progression of atherosclerosis in coronary vessels with minimal lesions that are bypassed. N Engl J Med 1984;311(13):824-828.

8. Winslow CM, Kosecoff JB, Chassin M, et al. The appropriateness of performing coronary artery bypass surgery. JAMA 1988;260:505-509.

9. Assessing the Efficacy and Safety of Medical Technologies. Washington, DC, Congress of the United States, Office of Technology Assessment, publication No 052-003-00593-0. Government Printing Office, Washington, DC, 20402, 1978.

10. Kitchell JR, Palmon F, Aytan N, Meltzer LE. The treatment of coronary artery disease with disodium EDTA, a reappraisal. Am J Cardiol 1963;11:501-506.

11. Cranton EM, Frackelton JP Current status of EDTA chelation therapy in occlusive arterial disease. J Holistic Med 1982;4(l):24-33.

Introduction to the Second Edition

Elmer M. Cranton, M.D.

Much new information and research has become available since publication of the First Edition of this textbook. In this updated Second Edition, I have included data from a number of clinical trials performed since the original publication. Other chapters have been extensively updated to reflect current practice and theory.

Chapters are written by many different experts in this field. The reader will find some contradictions. This is an evolving field of science, and experts rarely agree in all areas of their expertise.

In the future, I will periodically post new information and updates on my Internet website: http://www.drcranton.com

Physicians interested in training courses, books, and information on this subject are referred to the professional association of physicians with special interest and expertise in chelation therapy and other innovative, complementary, and alternative therapies.

American College for Advancement in Medicine

23121 Verdugo Drive, Suite 204

Laguna Hills, CA 92653

949-583-7666

1-800-532-3688 in the U.S.A.

Fax: 949-455-9679

www.acam.org

Recent research studies reported in this Second Edition were initially published in the Journal of Advancement in Medicine, the official Journal of the American College for Advancement in Medicine (ACAM). The Board of Directors of ACAM kindly gave permission to incorporate them into this anthology.

Alternatives to traditional and mainstream medicine are rapidly gaining momentum worldwide. Medical schools now offer courses and workshops in Alternative Medicine. The National Institutes of Health of the United States Public Health Service has established a branch devoted entirely to research in alternative medicine. However, strictly speaking, I do not consider chelation therapy with intravenous EDTA to be in the same category as most other alternative therapies. EDTA is a prescription drug and its use is regulated by the FDA. The practice of EDTA chelation therapy is limited to health care professionals with unrestricted licenses to practice, prescribe, and administer intravenous therapy. Although EDTA chelation has an excellent safety record when properly administered, there remains the danger of adverse effects when improperly used. This textbook provides detailed guidelines in safe and effective use of EDTA chelation therapy.

A Plea for Research Funds

Although clinical studies of chelation therapy are all positive, none yet meet the FDA's very strict criterion needed for a change in marketing claims. Studies of that type cost many millions of dollars. Lacking patent protection, tax-supported funding by NIH remains the only potential source for a grant that large. To date, all applications to NIH for research money have been denied or otherwise blocked. Because EDTA chelation therapy has not been proven with large, double-blind, placebo-controlled studies, medical insurance continues to deny payment and mainstream medicine refuses to recognize this as a safe and effective treatment for atherosclerosis. More than a million Americans have benefited from EDTA chelation therapy. It is difficult to understand why NIH does not fund a study to satisfy requirements for reimbursement by Medicare and other insurance. The health and welfare of the American public require such a tax-funded study.

Use Outside the United States

Chelation therapy is becoming accepted worldwide. The complete protocol for administration of EDTA chelation therapy, as now used in the United States, includes a number of recent additions and embellishments. Because it is often difficult for physicians in less industrialized nations to obtain some of the materials routinely used in the complete protocol, an abbreviated protocol is often used. Although the complete protocol, as described in Chapter 32, does result in somewhat greater overall benefit, an abbreviated protocol will also work quite well, if all of the ingredients and supplies needed for the complete protocol are not readily available.

For the benefit of doctors in countries with limited access to all ingredients listed in the complete protocol, I will point out that for several decades, from the early 1950s through the mid-1980s, EDTA chelation therapy consisted of simply 3.0 grams disodium EDTA, infused over three hours in a 500 ml solution of either 5 percent dextrose, normal saline, or Ringer's lactate solution. Lidocaine or procaine was added to the infusion to prevent pain at the infusion site. Vitamin-mineral and trace element supplementations were given by mouth. For treatment of patients with normal renal function, that minimum protocol worked very well. For many years, reports of EDTA chelation's success were based on that simple protocol for administration.

Misleading Research Reports

In the past decade, three double-blind placebo-controlled studies have appeared in the medical literature alleging to demonstrate that EDTA chelation is not effective in treatment of cardiovascular ailments. These studies are referred to as the Danish study, the New Zealand study, and the Heidelberg study. Positive data from these studies were misinterpreted in a misleading negative manner. Two of those studies were conducted by cardiovascular surgeons. In addition, the surgeons conducting the Danish study freely admitted their bias and stated that the purpose of their research at the outset was to disprove EDTA chelation therapy. Although flawed and statistically underpowered, the three studies provide further support for the use of EDTA chelation therapy. A detailed analysis of the three studies is provided in Chapter 1. Although the three studies were reported as negative, a proper analysis of the data is quite positive.

In the Danish study, the chelation group's improvement was more than twice as great as the placebo group's, even though the chelation group was significantly sicker at the outset.¹, ²

In the New Zealand study, improvement in artery pulsatility (measurement of pulse intensity) in the EDTA group's worse leg reached statistical significance (p<0.001), compared with placebo.³, ⁴ One of the placebo patients in that study was what statisticians call an outlier—one whose results differ strikingly from everyone else in the group. This patient's walking distance increased by almost 500 meters with only placebo therapy, invalidating reproducibility of his baseline measurement. All of the statistical gain in the placebo group was due to this one individual's progress. Without him, the placebo group's walking distance decreased slightly. The EDTA group's walking distance increased by 25 percent, and would have been very significant statistically. The fact that most of the individuals in the chelation group were smokers would also have reduced the final benefit of EDTA chelation therapy.

The Heidelberg study was equally misleading and even more supportive of EDTA chelation therapy.⁵–⁶ Four patients in the EDTA group experienced more than a 1,000-meter increase in their pain-free walking distance following treatment. The average increase in walking distance in the EDTA-treated group was 400 percent—five times the 76 percent increase of the placebo group.

Low-Dose EDTA

The lowest effective dose of EDTA to provide optimum benefit is not yet certain. It is known that the maximum safe dose rate of infusion is 16.6 mg/min, reduced proportionate to renal impairment. Most studies to date have used that dose, infused over 3 hours, as described in detail in Chapter 32.

Clinical experience has shown that good results can be achieved with a lower dose of EDTA. What is not known is whether the benefits of a lower dose will equal those benefits seen in higher doses. There has never been a proper study comparing two groups of patients: one group treated with the traditional dose-rate of 50 mg/kg over 3 hours, and the other group treated with a lower dose.

One study alleged equal or better results with low-dose EDTA, but the endpoint erroneously used for comparison was systolic blood pressure in ischemic extremities.⁷ When the authors originally submitted their results for publication, they tabulated before-and-after Doppler systolic blood pressure measurements to indicate improvement. Although the authors clearly stated in the text that ankle/brachial Doppler blood pressure ratios are the accepted endpoint, they neglected to provide complete data of that type. They supplied only systolic blood pressure in the foot and ankle, with no brachial measurement for comparison. When the study was first submitted for publication to the Journal of Advancement in Medicine, that journal's peer-review committee requested that accepted endpoints be supplied, including ankle/brachial Doppler blood pressure ratios and maximum walking distance to claudication. The authors refused to submit that information and instead published their limited data in a non-peer-reviewed magazine.⁸ Because EDTA chelation often lowers blood pressure quite considerably following therapy, their findings that a lower dose of EDTA resulted in higher blood pressure could well indicate less benefit, quite the opposite of the authors' conclusion.

Bypass Surgery, Angioplasty, and Stents

For centuries, since a classical description of angina pectoris first appeared in the medical literature, there has been little for physicians to offer patients in the way of effective treatment until comparatively recently.

Through the end of the 1940s nitroglycerin was the standard treatment for angina, although it had little effect on long-term outcome. In 1950, a seemingly miraculous remedy appeared. Surgeons developed a new operation called internal mammary artery ligation that involved surgically tying off a blood vessel that carries blood to the chest wall. Because this artery is near the heart, surgeons hypothesized this action would force more blood to flow through coronary arteries and ease the pain of angina.

Results exceeded the most optimistic expectations. Remarkably, up to 90 percent of patients reported either total pain relief or dramatic symptom improvement. The operation, hailed as a miraculous advance, was widely advocated by many members of the medical profession. Enthusiasm mounted; angina victims lined up; surgeons maintained three-month waiting lists. Although the benefits rarely lasted more than a few months, the operation's effectiveness went unquestioned and untested for almost ten years. But then, as now, there were skeptics within the medical community. There was too much enthusiasm to suit some analytical physicians who doubted the procedure deserved such universal acclaim, inasmuch as it had a dubious scientific rationale. To test the questioned hypothesis, those skeptics designed a research protocol that would be unacceptable under today's more rigid ethical standards.

They divided surgical candidates into two groups, each equally afflicted with angina. All subjects were told they were to undergo ligation surgery, and went through identical hospital protocols with only one important difference: One group did have the ligation operation, but the control group was taken into the operating room, anesthetized, and then subjected to a sham operation. Their chests were opened, then closed—nothing else was done. When they awoke, both groups were told their operations had been successful.

To the astonishment of the entire medical community, the surgeons included, both groups reported relief from anginal pain and increased tolerance of exercise. Amazingly, the group that had undergone the sham surgery fared better than those who had undergone the genuine operation.⁸, ⁹ It was the first time medical researchers proved that placebo effect extends to surgery; and, not surprisingly, when word got out, the number of operations plummeted.

Placebo effects occur immediately and last only a few months at most. Unlike placebo effect, patients do not get full benefit from EDTA chelation therapy until three months after therapy is completed, and benefit continues for many months or years thereafter. This is totally unlike any placebo effect ever reported. At a point in time when placebo effect would disappear is when relief from chelation therapy reaches its peak.

Coronary bypass surgery, the most common major operation performed in the United States today, may well be the current equivalent of that sham surgery of 1950—at least in the majority of patients operated on. According to the American Heart Association, in 1995 there were 1,460,000 angiograms performed at an average cost of $10,880 per procedure. This resulted in 573,000 bypass surgeries at an average cost of $44,820, and 419,000 percutaneous transluminal (balloon) coronary angioplasties (PTCAs) at $20,370 each. The total bill in 1995 was thus more than $50 billion, or $137 million per day—$5.7 million per hour. That is very big business. The total annual cost of cardiovascular disease treatment in the United States is estimated at $274 billion per year.

I'm not opposed to surgery and angioplasty. I personally refer patients for those procedures when I feel the risk of surgery is less than the risk of non-invasive treatment. For most patients, whose conditions are stable and not worsening at a dangerous rate, I'm very opposed to immediately and aggressively resorting to invasive, expensive, and potentially dangerous procedures. I strongly urge that EDTA chelation therapy be first administered. Very convincing evidence supporting that form of therapy is presented in this book.

Despite the aggressive use of bypass surgery, it has never been conclusively proven to do much more than relieve the pain of angina (the exceptions are in a small subgroup consisting of 15 percent of patients who meet very specific selection criteria). As with any symptom-relieving treatment, there is a real possibility that the placebo effect is at least in part responsible. Because the legal and ethical climate today precludes sham operations, such as those used to study internal mammary ligation, bypass surgery has never been subjected to a placebo-controlled study.

Coronary artery bypass might well act as a type of surgical beta blocker, with an action paralleling that of a group of drugs that diminish angina pain by blocking nerve impulses that trigger arterial spasm and increase the force of cardiac contraction. It is not possible to perform bypass surgery without partially disrupting nerves that stimulate the beta receptors on arteries and myocardium. In addition, surgery also disrupts nerves that transmit the pain of angina.

Studies increasingly appear in the scientific literature showing only limited benefit from bypass surgery and angioplasty compared to non-surgical therapy—and serious complications of those invasive procedures are not unusual.

Subtle and lasting brain damage occurs in 23 percent of patients following bypass surgery.¹⁰ How often is this fact revealed to patients before surgery? Roach reported in the New England Journal of Medicine, Adverse cerebral outcomes after coronary bypass surgery are relatively common and serious; they are associated with substantial increases in mortality, length of hospitalization, and use of intermediate- or long-term care facilities. Five years after bypass, 23 percent of patients were found to experience difficulty understanding spatial relationships and an additional 16 percent had an abnormal reduction in the ability to remember words. Of those, 6.1 percent suffered more serious brain damage, including dementia, stupor, stroke, and epileptic seizures.

The Newark Star-Ledger reported in March 1999, that the statewide New Jersey death rate for deaths caused by bypass surgery complications was 3.37 percent, and in some hospitals it was as high as 8 percent.

The most important study of long-term results following bypass was the Coronary Artery Surgery Study (CASS), in which 780 patients were followed for more than 12 years. The study was conducted at 11 prominent medical centers: the University of Alabama, Alabama Medical College, Boston University, the Marshfield (Wisconsin) Clinic, Massachusetts General Hospital, Milwaukee Veterans Hospital, New York University, St. Louis University, Stanford University, Yale University, and the Montreal Heart Institute. Seven hundred eighty volunteer patients with uncomplicated heart disease or heart symptoms were divided into two groups. Half had bypass operations; the other half had medical treatment consisting of drugs and advice to start exercising sensibly and avoid risks like smoking, overeating, and consuming too much fat in their diets. When that long-awaited ten-year, government-funded study was released, it offered little encouragement for advocates of cardiovascular surgery.

After many years of followup, results now show that only the most severely diseased 15 percent of patients who submit to bypass surgery actually got a measurable increase in life expectancy.¹¹, ¹² But even for those few, the death rate was higher during the first two years following surgery because of deaths caused by surgical complications.

That 15 percent of patients who did get a small but statistically significant benefit fell into the following three categories: (1) patients with high-grade obstructions of the left main coronary artery system, including the left anterior descending artery, without adequate collateral flow around those blockages; (2) patients with high grade blockages of all three major coronary arteries without adequate collateral flow; and (3) patients with greatly reduced pumping action of the heart. Patients who met one or a combination of those criteria eventually experienced a small increase in survival rate lasting a few years. From the second to fifth years the death rate became about 10 percent less, compared to patients who did not have surgery. That advantage was gradually lost after the fifth year.

In other words, 85 percent of the bypass surgery patients had no increase in life expectancy when compared to the patients treated non-surgically. The remaining 15 percent of bypass surgery patients had a 10 percent lowering of death rate at five years, which amounts to a 1.5 percent overall lowering in death rate following bypass surgery. Bear in mind that from 3 percent to 8 percent (depending on the hospital) die immediately as a complication of surgery. Bypass surgery thus causes an increase in death rate during the first two postoperative years. Those percentages have been consistent in other studies published since.

It is true, nevertheless, that some patients—those who have been carefully selected and who suffer severely impaired quality of life from coronary heart disease—do experience dramatic improvements following either surgery or balloon angioplasty if they survive the procedures without lasting complications. A significant finding of the CASS study is that the death rate for patients who did not have bypass surgery or angioplasty was only 2 percent per year. That is a low death rate for patients with serious heart disease and does not seem to justify the use of dangerous and expensive invasive procedures.

After six years, 92 percent of the surgical patients and 90 percent of the medically treated patients were still alive. The researchers concluded that an estimated 25,000 bypass operations could be eliminated each year.

Dr. Eugene Braunwald, professor of cardiology at Harvard Medical School, pointed out in the New England Journal of Medicine, that the CASS data were already obsolete when the study came out, inasmuch as it was collected before the advent of new medical therapies, such as newer calcium-channel blockers and improved beta blockers. Non-surgical therapy has not stood still during the last six years, Dr. Braunwald noted, challenging the validity of findings that exclude recent advances in non-surgical cardiovascular treatment. If EDTA chelation therapy had been compared to surgery, it is my belief that surgery would have fared much worse by comparison.

It is widely agreed that bypass surgery or angioplasty can relieve symptoms of angina and is suitable for patients whose quality of life is greatly impaired by chest pain, not relieved by medicine. They must be willing to accept a risk of 2 percent chance of death (higher at many hospitals) and a 25 percent incidence of other serious or lasting complications.

In 1998, a report from the Veterans Administration Cooperative Study included 486 victims of atherosclerotic heart disease of the most critical kind with unstable angina pectoris. Half were subjected to bypass surgery, and the other half were treated without surgery. The overall two-year survival rate did not differ between surgically treated patients and those who were treated without surgery, and the incidence of heart attack was not significantly different.

A small fraction of patients with severely reduced pumping action of the heart did show an improvement in death rate of approximately 10 percent after two years. Those results are very similar to the previously reported CASS study. Both studies, however, were conducted prior to the use of calcium channel blockers (although beta blockers were administered to half of the CASS patients). Both types of prescription medicine have been shown to reduce the incidence of heart attacks, decrease death rate in heart disease, and relieve angina without surgery. None of the studied patients received EDTA chelation therapy. It is therefore not possible, without further research comparing bypass surgery with present-day medicines (including EDTA chelation therapy), to conclude whether a greater percentage of patients would do equally well or even better without surgery.

Arterial spasm can cause anginal pain and heart attack, even without atherosclerotic plaque; and spasm is best treated without surgery. Reversible spasm can also be triggered by irritation from the injected dye and reduced oxygen transport during angiograms, which can closely mimic blockage by plaque. Arteries are encircled by bands of muscle, like a belt around the waist. If that muscle contracts in spasm, like tightening a belt, blood flow is cut off.

Patients are often told that they must have bypass surgery because arteriograms show a 75 percent blockage, with no consideration for heart function or total blood flow. Overall cardiac efficiency and blood flowing past and around the blockage can be measured with isotope imaging prior to recommending surgery. Non-invasive imaging of the heart under exercise using radioisotopes may show efficient pumping action and adequate myocardial blood supply through collaterals, despite severely abnormal arteriograms.¹⁴

Arteriograms have become a major marketing tool for bypass surgery and balloon angioplasty (and now sometimes for laser vaporization or removal by rotating blades). Results of catheterization and arteriograms can be used to frighten patients into accepting unnecessary, dangerous, and expensive surgery or angioplasty, when non-surgical treatment might be equally effective or even more so, with much less danger and expense. The risk of harm or death to patients, even from the preliminary catheterization and arteriograms, is significant.

For almost 30 years, the coronary angiogram has been the diagnostic tool most revered by vascular surgeons, the one they invariably rely on for evidence of need for surgery. If the angiographer reports as much as a 75 percent occlusion of the so-called time-bomb artery (the left main coronary, or its major branch, the left anterior descending artery), the necessity for a bypass is considered confirmed. But a National Heart, Lung, and Blood Institute (NHLBI) study gave hard evidence that coronary angiography is more art than science. The NHLBI report, presented from the podium at an American Heart Association meeting in Anaheim, California, revealed that inaccurate assessments of arteriograms are commonplace and when experienced radiologists evaluate the same angiograms, they have conflicting opinions almost half the time.

The NHLBI conducted a three-pronged probe. In one study, three arteriographers, working independently, examined films of 28 patients who had died within 40 days of cardiac catheterizations. When their readings of the amount of occlusion of that all-important left main artery were compared with actual autopsy findings, it turned out they were more often wrong than right. In a whopping 82 percent of their judgments, the degree of narrowing was significantly under- or overestimated.

In the second stage of the research project, 30 films with distinct pathology were circulated among radiologists at three first-rate medical centers to discover how often first, second, and third opinions might agree. The discouraging results: only 61 percent of the time did two or more of the three groups reach the same conclusion.

Finally, in the third study, three months later, the same 30 films were recirculated to the same experienced radiologists, who did not know, of course, they were being asked to reevaluate films they had seen before. This time, the radiologists not only disagreed with each other, they also disagreed with themselves! In 32 percent of the readings, their second evaluations differed significantly from their first.

The overall conclusion from that study was that angiograms are, at most, accurate only to within 25 percent of the actual degree of arterial closure. Nonetheless, patients were being subjected to bypass surgery based on a reading of 75 percent, which we now know, in actuality, might only be 50 percent. How did the cardiovascular community respond to research that clearly indicated patients were being scheduled for surgery based on erroneous diagnoses? They didn't. Nothing's changed.¹⁴ Despite findings to the contrary, the coronary angiogram remains the gold standard of cardiovascular diagnosis and is still considered the final word when it comes to determining if bypass surgery is indicated.

Occluded arteries are to be expected. Atherosclerotic plaque begins accumulating in most adults before the third decade of life, and many men and women who are symptom free and considered healthy have been found to have 75 percent or more arterial blockage when autopsied after accidental death from causes unrelated to arterial disease. Although they obviously had adequate collateral circulation, if for any reason they had been subjected to coronary angiogram, surgery would have been recommended.

Recent data show that patients whose conditions are stable after a myocardial infarction and who are nonetheless treated with angiography and invasive procedures have a 71 percent higher mortality rate at hospital discharge, a 60 percent increase in death rate 30 days after discharge, and a 30 percent increased death rate at 44 months follow-up, compared to patients treated conservatively.¹⁵, ¹⁶

In a recent study of balloon angioplasty, 1,018 patients were randomized into two groups. One group received percutaneous transluminal coronary balloon angioplasty (PTCA), and the other group was treated medically. These patients were followed for almost three years. The study revealed that only those patients with the most severe angina had better pain relief, and it also showed that improvement is lost beginning a few months after PTCA, with no improvement at two years, compared to the medically treated group, presumably from reblockage. Those conclusions were based on symptoms of breathlessness, grade of angina, and treadmill exercise time. Death and non-fatal myocardial infarction occurred in 6.3 percent of PTCA patients and only 3.3 percent of medically treated patients. There was one death and seven non-fatal myocardial infarctions at the time of PTCA.¹⁶, ¹⁷ It remains to be seen whether the advent of stents will improve those percentages.

Many other published studies contain similar data, and close study of the actual data tells a similar story.¹⁸–²³

An editorial in a 1998 issue of the New England Journal of Medicine stated that after reviewing four recent, large, prospective, randomized studies comparing invasive and aggressive therapy with conservative, non-invasive, medical management of acute coronary syndromes (angina, ischemia, infarctions), …studies show that routine angioplasty and revascularization (bypass or angioplasty) do not reduce the incidence of non-fatal myocardial infarctions or death…¹⁴ It further states that despite the fact that adverse events are similar or even greater in patients managed aggressively, physicians in the U.S. continue to choose the more aggressive and invasive approaches. The authors point out that while angioplasty and bypass are performed less than half as frequently on similar patients in Canada, the incidence of myocardial infarction and death in three years of follow-up is no different. In this editorial the authors ask, Why are coronary angiography and revascularization (bypass and balloon angioplasty) often performed in patients with acute coronary syndromes in the United States, even without an obvious indication?

Oral and Rectal EDTA

Marketing companies have been targeting the public with mass mailings and advertisements for so-called oral chelation—selling nutritional supplements containing EDTA, while deceptively using data from studies of intravenous EDTA to support such products. Recently that practice spread to the aggressive marketing of EDTA as a rectal suppository. In my opinion, those practices are deceptive and potentially dangerous. No statistically significant scientific evidence for effectiveness exists. EDTA is poorly absorbed by either the oral or rectal route. All statistically significant published data for effectiveness applies only to intravenous EDTA. DMSA, a chelating drug that is well absorbed orally, does not have the beneficial effect of intravenous EDTA on atherosclerosis and diseases of aging.

What About So-Called Oral Chelation?

Because EDTA is poorly absorbed by mouth, 95 percent remains in the digestive tract, where it binds tightly to essential nutritional minerals and trace elements from food and from nutritional supplements, blocking their absorption. Important minerals, including zinc, copper, manganese, chromium and others, are lost in the stool—tightly bound to EDTA. Taken for months at a time, this can lead to serious nutritional deficiencies.

There has recently been an upsurge of aggressive marketing and advertising for oral products containing EDTA, which are added to garlic tablets and vitamin supplements. After taking such products every day for a year or more, a person may assimilate the same total amount of EDTA that would be received in a course of intravenous chelation therapy. However, the problem remains that 95 percent of the oral EDTA remains in the digestive tract and passes on through, tightly bound to nutritional minerals, blocking their absorption. That is potentially dangerous.

Intravenous EDTA is given only 30 to 45 times in a year at most. Although it does remove essential nutritional elements from the body on the days when given, those losses can easily be restored with supplementation. Preexisting deficiencies are replenished by supplementation during more than 300 days of the year when there is no EDTA in the body to counteract absorption or cause losses.

One hundred percent of intravenous EDTA is absorbed on the day it is infused, allowing a full course of therapy to be administered between 30 and 45 days, spread out over several months. Oral EDTA is so poorly absorbed that it must be taken every day for months or years at a time, and there is never a time to make up the losses. It is therefore not possible to replenish trace elements and minerals when taking EDTA by mouth. They are merely trapped in the gut and carried out.

High-potency formulas containing vitamins, antioxidants, amino acids, and chelated minerals are sometimes advertised as Oral Chelation. Although it's true that vitamin C and some amino acids found in food are weak chelators, those products are relatively inexpensive and can be purchased cheaply, without the hype and without the high prices found when they are sold as oral chelation. Nutrients with chelating potential are quickly used up in the body when they are being converted to other substances by cellular metabolism. They are not absorbed intact, and therefore do not carry unwanted metals out in the urine, as does intravenous EDTA.

People naturally feel better while taking a high-potency vitamin preparation, but that is not chelation therapy. Testimonials for such products can relate to the expected benefits from ingredients other than EDTA. Deficiencies caused by oral EDTA come on slowly, while the pick-up from high-potency vitamins occurs quickly. This can mistakenly cause customers to think they are getting benefit from oral chelation.

Minerals and nutritional trace metals used in supplements are often chelated (bound together) with amino acids to improve absorption. The label may therefore state chelated. That is the reverse process of infusing a metabolically inert chelator like EDTA, which is very rapidly passed out in the urine, removing metals from the body. EDTA by mouth blocks absorption instead of enhancing it. Most products deceptively marketed as oral chelation are essentially multiple vitamin/mineral supplements with excessively high prices.

EDTA by mouth has never been studied in a large group of people for a long enough period of time to determine the extent to which nutritional deficiencies occur. It is therefore not possible to state that oral EDTA in therapeutic doses is safe when given daily for months at a time. Before safety can be claimed, we need studies with measurements of before and after body zinc content, copper status, manganese status, etc., during continuous oral EDTA treatment. I have never seen such data, and I do not believe it exists.

Although EDTA is used as a preservative in some foods such as mayonnaise, it is present in very small amounts, and it is highly unlikely that a person could consume enough on a daily basis to cause problems from this ingredient. So-called oral chelation products contain a much higher amount of EDTA.

There is no evidence that daily EDTA by mouth brings significant benefit for atherosclerosis, when compared to periodic intravenous infusions. Marketing claims thus far are unsubstantiated by any scientific evidence. They consist mainly of unsubstantiated advertising claims from companies that profit from sales, supported by a few testimonials without scientific and objective data. Even those testimonials are often provided by people who profit from sales in multilevel marketing schemes.

In my own practice, I had one patient who took 200 mg of EDTA daily for ten years (not prescribed by me). He developed severe, far-advanced coronary heart disease during that time. He was quite healthy when he started. He also developed significant mineral and trace element deficiencies, despite high doses in his daily supplements. He stopped taking oral EDTA and then took a full course of 30 intravenous EDTA chelation infusions. Repeat testing showed that his heart went back to normal. Cardiac enlargement reversed and heart wall motion abnormalities under exercise, from blocked coronary arteries, reverted to normal.

Until proven otherwise, it seems to me that it is deceptive, irresponsible, and possibly dangerous, to promote oral EDTA as a treatment or preventive for heart disease, atherosclerosis, and other age-related diseases.

However, oral DMSA is an effective chelator of mercury. For treatment of elevated mercury, DMSA (dimercaptosuccinic acid) by mouth is a very safe and effective oral chelator. It is also highly effective for lead. EDTA does not effectively remove mercury from the body. DMSA is only available on prescription by a licensed health care professional in therapeutic strengths. The brand name is Chemet®, and the generic name is succimer. Compounding pharmacists can provide this product generically at a cost savings.

EDTA Suppositories

EDTA rectal suppositories are also being promoted as a substitute for intravenous chelation, despite research that shows EDTA is very poorly absorbed by that route. There is also reason to question the safety of this practice.

Published data show that the colon absorbs very little EDTA.²⁴ Cr-labeled EDTA was used as a marker to study increases in intestinal permeability, precisely because it is not well absorbed. A saline solution of EDTA was administered by enema and only …7.0 percent of the Cr-EDTA instilled into the colon can be recovered in urine over the next 6h.¹ The authors also documented that 85 percent of an intravenous dose of EDTA was recovered in urine after 6 hours. Therefore, very little EDTA is absorbed when instilled throughout the colon by enema, and even less would be absorbed when localized in the rectum by suppository.

Another study has mistakenly been cited to support safety of EDTA rectal suppositories.²⁵ In that study, a 250-ml enema of 0.5 percent solution of EDTA was purported to cause no immediate problems for dogs, even though half the dogs studied showed mucosal hemorrhages in the colon from the EDTA solution. A rectal suppository will release all of its EDTA in one small area, producing a much higher local concentration than an enema, which then persists for some time. An enema dilutes the EDTA and distributes it throughout the entire surface of the colon. The concentration of EDTA in any one area is therefore very much less by enema than by suppository. Even then, only 7 percent or less is absorbed.

Rectal cancer is not an uncommon condition. An important defense against cancer is superoxide dismutase (SOD), a metallo-enzyme that absolutely requires zinc, copper, or manganese to function. EDTA has a very high affinity for all three of those metals. If EDTA is released by suppository adjacent to rectal mucosal cells, the resulting high local concentration could easily bind those metals, inactivating intracellular mucosal SOD and other vital metalloenzymes. Latency for rectal cancer can take years for transformation from benign to malignant cells. It would require quite a long study to prove that repeated use of rectal EDTA is safe.

References

1. Guldager B, Jelnes R, Jorgensen SJ, et al. EDTA treatment of intermittent claudication—a double-blind, placebo-controlled study. Journal of Internal Medicine 1992; 231:261-267.

2. Sloth-Nielsen J, Guldager B, Mouritzen C, et al. Arteriographic findings in EDTA chelation therapy on peripheral atherosclerosis. The American Journal of Surgery 1991;162:122-125.

3. Van Rij AM, Solomon C, Packer SG, Hopkins WG. Chelation therapy for intermittent claudication. A double-blind, randomized, controlled study. Circulation 1994 Sep;90(3):1194-1199.

4. Chappell LT. Disputes author's conclusions on effectiveness of EDTA chelation therapy. Alternative Therapies Sep 1996;2(5):16-17.

5. Diehm C, Wilhelm C, Poeschl J, et al. Effects of EDTA-chelation therapy in patients with peripheral vascular disease—a double-blind study. An unpublished study performed by the Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany in 1985. Presented as a paper before the International Symposium of Atherosclerosis, Melbourne, Australia, October 14, 1985.

6. Carter JP. If EDTA chelation therapy is so good, why is it not more widely accepted? Journal of Advancement in Medicine 1989;2(l&2):213-226.

7. Born GR, Geurkink TL. Improved peripheral vascular function with low dose intravenous ethylene diamine tetraacetic acid (EDTA). The Townsend Letter for Doctors July 1994:722-726.

8. Cobb LA, Thomas GI, Dillard DH, Merendino KA, Bruce R. An evaluation of internal-mammary-artery-ligation by a double-blind technique. N Engl J Med 1959;260:1115-1119.

9. Dimond KG, Kirtle CF, Crockett JE. Comparison of internal mammary ligation and sham operation for angina pectoris. Am J Cardiol 1960;5:483-486.

10. Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996 Dec 19;335(25):1857-1863.

11. CASS Principal Investigators and Their Associates: Coronary artery surgery study (CASS): A randomized trial of coronary artery bypass surgery. Circulation 1983;68(5):951-960.

12. CASS Principal Investigators and Their Associates: Myocardial infarction and mortality in the coronary artery surgery study (CASS) randomized trial. N Engl J Med 1984;310(12):750-758.

13. Peduzzi P, Kamina A, Detre K. Twenty-two year follow-up in the VA cooperative study of coronary artery bypass surgery for angina. Am J Cardiol 1998 Jun 15;81(12):1393-1399.

14. Lange R, Hillis DL. Use and overuse of angiography and revascularization for acute coronary syndromes. N Engl J Med 1998;338(25):1838-1839.

15. Henderson RA, Pocock SJ, Sharp SJ, et al. Long-term results of RITA-1