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From the Townsend Letter
May 2013

Chelation Therapy: Stepping Into the Next 60 Years
A Historical Commentary

by John Parks Trowbridge, MD
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Peripheral Vascular Disease
Being listed as a "labeled indication" by the Food and Drug Administration usually allows for insurance approval and reimbursement of treatment for a particular condition. Few people know that EDTA was listed in late-1950s editions of the Physician's Desk Reference (PDR) as "indicated" for the treatment of peripheral vascular disease. A study with about half a dozen patients showing marked improvement had led to labeling approval. Then came the 1962 Kefauver-Harris Amendment to the Federal Food, Drug, and Cosmetic Act, requiring a review of both safety and efficacy in the approval process. When studies were considered insufficient to conform to the new standards, the indication was dropped from the label.

While early studies concentrated on cardiac improvements, concurrent benefits for occluding leg arteries attracted attention. Carlos P. Lamar, MD, in 1964 reported on legs saved from amputation. H. Richard Casdorph, MD, and Charles H. Farr, MD, PhD, confirmed these improvements in a small series in 1983, as did James P. Carter, MD, DrPH, and Efrain Olszewer, MD, in a double-blinded study published in the Journal of the National Medical Association in 1990. McDonagh and Rudolph in the 1980s documented marked enhancement of the ankle/brachial index in 117 patients with occlusive disease. Carter and Olszewer reported in 1988 on a 28-month retrospective analysis of 2870 patients treated with intravenous EDTA: peripheral arterial disease patients showed marked improvement in 91% and good improvement in another 8%. Given that surgical success is lessened with smaller vessels and when near or crossing joints, chelation as a nonsurgical alternative offers hope to thousands.

Thermography specialist Philip P. Hoekstra III, PhD, reported privately to me in 2009 the results of his 13-year study of 19,147 patients with peripheral (leg and arm) artery stenosis, not yet severe enough to require amputation. Arterial perfusion of all extremities demonstrated significant "warming"in 86% of chelated patients.

Carotid Arteries
Carotid arteries act as a special case of the peripheral vascular bed – and their improvements with chelation have been documented repeatedly. Rudolph and McDonagh described in 1991 the striking and highly significant reversal of atherosclerotic stenosis of bothinternal carotid arteries in 30 patients treated with only 30 EDTA infusions over a 10-month period. Ultrasound imaging showed that overall obstruction was decreasedby 21% – and those who showed more severestenosis had even greater reductionof blockage. Their study had been planned after their 1990 case report of one patient having an original 98% occlusion reduced to only 33% after just 30 chelation therapy treatments. Given that strokes can occur as a complication of otherwise successful carotid endarterectomy, chelation can reduce such misadventures for many. Where surgical intervention is warranted, pretreatment with chelation theoretically can improve the postoperative result. Again, more sophisticated equipment can allow easy, inexpensive, and noninvasive documentation of improvement.

Intracranial circulation responds less well. Casdorph in 1981 documented marked improvement in brain arterial flow in a small series of patients. Carter and Olszewer's 1988 retrospective review showed markedimprovement in 24% and goodimprovement in 30% of patients with cerebrovascular and other degenerative brain diseases. Surprising results are possible. One patient presented to me 18 months poststroke, still severely limited despite constant physical therapy. After 8 chelation treatments, he proudly showed that he could walk down the hall with an assistant holding his belt in the back, and he described having gotten into and out of the tub (with assist) for the first time since his CVA. "Small-vessel ischemic disease," with or without dementia changes, generally shows stabilization or some improvement. Alzheimer's dementia, especially when associated with significant toxic heavy metal patterns, can show encouraging benefits when treated early with chelation.

A Potpourri of Problems
Macular degeneration is a special case of vascular supply directly to a central nerve. Direct ophthalmic observation can show gradual deterioration … and gradual improvements. The most rewarding part, though, is having a patient resume reading or once again being able to thread a needle. I asked one patient, who received several dozen chelation treatments, to read this note on a chart cover: "PATIENT IS LEGALLY BLIND." I then asked him to read whose chart … "Why, that's mine!" Without glasses.

Atrial fibrillation is the most common arrhythmia, and its frequency elevates with advancing age. The risk of stroke increases considerably, so rhythm control has benefits beyond rising perfusion efficiency. Alfred Soffer, MD, reported on chelation for various heart rhythm disturbances in his 1964 monograph; results were variable but promising. Long-experienced chelation physicians have their anecdotal stories of patients reverting to and maintaining sinus rhythm.

Cardiac valvular sclerosis, sometimes proceeding to calcific stenosis restricting flow and allowing regurgitation, is a troubling problem. Although new percutaneous operations (using technology similar to angiography) are growing in popularity, their risks and success rates are still being evaluated. Theoretically, the decalcifying effect of EDTA chelation therapy should slow (perhaps even reverse?) sclerotic-to-stenotic change. At the very least, chelation should be expected to aid the intended surgical result by increasing the pliability of tissues. Neither angiography nor echocardiography is yet sensitive enough to detect slight reductions in calcium deposits.

Scleroderma is another special case, where distinctive arteriolar changes (in all organs but especially the skin) are associated with autoimmune patterns. Raynaud's phenomenon appears to be prodromal in many patients. Conventional medications are often frustrating, and the addition of EDTA chelation therapy has been quite successful for many patients. Similarly, other autoimmune patterns – rheumatoid arthritis and systemic lupus erythematosus – have shown promising improvements with chelation. Benefits with "fibromyalgia" have routinely been reported by patients. These observations raise speculation that EDTA might be affecting membrane pathology, possibly related to or amplified by toxic heavy metals – induced through the mechanism of free radical attack? D-penicillamine, loosely called a "chelator" but acting by means of paired thiol groups, has long been used in conventional medicine to help with scleroderma and rheumatoid patterns.

Mitochondrial pathology has been recognized in many forms over the past decade, but the contribution of toxic heavy metals has been poorly appreciated. In the 1990s, laboratory studies by the Environmental Protection Agency showed startling changes in mitochondrial protein production seen in isolated organelles after exposure to "physiologic" levels of lead. Research into toxic heavy metal effects on mitochondria, endoplasmic reticulum, nuclear membranes, and cell-limiting membranes might offer the most fruitful future explanations for pathology and chelation benefits – but the laboratory funding required would be substantial.

Along Came A Spider …
A little-known effect of chelation is to neutralize biological venoms from snakes, spiders, scorpions, and the like. These poisons are a mixture of metalloenzymes, and inactivation occurs with displacement or removal of the critical metal cation. Appropriate research could lead to treatment protocols (intravenous, oral, topical) far more effective – and dramatically less expensive – than current antivenom preparations, which can cost thousands of dollars.

Venoms, as metalloenzymes, bring up a whole realm of possible treatments aimed at specific induction and function of enzymes throughout the body. In perhaps a third of instances, physiologic cations (magnesium, zinc, iron, manganese, molybdenum, copper, others) are positioned in the active site and help establish the functional conformation of the protein. As research shows which enzyme clusters are more sensitive to inhibition by toxic heavy metals displacing the expected cation, the prospect of targeted chelation could become a reality. One factor complicating targeted treatment is that chelators need to penetrate through the interstitial space into the cytoplasm and into mitochondria and even into the nuclear space. Similar concerns arise with penetrating the blood–brain barrier. Nanoparticle delivery systems, being developed for targeted chemotherapy, might be designed to enhance chelation efficiency at the "end-organelle" level rather than merely the "end-organ." Again, laboratory and clinical expenses could be a major barrier.

Nutritional physiology is still poorly understood, and studies might reveal new ways to increase the benefits of chelation treatments. Mildred S. Seelig, MD, MPH, confirmed in the 1980s that higher blood levels of magnesium are correlated with reduced complications of myocardial infarction. Chelation therapists have long added extra magnesium to intravenous EDTA in order to amplify many of the cardiovascular benefits of treatment. Realizing that lower magnesium levels are common in diabetes, hypertension, atherosclerosis, cardiomyopathy, and a panoply of other pathologies opens an interesting door: what minerals (and vitamins), when supplemented specifically, might enhance the effectiveness of chelation treatments in particular clinical settings? Incidentally, in patients who appear to have an "allergic" reaction to a chelating drug, supplementation with molybdenum might blunt that response for the future.

Stem cell implants offer special considerations here – could they be more effective when combined with certain minerals … or after bathing in selective chelation solutions? Rotifers are primitive multicellular microscopic waterborne "animals" that accumulate calcium over their lifespan. Alfred M. Sincock, PhD, reported in 1975 on almost doubling the lifespan by bathing the organisms in various calcium-binding chelators. Similarly, the length of DNA telomeres – hence, the potential number of cell replications before genetic losses – might also be preserved by chelation treatments. The possible interactions of hormones and EDTA or other chelators is a field ripe for investigation. These cell physiology studies are technical and expensive, but the benefits might be unexpectedly rewarding.

Cost/Benefit Comparisons
Given the socioeconomic impact of medical and health choices, no discussion is complete without highlighting the "competing therapies" for cardiovascular and other diseases. Chelation treatments reasonably cost about $5 to $10,000 to produce outstanding benefit for about 90% of patients with coronary, carotid, or peripheral vascular disease. Or all three at the same time. While surgery addresses only a few inches of "blockage" with each operation, chelation works throughout the body – a real bargain for the majority of patients, who have diffuse disease. Charges for CABG range about $75 to $150,000 – for each operation – assuming no serious complications requiring extended hospitalization. A small but certain percentage of bypass patients (perhaps 2% to 3% or more, depending on many factors, especially comorbidities or more profound blockage) never return home. Many patients suffer with postoperative morbidity, including myocardial infarction, stroke, rhythm disturbances, worsening high blood pressure, and neurocognitive changes ("pump syndrome"). Repeat operations are frustratingly common, often within 10 years. (If it worked so well the first time, why is another operation needed?) Aorta and peripheral vascular operations usually cost one-third to one-half of heart bypass procedures. Balloon angioplasty and stenting are increasingly popular (with a failure rate of about 5%), reducing the need for open surgery of the chest or limbs except for those with critical ischemia. Perhaps 20% of patients require repeated angioplasty procedures, dramatically changing the cost profiles with each session ranging from about $30 to $50,000. L. Terry Chappell, MD, and John P. Stahl, MD, in 1993 published a meta-analysis of 19 carefully qualifying studies, concluding that almost 90% of cardiovascular patients showed objective clinical improvements. The savings possible with the early choice of chelation rather than the later choice of repeated operations will become increasingly important for an aging population.

Intracranial small vessel ischemic disease is virtually untreatable by conventional means, so even slight improvements with chelation therapy are a bargain at any price. Similarly, degenerative patterns such as scleroderma, rheumatoid arthritis, macular degeneration, distal peripheral arterial occlusion, and nondiabetic chronic renal failure are poorly treated with traditional approaches, making chelation appealing and very cost effective. Perhaps the "greatest value" is seen in vague or poorly diagnosable medical conditions – including fatigue, asthenia, delayed healing, a sense of "unwellness," multiple sclerosis – wherein chelation can provide benefits not seen with aggressive drug treatments or even surgery. Stubborn infectious diseases, such as Lyme disease or even MRSA, can show improvement with chelation. While the mechanisms of action often remain obscure, the clinical benefits can be quite obvious in patients' lives. A "chelation registry" might document improvements across a broad range of pathologies, but the effort would be expensive and likely of little value in convincing skeptics.

One other factor should be addressed: cancer prevention. Walter Blumer, MD, in Switzerland reported his experience in 1980 with calcium EDTA intravenous treatments administered over 10 years, showing a 90% reduction in cancer incidence in the 59 patients. His follow-up report showed a 90% reduction in cancer deaths over 18 years, compared with the untreated controls similarly exposed to lead from automobile exhaust, industrial pollution, and other carcinogens. When treating heart and vascular disease, magnesium EDTA is preferred, in order to "mobilize calcium and reduce blockage." In a private communication related to me by Garry Gordon, DO, MD(H), Blumer noted that his patients "didn't suffer with heart attacks." These delightful results are most likely related to removal of toxic heavy metals, since calcium EDTA does not perturb ionized calcium levels, but unknown effects of EDTA might contribute as well. Considering that cancers of all cell types are the third leading cause of death in the US, what could be the true prevention benefit when the cost of chelation treatment is compared with that of traditional oncology care?

Any review of environmental toxic metal exposures shows the alarming explosion of pollution concentrating up the food chains in the biosphere. One area where unexpected progress is coming is with mercury exposure from dental amalgams. The just-completed World Mercury Treaty, a three-year project of the World Health Organization, proposes that countries completely phase out their reliance on mercury restorations in both children and adults. Controversial studies have related mercury to autism and Alzheimer's dementia, among other problems. The startling fact is that many adults are unknowingly carrying around their primary source of the world's most potent neurotoxin, in their "fillings" or root canals. This raises the specter of worsening environmental pollution through the water effluent from dental offices as these restorations are replaced, because mercury scavenging units – to be disposed of as biohazard waste – are not yet in widespread use. Boyd Haley, PhD, emeritus chair of chemistry at the University of Kentucky, assures us that newer chelating compounds are in development and that they could be used not only orally in humans but also to remediate mercury-contaminated rivers and bodies of water.

Blumer's study, among others, provokes a critical question: If removal of toxic heavy metals is the most important factor in producing clinical results, how much can be accomplished by using oral "chelating" drugs, alone or in combination with intravenous chelation? Oral administration is much easier, has fewer risks, and can be applied across broad populations, especially in a preventive context or to address early pathophysiology. Since 1995, I've used customized combined programs of oral chelators along with intravenous EDTA. Our early studies suggested more rapid reductions in the body burden of toxic heavy metals. Further research into dithiol compounds as well as classical chelators might be very cost effective and exceptionally fruitful. If taste-enhancing technology can mask the noxious sulfur aroma of oral chelators, the potential exists for design of prescription "chelator foods," vastly expanding the access for this treatment approach. These would be "drug-supplemented" foods, not merely sulfur-rich onions and garlic.

Some Final Thoughts
The great majority of our "medical" problems are directly related to "personal health choices," known as lifestyle issues: tobacco use, alcohol excess, caloric surplus, nutritionally bereft foods, poor choice of food variety, sedentary habits, dental deterioration, limited sleep, unlimited stress, and so on. Unsuspected toxic heavy metal and chemical exposures challenge our organ performance at a rapidly expanding pace. Where personal responsibility fails to minimize our survival threats, what should be the societal commitment of resources to restore function and comfort?

The future face of medical care is difficult to predict. An enlarging patient base in the US poses increasing financial demands on already stressed budgets. Technological advances can be expected in virtually every arena, from diagnostic testing through treatment planning. CT scans, MRIs, and PET scans have sharpened our accuracy and understanding to allow earlier diagnosis and treatment, for better outcomes and longer survival. Same-day surgicenters and endoscopic procedures dramatically reduced the costs associated with many common procedures, such as cholecystectomy and most knee repairs. Will the changes still to come bring similar cost savings or will they, like organ transplant procedures, impose greater economic strains on a nation unprepared to ration "high-tech" care?

Victor Fuchs, PhD, in his seminal book Who Shall Live?, claimed in 1974 that we must deliver the very best care to the president because of his critical position in the society – but he cautioned that we simply cannot afford to deliver "presidential medicine" to the people. Just because we can do it – CABG surgery, angioplasty, total joint replacement, organ transplants – challenges us with the ethical question of whether we should do it. Or do it for some but not for others. Or do it for younger adults but not for "the elderly." The reasonable cost and minimal resources required to offer chelation therapy "to the masses" suggest that this largely ignored treatment might soon evolve to play central roles in both preventive and therapeutic spheres in our emerging care system.

© 2013 John Parks Trowbridge

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John Trowbridge, MDJohn Parks Trowbridge, MD, has been certified since 1985 as a chelation specialist by the American Board of Clinical Metal Toxicology, for which he now serves as secretary. A Fellow of the American College for Advancement in Medicine, he has served as director, officer, or president of a number of professional and public associations. Popular as a professional and public speaker, he coauthored Bantam's bestselling The Yeast Syndrome among several other books, and dozens of CDs and DVDs. His upcoming book, Life Long Health, presents chelation perspectives gathered from 30 years of offering this treatment. He provides a broad array of integrative medical therapies at his solo practice, Life Celebrating Health in Humble (Houston), Texas:, 800-FIX-PAIN.

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