INTRODUCTION:
There are techniques that the general population knows nothing about because the traditional medical establishment isn’t aware they exist, having this knowledge suppressed over the years by various powerful organizations. The techniques I?m talking about deal with the treatment and prevention of diseases involving the blood vessels of the body.
These diseases?coronary artery disease, cardio-vascular disease (precursors to stroke), peripheral vascular disease (precursor to gangrene), and cerebrovascular disease (precursor to stroke and dementia) are the major causes of disability and death in our world today.
The traditional approach to these diseases relates to surgery and drugs. Your case of severe hardening of the arteries need not lead to bypass surgery, heart attack, amputation, stroke or senility.
The use of a chemical called EDTA (ethylene diamine tetraacetic acid) has been used in this country for these diseases for decades. Probably 700,000 people have benefitted by this technique. Despite what you might have heard about chelation therapy, administered by a properly-trained physician and given in conjunction with lifestyle and dietary changes with the use of specialized nutritional supplements, the procedure is an option to be seriously considered by persons suffering from coronary artery disease, cerebral vascular disease, brain disorders resulting from circulatory disturbances, generalized atherosclerosis and related ailments which lead to senility and accelerated physical decline.
Clinical benefits from chelation therapy vary with the total number of treatments received and with the severity of the condition being treated. More than 75% of patients treated have shown significant improvement from chelation therapy. More than 90% of patients receiving 35 or more treatments have benefited when they have also corrected dietary exercise and smoking habits, which are known to aggravate arterial disease. Symptoms improve, blood flow to diseased organs increases, need for medication decreases, and the quality of life improves.
WHAT IS CHELATION
Chelation (key-lay-shun) is a chemical process by which a metal or mineral (like lead, mercury, copper, arsenic, aluminum, calcium, etc.) is bonded to another substance. It is a process basic to life itself and goes on naturally in our body at all times. The chelation that we do artificially is similar to just using a chemical (EDTA) instead of the natural chemicals of the body. Chelation is one mechanism by which such common substances such as aspirin, antibiotics, vitamins, minerals, and trace elements work in the body.
Hemoglobin, the red pigment in blood which carries oxygen, is a chelate of iron.
WHAT IS CHELATION AS A MEDICAL TREATMENT
Chelation is a treatment by which a man-made amino acid called ethylene diamine tetraacetic (EDTA) is administered to a patient intravenously, prescribed by and under the supervision of a fully-licensed physician. The fluid containing EDTA is infused through a small needle placed in the vein of a patient’s arm. The EDTA in solution bonds with metals in the body and carries them away in the urine. Abnormally-situated nutritional metals, which speed free radical damage, and toxic metals, such as lead, are most easily removed by EDTA.
Also, EDTA rearranges essential minerals in the body, meaning that the EDTA takes some essential minerals that are where they are not supposed to be and puts them into areas of the body where they are supposed to be and where the body needs them.
How often is the chelation therapy given?
Chelation therapy is a course of treatments which usually consists of anywhere from 12 to 50 separate infusions, depending on each patient’s individual status. Twelve to fifteen treatments once or twice yearly is the average number required for definite benefit in patients with various pathologies. Some patients may eventually receive more than 100 infusions. Each treatment takes from three to four hours or longer and patients normally receive one or more treatments each week. Over a period of time, these injections halt the progress of the free radical disease, which is the underlying condition triggering the development of atherosclerosis?and many other degenerative diseases of aging?giving the body time to heal and time to restore blood flow through diseased blood vessels. After several months these injections bring profound improvement to many metabolic and physiologic processes in the body. The body’s regulation of calcium and cholesterol is improved by normalizing the internal chemistry of cells.
Chelation benefits every blood vessel in the body, from the largest to the tiniest capillaries and arterioles, most of which are far too small for surgical treatment or are deep within the brain and other vital organs where they cannot be safely reached by surgery. In many patients, the smallest blood vessels are the most severely diseased. The benefits of chelation occur from the top of the head to the bottom of the feet, not just in short segments of a few large arteries which can be bypassed or opened by other invasive treatments.
Do you have to go to a hospital to be chelated?
No, in most cases it is an outpatient treatment available in a physician’s office or clinic.
Does it hurt? What does it feel like to be chelated?
Being ?chelated? is quite a different experience from other medical treatments. There is no pain, and in most cases, very little discomfort. Patients are seated in reclining chairs and can read, nap, watch television, do needlework or chat with other patients while the fluid containing the EDTA flows into their veins. If necessary, patients can walk around. They can visit the restroom, eat and drink as they desire, or make telephone calls, being careful not to dislodge the needle attached to the intravenous infusion they carry with them. With the newer Calcium-EDTA IV push there is even less discomfort since the calcium helps the veins and this push takes only a few minutes, specially if your varicose veins are sore, or red and swollen. Before varicose vein surgery, there are a number of tests that need to be done. These are of two types: those to assess whether you qualify for varicose vein surgery, and some immediate pre-operative tests. Tests to see whether you qualify for the operation have already been done. These will always include examination with a handheld Doppler, and may include an ultrasound scan.
Are there risks or unpleasant side effects?
EDTA is relatively non-toxic and risk-free, especially when compared with other treatments. The risk of serious side effects, when properly administered, is less than 1 in 10,000 patients treated. By comparison, the overall death rate as a direct result of bypass is approximately 3 out of every 100 patients undergoing surgery, varying with the hospital and the operating team. The incidence of other serious complications following surgery is much higher, including heart attacks, strokes, blood clots, permanent brain damage with personality changes and prolonged pain. Chelation is more than 300 times safer than bypass surgery.
Occasionally, patients may suffer minor discomfort at the site where the needle enters the vein. Some temporarily experience mild nausea, dizziness, or headache as an immediate aftermath of treatment, but in the vast majority of cases, these minor symptoms are easily relieved. When properly administered by a physician expert in this type of therapy, chelation is as safe as taking aspirin. Patients routinely drive themselves home after treatment with not difficulty.
If EDTA is given too rapidly or in too large a dose, it may cause harmful side effects, just as an overdose of any other medicine can be dangerous. Reports of serious and even rare fatal complications have stemmed from excessive doses of EDTA, improperly administered. If you choose a physician with proper training and experience, one who is an expert in the use of EDTA, the risk of chelation therapy will be kept to a very low level. The American College of Advancement in Medicine (ACAM) provides training and examines physicians for competence in the specialized field of chelation therapy. A physician who has successfully completed the ACAM courses is knowledgeable in the safe and effective use of EDTA chelation therapy.
While it has often been stated that EDTA chelation therapy is damaging to the kidneys, the newest research (in one study consisting of kidney function tests done on 383 consecutive chelation patients, before and after treatment with EDTA for chronic degenerative diseases) indicates the reverse is often true. On the average, there is significant improvement in kidney function following chelation. An occasional patient may be unduly sensitive, however, and physicians expert in chelation monitor kidney function very closely to avoid overloading the kidneys. Treatments must be given more slowly and less frequently if kidney function is not normal. Patients with some types of severe kidney problems should not receive EDTA.
What types of examinations and testing must be done prior to beginning chelation therapy?
Prior to commencing a course of chelation therapy, a complete medical history must be obtained. A detailed listing of diet will be analyzed for nutritional adequacy and balance. Copies of pertinent medical records and summaries of hospital admissions will be obtained. A thorough, head-to-toe physical examination will be performed. A complete list of current medications will be recorded, including the time and strength of each dose. Special note will be made of any allergies.
Blood and urine specimens will be obtained for a battery of tests to insure that no conditions exist which may be worsened by chelation therapy. An electrocardiogram and chest x-ray will be ordered. A hair specimen will be tested for tissue levels of various nutritional and toxic metals. Non-invasive tests will be performed, as medically indicated, to determine the status of arterial blood flow prior to therapy. A consultation with other medical specialists may be requested. Follow-up examinations and testing will be performed at regular intervals during and after therapy.
Is chelation therapy new?
Not at all. Its earliest application with humans was during World War II when the British used another chelation agent, British Anti-Lewesite (BAL) as a poison gas antidote. BAL is still used today in medicine.
EDTA was first introduced into medicine in the United States in 1948 as a treatment for industrial workers suffering from lead poisoning in a battery factory. Shortly thereafter, the U.S. Navy advocated chelation therapy for sailors who had absorbed lead while painting government ships and dock facilities. Physicians then observed that adults receiving EDTA chelation treatments who had atherosclerosis also experienced health improvements?diminished angina, better memory, sight, hearing, sense of smell and increased vigor. A number of physicians then began to treat individuals suffering from occlusive vascular conditions with chelation therapy and reported consistent improvements.
Chelation therapy remains the undisputed treatment of choice for lead poisoning, even in children with toxic accumulations of lead in their bodies as a result of eating leaded paint from toys, cribs or walls.
But from 1964 on, despite continued documentation of its benefits and the development of refined treatment methods, the use of chelation for the treatment of arterial disease has been the subject of controversy.
Is it legal?
Absolutely. There is no legal prohibition against a licensed physician (M.D. or D.O.) using chelation therapy for whatever conditions he deems it to be correct, even though the drug involved, EDTA, does not yet have atherosclerosis listed as an indication on the FDA-approved package insert. The FDA does not regulate the practice of medicine, but merely approves marketing, labeling and advertising claims for drugs and devices in interstate commerce.
It costs millions of dollars to perform the required research and to provide the FDA with documentation for a new drug claim, or even to add a new use to marketing brochures of a long-established medicine like EDTA. Physicians routinely prescribe medicines for conditions not yet included on FDA approved advertising and marketing literature.
Several respected physician organizations sponsor educational courses in the proper and safe use of intravenous EDTA chelation. The American College of Advancement in Medicine publishes a physicians? protocol for the safe and effective method of treatment with EDTA. This protocol is used in training courses and in a certification program for chelating physicians. ACAM’s educational programs for physicians, followed by oral and written examinations, lead to credentials which certify demonstrated competence in the proper use of EDTA chelation therapy.
On the question of legality, the interpretation of laws pertaining to ?informed consent? is evolving in the courts and it is now possible that a physician who withholds information about the availability of other treatment choices, such as chelation therapy, prior to performing vascular surgery (along with all other treatment modalities) could be found legally liable. Withholding information about a different form of treatment may be tantamount to medical malpractice, if as a result, a patient is deprived of possible benefits. Thus, it is the doctors who refuse to recognize and inform their patients of chelations who are risking legal liability?not those chelating physicians who provide an innovative treatment which they feel to be the safest, the most effective and the least expensive for many of their patients.
What proof do you have that it works?
Initially, most patients, regardless of what their original medical problem might be, state that after about the 5th treatment they feel they have more energy and their mind is more clear.
Physicians with extensive experience in the use of chelation therapy observe dramatic improvement in the vast majority of their patients. They see angina routinely relieved, patients who suffered searing chest pains when walking only a short distance are frequently able to return to normal, productive living after undergoing chelation. Far more dramatic, but equally common, is seeing diabetic ulcers and gangrenous feet heal. Many individuals who had been told that their limbs would have to be amputated because of gangrene are thrilled to watch their feet heal with chelation, although some areas of dead tissue may have to be trimmed away surgically. The approximately one thousand American physicians practicing chelation therapy have countless files to prove they are able to reverse serious cases of arterial disease. Men and women often arrive at their offices near death with diseases caused by blocked arteries. Weeks or months later, they?re remarkably improved. There is a wealth of evidence from clinical experience that symptoms of reduced blood flow improve in more than 75 percent of patients treated.
In addition, several research studies have been published with results of before-and-after diagnostic tests using radioscopes which prove statistically that blood flow improves following chelation. Regardless of blood flow studies, if cladication is relieved, if angina becomes less bothersome, and if physical endurance or mental acuity improves, such benefits would be quite enough to justify EDTA chelation therapy. Quality of life and relief of symptoms are far more important than the results of laboratory tests.
What does it cost?
The older Sodium-EDTA therapy which consists of a 3 to 31/2 hour IV drip would cost about $100 per treatment. However, with the newer Calcium-EDTA which is given as an IV push over 5 to 7 minutes costs only $50 per treatment.
What about bypass surgery?
Coronary artery bypass surgery, the popularly-prescribed procedure in which occluded portions of major coronary arteries are bypassed with grafts from a patient’s leg veins, has never been proven by properly controlled studies to offer an advantage over non-surgical treatments, other than relief of pain in a minority of patients who cannot be controlled with medicine. It has even been suggested that the relief of pain following surgery might result from the cutting of nerve fibers which carry pain impulses from the heart and which also stimulate spasm of coronary arteries. It is not possible to perform bypass surgery without interrupting those nerves.
Indeed, the most recent research suggests that many of the 400,000 or more bypasses and other invasive procedures performed each year for the relief of pain and other symptoms brought on by clogged or blocked arteries are not necessary. A good case against rushing into surgery is made by the findings of a ten-year, $24 million study conducted by the National Institute of Health (NIH) which compared post-operative survival rates of ?bypassed? patients with a matched group of equally diseased patients treated non-surgically.
The study uncovered no additional benefits for most patients who had been operated upon, compared with non-surgical therapy. It is important to note that the non-surgical therapy reported in that study did not include either chelation therapy or the new calcium blocker drugs, and that only half of the patients received beta blocker drugs. Having surgery didn’t improve their chances to live longer, live healthier, live better, or enjoy life more, when the results where statistically analyzed. The incidence of heart attacks (myocardial infarction) and both employment and recreational status were the same in patients treated surgically and non-surgically, even without using chelation therapy for the non-surgical treatment group.
Most important, cardiovascular surgery does nothing to arrest or reverse the underlying disease which exist in varying degrees throughout the body. It is at best a piece-meal ?cure? for a system-wide problem. Bypassing a restricted portion of the body’s blood vessels can have little lasting benefit when the same degenerating condition which caused the most extreme blockage at one or two sites must of necessity be taking place everywhere, throughout the circulatory network.
One thing the general public is not fully aware of is that many people who have one bypass operation later have a second bypass. Sometimes the blood vessels that weren’t bypassed become clogged; sometimes the transplanted vessels used in the first graft become filled with new plaque; sometimes the transplants malfunction or turn out to be too small for the job. As a matter of fact, studies have shown that by ten years after surgery, grafted vessels had closed in 40 percent of patients, and in the remaining 60 percent, half developed further coronary narrowing. Once you?ve had a bypass, your chances of having another go up about five percent a year. After five years, some specialists estimate your chances of receiving a second operation could be as high as thirty to forty percent. And some patients go on to even a third operation, or more. And approximately two to three out of every 100 patients undergoing bypass surgery die as a result of the procedure?even more if they are severely ill at the time of surgery. The balloon treatments and other invasive procedures to open arteries are also risky.
Chelation patients are frequently able to return to work and to resume their sports and other activities, without the need to undergo surgery. Chelation is equally as effective in patients who have previously undergone one or more bypass operations or balloon procedures. If they stay on a proper diet, exercise regularly, continue to take the prescribed program of nutritional supplements and receive periodic maintenance chelation treatments (monthly, more or less, depending on the severity of the underlying medical diagnosis) they can usually go many years without suffering further heart attacks, strokes, senility or gangrenous extremities.
If you, like most people eager for additional information about chelation therapy, have been told you have advanced arterial disease, you may have been advised to have vascular surgery. If so, it is essential for you to understand the nature of your disease and all possible treatment choices, before you can make an intelligent decision concerning the various options. Even if chelation and other non-surgical therapies should fail, bypass still remains a choice.
Why can’t chelation be taken by mouth in pill form, instead of by intravenous injection?
Chelation therapy is gaining recognition so rapidly that there is growing interest in developing a safe and effective oral chelator. Many nutritional substances administered by mouth are known to have weak chelating properties. But, none have the spectrum of activity of intravenous EDTA. Many nutrients such as vitamin C and the amino acid cysteine have the ability to chelate metals weakly. To label nutritional supplements containing vitamins and amino acids as ?oral chelation? however, is misleading.
EDTA can be taken by mouth in small doses but less than 5 percent is absorbed and only if taken without food. The utilization of EDTA by mouth is not adequate to treat established disease, although preventive and maintenance benefits might be obtained by that route.
Claims are being increasingly made for the use of vitamin supplements containing weak chelators in patients with atherosclerosis. There is nothing new about the benefits of vitamin-mineral supplements, which have recently been aggressively and deceptively marketed as ?oral chelation.? The use of vitamin-mineral supplements by mouth is a routine adjunct to a total program of chelation therapy, but the do not provide significant chelation by themselves. There are no potent oral chelating agents now available which are safe to take by mouth and which produce improvement comparable to intravenous EDTA.
Is it true that chelation therapy combats atherosclerosis by acting like a ?liquid plumber??by leeching calcium out of the atherosclerotic plaque?
No. Before recent medical breakthroughs in the area of free radical pathology, it was hypothesized that EDTA chelation therapy had its major beneficial effect on calcium metabolism’that it stripped away the excess calcium from the plaque, restoring arteries to their pliable precalcified state. This frequently offered explanation’the so-called ?roto-rooter? concept?is not the real reason, as previously postulated, that chelation therapy produces its major health benefits. The fact that EDTA does remove some abnormal calcium is now felt to be one of the less prominent aspects of its benefits.
More importantly, EDTA has an affinity for the so-called transition metals, iron and copper, and for the related toxic metals, lead, mercury, cadmium and others, which are potent catalysts of excessive free radical reactions. Free radical pathology, it is now believed, is the underlying process triggering the development of most age-related ailments, including cancer, dementia and arthritis, as well as atherosclerosis. Thus EDTA’s primary benefit is that it greatly reduces the ongoing production of free radicals within the body by removing accumulations of metallic catalysts which accumulate as a person grows older at abnormal sites in the body, speeding the aging process.
This is a greatly oversimplified explanation of what actually occurs. For those of you with a decided interest in the scientific technicalities, you can send for the manuscript entitled ?Free Radical Pathology in Age-Associated Diseases: Treatment with EDTA, Nutrition and Antioxidants? by Doctors Elmer M. Cranton and James P. Frackelton. For a fuller explanation of the many issues involved, written in popular form for the general public, you might enjoy reading ??Bypassing Bypass? by Dr. Elmer M. Cranton and Arline Brecher. Both publications, as well as others, are available from the American College of Advancement in Medicine, 23121 Verdugo Drive Suite 204, Laguna Hills CA 92653, (714) 583-7666. Telephone before ordering to find out costs, or you may purchase them from our office or in the bookstore. Also, you can find information from Garry Gordon’s, M.D, web site at Gordon Research.
Why haven’t I heard about chelation before?
If EDTA chelation therapy is as safe and effective as indicated by scientific studies and by the experience of hundreds of doctors, why haven’t you heard more about it? That is a good question!
Until quite recently, relatively few patients have been informed that this therapy is available. Most heart specialists may not have even heard of the treatment and would be reluctant to prescribe it if they had. The American Medical Association has not yet approved chelation therapy for atherosclerosis, although it does endorse its use in the treatment of lead and other heavy metal poisoning. Many insurance companies will not compensate policy holders for chelation therapy unless it is given for lead poisoning. If chelation therapy is given for atherosclerosis, it is often labeled ?experimental? or ?not customary? by medical insurance companies and payment is denied. They deny payment to patients even though they do pay for bypass surgery, and even though chelation might have saved them tens of thousands of dollars.
Traditional medical organizations, politically powerful, have consistently attempted to suppress chelation therapy, perhaps because of large vested interests in other methods of health care. The cost of all medical care for victims of heart disease in the United States in 1986, including coronary bypass surgery and prescriptive drugs, exceeded $40 billion. Obviously, many hospitals and physicians would be in serious financial difficulty, and might even have to find other outlets for their services, if this procedure, which might displace a gigantic industry, become universally popular.
Physicians who remain skeptical about chelation are those who have never used it. They are either completely uninformed about the extensive research that has been done to document the safety and effectiveness of chelation therapy, or they are committed by training or source of income to other therapeutic procedures, such as vascular surgery.
What else is involved in a complete program of chelation?
Your Lifestyle Counts. Chelation therapy is only part of the curative process. Improved nutrition and improved lifestyle are absolutely imperative for lasting benefit from chelation treatments. Chelation is not in and of itself a ?cure-all??it merely reduces abnormal free radical activity, allowing normal control mechanisms to come into play so that free radical damage can be repaired and health can be restored with the help of applied clinical nutrition, antioxidant supplementation and lifestyle corrections. Chelation therapy involves all of these factors. Chelation is also compatible with other forms of therapy, including bypass surgery.
In addition to receiving the necessary number of chelation treatments, patients eager for long term benefits should be warned: chelation alone won’t last for long. Individuals suffering any form of free radical disease must be prepared to improved the diet that started the disease, take nutritional supplements, be physically active and eliminate destructive lifestyle habits such as tobacco and excessive alcohol.
Nutritional Supplements. A scientifically balanced regimen of nutritional supplements reinforces the body’s antioxidant defenses and should include vitamins E, C, B1, B2, B3, B6, B12, pantothenate, PABA, and beta carotene. A balanced program of mineral and trace element supplementation should include magnesium, zinc, selenium, manganese and chromium. The exact prescription for nutritional supplements is determined individually for each patient, based on nutritional assessment and laboratory testing. SEE OUR COMPLETE IV CHELATION PROTOCOL BELOW.
Destructive Habits. It is important to eliminate the use of tobacco altogether, but if that is not possible, a marked reduction in exposure would be helpful. This applies to cigarettes, pipe tobacco, cigars, snuff or chewing tobacco. It has been consistently observed that patients who continued to smoke following chelation have demonstrated less improvement and for a much briefer time in comparison to non-smokers.
Only relatively healthy adults are able to tolerate alcoholic beverages without generating more free radicals than they can detoxify. Anyone who drinks more than one or two ounces of pure ethanol in 24 hours (four eight-ounce glasses of beer, four small glasses of wine, or two to three shot glasses of hard liquor) risks free radical damage. Even that amount is harmful on a regular basis. Victims of chronic degenerative diseases should usually avoid the consumption of alcohol.
Exercise. Finally, physical exercise is very helpful. Even a brisk 45-minute walk several times per week will help maintain the health benefits and improved circulation resulting from chelation therapy. Lactate normally builds up in tissues during sustained exercise and lactate is a natural chelator produced within the body.
Which brings us to the final question!
Is chelation therapy for you?
Only you can make that decision. But Dr. Gordon says that at some time or another every man & woman should undergo a series of treatments to greatly benefit ones health since all of us have large quantities of heavy metals stored in our bodies.
Chances are your doctor won’t help you decide. Patients who choose chelation often do so against the advice of their personal physicians or cardiologists. Many have already been advised to undergo vascular surgery.
Occasionally, a patient never hears about chelation until he is hospitalized and a friend or relative begs him to look into this non-invasive therapy before proceeding to surgery. In an impressively large number of instances, a new patient comes for chelation on the recommendation of someone who has been successfully chelated.
Chelation therapy is probably the most successful method to extend maximum life span but this has yet to be proven by the scientific method. It certainly is the best procedure for having a healthy and more symptom-free time as you age.
1. We must have a recent BLOOD TEST (within the last 6 months)
a. General Metabolic Profile with Serum Iron & Ferritin
b. CBC (Complete Blood Count)
c. Differential
2. A recent U/A (Urinalysis)
3. CONSENT FORMS — must be read, understood and signed.
4. THE CHELATION PROGRAM IS AS FOLLOWS:
a. IV CHELATION — 12 to 15 IV Chelation Treatments of about 30 minute duration once weekly. This may be repeatd a second time in about 4 months for the first year only. Then you should have the IV Chelation Protocol for 2 to 15 sessions once yearly thereafter depending on health status
b. ORAL CHEALTION ?- which consists of 3 capsules of EDD (Essential Daily Defense) twice daily (morning & evening) on an empty stomach (30 minutes before a meal or 2 hours after a meal. This will continue while you are on the IV Chelation Protocol. ALSO, you should take 3 EDD capsules the day of your IV, preferably just before you are get your IV.
c. ORAL CHELATION ?- using PORPHYRA-ZYME ?at 5 tablets twice daily on an empty stomach when not using the IV Protocol for maintenance. Since skeletal bone is a continuing source of heavy metal poisoning for other tissues, using this maintenance protocol is important for the year.
d. MULTIVITAMIN-MINERAL – Females – take EQUI-FEM at 2 tablets twice daily after meals. Males – BIO-MULTI PLUS without IRON at 1 tablet twice daily after meals.
NOTE: EDD (Essential Daily Defense) — consists of EDTA which for the most part is not absorbed very well from the digestive tract. It is used to pick up any of the heavy metals that are excreted into the gut from the liver & gall bladder. This is will pick up another 10 to 18 % heavy metals chelated and excreted through the bowel.
PORPHRA-ZYME ?- is a systemic chelating agent which is absorbed very well from the digestive tract and will continue the chelating process throughout the body and is used when you are not using the more aggressive IV Chelation Protocol.
REMEMBER:
After your initial treatment session, we recommend you should do a 1 to 3 month Chelation treatment session once per year. This will consist of 4 to 12 IV Chelation sessions with the oral EDD and then we also suggest you follow with PORPHRY-ZYME for an additional 3 months. This would make your program 3 to 6 months long.
You then need to re-evaluate how you feel. Some may prefer more IV Protocols (with EDD) due to extenuating circumstances. Some may prefer to go the entire second year with Oral Chelation alone. It depends how you respond and how you feel.
CONCLUSION: This Protocol is designed to make you feel better, have more energy, reduce nagging health problems that no doctor can seem to diagnose; in essence, not only to help you liver longer but to FEEL REALLY HEALTHY.
SOME OF THE PHYSIOLOGICAL EFFECTS OF IV & ORAL EDTA
- Cleanses the body and Mitochondria of toxic heavy metals.
- Enhances the uptake of Vitamins & Minerals.
- Reduces dangerous clotting tendencies of blood.
- Lowers Cholesterol.
- Acts as an Anti-Oxidant by protecting Cell Membranes.
- Protects Mitochondira of the cell (ATP production).
- Stimulates Bone Growth (Osteoporosis).
- Reverses Congestive Heart Failure.
- Increases circulation throughout the body.
- Corrects & Reverses an array of health problems.
- Reduces Peripheral Vascular disease.
- Cures Dementia-Alzheimer’s (toxic heavy metals).
- Reduces most Blood Pressure problems.
- Improves Exercise Tolerance.
- Relieves Chronic Kidney Disease.
- Relieves Brain Dysfunction (Autism,,etc.)
- Reduces & Reverses ?Vulnerable Plaque?
- 90% reduction in Cancer Mortality.
- New Ca-EDTA takes only 30 minutes.
- New Ca-EDTA is one-third as expensive.
- Enhances Nitric Oxide Production
- Increases General Sense of Well-Being.
Original Paper:
EDTA and Chelation Therapy: History and Mechanisms of Action, an Update
Garry F. Gordon, MD, DO, MD(H)
ABSTRACT: Twenty-four years have elapsed since my first article on EDTA, co-authored with Dr. Robert C. Vance1 first appeared. In the past 50 years, it is estimated that over one million patients have received intravenous chelation therapy with one widely used chelator, EDTA.Unfortunately, I believe we may have still failed to discover the primary mechanism(s) of action responsible for the frequently dramatic clinical improvements seen in numerous apparently unrelated conditions treated with EDTA and/or other chelators, unless it is simply that the binding and/or removal of toxic metals permits improved metabolic functioning in a variety of conditions. With science documenting the adverse effects of commonly encountered low levels of heavy metals on health, it is possible that chelation therapy is being vastly underutilized in standard medicine and that combinations of new and existing Chelating agents may need to be employed to deal with the broader spectrum of toxic metals now being identified as contributors to many if not most diseases, including aging.
INTRODUCTION
I am currently a medical consultant to two companies that are involved in food supplement sales and both of these companies sell oral EDTA containing products. Since my initial review of the available literature1 many more references to EDTA are now available2 3. Unfortunately, today’s excessive focus on the potential benefits to patients suffering symptomatic cardiovascular disease has significantly, stifled the utilization of EDTA and other chelators in other conditions where I believe it should be routinely utilized, at least as an adjunct to other therapies. These indications include many common and difficult to treat conditions from acute rheumatoid arthritis and psoriasis, to cirrhosis of the liver and cancer, where clinical benefits have been described. I hope to refocus attention to the metal binding activity of chelating agents in general, so that this treatment may soon achieve its proper recognition as an adjunctive therapy in the management of many common health problems.
A BROAD VIEW OF CHELATION IN MEDICAL PRACTICE
Brain 4 and renal function 5 6 diseases, macular degeneration 7, arthritis 8 and arteriosclerosis 9 10,are all conditions that have been reported to show benefits from IV EDTA chelation. Over thirty documented mechanisms of action associated with the use of this form of chelation therapy have been published. Newer developments in molecular medicine and cell signaling suggest, however, that there may be other, far more important basic mechanisms waiting to be discovered. One of these might be regulation of transcription factor NFKappaá activity, which plays a pivotal role in immune dysregulation. The dramatic responses in some cases of rheumatoid arthritis in the literature may be explained with inhibition of Nfkappa by EDTA.11 12 13 14 This opens up many interesting possibilities for future chelation research in several seemingly unrelated conditions. Recent research in Alzheimer’s disease involves the cortical deposition of Abeta. This has been found to be completely reversible with zinc and copper chelation15.
I believe that Chelation therapy for subclinical metal toxicity could soon become far more widely employed by many health care practitioners, many of whom probably will never become trained by either one of the organizations providing advanced training, or become fully certified by the American and/or the International Board of Chelation Therapy. There are many natural substances, including all weak organic acids, that are chelating agents and the public will undoubtedly soon begin self-treating with these various chelators as the health benefits of lowered levels of toxic metals becomes more widely appreciated. Accurate medical advice concerning oral chelating agents is essential. For example, research strongly suggests that cysteine-based oral chelators may, for example, re-deposit tissue-extracted mercury in the brain16. Neither Chlorella, nor PCA (Peptidyl Clathrating Agent) significantly chelate mercury out of the body in spite of the claims17. Garlic, on the other hand, appears to be generally beneficial and is documented to lower the level of lead in tissues,18 as well as to decrease platelet aggregability19 and demonstrate significant cardiovascular and anti-atherosclerotic benefits.20,21,22
Chelators may also provide beneficial effects through their influences on other substances. For example, Morrison23 documented as much as 90% reduction24 in incidence of acute heart attacks, using his polysaccharide-based formula25. By adding EDTA to his orally administered formula, we found that blood coagulability was reduced using the Chandler Loop test26, 27Gordon, GF, unpublished observation).
BYPASS VERSUS NEW IMPROVED COMPREHENSIVE CHELATION THERAPY
New developments focusing on the role of inflammation in cardiovascular disease28 29 30 31 32 33.clearly suggest that intravenous EDTA chelation therapy can no longer reasonably be considered as a primary or single complete therapy for the long-term management of cardiovascular disease34.
Administration of IV EDTA offers many dramatic benefits including improved blood flow, and it deserves far greater recognition as a part of any comprehensive cardiovascular support program. With the recent recognition that some heart conditions have as much as a twenty thousand times increase in the level of some toxic heavy metals, chelation therapy, should be far more routinely employed. Some chelators believe that there is a worthwhile distinction between arteriosclerosis and atherosclerosis, which might improve treatment outcomes. They believe there is a higher content of calcium in the arteriosclerosis and a higher lipid content of the plaque seen in atherosclerosis. One of ACAM’s co-founders, David J. Edwards (written communication, October 14, 2000), has indicated that he is observing significantly enhanced benefits from IV chelation in the atherosclerotic patient by his addition of three lipolytic agents (choline, inositol, and methionine) to the IV treatment with the EDTA. Dr Edwards believes this treatment might be thought of as ?lipid stripping? enhanced chelation. He feels that the primary benefits of EDTA is related to its primary metal-binding activity, and thus arteriosclerosis with its higher calcium content should be expected to have better results than atherosclerosis where the lipid problem must be separately addressed. He tries to distinguish between atherosclerosis and arteriosclerosis by the use of either rapid CT scan or soft tissue extremity x-rays.
I believe that IV EDTA Chelation therapy for cardiovascular disease should never be employed without concurrent aggressive effective pharmacological and/or nutritional/natural product based therapy for all the newly recognized applicable cardiovascular risk factors. These include replenishment of deficient minerals that become relatively even more deficient in the face of the serious excesses of toxic metals in heart muscle cells. Furthermore it has now become essential to deal effectively with the infectious35 and resulting hypercoagulability36 aspects reflected in the newer cardiovascular risk panels.37
It is now established that about 85% of sudden cardio- and cerebro-vascular deaths are due to rupture of vulnerable, non-calcified arterial plaque and subsequent clot formation.28 This form of plaque, invisible by conventional angiography, initiates a terminal thrombo-embolic event superimposed on chronic vascular inflammation, hypercoagulation and metabolic derangement as in acquired homocysteinemia. Patients who choose I.V. chelation instead of by-pass surgery hope for more than symptomatic improvement, and when some learn that they still have seriously calcified coronary vessels on ultra high-speed cat scans, they are very disappointed. Some mistakenly opt for surgery at that time, even if they find they can easily sustain a far higher level of physical activity following their ?unsuccessful? chelation therapy. Unfortunately most patients are unaware of the new information about Vulnerable Plaque, the kind that is actually now believed to be involved in heart attacks, and they are not told that this truly life-threatening plaque is not readily seen on any currently widely available vascular tests, including angiograms. This failure has led me to consider the standard vascular tests relied on to sell by-pass and other invasive procedures to patients, as, at the very least, unreliable and misleading. Improved oxygenation of ischemic tissues is a reasonable goal of therapy and simple improvement in exercise tolerance testing is very useful in evaluating this.
I believe that most patients seldom are adequately informed regarding the severe limitations of all surgical approaches in the management of their vascular disease. In fact, since the vulnerable plaque involved in 85% of heart attacks and strokes cannot be seen with modern technology, their heart surgery is generally attacking the wrong plaque and thus is providing little, if any, long term benefit at great expense and risk. It is now widely believed that the underlying cause of death in heart attacks and strokes is from a blood clot related to vulnerable soft plaque due to an active infection in the arterial wall, often caused by herpes related cytomegalic virus or chlamydia pneumonia. Current research calls for treating the blood to prevent these life-threatening clots, not the blood vessel.24
I hope that wider dissemination of this new information will help lead to the end of the largely useless surgical attack on coronary vessels so rampant today. In fact, some believe that operating on infected tissue is poor medical practice, which happens frequently with unstable angina as shown by elevated C-reactive protein levels that standard medicine has such difficulty managing. In fact, Dr Terry Haws has informed me that using the cardioCRP test offered by Quest Labs, that the majority of his new patients are coming back reported as ?at risk? (verbal communication). It appears that just as ‘safe? levels of cholesterol and homocysteine tests, over time, were moved lower and lower, the same can be anticipated with c-reactive protein testing as more data regarding ?ideal? values is accumulated. The infection that apparently we all have in our vascular tissues causes hypercoagulability, resulting in local ischemia that is far better treated medically.38 Of course, intravenous chelation always has a place in the management of any ischemic process. We all routinely expect to see improved circulation in 85% or more of our chelation patients39 and there are over thirty potential beneficial actions of EDTA to help explain this improved blood flow.
I believe that with our improved understanding regarding the need for effective control of hypercoagulability in virtually all ill patients40, it may be beneficial to routinely add a more therapeutic level of intravenous or subcutaneous Heparin41, along with more aggressive therapeutic levels of intravenous Vitamin C, in our efforts to manage this newly identified epidemic of hypercoaguability/infection related problems. 4,000 to 6,000 units of Heparin, based on weight, administered subcutaneously b.i.d. are safe, for a therapeutic trial of several weeks, without doing specialized coagulation studies in patients without a history of serious bleeding disorder (personal communication with David Berg, May 3, 2000). Longer term use of oral enzymes42 or daily heparin injections to decrease fibrinogen concentrations and soluble fibrin monomers appear to greatly facilitate the treatment of any chronic infectious process36.
Appropriate enteric-coated oral enzymes containing bromalain and/or heparin injections decrease fibrinogen concentrations and soluble fibrin monomers to facilitate the treatment of any infectious process. A safe approach in helping to combat infection can be with colostrum and colostrum-based transfer factor,43 44 45 46 and other immune enhancing and cardiovascular supporting nutritional supplements.48 49 50 51 All are now better supported with a new, non-acidic, neutral pH, well-tolerated form of oral Vitamin C, and/or Vitamin C infusions. The already high efficacy of combinations of these natural approaches in dealing with any infectious process has recently been significantly enhanced by an effective extract of gram-positive bacteria known as muramyl polysaccharide glycan complex. This has been found to enhance immunity against all infections, and even shows anti-tumor activity.52
We no longer have to rely on the long-term use of largely ineffective antibiotics alone for the control of chronic and often resistant infections now recognized in the hypercoagulability problem. Antibiotics alone have been shown to be inadequate for long-term control of chlamydia, although currently some experts are recommending a full year of azithromycin,35 or the other chronic hidden infections found in the vascular wall that is now clearly implicated in deaths from vascular disease.53
I believe that the optimal use of EDTA in clinical practice needs to be totally repositioned, probably as an adjunct to most other therapies, providing improved management of most chronic diseases, since its primary function is eliminating excessive levels of metals. I fear negative outcomes from currently proposed and/or ongoing chelation cardiovascular studies where removal of the wrong plaque is the focus and the ethical dilemma in blinding any study may seriously jeopardize any studies.54 If, on the other hand, trace element studies are done to document the significant detoxification benefits seen with chelating agents, and long-term outcomes and quality of life data are compared to standard therapies, the combination of this data should offset any detected failure to simply remove plaque. Combined with safe, effective, natural treatment of all the newly recognized risk factors, such a comprehensive chelation protocol, I believe, would produce exceptional results. Since we have now entered the age of Einsteinian, molecular-based cardiology, nothing but the elimination of most by-pass surgery, a Newtonian concept, should be the goal.
Generally, the toxic metals removed by intravenous EDTA chelation simply start to re-accumulate once the treatment is discontinued. Thus, a number of oral chelators, including ascorbic, malic and lactic acids55, may help maintain chelation benefits more cost effectively over a lifetime. Another approach is to reduce the biologic availability of heavy metals. For example, selenium binds mercury, markedly diminishing its potential for biologic harm, and many naturally occurring substances such as rutin and lactoferrin have been shown to have chelating properties. There is however, no single chelator available today that can effectively deal with the wide spectrum of potentially toxic metals that have been implicated in the degenerative diseases associated with aging. Thus, I believe that a broad spectrum of natural and/or pharmacological agents with chelating ability would be predictably more effective. My experience is that a comprehensive preventive approach can be effective even in high-risk patients, i.e. those with documented hi-grade involvement of two or three vessels.
For example, eicosapentaenoic acid supplementation56 57 augmented with garlic58, ginkgo, EDTA activated polysaccharides, bromelain and rutin can all be effectively employed synergistically in such a comprehensive broadly based protection program.
There is no critical need for monitoring with bleeding or clotting tests patients maintained on such a program since there is no significant risk of pathologic bleeding. It is, however, important to emphasize to the patient that this protection must be continuously maintained. Aspirin and NSAID’s reportedly contribute to over 16,000 deaths each year59, largely as a result of induced G.I. bleeding. The benefits from aspirin and Coumadin are seriously limited24. The use of modern platelet aggregation and fibrinogen studies can show patients just how incomplete their standard drug protection is. By later repeating these tests after initiating a comprehensive natural product based anticoagulant program, patients can generally see the remarkably improved level of protection they now enjoy with little or no side effects.
The Homeopathic Medical Board of Arizona Chelation Peer review committee that I chair has currently advised physicians in Arizona that all chelation informed consent procedures for cardiovascular disease should specifically spell out the important caution that, even though patients may enjoy tremendous symptomatic improvement, actual (regular or visible) plaque reversal as measured and relied on today for prescribing life-threatening vascular surgery, may not be occurring.
BLOOD CLOTTING
Berg38 has shown that a coagulation panel that is more sensitive than hitherto available is capable of distinguishing healthy from unhealthy subjects with over 95% accuracy. In fact, hypercoagulability is associated with a large number of chronic diseases.39
Since EDTA prevents clotting in blood collection tubes used daily, I believe more sensitive tests may show some subtle reduction of hypercoagulability. Possibly lowering the number of adhesion molecules, or soluble fibrin monomers, may be one of its subtler, but life saving benefits. The combination of a polluted environment, stressful life style and chronic low-grade infection leading to hypercoagulability, initially called the AntiPhospholipid antibody syndrome, has now more recently been renamed ?immune system activation of coagulation? (ISAC). It appears to be surprisingly common and those at risk need long-term effective but safe lifelong anticoagulation treatment. Aspirin alone is too weak and too dangerous to handle this epidemic of hypercoagulability. It has also recently been reported to be too dangerous for men with hypertension to take on a regular basis.60 Effective aspirin substitutes include pancreatic enzymes (Wobenzym?)61 and properly stabilized bromelain supplements, preferably used in combination with garlic, Ginkgo, and salmon oil. A polysaccharide/ chelation based product, containing EDTA, also acts as an effective aspirin substitute and affordably helps to meet this nearly universal need.62
ORAL EDTA
Chelating agents are routinely added to our food supply so that EDTA, for example, is added to foods for its ability to bind with the transition metals, particularly iron and copper.63 These agents inhibit rancidity in substances such as oils.64 65 This has led me to consider the potential benefits from the non-absorbed fraction of orally ingested EDTA, which, I believe, may help prevent oxidative degradation within the intestinal tract, just as phytic acid has been reported useful in chelating iron, which acts as a catalyst in the development of colorectal cancer.66 Many oral-chelating agents, including EDTA, might provide long-term protection, including helping to prevent potential intravascular coagulation.67 68 69 70 Remarkable responses have been attributed to various chelating agents, including DMPS, Penicillamine, Desferoxamine, as utilized by Paul Cutler (personal conversation, October 7, 2000) in the treatment of diabetes, infections and cancer and EDTA71 72 in an extremely diverse number of conditions.73 74 75
There are, in fact, over 300 references to the use of oral EDTA3. Nonetheless, there are many knowledgeable clinicians who are very negative about the oral ingestion of EDTA and who raise questions about its long-term safety. Recently published research has more than adequately rebutted those concerns.63, 64, 76 I believe that the benefits of lowered levels of toxic metals and diminished availability of transition metals more than offsets any theoretical concerns about potential essential trace mineral depletion, about which I believe we have adequate knowledge to monitor and treat.77 78 and some research suggests that minerals become more bioavailable.79 Since only 5% of orally ingested EDTA is absorbed, taking 1200 mg for a year would provide at least some of the benefits seen from receiving 10 intravenous therapies of 3gm each a year.80 81
I am totally convinced that there are significant benefits from oral chelation for patients unable to undergo a more complete program of intravenous therapy, and further that oral EDTA helps provide for an effective maintenance program even for those who are concurrently undergoing a series of intravenous chelation treatments.82 Oral EDTA for the treatment of asymptomatic lead toxicity was FDA approved for the indication ‘to increase the excretion of lead.? This is described in the Physicians? Desk Reference (PDR) through 1976, with obvious supporting references in the FDA files, complete copies of which we are still attempting to obtain. We, as licensed physicians, specializing in Chelation Therapy, I believe are fully responsible and probably legally liable to become adequately informed about the pro and con of all forms of chelation therapy, if we are to adequately discuss all of the available choices with our prospective chelation patients. This would seem essential if we hope to obtain a totally informed consent before prescribing chelation therapy for any reason, to our patients.
Oral EDTA probably exerts some anticoagulant and antiplatelet effects partially by the effect of chelating calcium ions.83 84 It has also been shown to prolong prothrombin time85 86 and has effects on platelets87 88 and other blood components89 90 cell membranes91 and has cholesterol-lowering potential.92 EDTA has also has been the subject of a US patent93 because some therapeutic substances, especially sulfated polysaccharides, like heparin, which previously were only effective when given parenterally, became orally effective in the presence of EDTA.61 Oral EDTA therapy was discussed in the Waukegan News-Sun, because a soap manufacturer, Neil Purdy, was supplying EDTA powder to anyone who contacted him.94 A physician, Dr. James Mercer of Lenexa, Kansas, was favorably disposed to recommend this treatment to his cardiovascular patients. Dr. Mercer received a letter because of the improvement seen in a shared patient, from Dr. Sawyer, Professor of Surgery, State University of New York (written communication November 9, 1971) as well as a letter of support from Loren Parks, Director of Parks Electronics Laboratory, Cardiovascular Instrumentation of Beaverton, Oregon (written communication June 13, 2000). The oral EDTA therapy program recommended to those patients involved taking 3gm of sodium EDTA given in 6 ounces of preferably grapefruit juice or a Vitamin C drink. Additional mineral supplementation was advised for the patients. Dr. Mercer also reported a consistent lowering of cholesterol and triglycerides in the over 100 patients he treated with this regimen.
Studies have been published measuring urinary and fecal lead excretion induced by oral EDTA.95 However, the use of EDTA in the treatment of lead-poisoned workers fell into disfavor because of abuse by industrial-based physicians, who ignored the basic axiom of good medical practice, which is to remove as much as possible the source of exposure, rather than concentrating on the less expensive prescribing of oral EDTA tablets to lead workers.96 In spite of this, the PDR through 1976 under Riker continued to list calcium disodium Versenate tablets with the only approved indication, to increase the excretion of lead.97
The body has many metal binding substances, including albumin, metalothioneins, ferritin, ceruloplasmin, transferin, and others. A reasonable hypothesis may be that additional chelators further support our health by enhancing our body’s ability to handle free metal catalyzed reactions. The reason that EDTA is routinely added to the food supply today is to help prevent the oxidative degradation of nutrients by chelating the transition metals. Our individual consumption of EDTA from food sources is estimated to average between 15mg-50mg per day. There has been concern raised that the widespread use of EDTA in our food may have an adverse effect on the environment because EDTA was non-biodegradable and may have increased the solubilization of heavy metals, particularly cadmium.98 Increasing low levels of EDTA in the environment may lead to the enhanced uptake of heavy metals, particularly cadmium, in living tissues. Fortunately, I believe we can neutralize this concern because cadmium had been shown to respond to adequate therapeutic administration of oral EDTA.99 100 101 EDTA has a 40-year history of oral use in asymptomatic patients with laboratory evidence of lead accumulation and can safely be given continuously in doses of up to 1gm a day to adults. Concomitant administration of essential trace elements, especially zinc, is obligatory. Its safety seems to be firmly established, and the potential of mineral depletion seems to be minimal.63, 102
In fact, at the NIH/ODS Bioavailability Conference the ENVIRON International Corporation report on mineral absorption listed EDTA as a dietary factor enhancing absorption and bioavailability of zinc along with protein, cysteine, citrate and methionine.103
In a recent recorded and published interview by ACAM member and Diplomate of ABCT, Ron Kennedy, MD, of Santa Rosa, California, on the subject of oral chelation,104 I provided more of the historical background to further assist others in understanding some of the potential clinical applications of oral chelation.
The central role of iron in catalyzing free radical pathology, and consequently upon health span and longevity, belies the common clinical perception that iron saturation is preferable to the risk of deficiency. Epidemiological studies show that iron stores, as measured by serum ferritin, accumulate four times faster in males than pre-menopausal females and that cardiovascular disease is also four times more likely in age-matched men. Monthly menstrual iron losses may thus mitigate cardiovascular risks in a manner analogous with the chelation of excess free iron, inasmuch as hysterectomy, even with intact ovarian function, abolishes the protective effect.105 Similarly, regular blood donors show decreased incidence of myocardial infarction and cancer, recalling the Swiss experience with regular EDTA rapid IV injections of Calcium Disodium EDTA in carefully monitored patients over almost two decades. For example, the level of lead has now been shown to relate directly to IQ.106 This suggests that it would be prudent to offer some form of oral chelation to every student, recognizing the cost and importance of education in our society.
NOTE: While most of the research reports below do not specifically use EDTA or CaEDTA it must be seen that ridding the brain tissue of metals that should not be there is the job of any good chelating agent.
Neuron. 2001 Jun;30(3):641-2.
Metal chelator decreases Alzheimer beta-amyloid plaques.
Gouras GK, Beal MF.
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA.
Transgenic mice developing beta-amyloid (Abeta) plaques are advancing experimental treatment strategies for Alzheimer’s disease. The metal chelator, clioquinol, is reported by Cherny et al. (2001) to reduce Abeta plaques, presumably by chelation of Abeta-associated zinc and copper. This and other recent Abeta-modulating treatment approaches are discussed.
Ann N Y Acad Sci. 2000;920:292-304.
Metal chelation as a potential therapy for Alzheimer’s disease.
Cuajungco MP, Faget KY, Huang X, Tanzi RE, Bush AI.
Laboratory for Oxidation Biology, Massachusetts General Hospital, and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115, USA.
Alzheimer’s disease is a rapidly worsening public health problem. The current lack of effective treatments for Alzheimer’s disease makes it imperative to find new pharmacotherapies. At present, the treatment of symptoms includes use of acetylcholinesterase inhibitors, which enhance acetylcholine levels and improve cognitive functioning. Current reports provide evidence that the pathogenesis of Alzheimer’s disease is linked to the characteristic neocortical amyloid-beta deposition, which may be mediated by abnormal metal interaction with A beta as well as metal-mediated oxidative stress. In light of these observations, we have considered the development of drugs that target abnormal metal accumulation and its adverse consequences, as well as prevention or reversal of amyloid-beta plaque formation. This paper reviews recent observations on the possible etiologic role of A beta deposition, its redox activity, and its interaction with transition metals that are enriched in the neocortex. We discuss the effects of metal chelators on these processes, list existing drugs with chelating properties, and explore the promise of this approach as a basis for medicinal chemistry in the development of novel Alzheimer’s disease therapeutics.
Brain Res Brain Res Rev. 2003 Jan;41(1):44-56.
Zinc takes the center stage: its paradoxical role in Alzheimer’s disease.
Cuajungco MP, Faget KY.
Department of Neurology, Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA. cuajungc@helix.mgh.harvard.edu
There is compelling evidence that the etiology of Alzheimer’s disease (AD) involves characteristic amyloid-beta (Abeta) deposition, oxidative stress, and anomalous metal-Abeta protein interaction. New studies have implicated redox active metals such as copper, iron, and zinc as key mediating factors in the pathophysiology of Alzheimer’s disease. There is also evidence that drugs with metal chelating properties could produce a significant reversal of amyloid-beta plaque deposition in vitro and in vivo. This paper reviews current observations on the etiologic role of zinc in AD. We also discuss the interactions of zinc and copper with Abeta, a factor that purportedly facilitates disease processes. Finally, we review the protective role of zinc against Abeta cytotoxicity and hypothesize how the apparent effect of zinc on AD pathology may be paradoxical, The Zinc Paradox. Indeed, complex pathologic stressors inherent to the Alzheimer’s diseased brain dictate whether or not zinc will be neuroprotective or neurodegenerative. Further research on the zinc paradox in AD is needed in order to elucidate the exact role zinc plays in AD pathogenesis.
Front Biosci. 2002 Apr 1;7:d1016-23.
Transition metal chelator therapy–a potential treatment for Alzheimer’s disease?
Gnjec A, Fonte JA, Atwood C, Martins RN.
McCusker Foundation for Alzheimer’s Disease Research, Department of Psychiatry, University of Western Australia, Hollywood Private Hospital Nedlands, 6009 Western Australia.
A defining feature of Alzheimer’s disease (AD) pathology is the presence of amyloid beta known as A-beta (Abeta) within neuritic plaques of the hippocampus and neocortex of the brain. While early in vitro studies suggested that Abeta could itself be toxic to neuronal cells, recent studies have indicated that this peptide has both neurotoxic and neuroprotective properties that are modulated by the binding of transition metal ions. Transition metal ion binding was shown to modulate Abeta solubility as well as its hydrogen peroxide production, thereby providing explanations for both its trophic and toxic properties. These findings lead to the suggestion that interference with this interaction may reverse the neurotoxic properties of Abeta. More recently, in vivo and in vitro studies into the effects of transition metal chelator treatments on Abeta solubilisation and neurological function have been published. Such studies have yielded promising results, however the potential side effects of many such metal chelators may prove too great for clinical use. It is widely agreed that the ideal chelator for such interdiction would act only on those transition metals that complex with Abeta, and only at metal ion binding sites that contribute to Abeta aggregation and reactive oxygen species generation. The efficacy of metal chelators in reducing Abeta load in transgenic mouse brains demonstrates that this approach has considerable merit as a research tool and as a stimulus to develop second generation agents that can selectively prevent transition metals from binding to the Abeta peptide itself without perturbing the action of other important metal requiring biomolecules in the brain.
Neuron. 2001 Jun;30(3):665-76.
Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice.
Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, Barnham KJ, Volitakis I, Fraser FW, Kim Y, Huang X, Goldstein LE, Moir RD, Lim JT, Beyreuther K, Zheng H, Tanzi RE, Masters CL, Bush AI.
Department of Pathology, The University of Melbourne and, The Mental Health Research Institute of Victoria, Australia.
Inhibition of neocortical beta-amyloid (Abeta) accumulation may be essential in an effective therapeutic intervention for Alzheimer’s disease (AD). Cu and Zn are enriched in Abeta deposits in AD, which are solubilized by Cu/Zn-selective chelators in vitro. Here we report a 49% decrease in brain Abeta deposition (-375 microg/g wet weight, p = 0.0001) in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator. This was accompanied by a modest increase in soluble Abeta (1.45% of total cerebral Abeta); APP, synaptophysin, and GFAP levels were unaffected. General health and body weight parameters were significantly more stable in the treated animals. These results support targeting the interactions of Cu and Zn with Abeta as a novel therapy for the prevention and treatment of AD.