Participants in the Summit for New Direction in Chelation Therapy
From March 13 to 15, 2013, the International College of Integrative Medicine (ICIM) held a summit meeting about what should be accomplished next, now that EDTA chelation therapy has been supported as a useful treatment for vascular disease by the Trial to Assess Chelation Therapy (TACT). Experts from around the world were invited. This paper is a summary of the conclusions and recommendations of this gathering. Key presentations were given by Drs. John Trowbridge, Efrain Olzsewer, and Eleonore Blaurock-Busch. Representatives from the U.S., Canada, Indonesia, Brazil, Denmark, the Netherlands, Germany, Ecuador, and New Zealand participated, as well as the attendees for the Advanced Metals Workshop that was part of the spring meeting of ICIM. Recordings of the lectures are available from icimed.com. This paper was prepared prior to articles on TACT published in the Journal of the American Medical Association in the March 27, 2013 issue.
Background
EDTA has been used as a treatment for vascular disease since Norman Clarke, Jr.’s work in 1952. For a timeline of the many studies that have supported its effectiveness, see chelation.me. In 1981, the AMA challenged the proponents of chelation therapy to produce a large-scale, randomized, controlled, clinical trial to prove its safety and effectiveness. The members of the American College of Advancement in Medicine (ACAM) led by president Ross Gordon collaborated with Walter Reed Hospital to begin such a study for treatment of peripheral vascular disease in 1987. Unfortunately, the first Gulf War took the investigators away from the study, and it was not completed. In 1999, Congressman Dan Burton, Chair of the Committee on Oversight, held a hearing bringing together the head of the Heart, Lung, and Blood section of the National Institutes of Health and several physicians who testified about their experiences with chelation. NIH subsequently called for proposals, and eventually TACT was funded, with Gervasio Lamas as chief investigator.
TACT was unique in that it combined university research cardiologists and experienced chelation specialists with private offices. 134 sites from the U.S. and Canada participated in the randomized, placebo-controlled, double-blind, clinical trial. TACT continued for 7 years, and included 1708 patients with documented previous heart attacks who continued to receive evidence-based therapy. The primary end point was a composite of new cardiac events to include death, heart attack, stroke, hospitalization for unstable angina, and need for revascularization surgery. TACT showed that the therapy was unquestionably safe, and the group treated with chelation therapy had fewer cardiac events, which was statistically significant. The results were announced by Lamas at the American Heart Association meeting on November 4, 2012 in Los Angeles. Publication of the results is pending. The authors called for further studies to confirm the results and explore the mechanisms of action.
Where we stand now, according to the Summit
TACT conclusively showed that chelation therapy used according to the recommended protocol is safe.
TACT and the many other studies that proceeded it support the use of chelation therapy as an option for patients with vascular disease, especially for those who also have diabetes and those with a history of anterior wall myocardial infarction.
There is not yet enough evidence to state that chelation therapy should be given to all cardiac patients. More studies need to be done. A duplication of TACT would be ideal, as long as it included heavy metal testing. However, another $30 million to repeat the study might be difficult to find.
Strong consideration should be given to doing a challenge test for heavy metals (especially lead) for all patients with vascular disease. If high levels are found, the patients should be treated with chelating agents.
Regulatory agencies, such as medical boards, should immediately stop harassing physicians who offer chelation therapy to their patients who give appropriate informed consent. Physicians who offer chelation therapy have accomplished exactly what the AMA asked them to do in 1981 to justify its use.
Most physicians who offer chelation therapy are happy to serve as consultants for placebo-controlled RCT’s, but are uncomfortable with the ethics of giving placebos to patients who have come to them for help. Certainly, patients should not be asked to pay to receive placebos, especially for a potentially life-threatening illness. Physicians who provide chelation are almost always convinced that in their experience the therapy is very effective.
Many chelation doctors feel that their primary goals of showing efficacy and safety with a RCT have been accomplished with TACT. Gaining FDA approval of EDTA for use in vascular disease is secondary, and they encourage qualified investigators to move in that direction.
Recommendations of the Summit
More research should indeed be done on metal toxicity, free radical pathology, and on various diseases that have been linked to free radical pathology, especially vascular disease.
Chelation doctors do not have the resources to fund or carry out clinical trials, but they do have the expertise to help plan them.
The conditions that are most likely to show benefit with chelation treatment and thus should have the greatest research priority are as follows:
Patients waiting to have limbs amputated due to non-infected vascular disease. For end points, all that is needed is to count the remaining limbs. Claus Hancke’s work is most impressive in this regard.
b. Walking distance and A/B index in patients with peripheral vascular disease. In our experience, a very high percentage of patients improve. Ffrain Olzsewer and Jim Carter documented this. There have been a couple of negative studies published on this subject in prominent journals, but they have been seriously flawed. Stephen Olmstead has written a good research protocol to evaluate chelation treatment for peripheral artery disease that is almost ready to go. He is willing to share his work with others. Attendees to the summit expressed significant concern that opponents of the therapy might proceed with new studies that are designed to fail, which has happened in the past.
Brachial artery stiffness and other measurements of vulnerable plaque. Peter van der Schaar is beginning a study on arterial stiffness.
Diabetic patients who have evidence of vascular disease.
Patients who have suffered an anterior wall MI.
Patients who have angina that is difficult to control with drugs.
Macular degeneration.
Patients who have been told that revascularization surgery is an option
Quality of Life measurements should be included in all research projects. Chelating physicians insist that their patients feel considerably better with long-term treatment, even though the relatively short follow-up in TACT detect significant improvement.
Other areas that are important to study and are likely to show successful outcomes:
Patients with hypertension and elevated lead levels
Arterial intimal thickness and high resolution ultrasound of the carotid arteries (see the work of Robert Bard)
Osteoporosis
Mild to moderate Alzheimer’s disease associated with heavy metal toxicity
Autoimmune diseases, especially scleroderma
Fibromyalgia with high levels of toxic metals detected with a challenge test
Diseases that are familiar to the public should be studied in order to raise awareness and support for chelation.
There are many biomarkers in the laboratory that can help examine the mechanisms of action of chelation therapy. Expert biochemists (Blaurock-Busch, Jaffe, Quig) are happy to consult with investigators as to which ones are most appropriate to utilize in this assessment.
Various combinations of chelating agents, and different doses of such entities as EDTA and vitamin C are important to study.
Chelation therapy is useful to study at all stages, to include
a. Preventive
b. Pre-emptive (early signs of disease)
c. Treatment of established disease
d. Treatment following revascularization procedures
e. Maintenance treatments are very important
Such international lecturers as van der Schaar, Olzsewer, Rozema, Hancke, Dooley, and Godfrey continue to teach physicians on how to use chelation therapy safely and effectively. Organizations such as ACAM, ICIM, and A4M hold workshops in the United States. Excellent recent textbooks have been published by van der Schaar and Blaurock-Busch (both are available through the International Board of Clinical Metal Toxicology). There is a need to move toward consistent protocols and best practices.
Studies must be well-designed and conducted so that clear outcomes can be readily understood and will resonate with a large portion of the population, as well as stimulate Congressional action.
Use of NBMI—a compound being studied by Boyd Haley might turn out
to be a powerful therapeutic modality.
Conclusion
Raising public, political, and media awareness is now essential. Experienced chelating physicians can help provide solid data to support general understanding of efficacy, mechanisms, and positive outcomes in the treatment of vascular diseases. Registries might be the best way for clinicians to collect data without the constraints of a RCT. Self-insured corporations, such as Parker-Hannifin are now paying for chelation therapy. Cooperation among organizations with similar interests, such as ICIM, ACAM, AAEM A4M, ABCMT, IBCMT, and specialized laboratories is strongly encouraged to standardize protocols and set up registries. This can be done quickly and with minimal expense. Physicians from around the world should be included. Experienced chelating physicians can serve as consultants for researchers who are qualified to perform RCTs. NIH and various foundations are encouraged to fund projects discussed in this paper. Pollution with heavy metals continues to get worse, and evidence is mounting that their toxicity is an important factor in the development of chronic degenerative diseases.
In September of 2011, the Department of Health and Human Services (DHHS), the Centers for Disease Control(CDC), and the Centers for Medicare and Medicaid Services(CMS) jointly announced the Million Hearts Initiative(1,2). The goal is to prevent 1 million heart attacks and strokes over the next five years. Other groups such as the American Heart Association, the American College of Cardiology, the American Pharmacy Association, and Walgreen drug stores quickly joined the effort.
Unfortunately, the action plan to achieve this lofty goal as published is likely to fail. Nevertheless, those of us in Integrative Medicine should embrace the overall goal and use all of our skills to formulate a plan to prevent even more heart attacks and strokes than the efforts put forth by these prestigious organizations. This article analyzes the strengths and weaknesses of the Million Hearts Initiative(MHI) and shows how we can make it dramatically better.
Cardiovascular Disease as the Leading Cause of Death
In the United States there are about 2 million heart attacks and strokes each year with 800,000 fatalities. Not only is this the leading cause of death, but also the overall medical cost of these diseases is estimated to be $450 billion per year. From 1980 to 2000 there was a significant reduction in the death rate from cardiovascular disease, most of which was due to lifestyle changes and preventive medicine. Yet cardiovascular disease is still by far the leading cause of death. HHS Secretary, Kathleen Sebelius, states that heart disease is responsible for one of every three deaths in the U.S.
The MHI Plan to Prevent Heart Attacks and Strokes
The clinical interventions put forth by the MHI consist of four potential categories of drugs. The treatment acronym is the ABC’S of prevention: aspirin for high-risk patients, medications to control blood pressure, cholesterol management, and smoking cessation if needed (varenicline, nicotine patches, etc.). In addition, the MHI calls for improved nutrition through a reduction in the intake of sodium and trans-fats. The MHI hopes to coordinate activities with Obama’s Affordable Care Act. Electronic health records and quality recognition programs offered by both the government and various private insurance plans should also be useful for recruitment of patients to participate.
At present, only 47% of patients at risk take aspirin, 46% have blood pressure under control, and 33% have LDLs below 100. The specific goals of the MHI are to increase all of these numbers to 65% by 2017. A fourth clinical goal is to reduce smoking prevalence from 19% to 17%(1).
Emphasizing four interventions that might require drug therapy certainly makes one wonder about the influence of the pharmaceutical industry in this effort. There are at least 30 million people in the U.S. whose blood pressure and/or cholesterol are not under control. That is a pretty large target population, just with these two factors. Overall, Forbes estimates that the MHI seeks to put half of our adult population on drugs prescribed by doctors.
One of the strengths of the MHI plan is that it does not depend on intensive care by cardiologists and vascular surgeons. In fact, several popular blogs written by these specialists have complained that cardiologists are being left out of the campaign. Perhaps there is a reason for this omission. The OAT trial(3) in 2006 demonstrated that opening totally occluded arteries with stents after uncomplicated myocardial infarctions involving those vessels actually increased the mortality rate when compared to medical management. Soon afterwards, the COURAGE trial(4) showed that angioplasty and stents for stable coronary artery disease were no more effective than proper medical management. Before the COURAGE trial, 85% of all stents in the U.S. were surgically placed in patients with stable coronary artery disease. Both of these important studies have been virtually ignored in clinical practice. Vascular specialists continue to place unnecessary stents in many patients each year. A recent JAMA editorial(5) described this practice as an “expensive placebo”. The authors further commented that “some entire medical subspecialties (might be) based on little evidence”. No doubt there are valid indications for revascularization procedures and complex drug therapy. Cardiologists are necessary. Many of them would be more effective, however, if they focused more on nutritional biochemistry.
Of great interest is the study by Canto and associates(6) that analyzed 542,008 patients who had heart attacks from 1994 to 2006. For those patients who suffered their first heart attack, the in-hospital mortality was inversely proportional to the number of traditional risk factors that were identified. The risk factors they examined were hypertension, smoking, dyslipidemia, diabetes, and family history of heart disease. Obviously, other factors were contributing to the increased mortality for these patients. If we are to succeed, we must do a more thorough job of identifying risk factors and modifying them safely.
Criticism of the MHI Plan
The most obvious deficit in the MHI plan is that it does not include three commonly recognized lifestyle factors for the prevention of cardiovascular disease: regular exercise, stress coping measures, and weight reduction if needed. Exercise alone is probably more effective than any drug one can take. By excluding these important lifestyle factors it becomes highly unlikely that the MHI will succeed in real life.
The MHI appropriately states that we must reduce trans-fats and sodium in our diets, but it could do much more. At the very least, patients at risk should avoid foods that are high in the glycemic index, aspartame, high-fructose corn syrup, processed foods, and fried foods. We also could eat organic raw veggies as much as possible. The use of unrefined salt would add beneficial trace minerals. Not surprisingly, the potential benefits of nutritional and herbal supplements are not mentioned in the MHI.
Diabetes is another prominent risk factor for cardiovascular disease. Weight control and low carbohydrate diets are important for prevention and treatment of diabetes. Diet, exercise and supplements are often sufficient to achieve control of Type 2 disease without medications.
Poverty and inequality are factors that have been shown to increase cardiovascular disease. Not only do these factors cause economic stress, but they also result in poor quality food and increased smoking as a stress-coping measure. Such socioeconomic factors make it more difficult for the ABC’S of the MHI to succeed. A more comprehensive approach as I describe is required to overcome the twin risk factors of poverty and inequality.
The MHI is careful to note that aspirin and statin drugs for cholesterol management are to be used only for high-risk patients. However, that might serve to be the “fine print” that nobody reads. Recent reports show that for primary prevention of cardiovascular disease the “number needed to treat” to prevent one heart attack with aspirin is 163 and for statin drugs is 200(7). The “number needed to harm” for both of these interventions is much lower. Thus the use of these drugs for primary prevention is highly questionable. However, many physicians still prescribe them when not indicated, which is a waste of resources and the potential source of serious complications.
If we are going to succeed in saving a million hearts with our current socioeconomic and lifestyle stresses and our failure to change our therapies in response to definitive evidence, we should look at additional risk factors, especially ones whose remedies are much less likely to cause complications than the proposed drugs. We should emphasize powerful lifestyle changes and safe, optimal supplements instead of diverting our attention toward aspirin, anti-hypertensive drugs, and statins. For this, we can rely on and offer our patients the insights and experience of integrative medicine.
Let’s Get Serious About Saving a Million Hearts
Obviously, we cannot save a million hearts and strokes all by ourselves. But we can save way more than our share. First, we should identify the hearts that need saving (although the case can be made that all hearts need saving). We can determine if patients’ hearts are at risk mostly by performing a history and physical exam and gathering basic lab and other tests, some of which might have been previously been performed. If patients have a history of documented vascular disease, hypertension, hyperlipidemia, diabetes, smoking in the previous 5 years, or a family history of heart attacks or strokes, they automatically qualify.
Computerized risk assessments, usually based on the Framingham Risk Assessment, might or might not be helpful. They provide striking graphic displays that demonstrate the effect of improving basic risk factors. However, they don’t include the cumulative effect of a comprehensive risk factor plan like we are discussing. If patients are at least 50 years old or the physician suspects high-risk lifestyles, one or more screening tests to determine if they are beginning to develop plaque in their arteries is indicated. If a resting EKG has non-specific ST/T-wave changes, their heart might be at risk. A stress EKG can have false positives and false negatives, especially in women. A stress echocardiogram is more accurate in females. An ultra-fast CT scan for calcium score is a good screening test. A carotid intima media thickness(CIMT) ultrasound test by CardioRisk(www.cardiorisk.us) is also a very sensitive screening test that can be done by that company periodically in your office. The ankle/brachial index is a reasonable screen for peripheral artery disease, although not very sensitive, in my experience. If positive, however, there is an increased risk for heart attacks and strokes.
If we determine that a patient is at risk, a comprehensive cardiovascular risk factor evaluation is indicated. For our patients who join the MHI, we often recommend a VAP cholesterol panel, including Lp(a)(8), HbA1C, ferritin, fibrinogen, CRPsensitive, red cell magnesium, 25 [OH] vitamin D3(9), and homocysteine test. Virtually all of these tests and more are included in a comprehensive cardiovascular blood panel. Two companies that offer such panels are Doctors Data(www.doctorsdata.com) and Atherotech(www.Atherotech.com). We also do a EDTA challenge test for heavy metals, with special attention to lead(10). If available, heart rate variability testing frequently detects high sympathetic activity that is not balanced by parasympathetic output, even when the patient is unaware of excessive stress. A saliva test strip for nitric oxide (www.advancedbionutritionals.com) can detect low NO levels, which theoretically at least, can be improved with nutritional support. Other tests for nutritional factors can certainly be ordered, but they are beyond the scope of this article.
In our report of findings, we estimate how much risk we think each patient has and how we feel we can improve that risk with various interventions. Our individual patient data base is considerably larger than that of the MHI. Our recommended treatment interventions include more aggressive lifestyle measures, nutritional supplements, herbal therapies, and other treatments as indicated.
Integrative Treatment Plan
Start with the ABC’S. Instead of or in addition to aspirin, to reduce platelet aggregation, we can use fish oils, garlic, vitamin E (mixed tocopherols especially gamma), nattokinase, and/or lumbokinase. Donating blood several times a year is another way to decrease blood viscosity. One study showed an 88% reduction in the risk for myocardial infarction for 153 middle-aged men who donated blood in the previous 24 months(11) That study has been criticized, but a more recent study(12) delineated a more complex mechanism and confirmed that blood donation might reduce the risk of vascular disease. In addition to reduced blood viscosity, the resulting decrease in elevated ferritins substantially lowered free radical activity. Rheologics (610-524-5427) makes a machine that measures blood viscosity.
The blood pressure might respond to garlic, potassium, magnesium, and other phytonutrients. I have found rauwolfia with sandalwood and other herbs(BP Natural Relief) to be particularly effective(www.natrelief.com). Weight loss can often lower the blood pressure significantly. These measures might be sufficient by themselves, or they can be used in conjunction with medications to achieve good control.
For cholesterol, HDL, and LDL management, low carbs appears to be the most effective diet(13), especially if the triglycerides are high. But this remains controversial. The DASH, LEARN, Ornish and Mediterranean diets are alternatives. Red yeast is a natural statin that can effectively lower cholesterol and LDL, with much fewer side effects than the drugs. As with statin drugs, the main beneficial effect from red yeast rice might be to reduce arterial inflammation rather than to reduce LDL. Always replace coenzymeQ10 when prescribing any kind of statin. Both muscle inflammation and congestive heart failure have been attributed to low levels of coQ10, which is depleted by the statins. Fish oils can help reduce cholesterol and so can cinnamon, niacin, berberine, and lecithin. Intravenous essential phospholipids from lecithin have been used in Europe to treat coronary artery disease. Proteolytic enzymes might also be effective to reduce inflammation. Food allergies can be important, especially gluten and casein sensitivity. A therapeutic trial of an elimination diet can be very helpful.
To stop smoking, hypnosis and acupuncture are somewhat effective. The medication varenicline(Chantix) might have its place, but the incidence of side effects is troubling.
For better fitness compliance an exercise prescription is mandatory, depending on the physical capacities of patients. People often need to have specific goals to get the best results. Al Sears’ PACE program with brief periods of intense exercise makes sense to me. It is backed by the Harvard Professional Lifestyle Study(14). Adequate fitness, however, can usually be achieved by walking for 30 minutes 5 days per week.
Always be aware of how important stress can be for cardiovascular disease.
One of the best-documented treatment programs is Heart Math(15), which is a home tutorial using biofeedback. Yoga, meditation, progressive relaxation, visualization, deep breathing, emotional freedom technique, prayer and acupressure are procedures that can be utilized. All patients in the MHI should form a plan to improve their stress-coping activities, especially if their heart rate variability results are abnormal.
Nutrient deficiencies are frequently detected with the comprehensive cardiovascular risk profile, particularly magnesium. Antioxidants are indicated if an increased amount of oxidized LDL is detected. Linus Pauling’s admonition to treat patients who have elevated Lp(a) levels with vitamin C, proline, and lysine still rings true. The optimal level of 25 [OH] Vitamin D3 is 60-100 ng/ml, although the listed normal is usually as low as 30 ng/ml. Calcium might be given to lower the risk of osteoporosis or colon cancer, but always balance it with at least half of the milligram dose of magnesium. Do not prescribe the ultra-high doses of 1500-2000 mg of calcium a day. Studies have shown that high-dose calcium can lead to calcification of the arteries. Coenzyme Q10, d-ribose, and l-carnitine are helpful adjuncts, especially for congestive heart failure and fatigue. Medium chain triglycerides from coconut oil are useful to preserve brain function. The herb, apoaequorin(Prevagen) is particularly good to preserve memory, in my experience. The physician formulation of apoaequorin is four times as strong as the product available over-the-counter.
For many years, integrative physicians have found intravenous EDTA chelation therapy to be very effective in treating and preventing cardiovascular disease. This is especially true if a build-up of toxic metals is detected. Lead is the best-documented toxic heavy metal(10). It has been linked to heart disease, cancer and autoimmune problems. If mercury is found, DMPS or DMSA might be needed in addition to EDTA. The published intravenous EDTA protocol appears to be effective, even if heavy metals are not found. The author and associates demonstrated a dramatic decrease in subsequent cardiac events in high-risk patients who had received chelation therapy(16). The results of the Trial to Assess Chelation Therapy (TACT) are due to be published this summer.
An under-appreciated advantage of enrolling a patient in a course of chelation therapy is that the treatments are given once or twice a week during the basic course. That means that each week, the nurse has a teaching opportunity to reinforce diet, exercise, stress-coping, supplement compliance, and habit control, all of which are important for saving hearts. Our staff helps the patient set goals and identify barriers to reaching the goals. As with any class or program, repetition is key. It often helps to bring a friend. When patients share their experiences and goals with others, results can be better than trying to follow the program by themselves. Group visits to deal with risk factors and lifestyle might be a useful service to offer.
Monitoring and maintenance are two key concepts for a successful program. The risk factors identified must be monitored often enough to assure that interventions are effective. Too often the patient and the physician identify risk factors, correct them temporarily, but fail to be sure that the factors remain under control. Non-invasive vascular tests should be repeated to monitor progress. Lab biomarkers should be repeated at specified intervals. The CIMT and the heart rate variability are particularly good monitoring tests. However, the ultra-fast CT scan is not.
A summary of the integrative approach in seven steps is outlined in Table 1.
Research and New Frontiers
Several avenues of research are currently taking place, including genomics, molecular targeting, stem cell biology, and regenerative medicine(17). Both conventional and integrative medicine are active in these areas of interest. Progress is anticipated within the five-year target period of the MHI. For example, stem cells harvested from autologous bone marrow are being tested to treat myocardial infarction(18). Initial results were not impressive, but the authors were optimistic that revisions in protocol might yield better results. Mikirova and associates(19) recently showed that chelation of heavy metals improved the number of stem/progenitor cells in circulation. Our version of the MHI should be a fluid plan that can be improved as new evidence emerges.
One criticism of integrative medicine is that there are few large clinical trials to support the therapies that are utilized. Harvard professors Groopman and Hartzband in their book, Your Medical Mind (7), point out that too often the larger the clinical trial, the less significant the results. Their reason is that it takes a large study to have sufficient statistical significance to prove a minimal effect. Smaller studies with larger effects are often more useful.
On March 31, 2012 in Lexington, Kentucky, the International College of Integrative Medicine will hold a forum on the Million Hearts Initiative for clinicians experienced in the use of chelation therapy and other integrative techniques. Round table discussions by the experts will explore further the ideas presented in this article. Readers are invited to attend. The proceedings will be published in the Townsend Letter.
Conclusion
How much effort is required to prevent a heart attack or a stroke? How about a million heart attacks and strokes? We applaud the conventional medical community and government for setting the MHI as a lofty goal. Unfortunately, it is unlikely that goal will be reached with the plan that has been put forth. On the other hand, utilizing a comprehensive, integrative approach, we can make a huge impact for those one million individual hearts and brains that we want to save. Not infrequently, hypertension and hyperlipidemia can be controlled by detoxification of heavy metals, exercise, a healthy diet and stress management without the use of medications that might cause more adverse affects than beneficial ones. Nutritional and herbal supplements, as needed, can be added with greater safety than many medications, with similar benefits.
Patients must be presented with all the evidence in an unbiased manner. Then it is their responsibility to choose the therapies that suit them best. Individual treatment plans are more effective than rigid guidelines. Our goal is to reduce their chances of having heart attacks or strokes over the long term to the lowest incidence possible. With this effort, I am confident that we will prevent many heart attacks and strokes, while helping patients live longer. Many patients will have a better quality of life as well. Let’s start immediately, by providing comprehensive plans for our patients and letting the word spread, wide and far.
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