Why the NIH Trial to Assess Chelation Therapy (TACT) Should Be Abandoned

Kimball C. Atwood IV, MD; Elizabeth Woeckner, AB, MA; Robert S. Baratz, MD, DDS, PhD; Wallace I. Sampson, MD

Disclosures

Medscape J Med. 2008;10(5):115 

In This Article

I. A Brief History of EDTA Chelation for Cardiovascular Disease

Beginning in 1956, a few small, uncontrolled case series reported that IV Na2EDTA seemed to have striking, beneficial effects on CAD, PVD, and cerebrovascular disease.[32,50,51,52,53] By 1963 it became clear that those reports, which were based primarily on subjective outcomes, had been wrong. When followed for more than a few months, subjects with CAD had rates of death and MI similar to those expected for untreated patients at that time.[54] Two small series of subjects with intermittent claudication had also shown no evidence of improvement.[54,55] Several autopsies from various series had revealed no evidence of decalcification of plaques or reduction of plaque size. Within a couple of years, case series of IV Na2EDTA for cardiovascular disease no longer appeared in the academic medical literature.

Nevertheless, a tiny group of advocates continued to practice "chelation therapy," usually in the office. Then as now, it consisted of an initial series of IV infusions of disodium EDTA, magnesium, vitamins, and minerals, followed by monthly "maintenance" infusions. At first, chelationists called the treatment a "chemical Roto-Rooter" or a "chemical endarterectomy," but eventually promoted it as a near-panacea for conditions as disparate as multiple sclerosis, schizophrenia, autism, cancer, peptic ulcer, back pain, and chronic obstructive pulmonary disease.[34,56,57] According to a recent article reprinted on the Web site of the ACAM, the most conspicuous organization of chelationists, "heart patients undergoing chelation typically receive 30 to 40 weekly treatments, then are scheduled for lifelong monthly sessions to keep the arteries free of plaque.[58]" The article quoted the price of a single chelation treatment -- the ingredients of which cost a few dollars[59] -- to be $120-$125. In addition, according to the Trial Chelation Consultant for the TACT,[4] there are "nutritional supplements in the range of $20 to $200 per month [and] diagnostic study costs and professional fees...ranging from a few hundred to several thousand dollars.[57]"

The article on the ACAM Web site reported that TACT co-investigator and "prominent expert[4]" Allan Magaziner "said his center [was] treating 400 to 500 heart patients with chelation.[58]" L. Terry Chappell, another "prominent expert" and co-investigator, told a government hearing in 1999 that he had treated "at least 2500 to 3000 patients with chelation therapy" over a period of about 18 years, but that this represented "only 20-25% of [his] medical practice.[41]" Former ACAM president and convicted extortionist Ted Rozema,[60] also a TACT co-investigator, testified at the same hearing that in 16 years he had treated "over 2000 patients [with] over 80,000 infusions of EDTA.[41]" The 2001 TACT protocol states that Trial Chelation Consultant, prominent expert, and TACT co-investigator Dr. Martin Dayton, who was convicted of conspiracy and mail fraud in 1986,[61] "has clinical experience with over 75,000 chelation infusions.[4]" The late H. Ray Evers, a convicted felon revered by chelationists as a "pioneer of chelation therapy," reportedly claimed to treat, during the 1970s, 1000 patients per year at $3000 each.[62,63] According to a former practitioner, "chelation is a big cash cow.[59]"

The Rise of Activism-Based Medicine: Laetrile Spawns Chelation

In their early days many chelation advocates also favored, and some still favor, the lucrative quack cancer treatment Laetrile. Most chelationists still offer other dubious treatments, such as IV hydrogen peroxide, "detoxification," hair analysis, "antineoplastons," "live cell therapy," coffee enemas, "ozone therapy," magnets, homeopathy, and more, while denigrating the methods of modern medicine and public health, including surgery, pharmaceuticals, immunizations, fluoride, and controlled clinical trials.[7,64] By the mid-1970s, their activities had drawn the attention of the FDA, Medicare, state medical boards, professional ethics committees, and criminal prosecutors.[18,65,66,67] In an effort to protect themselves, advocates established organizations, symposia, "certification boards," journals, political connections, lobbies, and -- a few years later -- political action committees, IRBs, and "Achievement Awards" (at times bestowed upon, presumably, unsuspecting recipients[68]).

Among such early organizations were the National Health Federation, which had been around since the 1950s and included, among its officers and board members, Drs. H. Ray Evers, Garry Gordon, Michael Gerber, James Privitera, W. Douglas Brodie, and Bruce Halstead -- all chelationists[69]; and the Committee for Freedom of Choice in Cancer Therapy (later renamed the Committee for Freedom of Choice in Medicine), founded by John Bircher and Stanford lab technician Robert Bradford who, in addition to smuggling millions of dollars worth of Laetrile, hawked filmstrips entitled Chelation Therapy and the Killer Diseases.[63,70,71] Halstead was the Committee's vice president. Each of these organizations was primarily concerned with protecting its members' freedom to peddle Laetrile.[69,70,71,72,73]

In 1973 chelationists established the American Academy of Medical Preventics (AAMP) "to help educate physicians and to promote the use of EDTA chelation therapy for cardiovascular disease.[34]" Among the founders, officers, and key members were the 6 physician members of the Laetrile organizations named above. Four of the 6 -- Evers, Halstead, Brodie, and Privitera -- were subsequently convicted of felonies.[62,67,69,74,75] The first AAMP president was Harold W. Harper, another Laetrile advocate.[75] When Laetrile sales were mostly forced underground by the US Supreme Court's decision in the Rutherford case of 1979[76] (the AAMP had filed an amicus curiae brief in opposition to the eventual decision[77]), chelation emerged as heir-apparent to the title of "most successful medical fraud in history.[78]"

In its early years the AAMP mounted one of the first "direct-to-consumer" drug advertising campaigns in the form of "An Open Letter to Those Persons Interested in Chelation Therapy.[79]" The letter suggested that chelation was better, safer, and cheaper than the mainstream alternatives:

All too often, the remarkable benefits available from low fat dietary regimes, in conjunction with megavitamin, chelation, and hyperbaric oxygen therapy are not offered to patients who may be facing needless vascular surgery, such as bypass heart surgery, or even amputation of an extremity (because of impending gangrene), or a future of continual pain and disability and eventual premature death, when frequently these alternative approaches could have provided as good, if not better results at less cost, and without surgery.[79]

The letter recommended a "filmstrip presentation with sound, suitable for showing to all community groups," which "is self explanatory and does not require a physician's attendance.[79]" The filmstrip appears to have been Bradford's Chelation Therapy and the Killer Diseases: The reader could buy it for $50 from the "Committee for Freedom of Choice.[79]" The letter exhorted readers to "become involved in one or both of the lay organizations that are attempting to increase the general public awareness regarding these new therapies": the Association for Chelation Therapy and the National Educational Society for Natural Healing.

The AAMP also hired a law firm to advocate for chelation.[80] Within a few years, AAMP members had founded the American Board of Chelation Therapy (ABCT), GLACM, and the American Preventive Medical Association (APMA).[34] In 1986, the AAMP changed its name:

The members of the American Academy of Medical Preventics (AAMP), recognizing that their training, experience, and clinical practice would form the basis for emergence of new medical paradigm, [sic] changed the name of their organization to the American College for Advancement in Medicine (ACAM).[34]

The ACAM now refers to itself as "the voice of Complementary, Alternative and Integrative Medicine.[81]" In 1988, the ACAM created the Journal of Advancement in Medicine, which has since published most of the pro-chelation articles.[82] In 2000, the journal's name was changed to Clinical Practice of Alternative Medicine.[83] The AAMP offspring have also changed their names: the ABCT to the American Board of Clinical Metal Toxicology (ABCMT), the GLACM first to the Great Lakes College of Clinical Medicine (GLCCM) and recently to the International College of Integrative Medicine (ICIM), and the APMA to the American Association for Health Freedom (AAHF).[84,85,86]

The ACAM "Industry Directory" currently lists American Biologics as one of its "Legacy Partners.[87]" American Biologics has marketed numerous quack products, including Laetrile.[70] It is owned by convicted Laetrile smuggler Robert Bradford, who founded it in the early 1970s.[70,71]

Reports of uncontrolled series of IV Na2EDTA for cardiovascular and other diseases began to reappear in about 1980. Unlike the original reports, these were written exclusively by advocates, all members of the AAMP/ACAM, and published, with 1 or 2 exceptions, in little-known, nonrefereed journals. Several articles reported sample sizes in the hundreds or thousands. Each series reported dramatic improvements in 80% to 90% of subjects.[34,57,88,89]

Complications, if mentioned, were described as minor. Rates of death from any cause, if mentioned, were implausibly low. For example, in a report of 2870 subjects, most of whom were said to have CAD (844 subjects), PVD (1130 subjects), or cerebrovascular disease (504 subjects), followed in Brazil for a 2-year period in the early 1980s, the authors reported 7 deaths; 2 were in the CAD group.[90,91] In a subsequent report, the same authors wrote that when chelation had been "administered according to the ACAM protocol," there hadn't been "a single reported incident of renal failure or death since 1960.[92]" As discussed in Part III of this article, the claim was false and the authors had reason to know it.[18,93,94] One of those authors, James Carter, is now a TACT co-investigator.[7]

Two reports were "meta-analyses" of the others, reporting more than 20,000 subjects and creating, for their statistical analyses, imaginary control groups "defined to have no improvement in cardiovascular capability.[95,96]" The first author of those reports is "prominent expert" L. Terry Chappell, also now a TACT co-investigator.[4,7]

One of the most prolific chelation authors is Edward McDonagh, DO, the author or co-author of more than 30 exclusively pro-chelation articles.[89] According to a reporter:

In December 1996, the [Missouri medical] board brought suit against McDonagh, alleging 13 counts of negligence and malpractice.

[The] state investigation of McDonagh's records revealed a pattern: Since the late '70s, he'd diagnosed patients without obtaining their medical records or recording the results of their physical exams. Other mistakes were charted on the racked bodies of former patients. In the 1980s, he misdiagnosed a case of gangrene, which festered until the patient fell into a coma and had to have his leg amputated above the knee.

The only consistent thing about his files was that each record had serious inconsistencies, argued David Meyers, a KU cardiologist who analyzed McDonagh's records for the board's initial case against the doctor. Meyers testified that McDonagh hadn't used orthodox methods to treat anything. In some cases, McDonagh's prescriptions and diagnoses ran contrary to existing medical knowledge.

On the witness stand, McDonagh argued that he had kept slipshod records, recording only positives about his experiments, to avoid possible liability lawsuits.[44]

That admission resulted in the following exchange between the board's attorney and Dr. McDonagh:

Attorney Bradford: "Do you think it weakens the validity of your conclusions as represented by your papers that you can't show your underlying data?"

Dr. McDonagh: "I think it might.[44]"

Despite such testimony, the administrative hearing commission found in favor of McDonagh. The opinion was upheld by a circuit court, but in 2003 it was "reversed and remanded" by the Missouri Supreme Court.[97]

A few years before that testimony, Dr. McDonagh had "failed to pass the Special Purpose Examination after the Board found probable cause to question his competency to practice medicine," and thus in 1995 the Missouri Board revoked his license to practice medicine.[98] He continued to practice, however, because the "Board action [was] stayed by court order on 1/17/95 while appeal was pending.[98]" In 1997 the Board reinstated his license "in accordance with a Settlement Agreement.[98]" McDonagh was the subject of a series in the Kansas City Star investigating his peddling of chelation to trusting, scientifically naive Amish and Mennonite patients.[99]

As it became clearer that the decalcification theory was no longer taken seriously by medical scientists, chelationists sought new explanations for the putative effects of Na2EDTA, though never relinquishing the old one.[80,100] Several were proposed, among them platelet function inhibition, anticoagulation, lowering of serum lipids, and calcium channel blockade. The most popular one, which persists, was based on the removal of toxic heavy metals. Through the removal of iron, mercury, aluminum, lead, and other metals that, according to advocates, are toxic even at the miniscule levels found in most people, the panacea effects of chelation are explained.

Thus, proponents claim:

  • Chelation reverses autism by removing mercury introduced by childhood immunizations and dental amalgams.[101,102]

  • It reverses Alzheimer's disease by removing aluminum, copper, and zinc from the brain.[35,103]

  • It reduces high blood pressure, which "has been shown to be associated with increased total body burden of lead.[104]"

  • It prevents cancer because "the metals interact with the DNA, RNA, enzymes, mitochondria, and cellular components to contribute to the causation of diseases. The immune system appears to be effected [sic] to allow cancers already in the body to manifest into a diseased state.[104]"

  • It reverses atherosclerosis by reducing "free radical" production dependent upon iron.[105]

  • And more.

All in all, according to Elmer Cranton, a past president of the ACAM, one of the "prominent experts" named to the TACT Liaison Committee to the ACAM,[4] and author of Bypassing Bypass Surgery: Chelation Therapy: A Non-Surgical Treatment for Reversing Arteriosclerosis, Improving Blocked Circulation, and Slowing the Aging Process[106]:

The use of EDTA to restore the balance and distribution of essential metallic elements, while at the same time removing toxic heavy metals and catalytic free iron, has been shown to slow or arrest progression of diseases of aging. Other benefits of chelation occur from uncoupling of disulfide and metallic cross-linkages between molecules, by normalization of calcium metabolism, by reactivation of enzymes poisoned by lead and other toxic metals, and by restoration of normal prostacyclin production along blood vessel walls. Lasting benefits follow a series of intravenous EDTA infusions, plus nutritional supplementation and lifestyle improvements.

This well-documented, safe, and effective therapy deserves widespread recognition and acceptance.[105]

Removing toxic heavy metals has the additional appeal of parroting an approved use of the similarly named, but different drug: CaEDTA.[31] Chelationists and the TACT literature frequently conflate the 2 drugs, as in this statement posted on the NCCAM Web site: "When used as approved by the FDA...for treatment of heavy metal poisoning, chelation with EDTA has a low occurrence of side effects.[3]" Chelation advocacy organizations cloak their agenda in euphemism: The ICIM urges Web-surfing practitioners to "Check out our friends at ABCMT for more information about certification in Heavy Metal Toxicology[85]"; in 1998 the ACAM's phone number was 1-800-LEADOUT.[34]

Such explanatory sleight of hand has fooled not only patients, but regulators. After the recent hypocalcemic death of a 5-year-old autistic boy in the office of an ACAM member, the chief of the US Centers for Disease Control and Prevention (CDC) Lead Poisoning Prevention Branch mistakenly "determined 'without a doubt' that it was medical error, and not the therapy itself, that led to the death of [the] 5-year-old boy," because "'only Calcium Disodium EDTA should be used...No medical professional would ever have intended to give the child Disodium EDTA.[107]'" Similarly, the Pennsylvania Board of Medicine subsequently charged that the practitioner had "...used disodium EDTA to chelate [the boy] for metal toxicity which should be treated with CaNa2EDTA instead.[108]"

After the hypocalcemic death of a 53-year-old woman in Oregon in 2003, to whom a naturopath had administered chelation therapy in order to "remove heavy metals," the CDC reported: "The Oregon State Naturopath Licensing Board is conducting an investigation to determine whether Na2EDTA or CaEDTA was administered to this patient.[13]" The Oregon Board investigated and found that the naturopath "was medically negligent in performing a chelation procedure," but the order does not name the chelating drug.[109]

Curiously, the Oregon naturopathic formulary lists EDTA without a cation, adding, "Board approved certification required before therapeutic IV chelation is allowed.[110]" In 2003 such certification was likely to have come from the ACAM: The Oregon Naturopathic Board included, on its list of approved continuing education courses, an ACAM course entitled "Heavy Metal Detoxification.[111]" Thus, in our opinion it is virtually certain that Na2EDTA was the drug that killed the woman, and "therapeutic IV chelation" is a state-sanctioned oxymoron in Oregon. Would the Board have found the naturopath, himself an ACAM member, at fault for administering the very drug that its approved certification course had urged him to administer?

In each case, regulators missed the point and revealed their naiveté about fraudulent medical practices: These "medical professionals" almost certainly intended to give disodium EDTA, although there was no indication for any chelating agent. Each practitioner was, ipso facto, "medically negligent in performing a chelation procedure,[109]" not merely in performing it in an especially reckless way. In our opinion, no competent, ethical, medical professional would have given EDTA in any form.

Chelationists have also used the toxic heavy metals hypothesis for another purpose. Health insurers typically do not cover chelation treatments because of lack of demonstrated efficacy, so most patients pay out of pocket.[112] In order to collect payment from insurers, some chelationists falsely report that patients have toxic levels of heavy metals.[113]

The ACAM's "certification" organization is the ABCMT (formerly the American Board of Chelation Therapy). It is not recognized by the American Board of Medical Specialties. At the time of its creation in 1982, it offered this "Definition of Chelation Therapy":

A form of medical therapy designed to restore cellular homeostasis using various mechanisms including metal binding and restoring ionic balance. For optimal results Chelation Therapy should be complimented [sic] by utilizing other modalities such as nutrition and exercise.[114]

Chelationists have recently contrived to change both standards of care and third-party payments without having to resort to evidence. The ABCMT has implored all state medical boards to adopt its "Standard of Care for Increased Body Burden of Toxic Metals.[102]" This declares the ABCMT to be "the only professional organization with over twenty years of continual teaching, testing, monitoring results and seeing marked improvement in patients' symptoms with metal detoxification." It extols hair analysis and "provoked urine testing," and refers to "in office intravenous detoxification of documented toxic metals" without naming chelation per se. It "resolves" that "established detoxification techniques, which have been proven safe and effective over time, be employed to detoxify these patients.[102]"

In a "Cover Letter to all State Medical Boards" sent with the "Standard of Care" document in July 2004, Chairman Robert Nash wrote:

ABCMT is now ready to certify competence and assist in your concerns about patient and public safety.

Physicians who complete the toxic metals toxicology course and successfully pass the appropriate tests should be recognized as Physician Clinical Metal Toxicologists by each state's medical board.

If you have not provided us with a more thorough, updated Standard of Care within 30 days, we will conclude that our Standard of Care has been accepted.[115]

Nash is a former ACAM board member and is now, according to the abstract of a recent article by him, "on the Data and Safety Management Board" [sic] of the TACT.[47] Assuming that Nash is a member of the Data and Safety Monitoring Board of the TACT, he appears to have conflicting interests.

Nash was an "expert witness" called by chelationist Robban Sica, a TACT co-investigator who filed a federal lawsuit in 2004 in an attempt to prevent the Connecticut Bureau of Health Care Systems from disciplining her for numerous instances of substandard care.[116,117,118] In ruling against Dr. Sica, the federal judge wrote:

While most "mainstream" physicians would see Dr. Sica as treating, for example, cardiovascular disease with EDTA Chelation, Drs. Nash and Sica concede only that Dr. Sica was treating [heavy metal] toxicity....[119]

At least 1 state medical board appears to have been duped by the heavy metals ploy even prior to the "Standard of Care for Toxic Metals" project. In 2001 the Missouri Code of State Regulations added language about chelation. It begins with a promising statement:

...the board declares the use of ethylinediaminetetracetic acid (EDTA) chelation on a patient is of no medical or osteopathic value except for those uses approved by the Food and Drug Administration (FDA) by federal regulation.[120]

Notwithstanding that preamble:

The board shall not seek disciplinary action against a licensee based solely upon a non-approved use of EDTA chelation if the licensee has the patient sign the Informed Consent for EDTA Chelation Therapy form, included herein....[120]

The consent form warns that chelation "may be harmful" and "has been authoritatively demonstrated to be ineffective in the treatment of vascular diseases," (emphasis in the original) but also includes these statements:

My physician has explained to me and I fully understand:

(a) that the use of ethylenediaminetetracetic [sic] acid (EDTA) has been approved by the federal Food and Drug Administration (FDA) only for the use of removing heavy metals from the body;

(b) that the FDA has not approved the drug EDTA for treatment of diseases or conditions other than heavy metals poisoning;

...(i) that the Missouri State Board of Registration for the Healing Arts strongly recommends that Missouri citizens not undergo EDTA chelation therapy for the treatment of any human disease, illness, malady, or physical condition other than heavy metals poisoning;

Notwithstanding having read and understood the above, I hereby elect to undergo treatment with EDTA chelation therapy under the protocol recommended by the American College for the Advancement in Medicine (ACAM) [sic].[120]

It seems odd that the Missouri Board would warn citizens to avoid chelation, which it deems dangerous and ineffective, but declines to discipline licensees who push it. The Board appears to have been unaware, when it wrote that rule, that the statements about heavy metals undermine the statements urging citizens to refuse chelation, and are also quite false: The EDTA salt recommended by the ACAM protocol,[33] Na2EDTA, is not approved by the FDA for removing heavy metals.[12] Even the somewhat safer CaEDTA is approved for the removal of only 1 heavy metal (lead), not heavy metals.[31] Because there is nothing in the Missouri rule requiring a proper diagnosis of "heavy metals poisoning," chelationists can conform to the letter of the law by doing exactly what they've been doing for years: prescribing chelation ostensibly to remove heavy metals, no matter what may or may not ail the patient.

Several other state medical boards or practice acts have language addressing unapproved uses of EDTA or chelation.[121] They vary in the extent to which they tolerate or condemn the practice, but most appear to have been misled by the heavy metals gambit. Tennessee is a laudable exception.[122,123]

Statements that disodium EDTA removes toxic heavy metals suggest, at least in regard to CAD, that several unproven speculations are true: (1) that individuals are "poisoned" by trace amounts of ubiquitous environmental substances; (2) that these alleged poisonings cause atherosclerotic CAD; (3) that disodium EDTA safely and effectively removes these unnamed heavy metals; and (4) that it thereby reverses CAD.

Despite their organizational efforts during the 1970s and 1980s, chelationists continued to be inconvenienced by regulators and criticized by influential physicians. Alfred Soffer, the Editor-in-Chief of both Chest and Archives of Internal Medicine, had performed trials of Na2EDTA during its early days and concluded that it was not useful for CAD or PVD.[55] In a series of editorials, he called chelationists "pseudoscientific zealots" whose practices were "an abuse of the physician's freedom of choice.[9,10,11]" Others referred to promotions of chelation as "the next generation of medical sleight of hand," "deceptive," and "pseudoscience"; to chelation itself as "fringe medicine," "scientific chicanery," "sham therapy," and a "medical fraud" with "all the classical hallmarks of quackery"; and to its practitioners as "super salesmen" and "modern quacks," who "rip...willing victims off for $3000 to $5000 for a few weeks of injections of EDTA.[63,78,124,125,126]"

Chelation for atherosclerosis was condemned by the Medical Letter, the American Heart Association (AHA), the American College of Physicians, the American Academy of Family Physicians, the American Society for Clinical Pharmacology and Therapeutics, the American College of Cardiology, the American Medical Association, and the American Osteopathic Association.[127] In 1989, the FDA included chelation therapy on its list of "Top 10 Health Frauds.[128]" Within a few months, however, the FDA bowed to pressure from former AAMP President Ross Gordon to remove chelation from the list because of a pending "approved study" that was never completed.[34,129]

In response to such criticism, in the early 1990s the ACAM and the GLACM created their own IRBs.[34] The GLACM Web site explained the mission of its IRB:

With an increase in the number of physicians who are under review from state medical boards for practicing alternative medicine, the IRB may offer protection. The IRB recommends that any GLACM members who want to organize procedures in their offices and get peer-reviewed, officially-sanctioned research contact Karen at Dr. Chappell's office (419) 358-4627, to get guidelines for preparing a proposal.[130]

The GLACM IRB approved numerous projects eventually subjected to criminal, civil, and FDA actions, among which were "Evaluation of the Effect of the Immunotherapeutic Technique Enzyme Potentiated Desensitization (EPD) for a Considerable Variety of Illness/Conditions/Diagnostic Conditions," "Extracorporal Hemo-Infusion Therapy," "The Effects of DMPS (Dimercapto-propane sulfonate) in a Total Mercury Detoxification Protocol," "Insulin Potentiation Therapy," and "Gene-Activated Therapy (GAT) for Treatment of Cancer.[131,132]"

At least 2 projects involved the deaths of experimental subjects: The "induced malaria therapy for HIV" study conducted in China by Henry Heimlich, and the "DMPS Mercury Detoxification" study conducted by IRB member Paula Bickle, who had obtained her "PhD" from a mail-order degree mill.[133,134,135,136]

Another study approved by the GLACM IRB was exposed as a fraud after "Stimulated Autologous Immune Serum" was sold to a woman for $15,000 with the promise of "an excellent chance [that she] would respond favorably to the serum treatment and that it could effect a cure of her [ovarian cancer].[137]" A laboratory analysis subsequently found the "serum" to consist of "water, lactic acid, a dye substance, and no protein material.[137]" GLACM IRB member George Kindness was the president of the company, Amscot Medical Labs, Inc., that had manufactured the serum. According to a 22-count criminal federal indictment in 2003, Kindness "falsely represented to FDA investigators that he had an M.D. in general medicine.[138,139]"

In 1999 the FDA inspected the GLACM IRB and found multiple violations of federal regulations.[140,141] IRB members had voted to approve their own projects. Some projects involving new drugs were approved without having Investigational New Drug Applications. Several informed consent documents were found to lack "the basic elements"; the following examples are quoted from the inspector's report:

  • There is no statement indicating that the study involves research.

  • There is no description of the procedures to be followed.

  • Procedures that are experimental are not identified.

  • There is no description of any reasonably foreseeable risks or discomforts to the subject.

  • Exculpatory language is used through which the subject is apparently made to waive their [sic] legal rights.

  • There is no statement indicating that participation in the study is voluntary...

  • There is no description of additional costs...

  • [The] statement appears to suggest that this investigational therapy is superior to conventional therapies...

  • [The] statement...appears to suggest that this investigational therapy is safe.

  • There is no disclosure of appropriate alternative...treatment[s] that might be advantageous to the subject.[140]

Referring to "the IRB's written policies and procedures," the inspector wrote:

It appears that this document was written not for the purpose of having a relevant, functional, and useful document for the IRB's operations but more for the purpose of fulfilling a regulatory requirement for written procedures.[140]

In 2000 the FDA banned the GLACM IRB from approving new studies or admitting new subjects to ongoing studies. The FDA letter to the IRB secretary, L. Terry Chappell, concluded: "Based on the deficiencies found during this inspection, we have no assurance that your IRB procedures are adequately protecting the rights and welfare of the human subjects of research.[141]"

The FDA did not inspect the closely related ACAM IRB, but we believe that if it had the findings it would have been similar. That IRB's "Sample Protocol for Chelation Therapy for Arteriosclerotic Disease," updated in 1993, stated that the study's purpose "is to accumulate evidence to demonstrate the effectiveness and safety of chelation therapy for arteriosclerotic disease.[142]" It asserted that "3500 abstracts attest to the efficacy and validity of EDTA chelation therapy," but made no mention of a recent controlled trial failing to demonstrate effectiveness.[21,22] It recommended "self-selection" of subjects to receive EDTA after they had been told that it works. It did not stipulate real control groups or blinding, but recommended that patients serve as their own historical controls. It described mainly subjective outcome measures.

The Sample Protocol's Consent Form stated:

I understand that this project is conducted under the aegis of the Institutional Review Board ("IRB") of the American College for Advancement in Medicine ("ACAM"), for the purpose of establishing the effectiveness of treatment of arteriosclerotic diseases by intravenous ("IV") administration of EDTA with magnesium, according to protocol. The study will continue until this therapy is approved by the Food and Drug Administration.[142]

The Consent Form falsely suggested that the FDA had approved Na2EDTA for the treatment of heavy metal toxicities, and stated that for atherosclerosis the drug was "considered 'experimental' by most physicians." It referred to "persantin" [sic] as "experimental and unproven," thus implying that for treating atherosclerosis, "most physicians" would rate chelation at least as favorably as they rated dipyridamole (Persantine). The Consent Form required the subjects -- not the "treating physicians" -- to decide whether to consider standard medical and surgical therapies: "If I desire further information about these types of drug therapy, I will ask my physician...There are various kinds of vascular surgical procedures, and if I am interested in these I will ask my physician...I understand that all these therapies have certain risks about which I should ask my physician if I am interested.[142]"

Those statements and the following paragraph in the Consent Form illustrate what the FDA Inspector presumably meant when he criticized the GLACM consent forms as "exculpatory":

I understand that no compensation for participation in this study will be provided by Dr.________, his office, or the ACAM or the IRB, and I also understand that neither ACAM nor the IRB has a policy to medically treat or compensate for physical injuries incurred as a result of participating in biomedical or behavioral research. I understand and agree that ACAM is not a participant in the study and that the IRB merely serves as a reviewer and collator of the data produced under this study. I expressly agree, as a condition of my participation in this study, that ACAM and the IRB shall not in any manner be responsible for any physical injuries incurred as a result of my participation in the study and I waive, in advance, any claims against either and both of them [sic].[142]

In 2001 both the GLACM and the ACAM IRBs "ceased operations," citing FDA "requirements" and "restrictions.[143,144,145]" At least 8 former members of the GLACM and ACAM IRBs are now TACT co-investigators.[7] Two, Drs. Chappell and Ralph Miranda, are "prominent experts" named to the TACT Liaison Committee to the ACAM.[4] Dr. Chappell was also a member of the NIH Special Emphasis Panel that reviewed the original TACT proposal.[39,43] It is instructive to compare Dr. Chappell's opinion of the GLACM IRB[146] with that of the FDA.

Meanwhile, in response to the tiny but shrill minority of physicians promoting chelation (the ACAM had fewer than 400 members in 1986), a few academic investigators performed RCTs. Between 1991 and 2002, four adequately designed trials and several substudies, involving 285 subjects, were reported.[21,22,23,24,25,26,27,28] These compared Na2EDTA with placebo for several objective measures of CAD or PVD. None showed an advantage for Na2EDTA.

Other authors have challenged the hypothetical mechanisms by which Na2EDTA was claimed to attenuate the process of atherosclerosis:

  • The dosing of Na2EDTA, although capable of toxicity in the short run, is far too small to effect a significant, lasting reduction of metallic free radicals or calcium.[147,148]

  • EDTA is relatively ineffective in removing mercury, iron, and copper, as contrasted with lead, because the former metals are more tightly bound to tissues and proteins.[147,148]

  • There is evidence of EDTA's paradoxical generation of reactive oxygen species in the presence of iron, and a possible augmentation of that effect by high ascorbate concentrations, such as those in the chelation solution advocated by the ACAM and used in the TACT.[147,148,149,150] Thus, "instead of protecting against and neutralizing metallic free radicals, EDTA in the presence of iron and ascorbate produces free radicals and potentially induces the changes that it is intended to prevent.[148]"

More recently, it has become clear that clinical trials of antioxidants, even of those that had shown promise for preventing and treating atherosclerosis in laboratory and animal studies, have been disappointing.[151] Thus well before the TACT began to recruit subjects, 2 experts in atherogenesis had called for a moratorium on clinical trials of antioxidants: "Instead, we should concentrate on developing the scientific base that will enable us to design an appropriate trial to test the oxidation hypothesis.[151]"

Controlled trials notwithstanding, chelationists refused to accept negative results, claiming that the authors had been dishonest because of "vested interest[s] in catheterization and surgery"; that the trials hadn't followed the "ACAM protocol" closely enough; that the results had actually been favorable to chelation; that one trial had been too long, another too short; and more.[57,94,152,153,154,155,156,157,158,159,160,161,162] To counter the negative publicity of disconfirming RCTs in the 1990s, the ACAM posted "Consumer Information" on its Web site:

Chelation therapy is a safe, effective and relatively inexpensive treatment to restore blood flow in victims of atherosclerosis without surgery.

Every single study of the use of chelation therapy for atherosclerosis which has ever been published, without exception, has described an improvement in blood flow and symptoms. Adverse editorial comment to the contrary lacks evidence and stems primarily from physicians with a vested interest in catheterization and surgery.

Chelation therapy promotes health by correcting the major underlying cause of arterial blockage. Damaging oxygen free radicals are increased by the presence of metallic elements and act as a chronic irritant to blood vessel walls and cell membranes. EDTA removes those metallic irritants, allowing leaky and damaged cell walls to heal. Plaques smooth over and shrink, allowing more blood to pass. Arterial walls become softer and more pliable, allowing easier expansion. Scientific studies have proven that blood flow increases after chelation therapy.[152]

In 1998 the Federal Trade Commission (FTC) ordered the ACAM to stop advertising chelation as effective against cardiovascular disease.[163] Nevertheless, the ACAM continued to publish similar statements. According to its Position Paper on EDTA Chelation Therapy, posted on its Web site as recently as June 2003 and still posted on the HealthWorld Web site, "hundreds of doctors nationwide have successfully treated hundreds of thousands of patients with EDTA chelation therapy," not only for coronary and other vascular diseases, but for "dementia, cancer, arthritis and numerous other diseases...; it is a safe and effective treatment for atherosclerotic vascular disease, as it consistently improves blood flow and relieves symptoms associated with the disease in greater than 80% of the patients treated." It is not merely complementary to standard treatment, but "an effective first step alternative to surgical treatment for atherosclerotic vascular disease in most cases.[164]"

Most chelationists include promotional language on their own Web sites. Of the nearly 100 "chelation practices" involved in the TACT, about 80 have Web sites. Of those, at least 70 promote chelation.[7]

In 1997 and 2000, "complementary medicine" researcher Edzard Ernst authored 2 critical reviews of Na2EDTA for atherosclerosis, each concluding that the method "should now be considered obsolete.[165,166]" After the first review, chelationists L. Terry Chappell and John Wilson wrote an angry rebuttal to the editor of Circulation.[158] Dr. Ernst offered this response:

Regardless of what Chappell and Wilson state, chelation therapy is not based on good science.

A perhaps more important point relates to a repetitive pattern in the scientific investigation of "bogus" therapies. Proponents first manage to mobilize supporters to campaign in their favor. This brings financial gain. When skeptics ask about the evidence, the burden of proof is swiftly put on their shoulders, and the lack of evidence is made to look like a "conspiracy" of orthodoxy against the alternative. If scientists then decide to rigorously test the method, its proponents would celebrate this as a breakthrough for their method. Again, this amounts to financial gain. Subsequently, a study may prove that the method is ineffective. Proponents now claim that the research was flawed, did not adhere to their protocol, or was wrongly analyzed. The press coverage yet again brings financial gain. This pattern repeats itself with depressing regularity, e.g., when laetrile or Di Bella's cancer cure were promoted. I wonder whether chelation therapists are trying to play a similar game.[158]

That conjecture appeared in print in January 1999. Dr. Ernst was soon proven correct.

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