Thursday, January 26, 2006

Death by Chelation, Revisited

Regarding the latest report in the Pittsburgh Post-Gazette about the 5-year old boy who died after receiving disodium EDTA to treat his autism:

Roy Poses was absolutely correct that Dr. Mary Jean Brown, the CDC’s “expert in chelation therapy,” missed the real point of the tragedy: that the child was a victim of quackery, not merely of “medical error.” The truth is even more disturbing than that, however. Dr. Brown may have been technically correct that if calcium-disodium EDTA had been used instead of disodium EDTA, the child would likely not have died of hypocalcemia (though he might have died of another complication; calcium-disodium EDTA is also a dangerous drug). But this was not a simple case of mistaken drug identity, or "look-alike/sound-alike medications," as Dr. Brown supposed. Disodium EDTA is the form of EDTA preferred by the major advocacy group for all implausible uses of "chelation therapy," the American College for Advancement in Medicine (ACAM)*—the same organization that the FTC had cited in 1998 for “false or misleading” claims regarding “chelation therapy” and atherosclerosis.

The reason for that preference seems to be that when EDTA was first being pushed as a miracle cure for atherosclerosis (‘60s-‘70s), its purported mechanism was to leach calcium from plaques. That claim, which can still be found in pro-chelation literature, has largely given way to the theory that chelation works as an anti-oxidant by removing heavy metals such as mercury, lead, copper, and iron. Both of these theories are implausible on stoichiometric and physiological grounds. The disodium form of EDTA persists as the ACAM-recommended preparation, not only for atherosclerosis but for arthritis, Alzheimer’s, Parkinson’s, psoriasis, high blood pressure, scleroderma, cancer, macular degeneration, and more. The rationale for “chelation therapy” in autism, according to advocates, is that the disease is caused by mercury poisoning—mainly from childhood immunizations. This claim is not supported by epidemiologic studies

Dr. Brown might be disturbed to learn that disodium EDTA is the form used in the current, $30 million, Phase III "Trial to Assess Chelation Therapy" (TACT), jointly sponsored by the National Center for Complementary and Alternative Medicine and the National Heart, Lung, and Blood Institute. The reason that NIH investigators chose the more dangerous form of EDTA is that it was “recommended by the American College for Advancement in Medicine” Curiously, it’s almost impossible, merely by looking on the NCCAM website, to discover which salt of EDTA is used in the TACT. Except in the well-hidden RFA (Request for Applications), only “EDTA” is named, without reference to cations.

Thus most descriptions of the TACT are similar to this one posted by the NIH: “EDTA…is approved by the U.S. Food and Drug Administration (FDA) for use in treating lead poisoning and toxicity from other heavy metals. Although it is not approved by the FDA to treat coronary artery disease, some physicians and alternative medicine practitioners have recommended EDTA chelation as a way to treat this disorder.” On the contrary, disodium EDTA has not been approved by the FDA for the treatment of lead poisoning, but only for the emergency treatment of hypercalcemia and dig-toxicity (and for these purposes it is considered obsolete).

The NIH language implies that disodium EDTA for any other purpose is merely “off-label” and is safe, which is what chelationists and their influential champions assert (see p.2 of this slow-loading document). But this is misleading, because the FDA has specifically contraindicated disodium EDTA for atherosclerosis, and a “black box” warning states: “The use of this drug in any particular patient is recommended only when the severity of the clinical condition justifies the aggressive measure associated with this type of therapy.” Thus the numerous unapproved uses of disodium EDTA, prescribed by that strange subculture of practitioners who preach “detoxification” as a near-panacea, do not meet FDA standards for off-label use. On p. 37 of the TACT protocol, version 2, NIH investigators refer to such practitioners as “prominent experts.”

Perhaps unbeknownst to Dr. Brown, her statements would seem to challenge the NIH to explain why it would expose human subjects to a drug that the CDC considers highly dangerous, when a less dangerous substitute is readily available. The larger question is why the NIH would expose 2300 human subjects in a Phase III study of a treatment that has yet to successfully graduate from Phases I or II, and that has not been substantially studied in animals. Federal Code states: “Phase III studies…are performed after preliminary evidence suggesting effectiveness of the drug has been obtained…” The Declaration of Helsinki states: “Medical research involving human subjects must…be based on a thorough knowledge of the scientific literature…and on adequate laboratory and, where appropriate, animal experimentation.”

* Rozema TC. The Protocol for the Safe and Effective Administration of EDTA and Other Chelating Agents for Vascular Disease, Degenerative Disease, and Metal Toxicity. Journal of Advancement in Medicine. 1997;10, 1:5-100


Anonymous said...

FDA is not a body of doctors but merely a body of bureaucrats. I wouldn't trust a drug just because the FDA has approved it. Conversely I wouldn't pass a treatment just because it does not have FDA approval. I undertook a complex Oral Chelation terapy and so did my entire family including mother in law (she also had extremely high blood cholesterol). Well, it worked wonders for all of us. The ney sayers are mainly backing the heart surgeons who make a heck of a living chopping people. Try this one:

Anonymous said...

Currently over 500,000 patient in the U.S. undergo IV chelation therapy annually. The number of patients treated increases by over 10,000 per year.
In 1988 Olszewer, Sabbag, et. al. published data from treatment of 2870 patients treated with IV disodium EDTA. With statistically significant positive outcome.
In the New England Journal of Medicine (the most conservative peer review journal in this country) 2003; 348: 277:286, it is reported that IV Ca++disodium EDTA improve renal function in low level lead exposed patient with chronic kidney disease. IV EDTA supportive data has also been printed in JAMA in 1996 and 2003, the American Journal of Cardiology 1998, Diabetologia, Clin. Endocrin. (Oxford) 1990.
As a scientist,pharmacobiologist and physician, I would have to say that no one has enough evidence to jump to any conclusions to make claims for or against IV chelation with disodium or Ca++ disodium EDTA. Clearly better designed studies need to be carried out and duplicated in random double blind, placebo controlled fashion.
Until then, mavricks may continue to provide this treatment to those seeking it. If done so with protocols for safety set forth by those like Dr. Olmstead of University of Washington dept. of Cardioloy, or UCLA dept. of Cardiolgy, or as taught by ACAM, then currently the safety data and morbidity from treatment is much more favorable than angioplasty. So, no harm done. If future studies indicate positive results, then these mavrick physicians will become hailed pinoneers of medicine. If studies reveal no benefits from chelation tx, they will be forgotten as the blood letters and leach doctors of the 19th century.
In science we must always be open minded, for the unkown is just that... unknown. Our emotions and beliefs should not direct our willingness to investigate.

Thank you