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When the mechanism of action
of a substance used in alternative medicine is sufficiently known, the cause of its negative results in clinical trials is then understood.  This article is about the mechanism that explains why chelation therapy is a bust. 


The Pharmacology of Chelation Therapy

By Wallace Sampson, MD.

From Quackwatch, the best site on the ducks at http://www.quackwatch.org/01QuackeryRelatedTopics/chelationpharm.html

The Scientific Review of Alternative Medicine, Fall/Winter 1997.




A small group of physicians claim that "chelation therapy" (CT) can reduce or reverse atherosclerosis by removing calcium from atherosclerotic arterial plaques.[1,2,3] They also claim that CT neutralizes free radicals and eliminates dangerous metals such as lead.[2]

CT is distinguished from approved use of EDTA for indicated conditions. Chelation for hypercalcemia and heavy metal poisoning is approved and effective. It consists of repeated intravenous infusions of sodium EDTA (ethylenediaminetetra-acetic acid), the same material used as an anticoagulant in blood count tubes. The anion EDTA is negatively charged and exchanges its cation for another for which it has greater affinity. The calcium disodium salt exchanges calcium for lead and other heavy metals. It is approved for lead poisoning. The sodium salt exchanges sodium for calcium and is approved for hypercalcemia.[4] This is the molecular form used in CT.

CT as a treatment for atherosclerosis or to prevent degenerative diseases consists of repeated infusions several times per week for a month or more. The intravenous solution bearing the EDTA usually has added to it ascorbic acid, other nutrients, and salts.

Negative evaluations by the American Heart Association and professional societies have not discouraged this use of CT. Practitioners accuse the medical "Establishment" of prejudice and of favoring more expensive coronary artery bypass operations.[3] CT is allowed to continue because Food and Drug Administration regulations allow for use of approved drugs for unapproved purposes. State licensing boards often do not control practices in the absence of demonstrable harm.

The Problems of CT

CT can be criticized on several grounds. First, EDTA is nephrotoxic.[4] In early years of use, deaths occurred from acute renal failure.[5] Sudden death also occurred, presumably from cardiac arrhythmias caused by hypocalcemia[6,7] during the infusion. In recent years fatalities have been reduced by slower infusion of more dilute solutions.[3]

Second, there is no proved efficacy. Uncontrolled trials initially showed mixed or inconclusive results on angina and longevity.[8,9,10] Two recent controlled studies on peripheral vascular disease showed no effect.[11,12]

Third, there are no reasonable theoretical grounds for effectiveness. There is no evidence that ectopic calcium in arteries and elsewhere is mobilized in preference to bone calcium. In fact, present knowledge suggests that plasma calcium is exchanged preferentially with the calcium pool in bone.[13]

Therefore, one would get at least as much osteopenia as decrease in ectopic calcium. In addition, calcium makes up only a small fraction of the volume of atherosclerotic plaques. Even if a plaque's total calcium were removed, the greater part of occlusive material -- cholesterol and reactive fibrous tissue -- would remain.

CT could not be effective even if it were to work the way proponents claim. The stoichiometric features of EDTA binding show that the maximum effect would be negligible. EDTA binds calcium one mole to one. One gram of EDTA binds to 0.120 gm of calcium; 3.0 gm of EDTA -- the usual dose for one infusion -- bind to 0.360 gm of calcium. The average-sized person's total body calcium is about 1.7 kg or 1700 gm.[13] The calcium removed by one infusion is 0.360/1700, or about 2/10,000 of total body calcium. A one-month course of CT would remove at most 2-3/1,000 of the amount of calcium in arterial plaques. In order to remove only 1/10 of the calcium in any structure one would require 530 daily treatments -- or a total of two years at five days per week. At least, one would spend $50,000 in two years to remove less than 10% of the calcium in the arteries, leaving in place the major constituents and bulk of the calcium in the arterial walls.

Meanwhile, one absorbs 0.5-1.0 gm of calcium from the diet. More is absorbed when the serum calcium level drops, and the kidney also conserves calcium when serum calcium is low and parathormone rises in response. If compensatory mechanisms work normally, there would be little net loss of calcium from any structure.

CT and Free Radicals

Proponents have recently shifted ground to claim that EDTA removes other toxic metals such as lead and neutralizes "free radicals."[1,2,3] The former claim is false because sodium EDTA removes calcium, magnesium, zinc, and negligible amounts of iron and other heavy metals. Proponents usually do not even monitor these blood levels and often use unreliable hair analysis. Regarding the free radical claim, although oxygen free radicals are suspected as contributors to aging and degenerative diseases,[14] they are negatively charged so are not neutralized by the negatively charged EDTA.

EDTA could chelate other positively charged metal radicals, but the CT form preferentially binds to zinc, magnesium, and calcium. In addition, free radicals are formed constantly and last only fractions of a second before being neutralized or damaging tissue. EDTA would have to be present all of the time to be effective.

But assume that the 3 gm of EDTA supplies an excess of EDTA to neutralize all free radicals. For an average course of four weeks, the time of exposure to EDTA is about 100 hours (4-hour infusion, 95% excreted by 5 hours; 5 hours per day, 20 days per month). There are 657,000 hours in a 75-year lifetime. A one-month course would protect against less than 1/6,570 of the metallic free radicals one encounters in a lifetime. It is unlikely that this small fraction would make an impact on tissue damage.

An added threat of CT is that there is evidence that the ascorbate added to CT infusions reduces cations iron and copper to the ferrous and cuprous states, creating more peroxides and hydroxyl radicals in the process.[15] The binding of iron by EDTA leaves two unpaired electrons in the outer orbit, available to react with other substances and creating even more free radical damage.


Chelation therapy using small amounts of EDTA is ineffective, and could not work the way proponents claim it does. It is still potentially dangerous because it can produce increased free radical load instead of reducing it.

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