Argh! Chelationists are mailing pitches to my office!

A few days ago, I had been thinking that it's been a long time since I've blogged about alternative medicine. I was going over a list of potential topics, debating whether I should talk about alt-med in general or pick specific "therapies." And then, there it was, sitting in the in-box on my desk at work, a flyer.

Damn. Time to get busy. (On the other hand, I was grateful for the blogging idea!)

The flier was from a local nursing/rehab home, and it read:

Chelation Therapy: The Secret for a Healthier, More Energized Life!
GHL, MD - Guest Speaker
XXX Nursing/Rehab Center

Chelation therapy may be the most successful method to extend maximum life span. It is a safe, effective therapy utilizing EDTA (natural preservative), which is administered intravenously in a doctor's office. Often, angina pain goes away, an increase in energy is experienced, along with clarity of thought, and a reduction in pain.

To register for this free community program, call the XXX Education Foundation at (XXX) XXX-XXXX
Limited to the first 35 callers.

Chelation therapy has helped with:

Aches and pains
Hardened or blocked arteries
Alzheimer's
Elevated blood cholesterol
Leg cramp pain (claudication)
Diabetes
Angina pain
Osteoporosis
Poor circulation
Cold extremities
Elevated blood pressure
Skin ulcers
Kidney stones
Impaired memory or concentration

Damn again. This had to be perhaps the most exaggerated, deceptive sales pitch I had ever seen for chelation therapy! Osteoporosis and kidney stones? (Never mind that chelation therapy would be expected, if anything to make osteoporosis worse. Never mind that chelation therapy can actually damage the kidneys, rather than cure stones.) There were claims made in this flyer for chelation therapy that even I had never heard before! (And, having been a regular on misc.health.alternative, I thought I had heard them all.)

Before I go on, perhaps I should explain exactly what chelation therapy is and what its advocates claim it can do. Chelating agents (like EDTA) are ring-shaped molecules that are water-soluble and bind divalent metal ions like calcium, magnesium, manganese, mercury, aluminum, nickel, zinc, and iron, closing around them like a ring, preventing them from exercising their toxic effects and allowing them to be more easily excreted by the kidneys. The calcium salt of EDTA exchanges its calcium ion for ions for which EDTA has more affinity, like lead, and is used for lead poisoning; the sodium salt exchanges its sodium ions for calcium and is used to treat hypercalcemia (from malignancy, for example). Chelation agents are used in conventional medicine to treat heavy metal toxicity and are very effective for that purpose. One particular purpose for which a chelation agent (deferoxamine) is very effective is for the treatment of iron overload from multiple transfusions.

So where does cardiovascular disease come in? The atherosclerotic plaques that result in the narrowing of the lumen of blood vessels, causing low blood flow to the heart when in the coronary vasculature and claudication or limb loss when in the peripheral vasculature of the leg, often have calcium deposits in them. Back in the 1950's some scientists postulated that that "hardened" arteries might be "softened" if the calcium were removed with a chelation agent. Sounds nice, neat, and logical, right?

Neat, logical-sounding--and wrong.

Let's speculate why chelation as a therapy for atherosclerotic cardiovascular disease refuses to die. Chelation therapy is probably the form of alternative medicine most commonly pushed by M.D.'s, mainly because, unlike most alternative therapies, chelation therapy has to be given intravenously. The requirement for intravenous delivery means doctors have to administer it. "Healers" or "naturopaths" can't administer it, at least not without an M.D. to supervise. (Some alties claim to have come up with an oral regimen for chelation therapy, but these regimens are so bogus that even other alties have a hard time defending them without sounding ridiculous.) Chelation therapy is also highly profitable. A single infusion generally costs around $100-150, which has to be paid in cash because insurance companies won't pay for it. Most chelation therapy regimens require 20 to 40 treatments, and some end up requiring up to 100 treatments.

It doesn't take very much searching to find glowing testimonials about the joys of chelation therapy for heart disease and peripheral vascular disease. Its touted benefits include eliminating angina without the need for cardiac bypass surgery; reversal of atherosclerosis; healing of diabetic ulcers; improved cellular function (whatever that means); reversal of the aging process; lowring of cholesterol and triglyceride levels in the blood; and the claims listed above in the flyer. The problem is, there is no evidence that supports any of those claims. Remember what I said about cancer testimonials and how they are used to sell alternative cancer "cures." The same sorts of principles apply to chelation therapy, with the exception being that the reason for the glowing testimonials is almost certainly nothing more than the placebo effect, as I'll try to explain below.

First off, let's look at the claims one by one. I'm going to look at the less common claims first. Aches and pains? There is no scientific or clinical trial evidence that chelation relieves aches and pains. Alzheimer's? Ditto (although the chelationists are cleverly appropriating conflicting preclinical research that may--I repeat, may--implicate heavy metal toxicity in the pathogenesis of Alzheimer's). Diabetes? No evidence. Osteoporosis? Definitely no evidence. (In fact, if anything, based on mechanism alone, we would expect chelation to leech calcium out of the bone by lowering blood calcium and thus causing parathyroid hormone levels to rise.) Kidney stones? No data. (But there is evidence that EDTA and other chelators can be toxic to the kidneys.) Impaired memory or concentration? No evidence. Extend maximum life span? Definitely no evidence! Agh, enough!

Let's look at the most common use for chelation therapy, atherosclerotic vascular disease leading to heart disease or peripheral vascular disease and start with the basic science first. There have been four mechanisms by which chelation therapy has been said by its advocates to help atherosclerotic vascular disease. First was the "roto-rooter" hypothesis, in which the removal of calcium from the plaques causes the plaques to disintegrate. The problem is that plaque is made up of cells, debris, and fat. Calcium is usually not deposited until relatively late in the process, and it is quite possible to suffer a fatal heart attack from a calcium-free plaque. Chemically, EDTA can't even penetrate the lipid-rich cell membranes and fatty deposits anyway. Even worse, the stoichiometry is impossible, with the maximum possible amount of calcium bound by the usual dose of EDTA being negligible, about 0.02% of total body calcium removed per dose, or 0.3% of by a full course. Not unexpectedly, there has never been a study that shows a decrease in the amount of calcium in atherosclerotic plaques as a result of chelation therapy. By the 1980's, the "roto-rooter" hypothesis had been discredited. But alties are resourceful; they soon came up with another one, which was that lowering calcium in the blood, as chelation undeniably does, caused calcium to be removed from the bone, causing parathyroid hormone to be secreted and promote the remineralization of bone from calcium leeched from the atherosclerotic plaques. The problem is, the physiology doesn't work that way, as is explained here. A third hypothetical mechanism proposed (and still used today) was that EDTA blocks production of free radicals by binding heavy metal ions, particularly iron. Two problems: First, most iron is bound to proteins and unavailable to catalyze the generation of free radicals anyway. Second, in the case of iron at least, EDTA does not decrease its oxidative capability and may actually increase it. The fourth hypothesis is that chelation therapy prevents mutation of cells that become atheromas, the precursors to atherosclerotic lesions. The problem is, the cells that produce atheromas are not mutants, nor does the production of atheromas depend upon mutations in the vascular smooth muscle cells lining arteries. Finally, there is actually a fifth "hypothesis" I have recently heard of is that is winding its way through altieland; that is, that chelation somehow increases the generation of nitric oxide, a natural vasodilator. There is one study that suggests it might improve blood flow by this mechanism. This is the study all the chelationists tout. What the chelationists don't tell you is that it was a small study with only 8 patients and that a more recent, randomized, double-blind, placebo-controlled study failed to show any benefit in terms of increased blood flow.

There have been several clinical studies that are described in detail here, here, here, and here. I'll summarize briefly. There were several studies before 1990, but none of them were randomized and many didn't even have a control group. (Actually, even as far back as the 1963, Kitchell et al, based on a study of 38 patients, concluded that EDTA "was not a useful tool in the treatment of coronary disease.") Another notable series was reported in 1989, when Olszewer and Carter reported a study of 2,870 patients with severe claudication in which 75% reported subjective improvement with chelation. The problem is, there was no control group, nor was there any objective measure of improvement reported. These same two authors followed the study up in 1990 with a randomized study of patients with severe claudication that claimed to show the same sort of results, but only studied 10 patients. In 1992, a group of surgeons in Denmark tried to replicate Olszewer and Carter's results with a larger group of patients and saw no improvement in claudication pain in the chelation group compared to the placebo group. The most recent study was in 2002, a randomized, placebo-controlled, double-blind study that showed no benefit from chelation over placebo.

Despite all these negative studies, the combined weight of which should have been enough to put afinal stake through the heart of chelation as a tratment for atherosclerotic vascular disease and then shine sunlight on it so that it explodes in flame, so great is the clamor for chelation therapy by alties that the National Center for Complementary and Alternative Medicine decided to sponsor yet another clinical trial to test the efficacy of chelation therapy in cardiovascular disease. My guess is that this trial will be negative too, but it will be years before the results are known. Even in the unlikely event that it is not entirely negative, given the previous trials, I consider it unlikely that the NCCAM trial will show a large effect. Finding only a small effect would, in essence, disprove the extraordinary claims of chelationists, because the large effects claimed by chelationists should be mind-numbingly easy to spot in even small clinical trials. My further prediction is that, if the trial is negative, it still won't spell the end of doctors pushing chelation therapy for all the conditions listed in the flier above. (After all, there are still alt-med "healers" pushing laetrile, twenty years after it was shown to have no significant antitumor effect in humans.) The bottom line is that many studies have been done, but not a single well-designed, randomized, double-blind, placebo-controlled study has shown a benefit of chelation therapy in cardiovascular disease, nor has any well-designed study shown objective evidence that chelation decreases atherosclerotic plaque or increases blood flow.

So what's the harm? Chelation therapy is not without risks. Chelationists will claim that millions of treatments have been given safely. However, chelation can cause low blood calcium leading to tetany and cardiac arrhythmias, occasionally fatal, kidney failure, anticoagulation leading to bleeding complications, vasculitis, and autoimmune reactions. Chelation seriously depletes serum zinc, which can lead to compromise of the immune system. There's also another factor to consider, which is that the use of chelation over proven treatments can delay treatment, puttin the patient at risk for more serious complications, such as heart attack or limb loss. The American Heart Association has concluded that there is "no scientific evidence to demonstrate any benefit of this form of therapy."

So what should I do? I googled this doctor and haven't been able to find much about him other than a practice address. Nor could I find out much about this "Wellness Education Foundation" that is sponsoring the talk. (Oddly enough, it doesn't seem to have a website, as far as I can tell.) I thought of calling the number on the flyer and showing up to the talk, but it's the same evening as one of my clinic days. Getting out of clinic in time and making it there would be very difficult indeed. Still, it would have been quite amusing to see the look on Dr. GHL's face when he realized a fellow physician had come to his talk in the room, one who has made himself fairly familiar with the actual scientific literature (as opposed to the altie literature) on chelation. (Heh heh. The thought still tempts me.) No, I think my best bet is to find out who from the company running the nursing/rehab facility I should write to and then write a letter to them explaining my concerns. Boring, but possibly effective, especially if sent by old-fashioned snail mail. At the very least it ought to cause some annoyance.

I'll report back the results of this endeavor...