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"The Shocking Truth About Iron"

A Million Americans have a potentially fatal disease--iron overload. So why are we still focused on deficiency?

by Steven Finch

The oft-repeated first law of modern medical diagnosis is that when you hear hoofbeats, think horses not zebras. So in 1951, when 19-year old Roberta Crawford complained of constant fatigue and lingering flu symptoms, her doctor took one look at her pale skin and thin frame and heard the clipperty-clop of iron deficiency anemia. He sent her off with a prescription for a new iron supplement called Trinsicon. "At first it seemed to help," Crawford recalls, "but then I'd get clobbered by the flu again, only worse." She started with a single capsule each day, but when her doctors noted that the Trinsicon wasn't curbing her anemia, they bolstered the dose. by the time Crawford was up to five pills a day, she'd become disabled from sheer exhaustion. "I knew I didn't want the iron," she says, "but when I asked one doctor if I could give it up, he said, 'No. It's crucial for your life. You have to keep taking it forever.'"

Crawford took iron for her "deficiency" for the next 27 years. Then in 1978, Crawford's swollen liver led her gastroenterologist to make a lifesaving diagnosis. To the GI, a distended liver, coupled with her symptoms of fatigue and flu, sounded a lot like cancer. He ordered a biopsy. The liver sample came back clean, except that it was brimming with iron. He then ordered a series of blood tests, including one to determine her levels of the iron-binding protein, ferritin. Healthy adults have up to 160 grams in a deciliter of blood. A measure of 300 grams can indicate advanced iron overload. Roberta Crawford's ferritin approached 7,000. "You have an interesting, rare disease," her doctor told her. "Hemochromatosis".

The GI was right about the diagnosis, but he was off the mark about its frequency. A hereditary disease in which the intestine absorbs excess iron, hemochromatosis is, in fact, the most common and one of the most misunderstood--and most underdiagnosed--genetic disorders in the country. The hemochromatosis gene is 30 times more prevalent than the gene for Duchenne muscular dystrophy and occurs far more frequently than the genes for either Down syndrome, cerebral palsy, or cystic fibrosis. All told, more than a million Americans (about one out of every 250) suffer from hemochromatosis. And that's not counting the gene in the Americans (fully 23 million) who are carriers of the genes for the disease.

Normally, healthy people absorb about 10 percent of the iron in the foods they eat. Carriers, who have only one of the two hemochromatosis genes, can absorb half-again that much, while Crawford and others with full-blown hemochromatosis can soak in up to 20 percent or more. Since the body has no natural way of excreting iron (other than through a woman's menses and the minuscule amounts everyone sloughs off in dead skin), any extra iron that's absorbed is relentlessly dumped into tissues and vital organs, especially the heart, liver, and pancreas. The good news is that, if hemochromatosis is discovered early, phlebotomies, or bloodletting, will entirely prevent illness associated with the disease. But left unchecked, excess iron can turn the skin a coppery, bronze, or grayish color and clog vital internal organs to such an extent that initial, vague ailments such as stomach pain and fatigue can develop into arthritis, diabetes, cancer, heart disease, cirrhosis of the liver, and a host of other ills.

Unfortunately, iron overload is left unchecked all too often. Surveys of hemochromatosis patients conducted in 1985 and 1988 by the Iron Overload Diseases Association found that the average patient had to wait more than five years before being properly diagnosed. Most of those surveyed had consulted multiple doctors; 25 percent of them also had a type of anemia unrelated to iron status and, like Crawford, were actually first prescribed iron before anyone successfully diagnosed their hemochromatosis.

Given iron overload's prevalence and seriousness, why the long delay? For one thing, say a group of health experts who are trying to raise physicians' awareness, symptoms, such as fatigue and pain in the joints, are fairly nonspecific. For another, our decades-old preoccupation with iron deficiency anemia has too often led medical schools--and therefore the medical profession--to focus attention on the benefits of iron at the expense of its dangers.

Even today, says Kenneth Bridges, an assistant professor of medicine at Harvard who has spent the last 15 years researching iron's effects on the body, most doctors aren't taught enough. "A lot of medical schools still only skim over iron deficiency and don't even touch on hemochromatosis except to say that it's a rare iron disease that yellows the skin," he says. As a result, despite more than a million people at serious risk, hemochromatosis remains an invisible problem. Lack of physician awareness, Bridges says, extends even to his own clinical affiliation, Harvard's prestigious Brigham and Women's Hospital in Boston.

Iron is, of course, essential to life. Skimp on iron and the result is anemia, a condition that decreases hemoglobin in the blood, which in turn, cheats the body of enough oxygen for proper growth and functioning. Sic percent of Americans--almost exclusively infants, adolescents, and women in their childbearing years--need additional iron.

It's known, for example, that while adequate iron is vital to healthy pregnancies, about 20 percent of women of child-bearing age are iron deficient. Numerous studies have confirmed that low iron stores in children can impair physical and mental development. That's an alarming fact when you consider that, according to a 1994 Johns Hopkins study, at least 15 percent of all adolescent girls have some form of iron deficiency.

But as a group, Americans are in much more danger from overloading on iron than from getting too little. For one thing, although iron deficiency is the most common reason for anemia, it's far from being the only one. Anemias are caused by everything from vitamin deficiencies to defects in the hemoglobin itself or in the bone marrow's production of red blood cells. That distinction isn't always clearly understood. Like Crawford (whose anemia turned out to stem from insufficient vitamin B-12), many anemic patients are prescribed iron as a matter of course, sometimes with drastic consequences.

William Crosby, a former director of hematology at the Chapman Cancer Center in Joplin, Missouri, calls iron deficiency anemia a "nothing problem"--a statement that puts him at odds with many in the medical community.

"What I mean is that although a lot of women have iron deficiency anemia and are worn down and fatigued by it, their deficiency doesn't kill them, " says the 30-year military veteran, who introduced hematology as a specialty to the Army Medical Corps. "Iron overload is lethal."

Hematologist Victor Herbert, a professor of medicine at Mount Sinai and Bronx Veteran's Affairs Medical Centers in New York City, and one of the world's foremost experts on nutrition, echoes Crosby's concern. Except for high-risk groups like children and premenopausal women, it's pretty tough for other Americans to come up iron deficient, he says. Not only is iron abundant in unprocessed meat and vegetables, but since the early 1940's the FDA has required that virtually all four products be iron- enriched. so while in the rest of the world more than a billion people are iron-deficient, in this country you can't trip over a Twinkie without getting metal shavings on your sneakers. In fact, Americans who need extra iron are outnumbered nearly 20 to one by those who don't. Nevertheless, tens of millions of Americans regularly supplement their diets with multivitamins, minerals, or other iron products because they believe it will keep them healthier.

Worse, doctors frequently prescribe iron without fully diagnosing the cause of a patient's anemia or ruling out iron overload. "It happens all the time," says Herbert. "And that's just plain dangerous. No one should take a supplement without having their iron status checked." Most hemochromatosis carriers, for example, will live full, healthy lives despite absorbing twice as much iron as the average person. "But give carriers a bunch of multivitamins or a string of iron supplements like Geritol," says Herbert, "and you're going to throw them into iron overload too." The bottom line, he adds, is that people who take iron are twice as likely to be hurt by a supplement as they are to be helped by it.

What's needed, Herbert and his colleagues maintain, is a sharp increase in doctors' awareness of how serious a problem hemochromatosis is as well as universal screening for patients' iron status. The old definition for hemochromatosis won't do anymore, says David Witte, a University of Iowa pathologist who's written new guidelines on hemochromatosis due out sometime in early 1996. (See additional information attached to this article on how to order a copy of these guidelines).

"We have to move beyond thinking about this disease as a liver malady in old men," Witte says. "For one thing, the condition affects as many women as men. Women just have an early advantage, which they lose after menopause." For another, he adds, we're doing patients an inexcusable disservice by refusing to recognize hemochromatosis as a chronic, genetic disorder that makes people absorb excess iron. Using this new definition, he says, the challenge becomes to find these people and treat them before their excess iron causes complications.

"If you don't look for hemochromatosis until a patient displays clinical symptoms or until a liver biopsy turns up full of iron," Bridges says, "too much damage has already been done."

Screening would go a long way in reducing such damage, Witte and other experts insist. "People are getting bounced around from doctor to doctor, suffering from fatigue or headaches, and no one thinks to check for iron overload," Witte says. "A few patients are still being sent to psychiatrists, because their doctors pass them off as hypochondriacs."

Roberta Crawford remembers when doctors told her she was crazy. Now 63 and quite sane, Crawford's only concessions to iron overload are phlebotomies once or twice a year and regular yoga and swimming to ease her nagging arthritis. But she's come to realize how lucky she is to have survived her condition relatively unscathed. Since starting the Iron Overload Diseases Association in 1981, Crawford has met or talked to the families of hundreds of seemingly healthy people--many who'd never taken an iron supplement--who became permanently disabled or died in their thirties or forties, a few even younger. Crawford and her association have been trying to educate both doctors and the public alike about the need to know their iron status. A second goal is to convince public health officials that it's worth the cost to screen seemingly healthy patients for a hidden disease.

Managed care giant Kaiser Permanente may already be convinced. At Kaiser San Diego, home of the country's single largest preventive medicine program, doctors in its department of preventive medicine are testing the iron status of every patient they see (until they reach 30,000). So far, of the approximately 8,000 patients they've tested, about one out of every 250 has had hemochromatosis. Most have been treated. That's fine for a relatively few southern California patients, says Bridges, but until screening becomes universal, it's up to individual practitioners to decide. "Look at it this way," he says. "There just aren't many diseases out there that a million Americans have. And while there's nothing you and I can do about advanced colon cancer or diabetic end stage renal disease, we can save a whole lot of people from hemochromatosis.

Appendix

"Practice Parameter for Hereditary Hemochromatosis," David L. Witte et al., in press, College of American Pathologists, Northfield, Illinois.

"Diagnosis and Treatment of Iron Disorders," Victor Herbert et al., Hospital Practice Symposium Supplement, Vol. 26, Supplement 3, 1991.

The Iron Elephant: What You Should Know About the Dangers of Excess Body Iron, Roberta Crawford, Glyndon, Maryland: Vida Publishing, Inc. 1992.

National Heart Lung and Blood Institute Information Center, Bethesda, Maryland.

FERROUS FABLES: EIGHT MYTHS ABOUT IRON

Anyone whose family had a television probably grew up watching Popeye-the pipe-smoking, pip-squeak of a sailor who could transform his sagging biceps into twin turbines with a few gulps of iron-rich spinach. Well, Popeye lied. Extra iron, whether from spinach or supplements, doesn't make us any stronger, smarter, faster, or more attractive. Here are some other common ironclad misconceptions.

Iron supplements are good medicine. Almost certainly not for most men--who have no natural way of getting rid of excess iron--and probably not for women past menopause.

An anemic woman is always iron deficient. She could be, but iron deficiency is only one from a long list of underlying problems that can trigger anemia, including vitamin deficiencies, defective hemoglobin, and even iron overload.

An enlarged liver means your patient drinks too much. Not necessarily. Sure, some patients will flat out lie about how much alcohol they drink. But if you don't know why Mr. Jones' liver is enlarged; and he insists he's a teetotaler, screen for iron.

Women shouldn't worry about getting too much iron. The genes for hemochromatosis are equally distributed between genders. Though they are at lesser risk, women with hemochromatosis, even those in their childbearing years, can easily absorb more iron than is healthy.

You can cure hemochromatosis by eating less iron. It's impossible to avoid iron in the American diet. Iron resides in every living plant and animal cell, and virtually all commercials flours are iron-enriched.

Switching to a multivitamin without iron will help. Only marginally. Most multivitamins contain small amounts of elemental iron. More important, vitamin C enhances the body's ability to absorb iron.

Bloodletting is an outmoded medieval practice. Phlebotomy is the standard of care for hemochromatosis. Once you make the diagnosis, your patient needs to have his or her blood drawn regularly to reduce and keep down her body's store of iron.

--Steven Finch

IRON SCREENINGS

Many of the million Americans who have hemochromatosis will suffer potentially debilitating or fatal consequences unless their disorder is diagnosed and treated. The College of American Pathologists, working with the American Medical Association, recently drafted recommendations for physicians on the need to screen for and treat iron overload. The "Practice Parameter for Hereditary Hemochromatosis" is due out in early 1996, but physicians may obtain an early copy by calling Barbara J. Barrett at the College of American Pathologists, 800-323-4040, extension 513. Here's a synopsis of the main points:

Screening: Research suggests that the cost of screening healthy people for hemochromatosis is much less than the cost of waiting to treat the symptoms. The guidelines call for everyone older than 20 to be tested for the disorder. Children and siblings of people already identified with hemochromatosis should be tested every five years.

Testing: The guidelines suggest that family practitioners order from the lab their patient's transferrin saturation results. A transferrin saturation higher than 50 percent is cause for concern. A doctor might want to consider having the patient tested again in two to three months to make sure a fever or an inflammatory disease like rheumatoid arthritis didn't skew the initial results. According to the parameters, repeated, abnormally high transferrin saturation is the best available indication that a patient needs to be treated for iron overload and further evaluated for hemochromatosis.

Treating: Phlebotomy is the treatment for hemochromatosis. Elevated iron levels--not the onset of symptoms--are the first sign that a patient needs regular phlebotomy. How often depends on the patient. Your goal, though, will always be to remove as much excess iron from the patient as is possible--and safe.- -Steven Finch.

(c) 1995