Excess iron linked to heart disease.

High levels of iron stored in the body may boost the risk of heart disease, according to a new study by a team of Finnish researchers. In fact, stored iron may prove a more significant risk factor for coronary disease than total blood cholesterol levels, they say.

The new study, published in the September Circulation, provides the first empirical evidence for this theory. "It is the first time that iron stores have been looked at as a risk factor," comments Jerome L. Sullivan of the Medical University of South Carolina in Charleston. Sullivan first proposed the iron and heart disease hypothesis more than a decade ago.

Basil Rifkind of the National Heart, Lung, and Blood Institute calls the Finnish findings "interesting." He points out, however, that this is the first time scientists have shown a link between iron stores and heart disease. Other researchers must confirm the finding before public health experts can make any recommendations to reduce iron stores, he adds.

Epidemiologist Jukka T. Salonen of the University of Kuopio and his Finnish colleagues focused on 1,931 middle-aged men who showed no sign of heart disease at the study's start in 1984. The researchers drew blood to test for stored iron and cholesterol and asked the men about other risk factors for heart disease. The team then estimated dietary iron intake by asking the men to record their food choices during a four-day period.

After adjustment for risk factors such as cholesterol, the data revealed that men with high concentrations of ferritin in their blood (more than 200 micrograms per liter) were twice as likely to suffer a heart attack as men with lower ferritin values. Ferritin is a molecule that stores iron in the blood and other parts of the body. The researchers found that every 1 percent increase in blood ferritin was associated with a more than 4 percent rise in the risk of heart attack.

Men who typically ate iron-rich foods faced a higher likelihood of heart attack than did those who had an iron-poor diet, Salonen says. Red meats, which also contain a lot of fat, are rich in iron.

There's no doubt that iron-depleted blood can cause anemia, a medical disorder that can result in fatigue. But Sullivan and Salonen propose that, although people need a trace amount of iron in their diet to remain healthy, too much iron can promote the formation of free radicals.

Free radicals may injure the cells lining artery walls and damage heart muscle, Sullivan says. Free radicals may also lead to the formation of a dangerous type of cholesterol known as oxidized low-density lipoprotein (LDL). Scientists believe that oxidized LDL cholesterol is more likely than nonoxidized LDL to stick to artery walls and thus to trigger the buildup of fatty plaque that can clog arteries and lead to heart attacks.

The iron theory may help explain the mysterious gender gap in heart disease rates. Cardiologists have long noticed that premenopausal women remain largely protected from the ravages of heart disease, whereas men start suffering heart attacks in their forties. Many scientists believe the sex hormone estrogen helps women ward off heart disease until menopause, when the production of estrogen tapers off and heart attack rates go up.

Sullivan remembers puzzling over that gender gap during his medical training. At the same time, he was studying normal iron metabolism. "When I saw those curves for iron acquisition in men and women, I really had a eureka moment," he says, noting that men build up iron stores steadily, while women don't start accumulating iron until menopause.

Sullivan thinks that young women are shielded from heart disease because they lose iron every month during menstruation. After menopause, the stored iron in a woman's body builds up rapidly - and women's advantage in terms of heart disease gradually disappears, he adds.

The iron theory might also explain why aspirin and fish oil help protect people from heart attacks. Sullivan adds. He notes that both substances may increase chronic blood loss through minor bleeding and thus loss of iron.

The findings, if confirmed, could force public health experts to rethink dietary recommendations for iron ingestion. Even normal levels of stored iron may prove damaging, Sullivan says. Over-the-counter vitamin supplements often contain iron, as do some enriched foods such as cereals, he notes.

Sullivan offers a few simple solutions for people worried about the iron-heart disease connection. "I think we can say that adults should avoid iron supplements unless they have iron-deficiency anemia," Sullivan says. "Also, I think people should consider blood donation."