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What are some current issues and controversies about iron?

Iron and heart disease:

Because known risk factors cannot explain all cases of heart disease, researchers continue to look for new causes. Some evidence suggests that iron can stimulate the activity of free radicals. Free radicals are natural by-products of oxygen metabolism that are associated with chronic diseases, including cardiovascular disease. Free radicals may inflame and damage coronary arteries, the blood vessels that supply the heart muscle. This inflammation may contribute to the development of atherosclerosis, a condition characterized by partial or complete blockage of one or more coronary arteries. Other researchers suggest that iron may contribute to the oxidation of LDL (“bad”) cholesterol, changing it to a form that is more damaging to coronary arteries.

As far back as the 1980s, some researchers suggested that the regular menstrual loss of iron, rather than a protective effect from estrogen, could better explain the lower incidence of heart disease seen in pre-menopausal women [70]. After menopause, a woman’s risk of developing coronary heart disease increases along with her iron stores. Researchers have also observed lower rates of heart disease in populations with lower iron stores, such as those in developing countries [71-74]. In those geographic areas, lower iron stores are attributed to low meat (and iron) intake, high fiber diets that inhibit iron absorption, and gastrointestinal (GI) blood (and iron) loss due to parasitic infections.

In the 1980s, researchers linked high iron stores with increased risk of heart attacks in Finnish men [75]. However, more recent studies have not supported such an association [76-77].

One way of testing an association between iron stores and coronary heart disease is to compare levels of ferritin, the storage form of iron, to the degree of atherosclerosis in coronary arteries. In one study, researchers examined the relationship between ferritin levels and atherosclerosis in 100 men and women referred for cardiac examination. In this population, higher ferritin levels were not associated with an increased degree of atherosclerosis, as measured by angiography. Coronary angiography is a technique used to estimate the degree of blockage in coronary arteries [78]. In a different study, researchers found that ferritin levels were higher in male patients diagnosed with coronary artery disease. They did not find any association between ferritin levels and risk of coronary disease in women [79].

A second way to test this association is to examine rates of coronary disease in people who frequently donate blood. If excess iron stores contribute to heart disease, frequent blood donation could potentially lower heart disease rates because of the iron loss associated with blood donation. Over 2,000 men over age 39 and women over age 50 who donated blood between 1988 and 1990 were surveyed 10 years later to compare rates of cardiac events to frequency of blood donation. Cardiac events were defined as (1) occurrence of an acute myocardial infarction (heart attack), (2) undergoing angioplasty, a medical procedure that opens a blocked coronary artery; or (3) undergoing bypass grafting, a surgical procedure that replaces blocked coronary arteries with healthy blood vessels. Researchers found that frequent donors, who donated more than 1 unit of whole blood each year between 1988 and 1990, were less likely to experience cardiac events than casual donors (those who only donated a single unit in that 3-year period). Researchers concluded that frequent and long-term blood donation may decrease the risk of cardiac events [80].

Conflicting results, and different methods to measure iron stores, make it difficult to reach a final conclusion on this issue. However, researchers know that it is feasible to decrease iron stores in healthy individual through phlebotomy (blood letting or donation). Using phlebotomy, researchers hope to learn more about iron levels and cardiovascular disease.

Iron and intense exercise:

Many men and women who engage in regular, intense exercise such as jogging, competitive swimming, and cycling have marginal or inadequate iron status [1,81-85]. Possible explanations include increased gastrointestinal blood loss after running and a greater turnover of red blood cells. Also, red blood cells within the foot can rupture while running. For these reasons, the need for iron may be 30% greater in those who engage in regular intense exercise [1].

Three groups of athletes may be at greatest risk of iron depletion and deficiency: female athletes, distance runners, and vegetarian athletes. It is particularly important for members of these groups to consume recommended amounts of iron and to pay attention to dietary factors that enhance iron absorption. If appropriate nutrition intervention does not promote normal iron status, iron supplementation may be indicated. In one study of female swimmers, researchers found that supplementation with 125 milligrams (mg) of ferrous sulfate per day prevented iron depletion. These swimmers maintained adequate iron stores, and did not experience the gastrointestinal side effects often seen with higher doses of iron supplementation [86].

Iron and mineral interactions

Some researchers have raised concerns about interactions between iron, zinc, and calcium. When iron and zinc supplements are given together in a water solution and without food, greater doses of iron may decrease zinc absorption. However, the effect of supplemental iron on zinc absorption does not appear to be significant when supplements are consumed with food [1,87-88]. There is evidence that calcium from supplements and dairy foods may inhibit iron absorption, but it has been very difficult to distinguish between the effects of calcium on iron absorption versus other inhibitory factors such as phytate [1].