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Iron-Clad Solutions to Anemia

by Christine Haran

Aug 1, 2003 

When we work and play hard, we often pay for it with next-day fatigue. Fatigue and lethargy are also common complaints that can result from many medical conditions and sometimes their treatment. But one of the more well-known and common causes of chronic tiredness is anemia. Iron, which is mostly found in the red blood cells, is needed to courier oxygen to cells to perform their functions. Iron-deficiency anemia, the most common form of anemia, occurs when there is a lack of this mineral in the body. There are many causes for iron depletion: blood loss, red blood cell damage, low dietary intake, or poor absorption.

Although rates of iron-deficiency anemia are relatively low in the Unites States, where many people eat an iron-rich diet, it is still a concern among young children and pregnant women, whose iron requirements are high. That's why the Centers for Disease Control and Prevention recommends periodic screening for anemia among infants, preschool age children and pregnant women and non-pregnant women during the reproductive years. And iron-deficiency rates are higher among women in general, and in highly trained athletes.

Fortunately, most iron-deficiency anemia can be treated with dietary modifications or over-the-counter iron supplements taken under the guidance of a physician. Below, anemia researcher John Beard, a professor in the department of nutritional sciences at Pennsylvania State University, explains the causes, detection methods and treatment for iron deficiency anemia.

What is iron deficiency anemia?

Anemia is the result of an individual being in a negative iron balance. The deficiency of iron over a long period of time will lead to an insufficient amount of iron going to bone marrow, which is where red blood cells are produced. Over a long enough period of time, people who are iron deficient will end up a lower than optimal concentration of hemoglobin, which is the iron-rich protein in red blood cells that carries oxygen to the tissues, and a lower number of red blood cells circulating in the bloodstream. Iron goes into all the tissues in the body and is required for functioning of basically all tissues because it's essential for the production of the energy currency for cells. In order to have muscles contract or neurons fire or anything like that, cells need to expend chemical energy.

What are some of the signs and symptoms of low iron status?

What's frequently mentioned is a feeling of lethargy and lack of energy. But it's quite clear that, in the more severe stages of iron deficiency, there's a decrease in physical work capacity; the muscles will not work as well or as long. And it's been proven many times in exercise studies, for instance, that the maximal aerobic capacity is diminished in people who are iron deficient. Endurance capacity is also affected.

The problem is that most people who are mildly iron deficient don't know it. It's like most hypertensives: Unless they are really hypertensive, they don't know that they're hypertensive. So most people are just made aware of the need for iron supplements after they've been diagnosed by the family doctor, or perhaps they tried to donate blood and they were rejected because they were anemic.

What are some of the long-term consequences of low iron?

More recently, our research group and others have been spending a lot of our investigative energy looking at the effect of iron deficiency on brain function and brain development. Evidence tells us that infants who are iron deficient from about 12 to 24 months have a developmental delay, and there is new evidence that there is an irreversible change in brain functioning.

How is anemia diagnosed?

There are many different tests for anemia. The hemocrit measurement is a measure of how many red cells you have in a particular volume of blood. The hemoglobin test is a measure of the amount of this oxygen-carrying protein in a particular volume of blood. But these tests don't distinguish between different forms or causes of anemia.

The most common secondary test measures ferritin, which is a storage protein for iron. The amount of this protein that's found in blood is proportional to the amount of storage in the liver and spleen, the main storage sites. And so, when we measure the amount of ferritin in blood, if it's low we oftentimes conclude that the person is iron-deficient anemic.

The one problem is that the ferritin value is very strongly affected by whether somebody has an infection. There are certain proteins that are elevated whenever we have an acute infection or even sometimes a longer-term infection, or an autoimmune disease like lupus.

Then there is another test but, this is generally only available in research labs. This new marker protein—transferrin receptor protein—gives us an indirect signal that non-red blood cells are iron-deficient. And so that gives us an indirect signal that we have iron deficiency that is occurring in cells in the tissues.

Finally, there is another measure, which is called protoporphyrin. And that's a nifty little measurement, because that tells us the availability of iron to newly developing red cells in bone marrow. If there's not enough iron going to the bone marrow, the protein inside the red cell is formed without the iron molecule.

And so with those five measurements, one can have a pretty high level of confidence when diagnosing somebody with iron-deficiency anemia or not.

Why are women at higher risk for iron deficiency anemia?

The predominant risk factor is the imbalance between losses of iron, which primarily occurs through blood loss, and the intake of iron, which is, in our society, predominantly in meat. So any imbalance between these two things would put somebody at risk.

As a result, women who have heavy menstrual flows are more likely to be iron-deficient. And women may have an increase in requirements because of pregnancy or blood loss at delivery.

The American diet is generally able to meet iron requirements for most of the population, except for pregnant women. That's why we've been prescribing iron pills in pregnancy for a good 25 or 30 years now. The deficiency is due to the expansion of the maternal blood volume, and fetal and placental growth. Of course, the mom gets to recover part of that iron in the first two or three weeks after delivery because her blood volume contracts back to what it was in the prepartum phase.

Birth weight and gestational age of the infant seem to affect maternal iron status, at least the severity of anemia. It's very difficult to keep women from getting somewhat anemic, but to avoid severe anemia is highly desirable.

When else does the demand for iron increase?

It increases during periods of really rapid growth. For instance, the adolescent growth spurt in boys increases requirements. They can essentially double within a 12- to 18-month timeframe. Girls go through maturation at a slower rate than boys do, but they, of course, are acquiring menstrual flows, so iron requirements dramatically increase in preadolescent to adolescent girls.

Other situations that increase risk are post-surgical situations where there was blood loss. Any medical condition that causes a high rate of blood loss such as bleeding ulcers would increase risk. Not so much in our culture, but elsewhere in the world, roundworms, hookworms and other worms that cause loss of blood out of a gastrointestinal tract, would be a reason to suspect a negative iron balance.

Why might athletes be at increased risk?

Repeated high levels of exercise cause the red cells to break apart at an earlier age than they normally would. Most of our red cells will stay in circulation for about 120 days. With highly trained athletes—and it seems to be not dependent on sport—the red cell lifespan may decrease by as much as 20 percent or 30 percent. Instead of red cells being around for 120 days, they're really maybe only around for 95 or 100 days. We recycle most of that iron, but there is some fraction that we lose from our body every day. The higher the rate of red cell turnover, the higher the rate of expected loss of iron.

The other factor is that heavily trained athletes tend to diet frequently. And they are, a lot of times, not meat-eaters, and that leads to a relatively lower iron intake and a higher iron loss.

How do infants meet the requirement?

Iron deficiency in early infancy used to be a big problem in the United States 25, 30 years ago, but it really is not any more. We've pretty well taken care of the problem with the introduction of iron-fortified formulas and then iron drops for infants who are being exclusively breast-fed. We recommend that mothers who exclusively breast-feed their infants start providing iron drops at about six months of age in order to increase their iron intake because breast milk has a very low concentration of iron.

How is iron-deficiency anemia treated?

Treatment depends on the severity of the iron deficiency. Dietary approaches are often effective, but I think most clinicians will go with over-the-counter supplements.

Over-the-counter iron supplements are usually in a form that is absorbed efficiently. The ferrous sulfate forms are quite absorbable. Many people tolerate the delayed or slow-release forms of iron supplements much better than the normal regular release dose. These forms are gradually dissolved in the stomach over the course of the whole day, so gastrointestinal upset and distress is not quite as prominent as it is with some of the other forms. I would tend to not recommend multivitamins that contain iron, because there's a real question as to whether or not the iron that's in a multivitamin is really absorbable.

Whenever we do studies where we're doing iron repletion, or replenishment, we always use ferrous sulfate in a low-dose once or a twice a day. And that seems to be quite effective in treating mildly iron-deficient anemic women. Within three months, they are iron-repleted. We use the lowest over-the-counter dose that you can pick up at the pharmacy, which is about 125 mg of ferrous sulfate; the actual amount of iron that's there is 39 mg.

What foods are high in iron?

Any of the meats are higher in iron: fish, poultry, red meats. They all have forms of iron that are more absorbable than the forms of iron that are in most of our vegetables or grains. That's because they also contain compounds that inhibit the absorption of iron. So the net gain is not very large. So vegetarians are at greater risk for iron deficiency anemia, but they can avoid it if they are very diligent about how they plan their menus.

The average American diet probably has an efficiency of iron absorption of only somewhere between 5 percent and 7 percent. So of that 15 mg to 18 mg of iron that's actually in your daily diet, only 5 percent to 8 percent of that actually gets across the gastrointestinal cell into the blood. It might be a little bit higher in some other places in the world where iron deficiency is more common. The body physiology is set up so that if you are iron deficient, you try to absorb more iron.

Would you recommend that people buy supplements only if they have been advised to by a physician? I do, though a lot of women know whether they have higher than what is perceived to be normal menstrual blood losses. And they will self-prescribe an iron supplement and I think that makes a lot of sense.

Are there any risks associated with the iron supplements?

At low doses, most people do not get upset stomachs or constipation. But at progressively higher doses, a higher proportion of individuals would report gastrointestinal distress. And it's one of the biggest problems with measuring compliance to iron supplements in pregnancy studies, for instance.

There is an approach that we and other people have been trying to use in the last number of years, which is called intermittent iron therapy. That involves taking an iron supplement every three days instead of every day. There have been a number of studies that tell us that, as long as you're not treating somebody that has a real high iron requirement like in pregnancy—in pregnancy, daily iron does seem to be better—a low dose every three days or even two times a week seems to do a quite a good job.

Are there people who should not take iron supplements?

Any sort of high dietary iron intake is dangerous for people with a genetic disease called hemochromatosis. It is probably the most prevalent blood genetic disorder that exists. Reportedly, it's just in people of Anglo-Saxon ancestry. And so it's prevalent in northern Europe, of course, Australia and United States.

Perhaps one in 20 white Anglo-Saxon individuals in the United States has inherited one of their sets of genes for this defect. And the defect is in regulating iron absorption across the gastrointestinal tract. And so, an individual with hemochromatosis can't limit the amount of iron they absorb.

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