Iron as a therapeutic supplement

• DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.
• PRINCIPAL PROPOSED USES: Iron deficiency, sports performance enhancement
• OTHER PROPOSED USES: Attention deficit disorder, enhancing mental function in women, fatigue, human immunodeficiency virus infection support, menorrhagia, reducing side effects of angiotensin-converting enzyme-(ACE) inhibitor, restless legs syndrome, stimulating flow of saliva

Overview

The element iron is essential to human life. As part of hemoglobin, the oxygen-carrying protein found in red blood cells, iron plays an integral role in furnishing every cell in the body with oxygen. It also functions as a part of myoglobin, which helps muscle cells store oxygen. Without iron, the body could not make adenosine triphosphate (ATP, the body’s primary energy source), produce deoxyribonucleic acid (DNA), or carry out many other critical processes.

Iron deficiency can lead to anemia, learning disabilities, impaired immune function, fatigue, and depression. However, individuals should not take iron supplements unless laboratory tests show that they are genuinely deficient in iron.

Requirements and Sources

The official U.S. recommendations (in milligrams, mg) for daily intake of iron are as follows:

Infants up to six months (0.27) and seven to twelve months (11); children one to three years (7) and four to eight years (10); males nine to thirteen years (8) and nineteen years and older (8); females nine to thirteen years (8), fourteen to eighteen years (15), nineteen to fifty years (18), and fifty years and older (9); pregnant women (27); and nursing women (9; 10 mg if age eighteen years or younger).

Iron deficiency is a widespread nutrient deficiency impacting about 30 percent of the global population, though iron deficiency without anemia is more common than iron deficiency with anemia. Some populations are at an increased risk for low iron levels. For example, around 60 percent of individuals with chronic heart failure experience iron deficiency. Other high-risk groups include children, teenage girls, menstruating women (especially those with excessively heavy menstruation, known as menorrhagia), pregnant women, and older adults.

There are two major forms of iron: heme iron and nonheme iron. Heme iron is bound to the proteins hemoglobin or myoglobin, whereas nonheme iron is an inorganic compound. (In chemistry, “organic” has a very precise meaning that has nothing to do with farming. An organic compound contains carbon atoms. Thus, “inorganic iron” is an iron compound containing no carbon.) Heme iron, obtained from red meats and fish, is easily absorbed by the body. Nonheme iron, usually derived from plants, is less easily absorbed, but eating it with meat, poultry, seafood, and foods with high vitamin C content may help the body absorb more iron.

Rich sources of heme iron include oysters, meat, poultry, and fish. The main sources of nonheme iron are dried fruits, molasses, whole grains, legumes, leafy green vegetables, nuts, seeds, and kelp. Contrary to popular belief, there is no meaningful evidence that cooking in an iron skillet or pot provides a meaningful amount of iron supplementation.

Iron absorption may be affected by antibiotics in the quinolone (Floxin, Cipro) or tetracycline families, levodopa, methyldopa, carbidopa, penicillamine, thyroid hormone, captopril (and possibly other angiotensin-converting enzyme [ACE] inhibitors), calcium, soy, zinc, copper, manganese, or multivitamin/multimineral tablets. Conversely, iron may also inhibit the absorption of these drugs and supplements. In addition, drugs in the H₂ blocker or proton pump inhibitor families may impair iron absorption.

Therapeutic Dosages

The typical short-term therapeutic dosage to correct iron deficiency is 100 to 200 mg daily. Once the body’s stores of iron reach normal levels, however, this dose should be reduced to the lowest level that can maintain iron balance. The typical upper intake limit for adults is 45 mg, and for those under thirteen, 40 mg.

Supplements may contain a variety of iron types and may also contain vitamin D or other nutrients. For example, Thorne’s iron bis-glycinate supplements contain 25 to 45 mg of a highly absorbable form of iron that is usually well tolerated. Other forms of iron include ferrous gluconate, ferric citrate, ferric sulfate, and ferrous fumarate. Because each form of iron is absorbed at different rates in the body, it is difficult to recommend dosages. However, some research indicates ferrous bisglycinate may be the easiest form to absorb and is more effective than other forms of iron supplementation in increasing hemoglobin concentration while causing minimal stomach upset.

Therapeutic Uses

The most obvious use of iron supplements is to treat iron deficiency. Severe iron deficiency causes anemia, which causes many symptoms. Iron deficiency that is too slight to cause anemia may also impair health. Several, though not all, double-blind trials suggest that mild iron deficiency might impair sports performance. In addition, a double-blind, placebo-controlled study of 144 women with unexplained fatigue who also had low or borderline-low levels of ferritin (a measure of stored iron) found that iron supplements enhanced energy and well-being. Another study found that iron supplements improved mental function in women who were iron deficient. However, individuals should not take iron just because they feel tired; they should get tested to see whether they are indeed deficient. With iron, more is definitely not better.

Excessively heavy menstruation (menorrhagia) can certainly cause iron loss, and thereby may warrant iron supplements. Interestingly, a small double-blind trial found evidence that iron supplements might actually help reduce menstrual bleeding in women with menorrhagia who are also iron-deficient.

A study of seventy-one human-immunodeficiency-virus-positive (HIV-positive) children noted a high rate of iron deficiency. One observational study of 296 men with HIV infection linked high intake of iron to a decreased risk of acquired immunodeficiency syndrome (AIDS) six years later.

Individuals taking drugs in the ACE inhibitor family frequently develop a dry cough as a side effect. One study suggests that iron supplementation can alleviate this symptom. However, iron can interfere with ACE inhibitor absorption, so it should be taken at a different time of day.

Pregnant women commonly develop iron deficiency anemia. Iron supplements, however, can be hard on the stomach, thereby aggravating morning sickness. One study found evidence that a fairly low supplemental dose of iron (20 mg daily) is nearly as effective for treating anemia of pregnancy as 40 mg or even 80 mg daily and is less likely to cause gastrointestinal side effects. Additionally, some types of iron supplements are easier for the body to digest than others, and using forms designed for pregnant women can help limit gastrointestinal upset.

Iron has been suggested as a treatment for attention deficit hyperactivity disorder (ADHD). However, there is only preliminary evidence that it may be effective in hyperactive children with low iron levels as indicated by ferritin levels. In one study, twelve weeks of 80 mg of ferrous sulfate improved symptoms in a small group of adolescents. Some evidence suggests that iron supplements with zinc improve ADHD symptoms. Further research is warranted in children and adults with ADHD.

Preliminary studies have linked low iron levels to restless legs syndrome. However, a small double-blind study found no benefit when iron supplements were given to healthy people, that is, those who were not iron-deficient. In addition, one study tested whether supplemental iron could increase the rate of saliva flow, but it failed to find a benefit.

Scientific Evidence

Sports performance. A double-blind, placebo-controlled trial of forty-two women without anemia but with evidence of slightly low iron reserves found that iron supplements significantly enhanced sports performance. Participants were put on a daily aerobic training program for the latter four weeks of this six-week trial. At the end of the trial, those receiving iron showed significantly greater gains in speed and endurance compared with those given placebo. In addition, a double-blind, placebo-controlled study of forty elite athletes without anemia but with mildly low iron stores found that twelve weeks of iron supplementation enhanced aerobic performance.

Benefits of iron supplementation were observed in other double-blind trials also involving mild cases of low iron stores. However, other studies failed to find significant improvements, suggesting that the benefits of iron supplements for nonanemic, iron-deficient athletes are small at most.

Menorrhagia. One small double-blind study found good results using iron supplements to treat heavy menstruation. This study, which was performed in 1964, saw an improvement in 75 percent of the women who took iron, compared to 32.5 percent of those who took placebo. Women who began with higher iron levels did not respond to treatment. This suggests once more that supplementing with iron is a good idea only if an individual is deficient in it.

Safety Issues

Iron supplements commonly cause gastrointestinal upset, but when they are taken at recommended dosages, serious adverse consequences are unlikely. However, excessive dosages of iron can be toxic, damaging the intestines and liver and possibly resulting in death. Iron poisoning in children is a common problem, so iron supplements should be kept out of the reach of children.

Mildly excessive levels of iron may be unhealthy for another reason: Iron acts as an oxidant (the opposite of an antioxidant), perhaps increasing the risk of cancer and heart disease (although this is controversial). Elevated levels of iron may also play a role in brain injury caused by stroke. In addition, excess iron appears to increase complications of pregnancy, and if breastfed infants who are not iron-deficient are given iron supplements, the effects may be negative rather than positive.

The simultaneous use of iron supplements and high-dose vitamin C can greatly increase iron absorption, possibly leading to excessive iron levels in the body. One study found that iron does not impair absorption of the drug methotrexate.

Important Interactions

People who are taking antibiotics in the tetracycline or quinolone (Floxin, Cipro) families, levodopa, methyldopa, carbidopa, penicillamine, thyroid hormone, calcium, soy, zinc, copper, or manganese can avoid iron absorption problems by waiting at least two hours following their dose of medication or supplement before taking iron. Individuals who take drugs that reduce stomach acid, such as antacids, H₂ blockers, and proton pump inhibitors, may need extra iron.

Individuals taking iron simultaneously with high doses of vitamin C may be absorbing too much iron. For people taking ACE inhibitors, iron may reduce coughing, a common side effect of ACE inhibitors. However, to avoid absorption problems, these individuals should wait at least two hours following their dose of medication before taking iron.

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