Iron is a supplement that is important for several different functions within the body. Iron can be found naturally in a number of foods such as soybeans, spinach, sesame seeds, pumpkin seeds, and several different types of beans including kidney and garbanzo beans. You can have iron deficiency, as well as iron toxicity. Since iron is found naturally in your body’s cells that aid breathing, iron is very important for overall respiratory health. Treatment of anemia (iron deficiency) should only be done under medical supervision. Pregnant and nursing women should limit their amount of supplemental iron intake. Iron supplements can also be toxic to small children. Caffeine, dairy, oxalic acid, phytic acid, and teas can decrease the absorption of iron. Iron can be found in tablet, or capsule form.
Iron is an essential trace mineral involved in the entire process of respiration, including oxygen and electron transport. The function and synthesis of hemoglobin, which carries most of the oxygen in the blood, is dependent on iron. Iron is also involved in the production of cytochrome oxidase, myoglobin, L-carnitine, and aconitase, all of which are involved in energy production in the body. In addition to its fundamental roles in energy production, iron is involved in DNA synthesis and may also play roles in normal brain development and immune function. Iron is also involved in the synthesis of collagen and the neurotransmitters serotonin, dopamine, and norepinephrine.
Iron-deficiency anemia is the most common nutritional disorder in the world. Although about 25% of the world's population is iron deficient, it should be noted that anemia is not always associated with iron deficiency. Low iron levels can occur from insufficient dietary intake, impairment of iron absorption, or loss of iron through bleeding. It is important to determine the cause before treating. Whether to treat iron deficiency (ferritin <20 mcg/L) in the absence of anemia (hemoglobin 11 g/dL or greater) is controversial. Preliminary data from NHANES III demonstrate that the prevalence of iron-deficiency anemia in the United States is very low. There is no known benefit of high iron storage status, and some evidence exists that a moderate increase in iron stores is a possible risk factor for ischemic heart disease and cancer. The safe upper range of iron intake is difficult to specify due to the complexity of the Western diet and iron physiology (Lynch et al 1996).
The best dietary sources of iron are green vegetables, legumes, and meat. Much of the iron ingested in the American diet in the form of enriched breads and cereals is not well absorbed. The average dietary intake of iron in the United States ranges from 10 to 20 mg daily. Some individuals, including adolescents and pregnant and lactating women, may be at risk for iron deficiency.
Actions & Pharmacology
Iron has putative immune-enhancing, anticarcinogenic, and cognition-enhancing activities.
The role of iron in resistance to infection is complex. Iron deficiency is known to impair response of T lymphocytes to mitogens and to decrease the bactericidal activity of neutrophils. On the other hand, bacteria require iron for growth, and bacterial virulence is enhanced by increased iron availability. Also, the presence of infection or inflammation changes the cytokine-mediated metabolism of iron, which complicates attempts to define the relative benefits and hazards of iron therapy for prophylaxis of infectious disease (Walter et al 1997). Some studies have shown that iron supplementation given to infants reduces the incidence of respiratory infections. Other studies have found no difference in groups of infants given either iron or a placebo. Adult studies cited in this review found no benefit of iron use for reducing infection rates, and suggested that more illness may occur with supplementation (Oppenheimer 2001).
Breath-holding spells in children have been overcome by iron supplementation. Along with improved iron status in these children, autonomic cardiovascular control during sleep was improved (i.e., increased heart rate variability, reduced ratio of low-frequency/high-frequency powers) (Orii et al 2002).
Researchers have theorized that excess iron could play a role in the etiology of cancer and coronary heart disease. Iron is able to catalyze reactions that produce free radical metabolites, which may damage cell membranes, cause chromosomal mutations, or oxidize low-density lipoproteins (LDL) into more atherogenic particles (Sempos et al 1996; Minotti 1993; Imlay et al 1988). Animal studies have confirmed that atherosclerotic plaques contain a high concentration of iron, and rats given large amounts of iron have increased LDL lipid peroxidation. In human studies, atherosclerosis has been associated with increased iron levels (Meyers 2000).
Cognitive Function/Children & Adolescents
One review assessed the various benefits of iron supplementation in early childhood based on reports from 26 studies of iron supplementation in children aged 0 to 4 years. Among the eight randomized, controlled trials addressing developmental issues, some positive effects on a variety of developmental outcomes, including cognitive function, were noted in five. A meta-analysis of randomized, clinical trials cited in the review found significant beneficial effects on mental development with supplementation—especially among those identified as anemic or iron deficient at baseline. In addition, the meta-analysis revealed that all children >7 years old significantly benefited from iron supplementation, obtained from either oral doses, fortified food and milk, or through parenteral administration. Lower, longer-term doses (2-12 months) seemed to provide greater benefit than very short courses of therapy (Iannotti et al 2006).
One trial in the review cited above bears mention. A randomized, double-blind, placebo-controlled trial of iron administration among preschoolers aged 3-4 years old (n=49) showed that 15 mg of iron supplementation in iron-deficient anemic subjects resulted in cognitive improvements including discrimination and information processing. Supplemented children exhibited 8% higher accuracy (p<0.05) and were significantly more efficient (mean difference = 1.09, p<0.05) than their untreated anemic counterparts, and made significantly fewer errors of commission (14% higher specificity, p<0.05). These effects did not extend to those preschoolers with adequate iron status (Metallinos-Katsaras et al 2004).
Iron supplementation improved hematological status and some measures of cognitive functioning in a double-blind, placebo-controlled study of 81 iron-deficient, nonanemic adolescent girls. Participants were randomly assigned to receive oral ferrous sulfate 650 mg twice daily or placebo for 8 weeks. Four tests of attention and memory were administered before and after the intervention. The supplemented group had significantly higher serum ferritin levels and performed significantly better than controls on a test of verbal learning and memory. Other measures of attention and learning were unchanged (Bruner et al 1996).
Positive results were also found in a randomized, double-blind, placebo-controlled study of 59 primarily nonanemic girls aged 16 or 17 years who took 105 mg daily of elemental iron as a liquid syrup or placebo. After 2 months, iron supplementation significantly improved subjective reports of lassitude, ability to concentrate in school, and mood. The majority of subjects reporting improvement had been hypoferremic prior to treatment. Physical fitness scores and subjective measures of appetite and sleep quality were unaffected by iron therapy (Ballin et al 1992).
One 3-year study demonstrated a relationship between iron status and cognitive abilities in young women of reproductive age—a group vulnerable to iron-deficiency. In this randomized, controlled trial, 152 women were assigned to one of three iron-status groups: iron sufficient (control group, CN); nonanemic, but with iron deficiency (ID group); or iron deficiency with anemia (IDA group). The groups were blinded to treatment with iron supplements or placebo. Significant improvements in serum ferritin following treatment were associated with a 5- to 7-fold improvement in cognitive performance, while faster completion of cognitive tasks was associated with significant improvements in hemoglobin levels (Murray-Kolb and Beard 2007).
Iron supplementation may reduce unexplained fatigue in nonanemic women. In a randomized, double-blind, placebo-controlled trial, 144 nonanemic women (aged 18 to 55 years, hemoglobin above 11.7 g/dL) with fatigue as a primary complaint were given placebo or long-acting ferrous sulfate providing 80 mg of elemental iron per day for 4 weeks. On a 10-point visual analog scale, fatigue scores at 1 month, relative to baseline, were reduced significantly more in the iron group than in the placebo group (p=0.004). After adjustments for age, depression and anxiety, and serum ferritin concentration, iron supplementation was the variable most associated with decrease in fatigue. Younger age was associated with a greater decrease in intensity of fatigue (Verdon et al 2003).
In adult and pediatric trials, both oral and intravenous iron supplementation were shown to overcome documented iron-deficiency anemia (Komolafe et al 2003; Shobha et al 2003; Kianfar et al 2000; Fridge et al 1998; Singh et al 1998). Athough an earlier study found that intravenous iron sucrose therapy was safer, more effective, and more convenient than oral ferrous sulfate in the treatment of severe anemia in pregnant women (Al-Momen et al 1996), a more recent trial reported equivalent short-term efficacy and overall tolerability with either route of administration. However, in this randomized, controlled study of anemic patients with inflammatory bowel disease (n=46), a better gastrointestinal tolerability for iron sucrose was observed (Schroder et al 2005). One large review found that levels of hemoglobin were consistently increased in iron-supplemented children who were anemic or had iron-deficient anemia at baseline (Iannotti et al 2006).
A Cochrane review of the effects of oral iron supplementation with or without folic acid during pregnancy identified 40 trials for inclusion involving 12,706 women. An overall lack of data on clinical maternal and infant outcomes precluded the reviewers from making definitive conclusions regarding the effects of supplementation on these parameters. The types of treatments studied were four main regimens of daily or intermittent iron, with or without folic acid, compared to placebo or each other. Weekly (intermittent) supplementation appeared to be as effective at preventing low hemoglobin levels as daily dosing (Pena-Rosas and Viteri 2006). A randomized, controlled study published around the same time as the review enrolled pregnant women of less than 20 weeks' gestation and randomized 429 of those with adequate hemoglobin and ferritin levels to treatment with a multivitamin containing 30 mg of ferrous sulfate (n=218) or placebo (n= 211). Mean birth weights increased by 108 g (p=.03) among the offspring of mothers receiving iron compared to the offspring of placebo-treated subjects. Additionally, the incidence of premature delivery was lower in the supplemented group compared to the control group (8% vs 14%; p=.05). These observations suggest a prophylactic role for iron supplementation started in early pregnancy beyond the commonly reported reduction of iron-deficiency anemia (Siega-Riz et al 2006).
The frequency of breath-holding spells (BHS) diminished significantly in children with this disorder (n=33) given iron 5 mg/kg/day for 16 weeks compared with controls (n=34). Some 88% of those given iron had complete or partial responses compared with 6% in the placebo group (Daoud et al 1997). In another study, children receiving iron supplements showed improved autonomic cardiovascular control during sleep (eg, increased heart rate variability and reduced ratio of low-frequency/high-frequency powers) (Orii et al 2002).
Indications & Usage
Approved by the FDA:
- Iron-deficiency anemia (prophylaxis and treatment)
Limited research suggests that supplemental iron could be helpful for reducing the frequency of breath-holding spells in children. It may also enhance cognition in children and adolescents who have a documented iron deficiency. Likewise, iron may have some favorable effects on immunity and exercise performance—but again, these benefits are most likely limited to those with acute or borderline iron deficiency. Iron supplementation has also been used for the following: Plummer-Vinson syndrome, malaria, herpes simplex outbreaks, pediatric diarrhea, intestinal helminth infection, microcephaly prophylaxis, and decreased thyroid function during very-low-calorie diets.
Iron supplements are contraindicated in patients with hemochromatosis and hemosiderosis. They are also contraindicated for treating anemias not caused by iron deficiency, such as hemolytic anemia or thalassemia, due to the risk of excess iron storage.
Parenteral preparations are not for subcutaneous administration. Sustained-release dosage forms should be avoided in patients who have conditions associated with intestinal strictures.
Precautions & Adverse Reactions
Treatment of iron-deficiency anemia must only be done under medical supervision. Iron supplements should be used with extreme caution in those with chronic liver failure, alcoholic cirrhosis, chronic alcoholism, and pancreatic insufficiency. Iron should also be used cautiously in those with a history of gastritis, peptic ulcer disease, and gastrointestinal bleeding. Patients with elevated serum ferritin levels should generally avoid iron supplements, as should those with an active or suspected infection.
In addition, patients should be aware that a moderate increase in iron stores has been associated with an increased risk of ischemic heart disease and cancer (Lynch et al 1996).
The most common side effects of iron supplements are gastrointestinal problems, including nausea, vomiting, bloating, abdominal discomfort, black stools, diarrhea, constipation, and anorexia. Enteric-coated iron preparations may prevent some of the gastrointestinal complaints associated with iron therapy. Temporary staining of teeth may occur from iron-containing liquids. Adverse effects from intramuscular iron injections include cutaneous pigmentation with iron deposits, sarcoma, nausea, vomiting, fever, chills, backache, headache, myalgia, malaise, and dizziness.
FDA-rated as Pregnancy Category C. Pregnant women should not use supplemental doses of iron higher than RDA amounts (27 mg daily) unless their physician recommends it.
Nursing mothers should not use supplemental doses of iron higher than RDA amounts (9 or 10 mg daily, depending on age) unless their physician recommends it.
Iron supplements can be highly toxic or lethal to small children. Those who take iron supplements should use childproof bottles and store them away from children.
Potential Supplement Interactions
Beta-carotene, l-cysteine, n-acetyl-l-cysteine
Using iron with these supplements may result in enhanced absorption of iron
Inositol hexphosphate, vanadium
Using iron with these supplements may result in decreased absorption of iron:
Using iron with copper may result in decreased copper status.
Tocotrienols, tocopherols (alpha-tocopherol, gamma-tocopherol, mixed tocopherols))
Concomitant use of iron and nonesterified tocopherols and tocotrienols, which are typically used in their nonesterified forms, may cause oxidation of tocotrienols and tocopherols.
Potential Food Interactions
Concomitant use may decrease the absorption of iron.
Concomitant use may decrease the absorption of iron.
Oxalic Acid (contained in spinach, sweet potatoes, rhubarb, beans)
Concomitant use may decrease the absorption of iron.
Phytic Acid (contained in unleavened bread, raw beans, seeds, nuts and grains, soy isolates)
Concomitant use may decrease the absorption of iron.
Teas and Other Tannin-Containing Herbs
Concomitant use may cause decrease the absorption of iron.
Concurrent use may result in decreased unconjugated captopril levels resulting in possible blood pressure elevations. Clinical Management: An alternative angiotensin converting enzyme (ACE) inhibitor may need to be prescribed to avoid interaction with iron preparations.
Concurrent use may result in decreased cefdinir efficacy. Clinical Management: The administration of cefdinir and iron supplements or vitamins containing iron should be separated by at least 2 hours.
Concurrent use may result in decreased enoxacin effectiveness. Clinical Management: Avoid concurrent use. However, if used concurrently, the dose of the iron salt should be given at least 6 hours before or 4 hours after the enoxacin dose.
Concurrent use may result in decreased etidronate absorption. Clinical Management: The administration of etidronate and iron or any supplement containing iron should be separated by at least 2 hours.
Concurrent use may result in decreased levodopa effectiveness. Clinical Management: If products containing iron, such as vitamins or iron supplements, are used in a patient receiving levodopa, monitor for an increase in Parkinson's disease symptoms. If symptoms worsen, consider adjusting the levodopa dose or avoiding iron-containing products, if possible.
Concurrent use may result in worsened hypothyroidism. Clinical Management: Separate the administration of iron salts and levothyroxine as much as possible. Monitor thyroid function tests.
Concurrent use may result in decreased methyldopa effectiveness. Clinical Management: Monitor for decreased methyldopa efficacy if both drugs are administered concurrently.
Concurrent use may result in decreased mycophenolate mofetil efficacy. Clinical Management: The administration of mycophenolate mofetil and iron supplements or vitamins containing iron should be separated by at least 2 hours.
Concurrent use may result in decreased penicillamine effectiveness. Clinical Management: If penicillamine and iron are used concurrently, separate administration of each by at least 2 hours.
Quinolones (ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, sparfloxacin, temafloxacin, trovafloxacin)
Concomitant use may decrease the absorption of both the quinolone and iron supplement. Clinical Management: If possible, avoid concurrent use. If both agents are administered together, separate doses by 2 to 6 hours before and 2 to 8 hours after, depending on dosing schedule.
Tetracyclines (demeclocycline, doxycycline, methacycline, minocycline, oxytetracycline, rolitetracycline, tetracycline)
Concomitant use may decrease the absorption of both the tetracycline and iron supplement. Clinical Management: If both medicines must be used concurrently, iron salts should be given not less than three hours before or two hours after the tetracycline dose.
Concurrent use may result in decreased gastrointestinal absorption of both drugs. Clinical Management: If it is necessary to administer iron supplements during trientine therapy, allow a minimum of 2 hours between administrations of each drug.
Aluminum, calcium or magnesium containing products
Concomitant use may result in decreased iron effectiveness. Clinical Management: Concurrent administration of iron salts and aluminum, calcium, or magnesium containing products is not recommended. If concurrent use cannot be avoided, iron salts should be taken at least one hour before or two hours after aluminum, calcium or magnesium containing products.
Concurrent use may result in decreased iron effectiveness. Clinical Management
Avoid chloramphenicol in patients receiving iron therapy for iron deficiency anemia.
Concurrent use may result in decreased iron effectivene ss. Clinical Management: To prevent cholestyramine from binding dietary iron, separate administration of each drug by at least 4 hours.
Concurrent use may result in reduced iron absorption. Clinical Management: Increased iron dosage may be required by patients who take gossypol with iron supplements.
Proton Pump Inhibitors (PPIs) (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)
Concurrent use may result in reduced iron bioavailability. Clinical Management: Monitor the patient for iron efficacy if a PPI is used concomitantly.
Concurrent use may result in decreased gastrointestinal absorption of zinc and/or iron. Clinical Management: Separate administration of zinc and iron by at least 2 hours.
Concurrent use may result in reduced absorption of both iron and acetohydroxamic acid.
Concurrent use may result in increased liver iron stores.
Concurrent use may result in enhanced absorption of iron.
Concurrent use may result in decreased absorption of iron.
Concurrent use may result in reduced iron absorption.
Concurrent use may result in decreased iron effectiveness.
Concurrent use may result in decreased bioavailability of iron.
Concurrent use may result in inhibition or iron absorption.
Concurrent use may result in poor iron absorption.
Concurrent use may result in a decrease in sulfasalazine concentration.
Acute iron overdose can be divided into four stages. In the first, which occurs up to 6 hours after ingestion, the principal symptoms are vomiting and diarrhea. Other symptoms include hypotension, tachycardia, and CNS depression ranging from lethargy to coma. The second phase may occur at 6 to 24 hours after ingestion and is characterized by a temporary remission. In the third phase, gastrointestinal symptoms recur accompanied by shock, metabolic acidosis, coma, hepatic necrosis and jaundice, hypoglycemia, renal failure, and pulmonary edema. The fourth phase may occur several weeks after ingestion and is characterized by gastrointestinal obstruction and liver damage.
In a young child, 75 mg/kg is considered extremely dangerous. A dose of 30 mg/kg can lead to symptoms of toxicity. The lethal dosage range is estimated at ≥ 180 mg/kg. A peak serum iron concentration of 5 mcg/mL or more is associated with moderate to severe poisoning.
Mode of Administration
Capsule, elixir, suspension, tablet
Ferrous fumarate is available in the following forms and strengths:
Chewable tablets — 100 mg
Suspension — 100 mg/5 mL
Tablets — 200 mg, 300 mg, 325 mg, 350 mg
Ferrous gluconate is available in the following forms and strengths:
Enteric-coated tablets — 325 mg
Tablets — 300 mg, 320 mg, 324 mg, 325 mg
Ferrous sulfate is available in the following forms and strengths:
Capsules, extended-release — 250 mg
Enteric-coated tablets — 324 mg, 325 mg
Elixir — 220 mg/5 mL
Liquid — 75 mg/0.6 mL
Tablets — 195 mg, 300 mg, 324 mg, 325 mg
Exsiccated ferrous sulfate is available in the following forms and strengths:
Capsules — 150 mg, 159 mg
Enteric-coated tablets — 200 mg
Tablets — 200 mg
Tablet, extended-release — 160 mg
The following lists the elemental iron content of various forms:
Iron Salt % Iron *brFerrous fumarate 33 *brFerrous gluconate 11.6 *brFerrous sulfate 20 *brFerrous sulfate, anhydrous 30
All doses are for oral administration unless otherwise note. Iron supplementation should be done only under a physician's supervision.
The following lists the Recommended Dietary Allowance (RDA) for iron:
Males and females — Infants to 6 months 0.27 mg /d; 7 to 12 months
11 mg/d; 1 to 3 years
7 mg/d; 4 to 8 years 10 mg/d; 9 to 13 years 8 mg/d.
Males — 14 to 18 years
11 mg/d; ≥ 19 years: 8 mg/d
Females — 14 to 18 years
15 mg/d; 19 to 50 years
18 mg/d; ≥ 51 years: 8 mg/d
Pregnancy — all ages
Lactation — 14 to 18 years
10 mg/d; 19 to 50 years 9 mg/d
Decreased Thyroid Function During Very-Low-Calorie Diets: 9 mg/d or more to bring total iron intake to 1.5 times the RDA.
Impaired Athletic Performance: Treat only confirmed iron deficiency.
Inflammatory Bowel Disease: Treat only confirmed iron deficiency.
Iron-Deficiency Anemia (intramuscular injection): The total parenteral dose required for restoration of hemoglobin and body stores of iron can be approximated using the following formula: Adults and children over 15 kg: dose (mL) = 0.0442 (desired hemoglobin − observed hemoglobin) x lean body weight in kg + (0.26 x lean body weight in kg).
Iron Deficiency In Pregnancy: 60 to 100 mg/d.
Iron Insufficiency Therapy: immediate-release dosage forms: 2 to 3 mg/kg daily in 3 divided doses; sustained-release dosage forms: 50 to 100 mg daily.
Plummer-Vinson Syndrome: 2 to 3 mg/kg/d.
Prevention of Iron Deficiency in Pregnancy: 400 to 1,000 mg daily.
Adolescent Girls With Low Ferritin: 105 to 260 mg daily.
Breath-Holding Syndrome (ferrous sulfate solution): 5 mg/kg daily.
Cognitive Function: 105 to 260 mg daily.
Iron Deficiency: 6 mg/kg/d for 2 to 3 months; absorption of iron is increased if given with a source of vitamin C.
Iron-Deficiency Anemia: premature infants, 2 to 4 mg/kg/d in 2 to 4 divided doses, up to a maximum of 15 mg/d; children, 3 to 6 mg/kg/d in 1 to 3 divided doses. Intramuscular injection
The total parenteral dose required for restoration of hemoglobin and body stores of iron can be approximated using the following formula: Children 5 to 15 kg: dose (mL) = 0.0442 (desired hemoglobin − observed hemoglobin) x weight in kg + (0.26 x weight in kg).