Iron deficiency is the most common nutritional deficiency in the U.S. It affects 30-50% of infants under the age of two, teenage girls, pregnant women, and the elderly, who are at higher risk for iron deficiency. Iron deficiency is the leading cause of anemia in the U.S. 1
Even though iron is a mineral that is essential to human health, the human body contains only 3-4 grams. The total quantity of iron in the body varies with weight, hemoglobin concentration, sex, and storage compartment size.
Average daily intake of iron in North America and Europe is between 10 and 30 mg. Healthy individuals absorb 5-10% of dietary iron, whereas those who are iron deficient absorb 10-20%. Absorption of iron mainly occurs in the duodenum of the small intestine. 2
There are two forms of dietary iron: heme and non-heme iron. Heme iron, found in animal products, originates from hemoglobin and myoglobin and is the most efficiently absorbed form of iron. Non-heme iron, found in plant foods and iron-enriched or iron-fortified foods, is poorly absorbed compared to heme iron.
Iron supplements are available in the ferrous (Fe2+) or the ferric (Fe3+) form; ferrous iron supplements are better absorbed that ferric iron supplements. Ferrous iron supplements include ferrous fumarate (33% elemental iron), ferrous sulfate (20% elemental iron), and ferrous gluconate (12% elemental iron).3,4 Ferric iron supplements are reduced to the ferrous form once in the body.
Iron concentrations in the body are tightly controlled, principally through sequestration of iron in proteins for use or storage. If iron is not well-controlled, such as in certain disease states, redox cycling may occur which produces damaging reactive oxygen species.
Iron is necessary for function and synthesis of hemoglobin, which transports oxygen through the circulatory system to all tissues of the body. 5,6 Reduced oxygen transport can increase fatigue and impair immune function through oxidation-reduction reactions.5,7,8 It is necessary for production and function of cytochromes in the electron transport chain, as well as for activating enzymes in the Krebs cycle.
Iron is involved in synthesis of DNA and plays a role in immune function.
Iron is a necessary component in brain development and function, and is needed to synthesize certain neurotransmitters (e.g. serotonin, dopamine, norepinephrine) and collagen. Iron deficiency may cause learning problems in children and adolescents, probably because iron has a role in synthesizing neurotransmitters.
* Values are Adequate Intakes (AI), others are RDA.
Iron supplementation is strongly recommended when a true deficiency is present, especially in certain populations. Iron deficiency can be evaluated by 3 different measurements: 10
1) Plasma Ferritin
2) Transferrin Saturation
<10 g/dl - females** <12 g/dl - males
<31% -- females** <37% -- males
*Hemoglobin (Hgb) concentration is
unsuitable as a diagnostic tool of iron deficiency anemia by itself, because:»
it is affected only late in the disease» it does not separate iron deficiency
from other anemias» the values of normal individuals vary widely**In pregnancy:
Hgb <9.5 g/dl in the 2nd trimester, Hgb <9.0 g/dl in the 3rd trimester;
Hct <30% in the 2nd and 3rd trimesters
Iron deficiency is second only to hunger as a major nutritional problem in the world; the World Health Organization considers iron deficiency to be the number one nutritional disorder in the world.11 It has been estimated that as many as 80% of people in the world may be iron deficient with up to 30% of people having iron deficiency anemia. 12
Infants and women of childbearing age are at greatest risk for iron deficiency in the United States.13 Evaluation of data from the 1999-2000 National Health and Nutrition Examination Survey (NHANES)estimates that 7% of toddlers and 9 to 16% of adolescent and adult females are iron deficient. 13 Poverty is the greatest risk factor for iron deficiency and anemia.
Other conditions associated with increased risk for iron deficiency are: hemorrhage, anemia, nephrosis, infection, achlorhydria, steatorrhea, malabsorption, parasites, protein-calorie malnutrition, and decreased GI transit time.
Inadequate dietary iron can cause symptoms such as weakness, impaired cognition, decreased athletic performance, and lack of endurance. Infants born to anemic mothers are more likely to develop anemia in the first year.
If insufficient dietary iron persists, iron-deficiency anemia may result. Symptoms of iron-deficiency anemia include pale skin and mucous membranes, fatigue, dizziness, sensitivity to cold, shortness of breath, rapid heartbeat, and a tingling sensation in the extremities.
Iron supplements can be extremely toxic to small children. Doses of 3 to 10 grams can be fatal to children. Iron can cause irritation to the mucosa with ulceration and bleeding, hypoxia, metabolic acidosis, liver damage and renal failure. Death can occur in 12 to 48 hours. Extreme care should be taken to prevent small children from consuming iron supplements (including multivitamins and prenatal vitamins).
Iron should be used with caution in those with a history of gastrointestinal (GI) bleeding, peptic ulcer disease or gastritis.
People with hemochromatosis or hemosiderosis should not use iron supplements. Other people who are at high risk for iron overload are those with the iron-loading anemias, thalassemia and sideroblastic anemia. Elevated erythropoiesis in individuals causes an increased absorption of iron.
Iron in food is either heme iron, found only in animal products, or non-heme iron, which is in plant foods and about 60% of iron in animal products. Non-heme iron is not as well absorbed as heme iron.
The best dietary sources of iron are dark green vegetables and legumes. Good dietary sources of iron are kelp, brewer's yeast, blackstrap molasses, clams, oysters, wheat bran, nuts and seeds, dried fruits, and beef liver.
Although non-heme iron is found in some breads and cereals in the American diet, much of the iron is not well absorbed.
The iron in many foods is not readily available to the human body. Iron absorption is decreased by the presence of fiber, phytates, phenolic compounds, soy proteins, coffee, and tea.14 Tea and coffee reduce the absorption of iron by 60% and 40% respectively, by forming insoluble complexes.
Iron absorption is enhanced by vitamin C and elevated need for iron in the body.14
The prevalence of iron deficiency among adolescents is high, especially among girls. A published study using the NHANES III data to examine the iron status of a sample of school-aged children in the U.S., found that iron deficiency was most prevalent among adolescent girls. 15
Vegetarians are at risk for impaired iron status, despite consumption of relatively high levels of dietary iron. Since the iron in plants is exclusively non-heme iron, plant sources of iron have limited bioavailability.2 Female vegetarians are at especially high risk for iron insufficiency. However, rates of iron-deficiency anemia are similar for vegetarians and non-vegetarians.16
It has been suggested that demands for iron are the highest in the third trimester of pregnancy, in order to support fetal erythropoiesis and placental iron accumulation.17
18,19,20 Antacids may reduce GI absorption of iron. Administration of these agents should be as far apart as possible.
Ascorbic acid at doses more than 200 mg has been shown to enhance absorption of iron by more than 30%.
Chloramphenicol, an antibiotic agent, may delay responses to iron therapy. Patients with iron-deficient anemia receiving iron supplements should avoid chloramphenicol.
Gastrointestinal absorption of quinolones or antibiotics may be decreased because of formation of ferric ion-quinolone complex. Oral preparations containing iron should not be administered within 2 hours of oral quinolones.
Concomitant use within two hours of iron and a tetracycline antibiotic may decrease absorption and serum iron concentrations. Absorption of iron salts may also be decreased. If concomitant therapy is necessary, patients should take the drug 2 hours before or 4 hours after oral iron administration.
Cimetidine, an H2 blocker, may reduce GI absorption of iron. If possible, cimetidine should be either separated from or avoided with iron therapy.
Absorption of methyldopa, a hypertension medication, may be decreased with concomitant iron therapy, possibly resulting in decreased efficacy and increased urinary excretion of the sulfate conjugate of the drug. Levodopa appears to form chelates with iron salts, decreasing absorption and serum concentrations. People receiving chronic methyldopa with oral ferrous sulfate may experience an increase in blood pressure; discontinuation of the iron supplement may cause a decrease in blood pressure. Patients who have to take both iron supplements and methyldopa should consult a physician for decreased hypotensive effect of methyldopa.
Efficacy of levothyroxine, a thyroid agent, may be decreased with concomitant administration of iron, resulting in hypothyroidism. If both iron and thyroxine are necessary concomitantly, the agents should be separated by at least 2 hours, and thyroid function should be monitored.
Gastrointestinal absorption of penicillamine, used for copper toxicity, may be reduced due to its chelation of iron molecules. Administration of the drug and iron therapy should be at least 2 hours apart.
Iron supplements can interfere with the absorption of catopril, angiotensin-converting enzyme (ACE) inhibitor, used for hypertension, and other ACE inhibitors. It is recommended that iron supplements and ACE inhibitors be taken at least 2 to 3 hours apart.
Dairy products or calcium supplementation may interfere with iron absorption. Coffee and tea consumed with a meal or within 1 hour after a meal may inhibit absorption of dietary iron. Iron supplements
should be taken between meals.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
Topic: Iron status and supplementation for athletes
Randomized, double-blind, placebo-controlled trial of iron supplementation in female soldiers during military training: effects on iron status, physical performance, and mood.
A randomized, double blind, placebo controlled trial investigated the iron status and effects of iron supplements on a group of female soldiers during basic training. Two-hundred-nineteen women participated in the eight week trial. Participants were randomly assigned to receive 100 mg ferrous sulfate or a placebo during basic combat training. Iron status, running time (2 mile), and mood were assessed. Iron status was altered by basic combat training. Red blood cell distribution width and soluble transferrin receptor were elevated during basic combat training (P<0.05); serum ferritin was lowered by basic combat training (P<0.05). For the participants consuming iron supplements, iron loss was reduced. Group-by-time interactions were observed for serum ferritin and soluble transferrin receptor (P<0.01). For participants who had iron deficiency anemia at the beginning of the trial, iron supplements improved vigor scores (P<0.05). Participants with iron deficiency anemia at the beginning of the trial also had improved running times (P<0.05) after iron supplementation. This trial demonstrated that basic combat training negatively affects iron status and that iron supplements can help to limit the amount of iron lost. Women with iron deficiency anemia at the beginning of the trial benefited the most from iron supplements.21
Oral iron treatment has a positive effect on iron metabolism in elite soccer players.
A study of 35 elite soccer players in Spain investigated the effects of iron supplements in athletes. Twenty four athletes were assigned to receive 80 mg iron supplement daily for three weeks; iron status markers were assessed at baseline and at the end of the trial. Eleven athletes received no supplement; iron status markers were assessed only at the end of the trial. Iron supplements were associated with an increase in (versus baseline): serum iron (P < 0.05), serum ferritin (P < 0.01), and transferrin saturation (P < 0.01). Compared to the control group, iron supplements were associated with higher hematocrit (P < 0.01), mean corpuscular volume (P < 0.01), ferritin (P < 0.01), and transferrin saturation (P < 0.01). The control group had a higher percentage of low serum ferritin compared to the iron supplemented group (P<0.01). Iron supplements were found to positively benefit elite athletes’ iron status in this study.[~22~]
Relation of iron and red meat intake to blood pressure: cross sectional epidemiological study.
An epidemiological study investigated the associations between iron or red meat intake and blood pressure in an international group of participants. The study included 4,680 people from Japan, China, the United Kingdom, and the United States (participants in the INTERMAP study). Participants’ ages ranged from 40-59 years. The primary outcome measure was the average of eight blood pressure readings; findings were adjusted for potential confounders. Total dietary iron intake higher by 4.20 mg (P<0.01) and dietary non-heme iron intake higher by 4.13 mg (P<0.001) were associated with lower systolic blood pressure (-1.39 mmHg and -1.45 mmHg, respectively). Supplemental iron intake had smaller associations with blood pressure than dietary iron intake. In agreement with prior studies, red meat intake was associated with blood pressure: 102.6 g in 24 hours higher intake was associated with higher systolic blood pressure (1.25 mmHg). Dietary non-heme iron may have a beneficial effect on systolic blood pressure but these results need to be followed up with experimental trials to investigate the mechanisms.[~23~]
Iron treatment normalizes cognitive functioning in young women.
A blinded, placebo-controlled, stratified trial investigated the effects of iron supplements on cognitive function in women aged 18 to 35 years. One-hundred-forty-nine women participated in the study. Participants were randomly assigned to receive iron supplements (160 mg ferrous sulfate) or a placebo daily during the 16 week trial. Cognitive performance tests were completed at baseline and after 16 weeks of supplements/placebo. Before the intervention, women with iron deficiency anemia (n=34) demonstrated deficits compared to iron-sufficient women (n=42). Specifically, iron-sufficient women performed better on cognitive tasks and completed cognitive tasks faster than women with anemia (P=0.011 and P=0.038, respectively). Iron supplements were associated with significant improvements in serum ferritin and hemoglobin. Such improvements were also associated with 5 to 7 fold improvements in cognitive performance (serum ferritin) and improved speed with completion of tasks (hemoglobin). These results suggest that iron status impacts the cognitive function of young women.[~24~]
Topic: Iron during pregnancy and the postpartum period
Maternal iron deficiency anemia affects postpartum emotions and cognition.
A prospective, randomized, placebo-controlled intervention trial investigated the relationship between iron deficiency anemia, postpartum emotional state, and cognition. Eighty-one women who had given birth to normal birth-weight, full-term babies participated in the trial. Participants were divided into three groups: nonanemic controls, anemic mothers given a placebo (10 mcg folate and 25 mg vitamin C), and anemic mothers given an iron supplement (125 mg ferrous sulfate, 10 mcg folate, and 25 mg vitamin C). All mothers were assessed for hematologic status (including iron), socioeconomic status, cognitive function, emotional status, and mother-infant interactions at 10 weeks and 9 months postpartum. Infants were also assessed for development at 10 weeks and 9 months. At 10 weeks, there was no difference between anemic and nonanemic mothers behavioral and cognitive scores. For anemic mothers, iron supplements improved depression scales, stress scales, and Raven’s Progressive Matrices test by 25% (P<0.05). Strong associations were found between hemoglobin, mean corpuscular volume, and transferrin saturation and cognitive variables (Digit Symbol) and behavioral variables (anxiety, stress, and depression). This study demonstrated that iron deficiency affected postpartum emotions and cognition and suggests that iron supplements significantly improve both behavioral and cognitive function.[~25~]
Treatments for iron-deficiency anaemia in pregnancy.
A meta-analysis of international randomized, controlled trials evaluated a variety of treatments for iron-deficiency anemia during pregnancy. Twenty-three trials were included in the analysis which totaled 3,198 women. Oral iron supplements during pregnancy were evaluated in one trial which included 125 women. The risk ratio for anemia was 0.38 (95% confidence interval 0.26 to 0.55) indicating that oral iron reduced the incidence of anemia during pregnancy. It was not possible to stratify the results by dose or severity of anemia. Two trials found better hematological measures with iron supplements than placebo. Adverse effects were increased with increasing results. The results of this meta-analysis and systematic review indicate that low-dose daily iron supplements may be effective for preventing iron deficiency anemia during pregnancy. Low-dose supplements may be better tolerated than higher dose supplements.[~26~]
Effect of routine iron supplementation with or without folic acid on anemia during pregnancy.
A systematic review was conducted to evaluate the efficacy of iron supplements or iron supplements with folic acid for anemia during pregnancy. Thirty-one randomized or quasi-randomized trials were included in the analysis. At term, incidence of anemia was reduced by 73% (RR=0.27; 95% CI: 0.17-0.42; random effects model; versus placebo) and incidence or iron-deficiency anemia was reduced by 67% (RR=0.33; 95% CI: 0.16-0.69; random effects model; versus placebo) by daily iron supplementation alone. Daily supplements including both iron and folic acid reduced anemia by 73% at term (RR=0.27; 95% CI: 0.12-0.56; random effects model; versus placebo) but the effect of iron and folic acid on iron-deficiency anemia was non-significant (RR=0.43; 95% CI: 0.17-1.09; random effects model). Intermittent supplements were not found to be different from daily supplements of iron plus folic acid (RR=1.61; 95% CI: 0.82-3.14; random effects model). The results of this systematic review suggest that iron or iron plus folic acid are equally effective for preventing anemia during pregnancy. However, only iron alone was found to be effective for preventing iron-deficiency anemia.[~27~]
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