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Iron

Also indexed as: Ferrous Sulfate

Illustration

Iron is an essential mineral. It is part of hemoglobin, the oxygen-carrying component of the blood. Iron-deficient people tire easily in part because their bodies are starved for oxygen. Iron is also part of myoglobin, which helps muscle cells store oxygen. Without enough iron, adenosine triphosphate (ATP; the fuel the body runs on) cannot be properly synthesized. As a result, some iron-deficient people become fatigued even when their hemoglobin levels are normal (i.e., when they are not anemic).

Where is it found?

The most absorbable form of iron, called “heme” iron, is found in oysters, meat and poultry, and fish. Non-heme iron is also found in these foods, as well as in dried fruit, molasses, leafy green vegetables, wine, and iron supplements. Acidic foods (such as tomato sauce) cooked in an iron pan can also be a source of dietary iron.

Iron has been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings Health Concerns
3Stars

Childhood intelligence (for deficiency only)

Depression (for deficiency only)

Iron-deficiency anemia

Menorrhagia (heavy menstruation) (for deficiency only)

2Stars

Athletic performance (for deficiency only)

Attention deficit–hyperactivity disorder (for deficiency only)

Breast-feeding support

Canker sores

Celiac disease (for deficiency only)

Pre- and post-surgery health (for deficiency or for major surgery)

Pregnancy and postpartum support (with medical supervision)

Restless legs syndrome (for deficiency only)

1Star

Alzheimer’s disease (in combination with coenzyme Q10 and vitamin B6)

Dermatitis herpetiformis

HIV support

Infertility (female) (for deficiency only)

3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

Vegetarians eat less iron than non-vegetarians, and the iron they eat is somewhat less absorbable. As a result, vegetarians are more likely to have reduced iron stores.1 However, iron deficiency is not usually caused by a lack of iron in the diet alone. An underlying cause, such as iron loss in menstrual blood, often exists.

Pregnant women, marathon runners, people who take aspirin, and those who have parasitic infections, hemorrhoids, ulcers, ulcerative colitis, Crohn’s disease, gastrointestinal cancers, or other conditions that cause blood loss or malabsorption are likely to become deficient.

Infants living in inner city areas may be at increased risk of iron-deficiency anemia2 and suffer more often from developmental delays as a result.3 4 Supplementation of infant formula with iron up to 18 months of age in inner city infants has been shown to prevent iron-deficiency anemia and to reduce the decline in mental development seen in such infants in some,5 but not all,6 studies.

Breath-holding spells are a common problem affecting about 27% of healthy children.7 These spells have been associated with iron-deficiency anemia,8 and several studies have reported improvement of breath-holding spells with iron supplementation.9 10 11 12

People who fit into one of these groups, even pregnant women, shouldn’t automatically take iron supplements. Fatigue, the first symptom of iron deficiency, can be caused by many other things. A doctor should assess the need for iron supplements, since taking iron when it isn’t needed does no good and may do some harm.

Which forms of supplemental iron are best?

All iron supplements are not the same. Ferrous iron (e.g. ferrous sulfate) is much better absorbed than ferric iron (e.g. ferric citrate).13 14 The most common form of iron supplement is ferrous sulfate, but it is known to produce intestinal side effects (such as constipation, nausea, and bloating) in many users.15 Some forms of ferrous sulfate are enteric-coated to delay tablet dissolving and prevent some side effects,16 but enteric-coated iron may not absorb as well as iron from standard supplements.17 18 19 Other forms of iron supplements, such as ferrous fumarate,20 21 ferrous gluconate,22 heme iron concentrate,23 24 25 26 and iron glycine amino acid chelate27 28 are readily absorbed and less likely to cause intestinal side effects.

How much is usually taken?

If a doctor diagnoses iron deficiency, iron supplementation is essential. To treat iron deficiency, a common recommended amount for an adult is 100 mg per day; that amount is usually reduced after the deficiency is corrected. When iron deficiency is diagnosed, the doctor must also determine the cause. Usually it’s not serious (such as normal menstrual blood loss or blood donation). Occasionally, however, iron deficiency signals ulcers or even colon cancer.

Some premenopausal women become marginally iron deficient unless they supplement with iron. However, the 18 mg of iron present in many multivitamin-mineral supplements is often adequate to prevent deficiency. A doctor should be consulted to determine the amount of iron that is needed.

Are there any side effects or interactions?

Iron (ferrous sulfate) is the leading cause of accidental poisonings in children.29 30 31 The incidence of iron poisonings in young children increased dramatically in 1986. Many of these children obtained the iron from a child-resistant container opened by themselves or another child, or left open or improperly closed by an adult.32 Deaths in children have occurred from ingesting as little as 200 mg to as much as 5.85 grams of iron.33 Keep iron-containing supplements out of a child’s reach.

Hemochromatosis, hemosiderosis, polycythemia, and iron-loading anemias (such as thalassemia and sickle cell anemia) are conditions involving excessive storage of iron. Supplementing iron can be quite dangerous for people with these diseases.

Supplemental amounts required to overcome iron deficiency can cause constipation. Sometimes switching the form of iron (see “Which forms of supplemental iron are best?” above), getting more exercise, or treating the constipation with fiber and fluids is helpful, though fiber can reduce iron absorption (see below). Sometimes the amount of iron must be reduced if constipation occurs.

Some researchers have linked excess iron levels to diabetes,34 cancer,35 increased risk of infection,36 systemic lupus erythematosus (SLE),37 exacerbation of rheumatoid arthritis,38 and Huntington’s disease.39 The greatest concern has surrounded the possibility that excess storage of iron in the body increases the risk of heart disease.40 41 42 Two analyses of published studies came to different conclusions about whether iron could increase heart disease risk.43 44 One trial has suggested that such a link may exist, but only in some people (possibly smokers or those with elevated cholesterol levels).45 The link between excess iron and any of the diseases mentioned earlier in this paragraph has not been definitively proven. Nonetheless, too much iron causes free radical damage, which can, in theory, promote or exacerbate most of these diseases. People who are not iron deficient should generally not take iron supplements.

Patients on kidney dialysis who are given injections of iron frequently experience “oxidative stress”. This is because iron is a pro-oxidant, meaning that it interacts with oxygen molecules in ways that can damage tissues. These adverse effects of iron therapy may be counteracted by supplementation with vitamin E.46

Supplementation with iron, or iron and zinc, has been found to improve vitamin A status among children at high risk for deficiency of the three nutrients. 47

People with hepatitis C who have failed to respond to interferon therapy have been found to have higher amounts of iron within the liver. Moreover, reduction of iron levels by drawing blood has been shown to decrease liver injury caused by hepatitis C.48 Therefore, people with hepatitis C should avoid iron supplements.

In some people, particularly those with diabetes, insulin resistance syndrome, or liver disease, a genetic susceptibility to iron overload has been reported.49

Many foods, beverages, and supplements have been shown to affect the absorption of iron.50

Foods, beverages and supplements that interfere with iron absorption include

  • Green tea (Camellia sinensis).51 52 53 54 This effect may be desirable for people with iron overload diseases, such as hemochromatosis. The inhibitory effect of green tea on iron absorption was 26% in one study.55

  • Coffee (Coffea arabica, C. robusta).56 57 58

  • Red wine, particularly the polyphenol component (also found in tea).59 60 Since wine is also a dietary source of iron, it is not clear whether drinking red wine would lead to a deficiency of iron.

  • Phytate (phytic acid), found in unleavened wheat products such as matzoh, pita, and some rye crackers; in wheat germ, oats, nuts, cacao powder, vanilla extract, beans, and many other foods, and in IP-6 supplements.61 62 63

  • Whole wheat bran, independent of its phytate content, has been shown to inhibit iron absorption.64

  • Calcium from food and supplements interferes with heme-iron absorption.65 66

  • Soy protein.67 68

  • Eggs.69 70

Foods and supplements that increase iron absorption include

Although vitamin C increases iron absorption,76 77 78 79 the effect is relatively minor.80

Taking vitamin A with iron helps treat iron deficiency, since vitamin A improves the absorption and/or utilization of iron.81 82

Although soy protein has been shown to decrease iron absorption (see above), certain soy-containing foods (e.g. tofu, miso, tempeh) have significantly improved iron absorption.83 Some soy sauces may also enhance iron absorption.84

Alcohol, but not red wine, has been reported to increase the absorption of ferric, but not ferrous, iron.85 86

Iron has been reported to potentially interfere with manganese absorption. In one trial, women with high iron status had relatively poor absorption of manganese.87 In another trial studying manganese/iron interactions in women, increased intake of “non-heme iron”—the kind of iron found in most supplements—decreased manganese status.88 These interactions suggest that taking multiminerals that include manganese may protect against manganese deficiencies that might otherwise be triggered by taking isolated iron supplements.

Are there any drug interactions?
Certain medicines may interact with iron. Refer to drug interactions for a list of those medicines.

References:

1. Sullivan JL. Stored iron and ischemic heart disease. Circulation 1992;86:1036 [editorial].

2. Pollitt E. Poverty and child development: relevance of research in developing countries to the United States. Child Dev 1994;65(2 Spec No):283–95.

3. Hurtado EK, Claussen AH, Scott KG. Early childhood anemia and mild or moderate mental retardation. Am J Clin Nutr 1999;69:115–9.

4. Roncagliolo M, Garrido M, Walter T, et al. Evidence of altered central nervous system development in infants with iron deficiency anemia at 6 mo: delayed maturation of auditory brainstem responses. Am J Clin Nutr 1998;68:683–90.

5. Williams J, Wolff A, Daly A, et al. Iron supplemented formula milk related to reduction in psychomotor decline in infants from inner city areas: randomised study. BMJ 1999;318:693–7

6. Morley R, Abbott R, Fairweather-Tait S, et al. Iron fortified follow on formula from 9 to 18 months improves iron status but not development or growth: a randomised trial. Arch Dis Child 1999;81:247–52.

7. Bridge EM, Livingston S, Tietze C. Breath-holding spells: their relationship to syncope, convulsions and other phenomena. J Pediatr 1943;23:539–61.

8. Holowach J, Thurston DL. Breath-holding spells and anemia. N Engl J Med 1963;268:21–3.

9. Bhatia MS, Singhal PK, Dhar NK, et al. Breath holding spells: an analysis of 50 cases. Indian Pediatr 1990;27:1073–9.

10. Colina KF, Abelson HT. Resolution of breath-holding spells with treatment of concomitant anemia. J Pediatr 1995;126:395–7.

11. Daoud AS, Batieha A, al-Sheyyab M, et al. Effectiveness of iron therapy on breath-holding spells. J Pediatr 1997;130:547–50.

12. Mocan H, Yildiran A, Orhan F, Erduran E. Breath holding spells in 91 children and response to treatment with iron. Arch Dis Child 1999;81:261–2.

13. Dietzfelbinger H. Bioavailability of bi- and trivalent oral iron preparations. Investigations of iron absorption by postabsorption serum iron concentrations curves. Arzneimittelforschung 1987;37:107–12 [review].

14. Davidsson L, Kastenmayer P, Szajewska H, et al. Iron bioavailability in infants from an infant cereal fortified with ferric pyrophosphate or ferrous fumarate.Am J Clin Nutr 2000;71:1597–602.

15. Hansen CM. Oral iron supplements. Am Pharm 1994 Mar;NS34:66–71 [review].

16. Simmons WK, Cook JD, Bingham KC, et al. Evaluation of a gastric delivery system for iron supplementation in pregnancy. Am J Clin Nutr 1993;58:622–6.

17. Ricketts CD. Iron bioavailability from controlled-release and conventional iron supplements. J Appl Nutr 1993;45:13–19.

18. Rudinskas L, Paton TW, Walker SE. Poor clinical response to enteric-coated iron preparations. Can Med Assoc J 1989;141:565–6.

19. Walker SE, Paton TW, Cowan DH, et al. Bioavailability of iron in oral ferrous sulfate preparations in healthy volunteers. Can Med Assoc J 1989;141:543–7.

20. Bender-Gotze C. Therapy of juvenile iron deficiency with bivalent iron dragees (Fe2-fumarate, succinate, sulfate). Controlled double-blind study. Fortschr Med 1980;98:590–3 [in German].

21. Hurrell RF, Furniss DE, Burri J, et al. Iron fortification of infant cereals: a proposal for the use of ferrous fumarate or ferrous succinate. Am J Clin Nutr 1989;49:1274–82.

22. Casparis D, Del Carlo P, Branconi F, et al. Effectiveness and tolerability of oral liquid ferrous gluconate in iron-deficiency anemia in pregnancy and in the immediate post-partum period: comparison with other liquid or solid formulations containing bivalent or trivalent iron. Minerva Ginecol 1996;48:511–8 [in Italian].

23. Frykman E, Bystrom M, Jansson U, et al. Side effects of iron supplements in blood donors: superior tolerance of heme iron. J Lab Clin Med 1994;123:561–4.

24. Martinez C, Fox T, Eagles J, Fairweather-Tait S. Evaluation of iron bioavailability in infant weaning foods fortified with haem concentrate. J Pediatr Gastroenterol Nutr 1998;27:419–24.

25. Hertrampf E, Olivares M, Pizarro F, et al. Haemoglobin fortified cereal: a source of available iron to breast-fed infants. Eur J Clin Nutr. 1990;44:793–8.

26. Calvo E, Hertrampf E, de Pablo S, et al. Haemoglobin-fortified cereal: an alternative weaning food with high iron bioavailability. Eur J Clin Nutr 1989;43:237–43 [review].

27. Fox TE, Eagles J, Fairweather-Tait SJ. Bioavailability of iron glycine as a fortificant in infant foods. Am J Clin Nutr 1998;67:664–8.

28. Pineda O, Ashmead HD, Perez JM, Lemus C. Effectiveness of iron amino acid chelate on the treatment of iron deficiency anemia in adolescents. J Appl Nutr 1994;46:2–13.

29. FDA Medical Bulletin, U.S. Government Printing Office, document number 386–942/00002; February 6, 1995.

30. Nightingale SL. Action to prevent accidental iron poisoning in children. JAMA 1997;27:1343.

31. Krezenlok EP, Hoff JV. Accidental iron poisoning. A problem of marketing and labeling. Pediatrics 1979;63:591–6.

32. Morris CC. Pediatric iron poisonings in the United States. South Med J 2000;93:352–8.

33. Mills KC, Curry SC. Acute iron poisoning. Emerg Med Clin N Am 1994;12;397–413.

34. Cutler P. Deferoxamine therapy in high-ferritin diabetes. Diabetes 1989;38:1207–10.

35. Stevens RG, Graubard BI, Micozzi MS, et al. Moderate elevation of body iron level and increased risk of cancer occurrence and death. Int J Cancer 1994;56:364–9.

36. Weinberg ED. Iron withholding: a defense against infection and neoplasia. Am J Physiol 1984;64:65–102.

37. Oh VMS. Iron dextran and systemic lupus erythematosus. Br Med J 1992;305:1000 [letter].

38. Dabbagh AJ, Trenam CW, Morris CJ, Blake DR. Iron in joint inflammation. Ann Rheum Dis 1993;52:67–73.

39. Bartzokis G, Cummings J, Perlman S, et al. Increased basal ganglia iron levels in Huntington disease. Arch Neurol 1999;56:569–74.

40. Salonen JT, Nyyssonen K, Korpela H, et al. High stored iron levels associated with excess risk of myocardial infarction in western Finnish men. Circulation 1992;86:803–11.

41. Kechl S, Willeit J, Egger G, et al. Body iron stores and the risk of carotid atherosclerosis. Circulation 1997;96:3300–7.

42. Tzonou A, Lagiou P, Trichopoulou A, et al. Dietary iron and coronary heart disease risk: a study from Greece. Am J Epidemiol 1998;147:161–6.

43. Danesh J, Appleby P. Coronary heart disease and iron status. Meta-analyses of prospective studies. Circulation 1999;99:852–4.

44. de Valk B, Marx MMJ. Iron, atherosclerosis, and ischemic heart disease. Arch Intern Med 1999;159:1542–8 [review].

45. Klipstein-Grobusch K, Koster JF, Grobbee DE, et al. Serum ferritin and risk of myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr 1999;69:1231–6.

46. Roob JM, Khoschsorur G, Tiran A, et al. Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol 2000;11:539–49.

47. Muñoz EC, Rosado JL, Lopez P, et al. Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers. Am J Clin Nutr 2000;71:789–94.

48. Di Bisceglie AM, Bonkovsky HL, Chopra S, et al. Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: a multicenter, prospective, randomized, controlled trial. Hepatology 2000;32:135–8.

49. Ferrennini E. Insulin resistance, iron, and the liver. Lancet 2000;355:2181–2 [letter].

50. Hallberg L, Hulthen L. Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr 2000;71:1147–60.

51. Disler PB, Lynch SR, Charlton RW, et al. The effect of tea on iron absorption. Gut 1975;16:193–200.

52. Derman D, Sayers M, Lynch SR, et al. Iron absorption from a cereal-based meal containing cane sugar fortified with ascorbic acid. Br J Nutr 1977;38:261–9.

53. Hallberg L, Rossander L. Effect of different drinks on the absorption of non-heme iron from composite meals. Hum Nutr Appl Nutr 1982;36:116–23.

54. Kaltwasser JP, Werner E, Schalk K, et al. Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis. Gut 1998;43:699–704.

55. Samman S, Sandstrom B, Toft MB, et al. Green tea or rosemary extract added to foods reduces nonheme-iron absorption. Am J Clin Nutr 2001;73:607–12.

56. Derman D, Sayers M, Lynch SR, et al. Iron absorption from a cereal-based meal containing cane sugar fortified with ascorbic acid. Br J Nutr 1977;38:261–9.

57. Hallberg L, Rossander L. Effect of different drinks on the absorption of non-heme iron from composite meals. Hum Nutr Appl Nutr 1982;36:116–23.

58. Morck TA, Lynch SR, Cook JD. Inhibition of food iron absorption by coffee. Am J Clin Nutr 1983;37:416–20.

59. Bezwoda WR, Torrance JD, Bothwell TH, et al. Iron absorption from red and white wines. Scand J Haematol 1985;34:121–7.

60. Cook JD, Reddy MB, Hurrell RF. The effect of red and white wines on nonheme-iron absorption in humans. Am J Clin Nutr 1995;61:800–4.

61. Hallberg L, Hulthen L. Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr 2000;71:1147–60.

62. Sandberg AS, Brune M, Carlsson NG, et al. Inositol phosphates with different numbers of phosphate groups influence iron absorption in humans. Am J Clin Nutr 1999;70:240–6.

63. Hallberg L, Brune M, Rossander L. Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. Am J Clin Nutr 1989;49:140–4.

64. Simpson KM, Morris ER, Cook JD. The inhibitory effect of bran on iron absorption. Am J Clin Nutr 1981;34:1469–78.

65. Hallberg L, Brune M, Erlandsson M, et al. Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans. Am J Clin Nutr 1991;53:112–9.

66. Hallberg L, Rossander-Hulthén L, Brune M, Gleerup A. Inhibition of haem-iron absorption in man by calcium. Br J Nutr 1992;69:533–40.

67. Cook JD, Morck TA, Lynch SR. The inhibitory effect of soy products on nonheme iron absorption in man. Am J Clin Nutr 1981;34:2622–9.

68. Hallberg L, Rossander L. Effect of soy protein on nonheme iron absorption in man. Am J Clin Nutr 1982;36:514–20.

69. Cook JD, Monsen ER. Food iron absorption in human subjects. III. Comparison of the effect of animal proteins on nonheme iron absorption. Am J Clin Nutr 1976;29:859–67.

70. Rossander L, Hallberg L, Bjorn-Rasmussen E. Absorption of iron from breakfast meals. Am J Clin Nutr 1979;32:2484–9.

71. Hallberg L. Bioavailability of dietary iron in man. Annu Rev Nutr 1981;1:123–47 [review].

72. Layrisse M, Martinez-Torres C, Roche M. Effect of interaction of various foods on iron absorption. Am J Clin Nutr 1968;21:1175–83.

73. Cook JD, Monsen ER. Food iron absorption in human subjects. III. Comparison of the effect of animal proteins on nonheme iron absorption. Am J Clin Nutr 1976;29:859–67.

74. Bjorn-Rasmussen E, Hallberg L. Effect of animal proteins on the absorption of food iron in man. Nutr Metab 1979;23:192–202.

75. Hallberg L, Rossander L. Improvement of iron nutrition in developing countries: comparison of adding meat, soy protein, ascorbic acid, citric acid, and ferrous sulphate on iron absorption from a simple Latin American-type of meal. Am J Clin Nutr 1984;39:577–83.

76. Hunt JR, Gallagher SK, Johnson LK. Effect of ascorbic acid on apparent iron absorption by women with low iron stores. Am J Clin Nutr 1994;59:1381–5.

77. Hallberg L, Brune M, Rossander L. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl 1989;30:103–8.

78. Lynch SR, Cook JD. Interaction of vitamin C and iron. Ann N Y Acad Sci 1980;355:32–44.

79. Hallberg L, Brune M, Rossander L. Effect of ascorbic acid on iron absorption from different types of meals. Studies with ascorbic-acid-rich foods and synthetic ascorbic acid given in different amounts with different meals. Hum Nutr Appl Nutr 1986;40:97–113.

80. Hunt JR, Gallagher SK, Johnson LK. Effect of ascorbic acid on apparent iron absorption by women with low iron stores. Am J Clin Nutr 1994;59:1381–5.

81. Suharno D, West CE, Muhilal, et al. Supplementation with vitamin A and iron for nutritional anemia in pregnant women in West Java, Indonesia. Lancet 1993;342:1325–8.

82. Semba RD, Muhilal, West KP Jr, et al. Impact of vitamin A supplementation on hematological indicators of iron metabolism and protein status in children. Nutr Res 1992;12:469–78.

83. Macfarlane BJ, van der Riet WB, Bothwell TH, et al. Effect of traditional oriental soy products on iron absorption. Am J Clin Nutr 1990;51:873–80.

84. Baynes RD, Macfarlane BJ, Bothwell TH, et al. The promotive effect of soy sauce on iron absorption in human subjects. Eur J Clin Nutr 1990;44:419–24.

85. Charlton RW, Jacobs P, Seftel H, Bothwell TH. Effect of alcohol on iron absorption. Br Med J 1964;5422:1427–9.

86. Hallberg L, Rossander L. Effect of different drinks on the absorption of non-heme iron from composite meals. Hum Nutr Appl Nutr 1982;36:116–23.

87. Finley JW. Manganese absorption and retention by young women is associated with serum ferritin concentration. Am J Clin Nutr 1999;70:37–43.

88. Davis CD, Malecki EA, Gerger JL. Interactions among dietary manganese, heme iron, and nonheme iron in women. Am J Clin Nutr 1992;56:926–32.

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