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.
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.