Iron
• Iron Sulfate, Chelated Iron
• Attention Deficit Disorder , Enhancing Mental Function in Women , Fatigue , HIV Support , Menorrhagia (Heavy Menstruation), Reduction of ACE Inhibitor Side Effects , Restless Legs Syndrome , Stimulating flow of Saliva
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 nourishing every cell in the body with oxygen. It also functions as a part of myoglobin, which helps muscle cells store oxygen. Without iron, your body could not make ATP (adenosine triphosphate, the body's primary energy source), produce DNA, or carry out many other critical processes.
Iron deficiency can lead to anemia, learning disabilities, impaired immune function, fatigue, and depression. However, you shouldn't take iron supplements unless lab tests show that you are genuinely deficient.
Requirements/Sources
The official US recommendations for daily intake of iron are as follows:
- Infants
- 0-6 months: 0.27 mg
- 7-12 months: 11 mg
- Children
- 1-3 years: 7 mg
- 4-8 years: 10 mg
- Males
- 9-13 years: 8 mg
- 14-18 years: 11 mg
- 19 years and older: 8 mg
- Females
- 9-13 years: 8 mg
- 14-18 years: 15 mg
- 19-50 years: 18 mg
- 50 years and older: 8 mg
- Pregnant Women :27 mg
- Nursing Women : 9 mg (10 mg if 18 years old or younger)
Iron deficiency is the most common nutrient deficiency in the world; worldwide, at least 700 million individuals have iron-deficiency anemia. 1 While iron deficiency is widespread in the developing world, it is also prevalent in developed countries. Groups at high risk are children, teenage girls, menstruating women (especially those with excessively heavy menstruation, known as menorrhagia), pregnant women, and the elderly. 2,3
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.
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. 65
Iron absorption may be affected by the following substances: antibiotics in the quinolone (Floxin, Cipro) 4-8 or tetracycline9-11 families, levodopa , 12methyldopa , 13,14carbidopa , 15penicillamine , 16thyroid hormone , 17captopril (and possibly other ACE inhibitors ), 18calcium , 19-22soy , 23zinc , 24copper , 25 or manganese , 26 or multivitamin/multimineral tablets. 58-59 Conversely, iron may inhibit their absorption, too.
In addition, drugs in the H 2 blocker or proton pump inhibitor families may impair iron absorption. 27
Therapeutic Dosages
The typical short-term therapeutic dosage to correct iron deficiency is 100 to 200 mg daily. Once your body's iron stores reach normal levels, however, this dose should be reduced to the lowest level that can maintain iron balance.
Therapeutic Uses
The most obvious use of iron supplements is to treat iron deficiency. Severe iron deficiency causes anemia, which in turn causes many symptoms. Iron deficiency too slight to cause anemia may impair health as well. Several, though not all, double-blind trials suggest that mild iron deficiency might impair sports performance . 28,36,51-55 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 supplement enhanced energy and wellbeing. 56 Another study found that iron supplements improved mental function in women who were iron deficient. 63 However, don't take iron just because you feel tired. Make sure to get tested to see whether you are indeed deficient. With iron, more is definitely not better. (See Safety Issues .)
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. 38
A study of 71 HIV-positive children noted a high rate of iron deficiency. 34 One observational study of 296 men with HIV infection linked high intake of iron to a decreased risk of AIDS 6 years later. 35
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. 50 (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 very 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. 64
Iron has been suggested as a treatment for attention deficit hyperactivity disorder , but there is only preliminary evidence that it may effective in hyperactive children with low iron levels as indicated by ferritin levels. 66
Preliminary studies have linked low iron levels to restless legs syndrome . 30-32 However, a small double-blind study found no benefit when iron supplements were given to healthy people (eg, those who were not iron deficient) 33
One study tested whether supplemental iron could increase rate of saliva flow, but it failed to find benefit. 62
What Is the Scientific Evidence for Iron?
Sports Performance
A double-blind, placebo-controlled trial of 42 non-anemic women with evidence of slightly low iron reserves found that iron supplements significantly enhanced sports performance . 36 Participants were put on a daily aerobic training program for the latter 4 weeks of this 6-week trial. At the end of the trial, those receiving iron showed significantly greater gains in speed and endurance as compared to those given placebo.
In addition, a double-blind, placebo-controlled study of 40 non-anemic elite athletes with mildly low iron stores found that 12 weeks of iron supplementation enhanced aerobic performance. 37
Benefits with iron supplementation were observed in other double-blind trials as well also involving mild low iron stores. 51,52 However, other studies failed to find significant improvements, 53-55 suggesting that the benefits of iron supplements for non-anemic, iron-deficient athletes is 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% of the women who took iron (compared to 32.5% of those who took placebo). Women who began with higher iron levels did not respond to treatment. 38 This suggests once more that supplementing with iron is only a good idea if you are deficient in it.
Safety Issues
Iron supplements commonly cause gastrointestinal upset, but, when 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 surprisingly common problem, so make sure to keep your iron supplements out of their reach.
Mildly excessive levels of iron may be unhealthy for another reason: it acts as an oxidant (the opposite of an antioxidant), perhaps increasing the risk of cancer and heart disease (although this is controversial). 39, 60 Elevated levels of iron may also play a role in brain injury caused by stroke . 40 In addition, excess iron appears to increase complications of pregnancy , 41 and, if breastfed infants who are not iron-deficient are given iron supplements, the effects may be negative rather than positive. 57
Note : Simultaneous use of iron supplements and high-dose vitamin C can greatly increase iron absorption, possibly leading to excessive iron levels in the body. 42-49
One study found that iron does not impair absorption of the drug methotrexate . 61
Interactions You Should Know About
If you are taking:
- Antibiotics in the tetracycline or quinolone ( Floxin , Cipro ) families; levodopa ; methyldopa ; carbidopa ; penicillamine ; thyroid hormone ; calcium ; soy ; zinc ; copper ; or manganese : To avoid absorption problems, wait at least 2 hours following your dose of medication or supplement before taking iron.
- Drugs that reduce stomach acid such as antacids , H 2 blockers , and proton pump inhibitors : You may need extra iron.
- High doses of vitamin C : You may absorb too much iron.
- ACE inhibitors : Iron may reduce coughing side effect; however, to avoid absorption problems, you should wait at least 2 hours following your dose of medication before taking iron.
References
1. Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins; 1999: 1772.
2. Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins; 1999: 210,860,1422,1424.
3. Nelson M, Ash R, Mulvhill C, et al. Iron status, diet and cognitive function in British adolescent girls. Poster presented at: The Nutrition Society's Nutrition 2000—Research Themes for the New Millenium; June 26-30; University College, Cork, Ireland.
4. Kara M, Hasinoff BB, McKay DW, et al. Clinical and chemical interactions between iron preparations and ciprofloxacin. Br J Clin Pharmacol. 1991;31:257-261.
5. Polk RE, Healy DP, Sahai J, et al. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1989;33:1841-1844.
6. Campbell NR, Kara M, Hasinoff BB, et al. Norfloxacin interaction with antacids and minerals. Br J Clin Pharmacol. 1992;33:115-116.
7. Lehto P, Kivisto KT. Different effects of products containing metal ions on the absorption of lomefloxacin. Clin Pharmacol Ther. 1994;56:477-482.
8. Lehto P, Kivisto KT, and Neuvonen PJ. The effect of ferrous sulphate on the absorption of norfloxacin, ciprofloxacin and ofloxacin. Br J Clin Pharmacol. 1994;37:82-85.
9. Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs. 1976;11:45-54.
10. Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31:251-255.
11. Heinrich HC, Oppitz KH, Gabbe EE. Inhibition of iron absorption in man by tetracycline [in German]. Klin Wochenschr. 1974;52:493-498.
12. Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31:251-255.
13. Campbell N, Paddock V, Sundaram R. Alteration of methyldopa absorption, metabolism, and blood pressure control caused by ferrous sulfate and ferrous gluconate. Clin Pharmacol Ther. 1988;43:381-386.
14. Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31:251-255.
15. Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31:251-255.
16. Osman MA, Patel RB, Schuna A, et al. Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate. Clin Pharmacol Ther. 1983;33:465-470.
17. Campbell NR, Hasinoff BB, Stalts H, et al. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med. 1992;117:1010-1013.
18. Campbell NR, Hasinoff BB. Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol. 1991;31:251-255.
19. Hallberg L. Does calcium interfere with iron absorption? Am J Clin Nutr. 1998;68:3-4.
20. Cook JD, Dassenko SA, Whittaker P. Calcium supplementation: effect on iron absorption. Am J Clin Nutr. 199153:106-111.
21. Dawson-Hughes B, Seligson FH, Hughes VA. Effects of calcium carbonate and hydroxyapatite on zinc and iron retention in postmenopausal women. Am J Clin Nutr. 1986;44:83-88.
22. Sokoll LJ, Dawson-Hughes B. Calcium supplementation and plasma ferritin concentrations in premenopausal women. Am J Clin Nutr. 1992;56:1045-1048.
23. Hallberg L, Rossander L, Skanberg AB. Phytates and the inhibitory effects of bran on iron absorption in man. Am J Clin Nutr . 1987;45:988-996.
24. Sandstrom B, Davidsson L, Cederblad A, et al. Oral iron, dietary ligands and zinc absorption. J Nutr. 1985;115:411-414.
25. Haschke F, Ziegler EE, Edwards BB, et al. Effect of iron fortification of infant formula on trace mineral absorption. J Pediatr Gastroenterol Nutr. 1986;5:768-773.
26. Freeland-Graves JH. Manganese: an essential nutrient for humans. Nutr Today . 1988;23:13-19.
27. Champagne ET. Low gastric hydrochloric acid secretion and mineral bioavailability. Adv Exp Med Biol. 1989;249:173-184.
28. Hinton PS, Giordano C, Brownlie T, et al. Iron supplementation improves endurance after training in iron-depleted, nonanemic women. J Appl Physiol. 2000;88:1103-1111.
29. Nelson M, Ash R, Mulvhill C, et al. Iron status, diet and cognitive function in British adolescent girls. Poster presented at: The Nutrition Society's Nutrition 2000—Research Themes for the New Millennium; June 26-30; University College, Cork, Ireland.
30. O'Keeffe ST. Restless legs syndrome. A review. Arch Intern Med. 1996;156:243-248.
31. Sun ER, Chen CA, Ho G, et al. Iron and the restless legs syndrome. Sleep. 1998;21:371-377.
32. O'Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly . Age Ageing. 1994;23:200-203.
33. Davis BJ, Rajput A, Rajput ML, et al. A randomized, double-blind placebo-controlled trial of iron in restless legs syndrome . Eur Neurol. 2000;43:70-75.
34. Castaldo A, Tarallo L, Palomba E, et al. Iron deficiency and intestinal malabsorption in HIV disease. J Pediatr Gastroenterol Nutr . 1996;22:359-363.
35. Abrams B, Duncan D, Hertz-Picciotto I. A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men. J Acquir Immune Defic Syndr . 1993;6:949-958.
36. Hinton PS, Giordano C, Brownlie T, et al. Iron supplementation improves endurance after training in iron-depleted, nonanemic women. J Appl Physiol. 2000;88:1103-1111.
37. Friedmann B, Weller E, Mairbaurl H, et al. Effects of iron repletion on blood volume and performance capacity in young athletes. Med Sci Sports Exerc. 2001;33:741-746.
38. Taymor ML, Sturgis SH, Yahia C. The etiological role of chronic iron deficiency in production of menorrhagia. JAMA . 1964;187:323-327.
39. Sempos CT, Looker AC, Gillum RE, et al. Serum ferritin and death from all causes and cardiovascular disease: the NHANES II Mortality Study. Ann Epidemiol . 2000;10:441-448.
40. Davolos A, Castillo J, Marrugat J, et al. Body iron stores and early neurologic deterioration in acute cerebral infarction. Neurology. 2000;54:1568-1574.
41. Lao TT, Tam K, Chan LY. Third trimester iron status and pregnancy outcome in non-anaemic women; pregnancy unfavourably affected by maternal iron excess. Hum Reprod. 2000;15:1843-1848.
42. Maskos Z, Koppenol WH. Oxyradicals and multivitamin tablets. Free Radic Biol Med. 1991;11:609-610.
43. Conrad ME, Schade SG. Ascorbic acid chelates in iron absorption: a role for hydrochloric acid and bile. Gastroenterology. 1968;55:35-45.
44. Brise H, Hallberg L. Effect of ascorbic acid on iron absorption. Acta Med Scand. 1962;171(Suppl 376):51.
45. Lynch SR, Cook JD. Interaction of vitamin C and iron. Ann N Y Acad Sci. 1980;355:32-44.
46. 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;59:1381-1385.
47. Diplock AT. Safety of antioxidant vitamins and beta-carotene. Am J Clin Nutr. 1995;62(Suppl 6):1510S-1516S.
48. Hoffman KE, Yanelli K, Bridges KR. Ascorbic acid and iron metabolism: alterations in lysosomal function. Am J Clin Nutr. 1991;54(Suppl 6):1188S-1192S.
49. Siegenberg D, Baynes RD, Bothwell TH, et al. Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption. Am J Clin Nutr. 1991;53:537-541.
50. Lee SC, Park SW, Kim DK, et al. Iron supplementation inhibits cough associated with ACE inhibitors. Hypertension. 2001;38:166-170.
51. Brutsaert TD, Hernandez-Cordero S, Rivera J, et al. Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women. Am J Clin Nutr . 2003;77:441-448.
52. Rowland TW, Deisroth MB, Green GM, Kelleher JF. The effect of iron therapy on the exercise capacity of nonanemic iron-deficient adolescent runners. Am J Dis Child . 1988;142:165-169.
53. Celsing F, Blomstrand E, Werner B, et al. Effects of iron deficiency on endurance and muscle enzyme activity in man. Med Sci Sports Exerc . 1986;18:156-161.
54. Klingshirn LA, Pate RR, Bourque SP, et al. Effect of iron supplementation on endurance capacity in iron-depleted female runners. Med Sci Sports Exerc . 1992;24:819-824.
55. LaManca JJ, Haymes EM. Effects of iron repletion on VO2max, endurance, and blood lactate in women. Med Sci Sports Exerc . 1993;25:1386-1392.
56. Verdon F, Burnand B, Fallab-Stubi CL, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ . 2003;326:1124.
57. Dewey KG, Domellof M, Cohen RJ, et al. Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in sweden and honduras. J Nutr . 2002;132:3249-3255.
58. Moriarty-Craige SE, Ramakrishnan U, Neufeld L et al. Multivitamin-mineral supplementation is not as efficacious as is iron supplementation in improving hemoglobin concentrations in nonpregnant anemic women living in Mexico. Am J Clin Nutr . 2004;80:1308-1311.
59. Sankaranarayanan S, Untoro J, Erhardt J et al. Daily iron alone but not in combination with multimicronutrients increases plasma ferritin concentrations in indonesian infants with inflammation. J Nutr. 2004 ;134:1916-1922.
60. Binkoski AE, Kris-Etherton PM, Beard JL. Iron Supplementation Does Not Affect the Susceptibility of LDL to Oxidative Modification in Women with Low Iron Status. J Nutr . 2004;134:99-103.
61. Hamilton SF, Campbell NR, Kara M, et al. The effect of ingestion of ferrous sulfate on the absorption of oral methotrexate in patients with rheumatoid arthritis. J Rheumatol . 2003;30:1948-1950.
62. Flink H, Tegelberg A, Thorn M et al. Effect of oral iron supplementation on unstimulated salivary flow rate: a randomized, double-blind, placebo-controlled trial. J Oral Pathol Med. 2006;35:540-547.
63. Murray-Kolb LE, Beard JL. Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr . 2007;85:778-787.
64. Zhou SJ, Gibson RA, Crowther CA, et al. Should we lower the dose of iron when treating anaemia in pregnancy? A randomized dose-response trial. Eur J Clin Nutr. 2007 Oct 10. [Epub ahead of print]
65. Sharieff W, Dofonsou J, Zlotkin S. Is cooking food in iron pots an appropriate solution for the control of anaemia in developing countries? A randomised clinical trial in Benin. Public Health Nutr. 2007 Oct 15. [Epub ahead of print]
66. Konofal E, Lecendreux M, Deron J, et al. Effects of iron supplementation on attention deficit hyperactivity disorder in children. Pediatr Neurol. 2008;38:20-26.
Last reviewed April 2009 by EBSCO CAM Review Board
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