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Iron

Iron is an essential mineral best known for allowing blood to carry oxygen between tissues. Except in case of deficiency, iron supplementation has no proven benefit; on the contrary, it can lead to iron poisoning.

Our evidence-based analysis on iron features 51 unique references to scientific papers.

Kamal Patel
Research analysis led by Kamal Patel.
All content reviewed by the Examine.com Team. Published: Sep 3, 2014
Last Updated:

Summary of Iron

Primary Information, Benefits, Effects, and Important Facts

Iron is an essential dietary mineral present in a wide variety of foods, but the iron found in plants (notably grains and legumes) is less bioavailable than the iron found in meat (in the form of heme).

In our bodies, iron can bind with porphyrin to make heme; it can then carry oxygen. Proteins with a heme group are called hemoproteins, of which the best known are erythrocytes (the red blood cells). Therefore, having enough iron in your diet is necessary for your red blood cells to deliver oxygen to your tissues. In addition, iron is a cofactor for many enzymes.

Iron deficiency leads to anemia, whose first symptoms are pallor and fatigue. Iron deficiency is the only reason to consider iron supplementation, though getting more iron through foods should be preferred when possible. For people who already have enough iron, taking an iron supplement has no proven benefit; on the contrary, it can lead to iron overdose.

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Things To Know & Note

Is a Form Of

Primary Function:

Caution Notice

Examine.com Medical Disclaimer

  • Taking some food and liquid with your iron supplement will reduce the chance of a stomach upset.

How to Take Iron

Recommended dosage, active amounts, other details

Make sure you get the recommended daily allowance (RDA) for your gender, age, and situation:

  • 8 mg for men and non-menstruating women

  • 15 mg for menstruating women under 19

  • 18 mg for menstruating women over 18

  • 27 mg for pregnant women

  • 9 mg for lactating women under 19

  • 10 mg for lactating women over 18

Those numbers include the iron in your diet. Getting enough iron through foods makes supplementation unnecessary. Be careful not to ingest more iron than the daily tolerable upper intake level (UL) for your age: 45 mg for people over 13.

For more details, see the Recommended Intake section below.

Scientific Research on Iron

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1Sources and Composition

1.1Biological Significance

Iron is one of the most abundant minerals on Earth (the planet’s crust itself is 4.7% iron).[1] Because iron works well as an enzyme cofactor, it fulfills essential functions in all known organisms, but for some species of bacteria.[1][2] In humans, iron also binds with porphyrin to make heme, which is required to deliver oxygen to tissues.[1][3]

Outside of hemoproteins, iron can also exist in iron-sulfur clusters (ISCs), which are part of over 200 different proteins, including many enzymes.[4] Like hemoproteins, ISCs exist in nearly all forms of life, including eukaryotes,[5] bacteria,[6] and plants.[7] In humans, these proteins have been associated with energy production: they can be found in mitochondria and seem to be linked to some mitochondrial diseases, such as Friedreich’s ataxia.[8][9]

Because of the conversion of iron between the reduced form (ferrous) and the oxidized form (ferric), iron can induce oxidative stress in the body. Beneficial effects can result, but, since iron is insoluble, an excess of free iron can also damage proteins and cells.[10][11]

In humans, in addition to serving as an enzyme cofactor, iron helps ferry oxygen between tissues and cause oxidative damage (for the purpose of initiating various cellular processes). As a result of this latter function, iron also exists in forms that can cause unnecessary damage to cells when its regulation is thrown into disarray.

1.2Recommended Intake

The Institute of Medicine provides the following recommendations:[12]

  • For infants up to 6 months of age, the adequate intake (AI) is 0.27 mg. Both the Canadian Paediatric Society[13] and the American Academy of Pediatrics[14] have suggested that infants fed little to no breast milk may need to drink a specialized infant formulation fortified with iron.

  • For infants between 7 and 12 months of age, the estimated average intake (EAR) is 6.9 mg, whereas the recommended daily allowance (RDA) is 11 mg. The large difference in iron requirements between younger and older infants is probably due both to an increase in body mass and to an increased capacity to store iron safely.

  • For children between 1 and 3, the EAR is 3 mg; the RDA, 7 mg.

  • For children between 4 and 8, the EAR is 4.1 mg; the RDA, 10 mg.

  • For youths between 9 and 18, the EAR and RDA differentiate between sexes, due to menstruation. For males, the RDA is 8 mg under 14, then 11 mg between 14 and 18. For females, the RDA is also 8 mg under 14, but 15 mg between 14 and 18, with an added recommendation that menstruating females under 14 increase their intake by around 2.5 mg (resulting in an intake of 13.5 mg).

  • For men over 18, the RDA is 8 mg.

  • For women between 19 and 50, the RDA is 18 mg. For women over 50, the RDA is 8 mg, same as for men. The “50 years of age” boundary is arbitrary and represents the menopause.

  • For pregnant women, the EAR and the RDA increase to 22–23 mg and 27 mg respectively.

  • For lactating women, the EAR and the RDA decrease to 6.5–7 mg and 9–10 mg respectively, due to a temporary cessation of menstruations.

For men, iron recommendations are based on age. For women, they are based on age (the ages of first and last menstruations being mere estimations) and the states of pregnancy and lactation.

Someone who gives half a liter (0.5 L) of blood over the course of a year needs an additional 0.6–0.7 mg iron per day.[15] Someone who frequently partakes in strenuous training needs an additional 30–70% over the EAR.[12] Although vegetarians and vegans have the same recommended intakes as omnivores, they are more likely to be deficient, because the iron in plants is less bioavailable than the heme iron in animals.

An increase in iron intake can be made necessary by menstruations, pregnancy, and lactation, but also by blood donations, strenuous exercise, and a vegetarian or vegan diet.

1.3Deficiency

Iron deficiency in infants and children is associated with cognitive impairments, including psychomotor[16] and behavioural[17] issues.

2Neurology

2.1Depression

A high iron intake seems to translate into a lesser chance of depression, according to a (relatively small) meta-analysis on the topic.[18]

3Cardiovascular Health

3.1Red Blood Cells

In our bodies, iron can bind with porphyrin to make heme. The best-known hemoproteins (proteins with heme) are hemoglobin and myoglobin, found in erythrocytes (the red blood cells).[19] The iron in heme can become oxygenated (i.e., bound to oxygen) or unoxygenated in a reversible manner,[20] which is what allows red blood cells to deliver oxygen to body tissues.[21]

A body without enough red blood cells, or whose red blood cells are unhealthy, suffers from anemia. There are different forms of anemia: some are genetic, such as sickle cell anemia;[22] others derive from a dietary deficiency, such as pernicious anemia (linked to a Vitamin B12 deficiency).[23] 

Iron-deficiency anemia, the most common form of anemia worldwide, can be caused by a lack of iron in the diet or by the body having difficulties processing the ingested iron. It primarily affects premenopausal women with low meat intake, due to a combination of iron loss from menstruation and lack of dietary heme iron.[24] It can be treated by increasing dietary iron, by taking an iron supplement (under medical supervision), or by enhancing the body’s ability to absorb and use iron[25][26][27] — by increasing the bioavailability of plant forms of iron, for instance.

Red blood cells ferry oxygen to body tissues thanks to the iron in hemoglobin and myoglobin. Optimal iron stores in the body support this function; an excess of iron does not necessarily enhance it, but an iron deficiency does hinder it, leading to iron-deficiency anemia.

4Inflammation and Immunology

4.1Macrophages

Macrophages are immune cells. In addition to eliminating foreign bodies determined to be harmful, they play roles in both inflammation and anti-inflammation[28] and fulfill different maintenance functions,[29] including the recycling of iron.[30]

Red blood cells, like all cells, eventually degrade with age — a process known as senescence. As they do, they release their heme, which can then damage tissues and DNA.[31] To prevent this, the erythrophagocytic macrophage detects senescent red blood cells and eliminates them.[32]

Some macrophages detect and eliminate damaged or senescent red blood cells, which prevents the iron in those cells from floating free around the body, damaging tissues.

5Peripheral Organ Systems

5.1Female Sex Organs

Taking an iron supplement around the time of menstruation appears to increase both ferritin and hemoglobin and to reduce the risk of anemia (RR 0.73; 95% CI of 0.56–0.95). However, despite similar improvements in hemoglobin, daily supplemention appears to better reduce the risk of anemia.[24] 

Taking an iron supplement around the time of menstruation appears to reduce anemia, but not as much as taking an iron supplement every day.

6Nutrient-Nutrient Interactions

6.1Chelation

Several plant-derived compounds can bind iron and sequester it in the intestines, thus reducing its absorption.

Curcumin (the most active component of turmeric) has shown this potential in mice, but only when high doses (estimated human dose: 8–12 g) were paired with a diet low in iron.[33] When mice were fed diets with adequate levels of iron, curcumin did not seem to significanctly hinder iron absorption.[33] Finally, in humans, 500 mg of turmeric did not seem to hinder iron absorption.[34]

The addition of 4.2 g of ground chili (Capsicum annuum) to a meal fortified with 4 mg of non-heme iron showed a moderate inhibitory effect on iron absorption (38%). Due to the addition of chili, the meal was relatively high in phytic acid.[34]

Rosemary (source of rosmarinic acid) has also been shown to reduce non-heme iron absorption.[35]

Ingesting iron at the same time as spices rich in phytic acid or phenolic acid may reduce its absorption.

Psyllium is a dietary fiber (roughly half-soluble, half-insoluble). It has the potential to reduce non-heme iron absorption (with no effect from vitamin C),[36] but also to raise the PH in the colon and thus increase calcium resorption[37] — an increase thought to apply to other minerals as well.

In humans, one study noted a reduction in iron accumulation when non-heme iron was coingested with psyllium,[38] but other studies saw no effect on iron metabolism from the prolonged supplementation of around 10 g of psyllium.[39][40][41]

Dietary fibers may have an acute inhibitory effect on iron absorption, but on the other hand fermentable dietary fibers may increase mineral resorption in the colon.

The following beverages are known to inhibit iron absorption when coingested with non-heme iron:

A wide variety of beverages with a high antioxidant content, including coffee and tea, have some acute inhibitory effect on iron.

6.2Vitamin C

Vitamin C (ascorbic acid) increases the rate at which non-heme iron is absorbed from the intestines into the bloodstream.[45][46] Ascorbate (a mineral salt of ascorbic acid) cycles back and forth between intestinal cells:[47] outside the cells, it reduces iron to a form more readily absorbed;[48] inside the cells, it helps transfer iron to transferrin.[49]

Transferrin is a transfer protein that delivers iron to cells, which is why scurvy (which results from a vitamin C deficiency) is often associated with some degree of iron-deficiency anemia.[50][51]

References

  1. ^ a b c Beard JL, Dawson H, Piñero DJ. Iron metabolism: a comprehensive review. Nutr Rev. (1996)
  2. ^ Sánchez M et al.. Iron chemistry at the service of life. IUBMB Life. (2017)
  3. ^ Gozzelino R, Arosio P. Iron Homeostasis in Health and Disease. Int J Mol Sci. (2016)
  4. ^ Bandyopadhyay S, Chandramouli K, Johnson MK. Iron-sulfur cluster biosynthesis. Biochem Soc Trans. (2008)
  5. ^ Lill R, Mühlenhoff U. Iron-sulfur protein biogenesis in eukaryotes: components and mechanisms. Annu Rev Cell Dev Biol. (2006)
  6. ^ Ayala-Castro C, Saini A, Outten FW. Fe-S cluster assembly pathways in bacteria. Microbiol Mol Biol Rev. (2008)
  7. ^ Balk J, Lobréaux S. Biogenesis of iron-sulfur proteins in plants. Trends Plant Sci. (2005)
  8. ^ Muthuswamy S, Agarwal S. Friedreich Ataxia: From the Eye of a Molecular Biologist. Neurologist. (2005)
  9. ^ Bruni F, Lightowlers RN, Chrzanowska-Lightowlers ZM. Human mitochondrial nucleases. FEBS J. (2016)
  10. ^ Eid R, Arab NT, Greenwood MT. Iron mediated toxicity and programmed cell death: A review and a re-examination of existing paradigms. Biochim Biophys Acta. (2017)
  11. ^ Koskenkorva-Frank TS, et al. The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress. Free Radic Biol Med. (2013)
  12. ^ a b Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. . (2001)
  13. ^ The Canadian Paediatric Society. Meeting the iron needs of infants and young children: an update. Nutrition Committee, Canadian Paediatric Society. CMAJ. (1991)
  14. ^ The American Academy of Pediatrics. Iron Fortification of Infant Formulas. . (1999)
  15. ^ Milman N, Kirchhoff M. Influence of blood donation on iron stores assessed by serum ferritin and haemoglobin in a population survey of 1433 Danish males. Eur J Haematol. (1991)
  16. ^ Walter T et al.. Iron deficiency anemia: adverse effects on infant psychomotor development. Pediatrics. (1989)
  17. ^ Lozoff B et al.. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev. (2006)
  18. ^ Li Z. Dietary zinc and iron intake and risk of depression: A meta-analysis. Psychiatry Res. (2017)
  19. ^ Chung J, Chen C, Paw BH. Heme metabolism and erythropoiesis. Curr Opin Hematol. (2012)
  20. ^ Bonaventura C et al.. Molecular controls of the oxygenation and redox reactions of hemoglobin. Antioxid Redox Signal. (2013)
  21. ^ Kosman DJ. Redox cycling in iron uptake, efflux, and trafficking. J Biol Chem. (2010)
  22. ^ Bender MA, Douthitt Seibel G. Sickle Cell Disease. Gene Reviews. (2003)
  23. ^ Chan CQ, Low LL, Lee KH. Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. Front Med (Lausanne). (2016)
  24. ^ a b Fernández-Gaxiola AC, De-Regil LM. Intermittent iron supplementation for reducing anaemia and its associated impairments in menstruating women. Cochrane Database Syst Rev. (2011)
  25. ^ Johnson-Wimbley TD, Graham DY. Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol. (2011)
  26. ^ Clark SF. Iron deficiency anemia: diagnosis and management. Curr Opin Gastroenterol. (2009)
  27. ^ Bairwa M et al.. Directly observed iron supplementation for control of iron deficiency anemia. Indian J Public Health. (2017)
  28. ^ Italiani P, Boraschi D. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front Immunol. (2014)
  29. ^ Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. (2013)
  30. ^ Alam MZ, Devalaraja S, Haldar M. The Heme Connection: Linking Erythrocytes and Macrophage Biology. Front Immunol. (2017)
  31. ^ Kumar S, Bandyopadhyay U. Free heme toxicity and its detoxification systems in human. Toxicol Lett. (2005)
  32. ^ Bratosin D et al.. Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review. Biochimie. (1998)
  33. ^ a b Jiao Y1, et al. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood. (2009)
  34. ^ a b Tuntipopipat S1, et al. Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal. J Nutr. (2006)
  35. ^ a b c Samman S1, et al. Green tea or rosemary extract added to foods reduces nonheme-iron absorption. Am J Clin Nutr. (2001)
  36. ^ Fernandez R, Phillips SF. Components of fiber bind iron in vitro. Am J Clin Nutr. (1982)
  37. ^ Trinidad TP1, Wolever TM, Thompson LU. Availability of calcium for absorption in the small intestine and colon from diets containing available and unavailable carbohydrates: an in vitro assessment. Int J Food Sci Nutr. (1996)
  38. ^ Rossander L. Effect of dietary fiber on iron absorption in man. Scand J Gastroenterol Suppl. (1987)
  39. ^ Bell LP1, et al. Cholesterol-lowering effects of soluble-fiber cereals as part of a prudent diet for patients with mild to moderate hypercholesterolemia. Am J Clin Nutr. (1990)
  40. ^ Dennison BA1, Levine DM. Randomized, double-blind, placebo-controlled, two-period crossover clinical trial of psyllium fiber in children with hypercholesterolemia. J Pediatr. (1993)
  41. ^ Anderson JW1, et al. Cholesterol-lowering effects of psyllium hydrophilic mucilloid for hypercholesterolemic men. Arch Intern Med. (1988)
  42. ^ a b c Hurrell RF1, Reddy M, Cook JD. Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br J Nutr. (1999)
  43. ^ Kono Y1, et al. Iron chelation by chlorogenic acid as a natural antioxidant. Biosci Biotechnol Biochem. (1998)
  44. ^ O'Coinceanainn M1, et al. Reaction of iron(III) with theaflavin: complexation and oxidative products. J Inorg Biochem. (2004)
  45. ^ Atanassova BD, Tzatchev KN. Ascorbic acid--important for iron metabolism. Folia Med (Plovdiv). (2008)
  46. ^ 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)
  47. ^ Lane DJ, Lawen A. Non-transferrin iron reduction and uptake are regulated by transmembrane ascorbate cycling in K562 cells. J Biol Chem. (2008)
  48. ^ May JM, Qu ZC, Mendiratta S. Role of ascorbic acid in transferrin-independent reduction and uptake of iron by U-937 cells. Biochem Pharmacol. (1999)
  49. ^ Lane DJ et al.. Transferrin iron uptake is stimulated by ascorbate via an intracellular reductive mechanism. Biochim Biophys Acta. (2013)
  50. ^ Clark NG, Sheard NF, Kelleher JF. Treatment of iron-deficiency anemia complicated by scurvy and folic acid deficiency. Nutr Rev. (1992)
  51. ^ Cox EV. The anemia of scurvy. Vitam Horm. (1968)

This page is regularly updated, to include the most recently available clinical trial evidence.

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This page features 51 references. All factual claims are followed by specifically-applicable references. Click here to see the full set of references for this page.

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