Iron Deficiency Anemia

Last Updated: April 10, 2023

Iron deficiency anemia occurs when the body does not have enough iron to produce healthy red blood cells to transport oxygen in the blood. Iron deficiency anemia can be caused by excessive blood loss or reduced iron absorption or intake. It can be treated with oral iron supplementation, though there is a wide range of individual tolerance for, and effectiveness of, iron supplements.

Iron Deficiency Anemia falls under theCardiovascular HealthandEnergy & Fatiguecategories.

What is iron deficiency anemia?

Iron deficiency anemia is a condition where the body does not have sufficient iron to produce enough hemoglobin (Hb) for healthy red blood cells. It is characterized by the presence of microcytosis, or small red blood cells (RBCs), as a result of decreased Hb production. The Hb molecule is made with iron, and is a required component of RBCs; within the Hb molecule, it is the iron atoms that carry oxygen to the body’s tissues.[1]

What are the main signs and symptoms of iron deficiency anemia?

While a person can often have no symptoms of iron deficiency anemia, weakness, fatigue, pallor (looking pale), irritability, headache, and poor exercise tolerance can be present. Pica (craving and eating for non-nutritive substances) is sometimes present as well, particularly for ice, and even clay or soil.[2][3]

How is iron deficiency anemia diagnosed?

Anemia is defined as a Hb less than 12 grams per deciliter of blood (g/dL) in non-pregnant women, less than 11 g/dL in pregnant women, or under 13 g/dL in men.[4][1][2]

Iron deficiency is the most common cause of anemia. Serum ferritin testing is recommended in patients with anemia to diagnose iron deficiency, as it has good accuracy compared to the (invasive) gold standard for diagnosis of bone marrow biopsy. It is the best biochemical test to indicate iron stores, and a ferritin level below 30 micrograms per liter of blood (µg/L) can indicate iron deficiency in anemia.

Serum ferritin is also an acute phase reactant — in other words, a marker of inflammation — therefore, C-reactive protein should also be measured to rule out a false elevation of ferritin from an inflammatory condition or infection. Depending on the condition, a cutoff value of less than 100 µg/L may be used for ferritin.[4][5][2]

Iron deficiency anemia may also show the following signs on bloodwork:

  • Mean corpuscular volume (MCV), a measure of RBC size: less than 80 femtoliters (fL)
  • Mean cell hemoglobin (MCH), a measure of RBC iron content: less than 25 g/dL
  • Percentage transferrin saturation less than 16% (or <20% in the presence of inflammation)[6][5][2]

In addition: serum transferrin may be high, serum iron may be low, and total iron-binding capacity may be high.[7][8]

If iron deficiency anemia is diagnosed, and the clinician suspects it may have a gastrointestinal cause, then tests such as a urea breath test (for H. pylori infection), serologic testing for celiac disease (tissue transglutaminase IgA), fecal occult blood testing (i.e., stool sample), upper endoscopy (i.e., viewing the esophagus, stomach, and upper intestines), or colonoscopy may also be performed to investigate for causes of blood loss.[4][7]

What are some of the main medical treatments for iron deficiency anemia?

The first-line therapy for iron deficiency anemia is oral supplementation.[9] This therapy can even be effective in the demographic with the highest daily iron requirement: pregnant women; oral iron, when taken during pregnancy, was found to reduce maternal iron deficiency anemia and low birthweight (a side effect of maternal iron deficiency anemia).[10]

A common form and dose of oral iron is ferrous sulfate at 100–200 milligrams per day, though there’s no evidence to suggest any particular iron preparation is more effective than another. Lower doses of iron may be equally effective while reducing adverse effects.[9][11][12]. Some studies suggest that alternate-day dosing may be superior to consecutive-day dosing for increasing iron absorption.[9]

Common side effects of iron supplementation are constipation, abdominal discomfort, nausea, and vomiting. Other oral forms, such as ferrous fumarate, ferrous gluconate, or iron suspensions, may be tolerated better, though there is inconsistent evidence.[7][2][1][13] Enteric-coated iron supplements may reduce gastrointestinal side effects, but have lower absorption.[7]

Have any supplements been studied for iron deficiency anemia?

Supplementation with algae such as spirulina and chlorella might improve iron deficiency, though most research is in rats.[14][15][16] One human trial showed that spirulina-containing flour benefitted the iron status and survival rates of infants (aged 6-24 months) when compared to flours without iron. However, the study participants were malnourished infants in Kenya who were hospitalized, decreasing applicability of results to other populations.[17]

Iron supplements will often include vitamin B12 and folate, since iron deficiency can mask symptoms of a deficiency of either of these vitamins. Vitamin B12 and/or folate deficiency can cause a dysfunction of RBCs known as macrocytic anemia (where RBCs are enlarged), but this can be masked by iron deficiency (which would typically make RBCs smaller).

It has been shown that individuals with iron deficiency anemia have higher levels of oxidative stress and lower levels of endogenous antioxidants. Therefore, supplementing with antioxidant vitamins (e.g., vitamin C, vitamin E, and beta-carotene) may be considered in iron deficiency anemia.[18]

How could diet affect iron deficiency anemia?

Dietary counseling to increase iron intake can be effective at prevention or treatment of anemia in pregnant women. Counseling was typically given over a period of several months, and was found to be effective whether focusing only on iron intake, or several nutrients in addition to iron (such as vitamin B12 and folate).[19]

Are there any other treatments for iron deficiency anemia?

Supplementation with ascorbic acid (vitamin C) in a dose of 250–500 milligrams twice per day is often recommended to increase iron absorption due to its acidic nature, though it is uncertain whether this ultimately increases the effectiveness of treatment for iron deficiency anemia.[2][7]

Supplementation with high amounts of calcium, zinc, or magnesium in iron deficiency is cautioned against, as these may reduce iron absorption.[20]

In more serious cases of iron deficiency anemia, erythropoiesis-stimulating agents (ESAs) may be used. ESAs are medicines that help the bone marrow to produce red blood cells; they’re often used in conjunction with oral iron therapy for people who also have a condition such as chronic kidney disease that is causing their iron deficiency anemia. Blood transfusions may also be used; they rapidly elevate red blood cells and iron in the body, but this procedure is rare and only used for serious cases of iron deficiency anemia.[21]

What causes iron deficiency anemia?

Maintenance of iron-related blood markers requires a positive iron balance — iron absorption through dietary sources needs to be greater than the amount of iron we lose. It is normal to lose a small amount of iron per day,[4] though a daily blood loss greater than 5-10 milliliters per day exceeds the amount of iron that can be absorbed from the average diet.[7] The following are potential causes of iron deficiency anemia, since they can affect either iron loss or iron absorption. These are listed in approximate order of decreasing prevalence:

Certain medications may reduce iron absorption, such as antacids, H2 blockers, and proton pump inhibitors, since these reduce acidity in the stomach.[7]

The presence of iron deficiency anemia in people without a menstrual cycle, especially in those over 50 years old, can be concerning since there may be blood loss occurring from a serious issue like gastric or colorectal cancer.[7][2]

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  2. ^Goddard AF, James MW, McIntyre AS, Scott BB,Guidelines for the management of iron deficiency anaemia.Gut.(2011-Oct)
  3. ^Borgna-Pignatti C, Zanella SPica as a manifestation of iron deficiency.Expert Rev Hematol.(2016-Nov)
  4. ^Ko CW, Siddique SM, Patel A, Harris A, Sultan S, Altayar O, Falck-Ytter YAGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia.Gastroenterology.(2020-Sep)
  5. ^Skikne BS, Punnonen K, Caldron PH, Bennett MT, Rehu M, Gasior GH, Chamberlin JS, Sullivan LA, Bray KR, Southwick PCImproved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.Am J Hematol.(2011-Nov)
  6. ^Cotter J, Baldaia C, Ferreira M, Macedo G, Pedroto IDiagnosis and treatment of iron-deficiency anemia in gastrointestinal bleeding: A systematic review.World J Gastroenterol.(2020-Dec-07)
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  9. ^Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MBIron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic womenHaematologica.(2019 Aug 14)
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  11. ^Stoffel NU, Cercamondi CI, Brittenham G, Zeder C, Geurts-Moespot AJ, Swinkels DW, Moretti D, Zimmermann MBIron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trialsLancet Haematol.(2017 Nov)
  12. ^D'Adamo CR, Novick JS, Feinberg TM, Dawson VJ, Miller LEA Food-Derived Dietary Supplement Containing a Low Dose of Iron Improved Markers of Iron Status Among Nonanemic Iron-Deficient Women.J Am Coll Nutr.(2018)
  13. ^Rogozińska E, Daru J, Nicolaides M, Amezcua-Prieto C, Robinson S, Wang R, Godolphin PJ, Saborido CM, Zamora J, Khan KS, Thangaratinam SIron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis.Lancet Haematol.(2021-Jul)
  14. ^Matsuura E, Nemoto T, Hozumi H, Izumi K, Saito Y, Ishida H, Fukimbara T, Kawahara HEffect of chlorella on rats with iron deficient anemia.Kitasato Arch Exp Med.(1991-Dec)
  15. ^Gao F, Guo W, Zeng M, Feng Y, Feng GEffect of microalgae as iron supplements on iron-deficiency anemia in rats.Food Funct.(2019-Feb-20)
  16. ^Kumar R, Sharma V, Das S, Patial V, Srivatsan V() fortified functional foods ameliorate iron and protein malnutrition by improving growth and modulating oxidative stress and gut microbiota in rats.Food Funct.(2023-Jan-23)
  17. ^Othoo DA, Ochola S, Kuria E, Kimiywe JImpact of Spirulina corn soy blend on Iron deficient children aged 6-23 months in Ndhiwa Sub-County Kenya: a randomized controlled trial.BMC Nutr.(2021-Nov-09)
  18. ^Aslan M, Horoz M, Çelik HEvaluation of oxidative status in iron deficiency anemia through total antioxidant capacity measured using an automated method.Turk J Haematol.(2011-Mar-05)
  19. ^Skolmowska D, Głąbska D, Kołota A, Guzek DEffectiveness of Dietary Interventions in Prevention and Treatment of Iron-Deficiency Anemia in Pregnant Women: A Systematic Review of Randomized Controlled Trials.Nutrients.(2022-Jul-23)
  20. ^Shubham et alIron deficiency anemia: A comprehensive review on iron absorption, bioavailability and emerging food fortification approachesTrends in Food Science and Technology.(May 2020)
  21. ^Iron-Deficiency Anemia: National Heart, Lung and Blood Institute. Bethesda, MD: National Institute of Health, cited April 2023(2022-03-24)
  22. ^Pamela S HintonIron and the endurance athleteAppl Physiol Nutr Metab.(2014 Sep)
  23. ^Govindappagari S, Burwick RMTreatment of Iron Deficiency Anemia in Pregnancy with Intravenous versus Oral Iron: Systematic Review and Meta-Analysis.Am J Perinatol.(2019-Mar)
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  25. ^Shubham et alIron deficiency anemia: A comprehensive review on iron absorption, bioavailability and emerging food fortification approachesTrends in Food Science and Technology.(May 2020)
Examine Database References
  1. White Blood Cell Count - Selmi C, Leung PS, Fischer L, German B, Yang CY, Kenny TP, Cysewski GR, Gershwin METhe effects of Spirulina on anemia and immune function in senior citizensCell Mol Immunol.(2011 May)
  2. Anemia Risk - Shiro Nakano, Hideo Takekoshi, Masuo NakanoChlorella pyrenoidosa supplementation reduces the risk of anemia, proteinuria and edema in pregnant womenPlant Foods Hum Nutr.(2010 Mar)
  3. Anemia Risk - Andersen CT, Marsden DM, Duggan CP, Liu E, Mozaffarian D, Fawzi WWOral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials.BMJ Glob Health.(2023-Feb)
  4. Fatigue (non-anemic) - Favrat B, Balck K, Breymann C, Hedenus M, Keller T, Mezzacasa A, Gasche CEvaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women--PREFER a randomized, placebo-controlled studyPLoS One.(2014 Apr 21)
  5. Fatigue (non-anemic) - Waldvogel S, Pedrazzini B, Vaucher P, Bize R, Cornuz J, Tissot JD, Favrat BClinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trialBMC Med.(2012 Jan 24)
  6. Fatigue (non-anemic) - McClung JP, Karl JP, Cable SJ, Williams KW, Nindl BC, Young AJ, Lieberman HRRandomized, double-blind, placebo-controlled trial of iron supplementation in female soldiers during military training: effects on iron status, physical performance, and moodAm J Clin Nutr.(2009 Jul)
  7. Hemoglobin - Ali SA, Razzaq S, Aziz S, Allana A, Ali AA, Naeem S, Khowaja N, Ur Rehman FRole of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.BMC Womens Health.(2023-Apr-17)
  8. Iron Absorption - Charlotte N Armah, Paul Sharp, Fred A Mellon, Sandra Pariagh, Elizabeth K Lund, Jack R Dainty, Birgit Teucher, Susan J Fairweather-TaitL-alpha-glycerophosphocholine contributes to meat's enhancement of nonheme iron absorptionJ Nutr.(2008 May)
  9. Iron Absorption - Olivares M, Pizarro F, Ruz MZinc inhibits nonheme iron bioavailability in humansBiol Trace Elem Res.(2007 Summer)
  10. Transferrin - Milinković N, Zeković M, Dodevska M, Đorđević B, Radosavljević B, Ignjatović S, Ivanović NMagnesium supplementation and iron status among female students: The intervention study.J Med Biochem.(2022-Jul-29)