Iron has an essential physiologic role, as it is involved in oxygen transportation and energy formation. The body cannot synthesize iron and must acquire it. Food is the only natural source of iron, and the mineral is ingestable in supplement form. Although the human body can recycle and reutilize this mineral, it loses some iron daily; these lost pools need replacement. Recycling the iron from senescent erythrocytes meets the majority of the body's iron needs by macrophages; only 5 to 10% of iron requirements come from food.[1]
The average iron content in a 70 kg male is about 3 grams. Of this amount, 65% is incorporated into the hemoglobin molecule in red blood cells, which serves a vital role in carrying oxygen from the lungs to tissue cells. Iron is also involved in energy production through its role in the electron transport chain (ETC). Several heme-containing molecules also called cytochromes, are directly involved in electron transport for ATP production by the reduction of iron in the heme from its ferric form (Fe3+) to its ferrous form (Fe2+) and vice versa. Additionally, by these same ionic properties of electron transfer, iron plays a crucial role as a cofactor for enzymes involved in oxidation-reduction reactions such as those involved in the synthesis of amino acids, neurotransmitters, collagen, and hormones. Considering these vital functions for iron, it becomes clear why maintaining physiologic stores and replenishing the daily losses in the iron the cycle, mostly via dietary intake, is crucial for life and health.
Before reviewing dietary iron and factors affecting its intake and bioavailability, it is important to understand how the body handles and regulates iron physiologically. Special proteins such as ferritin and transferrin help in the process of iron absorption, distribution, and storage.[2] Transferrin binds with iron in plasma to transport it to where it is necessary for tissues, and by this transferrin binding, iron does not exist in its free form, where it could damage cell proteins and membranes by free radical formation. Ferritin is the storage form of extra iron and is usually present in the liver and reticular-endothelial system. Iron elimination from the body is limited and commonly occurs through the shedding of intestinal endothelial cells into the feces.[3] The body achieves iron balance mostly through the regulation of iron absorption, and this is where iron differs from other body minerals due to the absence of any physiological process of excretion.[4][5] The peptide hepcidin is a primary regulator of iron homeostasis in the liver, and it has been implicated in anemia of chronic diseases.[6] The types of dietary iron play some role in influencing iron absorption.
Dietary iron requirements are estimated using multifactorial modeling. Factors that affect iron needs include the basal physiologic iron loss, periodic loss of iron in females with menstruation, fetal requirements in pregnancy, elevated requirements during growth stages of life, iron storage, etc.[7] A normal individual loses about 1 mg of iron in feces daily.[8] This loss increases in menstruating women by an additional 0.5 mg/day or approximately 14 mg of iron loss in 28 days. So women of childbearing age require higher iron intake than men. Bioavailability of iron differs in various food sources depending on the types of dietary iron as well as the presence or absence of iron absorption enhancers or inhibitors.
Types of Dietary Iron:
Dietary iron has two primary forms: heme and nonheme.
All plant-derived and animal-derived foods contain nonheme iron while heme iron is found only in the foods derived from animals, mainly meat, fish, poultry, and eggs. Heme iron has a higher bioavailability and is absorbed easier without the need for absorption enhancing cofactors. Nonheme iron, which is the most important dietary source in vegetarians, shows lower bioavailability; and its absorption is dependent on the balance between dietary enhancers and inhibitors as well as body iron stores.
About 25% of dietary heme iron gets absorbed, while 17% of dietary nonheme iron gets absorbed. Based on the studies, iron bioavailability is estimated to be 14 to 18% for mixed diet consumers and 5 to 12% for vegetarian diet consumers.[9] Therefore, less than one-fifth of the amount of dietary iron gets absorbed by the body. In western populations, heme iron contributes 10 to 15% of total dietary iron intake. Due to its higher bioavailability, it represents up to 40% of the total absorbed iron.[10]
Factors influencing Dietary Iron Intake:
Dietary factors:
Many different dietary components either enhance or inhibit dietary iron absorption when they are simultaneously present in the diet.
Enhancers:
Inhibitors:
Person-related factors:
GI Disorders:
Any of the following medical problems could interfere with iron absorption and lead to a higher demand for iron through either dietary means or medical supplementation.
Recommended Dietary Allowance of Iron: Illustrated in Table 1.
Sources of Iron:
Iron is a crucial mineral for the body. It is naturally present in a variety of food substances in addition to being available as a dietary supplement that can be taken alone or can be added to fortify other foods. Iron is an integral component of the hemoglobin and myoglobin molecules and, therefore, plays a vital role in oxygen transport. Iron also plays a role in the structure of enzymes and the proper function of cells and is needed for growth and development. Most of the 4 grams of iron in the adult human body are in hemoglobin.[23] Iron deficiency is often associated with poor diet and malnutrition, malabsorptive disorders, or conditions leading to loss of iron in hemoglobin through blood loss. There are populations and groups at risk of iron deficiency and resultant anemia. Iron deficiency anemia can affect infants, children, teenagers, menstruating women, and those who are pregnant. Additionally, frequent blood donors, people with cancer, heart failure, or those who have gastrointestinal disorders affecting iron absorption or contributing to iron loss through gastrointestinal bleeding can all develop iron deficiency anemia. Caregivers need to be cognizant of these groups to recognize the need for early diagnosis and treatment and, thereby, benefit from coordinating care with appropriate specialists.
Primary care providers can solicit symptoms and look for signs to suggest the presence of anemia and use simple laboratory tests to confirm the diagnosis. Women of childbearing age and those who are pregnant would benefit from coordinating their care with their gynecologist or obstetrician, where appropriate and timely dietary iron supplementation can be provided to meet the maternal physiologic demands of pregnancy and those of fetal development. Pediatricians often recommend iron-fortified formula or foods rich in bioavailable iron to young children to minimize the risk of deficiency developing at 6 to 9 months of age.[24] Adults, especially males, with anemia should undergo evaluation for gastrointestinal conditions such as celiac disease, inflammatory disease, or colon cancer that are common causes of iron deficiency. Referral to a gastroenterologist can help the primary care provider in the evaluation and workup, as specialized endoscopic testing and tissue biopsy can be performed via foregut endoscopy or colonoscopy. Given that iron has such an important role in health, nutritionists and educators are often the first line individuals to suspect a deficiency in young children or adults and request evaluations from appropriate specialists, whether that be in outpatient settings like schools and clinics or when patients present to hospital for care for other ailments. Hospitals need to be aware that iron can interact with multiple medications routinely used today, especially in our aging population. Examples of such medication include levothyroxine, levodopa, and proton pump inhibitors.[25][26][27] In these situations, attention is necessary to make appropriate dose adjustments or separate medication dosing to minimize interactions and influence on drug absorption.
[1] | Coad J,Pedley K, Iron deficiency and iron deficiency anemia in women. Scandinavian journal of clinical and laboratory investigation. Supplementum. 2014; [PubMed PMID: 25083899] |
[2] | von Drygalski A,Adamson JW, Iron metabolism in man. JPEN. Journal of parenteral and enteral nutrition. 2013 Sep; [PubMed PMID: 22968710] |
[3] | Hunt JR,Zito CA,Johnson LK, Body iron excretion by healthy men and women. The American journal of clinical nutrition. 2009 Jun [PubMed PMID: 19386738] |
[4] | Han O, Molecular mechanism of intestinal iron absorption. Metallomics : integrated biometal science. 2011 Feb; [PubMed PMID: 21210059] |
[5] | Hunt JR,Roughead ZK, Adaptation of iron absorption in men consuming diets with high or low iron bioavailability. The American journal of clinical nutrition. 2000 Jan; [PubMed PMID: 10617952] |
[6] | Singh B,Arora S,Agrawal P,Gupta SK, Hepcidin: a novel peptide hormone regulating iron metabolism. Clinica chimica acta; international journal of clinical chemistry. 2011 May 12; [PubMed PMID: 21333642] |
[7] | Dainty JR,Berry R,Lynch SR,Harvey LJ,Fairweather-Tait SJ, Estimation of dietary iron bioavailability from food iron intake and iron status. PloS one. 2014; [PubMed PMID: 25356629] |
[8] | Green R,Charlton R,Seftel H,Bothwell T,Mayet F,Adams B,Finch C,Layrisse M, Body iron excretion in man: a collaborative study. The American journal of medicine. 1968 Sep; [PubMed PMID: 5672736] |
[9] | Hurrell R,Egli I, Iron bioavailability and dietary reference values. The American journal of clinical nutrition. 2010 May; [PubMed PMID: 20200263] |
[10] | Carpenter CE,Mahoney AW, Contributions of heme and nonheme iron to human nutrition. Critical reviews in food science and nutrition. 1992; [PubMed PMID: 1581009] |
[11] | Lynch SR,Hurrell RF,Dassenko SA,Cook JD, The effect of dietary proteins on iron bioavailability in man. Advances in experimental medicine and biology. 1989; [PubMed PMID: 2658489] |
[12] | Björn-Rasmussen E,Hallberg L, Effect of animal proteins on the absorption of food iron in man. Nutrition and metabolism. 1979; [PubMed PMID: 570683] |
[13] | Taylor PG,Martínez-Torres C,Romano EL,Layrisse M, The effect of cysteine-containing peptides released during meat digestion on iron absorption in humans. The American journal of clinical nutrition. 1986 Jan; [PubMed PMID: 3942093] |
[14] | Lynch SR,Cook JD, Interaction of vitamin C and iron. Annals of the New York Academy of Sciences. 1980; [PubMed PMID: 6940487] |
[15] | Conrad ME,Schade SG, Ascorbic acid chelates in iron absorption: a role for hydrochloric acid and bile. Gastroenterology. 1968 Jul; [PubMed PMID: 5663503] |
[16] | Roy A,Fuentes-Afflick E,Fernald LCH,Young SL, Pica is prevalent and strongly associated with iron deficiency among Hispanic pregnant women living in the United States. Appetite. 2018 Jan 1; [PubMed PMID: 28864256] |
[17] | De la Cruz-Góngora V,Villalpando S,Shamah-Levy T, Prevalence of anemia and consumption of iron-rich food groups in Mexican children and adolescents: Ensanut MC 2016. Salud publica de Mexico. 2018 May-Jun; [PubMed PMID: 29746746] |
[18] | Sood M,Sharada D, Iron food supplement. Indian journal of pediatrics. 2002 Nov; [PubMed PMID: 12503656] |
[19] | Manoguerra AS,Erdman AR,Booze LL,Christianson G,Wax PM,Scharman EJ,Woolf AD,Chyka PA,Keyes DC,Olson KR,Caravati EM,Troutman WG, Iron ingestion: an evidence-based consensus guideline for out-of-hospital management. Clinical toxicology (Philadelphia, Pa.). 2005; [PubMed PMID: 16255338] |
[20] | Bailey RL,Gahche JJ,Lentino CV,Dwyer JT,Engel JS,Thomas PR,Betz JM,Sempos CT,Picciano MF, Dietary supplement use in the United States, 2003-2006. The Journal of nutrition. 2011 Feb; [PubMed PMID: 21178089] |
[21] | Pfeiffer CM,Looker AC, Laboratory methodologies for indicators of iron status: strengths, limitations, and analytical challenges. The American journal of clinical nutrition. 2017 Dec [PubMed PMID: 29070545] |
[22] | Clark SF, Iron deficiency anemia. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2008 Apr-May; [PubMed PMID: 18390780] |
[23] | Gozzelino R,Arosio P, Iron Homeostasis in Health and Disease. International journal of molecular sciences. 2016 Jan 20 [PubMed PMID: 26805813] |
[24] | Wan D,Wu Q,Ni H,Liu G,Ruan Z,Yin Y, Treatments for iron deficiency (ID): Prospective organic iron fortification. Current pharmaceutical design. 2019 Mar 18 [PubMed PMID: 30892157] |
[25] | Ajmera AV,Shastri GS,Gajera MJ,Judge TA, Suboptimal response to ferrous sulfate in iron-deficient patients taking omeprazole. American journal of therapeutics. 2012 May [PubMed PMID: 21150767] |
[26] | Campbell NR,Hasinoff BB,Stalts H,Rao B,Wong NC, Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Annals of internal medicine. 1992 Dec 15 [PubMed PMID: 1443969] |
[27] | Campbell RR,Hasinoff B,Chernenko G,Barrowman J,Campbell NR, The effect of ferrous sulfate and pH on L-dopa absorption. Canadian journal of physiology and pharmacology. 1990 May [PubMed PMID: 2340448] |