[icon name=”user” class=”” unprefixed_class=””] SwapnaliHalder, Ph.D.
Humans receive iron from the diet or iron supplement pills. In some medical conditions related to iron deficiency, iron can be obtained through intravenous injection or blood transfusion.
HEME AND NON-HEME IRON
Heme iron means iron in a heme complex, as found in the hemoglobin of red blood cell, or in the myoglobin protein of animal tissues. Animal based food products contain both heme and non-heme iron. About 40% of the iron in the meat, fish and poultry belongs to heme iron, another 55-60% is non-heme iron.1 Iron present in the plant based dietary products is mostly non-heme iron.
Hemoglobin is a protein molecule that constitutes of a heme iron and four globulin protein chains. Hemoglobin carries oxygen (O2) to tissues and returns carbon dioxide (CO2) from tissues to the lungs through the blood.
Seventy percent of the iron in a human body is found in hemoglobin, and it is also because of the hemoglobin that the blood has its red color. Iron is also present in several other proteins that are involved in crucial enzymatic functions.
IRON STORAGE AND METABOLISM
Iron storage, metabolism and transport in the body are regulated by several factors including the activity of a special enzyme called hepcidin.2 As previously mentioned, 70% of the iron in human is found in the red blood cell in the form of hemoglobin. Ferritin is a protein that stores iron in tissues and in blood serum.
Hence serum ferritin level is directly related to the stored iron level in the body. About 25% of the body’s iron is stored in the ferritin, with a cut off point of 300-360 microgram/DL.3 When the accumulated iron exceeds the storage capacity of ferritin, it forms a complex called hemociderin.
Hemociderin remains inside the cells as opposed to circulating in blood, and it is less effective in supplying iron compared to ferritin. Excessive accumulation of hemociderin may cause organ damage. Apart from blood, iron is stored in the liver cells, spleen, and bone marrow in our body.
Normally, a substantial amount of absorbed iron is excreted from the body through feces, and also a trace amount is excreted through urine, sweat or dead cell exfoliation.
There is a genetic disorder called hemochromatosis that also leads to excessive iron load in the joints and vital organs like heart, liver, pancreas, and pituitary gland. This excessive iron cannot flush out of the body itself. If not removed medically, it may give rise to serious pathological conditions.
IRON DEFICIENCY ANEMIA (IDA)
According to World Health Organization (WHO) Hemoglobin level cut off points in the blood are 130 g/L (13 g/DL) for men, 120 g/L (12g/DL) for non-pregnant women, and 110 g/L (11g/DL) for pregnant women.4 Hemoglobin concentration is measured to diagnose iron-deficiency anemia, a common medical condition where the number of red blood cell is insufficient, hence hemoglobin level is also lower than the designated cut off point. Low hemoglobin production results in depletion of oxygen supply.
Normally a minimal amount of iron is lost from a healthy human body in several ways, such as through sweating, urination, defecation, or exfoliation of old skin cells, however it does not cause iron deficiency anemia. Rather, underlying causes of iron deficiency anemia could range from worm infection, malnutrition to iron loss during menstruation bleeding in women.
Additionally, injury, bleeding, hemorrhage, gastrointestinal disease or even cancer may also lead to iron deficiency anemia. Iron deficiency is anemia is a global problem that prevails not only in underdeveloped or developing countries, but in developing countries as well.5
Typical symptoms of anemia include pale skin, weakness, fatigue, rapid heart beats, shortness of breath, dizziness, cold hand and feet, brittleness of nails, leg cramp, and insomnia. Iron is important for muscle contraction; therefore muscle tone and elasticity is lost without proper supply for iron. Adequate amount of iron intake through diet or supplements can give relief from these physical ailments.
Mild to moderate anemia can be treated with daily iron supplementation in the form of iron salts, such as iron sulfate, iron fumarate or polimaltose iron complex 3 (see table 1. for daily allowances of iron for different age groups) . In more serious medical conditions, iron injections or blood transfusion are often the mode of clinical interventions.
TABLE 1. DIETARY ALLOWANCES (RDAS) FOR IRON, AS RECOMMENDED BY NIH[custom_table]
|Birth to 6 months||0.27 mg*||0.27 mg*|
|7–12 months||11 mg||11 mg|
|1–3 years||7 mg||7 mg|
|4–8 years||10 mg||10 mg|
|9–13 years||8 mg||8 mg|
|14–18 years||11 mg||15 mg||27 mg||10 mg|
|19–50 years||8 mg||18 mg||27 mg||9 mg|
|51+ years||8 mg||8 mg|
The asterisk (*) indicates adequate intake.
REQUIREMENT OF IRON FOR GROWTH AND DEVELOPMENT OF CHILDREN
High level of iron is required during growth and development. Breast milk contains iron, however the amount is not sufficient to meet the daily iron requirement of an infant older than 4-6 months.6 So breastfed infants should be given some oral iron supplements (1mg/kg body weight per day), starting after 4 months of age until the age when they can take iron directly from fortified foods.6
However, it is recommended to consult your pediatrician to assure the suitability of an iron supplement before introducing it to your child. Toddlers or children may develop iron deficiency anemia if iron absorption from their diet is not adequate to accommodate their increasing need for iron supply during their growing age. Proper iron supply is believed to pace up brain development and motor coordination (movement of body parts or limbs) in developing children.
Some scientific studies reported that iron deficiency in toddlers might lead to psychological effects or even social withdrawal.6
IRON NEEDS FOR PREGNANT 7AND LACTATING WOMEN
Iron deficiency in pregnancy is a high risk factor since it may lead to consequences like premature birth, low birth-weight of the infant, low iron stores, and impaired cognitive and behavioral development.7, 8 Maternal factors such as gestational diabetes, anemia, or maternal hypertension with growth restriction may hinder iron supply to the fetus.
A survey by World Health Organization revealed an alarming fact, that between the years of 1993 and 2005, 42% of women worldwide suffered from anemia during their pregnancies. Iron supplements are needed not only during pregnancy, but also after childbirth, or even after a miscarriage to compensate the depleted iron.
OTHER GROUPS OF PEOPLE WITH HIGH RISK OF IRON DEFICIENCY
Apart from pregnant and lactation women or growing children, there are other people who might bear high risk of iron deficiency. Frequent blood donors, patients with cancer or heart failure or gastrointestinal disorders9 may suffer from iron deficiency due to mal-absorption.8
WHERE DO WE GET IRON FOR OUR BODY?
We do not synthesize iron in our body. A normal healthy human being must obtain iron from dietary sources and/or from iron supplements. Cereal, legume, lentil, beans, tofu, dry fruits, meat & poultry, fish, green and leafy vegetables are enriched in irons. (See the table 2. for amount of iron present in different food ingredients). Infant formulas are generally fortified with iron in the US.[custom_table]
|Food||Mg per serving||% DV*|
|Breakfast cereals, fortified with 100% of the DV for iron, 1 serving||7||39|
|Oysters, eastern, cooked with moist heat, 3 ounces||5||28|
|White beans, canned, 1 cup||3||17|
|Chocolate, dark, 45%–69% cacao solids, 3 ounces||3||17|
|Beef liver, pan fried, 3 ounces||3||17|
|Lentils, boiled and drained, ½ cup||2||11|
|Spinach, boiled and drained, ½ cup||2||11|
|Tofu, firm, ½ cup||2||11|
|Kidney beans, canned, ½ cup||2||11|
|Sardines, Atlantic, canned in oil, drained solids with bone, 3 ounces||2||11|
|Chickpeas, boiled and drained, ½ cup||2||11|
|Tomatoes, canned, stewed, ½ cup||2||11|
|Beef, braised bottom round, trimmed to 1/8″ fat, 3 ounces||1||6|
|Potato, baked, flesh and skin, 1 medium potato||1||6|
|Cashew nuts, oil roasted, 1 ounce (18 nuts)||1||6|
|Green peas, boiled, ½ cup||1||6|
|Chicken, roasted, meat and skin, 3 ounces||1||6|
|Rice, white, long grain, enriched, parboiled, drained, ½ cup||1||6|
|Bread, whole wheat, 1 slice||1||6|
|Bread, white, 1 slice||1||6|
|Raisins, seedless, ¼ cup||1||6|
|Spaghetti, whole wheat, cooked, 1 cup||1||6|
|Tuna, bluefin, fresh, cooked with dry heat, 3 ounces||1||6|
|Turkey, roasted, breast meat and skin, 3 ounces||1||6|
|Nuts, pistachio, dry roasted, 1 ounce (49 nuts)||1||6|
|Broccoli, boiled and drained, ½ cup||1||6|
|Egg, hard boiled, 1 large||1||6|
|Rice, brown, long or medium grain, cooked, 1 cup||1||6|
Note: Table 2. was adapted from ods.od.nih.gov/factsheets. *DV or Daily Value is a measure developed by US Food and Drug Administration (FDA) to help consumer compare nutrient contents of products in the context of a standard daily diet.
In emergency medical conditions with low iron supply, the immediate need for iron in the body is met by iron injections or blood transfusion.
CERTAIN FOODS DISRUPT OR ENHANCE IRON ABSORPTION
For average people, 20%-25% of the consumed heme iron is actually absorbed in the body. Many substances including, caffeine, eggs, dairy products such as milk, cheese and yogurt, and other calcium containing food products interfere with non-heme iron absorption in the gut.
Though calcium, zinc and manganese are essential minerals themselves, they interfere with iron absorption as well. To avoid this interference with iron absorption, it is recommended not to consume these dietary products or supplements and iron-enriched food or with an iron pill at the same time of a day.
Same warning is applicable regarding consumption of tea, coffee, and oregano (a herb), phytates (found in soy) while taking an iron rich/fortified food with an intention to increase iron levels in the body. The good news is that vitamin C increases iron absorption from other food.
Citrus fruits like orange, tangerine, grapefruit, pineapple, cantaloupe, strawberry, raspberry and kiwi fruit are remarkable sources of vitamin C that may help increase iron absorption from the food. Also including green, red, and yellow bell pepper, broccoli, tomato, cabbage, potato, cauliflower, and leafy green vegetables in one’s diet would aid iron absorption from food.6
INTERACTION OF IRON WITH DIFFERENT MEDICATIONS
Certain drugs interfere with the absorption of iron in the body. On the other hand, iron also showed interference with the absorption of some medications. Therefore, if you are taking any medications, it is recommended that you consult your health care provider before taking any iron supplement.
Also maintaining a substantial time gap between intake of a potentially interfering drug and an iron supplement may help reduce the interference. Following are examples of some common drugs that are known to interfere with iron absorption 10 or the drugs whose absorptions are interfered by iron intake.
Cholestyramine, an effective drug to lower blood cholesterol levels, interferes with absorption of iron.11
Angiotensin-converting enzyme inhibitors or ACE inhibitors are used as medications to reduce high blood pressure and congestive heart failure. Iron was reported to inhibit ACE inhibitors.10
METHYLDOPA AND LEVODOPA
orally administered iron supplement in the form of ferrous sulfate reduces absorption of the drug methyldopa and levodopa in the intestine.12
Iron intake reduces absorption of orally administered levothyroxine, a medicine that is used to treat hypothyroidism.13
Iron intake impairs absorption of the antibiotic tetracycline and its derivative oxytetracycline, methacycline, and doxycycline.14
PROTON PUMP INHIBITORS
Gastric acid plays an important role in the absorption of iron from the diet. Medicines with proton pump inhibitors, such as lansoprazole and omeprazole, reduce the acidity of stomach; hence they reduce iron absorption as well.8
Birth control medications may increase iron level.15 Therefore taking an oral contraceptive and an iron supplement or iron containing multivitamin at the same time of a day may run the risk of excessive iron accumulation in the body.
EXCESSIVE IRON INTAKE ASSOCIATED HEALTH RISKS
While taking iron supplement one must consult his or her healthcare provider regarding appropriate dosage since excessive iron intake may lead to complications that outweigh its benefits. Acute intakes of more than 20 mg/kg iron per day can lead to gastric upset, constipation, nausea, abdominal pain, vomiting, and faintness.16
Excessive iron can trigger reactions that cause reactive oxygen species (ROS) or free radical production resulting in lipid peroxidation, thereby increased cardiovascular risks.17
Excessive tissue iron may cause alteration in iron metabolism and is associated with insulin resistance and type II diabetes.18 Research showed that mitochondrial dysfunction and hepatic gluconeogenesis are responsible for this kind of alterations. Another study reported that mitochondrial breakdown due to iron overload caused damage to hippocampal neurons19 in the brain, which may contribute to disorders like Parkinson’s disease.20, 21
Also, there is a genetic disorder called hemochromatosis2 where iron metabolism is disrupted and iron accumulation may affect the liver, heart and endocrine glands.23 Also there are incidents of poisoning from accidental iron overdose that are fatal, particularly for children.
To conclude, the take-home message of this article is that in order to stay healthy, we must incorporate iron-enriched food and supplements in our diet that help meet the daily need for iron. However, one should be mindful about how much iron to consume since both iron deficiency and iron overload could be harmful for health.
- Iron Disorders Institute. Iron we consume. 2015. http://www.irondisorders.org/iron-we-consume/. Accessed September 28, 2015.
- Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J. Body iron metabolism and pathophysiology of iron overload. Int J Hematol. 2008; 88(1): 7–15. doi: 10.1007/s12185-008-0120-5
- Montoya Romero Jde J, Castelazo Morales E, Valerio Castro E, et al. [Review by expert group in the diagnosis and treatment of anemia in pregnant women. Federación Mexicana de Colegios de Obstetricia y Ginecología]. Ginecol Obstet Mex. 2012;80(9):563-80.
- World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. http://www.who.int/vmnis/indicators/haemoglobin.pdf accessed September 28, 2015.
- World Health Organization. Micronutrient deficiencies. http://www.who.int/nutrition/topics/ida/en/. Accessed September 28, 2015.
- Baker RD, Greer FR; Committee on Nutrition American Academy of Pediatrics.
Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age). Pediatrics. 2010;126(5):1040-50. doi: 10.1542/peds.2010-2576.
- Khambalia AZ, Collins CE, Roberts CL, et al. Iron deficiency in early pregnancy using serum ferritin and soluble transferrin receptor concentrations are associated with pregnancy and birth outcomes. Eur J Clin Nutr. 2015 Sep 16. doi: 10.1038/ejcn.2015.157. [Epub ahead of print]
- National Institutes of Health. Office of dietary supplements. Iron. 2015. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/#h7. Accessed September 25, 2015.
- Bayraktar UD, Bayraktar S. Treatment of iron deficiency anemia associated with gastrointestinal tract diseases. World J Gastroenterol. 2010;16(22):2720-5.
- University of Maryland Medical Center. Possible interactions with: iron. 2015. https://umm.edu/health/medical/altmed/supplement-interaction/possible-interactions-with-iron. Accessed September 27, 2015.
- Watkins DW, Khalafi R, Cassidy MM, Vahouny GV. Alterations in calcium, magnesium, iron, and zinc metabolism by dietary cholestyramine. Dig Dis Sci. 1985;30(5):477-82.
- Greene RJ, Hall AD, Hider RC. The interaction of orally administered iron with levodopa and methyldopa therapy. J Pharm Pharmacol. 1990;42(7):502-4.
- Shakir KM, Chute JP, Aprill BS, Lazarus AA. Ferrous sulfate-induced increase in requirement for thyroxine in a patient with primary hypothyroidism. South Med J. 1997;90(6):637-9.
- Neuvonen PJ, Gothoni G, Hackman R, Björksten K. Interference of iron with the absorption of tetracyclines in man. Br Med J. 1970;4(5734):532-4.
- Margen S, King JC. Effect of oral contraceptive agents on the metabolism of some trace minerals. Am J Clin Nutr. 1975; 28; 392-402.
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc: a Report of the Panel on Micronutrients . Washington, DC: National Academy Press; 2001.
- Toxqui L, De Piero A, Courtois V, Bastida S, Sánchez-Muniz FJ, Vaquero MP.
Iron deficiency and overload. Implications in oxidative stress and cardiovascular health. Nutr Hosp. 2010;25(3):350-65.
- Lee HJ, Choi JS, Lee HJ, Kim WH, Park SI, Song J. Effect of excess iron on oxidative stress and gluconeogenesis through hepcidin during mitochondrial dysfunction. J Nutr Biochem. 2015 Jul 29. pii: S0955-2863(15)00172-2. doi: 10.1016/j.jnutbio.2015.07.008. [Epub ahead of print]
- Park J, Lee DG, Kim B, Park SJ, Kim JH, Lee SR, Chang KT, Lee HS, Lee DS. Iron overload triggers mitochondrial fragmentation via calcineurin-sensitive signals in HT-22 hippocampal neuron cells. Toxicology. 2015;337:39-46. doi: 10.1016/j.tox.2015.08.009. [Epub ahead of print]
- Hare DJ, Arora M, Jenkins NL, Finkelstein DI, Doble PA, Bush AI. Is early-life iron exposure critical in neurodegeneration? Nat Rev Neurol. 2015;11(9):536-44. doi: 10.1038/nrneurol.2015.100
- Isaya G, Hare DJ, Arora M, et al. Mitochondrial iron-sulfur cluster dysfunction in neurodegenerative disease. Front Pharmacol. 2014;5:29. doi: 10.3389/fphar.2014.00029.
- Crownover BK, Covey CJ. Hereditary hemochromatosis. Am Fam Physician. 2013;87(3):183-90.
- Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology. 2010;139(2):393-408, 408.e1-2. doi: 10.1053/j.gastro.2010.06.013.