Key Takeaways (expand)
- Iron is an essential mineral needed for the metabolism of all living organisms.
- The adult human body contains about 4 grams of iron, mostly in the form of hemoglobin and myoglobin.
- In food, iron is present in one of two forms: as a component of heme (a hemoglobin precursor that contains an iron atom), or nonheme iron (the predominant form in plant foods and dairy).
- The bioavailability of heme iron is significantly higher than non-heme: only about 2 – 20% of nonheme iron is absorbed (although other components of the diet can increase this, like the presence of vitamin C)!
- Iron is essential for the functioning of a wide variety of proteins involved in oxygen transport and storage, electron transport, energy metabolism, oxygen sensing, and DNA replication and repair.
- Some iron-dependent proteins also act as antioxidants or beneficial pro-oxidants.
- Among the many iron-dependent proteins that exist, some of the most important are hemoglobin and myoglobin (which are vital for keeping tissues throughout the body oxygenated), iron-dependent cytochromes (which are essential for cellular energy production), and iron-dependent ribonucleotide reductases (which are needed for DNA replication and repair).
- Iron also plays a role in immune function: during times of infection, the body has iron-withholding defenses that help keep iron away from the pathogens that need it to survive!
- Iron homeostasis is regulated by a hormone called hepcidin, which helps reduce the absorption and bioavailability of iron in times of excess, and increases iron absorption and mobilization when body stores become too low.
- When too much free iron accumulates in the body (often due to inherited genetic conditions, such as hereditary hemochromatosis), it can lead to oxidative stress and cellular damage, eventually impacting organ function, increasing the risk of cancer and heart disease, and potentially becoming fatal.
- Even in the absence of iron overload disorders, excess iron intake has been linked with a higher risk of cardiovascular disease.
- Iron absorption and metabolism depends on adequate levels of several other nutrients, including vitamin A, copper, and zinc.
- Iron is needed for the development of the central nervous system, especially during childhood.
- During pregnancy, adequate iron helps promote healthy gestation and prevent some adverse outcomes, including preterm birth and low birth weight.
- Iron deficiency is the most common nutrient deficiency among humans, and when it progresses to clinical anemia, causes symptoms such as brittle nails, mouth sores, fatigue, heart palpitations, rapid breathing, rapid heart rate, difficulty swallowing, and impaired thyroid function.
- People at highest risk of iron deficiency are children, adolescents, pregnant people, menstruating individuals, people with inflammatory disorders, athletes, people with malabsorption disorders (like celiac disease or inflammatory bowel diseases), and vegans and vegetarians.
Along with being abundant in the earth’s crust, iron is one of the most thoroughly studied minerals in nutritional science, and is essential for the metabolism of all living organisms. The adult human body contains about 4 grams of iron (mostly in the form of hemoglobin and myoglobin)! Chemists first discovered the presence of iron in blood in 1713, but it was being used for therapeutic purposes as far back as the Iron Age (from about 1200 to 1000 BCE)! The word iron is thought to come from the Proto-Germanic word isarnan, which roughly means “holy metal” or “powerful metal”—referring to the use of iron to make swords during in the Crusades. However, the Latin word for iron, ferrum, is the source of its atomic symbol (Fe), as well as iron-related words like ferritin (a protein that stores iron) and transferrin (a glycoprotein that binds to iron and transports it through the blood).
Iron is an essential part of hundreds of enzymes and proteins involved in oxygen transport, energy production, DNA synthesis, cellular growth, cellular replication, and more! It’s also needed for some vital functions like reproduction, healing, and immunity.
Food can contain one of two forms of iron: iron as a component of heme (a precursor to hemoglobin that’s composed of a ring-like organic compound with an iron atom attached) or nonheme iron (the predominant form in plant foods and dairy, although it’s also present in meat). Heme iron-rich foods include liver, red meat, and some shellfish (especially oysters, mussels, and clams). The best sources of iron in its non-heme form are dark leafy greens, legumes (such as lentils, kidney beans, peas, white beans, and chickpeas), and blackstrap molasses. And, some foods that normally have a low iron content are commercially fortified with iron, such as breakfast cereals, flour, and rice.
The Biological Roles of Iron
Iron is essential for the functioning of a wide variety of proteins in the body—many (but not all!) of which have enzyme activity, and that are variously involved in oxygen transport and storage, electron transport, energy metabolism, oxygen sensing, DNA replication and repair, oxidation, and free radical scavenging. Some iron-dependent proteins even exhibit antioxidant or beneficial pro-oxidant functions.
On a technical level, these proteins fall into several distinct categories:
- iron-sulfur cluster proteins that help transfer electrons between molecules, and which are involved in DNA replication and repair (such as DNA polymerases and DNA helicases) or energy production (such as succinate dehydrogenase, aconitase, ferredoxin-1, isocitrate dehydrogenase, NADH dehydrogenase, and xanthine oxidase);
- heme enzymes involved in electron transfer (such as cytochrome c oxidase and cytochromes a, b, and f) or with oxidase activity (such as the cytochrome P450 family, sulfite oxidase, myeloperoxidase, catalase, peroxidases, cyclooxygenase, and endothelial nitric oxide synthase);
- nonheme enzymes that use iron as a cofactor (such as several amino acid hydroxylases and ribonucleotide reductase);
- nonheme proteins needed to transport and store iron (such as ferritin, transferrin, lactoferrin, hemopexin, and haptoglobin); and lastly,
- globin-heme proteins, which are nonenzymatic proteins needed to transport and store oxygen—including hemoglobin (the protein in red blood cells responsible for carrying oxygen from the lungs to every other cell in the body), myoglobin (an oxygen-binding protein in the muscles), and neuroglobin (a protein found in both peripheral and central nervous system neurons).
Although the number of iron-dependent proteins is huge, a handful are particularly noteworthy. For example, hemoglobin and myoglobin are vital for keeping tissues throughout the body oxygenated: hemoglobin contains four iron-containing heme molecules (it’s the iron itself that binds to oxygen!), and has a unique ability to rapidly acquire oxygen when it makes contact with the lungs—after which it releases the oxygen as needed throughout other tissues. Likewise, myoglobin (which contains one iron-containing heme molecule) helps coordinate the supply-and-demand delivery of oxygen to muscles as they work, ensuring muscle tissue stays oxygenated. Meanwhile, iron-dependent cytochromes serve as electron carriers during ATP synthesis, making them essential for cellular energy production (and therefore life itself!). Cytochrome P450 is a particularly important family of enzymes needed for detoxifying and metabolizing pollutants and drugs, as well as metabolizing many biological molecules (such as fatty acids, organic acids, sterols, steroids, prostaglandins, vitamin A, vitamin D, and vitamin K). Some heme-containing peroxidases and catalase are important for protecting cells against reactive oxygen species (ROS), due to their ability to catalyze the conversion of hydrogen peroxide into oxygen and water. And, iron-dependent ribonucleotide reductases are needed for the conversion of nucleotides to deoxynucleotides, making them essential for DNA replication and repair.
In addition to its protein and enzyme functions, iron plays an important role in immunity. Most pathogens require iron in order to grow and spread, and some immune cells (namely T lymphocytes) likewise need iron to differentiate and proliferate. During times of infection, the body up-regulates hepcidin synthesis so that blood concentrations of iron decrease while concentrations of ferritin (which stores iron) increase—effectively keeping iron away from the pathogens that need it to survive!
While adequate iron is essential for life, too much free iron in the body can lead to oxidative stress and cellular damage, which can eventually impact organ function and become fatal. What’s more, the body excretes relatively little iron under most circumstances, bringing the the potential for toxic levels of buildup (especially compared to micronutrients that are more readily eliminated, such as water-soluble vitamins). To compensate, the body has mechanisms in place for tightly regulating iron metabolism, helping avoid both deficiency and overload. In particular, a hormone called hepcidin serves as the master regulator for iron homeostasis: when iron stores are sufficient, this hormone helps reduce the absorption of dietary iron, decreases iron bioavailability, and promotes cellular iron sequestration; when iron stores are too low, hepcidin levels decrease so that iron absorption and mobilization can increase! The body is also able to conserve iron by recycling it: in the spleen, macrophages engulf aging red blood cells, recovering about 20 mg of iron each day from heme; the recovered iron is then deposited in ferritin or exported to transferrin (which carries iron in the blood) to be delivered to other tissues.
Interactions with Other Nutrients
Iron has a number of important interactions with other minerals and vitamins. For example, vitamin A deficiency can alter iron metabolism, potentially worsening iron-deficiency anemia; supplementing with vitamin A has been shown to improve iron status in children and pregnant women. And, that relationship may be a two-way street: rodent studies have shown that iron deficiency can likewise alter the level of vitamin A in the liver and blood.
Copper, too, is needed for iron metabolism and for the transport of iron from the liver to the bone marrow, where red blood cells are formed; in both animals and humans, copper deficiency can lead to iron accumulation in the liver and even cirrhosis (a late-stage liver disease characterized by permanent scarring). Meanwhile, high iron intakes have been shown to interfere with copper absorption, especially in infants.
Zinc deficiency can also exacerbate iron-deficiency anemia, while iron supplements can inhibit the absorption of supplemental zinc when taken together on an empty stomach (though this issue goes away if taken with food!). Calcium is known to block both heme and nonheme iron absorption from food and supplements—but the body appears to compensate for this by adjusting iron homeostasis, because most studies don’t show a significant negative impact of calcium intake on iron status. Studies have also shown that chromium and manganese can inhibit iron absorption due to shared absorptive pathways.
Importantly, when vitamin C is consumed alongside nonheme iron, it reduces the iron into its ferrous (Fe2+) form—creating a highly absorbable iron-ascorbic acid complex that makes the nonheme iron much more bioavailable!
Iron in Health and Disease
Because of its diverse functions in the body, iron plays an important part in preventing disease and maintaining overall health.
Iron and Development
Iron is needed for central nervous system development, especially during childhood: due to the role of iron-dependent enzymes in neurotransmitter synthesis, nerve myelination, and the energy metabolism of neurons, iron can ultimately help support healthy psychomotor and cognitive development.
Studies have found that in older children, adolescents, and women with iron deficiency, iron supplementation was able to improve concentration and attention, and potentially even boost some measures of IQ!
Iron and Pregnancy
In pregnant women, adequate iron is needed for healthy gestation and to prevent adverse pregnancy outcomes. Observational studies have linked severe anemia during pregnancy to preterm birth, low birth weight infants, and higher risk of mortality for both the mother and newborn. Iron requirements significantly increase during the second and third trimesters, in particular, due to the rising iron needs for the placenta and developing fetus—making it particularly important to have adequate dietary intake during this time. In fact, research has shown that nearly 30% of women in their third trimester of pregnancy are iron deficient!
Iron and Restless Leg Syndrome
Iron may also play a role in of restless leg syndrome (also called Willis-Ekbom disease), which is a neurological disorder characterized by an irresistible urge to move your legs. Although its cause isn’t fully understood, it appears to have a genetic component (it’s inherited in about 50% of sufferers), and iron may be involved through affecting the activity of tyrosine hydroxylase—an enzyme used for synthesizing the neurotransmitter dopamine. But, more research is needed to test whether iron supplementation can relieve symptoms of this condition.
Health Effects of Iron Deficiency
Iron deficiency is the most widespread nutrient deficiency in the world, affecting up to 2 billion people globally. Children, adolescents, frequent blood donors, and menstruating or pregnant individuals are at the highest risk of not getting enough iron (in fact, nearly one out of five pregnant people have been shown to be iron deficient!). But, iron deficiency can also occur from chronic blood loss, especially gastrointestinal tract bleeding (such as from parasite infection, peptic ulcers, gastrointestinal tumors, hiatal hernia, diverticulosis, chronic kidney disease, and even heavy endurance exercise). People with celiac disease, atrophic gastritis, or inflammatory bowel diseases can also develop iron deficiency due to impaired iron absorption. Vegetarians and vegans may also be more susceptible to iron deficiency due to the lower bioavailability of plant-based iron sources (by some estimates, the bioavailability of iron from vegetarian diets is about half that of an omnivorous diet, meaning the amount of iron needed from the diet may be higher than recommended intakes for omnivores). And, people with acute or chronic inflammation resulting from cancer, critical illness, chronic infection, or other inflammatory disorders can cause abnormally low levels of circulating iron, leading to anemia (when this occurs, it’s known as “anemia of chronic disease”).
Iron deficiency happens when the body’s iron reserves get depleted, leading to an inadequate supply of iron to cells. When those iron stores drop low enough so that hemoglobin synthesis and red blood cell formation are impaired, the result is microcytic anemia—a condition where red blood cells become small and pale in color, and can’t deliver adequate oxygen to tissues and organs. Anemia officially occurs when hemoglobin concentrations drop below two standard deviations of the mean for the average healthy population of the same age, gender, and altitude (the decreased oxygen levels in high-altitude air can affect iron metabolism!). Importantly, anemia can also result from vitamin B12 or folate deficiency, making it important to screen for these deficiencies as well.
Although there aren’t obvious symptoms during early-stage iron deficiency (when iron stores are low but the functional supply is still sufficient), as it progresses to anemia, iron deficiency can cause fatigue, heart palpitations, rapid heart rate, and rapid breathing. Because there’s less hemoglobin in red blood cells (impairing the delivery of oxygen to body tissues) and less myoglobin in muscle cells (impairing the delivery of oxygen to mitochondria for energy production), anemia can reduce athletic performance and physical work capacity. Additionally, iron deficiency can impair thyroid hormone synthesis and thyroid function, making it hard to maintain a normal body temperature and reducing resiliency to cold exposure. Studies have shown that iron deficiency is particularly detrimental for people with heart disease, including coronary artery disease, heart failure, and pulmonary hypertension.
Additional symptoms of iron deficiency include brittle or spoon-shaped nails, atrophied taste buds, sore tongue, sores at the corners of the mouth, and impaired immune function. In very severe cases of iron-deficiency anemia, the pharyngeal muscles in the esophagus can degrade, leading to the formation of webs of tissue (called Plummer-Vinson syndrome) that make swallowing difficult.
In children, iron deficiency (even when present without clinical anemia) is associated with impaired cognitive development, abnormal behavioral patterns, and poor achievement in school. In pregnant women, iron deficiency can reduce gestation length and lead to low body-weight newborns.
For most people, iron deficiency is assessed by measuring circulating iron levels, iron stores, and certain blood parameters—in particular, serum iron, total iron binding capacity, the iron-storage protein serum ferritin, soluble transferrin receptor, and saturation of transferrin. But, inflammation and infection can alter blood levels of ferritin, so measuring inflammatory markers (such as C-reactive protein or fibrinogen) is recommended while assessing iron status! And, due to a tendency for iron status to decline throughout pregnancy, pregnant women have different iron level cut-offs to determine deficiency.
Iron deficiency is often treated with dietary supplements, but it’s important to note that this can cause some unpleasant side effects—including stomach ache, gastrointestinal irritation, nausea, vomiting, constipation, or diarrhea. In order to prevent these symptoms, the tolerable upper intake level for iron is set at 45 mg per day for most adults. Iron supplements can also interfere with the absorption and effectiveness of some medications, including antibiotics, hypothyroid medications, Parkinson’s disease medications, histamine receptor antagonists, proton pump inhibitors, and anti-osteoporosis drugs.
Problems From Too Much Iron
While iron is essential for human health and life, too much can increase the risk of some serious health conditions—particularly for people with certain genetic or acquired diseases that affect iron metabolism. For example, a group of late-onset, autosomal recessive disorders called hereditary hemochromatosis can cause the body to absorb too much iron from food, causing iron to build up in the vital organs (including the liver and heart). Over time, iron overload can lead to liver cirrhosis, heart muscle damage (cardiomyopathy), hypogonadism, joint problems, and increased skin pigmentation, as well as an increased risk of liver cancer, neurodegenerative diseases, and type 2 diabetes (due to the oxidative stress associated with iron overload causing damage to pancreatic beta-cells and impairing insulin secretion).
People with hereditary hemochromatosis are advised to avoid alcohol (due to the increased risk of liver cirrhosis) and high-dose vitamin C supplementation (due to its iron absorption-enhancing abilities), and may require phlebotomy or chelation therapy to help remove excess iron from the body.
In addition to hereditary hemochromatosis, the genetic disorders hypotransferrinemia, aceruloplasminemia, porphyria cutanea tarda, and Friedreich’s ataxia can also cause excessive iron to accumulate—as can some acquired iron-overload diseases such as beta-thalassemia (an inherited blood disorder affecting hemoglobin production), sideroblastic anemia (a family of blood disorders where the bone marrow can’t properly use iron to make red blood cells), pyruvate kinase deficiency, and hemolytic anemia (a disorder where red blood cells get destroyed more rapidly than they can be replaced).
Even among people without iron-related genetic disorders, high iron intake (especially heme iron) has been linked with an increased risk of cardiovascular disease. One meta-analysis of prospective studies found that people with the highest versus lowest heme iron intake had a 31% greater chance of developing heart disease over time.
In addition, iron toxicity can happen acutely from accidental overdose (in fact, among children under the age of six, the leading cause of poisoning fatalities is overdose from iron-containing products). Acute toxicity can occur from ingesting iron doses of 20 to 60 mg per kilogram of body weight, leading to initial symptoms of nausea, vomiting, lethargy, low blood pressure, fever, weak and rapid pulse, tarry stools, breathing difficulties, and even coma. If the acute toxicity isn’t immediately fatal, various body systems can begin to fail within the 48 hours immediately following iron ingestion—including problems with the cardiovascular system, liver, kidney, blood, and/or central nervous system. Long-term damage can then develop in the central nervous system, stomach, or liver.
How Much Iron Do We Need?
The recommended dietary allowance (RDA) for iron is 18 mg per day for premenopausal women, 27 mg per day during pregnancy, 9 mg per day while breast-feeding, and 8 mg daily for men and postmenopausal women. Because vegetarian and vegan diets predominantly contain the less bioavailable type of iron (nonheme), it’s recommended that people who don’t eat meat aim for about 1.8 times the normal iron RDA.
It’s worth noting that iron as a component of heme is significantly more bioavailable than nonheme iron. In fact, only about 2 – 20% of nonheme iron is absorbed, although the actual amount depends on a variety of factors. For example, vitamin C strongly enhances nonheme absorption, as do fermented foods and alcohol. A peptide in meat—called the meat-fish-poultry-factor—enhances the absorption of any nonheme iron present in the meal, whether of plant or animal origin. Conversely, phytic acid (such as from grains, legumes, nuts, and seeds) and polyphenols (such as from tea and coffee) can bind to nonheme iron, forming insoluble complexes that can’t enter intestinal cells. And, while meat contains both heme and nonheme iron, its heme iron can get converted to nonheme during extended high-temperature cooking, reducing its bioavailability! That being said, once they’re taken into intestinal cells, heme and nonheme iron are treated the same way by the body.
Good Food Sources of Iron
The following foods are also excellent or good sources of iron, containing at least 10% (and up to 50%) of the daily value per serving.
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