IRON DEFICIENCY IS COMMON in humans. On the other hand, excessive iron (for example, with hemochromatosis) is associated with an increased risk of developing several cancers, including breast, colorectal, liver, and prostate.

Today, we explore the promise and the perils of iron — why too little (or too much) of it harms health. But first, a quote from Iron Man, speaking in the film Avengers: Earth’s Mightiest Heroes:

“J.A.R.V.I.S., make a note. Remind me not to wake up in the morning ever again.”

Iron Man is in for a rude awakening when a villain starts the day on the wrong side of the bed. And when Iron Man doesn’t get his beauty sleep, he’s not thrilled about it, either.

So, after finally defeating the villain of the week, Iron Man gets a little help from his artificial intelligence J.A.R.V.I.S. to make a note. There’s nothing better than a long night’s rest after saving the world again.

What is Iron?

Iron is an essential dietary mineral, one that is primarily used by our red blood cells (erythrocytes). Iron is central to hemoglobin, the substance that gives red blood cells their color. Hemoglobin delivers oxygen to all of the cells in our body.

The extraordinary French physiologist Claude Bernard elucidated the role of hemoglobin in the blood. He also originated the term milieu intérieur and the associated concept of homeostasis.

Hemoglobin is a word derived from heme plus globin. Each hemoglobin subunit is a globular protein with a heme group at its center. The heme group has one iron atom that can bind one oxygen molecule. Human hemoglobin has found such subunits.

Max Perutz, an Austrian-born British molecular biologist, shared the 1962 Nobel Prize for Chemistry with John Kendrew for their studies of the structures of hemoglobin and myoglobin.

Iron — Dietary types

There are two forms of dietary iron:

• Heme iron: Heme is found only in animal flesh like meat, seafood, and poultry. Heme iron is absorbed more easily than non-heme iron.
• Non-heme iron: Non-heme iron is found in plant foods like whole grains, nuts, seeds, legumes, and leafy greens. Non-heme iron is in animal flesh (given animals eat plant foods containing non-heme iron) and fortified foods.

Those who have too little dietary heme are at risk of iron deficiency. For example, vegetarians have a high risk of suffering from a deficiency of some nutrients, such as vitamin B12 and iron.

Women have a higher risk of being iron deficient. Did you know that iron deficiency is the world’s most common mineral deficiency?

In summary, iron is an essential dietary mineral that is critical to the transport of oxygen to all of our tissues. Certain populations, including vegetarians, women of childbearing age, and children five and younger, are at higher risk of iron deficiency.

Regulation of iron stores

Iron levels are closely regulated, as iron is an essential nutrient to many of our basic body functions. We need small amounts of the mineral for health. On the other hand, too much iron is potentially toxic.

Our body regulates iron levels by adjusting how much we absorb through our digestive tract. Hepcidin is an iron-regulating hormone that can suppress iron absorption.

When we have high levels of iron in storage, hepcidin levels rise, and iron absorption drops. On the other hand, if our iron stores are low, hepcidin levels decrease, and iron absorption increases.

Physiology, Hepcidin

Hepcidin is a peptide hormone produced in the liver that plays a crucial role in iron homeostasis. Iron is an essential…

www.ncbi.nlm.nih.gov.

Disorders that suppress hepcidin can lead to iron overload, while ones that stimulate hepcidin formation may cause iron deficiency.

In addition, our iron balance is influenced by how much iron is in our diet. If we chronically have a low iron intake, we may develop iron deficiency; too much dietary iron can lead to iron poisoning.

Iron deficiency

Our bodies need iron for several biological functions. We use iron to make hemoglobin and myoglobin. In addition, cell regulation and proliferation processes require iron, as does D.N.A. synthesis and electron transport in our cellular powerhouses, the mitochondria.

Nearly two-thirds of our iron is in the hemoglobin in our circulating red blood cells. We store the remaining third in our liver, bone marrow, spleen, and muscle tissue as ferritin. The iron is delivered, as needed, throughout the body via transferrin (a blood protein that binds to iron). A healthcare professional may evaluate blood levels of these two components if a low red blood cell count (anemia) is suspected.

A ferritin test measures your blood levels of ferritin, the blood protein containing iron. If your ferritin level is too low, it indicates that your iron stores are low and you have iron deficiency. You may have anemia because of this lack of sufficient iron.

On the other hand, if your blood levels of ferritin are higher than normal, you may have a condition that results in your body storing too much iron. Alternatively, you may have hyperthyroidism, liver disease, rheumatoid arthritis, or another inflammatory condition.

Sideropenia (iron deficiency) is a state in which total body iron stores are insufficient to support the body's metabolic activities.

It is easy to miss iron deficiency without anemia; the symptoms can be vague and easily missed. We clinicians must be vigilant when we suspect a chronic iron deficiency in a patient with normal blood counts but symptoms similar to anemia and low ferritin. Iron deficiency may be present, and we should ask about blood loss.

Here are some populations with a higher risk of suffering from iron deficiency:

• Individuals with cancer. Upwards of six out of ten individuals with colon cancer have iron deficiency at diagnosis, likely due to chronic blood loss. Approximately 30 to 45 percent of other cancer types will have iron deficiency. Primary causes are anemia of chronic disease and chemotherapy-induced anemia. Others suffer from chronic blood loss or nutritional deficits (for example, a cancer-induced lack of appetite).
• Frequent blood donors. In the United States, adults may give blood as often as every eight weeks, which can deplete iron stores. Approximately 25 to 35 percent of regular blood donors develop iron deficiency.
• Pregnant women.
• Infants and young children.
• Women with heavy menstrual periods. Women of reproductive age with abnormally heavy bleeding during menstrual periods are at increased risk of iron deficiency.
• Those with heart failure. About six in 10 patients with chronic heart failure have iron deficiency. Chronic iron deficiency is associated with increased early mortality for those with heart failure.
• Individuals with gastrointestinal disorders (such as ulcerative colitis, Crohn’s disease, or celiac disease) or gastrointestinal surgery have a higher risk of iron deficiency.
• Elderly — Those with poor nutrition or chronic inflammatory diseases can lead to anemia.
• Vegetarians — Individuals who have a diet without heme iron from meat, fish, or poultry may develop iron deficiency anemia if they don’t include adequate non-heme iron foods. Because non-heme iron is not well-absorbed, greater quantities of these foods may be needed, or attention given to how they are consumed to improve absorption (consuming vitamin C-rich foods while avoiding eating calcium-rich foods, calcium supplements, or tea).
• Endurance athletes — Running can cause trace amounts of gastrointestinal bleeding, leading to so-called “foot-strike” hemolysis that breaks down red blood cells faster. Female endurance athletes who are menstruating have the greatest risk for iron deficiency anemia.
• People with chronic kidney failure on dialysis

Untreated iron deficiency can lead to cognitive impairment, poor quality of life, fetal brain maturation problems, and low birth weight. Maternal problems can include depression, systemic infection (sepsis), and a higher risk of death.

Iron deficiency anemia can cause fatigue and weakness; gastrointestinal disturbances; impaired cognitive functioning; poorer immune function, impaired body temperature regulation, and exercise or work impairment.

Iron deficiency anemia can lead to psychomotor and cognitive abnormalities and (left untreated) learning difficulties in infants and children.

Iron deficiency treatment

Those with uncomplicated iron deficiency without other significant health problems should receive treatment with oral iron therapy. Oral iron is readily available, cheap, effective, safe, and convenient.

Gastrointestinal (GI) side effects can be reduced using chelated forms of iron. Enteric-coated tablets lead to poor absorption and are not viable options. Selected patients may need intravenous (through a vein) iron treatment.

Interactions with medicines

Iron can interact with certain medications, and some medications can lower iron levels. Here are some selected examples: Iron-containing dietary supplements may lower levels of levodopa (a treatment for Parkinson’s disease or restless leg syndrome).

Levothyroxine is used to treat thyroid cancer, hypothyroidism, and goiter. When taken at the same time as iron, the effectiveness of levothyroxine may drop in some patients. Some drug product labels advise against taking levothyroxine within four hours of iron supplementation.

Proton pump inhibitors (such as lansoprazole (Prevacid®) and omeprazole (Prilosec®)) can be associated with suboptimal responses to iron supplementation.

Fortunately, iron deficiency is typically easily managed, and an excellent prognosis for those with uncomplicated cases and no significant medical problems.

Too much iron

Adults with normal intestinal function have a very low probability of suffering from iron overload secondary to dietary sources. If you take high-dose iron supplements, you may get gastrointestinal side effects. These problems can include gastric upset, nausea and vomiting, constipation, abdominal pain, and diarrhea.

Taking iron with food may help minimize gastrointestinal toxicities. Some develop more serious problems, including gastritis. Gastritis is a general term for a group of conditions with one thing in common: Inflammation of the stomach lining.

Supplements with 25 milligrams (or more) of iron can reduce zinc absorption and blood zinc levels. Finally, acute intakes of over 20 milligrams per kilogram of iron (about 1,365 mg iron for someone weighing 150 pounds) can lead to fluid and blood loss, tissue damage, shock, and organ failure.

Poisoning can occur when people, typically young children, overdose on iron supplements.

Hemochromatosis, a disease caused by a mutation in the hemochromatosis (H.F.E.) gene, is linked to an excessive buildup of iron in the body. Without treatment by regular chelation or removing blood, those with hereditary hemochromatosis often develop signs of iron toxicity by their 30s.

If untreated, hemochromatosis can lead to liver cirrhosis, hepatocellular carcinoma, heart disease, and impaired pancreatic function. The American Association for the Study of Liver Diseases recommends that hemochromatosis management include avoiding iron and vitamin C supplements.

Iron — Recommended iron

As we discussed, meats, seafood, and poultry are rich in heme iron. Do you want non-heme iron? Try some nuts, seeds, vegetables, legumes, and fortified grains. Heme iron is absorbed better than non-heme iron.

Vitamin C and heme iron taken at the same mean can optimize non-heme iron absorption. On the other hand, bran fiber, large calcium intake (such as from supplements), and some plant substances such as phytates and tannins can inhibit non-heme iron absorption.

Here is a source for the recommended intake levels:

Office of Dietary Supplements – Iron

This fact sheet is for health professionals. For a reader-friendly overview of Iron, see our consumer fact…

ods.od.nih.gov.

The maximum daily intake (unlikely to cause harm) for iron is 45 milligrams daily for all males and females ages 14 years or older. For younger ages, the maximum is 40 milligrams.

Heme iron sources

The Harvard T.H. Chan School of Public Health offers these sources of dietary iron:

• Oysters, clams, mussels
• Beef or chicken liver
• Organ meats
• Canned sardines
• Beef
• Poultry
• Canned light tuna

Sources of non-heme iron:

• Fortified breakfast cereals
• Beans
• Dark chocolate (at least 45%)
• Lentils
• Spinach
• Potato with skin
• Nuts, seeds
• Enriched rice or bread

If you want more specifics on the amount of iron in given foods, please check out this nice overview:

Office of Dietary Supplements – Iron

This is a fact sheet intended for health professionals. For a reader-friendly overview of Iron, see our consumer fact…

ods.od.nih.gov

Iron can be dangerous in excess. Fortunately, unless you have an iron overload disorder, it is unlikely that dietary iron will hurt you.

On the other hand, please be careful with iron supplements — they benefit those with iron deficiency but may cause harm for those without iron deficiency. Avoid supplements unless a valued healthcare provider recommends them for you.

Finally, there is low-level evidence (in the form of observational trials) that a high intake of heme iron may increase colon cancer risk. The association between red meat and cancer is debatable. While some plausible mechanisms could explain this association, most of the evidence is based only on observational studies.

Thank you for joining me in this look at how too much iron (or too little) puts your health at risk.