Iron

Iron in Human Physiology

Iron is a trace element fundamental to human health, serving as the central component of hemoglobin—the protein that transports oxygen throughout the bloodstream ^[1]. Additionally, iron functions as a cofactor in cytochrome P450 enzymes, mitochondrial respiratory complexes, and iron-sulfur cluster proteins essential for ATP production. The human body contains approximately 3-4 grams of iron, with about two-thirds present in hemoglobin and the remainder distributed in myoglobin, iron-storage proteins (ferritin and hemosiderin), and enzymatic systems ^[1]. Iron homeostasis is tightly regulated through absorption in the duodenum and iron-loss replacement, as the body has no active iron excretion mechanism ^[4].

Heme vs Non-Heme Iron

Dietary iron exists in two distinct forms with markedly different absorption characteristics. Heme iron, found in animal products like meat, seafood, and poultry, accounts for 10-15% of total iron intake in Western diets but delivers superior bioavailability with 15-35% absorption rates ^[1]. This form is absorbed intact through specific heme transporters and is less affected by dietary factors.

Non-heme iron, present in plant foods (beans, lentils, spinach, fortified cereals) and eggs, constitutes the majority of dietary iron but has lower and more variable absorption (2-20%) ^[1]. Its bioavailability depends heavily on the body's iron status and the presence of absorption enhancers or inhibitors. People following vegetarian diets require approximately 1.8 times more iron than meat-eaters to compensate for this reduced bioavailability ^[1].

Iron Absorption Enhancers and Inhibitors

Several dietary components can dramatically affect non-heme iron absorption:

Enhancers: Vitamin C (ascorbic acid) is the most potent enhancer, converting ferric iron to the more soluble ferrous form. Studies show consuming just 25mg of vitamin C with a meal can double iron absorption ^[1]. Other enhancers include citric acid, meat, poultry, fish, and fermentation products.

Inhibitors: Phytates in whole grains and legumes, tannins in tea and coffee, and polyphenols in chocolate and some vegetables can significantly reduce iron absorption. Calcium inhibits both heme and non-heme iron absorption, so experts recommend taking calcium and iron supplements at different times ^[1]. Combining these inhibitors can reduce absorption by up to 65%.

Iron Deficiency and Ferritin Levels

Iron deficiency represents the most common nutritional deficiency worldwide, affecting approximately 1.6 billion people ^[2]. It progresses through three distinct stages ^[3]:

Stage 1 - Iron depletion: Serum ferritin falls below 30 mcg/L, indicating depleted iron stores, but hemoglobin remains normal ^[5]. This stage often causes no symptoms but can impair cognitive function and athletic performance.

Stage 2 - Iron-deficient erythropoiesis: Transferrin saturation drops below 16%, and iron supply to red blood cell precursors becomes insufficient. Hemoglobin may still appear normal on routine tests.

Stage 3 - Iron deficiency anemia: Hemoglobin falls below 12 g/dL in women or 13 g/dL in men, accompanied by microcytic, hypochromic red blood cells ^[3]. Symptoms include profound fatigue, dyspnea, pale skin, brittle nails, and restless legs syndrome.

Ferritin reference ranges: Normal levels are typically 15-200 mcg/L for women and 15-300 mcg/L for men. Ferritin below 15 mcg/L confirms depleted iron stores, while levels below 30 mcg/L suggest iron deficiency ^[5]. Note that ferritin is an acute-phase reactant—levels can appear falsely normal or elevated during inflammation, infection, or malignancy.

Who is at Risk?

Certain groups face higher iron deficiency risk: women with heavy menstrual bleeding (10% of menstruating women), pregnant women (37% prevalence globally) ^[2], frequent blood donors (25-35% develop deficiency), endurance athletes (up to 60% of female athletes) ^[6], people with celiac disease or gastrointestinal disorders, and those on strict plant-based diets.

Iron Supplementation Guidelines

Oral iron supplements typically contain ferrous sulfate, ferrous fumarate, or ferrous gluconate. Ferrous forms are more bioavailable than ferric forms ^[1]. Standard dosing provides 65-200 mg elemental iron daily, though recent research suggests alternate-day dosing may improve absorption and reduce side effects ^[6].

Side effects affect 20-70% of users and include constipation, nausea, abdominal pain, and dark stools ^[1]. Taking iron with food reduces side effects but decreases absorption by 40-50%. The Tolerable Upper Intake Level for adults is 45 mg/day, but therapeutic doses often exceed this under medical supervision ^[1].

Intravenous iron is reserved for those who cannot tolerate oral iron, have malabsorption disorders, or require rapid repletion. IV iron carries rare but serious risks including anaphylaxis.

Hemochromatosis: When Iron Becomes Dangerous

Hereditary hemochromatosis is a genetic disorder causing excessive iron absorption and accumulation in organs. The most common form affects approximately 1 in 300 people of Northern European descent, caused by mutations in the HFE gene (particularly C282Y) ^[3]. Unlike iron deficiency, hemochromatosis causes iron overload that damages the liver, heart, pancreas, and joints.

Symptoms typically appear between ages 40-60 in men and later in women (due to menstrual iron loss). These include joint pain, fatigue, diabetes, skin bronzing, and organ failure. Without treatment, cirrhosis, liver cancer, and heart disease develop.

Diagnosis involves elevated serum ferritin (often >1000 mcg/L), increased transferrin saturation (>45%), and genetic testing. Treatment is periodic phlebotomy (blood removal) to reduce iron stores. People with hemochromatosis must avoid iron supplements and limit vitamin C intake with meals.