Trace and Ultratrace Minerals: Iron Focus

Trace and Ultratrace Minerals

• Learning objectives include identifying good food sources, explaining digestion/absorption/transport/storage/excretion, describing functions & mechanisms of action, explaining recommended intakes, deficiencies, and toxicities, and explaining how essential mineral status is assessed

Iron

• Iron exists in several oxidation states, but only Fe2+ (ferrous) and Fe3+ (ferric) are stable in the body and food.
• Heme iron (50-60% of iron in meat, fish, and poultry, especially red meats, oysters, and clams) is absorbed more readily than nonheme iron from plant foods, dairy (poor source), whole grains, nuts, legumes, tofu, and spinach.
• Nonheme iron requires hydrolysis and reduction to be absorbed.
• Fortified breads, rolls, pasta, cereals, and flour provide additional iron.
• High doses of oral iron supplements can cause problems such as constipation, stomach pain, and nausea.

Iron Content of Selected Foods

• Breakfast cereals provide 100% of the Daily Value (DV) for iron per serving.
• Other examples of iron-rich foods are Oysters, White beans, Dark Chocolate, Beef Liver, Lentils, Spinach, Tofu, Kidney beans, Chickpeas, Canned Tomatoes, Beef, Potatoes, and Cashew nuts. Iron content and percentage DV are listed for each.
• DV= 18 mg.

Digestion & Absorption

• Heme Iron: Proteases digest heme from the globin, leaving heme intact for absorption into the enterocyte. Inside the enterocyte heme is hydrolyzed into Fe²⁺ and protoporphyrin.
• Nonheme Iron: Food components must be hydrolyzed and iron is reduced to cross the intestinal membrane. Stomach acid (HCl) helps reduce Fe³⁺ to Fe²⁺; reductases at the brush border further reduce Fe³⁺ to Fe²⁺.
• Enhancers of iron absorption include sugars, vitamin C, meat, fish, or poultry consumed alongside nonheme sources, and low iron status (hypoxia).
• Inhibitors include polyphenols, oxalates, phytates, and divalent cations like calcium, zinc, and manganese and an alkaline pH.

Absorption

• Enhancers of nonheme iron absorption (factors that increase absorption):
  • Vitamin C, sugars, meat, fish, and poultry with nonheme iron
  • Low iron status (hypoxia).
• Inhibitors of nonheme iron absorption:
  • Polyphenols, oxalates, phytates, divalent cations (calcium, zinc, manganese), an alkaline pH.
• Acidic pH is optimal.

Iron Must Be Oxidized for Transport

• Fe2+ crosses the basolateral membrane through ferroportin.
• Hephaestin in the intestine, and ceruloplasmin in other cells and plasma, oxidize Fe2+ into Fe3+ as it leaves the cell.
• Fe3+ can then bind to transferrin for transport.

Transport and Cellular Uptake

• Free iron is potentially harmful, increasing free radical production.
• Transferrin transports and delivers iron to cells. It's a glycoprotein with two Fe-binding sites; 20-40% is saturated with iron in healthy conditions, while the remainder is available to bind other minerals.
• Transferrin receptors (TfR1 on almost all cells and TfR2 in hepatocytes and erythroblasts) take up transferrin-bound iron. TfR2 regulates liver iron and hepcidin synthesis.

Iron Storage

• Iron is stored primarily in the liver (60%), bone marrow, and spleen.
• Ferritin is the primary storage form, a spherical protein with a hollow core.
• The hollow core contains iron in a variety of ferric compounds.
• Iron is deposited in the center as a variety of ferric compounds.
• Damaged ferritin forms hemosiderin.

Systemic Iron Regulation

• The liver detects iron status via Tf saturation, triggering the release of hepcidin.
• Hepcidin binds to ferroportin, inhibiting iron transport from enterocytes, hepatocytes, and reticuloendothelial macrophages.
• Iron accumulates in these cells

Cellular Iron Regulation

• Iron regulatory proteins 1 and 2 (IRP1 and IRP2) bind to iron response elements (IREs) in specific mRNA segments, regulating the synthesis of iron-related proteins.
• Low iron: ↑ DMT1, TfR, DCYTB, ferroportin, ↓ ferritin, & ALAS.
• High iron: ↓ DMT1, TfR, DCYTB, ferroportin, ↑ ferritin, & ALAS.

Zinc

• Zinc is primarily found in its divalent form (Zn2+) in the body.
• Good sources: red meats (organ meats) and seafood, poultry, pork, dairy, whole grains, leafy vegetables, and root vegetables.
• Heating can reduce zinc bioavailability.
• Sources in pancreatic and biliary secretions are absorbed for re-use.
• Supplemental zinc comes in various forms (pills, lozenges).

Zinc Transporters

• ZIP transporters increase cytoplasmic zinc concentration.
• ZnT transporters facilitate zinc efflux.
• Both ZIP and ZnT genes can be up or downregulated in response to zinc.

Factors Influencing Zinc Absorption

• Enhancers include organic acids, glutathione, and amino acids.
• Inhibitors include phytic acid, oxalic acid, polyphenols, and selected nutrients.

Zinc Functions

• Crucial for protein synthesis, cell membrane structure and function, skin integrity, cell-mediated immunity, sexual maturation, fertility and reproduction, insulin synthesis and storage, taste, and basal metabolic rate.

Copper

• Copper exists in both cuprous (Cu1+) and cupric (Cu2+) forms, but most is in the Cu2+ form
• The richest sources are organ meats and shellfish.
• Other good sources include nuts, seeds, legumes, dried fruits, potatoes, whole grains, and cocoa

Copper Content of Selected Foods

• A list of various foods provides their content of Copper in µg and % daily value (DV).

Copper Absorption

• Enhancers include some amino acids, glutathione, and acids
• Inhibitors include phytic acid and zinc.

Copper Homeostasis

• Copper is transported to the liver in albumin and other protein complexes.
• The liver deals with copper uptake via CTR1, CTR2, DMT1, and other receptors.
• Copper binds metallothionein.
• Chaperones direct intracellular trafficking and Cu delivery for metabolism.

Copper Storage and Excretion

• Relatively little copper is stored, widely distributed throughout the tissues
• The liver is the major storage organ.
• Excreted mostly as bile into feces and smaller amounts in sweat and exfoliated skin cells.

Copper Functions and Mechanisms of Action

• Ceruloplasmin (and hephaestin) function as an oxidase that oxidizes minerals, e.g. Fe2+ → Fe3+, in the circulation.
• Antioxidant, modulating inflammatory and infection responses.
• Other functions: Superoxide dismutase (SOD), ATP production, connective tissue formation, neurotransmitter synthesis, and melanin synthesis.

Selenium

• Selenium exists in different oxidation states and is chemically similar to sulfur, replacing sulfur in certain amino acids.
• Selenium content varies in food based on soil concentrations.
• Animal foods generally have more selenium than plants.
• Absorption is not affected by nutritional status and directly related to food levels.

Selenium in Selected Food Sources

• A list of various foods provides their content of Selenium in µg and daily value (DV).

Selenium Transport, Storage, and Excretion

• Transported in blood attached to hemoglobin, albumin, and red blood cells.
• The liver takes up around 50% on the first pass.
• Se is metabolized into selenoprotein P (SePP1).
• Stored in liver, kidney, and spleen, and excreted mostly in urine and bile.

Selenium Functions

• Selenoproteins play a role in antioxidant activity (removing ROS (hydroperoxides).
• Roles include maintaining thyroid homeostasis, and reducing and removing signal molecules.

Recommended Intakes, Deficiency, Toxicity, and Assessment (for each mineral)

Deficiency

• Insufficient dietary intake, reduced absorption, and/or normal blood loss are sources of deficiency.
• Deficiency can appear in early stages, progressing to anemia.

Toxicity

• Related to excessive intake usually of supplements
• Chronic cases involve organ damage.

Assessment

• General methods to assess mineral status and identify potential deficiencies in relevant minerals.