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Iron
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Iron

Iron is a vital mineral essential for various physiological functions that plays a crucial role in supporting overall health and well-being. 

Iron is a mineral that is integral to the formation of hemoglobin, a protein in red blood cells responsible for transporting oxygen from the lungs to various tissues and organs throughout the body.  It plays a critical role in oxygen transport, energy production, DNA synthesis, and maintaining a healthy immune system.

This article serves as a comprehensive guide to understanding iron, covering its definition, functions, dietary sources, recommended intake, and supplementation, as well as laboratory testing and interpretation of results. Additionally, it offers insights into natural methods to optimize iron levels through dietary modifications, lifestyle adjustments, and supplementation. 

Understanding the significance of iron and its impact on health is essential for individuals aiming to maintain optimal energy levels, cognitive function, and overall vitality.

Definition and Function of Iron

Definition of Iron: What Is Iron?  [2., 7.]

Iron is an important mineral in various metabolic processes including DNA synthesis and oxygen transport as a component of hemoglobin. Hemoglobin, found in red blood cells produced by the bone marrow, facilitates oxygen delivery throughout the body. 

Iron deficiency can lead to symptoms like fatigue, pallor, and tachycardia, and it is the most prevalent cause of anemia globally, posing a significant public health concern.  Oral and intravenous iron therapies are available to treat iron-deficiency anemia, with guidelines recommending supplementation based on ferritin and transferrin saturation levels. 

While oral iron is absorbed in the duodenum, intravenous iron is taken up by macrophages and then transported to target sites like the bone marrow and liver. 

The body maintains iron balance by absorbing approximately 1-1.5 mg/day for men and higher amounts for menstruating women and during pregnancy. 

Oral iron absorption in the duodenum is facilitated by two pathways: heme iron uptake from animal sources and nonheme iron from plant and dairy foods. Once absorbed, iron is transported across cell membranes and binds to transferrin for distribution to various tissues. 

Excess iron is stored as ferritin or hemosiderin primarily in the liver, spleen, and bone marrow. Iron movement between cells relies on transferrin-mediated transport, regulated by cellular transferrin receptors and iron-responsive proteins. 

Iron losses are minimal under normal conditions, mainly occurring through feces, with basal daily losses ranging from 0.9 to 1.02 mg/day in non-menstruating women.

Approximately two-thirds of the body's iron is bound to hemoglobin within red blood cells, serving vital roles in oxygen transport. Another 25 percent is stored in a readily mobilizable form, while the remaining 15 percent is distributed across muscle myoglobin and various enzymes essential for cellular functions and oxidative metabolism. 

For instance, a typical 75-kg adult male harbors roughly 4 grams of iron (equivalent to 50 mg/kg), while a menstruating woman, due to her lower red blood cell mass and iron reserves, typically has about 40 mg/kg of iron.  [7.] 

Factors Affecting Iron Absorption  [1.] 

Various factors can increase or decrease iron absorption from the diet.

Factors Enhancing Iron Absorption:

  • Dietary Factors: ascorbate and citrate enhance iron uptake by acting as weak chelators, aiding in solubilizing iron in the duodenum. Ascorbic acid, in particular, facilitates iron absorption by reducing ferric to ferrous iron and overcoming the inhibitory effects of substances like phytate, polyphenols, and calcium found in certain foods.
  • Meat, Fish, and Poultry: these foods enhance iron absorption, with 30g of muscle tissue being equivalent to 25 mg of ascorbic acid. Adding these proteins to vegetarian meals can significantly increase nonheme iron absorption.

Factors Inhibiting Iron Absorption:

  • Phytate: found in plant-based diets, phytate inhibits iron absorption in a dose-dependent manner, with a higher phytate to iron ratio resulting in decreased absorption.
  • Polyphenols: present in various plant foods and beverages, polyphenols, such as those in tea and certain cereals and legumes, add to the inhibitory effect of phytate on iron absorption.
  • Calcium: calcium negatively affects both nonheme and heme iron absorption, particularly at doses of 75-300 mg when added to meals.
  • Animal Proteins: proteins from milk, eggs, and soybean inhibit iron absorption, with casein, whey, egg white, and soy proteins being notable examples.

Competition with Iron:

  • Other Heavy Metals: Lead, manganese, cobalt, and zinc may compete with iron for intestinal absorption, particularly affecting children's health when iron deficiency coexists with lead intoxication. Lead, in particular, not only inhibits iron absorption but also interferes with iron-dependent metabolic processes, leading to anemia and impairing cognitive development, posing significant health risks, especially in children.

Function of Iron: What Does Iron Do in the Body?  [1., 7., 11.]

Iron has critical functions at the cellular level, and iron deficiency has significant negative health effects.  

Iron is important for:

Oxygen Transport: iron is a crucial component of hemoglobin, the protein in red blood cells that carries oxygen from the lungs to oxygenate tissues throughout the body.  Oxygenation is essential for energy production.

Energy Production: iron is involved in the electron transport chain, where it facilitates the transfer of electrons, contributing to the production of adenosine triphosphate (ATP), the body's primary energy currency.

Cellular Respiration: iron-containing enzymes such as cytochromes play a vital role in cellular respiration, assisting in the conversion of oxygen into water and generating energy.

DNA Synthesis: iron is necessary for the synthesis of DNA, the genetic material in cells, which is crucial for cell growth, repair, and replication.

Immune Function: iron supports immune function by aiding in the proliferation and maturation of immune cells, such as lymphocytes and macrophages, which play a role in defending the body against infections.

Neurotransmitter Synthesis: iron is involved in the synthesis of neurotransmitters like dopamine, serotonin, and norepinephrine, which regulate mood, cognition, and behavior.  [3.] 

Muscle Function: iron is essential for muscle function, including muscle contraction and relaxation, as it is a component of myoglobin, which stores and transports oxygen within muscle cells.

Enzyme Activation: iron serves as a cofactor for various enzymes involved in essential metabolic processes, including the metabolism of carbohydrates, fats, and proteins.

Detoxification: iron-containing enzymes such as catalase and peroxidase participate in antioxidant defense mechanisms, neutralizing harmful free radicals and protecting cells from oxidative damage.  [10.]

Hormone Synthesis: iron is necessary for the synthesis of certain hormones including thyroid hormones which regulate metabolism and energy levels.  [14.] 

Brain Development: iron plays a critical role in brain development, particularly during fetal development and early childhood, where it is essential for the formation of neuronal connections and cognitive function.  [6.]

Temperature Regulation: iron contributes to thermoregulation by facilitating oxygen delivery to cells, which is essential for maintaining body temperature and metabolic function.  [13.] 

Wound Healing: iron is involved in the synthesis of collagen, a structural protein necessary for wound healing and tissue repair processes.

Hair, Skin, and Nail Health: iron supports the health of hair, skin, and nails by promoting the production of structural proteins like keratin, which are essential for their strength and integrity.

Cognitive Function: iron plays a role in cognitive function and brain health by supporting neurotransmitter synthesis and ensuring adequate oxygen supply to brain cells.

Pregnancy and Fetal Development: iron is crucial during pregnancy for the development of the placenta and fetus, supporting oxygen transport and cellular growth and development.  [6.] 

Regulation of Gene Expression: iron influences gene expression through its role in DNA synthesis and epigenetic modifications, which can impact various cellular processes and physiological functions.

Dietary Sources of Iron  [11.]

Animal-Based Sources of Iron:

  • Oysters, eastern, cooked with moist heat: 3 ounces provide 8 mg (44% DV)
  • Beef liver, pan fried: 3 ounces provide 5 mg (28% DV)
  • Sardines, Atlantic, canned in oil, drained solids with bone: 3 ounces provide 2 mg (11% DV)
  • Beef, braised bottom round, trimmed to 1/8” fat: 3 ounces provide 2 mg (11% DV)
  • Chicken, roasted, meat and skin: 3 ounces provide 1 mg (6% DV)
  • Turkey, roasted, breast meat and skin: 3 ounces provide 1 mg (6% DV)
  • Egg, hard boiled: 1 large egg provides 1 mg (6% DV)
  • Tuna, light, canned in water: 3 ounces provide 1 mg (6% DV)
  • Cheese, cheddar: 1.5 ounces provide 0 mg (0% DV)
  • Milk: 1 cup provides 0 mg (0% DV)
  • Cheese, cottage, 2% milk fat: 1/2 cup provides 0 mg (0% DV)

Plant-Based Sources of Iron:

  • Breakfast cereals, fortified with 100% of the DV for iron: 1 serving provides 18 mg (100% DV)
  • White beans, canned: 1 cup provides 8 mg (44% DV)
  • Lentils, boiled and drained: 1/2 cup provides 3 mg (17% DV)
  • Spinach, boiled and drained: 1/2 cup provides 3 mg (17% DV)
  • Tofu, firm: 1/2 cup provides 3 mg (17% DV)
  • Kidney beans, canned: 1/2 cup provides 2 mg (11% DV)
  • Chickpeas, boiled and drained: 1/2 cup provides 2 mg (11% DV)
  • Green peas, boiled: 1/2 cup provides 1 mg (6% DV)
  • Cashew nuts, oil roasted: 1 ounce provides 2 mg (11% DV)
  • Raisins, seedless: 1/4 cup provides 1 mg (6% DV)
  • Broccoli, boiled and drained: 1/2 cup provides 1 mg (6% DV)
  • Rice, brown, long or medium grain, cooked: 1 cup provides 1 mg (6% DV)
  • Spaghetti, whole wheat, cooked: 1 cup provides 1 mg (6% DV)
  • Pistachio nuts, dry roasted: 1 ounce provides 1 mg (6% DV)
  • Cantaloupe, diced: 1/2 cup provides 0 mg (0% DV)
  • Mushrooms, white, sliced and stir-fried: 1/2 cup provides 0 mg (0% DV)

Recommended Intake And Supplementation of Iron

RDA for Iron: How Much Iron Should I Get?  [7.]

The Recommended Dietary Allowance (RDA) for iron depends on various factors including gender and age.  

The RDA for adult men is 8 mg/day.  The RDA for adult women ages 19-50 is 18 mg a day, and it drops to 8 mg/day above age 50.  In pregnancy, the RDA is 27 mg/day, and 9 mg/day in lactation.  

Indications for Supplementation: Should I Take an Iron Supplement?

This question should be discussed with a licensed healthcare provider, who can order the appropriate testing for iron assessment and create an individualized plan and monitoring protocol to ensure safety.  

Iron deficiency anemia is the main indication for iron supplementation; it may present with a variety of symptoms, including:

  • Fatigue
  • Pallor (pale skin)
  • Weakness
  • Shortness of breath
  • Dizziness
  • Headaches
  • Cold hands and feet
  • Brittle or spoon-shaped nails (koilonychia)
  • Hair loss (alopecia)
  • Craving for non-food items like ice, dirt, or starch (pica)
  • Restless legs syndrome
  • Difficulty concentrating
  • Decreased exercise tolerance
  • Irritability
  • Poor appetite
  • Decreased immune function
  • Rapid heartbeat (tachycardia)
  • Chest pain, especially with exertion
  • Heart palpitations
  • Difficulty swallowing (dysphagia)
  • Soreness or inflammation of the tongue (glossitis)
  • Dry, sore, or inflamed mouth and throat
  • Brittle or ridged nails
  • Increased susceptibility to infections
  • Reduced cognitive function, including memory problems and decreased attention span
  • Depression or low mood
  • Anxiety
  • Restlessness or hyperactivity (especially in children)
  • Poor growth and development (especially in children)
  • Delayed physical and cognitive development (especially in infants and children)

People living with these symptoms should see a medical professional for a full assessment including iron blood panels.

Lab Testing for Iron Assessment

Lab Testing Info and Sample Requirements

A comprehensive iron analysis typically requires assessment of multiple markers, including:

  • Serum ferritin: represents the level of iron stores in the body. Levels below 30 ng/mL are generally considered diagnostic of iron deficiency, with values below 10-15 ng/mL being 99 percent specific for iron deficiency anemia.
  • % Transferrin saturation: indicates the proportion of transferrin (the protein that transports iron in the blood) that is saturated with iron. A transferrin saturation of under 20% generally indicates iron deficiency.
  • Serum iron: measures the amount of iron circulating in the blood. Low levels may indicate iron deficiency.
  • Total iron-binding capacity (TIBC): measures the capacity of transferrin to bind to iron. Elevated levels may indicate iron deficiency.
  • Complete blood count (CBC): can reveal characteristic findings of iron deficiency anemia, such as microcytic (small) and hypochromic (pale) red blood cells.some text
    • Hemoglobin and hematocrit: although not specific for iron deficiency, low levels may indicate anemia, which can be caused by iron deficiency.
    • Red blood cell indices: these include mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Low MCV and MCH values suggest microcytic, hypochromic anemia, characteristic of iron deficiency.

A comprehensive iron assessment requires a venipuncture.  Fasting may be recommended.

Interpreting Test Results

Reference Range for Iron Biomarkers

It is important to refer to the reference ranges of the lab company used.  Some general reference ranges given include:

Serum Iron:  [12.]

Male: 80-180 mcg/dL or 14-32 μmol/L (SI units)

Female: 60-160 mcg/dL or 11-29 μmol/L (SI units)

Newborn: 100-250 mcg/dL

Child: 50-120 mcg/dL

TIBC:  [4.]

240 mcg/dL to 450 mcg/dL, although reference ranges often vary

% Transferrin Saturation:  [12.]

Male: 20-50%

Female: 15-50%

Hemoglobin:  [12.] 

Male: 14-18 g/dL or 8.7-11.2 mmol/L (SI units)

Female: 12-16 g/dL or 7.4-9.9 mmol/L (SI units)

Pregnant female: >11 g/dL

Elderly: Slight decrease in values

Hematocrit:  [8.]

Males - 0.40-0.54/40-54%

Females - 0.36-0.46/36-46%

Newborns - 0.53-0.69/53-69%

Ferritin:  [5.]

Male: 12-300 ng/mL

Female: 10-150 ng/mL

Clinical Significance of High Levels of Iron  [9.]

Iron overload, characterized by excessive iron stores in the body, can arise from inherited genetic mutations or secondary causes such as transfusion, hemolysis, or excessive iron intake.  Hereditary hemochromatosis is the leading cause of iron overload.  

This excess iron deposition can lead to organ damage, particularly affecting the liver, heart, and endocrine glands. Symptoms may include fatigue, joint pain, abdominal discomfort, irregular heart rhythms, and hyperpigmentation, among others.

Undiagnosed iron overload can lead to serious health consequences if left untreated. Chronic iron deposition in organs such as the liver can progress to cirrhosis and hepatocellular carcinoma, while iron accumulation in the heart may result in heart failure and arrhythmias. 

Furthermore, untreated iron overload can exacerbate existing conditions such as diabetes, hypothyroidism, and joint disorders, significantly impacting the patient's overall health and quality of life. 

Early detection and intervention are crucial to prevent the progression of iron overload-related complications.

Clinical Significance of Low Levels of Iron  [15.]

Iron deficiency anemia (IDA) holds significant clinical importance due to its widespread prevalence and profound impact on various physiological functions. IDA affects individuals across all age groups and demographics, making it a global public health concern. 

IDA arises when there is an insufficient supply of iron to meet the body's demands for hemoglobin synthesis, leading to reduced oxygen-carrying capacity in red blood cells. Consequently, patients with IDA often experience symptoms such as fatigue, weakness, palpitations, and shortness of breath, which can impair their quality of life and functional capacity. 

Furthermore, IDA can exacerbate existing health conditions and contribute to complications such as impaired cognitive function, compromised immune response, and increased susceptibility to infections.

Iron deficiency anemia poses particular challenges and implications for both maternal and fetal health. During pregnancy, the demand for iron escalates to support the expansion of maternal blood volume, placental development, and fetal growth and development. Consequently, pregnant individuals are at heightened risk of developing iron deficiency anemia, especially in the later stages of gestation. 

Untreated IDA during pregnancy can lead to adverse outcomes such as preterm birth, low birth weight, and maternal morbidity, highlighting the critical importance of early detection and management. 

Similarly, the postpartum period represents a vulnerable phase where women may experience ongoing iron depletion due to blood loss during childbirth and lactation-related demands.

Natural Ways to Optimize Iron Levels  [7., 11.]

  • Incorporate iron-rich foods into your diet, such as lean meats, poultry, fish, beans, lentils, tofu, spinach, kale, and fortified cereals.
  • Pair iron-rich foods with sources of vitamin C, like citrus fruits, strawberries, bell peppers, and tomatoes, to enhance iron absorption.
  • Avoid drinking tea or coffee with meals, as they contain compounds that can inhibit iron absorption.
  • Cook in cast-iron pots and pans, as they can increase the iron content of food.
  • Consume fermented foods like yogurt, kefir, and sauerkraut, which can improve gut health and enhance iron absorption.
  • Limit consumption of calcium-rich foods and supplements during meals, as calcium can interfere with iron absorption.
  • Eat foods rich in folate, vitamin B12, and vitamin A, as they play crucial roles in red blood cell production and iron metabolism.
  • Consider incorporating iron supplements under the guidance of a healthcare professional if dietary sources alone are insufficient to meet your iron needs.

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What's 
Iron
?
Iron is an essential mineral that our bodies need to work properly. It is a main part of hemoglobin, a protein in our red blood cells that transports oxygen from our lungs to the rest of our body. Iron also plays a critical role in generating energy, as it helps change food into fuel for our cells. Moreover, it takes part in the production of certain hormones and connective tissues. Since our bodies can't make iron by themselves, it's crucial to get it from the food we eat. Iron-rich foods include red meat, poultry, seafood, beans, and leafy green vegetables.
If Your Levels Are High
Having too much iron in your body might mean that you're taking in more iron than you need. This can happen for a few reasons, like eating lots of iron-rich foods, taking iron supplements, or using certain medications that boost iron absorption. Sometimes, high iron levels can point to an underlying health issue that affects how your body handles iron, such as hemochromatosis, a genetic condition that makes you absorb too much iron. High iron levels can also be linked to liver problems or heavy alcohol use. Keep in mind that while iron is important for your body to function properly, having too much can cause harm by creating stress and inflammation, which can damage your tissues and organs.
Symptoms of High Levels
Symptoms of high levels of Iron could include fatigue, joint pain, abdominal pain, loss of libido, and in severe cases, heart problems or liver disease.
If Your Levels are Low
Low iron levels might mean your body isn't getting enough of this important mineral, which could be due to not eating enough iron-rich foods like red meat, poultry, seafood, beans, and leafy green vegetables. Sometimes, your body might have trouble absorbing iron from food, or you could be losing blood, which can also lead to low iron levels. Pregnancy, certain medications (like heartburn or acid reflux treatments), and health issues like gastrointestinal disorders or conditions causing chronic blood loss could also contribute to low iron levels in your body.
Symptoms of Low Levels
Symptoms of low levels of Iron may include fatigue, weakness, pale skin, cold hands and feet, brittle nails, and an increased susceptibility to infections.
See References

[1.] Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sci. 2014 Feb;19(2):164-74. PMID: 24778671; PMCID: PMC3999603. 

[2.] Barney J, Moosavi L. Iron. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542171/

[3.] Berthou C, Iliou JP, Barba D. Iron, neuro-bioavailability and depression. EJHaem. 2021 Dec 5;3(1):263-275. doi: 10.1002/jha2.321. PMID: 35846210; PMCID: PMC9175715. 

[4.] Faruqi A, Mukkamalla SKR. Iron Binding Capacity. [Updated 2023 Jan 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559119/ 

[5.] Ferritin: Reference Range, Interpretation, Collection and Panels. eMedicine. Published online October 16, 2020. https://emedicine.medscape.com/article/2085454-overview 

[6.] Georgieff MK. The role of iron in neurodevelopment: fetal iron deficiency and the developing hippocampus. Biochem Soc Trans. 2008 Dec;36(Pt 6):1267-71. doi: 10.1042/BST0361267. PMID: 19021538; PMCID: PMC2711433.

[7.] Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001. 9, Iron. Available from: https://www.ncbi.nlm.nih.gov/books/NBK222309/ 

[8.] Hematocrit: Reference Range, Interpretation, Collection and Panels. Medscape.com. Published November 9, 2019. https://emedicine.medscape.com/article/2054320-overview 

[9.] McDowell LA, Kudaravalli P, Chen RJ, et al. Iron Overload. [Updated 2024 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526131/ 

[10.] Nkengfack Nembongwe GS, Englert H. Antioxidants in HIV in Africa. HIV/AIDS. Published online 2018:95-106. doi:https://doi.org/10.1016/b978-0-12-809853-0.00009-2 

[11.] Office of Dietary Supplements - Iron. ods.od.nih.gov. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/#h16 

[12.] Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic & Laboratory Test Reference. 14th ed. St. Louis, Mo: Elsevier; 2019

[13.] Read “Nutritional Needs in Cold and High-Altitude Environments: Applications for Military Personnel in Field Operations” at NAP.edu. Accessed April 3, 2024. https://nap.nationalacademies.org/read/5197/chapter/19#248 

[14.] Temple LJ, Saigal P. Hypothyroidism. Integrative Medicine (Fourth Edition). Published online January 1, 2018. doi:https://doi.org/10.1016/b978-0-323-35868-2.00034-7 

[15.] Warner MJ, Kamran MT. Iron Deficiency Anemia. [Updated 2023 Aug 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448065/

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