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Iron

Also known as: Ferrous Sulfate, Ferrous Fumarate, Ferrous Gluconate, Ferrous Bisglycinate, Elemental Iron, Heme Iron Polypeptide

Overview

Iron is one of the most abundant minerals on Earth. It occurs naturally in various foods such as oysters, legumes, chocolate, spinach, beef, and potatoes, and is added to some foods as a fortification measure. Iron is also sold as a supplement in the form of capsules, tablets, or liquid. In hospital settings, it can be administered through intravenous or intramuscular injection. Dietary iron comes in two primary forms: heme iron and non-heme iron. Heme iron is more readily absorbed; it is formed when iron binds to a heterocyclic organic compound called porphyrin. Heme iron is a component of hemoproteins like hemoglobin, an oxygen transport protein, and myoglobin, an oxygen-storage protein found in muscle tissues. Animal products contain both heme and non-heme iron, whereas plant-based and iron-fortified foods only provide non-heme iron, which is less easily absorbed by the body.

Benefits

Understanding the process of iron absorption in the body is key to grasping its mechanism of action. The disparity in absorption between heme and non-heme iron has implications for the amount of elemental iron absorbed in the body, with heme iron, typically found in animal products, being absorbed more efficiently. Both heme and non-heme iron are primarily absorbed in the duodenum and, to a lesser extent, in the upper jejunum. Heme iron enters the gastrointestinal tract as ferrous iron, which is more easily absorbed, while non-heme iron is typically ingested in its ferric form. However, for non-heme iron to be absorbed, it must first be reduced into ferrous iron by reductase enzymes or other compounds like vitamin C. Ferrous iron is then taken up by enterocytes lining the intestine through the divalent metal transporter 1, and then leaves these cells and enters the bloodstream via ferroportin. Once in the bloodstream, iron is converted back from ferrous to ferric iron and transported by transferrin to various organs and tissues. After absorption, iron plays a crucial role in several reactions and biological processes within the body, many of which are centered around iron’s roles in protein function and oxygen transport and storage. Iron is required to form hemoglobin and myoglobin. Inadequate iron intake can hinder the production of healthy red blood cells, potentially leading to anemia. In mitochondria, iron serves as a cofactor in proteins that contain iron-sulfur clusters, other heme-containing proteins involved in the electron transport chain, and proteins that contain iron ions. Additionally, iron is involved in cell growth and differentiation, electron transfer reactions for energy production, and the regulation of the expression of some genes. Iron is also an essential nutrient for brain development and function. It plays a role in energy production and neurotransmitter synthesis, as well as in the uptake and degradation of neurotransmitters, all of which are involved in behavior, memory, learning, and sensory systems. It’s important to note that when iron supplements are taken to treat iron deficiency anemia, it usually takes about 3 months to replenish iron stores, and hemoglobin levels will increase gradually in the first month of supplementation.

How it works

Iron plays a pivotal role in numerous biological functions and is often the first-line treatment for iron deficiency anemia. While specific guidelines exist for treating iron deficiency anemia with iron, there is still insufficient evidence to prove the benefits of iron supplementation in individuals with iron deficiency who are not anemic. In clinical practice, iron is commonly prescribed to menstruating women due to the increased blood loss, and during pregnancy to meet heightened metabolic demands and prevent iron deficiency anemia, which could have serious consequences for both the mother and the baby. Iron deficiency is also a risk factor for heart failure. Iron supplementation in individuals affected by heart failure appears to reduce the rates of hospitalization and the severity of heart failure symptoms. Hemoglobin, ferritin and left ventricular ejection fraction levels also seem to be increased by iron, and one meta-analysis also noted that exercise capacity and quality of life were improved after iron supplementation in people with heart failure. Iron is also a key component in the brain, and studies involving children have shown that supplementation may improve memory and concentration. However, more quality research is needed to verify these results. The question of whether iron supplementation benefits infants and young adults remains a topic of debate necessitating further research. One meta-analysis, which included children and adolescents ranging from 1 month to 19 years old, found that iron supplementation increased hemoglobin and ferritin levels, particularly with frequent supplementation over longer periods, and resulted in reduced prevalence of overall anemia, iron deficiency, and iron deficiency anemia. Finally, one meta-analysis demonstrated that both oral and intravenous iron supplementation appeared to improve symptoms of restless leg syndrome. Specifically, intravenous supplementation with ferric carboxymaltose was associated with a significant improvement in quality of life scores, although it had no noticeable effect on sleep quality.

Side effects

The recommended daily allowance depends on gender, age, and whether you are pregnant or lactating: Age Male Female Pregnancy Lactation 0–6 months 0.27 mg 0.27 mg 7–12 months 11 mg 11 mg 1–3 years 7 mg 7 mg 4–8 years 10 mg 10 mg 9–13 years 8 mg 8 mg 14–18 years 11 mg 15 mg 27 mg 10 mg 19–50 years 8 mg 18 mg 27 mg 9 mg 51+ years 8 mg 8 mg These values correspond to the recommended daily allowance for total iron, which encompasses both dietary iron and iron supplements. The need for supplementation depends on the amount of iron absorbed from one's diet. It’s important to avoid exceeding the recommended daily allowance to prevent excessive iron intake. Notably, for infants up to 6 months of age, these values specifically refer to adequate intake, because there is insufficient evidence to establish a recommended daily allowance for this age group. The Institute of Medicine determined the daily adequate intake by multiplying the average iron content in human milk by the average milk intake of exclusively breastfed infants, resulting in an adequate intake of 0.27 mg/day of iron. These values don’t account for potential variations in the iron concentration of human milk. For preterm breastfed infants, a daily oral iron dosage of approximately 2 mg/kg is estimated to be appropriate for preventing iron deficiency or iron deficiency anemia in preterm breastfed babies. Term breastfed infants typically do not require additional iron until around 4 months, at which point supplementation with 1 mg/kg of iron may or may not be required depending on the infant's health status. Formula-fed preterm and term infants may require different dosages if iron supplementation is needed. It is worth noting that iron is most effective when administered on an empty stomach or 2 hours after a meal. However, if iron supplements are poorly tolerated due to gastrointestinal side effects, a dose reduction or administration after a meal may be more suitable.

Dosage

Iron supplements should be used cautiously, only when required, and in accordance with recommended doses. Prolonged use of iron supplements or an excess of iron in the system can lead to adverse side effects. Iron supplements frequently result in gastrointestinal discomfort, including symptoms such as nausea, abdominal pain, dark stool, heartburn, and constipation, and other side effects such as headache. This can be a significant challenge for individuals with iron deficiency anemia, who may find it difficult to adhere to their treatment recommendations. Although ferritin, hemosiderin, and transferrin play essential roles in regulating iron levels in the system, an excessive amount of free iron can trigger the production of free radicals and increase oxidative stress. This can potentially lead to damage to proteins and cells, and harm the body. Diseases characterized by iron overload include hemochromatosis, a hereditary disease in which iron builds up to toxic levels in the body, which can lead to damage to organs such as liver, joints pancreas or heart. Additionally, multiple observational studies have reported that regular consumption of dietary iron, especially heme iron sourced from meat products, may predispose one to numerous diseases and may increase the risk of some cancers. However, the majority of these claims are based on self-reported food diaries or food questionnaires, and the level of evidence is weak. Furthermore, it’s important to highlight that processed meat does not only contain heme iron, but other potentially harmful substances which may be confounding factors that also raise the risk of some diseases. In children, low doses of iron may cause diarrhea, but they do not appear to increase the risk of infections at the recommended dosage. Nevertheless, the World Health Organization advises monitoring children in countries at high risk of malaria when receiving iron supplementation, as it may both increase the risk of contracting the disease and potentially worsen its effects. The mechanism by which iron interacts with malaria is still not fully understood.