Iron is the most abundant transition metal on the Earth’s surface as well as in organisms and is an essential (vital) trace element for humans. It occurs in several oxidation states, but only Fe2+ – divalent iron, ferro compounds – and Fe3+ – trivalent iron, ferro compounds – have any significance for organisms. In compounds, iron is usually present in divalent form. Fe2+ then acts as a reducing agent and donates electrons. Fe3+ compounds, on the other hand, represent oxidizing agents and, as terminal electron acceptors, are capable of accepting electrons [7,19]. Since Fe2+ in aqueous solutions can spontaneously oxidize to extremely sparingly soluble Fe3+ – hydroxide, organisms possess certain proteins, such as hemoglobin (blood pigment), transferrin or ferritin, which bind iron. Thus, the trace element remains biologically available despite its poor solubility. A healthy person has a total body content of about 3-5 grams of iron – 45 to 60 mg/kg body weight. Approximately 80 % of this is present as functional iron. The majority of functional iron is required for erythrocyte (red blood cell) formation and development, and only a minor portion (12%) for myoglobin synthesis and the mitochondrial respiratory chain. In addition, iron must be available for the biosynthesis of iron-dependent enzymes that are essential for electron transport. Storage organs of iron account for about 20% of the total. The trace element is stored in the form of ferritin and hemosiderin mainly in the liver, spleen, intestinal mucosa and bone marrow. A distinction is made between heme iron – iron protoporphyrin, divalent Fe – and non-heme iron – ionized free iron, may be divalent or trivalent – as a component of inorganic compounds. Hemiron is an iron-protein complex, with a prosthetic group coupled to the protein molecule. The most important heme proteins essential for iron metabolism include hemoglobin, myoglobin and cytochromes. More than half of the functional iron is bound to hemoglobin (red blood pigment) and thus localized in erythrocytes (red blood cells). Myoglobin is a red muscle pigment and together with other iron-containing enzymes – cytochromes, catalases, peroxidases – makes up about 15% of functional iron. The non-heme iron in animal foods is in the form of ferritin, hemosiderin, and iron citrate.
Metabolism
The regulation of iron homeostasis occurs through the control of iron absorption in the small intestine, primarily in the duodenum (duodenum) and jejunum – middle section of the small intestine, also known as the “empty gut.” Absorption is influenced by numerous factors, such as:
- Physiological demand
- Amount and chemical form of ingested iron
- Individual supply status – basal iron absorption is about 1 mg/day, in iron deficiency the absorption rate increases to 3-5 mg/day, in excess iron absorption is lower by up to 50%.
- Extent of erythropoiesis (production of red blood cells).
- Quantitative ratios of various other organic and inorganic dietary components.
- Resorption ratios of the digestive tract.
- Age
- Diseases – for example, malabsorption such as celiac disease (gluten-induced enteropathy), Crohn’s disease, ulcerative colitis and chronic atrophic gastritis are associated with insufficient iron absorption
The trace element is absorbed through food both as non-heme iron, i.e. in ionized free form as free Fe2+ ions, and as heme iron.Most of the iron in food is bound to proteins, organic acids or other substances – iron protoporphyrin (heme), ferrihydroxide complexes. In animal foods, especially in meat, 40 to 60% of the iron is present as heme iron. Bivalent iron is absorbed 15-35% depending on the iron status due to its good solubility and thus has a high bioavailability. In contrast, the availability of non-heme iron, which is predominantly in trivalent form, is significantly lower. Non-heme iron is mainly found in plant foods and is rarely absorbed more than 5%. Trivalent iron is not soluble in the weakly alkaline environment of the upper small intestine and is therefore withdrawn from absorption.Simultaneous consumption of meat and plant foods can double the absorption rate of iron of plant origin. This is due to the low molecular weight complexing agents contained in meat, including animal proteins, which are of higher quality, due to the high number of valuable amino acids, than plant proteins (egg whites). Sulfhydryl group-containing amino acids – methionine, cysteine – favor the reduction of trivalent iron into the divalent form, which is more soluble and absorbable. Sufficient hydrochloric acid production in the gastric juice is also important for optimal utilization of dietary iron. Gastric hydrochloric acid cleaves complex-bound iron into more readily available free iron ions and loosely bound organic iron. Further increase the bioavailability of iron from food:
- Gastroferrin – secretion of the gastric mucosa.
- Vitamin C – promotes absorption of non-heme iron by ascorbic acid inhibiting the formation of poorly soluble trivalent iron; an intake of as little as 25 mg of vitamin C results in a significant increase in absorption
- Vitamin A binds iron during the digestive process, thereby removing it from the absorption-inhibiting influences of phytic acid (phytates) and polyphenols
- Fructose
- Polyoxicarboxylic acids in fruits and vegetables
- Other organic acids, such as citric acid, tartaric acid and lactic acid.
- Alcohol – promotes gastric acid secretion, increasing the absorption of trivalent iron.
By also promoting the conversion of Fe3+ to Fe2+, these substances increase iron absorption. For example, vitamin C – in 150 grams of spinach or kohlrabi – increases the bioavailability of non-heme iron by a factor of 3-4. The iron absorption strongly inhibit:
- Phytic acid (phytates) in cereals, corn, rice, and whole grain and soy products.
- Dietary fiber – not cellulose
- Oxalates in vegetables – especially spinach, rhubarb – and cocoa.
- Polyphenols – including tannins – in coffee, black tea, millet, spinach and red wine.
- Phosvitin in egg yolks
- Carbonates
- Phosphates
- Calcium salts – maximum inhibitory effect was found at dietary calcium levels of 300-600 mg.
- Drugs – antacids containing aluminum, magnesium, and calcium, as well as lipid-lowering drugs, can reduce iron absorption by up to 70% (colestyramine); chelating agents such as penicillamine, ethylenediaminetetraacetate – EDTA – and deferoxamine inhibit non-heme iron absorption in particular.
- Gastric acid binders
- Cadmium – Cd2+ – from the environment
- Excessive intake of other metal ions, such as manganese (Mn2+), cobalt (Co2+), copper (Cu2+), zinc (Zn2+), lead (Pb2+).
- Protein deficiency in the diet
These substances form a complex with iron that is difficult to absorb and therefore block its absorption. After iron is absorbed in the cells of the small intestinal mucosa, it is either stored as ferritin, the iron storage protein, or transferred to the plasma with the help of the transport protein mobilferrin. In plasma, the trace element is transferred to the iron transport protein transferrin. The normal transferrin concentration in plasma is 220-370 mg/100 ml. The level of serum transferrin is inversely correlated with the size of the iron pool. Accordingly, in iron deficiency, both plasma transferrin content and transferrin receptor concentration are increased. Transferrin saturation is an indicator of iron transport to tissues and is usually decreased in iron deficiency. Transferrin transports iron to all cells and tissues, where it subsequently binds to transferrin receptors and is taken up into cells. Of essential importance is mobilization to the bone marrow. There, iron is essential for ongoing hemoglobin formation, which takes priority over other synthesis steps. Approximately 70 to 90% of the iron bound to transferrin is required for the synthesis of hemoglobin. Finally, the formation and development of erythrocytes (red blood cells) is responsible for the predominant iron turnover.The remaining 10 to 30 % is available for building up enzymes and coenzymes or is stored as ferritin. If the storage capacity of ferritin is exceeded, iron is bound to the storage protein hemosiderin. The importance of ferritin lies in the storage, transport and detoxification of iron. When needed, iron can be rapidly released from storage and used for hemoglobin synthesis. Ferritin represents the most appropriate marker for iron status! Low serum ferritin levels are found in iron deficiency. Iron overloads, on the other hand, are detectable with increased serum ferritin concentrations. If total body iron reserves are depleted, the risk of anemia increases due to impaired hemoglobin biosynthesis. Depending on age, sex, and race, hemoglobin concentrations below 12 g/L in women and below 13 g/L in men indicate anemia. Hemosiderin is a condensation product of apoferritin and cellular components, such as lipids and nucleotides, localized primarily in hepatocytes and cells of bone marrow, liver, and spleen. In comparison to ferritin, hemosiderin is a permanent store of iron, in which the trace element is stored for metabolism in a form that is no longer available. Since iron balance is controlled exclusively by absorption, there is no regulated excretion of iron. In men and post-menopausal women, about 1-2 mg (19-36 µmol/L) of iron is lost daily with the shedding of intestinal epithelial and skin cells, with bile and sweat, and with urine. Greater iron losses occur with bleeding due to the associated loss of hemoglobin. Approximately 25-60 ml of blood is excreted with menstruation, resulting in the loss of 12.5-30 mg (225-540 µmol) of iron per month. A woman’s iron requirement is also increased during pregnancy due to the supply of iron to the fetus. About 300 mg of the trace element is supplied to the fetus through the placenta. In addition, blood losses occur as a result of childbirth and breastfeeding – 0.5 mg – but these are compensated for by the absence of menstruation for a few months after pregnancy. In addition, there are other risk groups for iron deficiency. Due to the fact that there are no regulated excretion mechanisms for iron, excessive dietary iron intake cannot be compensated by increased excretion. As a result of studies, elevated ferritin levels – > 200 µg/ml – are an independent risk factor for atherosclerosis (hardening of the arteries) and can double the risk of myocardial infarction (heart attack). Finally, iron status is optimal when there is sufficient iron available for the body to perform its functions, but iron stores are not full.
