Iron Deficiency: Causes, Consequences And Treatment

In nature, there is no metal more capricious than iron, and the story is sadder than its latent deficiency. Any damage to the gastric mucosa, gastritis, ulcers, erosion, hypoacidity (secretion of hydrochloric acid), and a new anemia girlfriend happily runs to get ready for the first date.

Why is so much time and attention devoted to the diagnosis of iron deficiency, and its replacement is always the first line of treatment? Let's figure it out.

The biological role of iron

1. It is part of hemoglobin (62% of the total amount of iron in the body). This is a complex compound consisting of two parts: the actual protein and heme (an iron complex and four pyrrole rings of porphyrin). The uniqueness, which consists in the ability to capture and give molecular oxygen to cells, is precisely iron that gives its structure.

   In addition, hemoglobin forms a compound with carbon dioxide (CO2), transporting it from the cells back to the alveoli of the lung tissue, and with carbon monoxide - this is already a pathological complex.

   In muscle tissue, a similar protein - myoglobin (8% of all iron stores in the body) - creates reserve oxygen reserves, filling its temporary shortage during active contraction of skeletal and cardiac muscles.

2. The cytochrome molecule also contains iron atoms - in particular, Cyp P50 (cytochrome P450), which provides the first phase of detoxification in the liver - somewhat "paradoxical": toxins, estrogens, neurotransmitters, drugs and other xenobiotics entering the body as a result of a number of biochemical transformations become even more dangerous and active due to the increase in the polarity of their molecules.

   In patients with iron deficiency anemia, in general, the elimination of toxic products from the body is impaired: the second and third phases are simply impossible in the absence of the first.

3. The enzymes catalase and peroxidase, one of the main defenders of mitochondria from relentlessly formed free radicals, also contain iron.

   Their function is to break down hydrogen peroxide - an invariable "by-product" of electron transport along the respiratory chain - in essence, the very process that provides energy (in the form of ATP, known to everyone since school biology lessons).

4. Ribonucleotide reductase, helicases, nucleases, glycosylases - enzymes of DNA synthesis and repair are used as an essential iron cofactor.

   Research: The elemental role of iron in DNA synthesis and repair

5. Lactoferrin is a protein with antimicrobial properties. Found in tears, milk, saliva and other body fluids of the human body.

   It competes with pathogenic bacteria for iron, absorbing the latter. Recent studies also show its bactericidal role - the ability to dissolve the cell wall (or rather lipopolysaccharide) of gram-negative microorganisms.

   In addition, iron regulates the specialization of such cells of the immune system as neutrophils and T-lymphocytes, thus being one of the important elements in the links of humoral and cellular immunity.

   It is impossible not to mention such an acute phase protein (its secretion increases during inflammatory processes in the body), like transferrin - however, we will talk about it in more detail a little later, in the diagnostics section.

6. Violation of iron metabolism associated with cell damage and oxidative stress is a common phenomenon in many neurodegenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases.

   Iron plays a crucial role in maintaining normal physiological functions in the nervous tissue of the brain through its participation in such vital processes as:

   • Mitochondrial (it is also intracellular) respiration.

   • Synthesis of myelin - an insulating sheath of neuron processes, due to which the speed of impulse conduction increases many times over.

   • Synthesis and further metabolic transformations of neurotransmitters.

   Study: Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics

   In the case of iron deficiency in the fetus, there is a negative effect on the processes of myelination of nerve fibers, psychomotor and cognitive functions, and the formation of synapses between neurons.

   Research: [Iron and Neurodevelopment]

7. Maintaining the energy needs of the whole organism.

   Depletion of intracellular iron stores leads to cell death by apoptosis - programmed death, comparable, in some way, to suicide.

   Interestingly, this microelement plays one of the key roles in the pathogenesis of HIV infection, as well as the course of hepatitis C - both diseases are characterized by a less favorable prognosis with an increase in serum iron content.

8. Iron is necessary for the synthesis of dopamine - a hormone that is responsible for motivation and achievement of goals, for the “bouquet period” of relationships and castles in the air that are built in thoughts.

Heme and non-heme iron

Iron from foods is absorbed by the intestinal mucosa from two separate pools: heme and non-heme.

Heme iron, obtained from hemoglobin and myoglobin of animal products, is well absorbed (by 25-30% compared to 2-8% of non-heme iron) and is much less susceptible to the overwhelming effect of various factors - that is why people on a traditional diet who consume meats are less at risk of developing iron deficiency than vegetarians.

Plant foods - vegetables and cereals - contain substances that inhibit the absorption of this mineral (for example, phosphates). There are also many studies on the adverse effects of dietary fiber on its absorption. The fact is that fiber is practically not digested by digestive enzymes - iron is fixed on it and is excreted in transit along with feces.

Sources of heme iron:

1. Pork liver (20 mg per 100 g of product)

2. Chicken liver (17 mg/100 g)

3. Egg yolk (6 mg/100 g)

4. Beef liver (6.9 mg/100 g)

5. Oysters (6 mg/100 g)

Sources of non-heme iron:

1. Lentils (12 mg/100 g)

2. Wheat bran (11 mg/100 g)

3. Soybeans (9.5 mg/100 g)

4. Peas (7 mg/100 g)

5. Mash (6 mg/100 g)

6. Peanut (4.5mg/100g)

iron metabolism

The human body is NOT capable of synthesizing iron. Initially, the child receives it from the mother - through the placenta. That is why in premature babies, with premature ligation of the umbilical cord, as well as with multiple pregnancies, iron deficiency can and will be observed with a high probability.

Then, after birth, it comes first from lactoferrin (a protein that plays an important role in maintaining humoral immunity) in milk, then from heme iron and what is found in plant foods.

In adults, the level of this trace element is maintained in the standard range: 4-5 g.

Every day, in the absence of any pathological processes, a person loses up to 2.5 mg of the total iron reserve: with sweating, feces, exfoliating epithelium of the skin.

At the same time, in the duodenum, approximately 1-2 mg of iron (transferred from the trivalent form, in which it is found in food products, to the divalent form under the action of the oxidoreductase enzyme; vitamin C also plays a significant role in this process is absorbed - thus, the losses are compensated.

Ascorbic, citric, succinic acids (keep it in its divalent form), cysteine, sorbitol and nicotinamide enhance iron absorption, while phosphates, carbonates, oxalates, tannins (found in tea), vegetable fibers, phenolic compounds in coffee and cocoa, phytates (in cereals, seeds, nuts) and dairy products (as part of calcium) suppress.

Absorption is mainly influenced by the following three processes:

1. The reserve supply of iron in the body - when it is depleted, absorption increases.

2. Erythropoiesis - regardless of the state of the iron depot, its absorption will increase with active hematopoiesis.

3. A recent intake of this mineral is when iron is taken from food, its absorption decreases within a few days.

From the intestine, iron in combination with the transferrin carrier protein is distributed: one part will go to the red bone marrow - to the site of synthesis of new blood cells, and the other - to be stored in tissues (mainly the liver, spleen, muscles) in combination with ferritin and hemosederin.

Transferrin, in addition to its transport function, performs a number of other, no less significant ones: by binding iron, it protects its various oxidizing agents (peroxides, free radicals) and deprives microorganisms that compete for this trace element with our body, the ability to use it in the course of their life.

When the life of red blood cells comes to an end (they circulate, on average, for 3-4 months), they will go to the places of the so-called cemeteries - to the spleen and liver. Here, the destruction of hemoglobin will occur, and the released iron will again form a bond with transferrin, going again to the places of hematopoiesis.

There is another equally important regulator of the metabolism of this mineral - hepcidin. This hormone is produced by the liver, and its main task is to suppress the protein responsible for the export of iron (ferroprotein) from the cells of the intestine, liver and immune system (macrophages) into the plasma. Thus, under physiological conditions, with an increase in the level of iron in the blood, the synthesis of hepcidin increases, which leads to the accumulation of this trace element inside the cells.

Very interesting experiments were carried out: for example, scientists found that in laboratory mice with increased hepcidin excretion, all offspring almost immediately after birth died from severe iron deficiency anemia - this prompted them to think about the negative role of this hormone in the mechanisms of iron transport from mother to fetus through the placenta, as well as its suppression of the absorption of this mineral from the intestines.

Hepcidin and the infectious process

Infectious agents, including elements of the bacterial cell wall (lipopolysaccharides), act on macrophages (cells of the immune system) by triggering the production of a signaling molecule - interleukin-6. The latter, in turn, stimulates the synthesis of hepcidin.

This will lead to inhibition of erythropoiesis due to depletion of iron stores, as well as suppression of its absorption in the duodenum. Thus, this hormone is a key structure in the mechanism of development of ANEMIA OF CHRONIC DISEASES - it is second only to iron deficiency in prevalence in the world.

Interestingly, the experiment was originally carried out on mice: by turning off the aforementioned gene, scientists observed a significant decrease in the number of circulating red blood cells, as well as their size (normally, the diameter of red blood cells is seven nanometers).

Although this study did not lead to an accurate determination of the methods of treatment for such patients, it nevertheless partly explained the lack of positive changes in them when taking tableted iron preparations - it is for them that intravenous administration is recommended.

Iron deficiency manifests itself:

1. The development of hypochromic anemia.

2. Sideropenic syndrome characterized by:

   • dry skin;

   • hair loss;

   • burning tongue;

   • perversion of taste;

   • change in smell: there is an addiction to the smells of acetone, exhaust gases, varnish;

   • stomatitis;

   • dyspeptic syndrome.

3. A decrease in muscle performance (due to a decrease in the content of myoglobin) - including cardiac.

4. Circulatory disorders.

5. neurotic reactions.

6. Fragility of the nail plates, transverse striation of the thumbs.

7. Plummer-Vinson syndrome (esophageal membrane).

8. Atrophy of the taste buds of the tongue.

9. Flies before the eyes.

10. Rapid heartbeat.

11. Wounds ("jamming") in the corners of the mouth.

12. Restless legs syndrome.

13. Fatigue, pale skin and other symptoms of hypoxia.

Rapid Hypoxia Test

Hypoxia is a state of oxygen starvation of cells. As you know, it is hemoglobin that transports this gas from the alveoli of the lungs to the tissues. Its amount decreases with insufficient protein intake, iron deficiencies, vitamins B9 and B12.

In addition to laboratory diagnostics, we suggest that you go through a simple but quite informative test at home: press down on the nail plate for a few seconds - it should turn white. Then release and observe: if after 2-3 seconds the normal pink color returns, then you have no problems with the blood supply to the tissues located on the periphery (relative to the heart). If the nail continues to be pale or blue, this is a clear sign of hypoxia.

Causes of iron deficiency

The lack of this mineral occurs when its consumption is exceeded relative to intake and absorption - this can be observed when:

1. Pregnancy (the need increases due to the development of the fetus and placenta, as well as blood loss during childbirth - they can reach 1700 mg) and breastfeeding.

2. period of rapid growth.

3. Uterine bleeding.

   Recall that abnormal uterine bleeding is any deviation from normal menstruation.

   The duration of the cycle should be 24-38 days, menstruation - 4.5-8 days.

   The volume of the allocated blood = 5-80 ml/cycle

   [Order No. 353 of the Ministry of Health of 13.04.2016]

4. Violation of absorption and parietal digestion in the small intestine - malabsorption syndrome (with tumors, Crohn's disease, exocrine pancreatic insufficiency, celiac disease).

   As well as gastritis, peptic ulcer of the stomach and duodenum, the presence of polyps in the gastrointestinal tract - all this negatively affects the absorption of iron.

5. Bleeding from the digestive tract is the most common cause of iron deficiency in men.

6. Unbalanced diet, vegetarian diet.

7. Hypochlorhydria - decreased secretion of hydrochloric acid. Hemoglobin in its composition has a protein part - globin, which is why it is so important to adequately supply amino acids and proteins with food, as well as well-established work on their breakdown and absorption.

Stages of iron deficiency

1. Prelatent - a decrease in the level of ferritin in the serum and the content of iron in the bone marrow. Iron absorption is increased.

2. Latent deficiency - in addition to the above, there is a decrease in serum iron and an increase in the concentration of transferrin.

3. Actually iron deficiency anemia - in addition, the levels of red blood cells, hemoglobin, and hematocrit decrease.

Criteria for iron deficiency

1. Laboratory diagnostics:

   • Serum iron < 13 µmol/l for men and < 11 µmol/l for women.

   However, you should not use only this indicator when making a diagnosis: its level fluctuates significantly during the day, and also largely depends on gender and age.

   Infections, injuries and especially chronic inflammation (rheumatoid arthritis!), as well as various neoplasms, cause its decrease in serum with normal iron stores in tissues.

   A decrease in plasma iron concentration is a late sign of iron deficiency.

   • TIBC (total iron-binding capacity of serum) increased to more than 70 µmol/l.

   This is the total amount of iron that can bind to plasma transferrin.

   • The transferrin saturation ratio is less than 20%.

   Normally, it is 33%.

   • Serum ferritin - less than 20 mcg / l.

   A value below 12 μg / l indicates a complete absence of iron stores. It should also be taken into account that ferritin is an acute-phase protein of inflammation and can be significantly increased in various types of inflammation (or be within the normal range against the background of general iron deficiency).

   • Decrease in hemoglobin, color index and the number of red blood cells in the general blood test.

   • Decrease (or lower limit of reference) in the mean volume of erythrocytes (MCV).

   At present, a more modern test has become available in many laboratories - the determination of soluble transferrin receptors in blood plasma - this indicator will increase by 2-3 times compared to the norm with iron deficiency in the body.

   However, its concentration increases only when the reserves of iron are exhausted - with anemia on the background of chronic diseases, its significant fluctuations are not observed.

   It is also diagnostically important to measure the concentration of hepcidin.

2. Clinical studies: fibrogastroscopy, colonoscopy, ultrasound examination of the abdominal cavity and small pelvis, etc.

Preparations for the treatment of iron

1. Iron salts:

   Ferrous sulfate (Aktiferrin, Ferroplex, Ferro-Folgamma, etc.):

   • The highest percentage of absorption.

   • Least toxicity compared to other iron compounds.

   Side effects:

   • Causes irritation of the gastrointestinal mucosa.

   • Mediates desquamation and necrosis of intestinal epithelial cells.

   • Hepatotoxicity - manifested by nausea, vomiting, constipation.

   • May be teratogenic and therefore not recommended during pregnancy.

   • Banned in several European countries.

   Ferrous fumarate:

   • Less soluble in water.

   • It dissolves well in gastric juice.

   • They do not have a glandular taste.

   (Heferol, Ferretab)

   Iron gluconates (Totema, Ferronal)

   General recommendations:

   Iron salts must be taken on an empty stomach to avoid binding to food components (pectin, proteins and calcium). They can lead to inflammation of the mucosa of the gastrointestinal tract, as well as cause constipation (iron binds hydrogen sulfide - a peristalsis stimulant).

   In addition, there may be pain in the epigastrium and darkening of the enamel of the teeth.

2. Preparations based on the hydroxide of the polymaltose complex - in structure resemble the ferritin molecule. This is a newer generation of drugs.

   • Highly effective and safe.

   • Enamel and gums do not darken.

   • Good tolerance.

   • There are no risks of intoxication and overdose.

   • Antioxidant properties.

   (Ferrum lek, maltofer)

3. Evidence-based medicine prescribes RBC TRANSFUSION only before surgical interventions, as well as at a hemoglobin level of less than 50 g / l.

4. Parenteral administration of drugs is indicated for:

   • The need for rapid saturation of the body with iron.

   • Damage to the mucosa of the gastrointestinal tract.

   • With complete intolerance to taking iron medications per os.

Iron chelate quickly gained its popularity - sometimes it comes to the point of absurdity: some patients evaluate its appointment as a progressive doctor.

Indeed, it managed to prove itself (at least in experiments on laboratory animals) as a relatively safe drug - its maximum administration to rats at a dosage of 500 mg per 1 kg of body weight did not cause toxic effects.

Other studies note that with the introduction of ferrous sulfate and chelate (together and then with different meals), it was noted that the absorption of the latter is almost twice as high.

High solubility in water (even at pH=6), high degree of absorption and insignificant interaction with food components - all this favorably distinguishes the chelated form of iron bisglycinate from its pharmaceutical predecessors.

IT IS NOT RECOMMENDED TO START IRON THERAPY UNTIL ELIMINATION OF BACTERIAL AND FUNGAL INFECTIONS: after all, there is no favorite mineral among microorganisms.

• Vitamin B5 - increases the resistance of red blood cells to hemolysis.

• Vitamin B12 - stimulates the synthesis of globin (the protein part of hemoglobin). Essential for red blood cell formation, energy production, and nutrient metabolism.

• Vitamin B6 - takes part in the first reaction of heme synthesis.

• Folic acid is one of the main factors in preventing intrauterine malformations in the fetus, it is required for the synthesis of DNA and RNA, methylation reactions and, in particular, the conversion of homocysteine, which negatively affects the capillary endothelium, into the amino acid methionine.

• Vitamin C.

Since the modern human diet is dominated by non-heme iron, which is much more susceptible to the action of various inhibitory factors, it is very important to monitor the normal level of ascorbic acid: it facilitates the absorption of this trace element by forming a chelate with ferric iron in the acidic environment of the stomach - this complex remains soluble in alkaline pH of the duodenum.

Vitamin C also inhibits the action of substances such as tea, calcium and phosphate, which greatly interfere with the absorption of this micronutrient.

At the same time, ascorbic acid, due to its pronounced antioxidant properties, largely prevents liver damage due to excessive iron intake - in fact, it plays the role of a “double agent”.

Unfortunately, it does not accumulate in the body - its excess is quickly excreted in urine and feces, and is also destroyed by heating and freezing, which greatly complicates the process of manufacturing its preparations.

Deficiency symptoms are: deterioration of wound healing, gingivitis, hemorrhage, bruising under the eyes, fatigue.

Sources of ascorbic acid: peppers, broccoli, tomatoes, kiwi, citrus fruits and mangoes.

• Vitamin D and iron

This fat-soluble vitamin is more and more often referred to as a hormone in reputable medical journals - its role is so great. And the pathogenesis of iron deficiency is no exception.

The study included 10,410 children and adolescents in the United States, all of whom had low levels of 25-hydroxycalciferol associated with an increased risk of anemia.

It should be noted that iron is an integral element in the structure of cytochromes, some of which (CYP27A1, CYP24A1) play an important role in vitamin D hydroxylation.

Scientists are conducting further research to more accurately determine the relationship between these two vital substances.

• Vitamin A and iron

Vitamin A supplementation has been associated with a reduced risk of anemia by increasing hemoglobin and ferritin levels.

It is believed that it has a modulating effect on the late stages of erythropoiesis (the process of formation of red blood cells) and the synthesis of erythropoietin. It is also thought to influence the formation and catabolism of proteins responsible for the accumulation and mobilization of iron in the liver.

Most likely, vitamin A is also able to form a complex with iron, keeping it soluble in the intestinal lumen and preventing the action of factors that inhibit its absorption.

• iron and quercetin

Quercetin is a widely distributed bioflavonoid. Its interaction with iron is a complex and not yet fully understood mechanism.

A study was conducted in which iron deficiency anemia was modeled in rats - it was induced by feeding them for 20 days a diet with a low iron content.

Then the animals were injected with preparations of ferrous sulfate, quercetin, and also their combination for 30 days. There was an increase in the level of this mineral in the serum, as well as its reserves in the parenchyma of the spleen - this may be due to the formation of a chelate and subsequent improvement in transport through membranes and absorption.

The positive charges of metal ions are, as it were, hidden (shielded) during chelation, thereby preventing their interaction with a negatively charged mucin (mucus): after all, we all remember that differently charged substances are attracted. This mechanism allows for increased lipophilicity (solubility in fats, oils, and other non-polar compounds), facilitating easier absorption.

In addition, quercetin has anti-inflammatory, antiproliferative, antimicrobial, and antiviral properties.

Drug Interactions

1. Reduce iron absorption:

   • Antacids (reduce the acidity of gastric juice): "Almagel", "Malox", etc.

   • Proton pump inhibitors (reduce the secretion of hydrochloric acid): omeprazole, lansoprazole.

   • H2-blockers of histamine receptors (similar function): tagamet, zantak.

   • Colestyramine resin.

2. Allopurinol increases iron stores in the liver.

3. Iron reduces absorption (therefore, 2 hours should elapse between doses):

   • Levodopa (a drug used to treat Parkinson's disease).

   • Levothyroxine (synthetic thyroid hormone).

   • Methyldopa (antihypertensive drug).

   • Quinolones (antibiotic).

   • Tetracyclines (antibiotic).

   • Bisphosphonates (used to treat osteoporosis).

• 0-6 months: 0.27 mg.

• 7-12 months: 11 mg.

• 1-3 years: 7 mg.

• 4-8 years: 10 mg.

• 9-13 years old: 8 mg.

• 14-18 year old boys: 11 mg.

• 14-18 year old girls: 15 mg.

• 19-50 years old men: 8 mg.

• 19-50 year old women: 18 mg.

• 51+ years: 8 mg.

• Pregnancy: 27 mg.

• Breastfeeding up to 18 years: 10 mg.

• Adult male vegetarians: 14 mg.

• Vegetarian adult women: 33 mg.

• Vegetarian teenage girls: 26 mg.

DAILY RATE: 18 mg

Iron deficiency is one of the most common problems around the world - from industrial, highly developed countries to poor and unfavorable in sanitary and hygienic terms. However, this condition is quite easily and quickly corrected - with the right approach, attitude and selection of drugs.