Such an important semi-vitamin. What is choline and why is it necessary for humans?

Vitamin B4 (choline, trimethylethanolamine) is a thermostable amino alcohol, the so-called lipotropic factor, and is part of the B complex of vitamins.
For the first time, the compound was obtained from bile, which influenced the name of the substance: translated from Greek choly - “bile”. As a donor of specific methyl groups, it participates in the processes of remethylation associated with the formation of methionine, adrenaline, methylnicotinamide and other compounds, and is part of phospholipids.

Choline belongs to the category of water-soluble vitamin-like substances that affect protein and fat metabolism. Lack of the compound in the body leads to excess weight gain. Therefore, vitamin B4 is an indispensable component of complex therapy for weight loss.

The structural formula of choline is C5H15NO2.

The peculiarity of the vitamin-like substance B4 is the ability to be produced in the body. Thanks to this, in most cases, the internal organs and tissues of a person do not “experience” a lack of useful compounds.

Physicochemical characteristics

Vitamin B4 is an amino-ethyl alcohol, the structure of which includes three methyl groups of nitrogen atoms. The functional compound is constantly in an ionized state, which makes choline a strong base.

Content:

• Physicochemical characteristics
• History of discovery
• Metabolism of vitamin B4
• Biological role
• Signs and consequences of choline deficiency and excess
• Daily requirement
• Choline during pregnancy
• Medicinal use
• Sources of vitamin B4
• Choline in medicine
• Instructions for use of cholinomimetic
• Interaction with other substances

Trimethylethanolamine is a colorless substance with a distinct odor of trimethylamine. The presence of highly hygroscopic crystals ensures their easy transformation into a viscous liquid. Choline is highly soluble in anhydrous ethanol and water, less soluble in acetone, chloroform, amyl alcohol, and insoluble in carbon tetrachloride, benzene, diethyl ether, carbon disulfide, and aromatic hydrocarbons.

Vitamin B4 is relatively stable, the threshold of thermal stability of the compound is 180 degrees, an increase in temperature leads to its destruction. Treatment of the substance with hot alkali promotes the death of the choline molecule and the formation of trimethylamine. Trimethylethanolamine reacts with organic and inorganic acids, forming salts, for example, hydrochloric acid.

Acting as part of phospholipids, vitamin B4 is part of almost all cells of the body. Moreover, a larger amount of it is found in human plasma. The content of the compound in the blood depends on the season and varies from 6.1 to 13.1 micromoles per liter. The lowest amount of choline in the human body is observed in July, and the highest in February-March.

In women, trimethylethanolamine is excreted in menstrual blood. Depending on the phase of the cycle, the highest amount of choline is observed on the 14th day, the lowest on the 26th day. In addition, vitamin B4 is part of the cerebrospinal fluid.

The level of free choline in the human body is 77 - 216 nanograms per milliliter, total - 104 - 423, respectively. A high concentration of the compound is found in seminal fluid.

Vitamin B4, its esters and salts are used as a food additive registered under the E1001 sign. Choline is used in the food production process as a glazing agent and anti-flaming agent, preventing the formation of foam. In addition, the substance is used as an emulsifier during the creation of fat emulsions (sauces, chocolate, ice cream, margarine, mayonnaise). It is also used in baking bread, making cheese, frozen products, sausages, and baby food.

According to the conclusion of scientists, B4 is considered a harmless supplement that has a beneficial effect on the functioning of the nervous system and is called an anti-sclerotic vitamin.

What is choline (vitamin B4) and what is it for?

Translated from Greek, this term means “bile”. Choline is an organic compound that is essential for normal human life and activity.

The substance has the texture of colorless crystals, which dissolve well in water and are destroyed at high temperatures.

According to the modern classification, choline is not directly classified as a vitamin. Unlike them, it is capable of being reproduced by the body independently, albeit in small quantities.

However, “own” choline is not enough for a person. People receive an additional dose of this component with food, and in modern conditions, also as part of specialized medications. One of them will be written below.

Considering the characteristics and properties of choline, it began to be called a semi-vitamin or a vitamin-like element. However, its original name “vitamin B4” continues to be used in scientific literature and reference books.

History of discovery

The first mention of choline dates back to the 19th century (1862), when scientists discovered a useful compound while studying animal tissue. However, people realized the importance of the substance for the human body half a century later.

Experiments on animals carried out in 1930 were a decisive factor in the research of the vitamin-like substance. Thus, during the test, the pancreas was removed from experimental animals, after which insulin was administered artificially. For a long time, research did not bring the desired result. Despite the fact that the animals survived after surgery, they started the process of fatty degeneration of the liver, which eventually stopped working. As a result, everything ended in the death of the animals.

In the process of numerous studies, scientists identified the reason for this outcome; it turned out to be a lack of choline in the animals’ bodies. Due to a deficiency of the compound, the liver did not process fat, and as it accumulated, it led to the replacement of normal liver tissue with fatty tissue and the occurrence of cirrhosis.

In the human body, processes occur similarly.

Choline bitartrate as a source of choline

Currently, quite a lot of B vitamins are produced. We always remind you that vitamins of this group, including vitamin B4, are better absorbed in the human body in a water-soluble form. This is precisely the property that the drug RINOVIT has. Choline bitartrate is present in it in an amount of 30% of the daily intake. This value is optimal, since in ordinary life, firstly, we obtain a significant part of choline from food, and, secondly, our liver is capable of independently producing a certain amount of vitamin b4. The element plays a vital role in processes such as memory, thinking, and learning.

When we ask ourselves: what is included in a particular vitamin complex, we open a reference book of drugs and study the instructions. You won't find vitamin b4 in almost any multivitamin. What does this mean? That the compositions of vitamin complexes are balanced according to the standards for the use of basic elements from vitamin groups. However, doctors and representatives of science rightly declare the importance of vitamin b4 - choline alfoscerate and choline bitartrate. This leads to the conclusion that you need to buy products containing choline separately. To find out the price and buy choline (vitamin b4) in a unique balanced composition, visit the RINOVIT page.

Metabolism of vitamin B4

Choline is a nitrogen compound that is similar in chemical structure to ammonia. The mammalian body forms a substance from the amino acid methionine. In addition, B4 comes from food.

During processing, choline is partially destroyed by intestinal microflora, forming trimethylamine. If a person’s diet contains a low amount of a vitamin-like substance, it is absorbed by active transport, if a large amount is absorbed by diffusion.

As part of lipoproteins, partially free choline, phosphocholine from the intestine (with the blood) is distributed to the tissues. Subsequently, the substance is “included” in the course of metabolic processes.

Phosphocholine plays an important role in the synthesis of phosphatidylcholine (lecithin).

The ingested choline is excreted from the body by sweat, bile, and urine. Up to 1.5% of the substance is excreted daily with urine. With sweat – 0.01% of the total amount of B4 taken.

If the excretory function of the kidneys is impaired, the breakdown products of the compound slowly leave the body, which leads to increased azotemia. Contrary to popular belief, choline is not excreted in feces (with the exception of diarrhea).

Protect eyesight

The carotenoid lutein, which scientists consider one of the best eye protectors against age-related macular degeneration of the retina and cataracts, is found in large quantities in egg yolk. Scientists believe that lutein from eggs is absorbed better
than from plant sources - since it is fat-soluble, and the yolk contains enough animal fat.
Experts call scrambled eggs with spinach
: these two products contain the largest amount of lutein. Of course, this dish will be healthy if cooked with a little fat and not eaten with fried bacon.

Biological role

Let's look at why choline is needed in the human body.

1. Nervous system. The vitamin plays a key role in creating the protective sheath of nerves and phospholipids that make up cell membranes. The connection protects them, as well as the myelin layer, from partial damage and complete destruction, which can lead to “exposure” of neurons and disruption of the nervous system as a whole. Trimethylethanolamine is a metabolic precursor of an important neurotransmitter, the so-called acetylcholine, which is responsible for the transmission of impulses. The systematic intake of choline into the human body prevents the occurrence of disorders of the nervous system.
2. Fat metabolism. The compound acts as a strong hepatoprotector, which helps accelerate the structural restoration of damaged liver tissue as a result of the toxic effects of alcoholic beverages, drugs, medications, and viruses. Choline prevents the formation of gallstones and improves the functioning of the digestive gland. Together with lecithin, it takes part in the transport and metabolism of fats in the liver, preventing its fatty degeneration (hepatosis). In addition, vitamin B4 promotes the absorption of vitamins E, K, A, D, normalizes fat metabolism, and accelerates the enzymatic breakdown of triglycerides.
3. The cardiovascular system. Trimethylethanolamine cleanses the walls of blood vessels from cholesterol plaques, reduces the concentration of fatty acids in the blood and reduces the level of bad cholesterol. Vitamin B4 is involved in the formation of methionine, which “fights” excess homocysteine, which increases the risk of developing atherosclerosis, Alzheimer’s disease, and memory loss. In addition, choline normalizes heart rate and strengthens the heart muscle.
4. Carbohydrate metabolism. The benefit of choline in the functioning of the pancreas is that the compound strengthens the membranes of beta cells, normalizes blood glucose levels by regulating insulin levels. The use of vitamin B4 in type I diabetes mellitus reduces the body's need for insulin. In type II disease, it compensates for the lack of polyunsaturated fatty acids in the body, reducing the excess level of pancreatic hormone, which in most cases is the main factor in the development of the disease.
5. Reproduction. The most important functions of choline are increasing sperm motility and participating in the synthesis of prostaglandins in the prostate gland. In old age, vitamin B4 inhibits prostate dysfunction.
6. Mental capacity. According to a test conducted at the end of the 20th century (a group of volunteers included 10 grams of B4 in their diet daily for 10 days), English psychophysicists came to the conclusion that the systematic use of choline improves the short-term memory of subjects.

Trimethylethanolamine is one of the most important building blocks for the brain. It is especially important to use the compound for children under 5 years of age and women during pregnancy, since it has been proven that the level of human intelligence is established in the womb and in the first years of a baby’s life, which means that a deficiency of choline during this period can lead to mental disorders in the development of the baby.

It turns out that vitamin B4 is a substance that helps preserve memory into old age, reducing the risk of sclerosis.

Until now, the phenomenal effect of choline on the course of processes in the brain has not been studied in detail. It is assumed that the compound slows down the aging process at the cellular level and helps build a kind of reserve - a strong network of neurons that process any information.

Thus, choline has a critical effect on the body. In addition to influencing the nervous, cardiovascular systems, reproductive function, mental abilities, carbohydrate and fat metabolism, it improves the physiological state of the body as a whole. Namely: it normalizes intestinal activity, regulates metabolism, has a positive effect on growth, triggers liver cell regeneration processes, promotes hematopoiesis, improves mood, and eliminates mental instability.

In the 1990s, scientists found that during the experience of severe emotional shock (stress), choline consumption doubles.

Remember, if there is a lack of vitamin-like substance B4 in the diet, a healthy body will still receive the vital compound by processing other foods. However, it is better to prevent this phenomenon from occurring and ensure a regular supply of the substance with food. Otherwise, the load on the body to transform the compound increases significantly.

Interaction with other elements

Vitamin B4 is better accepted by the body in combination with such active ingredients as:

• lecithin,
• folic acid,
• B vitamins.

In turn, choline promotes better absorption of vitamins A, D, E, K.

The amount of the substance in the body may decrease:

• with excessive alcohol consumption,

• as a result of taking antibacterial drugs,
• when using steroid hormones.

Signs and consequences of choline deficiency and excess

Characteristic symptoms of vitamin B4 deficiency in the body:

• noise in ears;
• depression, apathy;
• insomnia;
• irritability;
• frequent nervous breakdowns;
• headache;
• memory lapses;
• constipation;
• cardiac arrhythmia;
• state of fear;
• deterioration in concentration;
• constant fatigue;
• impaired milk formation during breastfeeding;
• sudden gain, retention of excess weight;
• decreased mental abilities;
• weakening of the immune system;
• impaired coordination of movements;
• weakness;
• increased cholesterol levels.

The appearance of at least a few signs may indicate the paucity of the daily diet for a beneficial compound. A negative reaction from the body can be eliminated by including foods rich in choline in the menu (see “Sources of the vitamin”) or through medication, by artificially adding the substance. The most common preparations containing vitamin B4 are Vitrum Beauty, Choline chloride, Duovit Memo. They are produced in ampoules or tablets.

Contraindications to the use of the drug: hypersensitivity to the components.

Vitamin B4 deficiency is caused by: lack of protein in the diet, physical overload, drinking strong drinks, antibiotics.

A long-term lack of trimethylethanolamine in the body leads to the following consequences:

• hypertension;
• atherosclerosis;
• circulatory disorders;
• slower growth in adolescents;
• a decrease in carotene synthesis, as a result of a slowdown in metabolism;
• obesity, liver dysfunction (cirrhosis, cancer);
• gastritis;
• disruption of the lactation process;
• oppression of the genital organs.

With prolonged “choline” starvation, the development of Alzheimer's disease is observed, accompanied by complete loss of memory. In addition, B4 deficiency in the body threatens mental disorders.

Thus, the above symptoms and consequences are a reason to consult a doctor about the use of choline. Timely therapy and treatment of the patient in most cases prevents the development of dangerous conditions and contributes to the restoration of human health.

An excess of the compound can harm the body, but does not lead to tragic irreversible consequences. Often, an overdose of vitamin B4 is accompanied by the following reactions: loss of appetite, fishy breath, increased blood pressure, diarrhea, excessive salivation and sweating, nausea. Typically, limiting your intake of foods high in choline will help quickly resolve these symptoms.

Possible side effects

Natural preparations based on choline have no contraindications and are usually well accepted by the body.

Negative reactions can only be observed in case of individual intolerance to the components or in case of significant overdose. The presence of these factors increases the likelihood of side effects, including:

• drop in blood pressure,
• excessive sweating,
• nausea,
• diarrhea.

To avoid such violations, preparations with vitamin B4 should be administered following the dosage indicated in the instructions.

Daily requirement

The daily intake of trimethylethanolamine is not regulated. However, the minimum requirement for a healthy person for the compound is 300 milligrams per day. Choline consumption directly depends on the amount of folic acid, protein, cobalamin (vitamin B12) in the body.

The daily dose of the vitamin-like substance B4 entering the body varies on average from 500 to 1000 milligrams per day.

The upper limit for consumption of the compound for children under 14 years of age is 2000 milligrams, for adults – 3500 milligrams.

In case of a stressful situation or high mental load, it is recommended to double the choline intake.

Precautions and contraindications

Choline preparations for therapeutic purposes are prescribed only by the attending physician. The maximum permissible dosage for adult patients is 3500 mg per day. This amount will not harm the body. It is extremely difficult to obtain such a volume of the active substance with food. The use of pharmaceuticals must be under medical supervision.

Risk of high mortality

. A study of 80,978 women and 39,434 men showed that high doses of choline cause the development of cardiovascular disorders, leading to death [].

Risk of developing prostate and colorectal cancer.

Increasing recommended dosages over a long period of time causes the development of malignant processes in the prostate in men and in the colon in women [34-35].

Choline during pregnancy

Remember, vitamin B4 is the most important nutrient for the normal ontogenesis of the fetus developing in the womb.

Choline is necessary as a substrate for DNA methylation in the child’s brain (due to the increased need for one-carbon residues), the construction of cell membranes (due to the rapid growth of tissues in both organisms), increasing the reserves of the compound in placental tissues, and increasing the production of lipoproteins.

The need for a useful substance is especially acute in the third trimester of pregnancy, when the myelin sheaths of fetal nerve fibers begin to be synthesized from sphingomyelin phospholipids.

Choline normalizes the psycho-emotional “background” of the mother by reducing the level of cortisol (stress hormone) in her body. This has a positive effect on the child’s nervous system (at later stages of life), protecting him from the onset of mental disorders and metabolic disorders. In addition, trimethylethanolamine stimulates the production of the neurotransmitter acetylcholine, which is “responsible” for the formation of synapses in the embryonic brain.

During pregnancy, the daily requirement of vitamin B4 is 1000 – 3000 milligrams. Retrospective studies of expectant mothers (case-control method) confirm numerous reviews from gynecologists about an increase (4 times) in the risk of having a child with neural tube pathologies when consuming a minimum portion of choline per day (400 milligrams) during pregnancy.

Interestingly, therapeutic doses of the vitamin can change fetal epigenetic markers that regulate the functioning of the endocrine gland. In this case, the hypothalamic-pituitary-adrenal system is stabilized, and as a result, the level of cortisol in the child’s blood decreases.

Vitamin B4 in combination with folic acid is an ideal prevention of neurological defects in the fetus, including childhood dementia. For this reason, in 1985, the American Academy of Pediatrics insisted on the introduction of an additional portion of vitamin B4 into infant formula (for every 100 calories - 7 milligrams of the substance).

Considering the fact that the brain of a newborn continues to actively develop in the first years of life, it is advisable for a nursing woman to take the nutrient during breastfeeding. At the same time, trimethylethanolamine, which enters the child’s body with milk, increases the concentration of its own choline in its blood. Scientists note that this component improves memory, cognitive and thinking functions in the children's brain.

Daily intake of choline for women, men and children

The norm for choline (vitamin B4) is 550 mg for men, and 425 mg for women over 18 years of age.

*Recommendations are given in milligrams (mg/day). The European Food Safety Authority (EFSA) has issued general recommendations for EU countries. The National Academy of Medicine (NAM) has made recommendations that apply in the United States, Australia, and New Zealand.

Source: en.wikipedia.org []

Medicinal use

Choline, along with improving fat metabolism and the functional state of the central nervous system, stimulates the production of red blood cells and increases the body's resistance to toxic substances. These properties of the vitamin are used in medicine to treat functional disorders.

Clinical uses of choline

Liver diseases

The lack of choline in the daily menu reduces the chemical synthesis of phospholipids (phosphatidylcholine and lipoprotein), as a result of which the outflow of fatty acids into the blood plasma is weakened. Because of this, triglycerides accumulate in the liver, which increases the risk of thrombosis. Vitamin deficiency leads to a decrease or cessation of the transport of fats to the peripheral tissues of the body. Moreover, at this stage, a laboratory examination reveals a normal level of triglycerides in the blood. Taking vitamin B4 in a therapeutic dosage (2000 - 3000 milligrams) helps prevent fatty infiltration of the liver, and in the presence of this pathology, accelerate the regeneration of degenerated tissues. Doctors suggest that trimethylethanolamine breaks down neutral fats and intensive excretion of phospholipids with bile begins in the diseased organ, which helps improve the functional state of the liver. In addition, oral administration of 100 milligrams of the substance per kilogram of body weight or parenteral administration of 1 milliliter of a 20% solution into a vein leads to intense bile secretion. This property of choline is used to reduce the increased production of phosphatase in patients suffering from liver cirrhosis. Daily intake of three grams of the substance for 15–20 days helps normalize organ function.

Heart pathologies

Vitamin B4 helps in the fight against “bad” cholesterol, as it dissolves deposits on the walls of blood vessels. This fact is confirmed by numerous studies, in particular, an experiment conducted by G. I. Koropova with the participation of 92 people. During the first month, patients were given choline chloride in combination with the amino acid methionine. After 30 days, patients showed positive dynamics in fat metabolism: a decrease in cholesterolemia, an increase in the content of phospholipids in the blood, and the release of fatty acids into the plasma (determined by analysis). When using vitamin B4 over the next 3–6 months, the detected changes had more pronounced symptoms. It is important to understand that the duration of choline therapy directly depends on the amount of “bad” cholesterol in the blood. In addition to dissolving atherosclerotic plaques, vitamin B4 increases performance, improves sleep, reduces headaches, prevents angina attacks, and normalizes intestinal evacuation function.

Neurology

Numerous studies confirm that mental health depends on the functional activity of the liver. Therefore, improving the functional state of the “filtering” organ by taking choline leads to normalization of emotional status, restoration of the balance of excitation and inhibition in the central nervous system, and resistance to adverse effects. In addition, lecithin (choline + inositol) is an essential nerve nutrient, as it makes up 30% of the brain and 17% of the peripheral nervous system.

Cognitive disorders

Choline is a substrate for the synthesis of lipids (phosphatidylcholine, sphingomyelin, lysophosphatidylcholine, choline-plasmalogen) and neurotransmitters (acetylcholine, signaling molecules), a donor of methyl groups necessary for the resynthesis of methionine and DNA methylation. Therefore, the substance is of enormous importance for the normal functioning of the brain. Laboratory experiments indicate the effectiveness of taking vitamin B4 in the complex treatment of cognitive disorders: decreased learning ability, concentration, memory and mental performance.

Cosmetology

Since phospholipids are the basis of cell membranes, their deficiency in the body, in 90% of cases, leads to disruption of the integrity of the dermis and deterioration of blood circulation in the tissues. To prevent these changes, including improving hair nutrition, it is important to take 500 milligrams of vitamin B4 daily. In addition, you can make your skin “lipostable” using cosmetics that contain choline (phosphatidylcholine). This phospholipid, when used externally, performs three functions: softening (emollient), restoration (repairant) and transport of nutrients to damaged tissues. The nutrient is also widely used in beauty salons as injections for skin rejuvenation (lipodissolution). Repeated injection of the solution into the subcutaneous fat in problem areas leads to the binding of the substance to lipoproteins, dissolution and removal from the cells. Before choosing “vitamin” cosmetics, it is important to carefully study the ingredient composition. The correct name of the substance in Latin is: 1,2-diacyl-glycero-3-phosphocholine, phosphatidylcholine, PtdCho and lecithin. Indications for the use of cosmetics with phosphatidylcholine: sensitive skin prone to redness, eczema, excessive dryness of the face, dysfunction of the hydrolipid mantle of the dermis, prevention of premature aging. The choline content in food has decreased sharply over the past 20 years, and the number of diseases associated with deficiency of the compound has doubled. To prevent the development of these conditions, it is advisable to take vitamin B4 in a prophylactic dosage of 500–900 milligrams per day, and for the treatment of functional disorders – 1000–6000.

For what diseases is it recommended to take

Indications for the use of choline are:

• nervous system disorders (including Parkinson's and Alzheimer's diseases),
• mental disorders,
• cardiovascular pathologies,
• atherosclerosis,
• anemia,
• arterial hypertension,
• traumatic brain injuries,
• memory impairment,
• fatty liver - steatosis,
• viral hepatitis,
• cholelithiasis,
• bronchial asthma,
• allergic rhinitis,
• overweight,
• alcoholism.

Vitamin B4 and its derivatives are widely used throughout the world as natural nootropics.

Sources of vitamin B4

To produce choline in sufficient quantities, the human body needs the following auxiliary substances: vitamin B12, glycine, methionine, serine, folic acid.

What foods contain these compounds?

Methionine and serine are found in cheese, eggs, fish, poultry and animals. Folic acid is found in cereals, brewer's yeast, vegetables, and fresh herbs, and vitamin B12 is found in the liver, heart, kidneys, milk, and cottage cheese.

Choline is found in many foods.
However, the largest amount of vitamin B4 is found in ingredients of animal origin, and less in ingredients of plant origin. The level of choline in eggs, milk, fish, meat, and dairy products is proportional to the content of phospholipids in them. Table “Which foods contain vitamin B2”

The table shows that the main source of choline is egg powder; a slightly smaller amount of the vitamin is contained in beef and pork liver. The smallest amount of the substance is found in fresh fruits and vegetables (apricot - 2.8 milligrams per 100 grams of product, sweet pepper - 5.5, grapes - 5.6, cucumbers - 6, nectarine - 6.2, tomato - 6.7, currants, mango, melon – 7.6 mg each, kiwi – 7.8, orange – 8.4).

Foods rich in choline lose some of the beneficial compound during heat treatment. When cooking meat and offal, the vitamin “evaporates” by 18%, plant foods - up to 40%, and when baking, the loss is 3%.

Record-breaking foods for choline content

The human liver is capable of independently synthesizing choline in the form of phosphatidylcholine. Natural choline is not enough for the body. To meet your vitamin needs, you should take foods that contain choline.

The leader in choline content are egg yolks of any animal. For example, 1 piece of chicken yolk contains 172 mg of choline (34% of the daily value). There is also quite a lot of choline in liver (and other offal), chicken breast, and fish. Beans are the leading plant products.

Egg Yolk Powder: 2403 mg Raw: 820 mg

Beef kidneys513 mg

Liver Beef: 426 mg Chicken: 326 mg Turkey: 220 mg

Eggs Chicken: 293 mg Goose: 263 mg Quail: 263 mg Duck: 263 mg

Shrimp135 mg

Chicken breast117 mg

Soy116 mg

Fish Pink salmon: 113 mg Salmon: 112 mg Sockeye salmon: 112 mg Coho salmon: 109 mg Herring: 104 mg Mackerel: 101 mg

Beans97 mg

Lentil96 mg

View the entire table of herbal products 290+ ➤

View the entire table of animal products 100+ ➤

Choline in medicine

Despite the fact that in 80% of cases lecithin is used as a source of choline, sometimes there is a need to take other types of nutrients.

Forms of release of vitamin B4

Choline citrate

The structure of the drug is identical to the structure of the molecules of the cell membranes of the brain. Thanks to this, it helps to quickly replenish vitamin reserves, which are intensively consumed during strength training. Choline citrate is primarily used to maintain the body’s energy needs in emergency cases (as an “ambulance”), improve psycho-emotional status, and increase performance and endurance in sports. Considering the fact that the “citrate” form of release improves the absorption of magnesium, it is advisable to use it for athletes who periodically experience muscle spasms. This medication is administered orally. Daily dosage – 250 – 900 milligrams.

Choline chloride

This drug is available in the form of a solution for intravenous administration and a powder for oral administration. It is prescribed to people suffering from atherosclerosis, hepatitis, Botkin's disease, liver cirrhosis (in the early stages), cystinuria, hypothyroidism and chronic alcoholism. Directions for use: 1% solution is administered through a dropper at a rate of 30 drops per minute. Single injection of liquid product – 200 – 300 milliliters. Remember, during intravenous administration, choline chloride can cause the following body reactions: nausea, vomiting, fever, heaviness in the head, bradycardia, decreased systolic pressure. These phenomena arise due to excitation of the parasympathetic nervous system. If these symptoms appear, administration of the drug should be stopped immediately. If it is necessary to take the medicine for a long time, as a rule, the powder is prescribed in the form of a 20% solution, which should be consumed in 5 milliliters 3 to 5 times a day. Course duration is 7 – 10 days.

Choline alphoscerate

A nootropic drug that activates cholinergic receptors in the postganglionic endings of the parasympathetic nerves. Choline alfoscerate, under the influence of brain enzymes, is broken down into free vitamin B4 and glycerophosphate. The first substance helps synthesize acetylcholine and improves the functioning of the central nervous system, and the second is converted into phosphatidylcholine, which increases the plasticity of neuronal membranes. Since the drug contains metabolically protected choline (40.5%), it is used to improve brain function.

Which choline supplement should you choose?

Medical products (medicines, vitamins, medicines) are mentioned for informational purposes. We do not recommend using them without a doctor's prescription. We recommend reading: “Why can’t you take medications without a doctor’s prescription?”

Lecithin. Available in the form of a dietary supplement. Contains 10–20% phosphatidylcholine. Phosphatidylcholine is produced in the form of powder or tablets, in which choline is approximately 13% of the total volume of the drug []. Other vitamin supplements contain choline in the form of chloride, CDP-choline, alpha-GPC and betaine.

Names of drugs and their costs

Instructions for use of cholinomimetic

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Indications: confusion, chronic cerebrovascular insufficiency, memory impairment, dementia (senile, Alzheimer's, post-stroke), emotional instability, senile pseudomelancholia, irritability, ischemic stroke (in the recovery phase), Huntington's chorea, traumatic brain injury (acute period), functional central nervous system disorders, decreased concentration, disorientation, cognitive disorders (with encephalopathy and dementia).

How to take choline alfoscerate?

In acute conditions (ischemic stroke, traumatic brain injury), 1000 milligrams of the substance are administered intravenously or intramuscularly (slowly). The frequency of injections, depending on the patient’s condition, is 1 – 4 times a day. The course of treatment is 10 – 20 days. After this, they switch to oral administration of the substance (3 capsules per day) for 4 to 6 months.

For dementia syndromes and chronic diseases of the central nervous system, the drug is prescribed orally, 400 milligrams 3 times a day before or after meals. The course of therapy is 3 – 6 months. If nausea occurs, reduce the dosage.

While carrying out “vitamin” therapy, it is important to consume protein foods that contain methionine (eggs, cottage cheese, liver, fish).

Remember, it is advisable to entrust the choice of medicine to an experienced specialist.

The above-described technologies for using drugs should not be taken as a basis; the material is for informational purposes only.

Symptoms of Choline Overdose

• The appearance of a “fishy” odor from the body.
• Vomit.
• Excessive sweating.
• Hypersalivation.

Against the background of excess amounts of choline, the liver experiences a toxic effect. The body activates the production of TMAO, which causes cardiovascular disorders.

Iron. Types and norms of consumption

It is necessary to maintain iron levels in the body.

This microelement must be included in the diet of any person. But there is a group of people whose iron intake should be kept under special control:

• women expecting a baby;
• representatives of the fair sex during menstruation;
• children and elderly people;
• patients in the recovery stage.

Doctors divide iron, which is absorbed by the human body, into 2 large groups:

O.A. Gromova1,2, K.V. Rudakov1,2, I.Yu. Torshin1,2

1Russian Satellite Center of the UNESCO Institute of Microelements, Moscow

2Laboratory of Computational and Systems Biology of the Computer Center named after. A.A. Dorodnitsyna, RAS, Moscow

Key words: choline, cellular biochemistry, physiological effects.

Choline is one of the vitamin-like substances. The biological effects of choline are most important in the neuromuscular system, where choline is a precursor to acetylcholine, an essential neurotransmitter. Choline is also necessary for regulating the mechanical properties of cell membranes and is a donor of methyl groups for the synthesis of S-adenosylmethionine. The above-mentioned cellular and biochemical effects of choline correspond to the spectrum of physiological effects of this substance. It should be noted that until now, the reliable range of physiological effects of choline has not been systematically analyzed based on objective data. The latter leads to unfounded speculation in order to promote choline drugs and an extreme exaggeration of the therapeutic significance of cholinergic drugs. In this work, we aim to determine the spectrum of physiological effects of choline based on data from basic medicine. Knowledge of the reliable spectrum of choline allows us to objectively assess the real applicability of choline drugs in various fields of medicine, including neurology. The results of the analysis are compared with available data on evidence-based medicine in order to indicate the real possibilities of choline drugs when used as part of personalized medicine. Introduction The creation and correct use of highly effective neuroprotective drugs of artificial and natural origin is the most important task in modern medicine. In Russia alone, the incidence of stroke is about half a million cases per year, which makes it necessary to develop effective therapeutic protocols based on individual drugs. Adequate implementation of protocols should be carried out within the framework of personalized medicine, i.e., take into account the individual characteristics of each patient. Known neuroprotective drugs differ in the range of their physiological effects on the body. There are drugs with an extremely wide spectrum of effects (for example, Cerebrolysin, which has a positive effect on dozens of physiological mechanisms [1]). There are also drugs with an extremely narrow spectrum of action (for example, thrombolytics, which act exclusively on hemostasis). Other drugs act on several specific physiological subsystems of the body. The intensity and versatility of these effects ultimately determine the degree of therapeutic effectiveness of the drugs. Choline, phosphatidylcholine, CDP-choline and other choline derivatives are well-known dietary supplements that are widely used in healthy eating schools (see, for example, [2]). The subject of this article is to analyze the spectrum of all possible physiological effects of choline-based drugs. It is obvious that the establishment of this spectrum based on data from fundamental medicine, clinical studies and post-genomic biology will allow us to establish the real area of ​​​​therapeutic applicability of this group of drugs. The analysis in this work was carried out using a search of public databases (including the human genome databases at www.genome.gov, ncbi.nlm.nih.gov) and the existing literature on basic medicine and clinical research. The need for choline, its availability in foods, the fundamental physiological mechanisms of choline and its derivatives, and clinical research data are reviewed in sequence.

Choline: its sources and dietary choline deficiency Choline (vitamin B4, Fig. 1) is part of lecithin, plays a role in the synthesis and metabolism of phospholipids in the liver, and is a precursor of the neurotransmitter acetylcholine. Choline is widely distributed in commonly used foods in the form of free choline; in animal sources and in soy as an integral part of the lecithin molecule. Main food sources of choline: eggs, liver, lean meat, fish, soybeans, oatmeal, cauliflower, spinach, cabbage, peanuts. It is a component of lecithin. The choline content of various foods is shown in Table 1. A typical diet contains 500-900 mg of choline. According to recommendations adopted in Russia, an adult’s need for choline is 500-1500 mg/day. The upper permissible level of consumption: 1000-2000 mg/day for children under 14 years of age, 3000-3500 mg/day for children over 14 years of age and adults [3]. Choline deficiency can only occur in extreme situations (chronic alcoholism, genetic defects), since choline is present in a large number of foods. Moreover, the human body can synthesize choline from other dietary components in the absence of choline in the diet. Choline deficiency (unlike, for example, magnesium or pyridoxine deficiency) is not a nosology according to ICD due to the rather low specificity of symptoms. With proven choline deficiency, the following disorders develop: fat intolerance (diarrhea and flatulence when eating fat), hypertension, impaired growth, stomach ulcers, changes in heart rate, failure of liver and kidney function. An upper permissible level of consumption has been established for choline (3000-3500 mg/day in Russia, Methodological recommendations of the Ministry of Health of the Russian Federation [3]). Large doses of choline (grams) lead to increased sweating, nausea, and a strong fishy odor of the skin. In the group of stroke patients taking 2000 mg/day, cases of headache and dizziness were more common [4]. Manufacturers of neurological choline drugs (citicoline) indicate side effects in the form of allergic reactions (rash, skin itching, etc.), and the development of shock is possible. Contraindications to the use of choline drugs are vagotonia (predominance of the tone of the parasympathetic part of the autonomic nervous system) and hypersensitivity to the drug. Again, in accordance with the manufacturers' recommendations, use in children under 18 years of age is not recommended (due to lack of data), and during pregnancy the drug is prescribed only if the expected benefit outweighs the potential risk.

Fundamental Mechanisms of Choline's Effect on Physiology From a basic medical point of view, choline and its metabolites are essential for three physiological processes (Fig. 2): maintaining the structural stability of membranes, cholinergic neurotransmission (via the synthesis of acetylcholine) and participation in DNA methylation through the choline derivative trimethylglycine (betaine). ). Based on betaine, a source of methyl groups, the S-adenosylmethionine molecule, is synthesized. Phosphatidylcholine (the main component of lecithin) is one of the phospholipids that form the cell membrane. Phospholipids, in addition to forming the cell membrane, also serve as intermediates in cell signaling systems. Released from the cell membrane by phospholipases, phospholipids participate in the arachidonic acid cascade that mediates proinflammatory responses. Phospholipase D catalyzes the hydrolysis of phosphatidylcholine to form phosphatidic acid and, again, choline, which is secreted into the cytosol. Signal transmission through phosphatidylcholine is an integral part of many molecular mechanisms of the cell (for example, signal transmission from the “cell colony stimulating factor” protein, which ultimately leads to an increase in the leukocyte population [5, 6]. Signaling through phosphatidylcholine cascades is what is associated likely to increase apoptosis of cells (e.g. lymphocytes [5]). Acetylcholine is a neurotransmitter in both the peripheral and central nervous systems. In the peripheral nervous system, acetylcholine activates muscle cells. In the central nervous system, acetylcholine forms the cholinergic system, including numerous types of acetylcholine receptors and enzymes catabolizing this neurotransmitter. Activation of the cholinergic system, in general, has an excitatory rather than inhibitory effect on the neuromuscular system [7, 8]. When acetylcholine interacts with the ACh receptors of skeletal muscles, sodium ion channels open, sodium enters the cell and stimulates contraction In the case of the myocardium, acetylcholine has the opposite effect - it reduces the contractility of cardiomyocytes. In the CNS, acetylcholine serves as a neuromodulator of synaptic function, and profound acetylcholine deficiency is associated with memory impairment in Alzheimer's disease [7]. The physiological effects of acetylcholine significantly depend on the localization of receptors in certain tissues and organs (Table 2) and can be very important when analyzing a patient in the context of personalized medicine (see below). There are two main classes of acetylcholine receptors: nicotinic and muscarinic. The names of the receptors are related to the ligands that activate these receptors. Nicotinic receptors are located on muscle cells in the central nervous system and change the permeability of the membrane to sodium, potassium and chloride ions. Muscarinic receptors are located in the central nervous system and periphery, also in the myocardium, lungs, upper gastrointestinal tract and sweat glands. Muscarinic acetylcholine receptors do not change the ionic conductivity of membranes, but initiate intracellular signal transmission through G proteins [9]. Acetylcholine and choline increase plasma nitric oxide and red blood cell nitrite levels. A possible mechanism is activation of M1 muscarinic acetylcholine receptors [10, 11]. Increased NO concentration leads to vasodilation. Nitric oxide is also the most likely mechanism for the disaggregant action of choline [12], and a decrease in red blood cell aggregation also contributes to a decrease in blood clotting [11]. Based on one of the choline derivatives, betaine, the molecule S-adenosylmethionine is synthesized, a component of cellular biochemistry important for maintaining the structure of the genome. S-adenosylmethionine is an intermediate product of the transformation of the amino acid methionine, which comes with excess protein foods (meat, cottage cheese, eggs). The methionine transformation cycle includes homocysteine, methionine, S-adenosylmethionine and S-adenosylhomocysteine ​​(Fig. 3). Homocysteine, an independent factor of atherosclerosis and stroke, significantly aggravates the rehabilitation of patients. Along with folate, vitamins B12 and B6, S-adenosylmethionine is involved in the neutralization of homocysteine ​​(Fig. 4). However, unlike the detoxification of homocysteine ​​in the folate cascade, the transformation of homocysteine ​​and methionine through S-adenosylmethionine can lead to:

1) increased DNA methylation due to higher levels of S-adenosylmethionine and 2) increased levels of catecholamines.

Excess choline can therefore negatively affect genome structure due to increased methylation. It should also be noted that cancer cells contain elevated levels of choline, which is apparently associated precisely with disorders of phospholipid metabolism characteristic of oncology [13]. Increased choline levels correspond to increased DNA methylation (due to increased levels of S-adenosylmethionine) and, therefore, worsening cancer-related chromosomal abnormalities. One of the interesting physiological effects of choline on cellular biochemistry is also its effect on catecholamine levels. Experiments on cells in culture have shown that choline stimulates the secretion of catecholamines (adrenaline, in particular) [14, 15]. Catecholamines are also dependent on S-adenosylmethionine levels [16] and are one of the main regulators of vasoconstriction. CDP-choline (cytidyl diphosphocholine, the basis of such drugs as citicoline, etc.) leads to an increase in plasma catecholamines [17]. Higher levels of catecholamines are associated with increased blood pressure and thus are not always beneficial for stroke and other diseases. Intraperitoneal administration of CDP-choline actually leads to an increase in blood pressure in the experiment [17]. The above-mentioned mechanisms of choline action are also confirmed from a post-genomic point of view, including data on all known genes through functional connectivity analysis [16]. In general, more than 40 proteins, encoded by approximately the same number of genes, interact with choline in the human body. The three pathways discussed above for the physiological effects of choline (phosphatidylcholine, acetylcholine, S-adenosylmethionine) are displayed in Table 3. The biological functions of these proteins clarify the range of influence of acetylcholine on human physiology. In particular, genome-wide analysis data made it possible to identify the main proteins involved in metabolism, choline transport and the functioning of the cholinergic receptor system. Numerous genetic defects (so-called “rare mutations”) of each of these genes will lead to certain biochemical and corresponding clinical manifestations. For example, loss-of-function mutations in choline metabolism proteins result in decreased choline requirements in a given patient. Conversely, mutations of these genes leading to increased function of the corresponding proteins lead to an increased need for choline.

Clinical studies of choline drugs Analysis of data from cell biology and basic medicine indicates that one of the main effects of choline drugs is the effect on cholinergic neurotransmission, which leads to optimization of nerve and neuromuscular conduction. A side effect of this is to slow down the processes of apoptosis in brain tissue. Both of these effects of choline may be important in post-stroke nerve tissue repair. Accordingly, clinical studies of choline drugs, such as citicoline and others, are aimed specifically at recovery after stroke. A meta-analysis of studies on oral administration, for example, cytidyl-diphosphocholine, showed some positive and short-term effect of taking the drug on the functioning of patients' memory [18]. A meta-analysis of 10 studies on citicoline (2,279 patients) indicated a decrease in the incidence of mortality and complications in the group taking the drug [19]. A meta-analysis of studies of 1,372 patients showed a small but statistically significant difference in the rate of recovery of patients (mRS, BI, and NIHSS) treated with oral cytidyl diphosphocholine for 3 months (odds ratio 1.33; 95% confidence interval 1.1 -1.6; p = 0.003) [20] when using drug doses of at least 2000 mg/day. Individual randomized trials of the effects of choline preparations vary in their quality and degree of reliability of the results. A study of the effect of citicoline on the volume of cerebral infarction in 100 patients in the acute period of ischemic stroke based on magnetic resonance imaging showed a significant decrease in the growth of the ischemic lesion in the group of patients receiving 500 mg/day of citicoline for 6 weeks [21]. In a multicenter, double-blind, placebo-controlled study of citicoline in 272 patients with moderate to severe stroke, 133 patients received 1000 mg/day IV citicoline daily for 14 days [22]. By day 14 there was a significant improvement in the citicoline group only in the case of cognitive functions. The result suggests that IV administration of citicoline during the acute period of stroke may promote functional recovery after reversible tissue damage. At the same time, a relatively large multicenter study of 899 patients with acute stroke in the middle cerebral artery showed extremely contradictory results [4]. Thus, taking citicoline at a dose of 2000 mg/day for 6 weeks contributed to a twofold change in the Barthel index compared to the group of patients taking placebo. The same was observed when taking a dose of 500 mg/day. Paradoxically, however, the results in patients taking citicoline 1000 mg/day were comparable to the group of patients taking placebo (Fig. 5). Moreover, although there was a significantly higher proportion of patients in the citicoline group who showed improvement after 6 weeks of therapy, there was no improvement when compared at week 12 of the study. This kind of inconsistency in one of the largest randomized trials of choline drugs for stroke, along with the results of meta-analyses, shows that the use of citicoline has a fairly small effect on improving outcomes in patients with acute ischemic stroke - the main area of ​​​​use of choline drugs/dietary supplements. The contradictions do not necessarily indicate poor quality of research, but rather are a consequence of neglecting to stratify patients according to blood choline levels and choline depot status. Neglect of stratified data analysis is one of the grossest and most common violations of the analysis of biomedical research results [23]. The relatively small magnitude of the observed therapeutic effect, along with the rather narrow window of physiological effect (acetylcholine-dependent neurotransmission) and the lack of stratification of the data, indicates the possibility that the beneficial effect is observed in only a small number of patients in the studied samples. For example, in a meta-analysis of 1,372 patients, the odds ratio was only 1.33 [20] with p = 0.003, corresponding to no more than a 33% chance of improvement compared with the placebo group. Our analysis of the distribution of c2 at p = 0.003 and other statistical parameters of the studies indicated in [20] confirms this assumption. Data analysis was carried out based on the deletion methodology for analyzing medical data [16]. Thus, obtaining an odds ratio of 1.33 at p = 0.003 becomes possible even with a difference in the number of respondents of 50 people between the control groups and patients taking the drug. Taking into account the large size of both groups (about 500-700 people), it becomes clear that the positive effects of choline drugs are observed in no more than 10% of patients taking the drug.

Choline preparations and personalized medicine Personalized medicine requires maximum consideration of the individual metabolic characteristics of a particular patient and, above all, the individual pharmacokinetics and pharmacogenetics of specific pharmaceuticals. A personalized approach allows you to assess the balance between the effectiveness and side effects of using pharmaceuticals in each individual case. The above analysis of the biological effects of choline indicates certain limitations associated with the use of choline drugs in specific patients. Efficiency. The above-mentioned analysis of trials of choline drugs showed that the effects of choline drugs were observed in no more than 10% of patients taking the drug. It can be assumed that these are patients with severe choline deficiency. Consequently, choline preparations will not be effective in patients with normal choline levels (which is the majority, including, especially, young hypertensive patients), even when using high doses of drugs. The effect of choline on vasodilation is controversial. On the one hand, studies on human cell cultures have shown an increase in nitric oxide when treated with choline and acetylcholine [10, 11]. Increased NO concentration corresponds to vasodilation. At the same time, the experiment established the vasoconstrictor and hypertonic effects of choline drugs when administered intraperitoneally [17]. The antithrombotic effect of choline drugs is observed at very high doses (250 mg/kg in the experiment) [12], which corresponds to taking 10-15 g/day in the case of adult patients. Such high doses (exceeding the maximum permissible by 4-5 times), along with a possible hypertensive effect, raise the question of the safety of using choline drugs (Fig. 6). Choline is required for acetylcholine synthesis [24] and administration of choline supplements, especially in hyperdoses, can increase systemic acetylcholine levels. When prescribing choline preparations, the doctor must take into account the individual pharmacology of acetylcholine. Classical pharmacology indicates different effects of acetylcholine on different organs (see Table 2). As the following examples illustrate, these pharmacological data can be effectively used in personalized medicine.

• For example, in an elderly patient with bradycardia and sufficient choline intake, supplemental choline supplementation may cause a further slowing of the rhythm. • In a patient with bronchial asthma and sufficient choline intake, taking choline supplements increases the risk of bronchospasm. • In a patient with any genetic defect of the “slow metabolizer” type in the genes serving choline metabolism (see Table 3), excessive administration of choline preparations will lead to an increased load on the elimination system and the appearance of the smell of decomposing fish in the patient. • In a patient with cholelithiasis and the presence of calcified gallstones, the use of choline preparations stimulates the tone of the wall of the gallbladder, bile ducts and can cause dangerous movement of gallstones and obstruction of the bile ducts.

Safety. According to the manufacturers, contraindications to the use of choline drugs are vagotonia, hypersensitivity to the drug; use in children under 18 years of age and during pregnancy is not recommended without assessing the risk-benefit balance. At high doses of choline (such as 2000 mg/day), headaches were more common [4]. The antiplatelet effect of choline preparations should be taken into account [12]. In particular, the decrease in red blood cell aggregation observed when taking choline helps reduce blood clotting [11]. Therefore, the use of choline drugs cannot be recommended for hemorrhagic stroke (and in the early period of ischemic stroke), when thrombolytics and antiplatelet agents can do more harm than good. Progressive manufacturers of choline drugs (Somazina, manufactured by Ferrer Internacional, Spain, https://www.ferrergrupo.com) indicate that for persistent intracranial bleeding, it is recommended to administer the drug as a very slow IV infusion (30 drops/min) and not exceed the daily dose of 1000 mg. Excess choline can lead to “fishy odor syndrome” due to the degradation of choline into trimethylamine. The fishy smell of trimethylamine is a sign of choline intoxication and the inability of elimination systems (the liver, first of all) to cope with excess choline intake. Intoxication will be significantly worsened in patients with kidney disease due to prolonged half-life, which should be taken into account in personalized medicine. As both clinical and basic research show, choline preparations are most effective in fairly high doses (grams). One of the most commonly used forms of choline, CDP-choline (citicoline, etc.) is also a significant source of phosphorus. Taking into account the excess phosphorus in the diet of Russians [25] due to excessive consumption of processed meat products (sausages, sausages, etc.), large doses of CDP-choline will only contribute to hyperphosphatemia and create additional stress on the excretory systems. Hyperphosphatemia contributes to an imbalance of macro- and microelements (primarily calcium and magnesium); prolonged hyperphosphatemia contributes to the development of oncology. High levels of phosphorus can also significantly accelerate the formation of kidney stones [26] and possibly gallstones [27].

Conclusion Choline is the basis for the synthesis of the neurotransmitter acetylcholine and one of the most popular dietary supplements. Drugs based on choline derivatives are being promoted for the treatment of stroke, in intensive care and obstetrics. However, both the evidence and the fundamental basis for the use of choline and its derivatives do not provide sufficient justification for the persistent widespread imposition of the use of choline drugs on all patients. In this work, we examined the spectrum of physiological manifestations of the effects of choline. From a neurochemical point of view, choline and drugs based on it are characterized by unidirectional effects (acetylcholine-dependent neurotransmission). In general, stroke involves disruption of multiple neurotransmission pathways (GABA, glutamate, catecholamines, NO, neuropeptides, endocannabinoids, eicosanoids, etc.), not to mention specific neurotrophic factors and interleukins. The effects of other neurotransmitters occur largely independently of acetylcholine. Analysis of evidence-based medicine indicates a high probability that choline-based drugs have a significant effect only in a relatively small proportion of patients (less than 10% of all patients). These patients may, for example, have genetic defects in choline metabolism, characterized by severe choline deficiency, or due to alcoholism or inadequate nutrition. Thus, the prescription of choline drugs requires a physician to assess the appropriateness of using drugs from this group in a given patient and a reasonable assessment of the “efficacy-safety” balance. Pharmacological neuroprotection is only part of a comprehensive program for patient recovery after a stroke. The greatest effectiveness of medications is manifested precisely in the context of comprehensive programs, including motor rehabilitation, physical therapy, classes with a speech therapist, swimming, massage, programmable electrical myostimulation, correction of walking patterns, etc. Prevention of recurrent stroke is very important, which must necessarily include lipid profile correctors and coagulation (aspirin, omega-3 PUFAs, selenium-containing, magnesium-containing drugs and an antiatherogenic diet).

Literature 1. Gromova O.A., Gupalo E.M., Torshin I.Yu. Cerebrolysin: analysis of basic and clinical studies. Methodological letter for doctors. M.: 2008; RSC Institute of Microelements UNESCO, 142. 2. Atkins R. Bioadditives of Dr. Atkins, RIPOL Classic. M.: 1999; 81. M.: 2008; 33. 3. Methodological recommendations of the Research Institute of Nutrition of the Russian Academy of Medical Sciences. Recommended standards for consumption of food and biologically active substances. Project. 2008; MP 2.3.1.1915-04, 39. 4. Clark WM, Warach SJ, Pettigrew LC, Gammans RE et al. A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline Stroke Study Group // Neurology. 1997 Sep; 49: 3: 671-8. 5. da Costa KA, Niculescu MD, Craciunescu CN, Fischer LM, Zeisel SH Choline deficiency increases lymphocyte apoptosis and DNA damage in humans // Am J Clin Nutr. July 2006; 84:1:88-94. 6. Jackowski S., Xu XX, Rock CO Phosphatidylcholine signaling in response to CSF-1 // Mol Reprod Dev. Jan 1997; 46:1:24-30. 7. Katzung, B. G. (2003). Basic and Clinical Pharmacology (9th ed.). McGraw-Hill Medical. ISBN 0-07-141092-9. 8. Kharkevich D.A. Pharmacology. GeotarMed, 2008; 113. 9. Hasselmo ME Neuromodulation and cortical function: modeling the physiological basis of behavior // Behav Brain Res. 1995; 67:1:1-27. 10. Carvalho FA, Mesquita R, Martins-Silva J, Saldanha C. Acetylcholine and choline effects on erythrocyte nitrite and nitrate levels // J Appl Toxicol. 2004; 24: 6: 419-427. 11. Santos T., Mesquita R., Martins E. Silva J., Saldanha C. Effects of choline on hemorheological properties and NO metabolism of human erythrocytes // Clin Hemorheol Microcirc. 2003; 29:1:41-51. 12. Masi I., Giani E., Galli C. Effects of CDP-choline on platelet aggregation and the antiaggregatory activity of arterial wall in the rat // Pharmacol Res Commun. 1986; 18: 3: 273-281. 13. Ackerstaff E., Pflug BR, Nelson JB, Bhujwalla ZM Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells // Cancer Res. 2001; 61:9:3599-3603. 14. Wurtman RJ Stimulation of catecholamine secretion by choline // Science. 1983; 222: 4620: 188. 15. Holz RW, Senter RA Choline stimulates nicotinic receptors on adrenal medullary chromaffin cells to induce catecholamine secretion // Science. 1981; 214: 4519: 466-468. 16. Torshin I.Yu. Bioinformatics in the post-genomic era: sensing the change from molecular genetics to personalized medicine. Nova Biomedical Books, NY, USA, 2009, In ​​“Bioinformatics in the Post-Genomic Era” series, ISBN: 978-1-60692-217-0. 17. Cansev M., Yilmaz MS, Ilcol YO, Hamurtekin E., Ulus IH Cardiovascular effects of CDP-choline and its metabolites: involvement of peripheral autonomic nervous system // Eur J Pharmacol. 2007; 577: 1-3: 129-42 Epub 2007 Au. 18. Fioravanti M., Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioral disturbances associated with chronic cerebral disorders in the elderly // Cochrane Database Syst Rev. 2005; 2:CD000269. 19. Saver JL Citicoline: update on a promising and widely available agent for neuroprotection and neurorepair // Rev Neurol Dis. 2008; 5:4:167-177. 20. Davalos A, Castillo J, Alvarez-Sabin J, Secades JJ et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials // Stroke. 2002; 33:12:2850-2857. 21. Warach S, Pettigrew LC, Dashe JF, Pullicino P et al. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging // Citicoline 010 Investigators. Ann Neurol. 2000;48(5):713-722. 22. Tazaki Y., Sakai F., Otomo E., Kutsuzawa T. et al. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study // Stroke. 1988; 19:2:211-216. 23. Torshin I.Yu. Bioinformatics in the post-genomic era: physiology and medicine. Nova Biomedical Books, NY, USA (2007), ISBN: 1600217524, 35-67. 24. Freeman JJ, Jenden DJ The source of choline for acetylcholine synthesis in the brain // Life Sci. 1976; 19: 7: 949-961. 25. Tutelyan V.A., Spirichev V.B., Sukhanov B.P., Kudasheva V.A. Micronutrients in the diet of a healthy and sick person. M.: Kolos, 2002; 423. 26. Guan X., Wang L., Dosen A., Tang R. et al. An understanding of renal stone development in a mixed oxalate-phosphate system // Langmuir. 2008; 24: 14: 7058-60. 27. Wolf P., Mannino F., Hofmann AF, Nickoloff B., Edwards DK Calcium oxalate-phosphate gallstones, a unique chemical type of gallstone // Clin Chem. 1982; 28:8:1804-1805.

Iron-containing foods

Fish and seafood contain a lot of iron.

It is believed that the maximum amount of iron contains apples, pomegranate juice and liver. Is it so? Let's look at the main iron-rich food groups:

1. Dark meats, offal - beef, lean parts of pig, lamb, poultry, any liver.
2. Fish, seafood - any.
3. Eggs - any kind.
4. Cereals – wheat, rye, oats, any bran.
5. Products of plant origin - legumes, spinach, beets, cauliflower and broccoli, radishes.
6. Dried fruits - any.
7. Nuts, seeds - any.

The list of iron-rich foods is quite large and varied. With the right approach, it is easy to create a balanced diet for meat lovers, vegetarians who do not eat meat, vegans who eat exclusively plant foods, and people with allergies to certain foods.

Interaction with other substances

It is worth taking into account that doctors advise taking anticonvulsants and oncoprotectors with caution at the same time as a microelement. When taken simultaneously, vitamin B4 is absorbed more slowly. Choline is suppressed by antibacterial drugs, certain types of hormones and alcohol drops. Birth control pills destroy vitamins, but vitamins D and K, on ​​the contrary, are absorbed much better with it.

Choline intake must be carried out taking into account the dosage. Today, the consumption standards established in Russia are up to 70 mg for children under one year old, up to 90 mg for children up to 3 years old, 200 mg for children under 7 years old. The maximum amount - 550 mg - is indicated only for women during pregnancy and lactation. Take care of your health, consult doctors in a timely manner, be happy.

Historical aspects

Vitamin B was first synthesized by Casimir Funk in 1911. He called the resulting compound a vitamin because it contained a nitrogen atom. Then, in 1929, Christian Eijkman received the Nobel Prize for the biosynthesis of a substance that cures beriberi disease, and therefore was named vitamin B. But with further research, substances very similar to this vitamin were discovered, they were given a group and number in their names in accordance with opening sequence. Now you can notice that when listing the vitamins of this group there are “gaps”: vitamin B4 is missing.

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More details

Vitamin B4 was first noticed back in 1849, and in 1862 it was possible to isolate the substance from bile, due to which it received the name choline (from the Greek “chole”), then in 1901, but it is impossible to say exactly where and how it was discovered no one can. The thing is that at the beginning of the 20th century there were no concepts about vitamins, and the technologies of those years could not explain its benefits to the body, so they forgot about the discovery. Then a group of scientists led by Best discovered fatty liver degeneration in dogs that received insulin and had enlarged pancreas. Treatment of this liver pathology was successfully carried out by adding lecithin, which is contained in raw egg yolk, to the feed. The substance that helped the dogs was called choline.

Further research showed that it is not a vitamin. Therefore, it is commonly called a vitamin-like substance. That is, it is only a metabolic factor that can be formed independently from amino acids.