Choline or vitamin B4 is a water-soluble and irreplaceable substance in the human body. It was opened in the 19th century. It can be produced by the body, but in small quantities. B4 protects cells from damage, lowers cholesterol levels and promotes normal metabolism. Its deficiency affects all organs and systems of the body.
What is choline for?
Choline is involved in metabolic processes in the body and prevents the development of atherosclerosis. It effectively lowers the level of bad cholesterol and is important for the nervous system. Choline protects the liver and is important in the process of hematopoiesis. Vitamin B4 is very necessary for active mental activity, as well as problems of the nervous system. In order for choline to be formed in the body, a constant supply of the amino acid methionine is necessary. An adult needs about 0.5 g of vitamin B4 per day.
B4 deficiency affects all body systems. First of all, the heart and muscles are affected. The body cannot cope with the utilization of fats and, as a result, excess weight arises. One of the signs of a B4 deficiency is high cholesterol levels. Choline deficiency will certainly affect the liver, leading to fatty deposits and disruption of basic functions. Choline is important for the nervous system.
Lack of vitamin leads to a feeling of constant fatigue, memory impairment and nervousness. Problems with the genitals may occur. In turn, an excess of choline negatively affects the body. Manifested by nausea, diarrhea and increased salivation... However, an excess of choline is observed in very rare cases due to uncontrolled use of medications.
Foods rich in this element are rarely likely to cause negative effects, as choline breaks down very easily. Diseases of the kidneys and liver, diet, as well as the intake of alcohol and antibiotics can cause a deficiency of this element.
What foods contain choline?
Choline deficiency is very rare as it is found in many foods. The main sources of choline are eggs and liver. A high percentage of this element is found in seafood, meat, oatmeal and cabbage. You can make up for the lack of choline by including peanuts and spinach in your diet.
Slightly lower amounts of choline are found in dairy products and legumes. But sprouted wheat and rice are effective with a deficiency of this element. It is advisable to include peas, lentils and potatoes in the diet.
If a person is taking medications, then you should not consume more than 1 g of choline. You should not independently prescribe yourself to take certain medications, since the dosage of vitamin B4 is selected individually.
Table of foods that contain choline
Choline deficiency is very rare. Its symptoms can be similar to some of the other more serious conditions. If a person's diet is varied, including fruits and vegetables, it is very easy to avoid deficiencies in nutrients such as choline.
What foods contain? How much is his daily requirement? How does choline work on the human body? What substances are its "enemies"? Preparations with vitamin B4. Signs of excess and deficiency.
Choline is called vitamin B4, although it is considered a vitamin-like substance that is synthesized in our body. It protects cell membranes from damage, normalizes cholesterol. Promotes metabolism in nervous tissue, reduces body weight, improves short-term memory, and prevents the appearance of gallstones.
It was discovered in the second half of the 19th century in the study of animal tissues, but its role in the human body was investigated in detail in 1930. In Greek, choline means bile.
The effect of B4 on the human body
When a person needs to concentrate, the body starts biochemical reactions, after which the accumulated vitamin B4 is converted into acetylcholine. Acetylcholine, in turn, conducts impulses through nerve tissues. It helps to activate the brain, which makes a person's ability to memorize and concentration of attention improve (important for schoolchildren, students and knowledge workers). Long-term deficiency threatens the destruction and death of nerve cells.
Choline is also needed for the sheath of nerves and brain cells, or rather, to maintain its constant consistency. Without it, cholesterol forms seals in the cells, which is why nutrients comes in less and less. Harmful cholesterol eventually "kills" cells and clogs brain signaling channels. It is difficult for a person to formulate his thoughts, he becomes inattentive, absent-minded, emotionally unstable.
Vitamin B4 is involved in the functioning of the genital organs, helps in the formation of a hormone in the prostate gland, and improves sperm motility.
This substance also normalizes blood sugar levels by strengthening the membranes of beta cells needed for insulin production. It participates in the growth process, promotes hematopoiesis, protects the liver from the destructive effects of alcohol and other lesions.
Enemies of Choline: alcohol, water, estrogens, sulfa drugs, food processing.
Preparations with vitamin B4: Duovit Memo, Vitrum Beauty.
Interaction with other substances:
- Choline deficiency can occur with low acid intake and.
- Deficiency of vitamin B4 leads to a decrease in the synthesis of carnitine, which is necessary for the work of the heart, muscles and the utilization of fats.
Although vitamin B4 is independently produced in the liver and intestinal microflora, this cannot fully cover all the body's needs for this compound.
Animal sources: egg yolk, dairy products, animal heart and liver.
Plant sources: oatmeal, wheat germ, cabbage, green leafy vegetables, brewer's yeast, soy, spinach.
Choline daily requirement
For an adult it is 0.5 g (500 mg) per day. Increased doses (up to 10-20 g) are required for diseases and all kinds of stress. Vitamin B4 is recommended to be taken with intense sports, exhaustion of the nervous system, stress (read which ones arise), damage to the brain, polyneuritis and other diseases of the nervous system.
Deficiency signs
- high blood cholesterol
- bad memory
- overweight
- violation of lactation in women who are breastfeeding
- dysfunction of the genitals
Signs of excess
- nausea, diarrhea
- increased sweating and salivation
- lowering blood pressure
- increased intestinal motility
- cardiac depression
; B vitamins
IUPAC name: 2-hydroxy-N, N, N-trimethylethanamine
Other names: bilineurin, (2-hydroxyethyl) trimethylammonium
Molecular Formula: C5H14NO
Molar mass: 104.17080
Density: 1.09 g / ml
Evaporating temperature: 305 ° C, 578 K, 581 ° F
Choline is a water-soluble vital nutrient and part of the B complex. Choline is a quaternary ammonium salt containing the cation of N, N, N-trimethylethinolammonium. This cation appears in the main group of phosphatidylcholine and sphingomyelin, two phospholipids that are abundant in cell membranes. The choline molecule is a precursor for the neurotransmitter acetylcholine, which is involved in many bodily functions, including memory and muscle control. A person needs to consume choline with food. This substance is used in the synthesis of structural components in the cell membranes of the body. Despite the purported benefits of choline, over-consumption of certain choline-rich foods (such as eggs and fatty meats) is not recommended. In 2005, the National Health and Nutrition Examination Survey released information that only 2% of postmenopausal women consume adequate amounts of choline. Choline is a molecule that is mainly used to enhance cognitive properties (by converting to acetylcholine, which is the neurotransmitter responsible for learning) or as a liver-protective agent, as this substance is able to reduce the accumulation of fat in the liver. It is found in large quantities in eggs, as well as in their yolks. Other names: trimethylethanolamine, choline bitartrate Not to be confused with: DMAE, lecithin Represents:
Cholinergic substance
Pseudovitamin
Works well with riboflavin (vitamin B12), which can suppress the fishy odor that some people experience with choline.
Choline: instructions for use
Dosages for choline can vary significantly. The usual dosage of 250 mg to 500 mg is used prophylactically once a day. For the mechanism of activation of acetylcholine, the dosages of choline are increased even with a single use, since higher doses are delivered to the brain to a greater extent. As a rule, such a dosage is 1-2 g. The dosage should be selected in accordance with individual factors, since exceeding the required dose can cause a headache. It is assumed that doses start at 50-100 mg per day, and then they can be increased depending on the tolerance.
Story
Choline was discovered in 1864 by Adolph Strecker. The chemical synthesis of choline was carried out in 1866. In 1998, the US Institute of Food and Nutritional Medicine classified choline as an essential nutrient. The importance of choline as a nutrient was first appreciated in the study of insulin functions, when it was found that choline is necessary to prevent fatty liver infiltration. In 1975, scientists discovered that the use of choline increases the synthesis and release of acetylcholine by neurons. These discoveries have led to increased interest in the effects of choline on brain function.
Recent research on choline
In 2010, a study was conducted of postmenopausal women with low levels of estrogen in order to identify the relationship of women's susceptibility to the risks of organ dysfunction with insufficient intake of choline. With a lack of choline in the diet, 73% of postmenopausal women taking placebo developed liver damage, which decreased to 17% with estrogen supplementation. The study also found that younger women need more choline because the body's need for choline increases during pregnancy. Choline is used in particular to support the developing nervous system of the fetus. During the intestinal metabolism of the microbiota of choline and phosphatidylcholine, trimethylamine (TMA) is produced, which is further metabolized to pro-atherogenic species, trimethylamine-N-oxide (TMAO).
Chemistry
Choline is a quaternary ammonium salt with the chemical formula (CH3) 3N + (CH2) 2OHX-, where X- is a counterion such as chloride, hydroxide, or tartrate. Choline chloride can form a deeply eutectic mixture with urea with a low melting point of solvents and unusual properties. Salicylate salt is used topically to relieve the pain of aphthous ulcers.
Choline hydroxide
Choline hydroxide is one of the class of phase transfer catalysts that are used to transfer hydroxide ion in organic systems, and therefore are considered strong bases. Choline hydroxide is the least expensive phase transfer catalyst and is used as a low cost removal agent for photoresist on printed circuit boards. Choline hydroxide is not a stable compound and gradually decomposes to trimethylamine.
The role of choline in the human body
Choline may (sporadically) exhibit stimulating properties
Choline and its metabolites are required for three main physiological functions: ensuring structural integrity and signaling of cell membranes, affecting cholinergic synapses (acetylcholine synthesis), and methyl group production. Choline acts through its metabolite, trimethylglycine (betaine), which is involved in the synthesis of S-adenosylmethionine.
Choline Deficiency Signs
The most common signs of choline deficiency are fatty liver and hemorrhagic kidney necrosis. Eating foods high in choline can help reduce the onset of deficiency symptoms. The study of this effect in animal models has generated some controversy due to the mismatch of dietary modifying factors.
Fishy odor syndrome (trimethylaminuria)
Choline is a precursor to trimethylamine, which some people are unable to metabolize due to a genetic disorder called trimethylaminuria. The body of a person suffering from this disorder, due to the release of trimethylamine, can emit a strong fishy or other unpleasant odor. The smell can be released even when eating regular food - that is, with a normal (not overestimated) choline content in food. People with trimethylaminuria are advised to limit their intake of foods high in choline, which can help suppress the person's unpleasant body odor.
Choline Deficiency Risk Groups
Athletes and alcohol abusers may be at risk for a choline deficiency and therefore may be advised to take choline supplements in these populations. Studies of a number of different populations have shown that, in general, the average intake of choline does not come up to the intake rate. Choline Research Scientist Dr. Stephen Seitzel wrote: “Recent analysis of NHANES data from 2003-2004. showed that in older [American] children, men, women and pregnant women, the average intake of choline was well below adequate levels. Ten percent of the population or less had a typical choline intake at or above normal levels. ”
What foods contain choline
Adequate choline intake for adult women is 425 mg per day, and even higher for pregnant and lactating women. Adequate choline intake for adult men is 550 mg / day. There are also consumption rates for children and adolescents.
32 grams of sunflower lecithin syrup: 544
15 grams of soy lecithin granules: 450
5 oz (142 g) raw beef liver: 473
Large hard-boiled egg: 113
Half a pound (227 g) cod: 190
Half a pound of chicken: 150
Liter of milk, 1% fat: 173
30 grams of brewer's yeast (2 tablespoons): 120
100 g dry soy: 116
Pound (454 grams) cauliflower: 177
Pound of spinach: 113
1 cup wheat germ: 202
Two cups (0.47 liters) hard tofu: 142
Two cups cooked beans: 108
A cup of raw quinoa: 119
A cup of raw amaranth: 135
Grapefruit: 19
Three cups (710 cm) brown rice: 54
1 cup (146 g) peanuts: 77
1 cup (143 g) almonds: 74
Besides cauliflower, other cruciferous vegetables can also be a rich source of choline. Sinapine is a quaternary ammonium alkaloid found in black mustard. It is a choline ester of sinapic acid.
Choline application
Below are the Adequate Daily Intake Levels and Upper Limits for Choline Intake in Milligrams, taken from a 2000 report by the American Institute of Medicine. - Infants 0-6 months: Adequate intake (mg / day) -150; Maximum acceptable level consumption (mg / day) - not established.
7-12 months: 150; not installed
Children 1-3 years old: 200; 1000
4-8 years old: 250; 1000
Males 9-13: 375
14-18 years old: 550 2000
19-30 years old: 550; 3000
31-50 years old: 550; 3500
50-70 years old: 550; 3500
70 years old: 550 3500
Women 9-13 years old: 375 2000
14-18 years old: 400 3000
19-30 years old: 425; 3500
31-50 years old: 425; 3500
50-70 years old: 425; 3500
70 years old: 425 3500
Pregnant women ≤ 18 years: 450 3000
19-30 years old: 450 3500
31-50 years old: 450 3500
Nursing ≤ 18 years: 550 3000
19-30 years old: 550; 3500
31-50 years old: 550 3500
Sources and structure
Biological significance
Choline is metabolized in mitochondrial cells (via mitochondrial choline oxidase), and then again in mitochondria using betaine aldehyde dihydrogenase; during this irreversible two-step process, trimethylglycine is formed.
Molecular targets
Methyl recoil
Methyl is known to be oxidized to the metabolite trimethylglycine (TMG) within mitochondrial cells, and TMG plays a role in maintaining the methyl group release process both directly (homocysteine methylation) and indirectly through supporting the body's production of S-adenosyl methionine. Supplemental choline may be indirectly involved in these two metabolites, which promotes whole body methylation.
Pharmacology
Blood serum
Consumption of 1000 mg of choline (via 2400 mg of choline bitartrate) can increase the sustained plasma concentration of choline from 7.33 microns to 11.11-11.7 microns (51-60%) in relatively healthy postmenopausal women.
Effects on the body
Neurology
Neuropharmacology
Although there was no difference between young people and older adults in the rate of absorption of choline in serum or serum levels of choline after supplementation (50 mg choline per kg of body weight in the form of choline bitartrate), it was found that an increase in the concentration of choline in the brain in older people (19% higher compared to baseline measurements) was significantly less than young people (60%).
Cholinergic neurotransmission
Choline is converted to acetylcholine (ACh) by the enzyme choline acetyltransferase (CAT).
Cardiovascular diseases
Atherosclerosis
It is known that trimethylamine compounds (choline and trimethylglycine) can be metabolized by intestinal bacteria to form trimethylamine gas (TMA), which resembles the smell of rotten fish, which is absorbed through the colon wall and metabolized by flavin monooxygenase (FMO3, in particular) to form trimethylamine oxide ( TMAO), odorless. When the mice switched to a diet high in choline (the proportion of choline increased from 0.08-0.09% to 0.5-1%), higher dosages could accelerate atherosclerotic lesions; these lesions were then corrected by serum TMAO and hepatic FMO3, which was 1000 times higher in female rats. This study also confirmed that suppression of the gastrointestinal tract flora (by antibiotics) was reduced by serum TMAO, which the body received from choline, preventing an increase in atorogenesis from choline (which is TMAO-mediated); isotopic foods containing choline and ingested orally are directly related to TMAO; this directly indicates the presence of metabolic transformations between them. This information provides some answers, revealing questions about possible solutions to “problem” metabolism, affecting intestinal metabolism, as well as the metabolomic approach. Preliminary, but rather convincing, evidence suggests that a metabolite of choline, namely TMAO, may be pro-atherogenic, while choline itself is not pro-atherogenic, although choline intake induces the metabolism of TMAO. The release of trimethylamine from ingested choline (27 mm) has been observed in humans with 18 mm choline chloride and 10 mm choline stearate, but not with lecithin. The lack of effect is noted with leticin and betaine. A subsequent study showed an increase in TMAO when phosphatidylcholine was obtained from food (two hard-boiled eggs) along with deuterium-labeled phosphatidylcholine; this increase could be avoided in the case of the use of broad-spectrum antibiotics to suppress the intestinal microflora with the assumption that TMAO is formed by the intestinal microflora from choline sources. Dietary sources of choline, including leticin (phosphatidylcholine), may increase serum TMAO in humans, although evidence for this is mixed. Higher levels of TMAO can lead to an increased risk of cardiovascular disease.
Sexuality and pregnancy
Pregnancy
One study that assessed maternal choline intake and its effect on offspring found that 930 mg daily choline intake (for 12 weeks in the third trimester) reduced the genetic expression of cortisol production in offspring.
Peripheral organ system
Liver
Choline deficiency in the diet is known to increase the accumulation of hepatic fatty acids (triglycerides), weakening the release of triglycerides from the liver into the blood plasma due to decreased synthesis of phosphatidylcholine (PC); PC synthesis promotes the synthesis of VLDL (lipoprotein), which increases the intensity of the outflow of triglycerides from the liver into the blood plasma; therefore, PC, in itself, is a necessary component for PC. Decreased production of PC occurs most often due to a reduced level of the choline metabolite, namely trimethylglycine (TMG), since TMG directly initiates PC production (methylation due to the BHMT enzyme), and by maintaining the production of S-adenosyl methionine, it supports the last stage of synthetic production (phosphatidylethanolamine N-methyltransferase, which requires S-Adenosyl methionine for creatine PC). Choline deficiency secondary to TMG deficiency can reduce or prevent the transport of triglycerides in the blood and to peripheral tissues from the liver (eg, skeletal muscle), causing low blood triglycerides and an increase in liver fat.
5interactions with nutrients
Trimethylglycine (TMG or Betaine)
(abbreviated as TMG, also known as betaine) is a metabolite of choline that is obtained from food; it mediates the methyl properties of choline. It seems that the use of TMG at a dosage of 1000 mg per day can increase the concentration of TMG from 31.4 +/- 13.6 μm to 52.5 +/- 26.5 μm (an increase of 67% compared to baseline measurements), in while consuming the same choline dosage (1000 mg choline from 2400 mg choline bitartrate) increased steady-state TMG from a median value of 30.7 μm to 54.6-65 μg (77-111% increase) along with an increase in choline in serum (from 7.33 microns to 11.1-11.7 microns). This suggests that 1000 mg choline and trimethylglycine are equally potent in increasing serum TMH levels and methylation. At a minimum, a dosage of 1000 mg of both TMG and choline will equally increase TMH levels and total methylation in the body.
Riboflavin
Trimethylamine (TMA) is a metabolite of many small amino acid molecules (eg choline); it has a fishy smell, and, as a rule, its level is too low to be felt in the urine, but if a person has an abnormally high level of this substance in the body, then the smell is clearly felt both in the urine and in other secretions of the body (trimethylaminuria), this condition is also called "fishy odor syndrome"; this condition is usually caused by mutations in the hepatic enzyme type 3 flavin-containing mono-oxygenase (FMO3), which metabolizes TMA, known as "primary trimethylaminuria", or due to excess production of TMG in the gastrointestinal tract from bacteria, this condition is called "secondary trimethylaminuria" ... These diseases are medically benign, but in such cases, the use of substances that caused the rotten fish odor is reduced; trimethylaminuria can affect anywhere from 1 in to up to 1 in 100 people. Traditionally, trimethylaminuria has been associated with dietary intake of choline, although it can also occur with high doses of trimethylglycine; in such cases, it is believed that 100 mg of riboflavin (vitamin B12) twice daily can reduce the smell of rotten fish in those who consume these supplements. It is possible that it can reduce the smell of fish, which occurs against the background of a mutation in the FMO3 gene (genetic predisposition to fish smell with a certain diet) when consuming choline.
Health Effects of Choline
Choline deficiency can affect the development of liver disease, atherosclerosis, and possibly neurological disorders. One of the symptoms of choline deficiency is an elevated level of the liver enzyme ALT (alanine aminotransferase). It is especially important for pregnant women to get enough choline in their diet, as low choline intake in the mother may increase the risk of developing neural tube defects in the baby and may affect the functioning of his memory. One study demonstrated that increased dietary intake of choline shortly before and after conception is associated with a reduced risk of developing neural tube defects in a baby. When choline intake is low, homocysteine levels increase, which increases the risk of preeclampsia, premature birth, and very low birth weight. One study also found that women who ate foods high in choline had a reduced risk of developing breast cancer, but other studies did not find such an association. Some evidence suggests an anti-inflammatory effect of choline. A study by ATTICA found that increased dietary intake of choline was associated with lower levels of markers of inflammation. A small study found that choline supplements may reduce the development of allergic rhinitis symptoms. Despite the importance of choline in central nervous system As a precursor for acetylcholine and phosphatidylcholine membranes, the role of choline in the development of mental illness is poorly understood. In a large population-based study, it was shown that blood choline levels in individuals aged 46-49 and 70-74 years are inversely correlated with the manifestation of anxiety symptoms. However, this study found no correlation between depression and choline levels. Adequate intake should be high enough to meet the needs of nearly all healthy people. Many people do not experience choline deficiency symptoms when consuming less choline than normal. The human body is able to synthesize some of the choline it needs. The need for choline from food also varies from person to person. In one study, researchers found that premenopausal women were less sensitive to low dietary choline levels than postmenopausal men or women. However, for some people, normal choline intake may not be sufficient. In the same study, six out of 26 people developed choline deficiency symptoms when consumed in adequate amounts. In another study of male subjects, adequate intake was also less than the optimal dose. The Nurses' Health study has shown that high dietary intake of choline is associated with an increased risk of colon adenoma (polyps) in women, but the disease may be due to other ingredients in the foods from which choline was derived. There was no evidence of an association between dietary choline intake and an increased risk of colon cancer Similar to the effect of choline on memory in newborns described below, choline deficiency has been shown to increase memory loss in adult rodents, while choline-rich foods have been shown to increase memory loss in adult rodents. In addition, older mice given choline supplements performed similarly to young 3-month-old mice.Mice supplemented with choline had more dendritic spines per neuron in the hippocampus. was the most affordable hall on the market. Another additive is lecithin from soy or egg yolk. Phosphatidylcholine is also available as a supplement, in tablet or powder form. Choline supplements are also available in the form of choline chloride, which, due to its hydrophilic properties, comes in liquid form. Sometimes the use of choline chloride is preferred because phosphatidylcholine can have negative effects on the gastrointestinal tract. It is well known that the addition of methyl group transfers of vitamins B6, B12 and folic acid causes a decrease in the titer of homocysteine in the blood, contributing to the prevention of heart disease. Choline or betaine supplements can also cause a decrease in homocysteine levels. Choline is an essential source of methyl groups. Choline supplements are often used as “smart drugs” or nootropics due to the role that the neurotransmitter acetylcholine plays in various cognitive systems in the brain. Choline is a chemical precursor or "building block" required for the production of acetylcholine, and research shows that memory, intelligence, and mood are mediated, at least in part, by acetylcholine metabolism in the brain. In a study in rats, a correlation was shown between choline intake during pregnancy and the mental performance of the offspring; however, this correlation could not be demonstrated in humans. However, this may be due to the fact that in the human study, “women ate regular food. They did not take choline-fortified foods or supplements. Thus, the results indicate that physiological choline concentrations in women who eat a normal diet during pregnancy are not associated with IQ changes in their offspring. The possibility cannot be ruled out that choline supplementation may have an impact on IQ. " Initial research on rhesus monkeys found that choline supplementation has adverse effects on the fetus in mothers who smoke. When taken together with nicotine, choline protects some areas of the fetal brain from damage, but worsens the effect of nicotine on other areas. That is, choline, generally considered a neuroprotective agent, can worsen some of the side effects of nicotine. The compound's polar groups, the quaternary amine and hydroxyl, render it non-fat-soluble, suggesting that it may cross the blood-brain barrier with choline. However, there is a choline transporter that allows choline to move across the blood-brain barrier. The effectiveness of these supplements in enhancing cognitive performance is the subject of ongoing controversy. The US FDA requires choline to be fortified in all infant formulas that are not made from cow's milk. Due to its role in lipid metabolism, choline is also found in many food additives for fat burning, but there is little evidence that the substance may have any effect on reducing excess body fat, or that taking large amounts of choline can increase the metabolic rate of fat.
Pharmaceutical Uses of Choline
Choline supplements can be used to treat liver disease, hepatitis, glaucoma, atherosclerosis, Alzheimer's disease, bipolar disorder, and possibly other neurological disorders. Choline also has a positive effect on alcoholics. The National Institutes of Health funded a study on the treatment of brain injury with Citicoline. Data were collected on the potential benefits of long-term use of the intermediate choline phospholipids (phosphatidylcholine) Citicoline for recovery from traumatic brain injury, but the study was terminated early due to lack of efficacy.
X-ray
Choline can be labeled with carbon-11 or fluorine-18, radioactive positron sources, allowing for x-rays to be taken on a positron emission tomography (PET) scanner. This type of scan is usually performed by a doctor who specializes in radiation medicine. Applications include X-rays of the prostate and breast cancer.
Pregnancy and brain development
The human body can synthesize choline when phosphatidylethanolamine is methylated by N-methyltransferase to form phosphatidylcholine in the liver. Choline can also be consumed from food. The lack of choline in the diet can provoke the development of fatty liver disease, liver damage and muscle damage. However, due to the close interaction between choline, folate, and vitamin B12, the function and role of choline in the body can be complicated. To begin with, methionine can be formed in two ways: either from methyl groups derived from folic acid or methyl groups derived from betaine (which takes its methyl group from choline). Changes in one of these mechanisms are compensated for by the other, and if these mechanisms cannot adequately supply methyl groups for production, the content in the body of the precursor, homocysteine, increases. Choline in food products exists in free or esterified form (choline through an ester bond binds to another compound, such as phosphitidylcholine). Although the body can use all forms of the substance, some data indicate their uneven bioavailability (use by the body). Lipid-containing forms (such as phosphitidylcholine) bypass the liver after absorption, while water-soluble forms (such as free choline) enter the circulation portal in the liver and are usually absorbed there. During pregnancy and lactation, the body's need for choline consumption increases sharply. This need can be met by regulating N-methyltransferase by increasing estrogen levels, which leads to an increase in the body's production of choline, but even with increased N-methyltransferase activity, the need for choline is so high that the body's reserves are usually completely depleted. This is supported by the fact that in mice lacking functional N-methyltransferase, in the absence of supplemental choline from food. on the 9-10th day of pregnancy, miscarriages occur. While the mother's choline stores are depleted during pregnancy and lactation, the placenta accumulates choline by pumping choline into the tissue, where it is then stored in various forms, the most interesting of which is acetylcholine (rarely found outside the nervous tissue). As a result, the fetus finds itself in an environment with an increased concentration of choline. In amniotic fluid, the concentration of choline is ten times higher than in the mother's blood. This high concentration is necessary for the abundance of choline in the tissues and the ability to effectively cross the blood-brain barrier.
Functions of choline in the fetus
Women during pregnancy need to take large amounts of choline as a substrate for building cell membranes (due to the rapid expansion of tissues in the fetus and mother), due to increased need in one-carbon residues (choline is a substrate for DNA methylation), to increase choline reserves in the fetus and in placental tissues, as well as to increase the production of lipoproteins (proteins containing portions of "fat"). In particular, there is an interest in the scientific community in studying the effects of choline on the brain. This is due to the use of choline as a material for the manufacture of cell membranes (especially phosphatidylcholine). The growth of the human brain is especially rapid during the third trimester of pregnancy and then for about five more years. At this time, there is a great need for sphingomyelin, which is made from phosphitidyl choline (hence from choline), as this substance is used to myelinate (isolate) nerve fibers. Choline is also required for the production of the neurotransmitter acetylcholine, which can affect brain structure and organization, neurogenesis, myelination, and synapse formation. Acetylcholine is present even in the placenta and can promote cell proliferation / differentiation (an increase in the number of cells and a change in multifunctional cells in isolated cellular functions) and is required during childbirth. Choline can also affect the methylation of DNA dinucleotides in the brain - this methylation can change the expression of the genome (which genes need to be turned on and which ones must be turned off), and thus has an impact on fetal programming (organizing the shutdown or activation of certain genes, without external forces). The functions of choline in the fetus are determined by its concentration. At low choline concentrations, he predominantly takes up phospholides. As the concentration increases, free choline is converted in the liver mitochondria into betaine, which is used as a source of methyl groups for DNA methylation, etc. However, with a decrease in the concentration of choline, the mechanism of N-methyltransferase is activated. N-methyltransferase allows the creation of new choline, even if it is not in the diet. With the help of this mechanism, up to 30% of the required amount of phosphatidylcholine is produced. Interestingly, phosphitidylcholine produced by N-methyltransferase tends to have longer and less saturated fatty acids than phosphitidylcholine produced directly from choline via cytidine-diphosphate-choline interaction. Concentration is also essential for the delivery of choline to the brain in the prevention of neuronal fusion and dementia. The release of choline to the brain is controlled by a low-affinity (not particularly efficient) transporter located in the blood-brain barrier. Transport occurs when plasma arterial concentrations of choline increase above 14 μmol / L, during a spike in choline concentration, for example, after eating choline-rich foods. In contrast, neurons take up choline via high and low affinity transporters. Choline is stored as membrane-bound phosphitidylcholine, which can then be used to synthesize the neurotransmitter acetylcholine. If necessary, acetylcholine is formed, which then passes through the synapse and transmits a signal to the next neuron. Acetylcholinesterase cleaves acetylcholine, and free choline is re-taken into the neuron by a high-affinity transporter.
Closure of the neural tube
Folic acid is the most well-known remedy for preventing neural tube closure (which is why it is added to vitamins for pregnant women). Folic acid metabolism and choline metabolism are interrelated. Both choline and folic acid (via vitamin B12) can act as methyl donors for homocysteine to form, which can then form SAM (S-adenosylmethionine) and act as a methyl donor for DNA methylation. A dietary choline deficiency with normal folate intake can reduce SAM concentrations, suggesting that folate and choline are important sources of methyl groups for SAM production. Inhibition of the uptake and use of choline in mice is associated with neural tube defects, which can also occur in humans. A retrospective case-control study (a study that collects ex post facto data on cases without a researcher) found that women with the lowest daily choline intake had a fourfold increased risk of having a baby with neural tube defects compared with women with higher choline intake.
Effects of Choline on Long-Term Memory in Infants
Dietary choline intake or lack of it during late gestation in rodents is associated with irreversible changes in hippocampal function in adult rodents, including changes in long-term memory. With an increase in choline intake in female rodents approximately four times higher than dietary recommendations at 11-17 days of gestation, an increase in hippocampal cell proliferation and a decrease in apoptosis (programmed cell death) in the fetus are observed. This can happen if choline-deficient cells in culture, as well as in the brain of the fetus of rodents born to a mother with a choline deficiency, do not properly methylate the CDKN3 promoter, a gene that inhibits cell proliferation in the brain. This supports CDKN3 activity by decreasing the proliferation of brain cells. Increased consumption of choline in female rodents improves auditory and visual memory in offspring, and also prevents age-related changes in memory with aging. Various memory tests have shown associations between choline intake in females and improved memory in their offspring, including tests such as the radial arm maze, Morris water maze, passive avoidance paradigms, and attention-seeking measures. The tests have been demonstrated in various rat models, including Sprague-Dawley and Long-Evans, as well as in mice. Test results suggest that choline has the universal effect of choline on fetuses in rodents. However, the mechanism of this effect is not fully understood. Choline affects memory in newborns, presumably due to an increase in the amount of choline in the brain, and thus the amount of acetylcholine that can be produced and released. However, the amount of choline accumulated in the brain after choline consumption by pregnant females is not sufficient to alter the release of acetylcholine. In contrast, female consumption of choline causes an increase in the amount of phosphocholine and betaine in the fetal brain. These data relate to rodents, species with faster brain maturation and more mature brains at birth than humans. In humans, the brain continues to develop after birth and becomes similar in structure to that of an adult about four years after birth. The developing brain of an infant may be influenced by feeding various supplements instead of natural milk, and presumably by differences in the amount of choline in mothers' breast milk, which may, in particular, influence the observed differences in memory and memorization in adults.
Impact of genetic polymorphisms (genetic variations)
With a low dietary intake of choline, some men and women develop organ dysfunction while others do not. The range of choline intake required for normal body function is quite large, ranging from 850 mg / 70 kg / day to 550 mg / kg / day. This difference is due to single nucleotide polymorphisms in the choline pathways (single nucleotide polymorphism changes the RNA code and can subsequently change the location of the protein synthesized from this RNA, resulting in differences in protein functioning between the normal version and the version with single nucleotide polymorphism). For example, folate pathway polymorphisms can limit the use of folic acid for SAM production, which increases a person's dependence on choline for SAM production. PEMT polymorphisms can alter the amount of choline that can be synthesized in the body (by increasing the amount of choline that must be absorbed through the diet). One study showed that a common genetic polymorphism, 5.10 methylenetetrahydrofolate dihydrogenase 1958A (MTHFDI) in folate metabolism, causes a 15-fold increase in the risk of developing signs of choline deficiency in premenopausal women who consume a diet low in choline, as they are not carriers of a single nucleotide polymorphism (p< 0,0001). Влияние этого полиморфизма довольно велико – у 63% включенных в исследование пациентов имелся, по крайней мере, один аллель с полиморфизмом. MTHFD1 аллели, как полагают, способны изменять поток между 5,10-метилен- и 10-формилтетрагидрофолатом, который влияет на наличие 5-метилтетрагидрофолата для метилирования гомоцистеина (в последующем – , а затем – производства SAM). Это означает метилирование большего количества холина, что компенсирует отсутствие участия фолиевой кислоты в этом механизме. В действительности эффектом этого является увеличение риска рождения ребенка с дефектами нервной трубки у матерей с однонуклеотидным полиморфизмом G1958A в MTHFD1. Кроме того, мыши с МТГФР -/- (МТГФР отсутствует) страдают от дефицита холина, что дает основания предполагать, что люди с генетическим полиморфизмом, который изменяет функциональные возможности фермента, могут также испытывать дефицит холина. Однонуклеотидный полиморфизм также наблюдался в гене PEMT (отвечающим за производство холина). Зейцел и соавт. вычислили, что однонуклеотидный полиморфизм имеется в промоторной области гена PEMT, и ученые связали это с повышенной восприимчивостью женщин к дефициту холина. Так как в воздействии этого однонуклеотидного полиморфизма были обнаружены половые различия, Зейцел предположил, что этот однонуклеотидный полиморфизм способен изменять эстрогенное реагирование промоторной области гена PEMT. Эта же группа ученых также обнаружила еще один однонуклеотидный полиморфизм в экзоне 8 (кодирующей части гена) из PEMT с 30% потери функции PEMT и повышенным риском неалкогольной жировой болезни печени. Однако не всегда однонуклеотидный полиморфизм в холин/фолат-родственных генах воздействует на потребности в холине. C677T и A1298C полиморфизмы в MTHFR и A80C полиморфизм в сниженном гене-носителе фолиевой кислоты не были признаны существенными.
Choline and lactation
The human mammary gland is made up of several types of cells, including fat cells, muscle, ductal epithelium, and mammary epithelium (sometimes called oactocyte). In the epithelium of the mammary gland, raw materials for milk, including choline, are secreted. This occurs through the secretion of the apocrine glands, due to the fatty component of milk, when the vacuoles containing the raw material cause the budding of cells into the lumen of the alveoli (mammary secretion glands). From here, milk will be released when stimulated by oxytocin during sucking. The mammary gland can affect the immune system of the newborn, and during lactation it can affect inflammation. The inflammatory signaling pathways, NF-kb and Jak / STAT, are involved in both inflammatory responses and lactation. This emphasizes the role of the mammary gland not only as a source of energy, but also as the most important mechanism for preparing offspring for survival in the outside world.
Choline in breast milk
Choline can be found in milk as free choline, phosphocholine, glycerophosphocholine, sphingomyelin, and phosphatidylcholine. Choline levels in breast milk correlate with maternal choline levels. Choline taken from breast milk affects blood choline levels in infants, suggesting that choline taken from breast milk goes into the fetus's circulatory system. Choline can pass into milk either directly from the maternal circulatory system, or choline-containing nutrients can be obtained from the epithelium of the mammary gland. Choline passes into milk via a choline-specific transporter from the maternal circulatory system to the epithelial cells of the mammary gland. At high concentrations (more than commonly seen in humans), choline can diffuse across the cell membrane into the mammary epithelial cells. At more normal concentrations, it passes through the calcium / sodium-dependent phosphorylation-associated active transporter into the cell. It can also be produced from the mammary epithelium through the N-methyltransferase mechanism. When choline-containing milk is consumed by newborns, choline is used to form acetylcholine, phosphatidylcholine, sphingomyelin, and plasmalogen choline for membrane cell production in mice, with most of the choline in human milk supplied as phosphocholine. James also demonstrated that the hormone insulin can stimulate the release of choline into mammary cells in mice, and prolactin promotes the incorporation of choline into lipids when the cells are simultaneously exposed to cortisol.
Differences between full-term and premature babies and their mothers
Holmes-McNary et al reported that the content of choline in breast milk of prematurely delivered mature mothers was significantly lower than that of mothers who gave birth on time. However, the concentrations of choline esters (choline-containing compounds) did not differ between preterm and preterm mothers. In pre-term mothers, the mammary glands are underdeveloped by the time of milk production. Perhaps because of this, the choline content in such mothers may be below normal. However, Lucas et al. Found significant improvements at 18 months and 7.5-8 years of age in IQ among tube-fed premature infants compared to non-breastfed infants. This suggests that, even if the mammary gland is "not ripe", the benefits of breast milk are still obvious. In addition, premature babies who were fed full-term formula had lower mental activity scores than infants who were fed the special premature formula. However, in premature babies who were fed with expressed breast milk from other mothers and formula for premature babies, this effect was reduced. In support of this, Lucas et al. Also showed that human milk intake is strongly associated with subsequent IQ levels. In addition, a meta-analysis by Anderson et al. Showed that infants born with a low birth weight received more benefits from breastfeeding (in terms of IQ scores later in life) than infants of normal weight who were also breastfed. Drain and Laugermann summarized the meta-analyzes of 24 studies and stated that “breastfed full-term infants [have] an IQ advantage of about five points versus eight points for low birth weight infants. It can be argued that the increase in IQ depends on these values, which has a relatively subtle effect on the individual level. However, the potential impacts at the population level must also be considered. ”
Differences between breast milk and formula
Human milk is a very rich source of choline, and formulas derived from other sources, in particular soy, have a lower total concentration of choline than human milk (and also lack other important nutrients such as long-chain polyunsaturated fatty acids, sialylated oligosaccharides, thyroid-stimulating hormone, neurotensin, nerve growth factor, as well as the enzymes lysozyme and peroxidase). Cow's milk and formula-derived mixtures contain similar or higher levels of glycerophosphocholine compared to human milk, while soy mixtures contain lower concentrations of glycerophosphocholine. Human and cow's milk contain similar concentrations of phosphatidylcholine and sphingomyelin, while soy formulas contain more phosphatidylcholine than human or cow's milk. Soy formulas contain less sphingomyelin than human milk. Sphingomyelin is used to produce myelin, which isolates neurons. Free concentrations of choline in mature human milk are 30-80% lower than in cow's milk or mixtures. Human milk also contains less free choline than human colostrum (a secretion from the mammary gland of mammals produced during the last days of pregnancy and in the first days after childbirth). Phosphocholine is found in especially large quantities in human milk. Overall, formulas, milk and breast milk contain choline in varying amounts and forms, and Holmes-McNary et al suggested that “this may have an impact on the relative balance between the use of choline as a methyl donor (via betaine), a precursor to acetylcholine (via choline) or a phospholipid precursor (via phosphocholine and phosphatidylcholine) ”. This fact is confirmed by Ilkol and co-authors, who found that serum concentrations of free choline with artificial feeding are lower than with breastfeeding. Quote: "Those who suggest that bottle feeding may be the same as breastfeeding will need to provide evidence of their position." Some scholars support this assumption. Lucas et al., Considering the impact of social and educational factors on development, found that preterm babies consuming breast milk through a tube showed more than half the standard deviation upward on IQ tests at 7.5 to 8 years than their peers did not. receiving breast milk. They have also previously found improvement in cognitive development as early as 18 months in premature babies who consume more breast milk compared to those who do not. It has been hypothesized that the increased IQ and performance gains in breastfeeding are due to the interaction between mother and baby, with or without actual milk supply. Drain and Logmann hypothesized that lactation increases the production of oxytocin and prolactin, which induces mothers' feelings of well-being and encourages maternal instinct. This can improve the relationship between mother and child, which can, in turn, generate improved neuronal performance. In addition, social class and maternal education are closely related to the type of infant feeding (formula or breastfeeding) and also correlates with observed differences in cognitive function. Lucas et al., However, disprove the assumption that breast milk fluid itself does not affect a child's cognitive function later in life.
Current Choline Intake Levels in Breastfeeding and Pregnant Women
Shaw et al. Showed that approximately 25% of pregnant women in California consume less than half the daily value of choline.
Breast Milk Choline to Cognition Ratio
As noted earlier, choline is essential for the development of the nervous system and is found in much higher amounts in breast milk than in formula. Choline may play a role in promoting better breastfeeding performance. However, in the meta-analysis discussed, the authors attributed the observed improvement in cognitive function to long-chain polyunsaturated fatty acids such as docosahexaenoic acid and arachidonic acid, which make up the lipid components of the brain. Docosahexaenoic acid is enriched in phospholipids produced through the PEMT mechanism (responsible for choline production). This means that choline production in the body affects the production of docosahexaenoic acid, and may interfere with the transport of docosahexaenoic acid / choline into breast milk. This meta-analysis also states that the difference between mixtures and breastfeeding observed precisely because of the absence of these substances in baby food(in the United States), and there is no data linking dietary choline to choline produced by the body (data on mixtures from other countries were also not provided). Since choline affects brain development and there are differences in choline levels in breast milk and formula, it is possible that choline may also play a role in the observed improvements in IQ scores in breastfed babies.
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Choline is a nutrient compound that is vitamin-like in its composition. It is often called vitamin B4. It got its name from the Greek word that translates as "bile". The fact is that some of the choline can be produced by the liver itself.
Choline functions in the human body
This substance was first recognized as significant for humans in 1998. (choline) has a membrane-protective property, that is, it helps to preserve the cell membrane, ensuring their normal functioning. The walls of the nerve cells are moist and oily. Choline helps maintain the correct consistency. Without it, cholesterol is oxidized and forms compounds with dead protein cells. This leads to the formation of seals: the nerve cell does not receive the necessary nutrients and dies. An important property of choline is to lower blood cholesterol levels. It also has a positive effect on the nervous system, providing an antidepressant effect: in the process, fibers with the ability to transmit nerve impulses are obtained from choline. At the right time, the mechanisms are triggered and hormones are formed that have a positive effect on the performance of the brain and the general condition of a person.
Foods containing vitamin B4
The largest amount of this substance is contained in egg yolk... Choline is part of lipoproteins (therefore, in a large number it is found in oils). So, the liver of animals has a high content of choline. It is also found in dairy products (in particular, in cheese and cottage cheese).
Now let's take a quick look at the question of what is the beneficial effect of choline on the human body.
The cardiovascular system
Choline balances the amount of bad and good cholesterol in the human body well, tipping the balance towards the latter. Thanks to this, it is a good tool in the prevention of cardiovascular diseases.
Nervous system
This vitamin has a relaxing and calming effect. Choline can help fight the signs of depression. The fact is that it prevents the destruction of the protective sheath of nerve cells (myelin). Thanks to this, it allows the nervous system to remain in order for a long time. Doctors also note that choline activates the brain and improves memory. Experiments have shown that after choline was administered to a group of subjects, their memory and intelligence improved. There is also a positive effect of choline on the fetus. While in the womb, the baby cannot produce choline on its own. However, this substance contributes to the formation of higher mental abilities.
Digestive system
Choline is a good hepatoprotector. It allows the liver cells to recover faster from various toxic effects, including alcohol and drugs. In addition, choline prevents the formation of gallstones and excessive bile production. The undoubted advantage of choline is its ability to dissolve fats with the help of enzymes. It helps to avoid liver dystrophy in obesity and can aid in weight loss. Also, thanks to vitamin B4, fat-soluble vitamins (A, E, K) are better absorbed in the human body.
Reproductive value
Choline is one of the substances involved in human reproduction. It increases sperm activity. In addition, thanks to choline, it reduces the risk of inflammation of the prostate gland.
Preparations containing choline
In pharmacies, you can find a number of names, the active ingredient of which is choline. First of all, these are drugs such as Choline Chloride, Choline Alfoscerat, as well as Choline-Borimed, Cerepro, Gliatelin. Each of these drugs has its own focus. So, the drug "Choline chloride" is prescribed for acute and chronic liver diseases, alcoholism or trauma. The drug "Choline alfoscerat" and it and "Gliatelin") are neuroleptics and are prescribed for brain injuries. To replenish the required amount of choline in a healthy body, you can simply contact the pharmacy with a request to give Vitamin B4 (for example, "Duovit Memo", where the content of vitamin B4 is sufficient to replenish the daily requirement). Choline is also prescribed for children. Daily requirement for an adult - 5-6 g, for a child - 4 g.
Choline absorption
Getting through the stomach, choline begins to be absorbed in the intestine along its entire length. Then, with the help of other substances, most often lecithin, it enters the bloodstream and liver. As noted above, choline is a substance that can be synthesized within the body itself. It does this through amino acids and natural metabolism.
Signs of hypovitaminosis
By the following signs, you can determine the lack of choline in your body:
Features of the substance and the consequences of its lack
It should be said that breast milk contains daily rate choline, which is necessary for an adult. The fact is that the baby's brain develops very intensively, and vitamin B4 contributes to its normal development. New and new brain cells and nerve appendages are being formed, and choline is the most important construction material for the brain. Scientists who argue about whether nerve cells in an adult are restored are increasingly inclined to believe that choline can help them revive. All you need is proper nutrition, healthy image life and foods containing vitamin B4 in large quantities. Lack of choline in the body can lead to serious consequences. These include Alzheimer's disease, which affects the elderly. It is accompanied by memory loss and personality disorder. The researchers note that soon the majority of older people will be exposed to it.