Homocysteine ​​test results. Homocysteine: functions, diagnosis and treatment of pathologies. When should you reduce homocysteine?

Homocysteine ​​is an important amino acid that affects many processes in the body. It is synthesized as a result of the metabolism of methionine, a substance found in meat, eggs and some other animal products.

Homocysteine ​​levels increase during pregnancy. This is very dangerous and sometimes ends tragically for the mother and the fetus she is carrying. In older people, this amino acid becomes a catalyst for severe vascular diseases.

Should I be concerned about elevated homocysteine ​​levels?

Homocysteine ​​is a very toxic substance. Its excess in the blood (homocysteinemia) causes vascular damage, which in turn leads to the development of many serious diseases. Take, for example, atherosclerosis. Homocysteinemia is one of the main factors in the development of this difficult-to-treat disease. The mechanism of its appearance is as follows: the walls of the vessels through which blood flows are damaged due to excess homocysteine. Cholesterol plaques then begin to form in the areas where the damage occurred. Over time, they turn into blood clots. This is how atherosclerosis appears.

In addition, a large number of serious illnesses of the cardiovascular system can increase homocysteine ​​levels. Due to the growth of the amino acid, Alzheimer's disease develops, senile dementia, myocardial infarction and heart failure occur. So you really should be afraid of homocysteinemia.

Why high concentrations of homocysteine ​​in the blood are dangerous for pregnant women

Today, many women experience miscarriages due to homocysteinemia. If it occurs in the 3rd–9th months of pregnancy (2nd–3rd trimesters), then there is a danger of asphyxia (suffocation) of the fetus or the formation of late toxicosis (preeclampsia).

Also, pregnant women with elevated levels of homocysteine ​​have a high likelihood of developing problems with the heart and blood vessels, which can cause childbirth to end tragically.

For women with this disorder, trouble awaits them even after childbirth, since their newborn child may suffer from dystrophy and have a weakened immune system.

What Causes High Homocysteine ​​Levels

It is caused by extremely many factors, and not just pregnancy or old age. We list only the most common of them:

• Dependence on harmful substances (drugs, alcohol, cigarettes and coffee). However, it should be noted that small doses of alcohol and no more than one cup of coffee per day even reduce homocysteine ​​levels.
• Postoperative period (in people who have undergone surgery on the gastrointestinal tract).
• Problems with excess weight (even the initial stages of obesity).

Vitamin deficiency is another reason for elevated homocysteine ​​levels. It increases if the body lacks vitamins B1, B6 and B12. Insufficient absorption of folic acid ends in the same way. To get rid of such vitamin deficiency, you need to take care of your stomach and intestines, because it is problems with the absorption of the above substances that lead to homocysteinemia.

There are a number of diseases that provoke an increase in homocysteine ​​levels. These include:

• congenital genetic pathologies (mutations of enzymes whose task is to synthesize methionine);
• hormonal imbalance;
• kidney problems (primarily kidney failure);
• endocrine diseases (mainly diabetes);
• heart and vascular diseases;
• leukemia;
• skin diseases (psoriasis and some others).

It also happens that the appearance of homocysteinemia is caused by the use of drugs. This is especially true for anticonvulsants, drugs for the treatment of autoimmune disorders (immunosuppressants), antimetabolites and folic acid antagonists, which are prescribed for psoriasis.

Pregnant women are often advised to take methionine tablets to help the liver cope better with additional stress. But it is undesirable to do this, since it may result in homocysteinemia.

Recent studies have shown that hormonal contraceptives also increase homocysteine.

Diagnostics

To find out the level of homocysteine ​​in the body, blood is taken from a vein for analysis. The doctor may also prescribe it with a so-called methionine load. Here we mean a comparison of two blood tests: taken on an empty stomach and after a meal (it is this that “loads” the body with methionine).

An analysis that determines the level of homocysteine ​​would not hurt anyone who is predisposed to cardiovascular diseases. It is also advisable to give it to diabetics.

Checking your homocysteine ​​levels is especially important for pregnant women who have had problems during a previous birth. Women expecting a child, whose relatives have had heart attacks, strokes or suffered from thrombosis, also need to be tested for homocysteine.

Ways to normalize homocysteine ​​levels

If homocysteine ​​is slightly elevated, then it is enough to change your living habits so that the level of this dangerous amino acid drops to normal levels. You just need:

• stop using harmful, addictive substances (alcohol, nicotine, coffee);
• start leading an active lifestyle (walk a lot in the fresh air, regularly engage in gentle exercise, visit the pool and jog).

You will also have to radically reconsider your menu and sharply reduce the amount of food high in methionine. This includes any meat, eggs and cheese.

You will need to eat more foods with omega-3 and vitamin B. Fish, vegetables, nuts and brewer's yeast are rich in them. As for omega-3, there is a lot of it in any seafood, especially in fish oil, which is sold in pharmacies.

If the excess of homocysteine ​​in the blood is large, then the above measures will not be enough and treatment cannot be avoided. It is strictly individual and depends on many related factors.

Usually the doctor prescribes taking vitamin B or folic acid. If the patient has vitamin deficiency, that is, his stomach and intestines do not normally absorb vitamins and acids, then the above-mentioned substances are administered using intramuscular injections.

In addition to vitamin B and folic acid, medications that thin the blood and prevent blood clots may be prescribed. Most often, in this case, the doctor prescribes the use of aspirin.

High levels of homocysteine ​​in the blood are fraught with insidious atherosclerosis and other life-threatening diseases. Therefore, you need to keep it normal and for this purpose follow a special diet, do not abuse harmful substances and do not forget about physical exercise.

Photo: Edgar181 - own work, Public domain

Homocysteine ​​- what is it? Few people have ever heard of this medical term, but it turns out that it is an amino acid found in blood plasma. Recently, doctors have recommended taking a blood test to determine the level of this acid. As it turned out, the normal functioning of the cardiovascular system depends on its content. Let's take a closer look at the meaning of homocysteine.

To control homocysteine ​​in the blood, you need to know the process of its formation. What is homocysteine? This is an amino acid formed during the processing of methionine. This is a product of biosynthesis, so it does not enter the body in its pure form. Its level is constantly changing, but a significant increase leads to health problems.

When there is an excess of homocysteine, part of it is converted to methionine. Folic acid, B6, B1 and B12 are involved in this process.

Methionine enters the human body with food; it is found in the following products:

• meat products;
• sour milk;
• eggs.

Homocysteine ​​is present in plasma; it consists of free and bound substances.

Normally, homocysteine ​​accumulates in the body and is excreted from it. For men, the norm is 6.2-15 µmol/ml, and for women - 4.6-12.4 µmol/ml.

The level of homocysteine ​​in the blood changes over time: throughout life, the level of the substance increases, and in women faster than in men. The increase in homocysteine ​​is explained by age-related disorders, for example, a decrease in the functioning of the kidneys, which remove the substance from the body.

What happens if the level of this amino acid increases?

If homocysteine ​​levels increase, it has a toxic effect on cells.

The substance accumulates mainly on the walls of blood vessels, causing damage to the endothelial cells that line the surface of the blood vessels.

This leads to the following health problems:

• blood clot formation;
• circulatory disorders;
• heart diseases;
• Alzheimer's disease;
• dementia.

The walls of blood vessels become loose, so cholesterol and calcium are deposited on the surface. Atherosclerotic plaques form, and the process of thrombus formation intensifies.

With an increase in the substance by 5 µmol/l, the likelihood of atherosclerosis increases by 80% in women, and by 60% in men.

If hyperhomocysteinemia appears in diabetics, the risk of nephropathy, retinopathy, and other vascular complications increases.

An increase in the concentration of the substance necessarily leads to cardiovascular diseases. Mortality from heart disease increases 1.5 times. Heart diseases occupy a leading place among the causes of mortality in the population. Homocysteine ​​is comparable to high blood pressure, which also increases the risk of mortality.

When the level of this substance increases, the following cardiovascular complications occur:

• atherosclerosis;
• coronary heart disease and vascular disease of the lower extremities;
• stroke;
• thrombosis;
• arterial stenosis.

Only lowering the substance in the blood is the best prevention of complications of heart disease.

If, after diagnosis, an increase in homocysteine ​​is detected, then it is necessary to determine the level of the following substances:

• folic acid;
• creatinine;
• thyroid-stimulating hormone;
• vitamin B12.

This will help identify the cause of HHC (hyperhomocysteinemia).

Many factors influence the increase in the level of this substance. Most often, the main cause is vitamin deficiency, that is, vitamin deficiency. The body is sensitive to a lack of B vitamins and folic acid.

In addition to the lack of these substances, the appearance of HHC is influenced by:

1. Smoking. This bad habit is the most powerful stimulant for increasing homocysteine.
2. Excessive coffee consumption. If you drink five cups of coffee every day, your amino acid levels can increase by 3 µmol/ml.
3. Kidney diseases, especially renal failure. If the functioning of this organ is impaired, homocysteine ​​is excreted in insufficient quantities.
4. Passive lifestyle. Moderate physical activity is the prevention of HHC.
5. Use of certain medications. Cyclosporine, Methotrexate, Phenytoin, nitrous oxide and others increase the amino acid content in the blood.
6. Hypothyroidism (thyroid hormone deficiency). This disease occurs due to a malfunction of the thyroid gland.
7. Genetic predisposition. HHC often appears in patients with congenital genetic diseases, such as homocystinuria. This disease is associated with a disorder of homocysteine ​​metabolism.
8. Hormonal diseases and psoriasis also provoke the development of HHC.

Drinking alcoholic beverages has an ambiguous effect on homocysteine ​​levels. With moderate alcohol consumption, the norm decreases, but with excessive alcohol consumption, it increases.

The homocysteine ​​level in women decreases during pregnancy. In the third trimester, homocysteine ​​remains low, but returns to normal two days after the baby is born.

A decrease in substances in women during pregnancy has a positive effect on health, because placental blood circulation improves.

But an increase in homocysteine ​​in pregnant women is a pathological condition. More often this occurs due to a deficiency of B vitamins (B12, B6, B1) and folic acid.

When the amino acid content increases, fetal implantation is disrupted, and the following problems arise:

• abortion;
• venous thromboembolism;
• preeclampsia;
• violation of fetoplacental circulation;
• intrauterine fetal hypoxia;
• acute placental insufficiency.

All of the above violations most often lead to miscarriage or fetal death. Complications of the neonatal period also develop. Children are born with low body weight and reduced vitality reserves.

At later stages, an increase in amino acid levels leads to emergency delivery to save the child’s life. In a woman, HGC in later stages manifests itself as late toxicosis, which brings severe complications during pregnancy.

Unfortunately, most early deliveries with HHC result in the death of the baby or severe neonatal complications.

It is especially necessary to carefully monitor the level of this substance in the blood of women who have previously had problems conceiving or bearing a child.

Signs of increased homocysteine ​​are:

• weight gain;
• swelling;
• decreased diuresis.

Only timely treatment will protect pregnancy.

Today, HHC is one of the causes of antiphospholipid syndrome, which is considered as an autoimmune reaction of the human body to an increase in amino acid levels. Do not forget that homocysteine ​​penetrates the placenta and has a toxic effect directly on the fetus itself.

What is the norm for amino acids during pregnancy?

In pregnant women, a value from 4.6 to 12.4 µmol/ml is acceptable, but deviations from these values ​​should not exceed 0.5 µmol/ml. Otherwise, problems with pregnancy arise.

The following groups of women in labor are at risk for HGC:

• women with a genetic predisposition;
• pregnant for the second time;
• women who have complications during pregnancy.

Homocysteine ​​must be monitored throughout pregnancy.

HHC also affects the ability to conceive a child. Violation leads to infertility.

Homocysteine ​​levels should be checked in the following population groups:

1. All people who suffer from high blood pressure, coronary heart disease or a tendency to form blood clots.
2. All patients over the age of 40 who have had a stroke, heart attack or thrombosis, as well as people of this age whose relatives suffered from heart disease.
3. It is mandatory to check the level of this substance in pregnant women who have previously had obstetric problems or complications during pregnancy.
4. Diabetics who have vascular complications.
5. Women who are planning pregnancy.

Additionally, a test for homocystinuria may be prescribed if there are signs of this genetic disease.

When levels are elevated, homocysteine ​​is removed from the blood to protect cells from toxic effects.

When hyperhomocysteinemia is diagnosed, fairly simple treatment is prescribed. As a rule, therapy is effective if complications do not appear. Otherwise, treatment of the resulting diseases begins.

How is this disease diagnosed? Homocysteine ​​and its norm are important indicators. To do this, donate blood to check homocysteine ​​levels. In some cases, samples with methionine are used. To do this, the examination is carried out twice: on an empty stomach and after methionine enters the body.

It is worth noting that absolutely healthy people can undergo examination to determine the likelihood of vascular and heart disease in order to take preventive measures in time.

The sooner the disorder is identified, the easier it is to bring the amino acid level back to normal and avoid serious health problems.

What should patients who have been diagnosed with HHC do? After diagnosis, the cause of this condition must be determined. If the problem is a lack of vitamins, then high doses of group B substances and folic acid are prescribed.

Vitamin deficiency is often associated with disorders of the digestive tract. In this case, simultaneously with taking vitamin-containing medications, a gastrointestinal (gastrointestinal) examination is prescribed. If homocysteine ​​does not decrease, then vitamins are administered intramuscularly.

When the norm is reached, the dose of vitamins is reduced, but their administration is not stopped.

Before planning a pregnancy, women are tested for homocysteine ​​levels. If it is elevated, vitamin therapy is prescribed.

Be sure to reduce the impact of adverse factors:

• you need to stop drinking coffee;
• get rid of bad habits;
• change a sedentary lifestyle to an active one.

Be sure to eat a balanced diet that contains B vitamins and folic acid. In some cases, blood thinners are prescribed.

When pregnancy occurs, you must regularly visit your doctor, monitor your diet and undergo all necessary examinations.

For a normal pregnancy, women who previously had amino acid abnormalities should take care of their health throughout the nine months and regularly see their gynecologist.

Homocysteine ​​is an amino acid that is formed in the body during the processing of methionine, an essential human amino acid. This amino acid was called essential due to the fact that it is not formed in the body by itself, but comes only from protein foods of animal origin.

Methionine is found in sufficient quantities in eggs, meat, dairy and other products rich in B vitamins. Throughout life, the level of homocysteine ​​in a person’s blood changes. It usually increases with age. Before puberty, both girls and boys have approximately the same level of homocysteine ​​and is about 5 µmol/l.

After puberty, its level increases. Men have higher levels of homocysteine ​​in the blood than women. The older a person is, the more likely it is that a blood test will reveal elevated levels of homocysteine. This is explained by the fact that age-related changes occur in the kidneys in the human body. Homocysteine ​​is usually elevated in overweight people.

During pregnancy, homocysteine ​​is usually low. Blood circulation in the placenta and intrauterine development of the fetus depend on it. This amino acid promotes successful conception and successful pregnancy.

Normal homocysteine ​​levels in the blood

Homocysteine ​​- normal:

• for men 5.9-16.0 µmol/l;
• for women 3.4-20.4 µmol/l

Homocysteine ​​is elevated

Homocysteine ​​is continuously synthesized in the human body, then decomposed, resulting in its normal concentration in the blood. But if a malfunction occurs in the body, the level of homocysteine ​​can increase sharply, which can lead to the development of many dangerous diseases.

An increase in homocysteine ​​in human blood (hyperhomocysteinemia - HHC) can be caused by for the following reasons:

• vitamin deficiency is the most common cause of increased homocysteine ​​in the blood. The body is especially sensitive to a lack of vitamins B-1, B-6 and B-12, as well as a lack of folic acid;
• renal dysfunction;
• hormone-dependent diseases;
• excessive consumption of drinks containing caffeine - one of the most powerful factors that increases homocysteine ​​in the human blood is the consumption of large amounts of coffee. People who drink 6 or more cups of coffee per day have homocysteine ​​levels 2-3 µmol/l higher than people who do not abuse coffee drinks;
• smoking - there are suggestions that people who smoke have elevated levels of homocysteine;
• Physical inactivity (sedentary lifestyle) also leads to an increase in homocysteine ​​levels in the blood. Conversely, moderate physical activity reduces its level in the blood;
• Alcohol abuse leads to an increase in homocysteine ​​in the blood, and drinking a small amount of alcohol, on the contrary, reduces its level.

The accumulation of homocysteine ​​in the body is dangerous because large amounts of it corrode and damage the internal walls of blood vessels. The body tries to heal these damages by compensating for them with calcium deposits or cholesterol plaques. As a result, this leads to the fact that the lumen of the vessel becomes smaller and becomes clogged over time, which leads to the formation of a blood clot. The consequences of this condition are extremely severe, including death.

An increase in homocysteine ​​by 5 µmol/l in the blood entails an increase in the risk of atherosclerotic vascular damage in men by 60%, in women by 80%. A condition where homocysteine ​​is elevated increases the risk of senile dementia and Alzheimer's disease. When diabetes mellitus and hyperhomocysteinemia are combined, vascular complications often develop - retinopathy, nephropathy, peripheral vascular disease, etc.

During pregnancy, an increase in homocysteine ​​levels is extremely undesirable. This can cause eclampsia, preeclampsia, venous thromboembolism, and also cause spontaneous abortion.

Homocysteine ​​is reduced

A condition where homocysteine ​​is low is often observed in diseases such as multiple sclerosis. Typically, homocysteine ​​is also low during pregnancy - at the end of the second, beginning of the third trimester. A decrease in this indicator in this period favors the onset of placental circulation. Then, a gradual increase in homocysteine ​​is observed.

True, too critical a deviation from the norm can negatively affect the condition of the expectant mother and her child, therefore, at a level of 4.1 µmol/ml, the doctor prescribes the woman to reduce physical activity and drink a cup of coffee in the morning

Indications for analysis

Indications for a blood test for homocysteine ​​levels are:

• patients with a history of arterial or venous thrombosis;
• patients with diabetes mellitus;
• persons receiving glucose-lowering, anticonvulsants, cytostatics;
• women with a burdened obstetric history, or patients whose blood relatives under 40-45 years of age suffered heart attacks, strokes or thrombosis;
• persons who have undergone gastric surgery;
• senile dementia or Alzheimer's disease;
• pregnant women;
• persons aiming to determine the risk of cardiovascular diseases.

Preparing for a homocysteine ​​blood test

Every person needs to know their level of homocysteine ​​in the blood, since a critical deviation from the norm may go unnoticed by you and lead to serious consequences over time. To check the level of homocysteine ​​in the body, you need to donate blood from a vein in the morning strictly on an empty stomach. The material that will be used for the study is blood serum.

To obtain a reliable result, the patient is informed in advance that during the day before blood is taken for analysis, he must avoid physical activity, drink alcohol and fatty foods. It is recommended to drink only plain water. The result will be known in 2 days.

Homocysteine ​​is a product of the conversion of methionine, one of the eight essential amino acids. From homocysteine, another amino acid, cysteine, which is not one of the essential amino acids, can subsequently be formed.

Excess homocysteine ​​that accumulates in the body can be converted back into methionine. Cofactors for enzymes in the methionine metabolic pathways in the body are vitamins, the most important of which are folic acid, pyridoxine (vitamin B6), cyanocobalamin (vitamin B12) and riboflavin (vitamin B1).

Homocysteine ​​is not a structural element of proteins, and therefore does not enter the body with food. Under physiological conditions, the only source of homocysteine ​​in the body is the conversion of methionine.

Homocysteine ​​has a pronounced toxic effect on the cell. To protect the cell from the damaging effects of homocysteine, there are special mechanisms for removing it from the cell into the blood. Therefore, if an excess of homocysteine ​​appears in the body, it begins to accumulate in the blood, and the main place of the damaging effect of this substance becomes the inner surface of the blood vessels.

To convert excess homocysteine ​​to methionine, high concentrations of the active form of folic acid (5-methyltetrahydrofolate) are required. The main enzyme that converts folic acid into its active form is 5,10 methylenetetrahydrofolate reductase (MTHFR). A decrease in the activity of this enzyme is one of the important reasons for the accumulation of homocysteine ​​in the body. (Fig. 1)

Please note that homocysteine ​​can only be formed from methionine. Homocysteine ​​can be converted either to cystathionine, which is subsequently used for the synthesis of cysteine, or to methionine. Vitamins play an important role in all key stages of methionine and homocysteine ​​metabolism. Red indicates the methionine conversion cycle, green indicates the folic acid conversion cycle. MTHFR - 5,10 methylenetetrahydrofolate reductase.
Methionine, homocysteine ​​and folic acid are amino acids. Amino acids are the most important substrates for nitrogen metabolism in the body. Proteins, enzymes, purine and pyrimidine bases (and nucleic acids), pyrrole derivatives (porphyrins), biologically active compounds of peptide nature (hormones), as well as a number of other compounds originate from amino acids. When needed, amino acids can serve as a source of energy, mainly through the oxidation of their carbon skeleton.
In living organisms, amino acids form a pool, the value of which in adulthood remains constant under physiological conditions. It corresponds to the difference between the supply of amino acids from the outside or sometimes from endogenous sources, and the consumption of amino acids that serve as substrates in anabolic and catabolic processes. Living organisms do not store amino acids and proteins for future use, so the required amount of nitrogen (preferably in the form of amino acids) must come from food. In an adult body under physiological conditions, the amount of nitrogen entering and exiting is the same (nitrogen balance).
Amino acids from exogenous sources (from food) are absorbed in the digestive tract and transported by the blood to the liver and other tissues and organs, where they are further used. In addition, the source of amino acids (endogenous source) can be tissue proteins of the body, which are constantly subject to metabolism to release the amino acids they contain. These amino acids are used to a small extent for the synthesis of new proteins, but endogenous sources are very important because they provide about two-thirds of the total amino acid pool, and only one-third of the amino acids come from food.
Essential amino acids are those amino acids that cannot be synthesized by a given body. For humans, these are valine, leucine, isoleucine, lysine, methionine, threonine, phenylalanine, tryptophan and, under certain conditions, also arginine and histidine.

Background

In 1932, De Vigneaud discovered homocysteine ​​as a product of methionine demethylation. A few years later, a second pathway for homocysteine ​​metabolism was discovered - transsulfuration. In 1962, homocyteinuria syndrome (homocysteine ​​in the urine) was discovered, associated with a deficiency of the enzyme cystathionine synthase. This disease causes mental retardation, bone deformities, lens displacement, progressive cardiovascular disease, and a very high incidence of thromboembolism. Kilmer McCully studied in depth patients with high levels of homocysteine ​​in the blood and found a link between hyperhomocysteinemia and the development of severe vascular disease. These studies served as the basis for the homocysteine ​​theory of atherosclerosis that he proposed in 1975. He was convinced that there was a connection between homocysteine ​​levels, vitamin deficiency and heart disease.

Research over the past 15 years has confirmed and deepened the homocysteine ​​theory of the development of vascular disorders. Every year dozens of publications appear devoted to different aspects of this problem. However, unfortunately, at present only a few laboratories can determine the level of homocysteine ​​in the blood.

Causes of increased homocysteine ​​levels in the blood

Homocysteine ​​levels in the blood gradually increase throughout life. Before puberty, homocysteine ​​levels are approximately the same in boys and girls (about 5 µmol/L). During puberty, homocysteine ​​levels rise to 6-7 µmol/l; in boys this increase is more pronounced than in girls.

In adults, homocysteine ​​levels fluctuate around 10-11 µmol/ml; in men this figure is usually higher than in women. With age, homocysteine ​​levels gradually increase, and in women the rate of increase is faster than in men. The gradual increase in homocysteine ​​levels with age has been attributed to decreased kidney function, and higher homocysteine ​​levels in men have been attributed to greater muscle mass.

During pregnancy, normal homocysteine ​​levels tend to decrease. This decrease usually occurs at the border of the first and second trimesters of pregnancy, and then remains relatively stable. Normal homocysteine ​​levels are restored 2-4 days after birth. It is believed that a decrease in homocysteine ​​levels during pregnancy favors placental circulation. The level of homocysteine ​​in the blood is inversely proportional to the weight of the fetus and newborn.

Homocysteine ​​levels in the blood can increase for many reasons. One of the factors is an increased intake of methionine from food. Therefore, during pregnancy, additional administration of methionine tablets, still practiced by some doctors, should be carried out with caution and under the control of homocysteine ​​levels. The most common causes of increased homocysteine ​​levels are vitamin deficiency conditions. The body is especially sensitive to a lack of folic acid and vitamins B6, B12 and B1. It is assumed that smokers have an increased tendency to hyperhomocysteinemia. Consuming large amounts of coffee is one of the most powerful factors in increasing homocysteine ​​levels in the blood. Individuals who drink more than 6 cups of coffee per day have homocysteine ​​levels that are 2-3 µmol/L higher than those who do not drink coffee. It is assumed that the negative effect of caffeine on homocysteine ​​levels is associated with changes in kidney function. Homocysteine ​​levels often increase with a sedentary lifestyle. Moderate physical activity helps reduce homocysteine ​​levels in hyperhomocysteinemia. Drinking small amounts of alcohol can lower homocysteine ​​levels, while large amounts of alcohol increase homocysteine ​​in the blood.

Homocysteine ​​levels are affected by a number of medications. The mechanism of their action may be related to the effect on the action of vitamins, homocysteine ​​production, kidney function, and hormone levels. Of particular importance are methotrexate (a folic acid antagonist, often used to treat psoriasis), anticonvulsants (phenytoin, etc., deplete folic acid reserves in the liver), nitrous oxide (a drug used for anesthesia and for pain relief in childbirth, inactivates vitamin B12), metformin (a drug used to treat diabetes mellitus and polycystic ovary syndrome) and H2 receptor antagonists (affect the absorption of vitamin B12), aminophylline (inhibits the activity of vitamin B6, often used in obstetric hospitals for the treatment of gestosis). Homocysteine ​​levels may be adversely affected by taking hormonal contraceptives, but this is not always the case.

Another factor that contributes to increased homocysteine ​​levels is certain concomitant diseases. The most important of these are vitamin deficiency conditions and renal failure. Thyroid diseases, diabetes mellitus, psoriasis and leukemia can contribute to a significant increase in homocysteine ​​levels in the blood.

One of the main causes of vitamin deficiency conditions leading to hyperhomocysteinemia are diseases of the gastrointestinal tract, accompanied by impaired absorption of vitamins (malabsorption syndrome). This explains the higher incidence of vascular complications in the presence of chronic gastrointestinal diseases, as well as the fact that with B12 vitamin deficiency, the common cause of death is not anemia, but strokes and heart attacks.

One of the important factors contributing to the increase in homocysteine ​​in the blood is hereditary predisposition. The most studied is a defect in the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR). MTHFR mediates the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is the main circulating form of folic acid in the body. In turn, folic acid is used in many biochemical pathways, including the methylation of homocysteine ​​and other substances and the synthesis of nucleotides. The MTHFR gene is located on chromosome 1 at locus 1p36.3. There are several allelic variants of this enzyme that cause severe MTHFR deficiency, but most of these variants are very rare. Two alleles are of practical importance: the heat-labile allele C677T and the allele A1298C (sometimes referred to as C1298A). The C677T allele is the result of a point mutation in which alanine is replaced by valine at position 677. In this case, the normal genotype is designated as CC (normal gene variants on both chromosomes), heterozygous - as CT (carrier, on one chromosome - a normal gene, and on the other - mutant), genotype homozygous for a mutant gene - as TT (mutant on both chromosomes). gene). Currently, DNA diagnostics of the C677T mutation is carried out in some medical centers in Moscow. The features of this mutation are presented in Fig. 2.

Rice. 2 C677T polymorphism of 5,10 methylenetetrahydrofolate reductase (MTHFR) affects the distribution of folic acid compounds (highlighted in green), used for the synthesis of DNA and RNA, and 5-methyltetrahydrofolate, necessary for the remethylation of homocysteine ​​(Hcy), and therefore for the synthesis squirrel. The pie chart shows the genotype distribution typical of European populations, and the sizes of the arrows indicate the relative enzyme activity of MTHFR.
Abbreviations: AdoMet, S-adenosylmethionine; CHOTHF, formyltetrahydrofolate; CHTHF, methenyltetrahydrofolate; CH2THF, 5,10-methylenetetrahydrofolate; CH3DNA, methylated DNA; CH3THF, 5-methyltetrahydrofolate; DHF, dihydrofolate; dTMP, dioxythymidine 5'-monophosphate; dUMP, deoxyuridine 5'-monophosphate; FAD, flavin adenine dinucleotide; Hcy, homocysteine; Met, methionine; THF, tetrahydrofolate; protein, protein; DNA, DNA; RNA, RNA; purines, purine bases. CC and TT are homozygous genotypes, CT is a heterozygous genotype.
When enzyme activity decreases, there may not be enough 5-methyltetrahydrofolate to effectively convert homocysteine ​​to methionine, and homocysteine ​​begins to accumulate in the body.

Table 1. Common causes of various degrees of hyperhomocysteinemia

1 Data on the causes of homocysteinemia and its frequency are based on European studies. These data may vary significantly among different populations. According to our data, the frequency of moderate hyperhomocysteinemia in Moscow significantly exceeds the European average. A moderate increase in homocysteine ​​in Muscovites is often detected even when taking large doses of vitamins, which may be associated with a high incidence of disturbances in the absorption of vitamins in the stomach and intestines.
Abbreviations: CBS - cystathionine beta synthase

Hyperhomocysteinemia and pregnancy pathology

Hyperhomocysteinemia leads to damage and activation of endothelial cells (the cells lining blood vessels), which significantly increases the risk of developing thrombosis. Not all details of the mechanism of the pathological action of hyperhomocysteinemia have been fully studied, but much is already known.

The thrombogenic effect of homocysteine ​​may be associated with damage to endothelial cells, nonspecific inhibition of prostacyclin synthesis, activation of factor V, inhibition of protein C activation, down-regulation of thrombomodulin expression, blockade of tissue plasminogen activator binding by endothelial cells. In addition, high homocysteine ​​levels increase platelet aggregation due to decreased endothelial synthesis of relaxing factor and NO, induction of tissue factor, and stimulation of smooth muscle cell proliferation.

Microthrombi formation and microcirculation disorders lead to a number of obstetric complications. Disorders of placentation and fetoplacental circulation can cause reproductive failure: miscarriage and infertility as a result of defects in embryo implantation. In later stages of pregnancy, hyperhomocysteinemia causes the development of chronic fetoplacental insufficiency and chronic intrauterine fetal hypoxia. This leads to the birth of children with low body weight and a decrease in the functional reserves of all life-supporting systems of the newborn and the development of a number of complications during the newborn period.

Hyperhomocysteinemia may be one of the reasons for the development of generalized microangiopathy in the second half of pregnancy, manifested in the form of late toxicosis (preeclampsia): nephropathy, preeclampsia and eclampsia. Hyperhomocysteinemia is characterized by the development of severe, often uncontrollable conditions that can lead to early termination of pregnancy for medical reasons. The birth of an immature premature baby in such cases is accompanied by high infant mortality and a high percentage of neonatal complications.

Homocysteine ​​freely crosses the placenta and can have teratogenic and fetotoxic effects. It has been proven that hyperhomocysteinemia is one of the causes of anencephaly and obstruction of the medullary canal ( spina bifida). Anencephaly leads to 100% mortality, and spina bifida- to the development of serious neurological problems in the child, including motor paralysis, lifelong disability and premature death. A direct toxic effect of excess homocysteine ​​levels on the fetal nervous system cannot be excluded.

Hyperhomocysteinemia can be not only the cause, but also a companion to obstetric complications. It is assumed that in some cases problems may be associated not only with high homocysteine ​​levels, but also with those conditions that cause the development of hyperhomocysteinemia (vitamin deficiency conditions, concomitant diseases, etc.)

It should be remembered that hyperhomocysteinemia can be accompanied by the development of secondary autoimmune reactions and is currently considered as one of the causes of antiphospholipid syndrome. Autoimmune factors can interfere with the normal development of pregnancy even after high homocysteine ​​levels are eliminated.

Diagnosis of hyperhomocysteinemia

To diagnose hyperhomocysteinemia, the level of homocysteine ​​in the blood is determined. For the differential diagnosis of various forms of homocysteinemia, stress tests with methionine are sometimes used (determining the level of homocysteine ​​on an empty stomach and after a methionine load).

To find out the causes of hyperhomocysteinemia, DNA diagnostics of hereditary defects in enzymes involved in the metabolism of methionine and folic acid, in particular MTHFR, and determination of the level of vitamins B6, B12, B1 and folic acid in the blood are carried out.

If high levels of homocysteine ​​in the blood are detected, tests are recommended to exclude additional risk factors for the development of vascular and obstetric complications. We recommend a hemostasiogram, a blood test for lupus anticoagulant, a test for antiphospholipid and anti-DNA antibodies, anti-thyroid antibodies, anti-nerve growth factor antibodies, and a blood test for hereditary hemostatic defects (Leiden mutation and hereditary prothrombin defects). Other tests may be prescribed according to indications.

Indications for a blood test for homocysteine

Given the seriousness of the possible consequences of hyperhomocysteinemia, the Center for Immunology and Reproduction recommends that all women preparing for pregnancy have their homocysteine ​​levels checked. It is mandatory to check homocysteine ​​levels in patients with previous obstetric complications and in women whose relatives had strokes, heart attacks and thrombosis before the age of 45-50 years.

Treatment of hyperhomocysteinemia

If hyperhomocysteinemia is detected, specially selected therapy is carried out with high doses of folic acid and B vitamins (B6, B12, B1). Considering that in many cases a vitamin deficiency state is associated with impaired absorption of vitamins in the gastrointestinal tract, treatment usually begins with intramuscular administration of B vitamins. After homocysteine ​​levels have decreased to normal (5-15 mcg/ml), maintenance doses are prescribed vitamins per os.

During pregnancy, antiplatelet therapy may be indicated (small doses of aspirin, which in this case acts as a kind of pregnancy vitamin, small doses of heparin drugs). If antiphospholipid syndrome is present, additional treatment may be prescribed.

Hyperhomocysteinemia is a pathological condition, the timely diagnosis of which in the vast majority of cases makes it possible to prescribe simple, safe and effective treatment, which reduces the risk of complications in mother and child tenfold.

Most likely, only those involved in medicine or chemical production know what homocysteine ​​is. However, this amino acid, containing sulfur and nitrogen, is essential for the body.

The optimal homocysteine ​​level is low because it is affected by certain substances. As a result, this amino acid is transformed and removed from the body.

By studying its concentration in the blood plasma, one can first predict and then prevent the development of many ailments, including cardiovascular diseases.

Normal homocysteine ​​level

Homocysteine ​​levels change throughout a person's life. Its normative content depends on both gender and age. The amount of amino acid in the blood of men is greater than that of women.

Reference values ​​for homocysteine ​​are:

With age, the amino acid content increases and approaches the maximum value.

It has been recorded that up to the age of fifty, men almost always have more homocysteine ​​than the fair sex. But after a woman also turns 50, her amino acid levels begin to increase rapidly.

Normal homocysteine ​​levels during pregnancy

When a woman is pregnant, natural changes inevitably occur in her body. This also applies to homocysteine. Its content is slightly different from usual.

For pregnant women, homocysteine ​​levels are in the following range (µmol/ml):

• minimum – 4.6;
• maximum – 12.4.

More detailed optimal homocysteine ​​levels by trimester are as follows:

The permissible deviation in both directions is 0.5 µmol/ml. More significant fluctuations have a negative impact on women's well-being.

The expectant mother's homocysteine ​​level decreases slightly, and this is not considered a pathology. The decrease in the amount of the substance is especially noticeable in the early stages of pregnancy: between the first and second trimester. Return to normal limits occurs four or five days after birth.

Reduced homocysteine ​​levels are safe for an unborn baby. According to doctors, it even improves blood supply to the placenta and nutrition of the fetus.

But not everything is so rosy. A significant deviation from the norm can affect the health of the expectant mother. Therefore, it is possible that the doctor will advise you to drink a small cup of coffee for breakfast and get more rest.

But increasing the level of a substance is always dangerous. Often this is what leads to premature termination of pregnancy in the early stages. In the last trimester, serious complications such as eclampsia and venous thromboembolism are possible.

Women should be especially careful:

• pregnant with their second child;
• with a genetic predisposition;
• with pregnancy complications.

An increased level of homocysteine ​​in the blood can cause the birth of a child with low body weight. Such babies often get sick because their immunity is reduced. The reason is that the fetus absorbs homocysteine, which negatively affects its further development.

To carry a child without problems, you will have to constantly monitor the amino acid level. If abnormalities are detected, the doctor will most likely prescribe vitamin therapy.

Normal homocysteine ​​levels in children

In young patients, the homocysteine ​​level is significantly lower than in adults. Until they reach 12 years of age, it does not depend on the gender of the child and is 5 µmol/l.

With the onset of adulthood, the amino acid content increases. The substance rate established for adolescents under sixteen years of age is as follows (µmol/l):

• boys – up to 7.0;
• girls – up to 6.0.

In boys, the optimal amount of homocysteine ​​is slightly higher than in girls. This situation continues into adulthood.

Deviation from the norm

The body does not obtain homocysteine ​​from food. Its biosynthesis is a complex multi-stage process. Homocysteine ​​is formed from one of the essential amino acids - methionine, which comes only from food: eggs, meat, fish, nuts. The list of food sources of the substance is considerable.

In a healthy body, homocysteine ​​is constantly synthesized and decomposed. It is important that both of these processes are in balance. The concentration of homocysteine ​​is low, and even a slight deviation from the norm affects health. Its content can increase significantly, which will provoke the emergence of dangerous diseases.

Homocysteine ​​above normal: reasons

Disturbances in homocysteine ​​balance and its excess growth can be caused by the following reasons:

• deficiency of vitamins, especially group B (B1, B6, B12), folic acid;
• kidney dysfunction;
• hormonal abnormalities;
• psoriasis;
• diabetes;
• lymphoblastic leukemia;
• Addison-Biermer anemia.

Hereditary causes should also be taken into account. In particular, one can distinguish a genetic predisposition to thrombosis, homocystinuria, which is characterized by impaired methionine metabolism.

An increase in amino acids can be triggered by taking medications: phenytoin, cyclosporine, methotrexate, carbamazepine.

There are also natural factors that violate the norm:

• A sedentary lifestyle greatly contributes to increasing homocysteine ​​levels.
• Drinking large quantities of coffee. Six or more cups of drink per day can increase the concentration of the substance by two or three units.
• A common bad habit is smoking.

Addiction to alcoholic beverages increases homocysteine ​​levels, and daily small amounts of alcohol decreases them.

Consequences

When homocysteine ​​accumulates in the body, the walls of blood vessels are corroded and damaged. Excess amino acids contribute significantly to this.

The body tries its best to make the damage heal: it deposits calcium and cholesterol plaques. The lumen of the vessels decreases, and the likelihood of thrombus formation increases. This is especially dangerous for those who have diabetes. Serious consequences are possible, and death is not excluded.

Exceeding homocysteine ​​by 5 units increases the risk of developing atherosclerosis in men by 60%, in women – by 80%.

Numerous clinical studies have led to a disappointing conclusion: if the amino acid norm is one and a half times higher, the likelihood of premature death from heart and vascular diseases increases by 70%.

At an advanced age, there is a danger of developing senile dementia and Alzheimer's disease.

By enriching your diet with B complex vitamins, you can reduce the amino acid level by a third. Elderly people who are at high risk of myocardial infarction may benefit from these medications.

Homocysteine ​​is reduced

A decrease in homocysteine ​​levels is uncommon. It is observed in patients with multiple sclerosis, a chronic disease that affects the brain and spinal cord.

As noted above, the amino acid content decreases in pregnant women in the early stages of gestation. This condition is positive, since a decrease in homocysteine ​​levels has a beneficial effect on the onset of placental circulation.

It happens that a decrease in the concentration of an amino acid occurs due to a dysfunction of the enzymes that are involved in its synthesis. This requires a thorough examination and treatment of ailments by specialized specialists. All other cases of decreased homocysteine ​​are safe. A healthy person can easily increase its content by adding methionine-rich foods to the menu.

Homocysteine ​​test

A blood test for homocysteine ​​content is necessary to realistically assess the risk of developing heart and vascular diseases. For a more complete picture, it is advisable to simultaneously determine the concentration of cholesterol, lipoproteins, and fibrinogen.

Venous blood is examined. The test must be performed in the morning, observing standard conditions before the procedure: postponing breakfast and taking medications until later.

Vascular diseases, in particular atherosclerosis, are serious and insidious enemies of modern man. Elevated levels of homocysteine ​​often become a factor provoking these ailments.

Maintaining optimal amino acid content in the body, moving more, eating right are simple conditions, the observance of which will preserve clean blood vessels, a clear mind and a healthy active life for a long time.

Photo: Edgar181 - own work, Public domain