Vitamins and oncopathology: a modern view from the perspective of evidence-based medicine. Folic acid: rules of administration, dosage, risks of developing cancer Folate-dependent malignant tumors

Not all vitamins can be synthesized by our body itself, so people receive many of them through the food they eat. In this article we will understand what folate and folic acid are, what is their difference and what is the effect of these substances on the body.

Folate and folic acid

The terms "folate" and "folic acid" are often used interchangeably. The only difference between the two is that folate is a naturally occurring substance. Known as vitamin B9. Folic acid is a synthetic substance that does not occur naturally, but is also known as vitamin B9. Both of these substances interact in the body almost identically, with the only difference being that the synthetic form (folic acid) is absorbed more easily in the intestines than folate. And this is very unusual, since synthetic forms of nutrients are usually absorbed more slowly than natural ones.

Folic Acid Formula

Meaning of Folic Acid/Folate

Like many B vitamins, this acid is essential for a huge number of biological functions, playing an important role in DNA protection, repair and replication, and is essential for cell division and growth. Since DNA plays an important role in cell division, it is important for pregnant women to make sure they are getting enough folic acid, as the fetus undergoes rapid cell division and therefore has a very high demand for folate. Lack of folic acid is becoming the most common cause of birth defects. One such defect is spina bifida, which results from a partially formed neural tube.

Any rapidly dividing cells in the body have a high need for folate. This applies to sperm production, red blood cell production, nail and hair growth.

Foods High in Folate/Folic Acid

Greens (such as spinach) or legumes are foods high in folic acid. Spinach contains one of the highest concentrations of folate, with 1 serving equaling approximately 15% of the RDA. Therefore, doctors often prescribe folate/folic acid to pregnant women. However, they need it in large quantities, so folate-fortified foods alone are not enough. During pregnancy, folate in the body is consumed especially quickly, which can lead to a deficiency of this substance, therefore, in order to avoid further consequences, a woman carrying a child takes folic acid medications. The dosage should be sufficient for both the woman expecting a child and her fetus. Otherwise, the fetus may develop various pathologies, which often leads to premature birth.


Deficiency and overdose

In addition to the previously discussed defect - spina bifida - a lack of folic acid can cause anemia, diarrhea and vomiting. Deficiency also affects normal brain function, which can manifest as depression or anxiety. Folate deficiency is rare in the general population (especially now that there are so many foods fortified with folic acid) but is common among pregnant women. This is due to the fact that their body requires folate in high concentrations. Folic acid has a very complex interaction with vitamin B12 - a deficiency of one can mask the symptoms of the other, which is why people suffering from folate deficiency may not notice it for a long time.

An overdose of folic acid is practically impossible, since this acid is water-soluble and is excreted from the body along with urine. The only negative side effect of consuming large amounts of folate will be to mask vitamin B12 deficiency, which can lead to nerve damage.

There is concern that folic acid may promote the growth of an existing malignant tumor. This happens because cancer cells replicate extremely quickly and have a huge need for folic acid: the more a person consumes folate/folic acid, the faster his tumor grows.

Folate and folic acid - what is the difference?

So, folate and folic acid are chemically identical, the only difference is that folate is a natural form, and folic acid is a synthetic one, both of these substances are known as vitamin B9. They behave the same in the body, but the synthetic form is more bioavailable (that is, easier to digest). Folic acid plays a number of complex roles in the human body, and is particularly important in the replication and maintenance of DNA, making it an essential part for cell growth. It is most common in leafy greens and is especially important for pregnant women. Folate overdose is rare, but can mimic vitamin B12 deficiency, and this acid can accelerate the development of already established cancer cells. However, using folic acid does not increase the risk of cancer.

People have known about the benefits of vitamin B9 (folic acid) for a long time, but only relatively recently doctors began to actively promote the use of this substance among the population. Folic acid is prescribed during pregnancy and is included in complex therapy in the treatment of heart diseases. There is a lot of debate about the extent to which this vitamin can provoke the development of cancer or whether it is an inhibitory factor in the growth of cancer cells. Only one thing is indisputable - every person’s body needs folic acid, but its intake is especially important for women.

Features of folic acid

The benefits of vitamins and minerals are known to everyone. Many of us know what calcium and magnesium are, why iron is needed in the body and what effect vitamins B6, B12, A and C, PP and D have. Vitamin B9 remains undeservedly forgotten - folic acid, in which the active substance is folate.

Note:Folic acid cannot be produced by the body itself, and its ability to accumulate in tissues and organs is zero. Even if a person introduces the maximum amount of foods containing vitamin B9 into his diet, the body will absorb less than half of the original volume. The main disadvantage of folic acid is that it destroys itself even with slight heat treatment (storing the product in a room at room temperature is enough).

Folates are a fundamental component in the process of DNA synthesis and maintaining its integrity. In addition, it is vitamin B9 that promotes the body’s production of specific enzymes that are actively involved in the prevention of the formation of malignant tumors.

Lack of folic acid in the body was detected in people aged 20-45 years, in pregnant and lactating women. This can lead to the development of megaloblastic anemia (oncology associated with decreased DNA synthesis) and the birth of children with developmental defects. There are also certain clinical symptoms that indicate a lack of folic acid in the body - fever, often diagnosed inflammatory processes, disorders of the digestive system (diarrhea, nausea, anorexia), hyperpigmentation.

Important:natural folic acid is absorbed much worse than synthetic one: taking 0.6 mcg of the substance in the form of a medication is equal to 0.01 mg of folic acid in its natural form.

How to take folic acid

The National Academy of Sciences published general guidelines for the use of folic acid back in 1998. The dosage according to these data will be as follows:

  • optimal – 400 mcg per day per person;
  • minimum – 200 mcg per person;
  • during pregnancy – 400 mcg;
  • during lactation – 600 mcg.

note: In any case, the dosage of vitamin B9 is determined individually and the above values ​​can only be used for a general understanding of the daily dosage of the drug. There are clear restrictions on the daily amount of the substance in question when planning pregnancy and during the period of bearing/feeding a child, as well as in the case of using folic acid for the prevention of cancer.

Folic acid and pregnancy

Folic acid is responsible for DNA synthesis, it is actively involved in cell division and their restoration. Therefore, the drug in question must be taken both during pregnancy planning, and during the period of bearing a child, and during breastfeeding.

Folic acid is prescribed to women who have stopped taking contraceptives and are planning a child. You need to start using the substance in question as soon as the decision is made to conceive and give birth to a child - the importance of the absolute supply of folic acid in the mother’s body in the first days/weeks of pregnancy is difficult to assess. The fact is that at two weeks of age the embryo’s brain is already beginning to form - at this stage a woman may not even suspect she is pregnant. In the early stages of pregnancy, the baby’s nervous system is also formed - folic acid is necessary for proper cell division and the formation of an absolutely healthy organism. Why do gynecologists prescribe vitamin B9 to women when planning pregnancy? The substance in question takes an active part in hematopoiesis, which occurs during the formation of the placenta - with a lack of folic acid, pregnancy can end in miscarriage.

A lack of folic acid in a woman’s body during pregnancy can lead to the development of birth defects:

  • "cleft lip";
  • hydrocephalus;
  • "cleft palate";
  • neural tube defect;
  • violation of the mental and intellectual development of the child.

Ignoring folic acid prescriptions from a gynecologist can lead to premature birth, placental abruption, stillbirth, miscarriage - according to scientific research, in 75% of cases, this development of events can be prevented by taking folic acid 2-3 months before pregnancy.

After childbirth, you should also not interrupt the course of taking the substance in question - postpartum depression, apathy, and general weakness are a consequence of a lack of folic acid in the mother’s body. In addition, in the absence of additional introduction of folates into the body, there is a deterioration in the quality of breast milk, its quantity decreases, which affects the growth and development of the child.

Dosage of folic acid during pregnancy and lactation

During the period of planning and carrying a pregnancy, doctors prescribe folic acid to a woman in the amount of 400 - 600 mcg per day. While breastfeeding, the body needs a higher dosage - up to 600 mcg per day. In some cases, women are prescribed a dose of 800 mcg of folic acid per day, but such a decision should only be made by a gynecologist based on the results of an examination of the woman’s body. An increased dosage of the substance in question is prescribed for:

  • Diabetes mellitus and epilepsy diagnosed in a woman;
  • existing congenital diseases in the family;
  • the need to constantly take medications (they make it difficult to absorb folic acid in the body);
  • previously born children with a history of folate-dependent diseases.

Important : The gynecologist should indicate in what quantities of folic acid a woman should take during periods of planning/gestation of pregnancy and lactation. It is strictly forbidden to choose a “convenient” dosage on your own.

If a woman is absolutely healthy, then vitamin B9 is prescribed in the form of multivitamin preparations, which a woman needs when planning pregnancy and bearing a child. They are sold in pharmacies and are intended for expectant mothers - “Elevit”, “Pregnavit”, “Vitrum prenatal” and others.

If the need for an increased dosage of folic acid is identified, the woman is prescribed drugs with a high content of vitamin B9 - “Folacin”, “Apo-Folik”.

note: to know exactly how many capsules/tablets you need to take per day, you need to study the instructions for the drug and consult a gynecologist.

The principle of taking medications containing folic acid is simple: before or during meals, with plenty of water.

Overdose and contraindications

Recently, it has become “fashionable” to prescribe folic acid to pregnant women in the amount of 5 mg per day - apparently, this is how they want to fill the body with vitamin B9. This is absolutely wrong! Despite the fact that excess folic acid is eliminated from the body 5 hours after admission, an increased dosage of folic acid can lead to the development of anemia, increased excitability, kidney dysfunction, and disturbances in the gastrointestinal tract. It is believed that the maximum permissible dose of folic acid per day is 1 mg, 5 mg per day is a therapeutic dose that is prescribed for diseases of the cardiovascular system and other parts of the body.

To be clarified : even with an overdose of folic acid as prescribed by a doctor, there is no negative effect on the intrauterine development of the fetus. Only the body of the expectant mother suffers.

A contraindication to the prescription of folic acid is individual intolerance to the substance or hypersensitivity to it. If such a disorder was not identified before the prescription, then after consuming drugs with vitamin B9, a rash and itching on the skin, facial flushing (redness), and bronchospasm may appear. If these symptoms occur, you should immediately stop taking the prescribed medications and tell your doctor.

The benefits of folic acid for pregnant women are described in detail in the video review:

Folic acid in foods

Folic acid and cancer: data from official studies

Many sources indicate that folic acid is prescribed in the treatment of cancer. But on this issue, the opinions of scientists/doctors are divided - some studies confirm that this particular substance is capable of inhibiting the growth of cancer cells and serving as prevention in oncology, but others have indicated an increase in malignant tumors when taking medications with folic acid.

General assessment of cancer risk from folic acid supplementation

The results of a large study assessing the overall risk of cancer in patients taking folic acid supplements were published in January 2013 in The Lancet.

“This study provides confidence in the safety of taking folic acid for a period not exceeding five years, both as supplements and as fortified foods.”

The study involved about 50,000 volunteers, who were divided into 2 groups: the first group was regularly given folic acid supplements, the other group was given a placebo “pacifier”. The group taking folic acid had 7.7% (1,904) new cancer cases, while the placebo group had 7.3% (1,809) new cases. No noticeable increase in overall cancer incidence was seen even in people with a high average folic acid intake (40 mg per day), experts say.

Risks of developing breast cancer when taking folic acid

In January 2014, the results of another study were published. Scientists studied the risks of breast cancer in women taking folic acid. Canadian researchers at St. Michael's Hospital in Toronto, including Dr. Yong-In-Kim, lead author of the study, found that folic acid supplements taken by breast cancer patients may promote the growth of malignant cells.

Previously, some scientists proved that folate can protect against various types of cancer, including breast cancer. However, research by Canadian scientists has shown that consumption of folic acid at a dosage of 2.5 mg 5 times a day for 2-3 months in a row significantly promotes the growth of existing precancerous or cancer cells in the mammary glands rodents. Important: This dosage is many times higher than the dosage recommended for humans.

Folic acid and prostate cancer risks

In March 2009, the Journal of the National Cancer Institute published the results of a study on the relationship between folic acid intake and the risk of prostate cancer.

Scientists from the University of Southern California, in particular study author Jane Figueiredo, found that taking vitamin supplements with folic acid more than doubles the risk of developing prostate cancer.

Researchers monitored the health of 643 volunteers for more than six and a half years: men whose average age was about 57 years. All men were divided into 2 groups: the first group took folic acid (1 mg) daily, the second group was given a placebo. During this time, 34 study participants were diagnosed with prostate cancer. Based on the data they had, scientists calculated the likelihood of developing prostate cancer in all participants over 10 years and came to the conclusion that 9.7% of people from group 1 (taking folic acid) and only 3.3% could develop cancer. men from the second group (taking “pacifiers”).

Folic acid and laryngeal cancer

In 2006, scientists from the Catholic University of the Sacred Heart found that taking large doses of folic acid contributes to the regression of laryngeal leukoplakia (a precancerous disease that precedes laryngeal cancer).

The experiment involved 43 people who were diagnosed with laryngeal leukoplakia. They took 5 mg of folic acid 3 times a day. The results of the study, published by its leader Giovanni Almadori, surprised doctors: regression was recorded in 31 patients. In 12 cases there was a complete cure, in 19 cases there was a reduction in spots by 2 or more times. Italian scientists conducted an analysis and found that the concentration of folic acid was reduced in the blood of patients with head and neck cancer, as well as patients suffering from laryngeal leukoplakia. Based on this, a hypothesis was put forward about low folate levels as a provoking factor in the development and progression of cancer.

Folic acid and colon cancer

Previously, scientists from the American Cancer Society proved that vitamin B9 significantly reduces the risk of development - it is enough to consume folic acid in the form of natural products (spinach, meat, liver, animal kidneys, sorrel) or synthetic preparations.

Tim Byers found that patients who took folic acid supplements had an increase in the number of polyps in their intestines (polyps are precancerous lesions). Important: scientists emphasized that we are talking about the use of drugs, not products containing folates.

Note: Most of the studies confirming the increased risk of malignant neoplasms are based on taking doses many times higher than the minimum recommended. Remember that the recommended dose is 200 – 400 mcg. Most folic acid supplements contain 1 mg of folate, which is 2.5 to 5 times the daily value!

Tsygankova Yana Aleksandrovna, medical observer, therapist of the highest qualification category

Folic Acid and Folate- It is the same? What is the difference between these substances. And why this should be important for planning pregnancy.

Perhaps the most common vitamin, besides, of course, multivitamins and Iron, Folic acid is prescribed to all pregnant women. Now it is prescribed even to those who are just about to become pregnant.

The reason is very important - it is the prevention of congenital neural tube defects of the fetus. This vitamin is especially important in the first trimester of pregnancy.

And only recently I found out that it turns out that Folic acid and Folate - or the natural substance that we get in food - are completely different things.

To me, as a girl for which the topic of pregnancy begins to become very relevant, it became interesting - so what is better for me to take - Folic acid, which prescribed by doctors or a natural form - Folate.

Folic Acid and Folate: What's the Difference?

It turns out that these 2 substances are, in principle, not the same thing.

Folate is a general term used for a group of water-soluble B vitamins, also known by the acronym “Vitamin B-9”. This substance is found naturally in nature and products.

Folic acid is an oxidized synthetic substance that can only be found in vitamin complexes and supplements. It was synthesized relatively recently, in 1943, and does not occur naturally in nature.

Let's now look at the mechanism of their action.

Folate enters our body under the guise Tetrahydrofolate. This form is formed during the natural metabolism of Folate in the small intestinal mucosa.

Folic acid first undergoes a process of reduction and methylation in our liver, where it is converted into a biologically active form Tetrahydrofolate requires a special enzyme, Dehydrofolate Reductase.

Problems can begin when our body does not have enough of this enzyme in the liver or when we take in large amounts of Folic Acid (such as during pregnancy), resulting in unnatural and abnormal levels. unmetabolized Folic acid in the blood.

What can high levels of Folic acid in our body cause? Research shows that this increases the risk of developing malignant tumors. Another study indicates that excess folic acid leads to anemia.

So what to do?

If you don't eat enough liver and greens, you will most likely have a folate deficiency during pregnancy.

And even if you eat liver, spinach, parsley, broccoli, cauliflower, beets almost every day (a very good source of not only Folate, but also beneficial bacteria necessary to create normal microflora, which we will pass on to our baby at birth ), peas - then anyway, for the sake of, so to speak, prevention, it is best to take Folate before becoming pregnant and during pregnancy.

Carefully review the ingredients in your prenatal multivitamin; most contain folic acid. For myself, I have already decided that I will take this complex, the vitamins and minerals of which are obtained from food sources, and not synthesized synthetically. This organic complex contains Folate, not Folic Acid. The only negative of this multivitamin is the insufficient amount of Folate. Therefore, you can also take Folate separately, it can be found under the name 5- Methyltetrahydrofolate or 5-MTHF. For example here this .

I plan to start taking Folate not during pregnancy, but several months before it, that is, one might say, during pregnancy planning. The normal dosage is 800-1200 mcg per day.

Of course, in the end, it's up to you whether you take Folic Acid or Folate. I, as a supporter of everything natural and natural, have already decided that I will give preference to Folate and will take it along with, of course, foods rich in it.

Did you know the difference between Folic acid and Folate? Which is preferable for you? As always, I will be glad to hear your opinion!

* Important: Dear readers! All links to the iherb website contain my personal referral code. This means that if you follow this link and order from the iherb website or enter HPM730 when you order in a special field (referral code), you receive a 5% discount on your entire order, I receive a small commission for this (this has absolutely no effect on the price of your order).

(Visited 42,012 times, 1 visits today)

Dear Colleagues!
The seminar participant certificate, which will be generated if you successfully complete the test task, will indicate the calendar date of your online participation in the seminar.

Seminar "IMPORTANCE OF FOLATES OUTSIDE OF PREGNANCY"

Conducts: Republican Medical University

The date of the: from 06/01/2015 to 06/01/2016

Determination of folates

Folates are chemical compounds based on folic acid and make up vitamin B9 altogether. They are irreplaceable components of basic metabolic processes, the most important of which are nucleotide synthesis and DNA replication, which ensure the physiological division and normal growth of all cells in the body.

With folate deficiency, the replication process is disrupted, which primarily affects rapidly proliferating cells, such as hematopoietic and epithelial cells. Damage to hematopoietic cells leads to disruption of hematopoiesis in the bone marrow with the formation of a megaloblastic type of hematopoiesis, the manifestation of which is folate deficiency megaloblastic anemia. As a result of damage to epithelial cells, the regeneration of the skin and mucous membranes deteriorates.

Also, folates take part in the methylation reactions of all metabolic substrates: proteins, hormones, lipids, neurotransmitters, etc. The most important substrate for methylation in the body is DNA. DNA methylation ensures the functioning of the cellular genome, regulation of ontogenesis and cellular differentiation. It is also associated with the activity of the immune system, which through methylation reactions recognizes and suppresses the expression of foreign genes. Methylation defects result in pathological conditions such as cancer, atherosclerosis, neurodegenerative, autoimmune and allergic diseases.

Along with hematopoietic and epithelial cells, rapidly proliferating cells include chorion tissue in a pregnant woman, which is also highly sensitive to the negative effects of folate deficiency. Disruption of the genome of embryonic cells during their division and differentiation leads to disruption of embryogenesis, the formation of malformations in the fetus and a complicated course of pregnancy.

Metabolism of folate in the body

Folates are not synthesized in the body and come to us with food. The highest amounts of folate are found in green leafy vegetables, legumes, citrus fruits and animal liver. The limited consumption of such foods is primarily responsible for the high incidence of folate deficiency among the population, which is detected in almost 90% of the population.

To compensate for folate deficiency, since 1998 in the USA, Australia and many European countries, food fortification programs with folic acid (bread, flour, pasta) have been carried out at the rate of an additional daily intake of about 100 mcg.

Folic acid consumed by the population during the fortification of food products, as well as most dietary folates, are biologically inactive. Only one form of folic acid is absorbed from the intestine into the circulatory system and then consumed by cells - monoglutamate 5-methyltetrahydrofolate (5-MTHF) (Fig. 1). The remaining forms of folate are polyglutamates, which, when absorbed from the intestine into the blood, under the influence of the enzyme MTHFR are also converted to monoglutamate 5-MTHF. 5-MTHF enters the cells of the body and participates in biological processes: cycles of cell replication and methylation (Fig. 2).

The methylation cycle involves the transformation of the amino acid methionine, which comes into the body from animal products (meat, milk and eggs), into S-adenosylmethionine and then homocysteine. S-adenosylmethionine is a methyl donor for all cellular methyltransferases that methylate various substrates (DNA, proteins, lipids, enzymes, etc.). After the loss of the methyl group, it is converted to homocysteine, part of which is metabolized by the B6-dependent enzyme cystathionine synthase and excreted by the kidneys, and part is re-methylated and converted to methionine, which leads to the resumption of the cell cycle of methylation. Re-methylation of homocysteine ​​occurs due to the methyl groups of 5-MTHF monoglutamate entering the cells, which are transported using the B12-dependent enzyme methionine synthase. Thus, folates provide a constant supply of methyl groups to the methylation cycles.

After participating in the methylation cycle, 5-MTHF is converted back into folic acid polyglutamates. Polyglutamates are involved in another equally important metabolic process: they provide the cycle of nucleotide synthesis and DNA replication, which allows cells to divide. As a result of these reactions, intermediate forms of folic acid are formed - polyglutamate dihydrofolate and 5,10-methylenetetrahydrofolate. Dihydrofolates are converted back into tetrahydrofolate polyglutamates by the enzyme dehydrofolate reductase (DHFR) and are again used in the synthesis of nucleotide precursors for DNA formation and cell division. 5,10-methylenetetrahydrofolates under the influence of the MTHFR enzyme are re-converted into the active monoglutamate 5-MTHF, which, together with 5-MTHF received from the blood, is used to re-methylate homocysteine ​​into methionine and participate in the latter’s methylation cycles.

Folate deficiency, hyperhomocysteinemia and risk of cardiovascular disease

Homocysteine ​​is an amino acid that is formed in the body from methionine as a result of the latter’s participation in methylation reactions. At the same time, it is a substrate for the resumption of the methylation cycle, turning back into methionine through the transfer of new methyl groups from folates.

With a lack of folate, the process of homocysteine ​​remethylation is disrupted and it accumulates in the body. In recent years, it has become apparent that any increase in blood homocysteine ​​levels causes an increased risk of thrombophilic complications such as myocardial infarction, stroke and venous thromboembolism. At the same time, homocysteine ​​does not directly participate in the activity of the blood coagulation system and its effect is carried out indirectly. Hyperhomocysteinemia causes damage to the vascular endothelium, which activates factors of the blood coagulation system and leads to increased thrombosis, while the activity of the anticoagulant component of hemostasis worsens. In addition, in places where the vascular wall is damaged, cholesterol, calcium and cell breakdown products are deposited with the formation of atherosclerotic plaques, as a result of which the lumen of the vessels narrows, leading to circulatory disorders and the development of coronary heart disease. Thus, hyperhomocysteinemia is a proven independent risk factor for cardiovascular diseases.

The lower limit for serum homocysteine ​​is 5 µmol/L, while the upper limit varies between 10 and 20 µmol/L depending on age, gender, ethnic group and folate intake. A number of large-scale studies have shown that at serum homocysteine ​​concentrations? 10 µmol/l there is a significant increase in the risk of developing coronary heart disease, stroke, heart attack, as well as malignant neoplasms. An increase in blood homocysteine ​​levels by just 5 µmol/l leads to an increase in the risk of atherosclerotic vascular damage by 80%, acute heart attack and stroke by 50%. Along with this, the overall mortality rate increases significantly, including mortality from both cardiovascular diseases and unrelated causes, including malignant neoplasms.

Hyperhomocysteinemia is a mixed form of thrombophilia because it can be acquired and hereditary. Acquired hyperhomocysteinemia occurs with insufficient consumption of foods rich in folic acid, as well as with impaired absorption of folate into the blood due to intestinal diseases. Alcoholism, smoking, the use of a number of medications (anticonvulsants, hormonal contraceptives, barbiturates, sulfonamides, antitumor drugs), hypothyroidism, and diabetes mellitus can also lead to folate deficiency and the development of hyperhomocysteinemia. The accumulation of serum homocysteine ​​may be a consequence of impaired excretion in kidney disease.

An important role in the metabolism of homocysteine ​​is also played by enzymes of the folate cycle: MTHFR, methionine synthase and cystathionine synthase. They provide both remethylation of homocysteine ​​and conversion to methionine, and removal of its excess through the urinary system. The functioning of methylene synthase and cystothionine synthase depends on the amount of vitamins B12 and B6 entering the body. Hereditary enzyme deficiencies also occur, resulting from polymorphisms in their genome.

The most common cause of hereditary hyperhomocysteinemia is polymorphism of the MTHFR enzyme gene. MTHFR is the main enzyme in folate metabolism. It converts all inactive forms of folate, both those entering the body, including synthetic folic acid in tablets, and those found in cells, into biologically active 5-MTHF (Fig. 2). Impaired function of this enzyme, which in the homozygous form of the polymorphism is reduced by 75% of the original and in the heterozygous form by 30%, leads to a sharp decrease in the formation of active folates and the development of folate deficiency. Women with MTHFR gene polymorphism are at high risk for developing cardiovascular diseases.

It was found that regular intake of folic acid (at a dose of about 200 mcg/day) significantly reduces homocysteine ​​levels in the blood and reduces mortality from cardiovascular diseases. In a retrospective cohort study, blood folate levels were analyzed in relation to mortality from myocardial infarction in 5056 patients with coronary artery disease. A significant inverse correlation was found between serum folate concentrations and mortality from myocardial infarction. There has been a clear trend towards a decrease in the incidence of hospitalization due to acute myocardial infarction in countries implementing a food fortification program with folates.

Over the past decades, the incidence of acute stroke has been decreasing in all countries. But a comparison of the degree of decline in this indicator in the USA and Canada in the period 1990-2002, using food fortification programs, with a similar indicator in the UK, where fortification is not mandatory, showed a more significant rate of decline in the incidence of strokes in countries with mandatory food fortification . A meta-analysis published in 2012, combining the results of a survey of 59 thousand patients, showed a reduction in the risk of stroke when taking folic acid.

At the same time, a meta-analysis of 8 studies involving 37,485 patients concluded that taking folic acid for 5 years had a negligible effect on the incidence of heart attacks and strokes. Moreover, a meta-analysis conducted by Wang et al. in 2007, did not reveal the protective effect of folates on the development of stroke. In contrast to these findings regarding folic acid supplementation, the authors demonstrated the effect of combined use of B vitamins (folic acid, vitamins B6 and B12), which reduced the risk of stroke by 18%.

Folate deficiency and cancer

With a lack of folate in the body, the replication and differentiation of epithelial cells is impaired, which is accompanied by a deterioration in the regeneration of the skin and mucous membranes. In addition, folate deficiency causes damage to the genome of rapidly proliferating cells and increases the risk of malignant diseases. Moreover, the genome of cancer cells becomes more sensitive to disturbances in folate metabolism than the genome of normal cells.

Hyperhomocysteinemia is an independent risk factor for the activation of carcinogenesis. Immunological and biochemical studies have shown that a lack of folate not only contributes to the accumulation of toxic homocysteine, but also reduces T-cell immune anticancer resistance.

In recent years, publications have appeared on the connection between folate deficiency and malignant diseases. The most commonly observed association with the risk of colorectal cancer and breast cancer. Impaired cell replication and DNA methylation contribute to the development of cancerous and precancerous conditions of the cervix. Women with HPV infection and low blood levels of folic acid and vitamin B12 had a 70% greater risk of CIN than women with normal folate levels.

Comparative meta-analysis of 12523 cases of malignant diseases of various localizations in the period 1991-2009. in Italy and Switzerland, compared with 22,828 control cases, showed that consumption of foods containing 100 mcg of folate per day significantly reduces the risk of any malignant diseases: esophagus, larynx, stomach, colorectal cancer, pancreas, trachea, breast, endometrium, ovaries, kidneys and prostate.

However, mixed findings have been reported for synthetic folic acid supplementation. As a result of epidemiological and clinical studies and the results of the implementation of food fortification programs with synthetic folic acid, a bidirectional relationship was identified between folic acid intake, blood folate levels and cancer. It was found that cancer risk increases with both folate deficiency and an overdose of synthetic folic acid. The use of synthetic folic acid in amounts greater than 400 mcg per day was associated with a significant increase in the risk of malignant diseases such as breast, colorectal, lung, prostate and ovarian cancer.

Folate deficiency and neuropathy

One of the manifestations of folate deficiency is neuropathy. It occurs as a result of damage to the sheath of nerve endings and disruption of the conduction of nerve impulses through them due to failure of methylation of its basic protein myelin.

Back in 1963, H. Gough et al. found an association of low folate concentrations with anxiety and depression. It has now been proven that more than a third of patients with depression have folate deficiency, while the severity of the disease and the effectiveness of treatment with antidepressants inversely correlates with the level of folate in erythrocytes. Population-based studies have demonstrated that with adequate dietary folate intake and dietary folate fortification, the prevalence of depression is reduced.

In recent years, the connection between folate deficiency and the development of schizophrenia and autism has become apparent. One of the main theories of the development of these diseases is congenital malformation (minor malformations) of the nervous system. The results of a 40-year study “Prenatal Risk Factors for Schizophrenia” conducted in the United States showed that high homocysteine ​​levels during pregnancy double the risk of developing schizophrenia and autism in a child.

Folate deficiency and age-related changes

A number of studies have shown an association of high levels of homocysteine ​​in the blood with degenerative changes in the blood vessels of the eye and visual impairment in older people. Daily use of folic acid in combination with vitamins B6 and B12 in 5,000 patients for 7 years showed a 34% reduction in the risk of developing these complications.

Low folate status correlates with hearing loss, especially in old age. A study conducted in the Netherlands showed improved hearing with folic acid supplementation (800 mcg/day) in 700 elderly patients.

In recent decades, many studies have described the relationship between decreased folate levels, low folate intake and cognitive impairment in older adults. A systematic review of retrospective studies published in 2009 found that hyperhomocysteinemia increases the risk of Alzheimer's disease and senile dementia.

Folic acid supplementation at 800 mcg/day reduced blood homocysteine ​​levels by 26% compared to placebo and reduced rates of cognitive impairment. With the combined use of folic acid with vitamins B6 and B12 in patients suffering from cognitive disorders and hyperhomocysteinemia, the decrease in serum homocysteine ​​concentration occurred more significantly (by 32%) and the progression of cognitive disorders slowed down by 53% compared to placebo.

Folate deficiency and anemia

The development of anemia is traditionally associated with folate deficiency. A decrease in the level of hemoglobin and red blood cells occurs as a result of impaired hematopoiesis in the bone marrow. For normal erythropoiesis, sufficient amounts of folate, vitamin B12 and iron are necessary. Deficiency of folate and/or vitamin B12 leads to disruption of the division of hematopoietic cells, which is accompanied by the replacement of the normoblastic type of hematopoiesis with megaloblastic, in which the number of blood cells decreases, their volume increases and functional activity decreases.

The administration of synthetic folic acid can significantly increase the level of hemoglobin and red blood cells in the blood, but subject to the normal functioning of the enzymes responsible for the metabolism of the folate cycle. In cases of polymorphism in the MTHFR and/or methionine synthase genes, the effectiveness of such tactics is much lower.

In addition, the administration of synthetic folic acid masks vitamin B12 deficiency, characteristic of pernicious anemia. Vitamin B12 is associated with the activity of the enzyme methionine synthase, which is responsible for the transfer of the methyl group of folates into methylation cycles. The most serious consequence of this is damage to the methylation of myelin, a protein that ensures the conduction of nerve impulses. Synthetic folates lead to the restoration of normal hematopoiesis and the treatment of anemia, but the restoration of methylation processes does not occur. The result is irreversible destruction of myelin and rapid progression of neurological symptoms: from depression to cognitive disorders and Alzheimer's disease.

Anemia associated with vitamin B12 deficiency occurs in 20% of adults and is more common in vegetarians, pregnant women and newborns. The number of people with low serum levels of vitamin B12 has increased by 70-87% as a result of fortification programs. A study of 1,500 older adults in the United States found that high serum folate levels associated with fortified foods were associated with low vitamin B12 levels and had the highest risk of anemia and cognitive impairment.

Folic acid and metafolin

As a result of the findings on the adverse effects of consuming high doses of synthetic folic acid, the “no such thing as too much” approach to folate supplementation is now considered controversial. The daily requirement for folate is only 400 mcg or 0.4 mg.

In addition, due to the widespread prevalence of genetic polymorphisms of folate cycle enzymes, the effectiveness of prescribing synthetic folic acid is not sufficient. Synthetic folic acid, like most dietary folates, is biologically inactive and can only be converted into active monoglutamate 5-MTHF with the help of the MTHFR enzyme (Fig. 1, 2). But, unlike dietary folates, synthetic folic acid in unmetabolized form can also enter the systemic circulation and be taken up by cells. The appearance of a non-metabolized form in the blood occurs already with a daily consumption of folic acid of more than 200 mcg, which is due to the limited capabilities of the enzymatic system of the intestinal mucosa. Synthetic folic acid entering the cells blocks the receptors and enzymes with which endogenous folates interact, which, as a result, cannot realize their effects. Apparently this is the reason for the development of adverse side effects when subsidizing high doses of folic acid.

Thus, with a high concentration of unmetabolized folic acid in the blood serum as a result of consumption of fortified products, the activity of natural killer cells - NK cells - is inhibited. NK cells are an important component of the nonspecific immune response that limits the activity of infectious agents and tumor cells.

Other studies have shown an increase in cognitive impairment in older adults with folic acid intake greater than 400 mcg/day. A cohort study of the results of a fortification program showed that one in three older Americans had serum levels of unmetabolized folic acid, which was associated with increased anemia and poor cognitive performance tests when combined with low vitamin B12 levels. The authors concluded that unmetabolized folic acid in the blood serum may have a negative effect on the functioning of the nervous system.

In contrast, another form of folic acid - 5-MTHF (L-methylfolate) or metafolin - is biologically active and is absorbed into the blood without the participation of intestinal enzymatic systems, including the MTHFR enzyme. It is directly captured by cells and used in metabolic processes - DNA replication and methylation cycles (Fig. 1, 2). When studying the level of folates in red blood cells in women with polymorphism of the MTHFR gene with different types of inheritance, it was shown that metafolin increases their content to a much greater extent than folic acid, in addition, metafolin more significantly reduces the level of homocysteine.

The biologically active form of folic acid metafolin is contained in the drug Femibion. It contains only 400 mcg of folate, half of which is folic acid and half is biologically active metafolin. In addition, it contains other representatives of the B vitamins, including B6 and B12, which are necessary for the activity of enzymes that ensure the metabolism of folate in the body, as well as vitamins C, E, PP and iodine.

As a multivitamin-mineral complex, Femibion ​​compares favorably with most other representatives of this group of food additives. Femibion ​​has a significantly lower load on the liver and gastrointestinal tract due to the number of components in its composition, which is 2/3 less than in a regular multivitamin tablet. In addition, the content of most vitamins and minerals does not exceed 50-75% of the daily requirement, which, in combination with food intake, does not lead to an excess of vitamins in the body, which is no less dangerous than their deficiency.

Conclusion

Folates play an irreplaceable role in the body: they participate in cell replication and differentiation, and ensure the methylation of all metabolic substrates. At the same time, 9 out of 10 people in the population have folate deficiency, which is associated both with insufficient consumption of foods containing folic acid and as a result of impaired formation of active folates due to polymorphism of folate cycle enzymes.

In the presence of genetic polymorphism of folate cycle genes, the most common of which is MTHFR polymorphism, it is pathogenetically justified to use the Femibion ​​multivitamin-mineral complex, which contains, in addition to 200 mcg of folic acid, 200 mcg of active folate - metafolin, as well as other representatives of the group of vitamins necessary to ensure the activity of folate cycle enzymes and the implementation of the function of folates in the body.

Fig 1.

Fig.2

Bibliography:

1. Bailey RL, McDowell MA, Dodd KW et al. Total folate and folic acid intakes from foods and dietary supplements of US children aged 1-13 y. Am J Clin Nutr 2010; 92: 353-8.

2. Bailey RL, Mills JL, Yetley EA, et al. Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged > or =60 y in the United States. Am J Clin Nutr 2010; 92: 383-9.

3. Bekkers MB, Elstgeest LE, Scholtens S, et al. Maternal use of folic acid supplements during pregnancy and childhood respiratory health and atopy: the PIAMA birth cohort study. Eur Respir J 2011.

4. Bentley S, Hermes A, Phillips D, et al. Comparative effectiveness of a prenatal medical food to prenatal vitamins on hemoglobin levels and adverse outcomes: a retrospective analysis. Clin Therapeut 2011;33:204–210.

5. Christen WG, Glynn RJ, Chew EY et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women’s Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med 2009; 169: 335-41.

6. Clarke R, Halsey J, Lewington S, et al. Effects of lowering homocysteine ​​levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37,485 individuals. Arch Intern Med 2010; 170: 1622-31.

7. Cotlarciuc I, Andrew T, Dew T, et al. The basis of differential responses to folic acid supplementation. J Nutrigenet Nutrigenomics 2011; 4: 99-109.

8. Crider KS, Bailey LB, Berry RJ. Folic acid fortification – its history, effect, concerns, and future directions. Nutrients 2011; 3: 370-84.

9. Crider KS, Yang TP, Berry RJ, Bailey LB. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr. 2012;3(1):21–38.

10. Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007; 369: 208-16.

11. Duthie SJ. Folat and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis. J Inherit Metab Dis. 2011;34:101-109.

12. EFSA. ESCO Report on Analysis of Risks and Benefits of Fortification of Food with Folic Acid. 2009

13. FIGO Working Group on Best Practice in Maternal–Fetal Medicine International Journal of Gynecology and Obstetrics 2015; 128:80–82

14. Gibson TM, Weinstein SJ, Pfeiffer RM, et al. Pre- and postfortification intake of folate and risk of colorectal cancer in a large prospective cohort study in the United States. Am J Clin Nutr 2011.

15. Haberg SE, London SJ, Nafstad P, et al. Maternal folate levels in pregnancy and asthma in children at age 3 years. J Allergy Clin Immunol 2011; 127: 262-4, 4 e1.

16. Haberg SE, London SJ, Stigum H, qt al. Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child 2009; 94: 180-4.

17. Kalmbach RD, Choumenkovitch SF, Troen AP, et al. A 19-base pair deletion polymorphism in dihydrofolate reductase is associated with increased unmetabolized folic acid in plasma and decreased red blood cell folate. J Nutr 2008; 138:2323-7.

18. Kidd PM. Alzheimer’s disease, amnestic mild cognitive impairment, and age–associated memory impairment: current understanding and progress toward integrative prevention. Altern Med Rev. 2008;13:85–115.

19. Kim YI. Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res. 2007;51(3):267–292.

20. Lamers Y, Prinz-Langenohl R, Bramswig S, Pietrzik K. Red blood cell folate concentrations increase more after supplementation with -5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr. 2006;84(1):156–161.

21. Magdelijns FJ, Mommers M, Penders J, et al. Folic Acid use in pregnancy and the development of atopy, asthma, and lung function in childhood. Pediatrics 2011; 128:e135-44.

22. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. Am J Clin Nutr 2010; 91: 1733-44.

23. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. Am J Clin Nutr. 2010;91:1733–1744.

24. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr 2007; 85: 193-200.

25. National Heart, Lung and Blood Institute,. Morbidity and mortality: 2009 chart book on cardiovascular, lung, and blood diseases. 2009

26. Pietrzik K, Bailey L, Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacok. 2010;49(8):535–548.

27. Piyathilake CJ, Macaluso M, Alvarez RD, et al. Lower risk of cervical intraepithelial neoplasia in women with high plasma folate and sufficient vitamin B12 in the post-folic acid fortification era. Cancer Prev Res (Phila) 2009; 2: 658-64.

28. Prinz-Langenohl R, Bramswig S, Tobolski O, et al. (6S)-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild-type 677C,T polymorphism of methylenetetrahydrofolate reductase. Br J Pharmacol 2009;158:2014-2021.

29. Sauer J, Mason JB, Choi SW. Too much folate: a risk factor for cancer and cardiovascular disease? Curr Opin Clin Nutr Metab Care. 2009;12(1):30-36.

30. Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment. A randomized controlled trial. PLoS ONE 2010; 5:e12244.

31. Troen AM, Mitchell B, Sorensen B, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006; 136: 189-94.

32. Tu JV, Nardi L, Fang J, et al. National trends in rates of death and hospital admissions related to acute myocardial infarction, heart failure and stroke, 1994-2004. CMAJ 2009; 180:E118-25.

33. Van Guelpen B. Folate in colorectal cancer, prostate cancer and cardiovascular disease. Scand J Clin Lab Invest. 2007;67(5):459-447.

34. Vogel S, Meyer K, Fredriksen A, et al. Serum folate and vitamin B12 concentrations in relation to prostate cancer risk – a Norwegian population?based nested case?control study of 3000 cases and 3000 controls within the JANUS cohort. Int J Epidemiol. 2013;42(1):201–210.

35. Wien TN, Pike E, Wisloff T, et al. Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ Open 2012; 2: e000653.

36. Wong Y, Almenda OP, McCaul KA, et al. Homocysteine, Frailty, and All-Cause Mortality in Older Men: The Health in Men Study. J Gerontol A Biol

37. Wyckoff KF, Ganji V. Proportion of individuals with low serum vitamin B-12 concentrations without macrocytosis is higher in the post folic acid fortification period than in the pre folic acid fortification period. Am J Clin Nutr 2007; 86: 1187-92.

38. Xiao Y, Zhang Y, Wang M, et al. Plasma S-adenosylhomocysteine ​​is associated with the risk of cardiovascular events in patients undergoing coronary angiography: a cohort study. Am J Clin Nutr Nov. 2013;98:1162-1169.

39. Yang IV, Schwartz DA. Epigenetic mechanisms and the development of asthma // J Allergy Clin Immunol. 2012;130(6):1243–1255.

40. Yang Q, Botto LD, Erickson JD, et al. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation 2006; 113:1335-43.

One of the important tasks in the development of methods for diagnosing and treating cancer is the production of agents that can selectively accumulate in tumor cells and tissues. In particular, in nuclear medicine, isotope labeling of radiopharmaceuticals is used to diagnose tumors using positron emission tomography and single-photon emission computed tomography. Recently, approaches based on the use of D -amino acids, folic acid and its derivatives (folates) for detecting tumors and delivering drugs to them.

In malignant neoplasms, the transport of amino acids into cells through the membrane increases sharply, associated with the intensification of protein synthesis in them. D -amino acids, unlike L -amino acids from which our proteins are built, when they get inside cells, are not metabolized, do not participate in protein synthesis, but accumulate in them, and in cancer cells they accumulate much more readily than in normal cells. In this regard, it was proposed to use D - amino acids as specific agents for the detection of malignant neoplasms, and subsequent studies in mice confirmed that, using 2-iodo- D -phenylalanine, isotope labeled I 123 , it is possible to achieve preferential accumulation of the drug in tumor tissue up to 350%. However, later evidence appeared that the real situation is not so simple and may depend on the species of cells and the type of tumor.

Another agent that has a selective affinity for malignant cells is folic acid. Cells transport folate through two types of membrane-bound proteins—the reduced folate transporter and the folate receptor. The former is present on virtually all cells and represents the main pathway for the physiological incorporation of folate. The second is responsible for binding oxidized forms of folate to the cell. Although low concentrations of reduced folate transporters are sufficient to supply folate to most normal cells, the folate receptor is overexpressed on malignant cells, giving them a competitive advantage when availability of this vitamin is limited. There are numerous indications that the folate receptor is often overexpressed on the surface of cancer cells. Folic acid has a very high affinity for its receptors, and the receptor is effectively taken up by the cell when it binds an agent containing folic acid. It is these features of folate transport into cells that are widely used to develop methods for delivering various agents, including drugs, to tumor cells. Today, many drugs based on folic acid are synthesized for these purposes.

Several years ago, the Department of Molecular and Radiation Biophysics of the PNPI proposed a strategy for searching for selective labeling of malignant tumors: by synthesizing amino acid derivatives, nucleic acid precursors and folic acid, labeled with iodine radioisotopes, and studying the characteristics of their binding to cancer cells. Further, based on the results of these studies, it is planned to develop on their basis diagnostics and therapeutic radiopharmaceuticals for the treatment of malignant tumors. The department has highly qualified chemists with extensive experience in the synthesis of radioactively labeled compounds, as well as cell biology specialists who have been working for many years on the problems of the degeneration of normal cells into cancer cells.

Preliminary studies have established the boundary conditions for the synthesis of iodofolic acidI 125 , based on the interaction of folic acid with a mild oxidizing agent - chlorine iodide (ICL), which proceeds extremely difficult according to the known scheme of introducing iodine atoms into the molecules of aromatic compounds with extremely low yields of the target compound (about 1%) and requires a synthesis lasting 18 hours under harsh conditions. We have developed conditions for the rapid synthesis of iodofolic acid under mild conditionsI 125 with high product yields (30-40%), which is very important for the successful synthesis of drugs labeled with short-lived isotopesI 121 AndI 123 .The drugs were further studied in biological experimentsin vitro on the binding of iodofolic acid to various malignant cell lines compared to normal cells. The first experiments, in which conditions were not optimized for maximum binding of the drug to cells, showed that iodofolic acid binds much more preferentially to the cells of some tumors. In particular, cancer cellsHeLaiodofolic acid was bound hundreds of times more preferentiallyI 125 compared with human embryonic lung fibroblasts. Already from these results it follows that iodofolic acid preparations labeled with radioisotopes are promising for the diagnosis of malignant tumorsin vivo . Next, experiments were launched to study the comparative sorption of folates by cancer and normal cells in order to establish the conditions for the maximum level of binding of iodofolic acid with various cell lines, which will determine the real prospects for its use for the diagnosis and therapy of tumors and the range of applications of this technique to various malignant formations. Such studies are being carried out and at the present time, for which it was necessary to develop original methods for the synthesis of iodine-containing reduced forms of folic acid, methylated and formylated derivatives of these folates. In experiments on the sorption of reduced folates by cellsHeLaThe presence of two sorption mechanisms was established - slow and fast components of the sorption process. Further, for the first time, we synthesized diiodofolic acid, which, according to assumptions, should exhibit a stronger affinity for cancer cells than monoiodofolic acid. Experiments have shown that diiodofolic acid binds to protein inside the cell 4 times more tightly than monoiodofolic acid.

Upon completion of this stage, it is planned to move on to studying the possibility of using bromofolic acid (Br 82 ) for the aforementioned diagnostic and therapeutic purposes. The fact is that some characteristics of the isotopeI 125 are far from ideal for drugs administered into the patient’s body. These include the long half-life of this gamma emitter - 60 days, as well as the danger of accumulation in the thyroid gland of radioactive iodine released during the metabolism of iodofolic acid in the patient's body, which can lead to high levels of local overexposure. The isotope does not have these disadvantagesBr 82 : its half-life is 35 hours, and, in addition, different forms of inorganic bromine do not have the property of preferential accumulation in any organs of animals. Therefore, in further research it is planned to develop the synthesis of bromofolic acid (Br 82 ) and conduct a detailed study of its possible use for the diagnosis and therapy of cancer tumors.

At the same time, the general disadvantages of isotopes I 125 and Br 82 is that they are gamma emitters, which during radiation therapy, due to the long range in the tissues, produce diffuse and rather large spots that affect not only tumors, but also healthy tissues. It is tempting to use radiopharmaceuticals based on alpha emitters, which have a range in tissues of the order of several microns, which is commensurate with the size of cells. A possible candidate for the role of the most effective therapeutic agent is astatine 211, which, however, cannot be produced on the low-power cyclotrons available today in the country, since the cyclotron installations at the IAE named after. Kurchatov and Tver are designed to achieve maximum particle energies of up to 30 MeV, which is not enough to obtain such isotopes. Halogen astatine 211 is an analogue of iodine, for which it seems natural in the form of astatfolic acid to travel to a particular tumor and most effectively and selectively destroy the cells of a malignant tumor. Taking into account the plans to build a cyclotron at PNPI in the near future, mainly for medical purposes at energies of 80 and 200 MeV, the prospects for creating these drugs do not seem so fantastic.

In the future, it is also planned to conduct research work on the synthesis of fluorinated aromatic amino acids and sugars with an eye to the development of biological compounds labeled with the short-lived isotope fluorine-18 for use in positron emission tomography. For the same purposes, it seems tempting to produce isotopes I 121, I 123, and also Br 76 , which are short-lived positron decayers, it will then be necessary to synthesize folic acid labeled with these isotopes and use them in PET to detect tumor formations. An important advantage of the method for the synthesis of folic acid labeled with halogen isotopes developed at PNPI is the short time required to obtain the final products - the synthesis time is calculated in minutes, in contrast to the many-hour procedures in existing methods for the synthesis of less effective preparations of folic acid derivatives.

The work listed above was carried out and is planned to be implemented in the future in close cooperation with departments of the Radium Institute named after. Khlopin and TsNIRRI, which are located on the territory of PNPI. These joint efforts of large industry institutes within the framework of the Nuclear Medicine program can lead, with the launch of the PIK reactor and the commissioning of the specified cyclotron installation, to the question of creating a regional oncology center in Gatchina, which has a wide arsenal of the most modern diagnostic and therapeutic tools for the successful fight against malignant tumors .

Leading researcher PNPI

G.A. Baghiyan

Loading...Loading...