I. Matasar, L. Petryshchenko, O. Lutsenko

The State Establishment “National Science Center for Radiation Medicine National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine

ABSTRACT. The article addresses the value of fat-soluble vitamins as a mean of increasing body radiation resistance under unfavourable environmental conditions resulting from the Chernobyl NPP accident. The radioprotective role of essential organic compounds with high biological activity that contribute to the functioning of the body under complicated environmental conditions. Insufficient dietary intake of vitamins increases the radiosensitivity of the human body. Data are given on the actual dietary intake of vitamins by different age groups (employable adults, children, pregnant women from different settlements in the District of Ivankiv of the Region of Kyiv for 2004–2018) living at the territories contaminated as the result of Chernobyl NPP accident. Analysis of literature and own data indicate that fat-soluble vitamins are essential food components that regulate biochemical and physiological processes in the human body due to the activation of metabolic and enzymatic reactions, have radioprotective properties and should enter the body in sufficient amounts in accordance with age and gender. This is especially true of the population affected because of the Chernobyl NPP accident. Study results have shown that retinol and calciferol deficiency in the body of the population living in the regions affected as a result of Chernobyl NPP accident, is due to changes in the conventional structure of diets and consumption of counterfeit products, first of all, butter and hard cheese. Despite the fact that average daily diet contains a wider range of products compared with the first post-accident years, level of fat-soluble vitamins, in particular vitamin A (even considering b-carotene) and vitamin D does not meet the physiological needs, which may cause dysmetabolic processes in various organs and systems and lead to an increase in alimentary and alimentary-dependent diseases.

Key Words: fat-soluble vitamins, physiological role of vitamins, vitamin deficiency, sources of vitamins, recommended daily intake, population of environmentally dangerous regions, Chernobyl NPP accident.

Introduction. As a result of man-made disasters, all living organisms on Earth have been exposed to additional ionizing radiation. With the development of atomic energetics and the expansion of atomic energy spheres, a large number of radioactive substances, in particular ¹³⁷Cs and ⁹⁰Sr, have penetrated the biosphere. This results in an increase in the radiation background of the environment. The biological action of ionizing radiation, especially in small doses, and the search for protective factors is an urgent problem, in particular when planning fundamental medical and biological studies. In Ukraine, this is an extremely sensitive issue, especially after the Chernobyl NPP disaster, which has the effect of losing health, disability not only among the responders of the accident, but also for the population living outside radioactively contaminated territories of the country.

The investigation of the state of health of the population of radioactively contaminated territories in the years after the Chernobyl NPP accident demonstrates the link between changes caused by the complex influence of negative factors and, above all, ionizing radiation [1–3].

Living conditions of the population of environmentally dangerous territories, formed after the accident, caused changes in the structure of nutrition. It has been established that the diets of the population are deformed by the content of plastic, energy and catalytic components [4–6]. Such food does not have a modifying effect on the manifestations of exogenous factors of chemical, physical and biological nature.

Among the ways of radionuclide penetration into the body (inhalation, alimentary and cutaneous), alimentary one is of paramount importance, since people are in close contact with the environment via food. The optimality of this association depends on biological, ecological (natural and historical) and socio-economic factors.

The modern concept of radioprotective nutrition is based on the maximum possible reduction in the intake of radionuclides with food, inhibition of the processes of their absorption and accumulation in the body, as well as on the principles of rational nutrition.

Scientific researches have proved that rational nutrition balanced in the content of essential nutrients has a protective effect under the action of toxicants, including alimentary radionuclides. The number of diseases due to the lack of minerals and vitamins is steadily increasing [7–9]. This is due to the consumption of poor quality food, including food contaminated with anthropogens and contaminants.

To solve the problem of minimizing radiation loads on the population living in areas contaminated with radionuclides, it is necessary to reduce the level of contamination by radionuclides in food and absorption of toxicants in the digestive tract. These measures are implemented to ensure a balanced diet and, above all, using vitamins and antioxidants.

Vitamins are compounds of organic nature essential for the human body. Depending on the branching of the atoms, the molecule contains many vitamers of the same vitamin. Unlike amino acids, fatty acids, trace elements, etc., vitamins are not ingredients that are involved in plastic processes. They are also not utilised by the body as an energy source. Vitamins are involved in the regulation of metabolism, increase the body’s resistance under the action of anthropogens of chemical, physical and biological origin [10, 11]. Therefore, for people affected by the Chernobyl NPP accident, it is important to consume foods containing nutrients with radioprotective properties. Such compounds include antioxidative vitamins, in particular fat-soluble: A (retinol), D (calciferol), E (tocopherol). Vitamin deficiency impairs body resistance, and under the action of ionizing radiation, this process is enhanced by the inactivation of vitamins via radiation.

Currently, the most positive is the therapeutic agents containing a complex of physiologically active substances such as: flavonoids, carotenoids, fat- and water-soluble vitamins, which exhibit adaptogenic, immunomodulatory and antioxidant properties, increasing body radioresistance together [12–15].

Objective of the study is to summarize information about the properties, history of the discovery of vitamins, their modern classification; we provided information about their sources, daily intake of the population of different age groups and their importance for the persons who suffered from the Chernobyl NPP accident and live in environmentally dangerous territories.

Materials and methods. The following materials and methods were used: theoretical analysis and generalization of literature data were carried out, the actual content of vitamins in the diets of different age groups of the population (employable adults, children, pregnant women from different settlements in the District of Ivankiv of the Region of Kyiv) living in the territories contaminated due to Chernobyl NPP accident. The questionnaire, mathematical and statistical methods were used in the study.

Vitamin A (Lat. Retinolum) is carotenoids or antixerophthalmia factors grouped together in a chemical family of substances that exhibit similar biological activity. The chemical formula of retinol — С₂₀Н₃₀О. Retinols include: retinal (retinene, vitamin A₁ aldehyde), dehydroretinol (vitamin A₂) and retinoic acid. Provitamins include carotenoids, which are the metabolic precursors of vitamin A, the most important of which is β-carotene. Carotenoids are found in plants and retinoids — in animal products.

The highest amount of β-carotene is found in carrots, where its concentration depends on the variety and season of the year and ranges from 8 to 25 mg per 100 g of product. Fruits and vegetables of orange, yellow and green are a good source of carotene. They include:

– fruits: apple, pear, peach, apricot, cherry plum, cherry, lemon, orange, mango, grapefruit, persimmon, etc.;
– berries: raspberries, blackberries, currants, red currants, rose hips, etc.;
– vegetables: carrots, broccoli, bell peppers, tomatoes, etc.;
– gourds: pumpkin, watermelon, melon, zucchini, etc.;
– legumes: peas, soybean, beans, etc.;
– herbs: parsley green, hops, horsetail, borage, lemongrass, nettles, sage, sorrel, mint, etc.

The source of retinoids is fish oil, liver (especially beef), fish eggs, milk, butter, sour cream, cheese, egg yolk. Vitamin A is deposited in the liver, and it can also accumulate in other organs and tissues of the body.

Vitamin A was discovered in 1913 when two groups of scientists — Elmer McCallum and Margaret Davis of the University of Wisconsin, and Thomas Osborne and Lafayette Mendel of the Yale University, independently, concluded after a series of studies that butter and egg yolk contains unknown substance, that is, however, necessary for the normal functioning of the body. In 1931, Swiss chemist Paul Karrer described the chemical structure of vitamin A, for which in 1937 he was rewarded with the Nobel Prize in Chemistry. The same year, American chemists Harry Nicholas Holmes and Ruth Elizabeth Corbett crystallized this vitamin. In 1946, David Adrian Van Dorp and Joseph Ferdinand Arens synthesized artificial vitamin A, and in 1947, Otto Esler has developed a method for its industrial production [16].

The average daily demand of vitamin A for an adult is: 900 µg for men and 700 µg for women. The upper consumption limit for adults is 3,000 µg daily (Table 1) [17, 18]. Toxicity develops in case of excessive intake.

 

Table 1

Recommended daily intake of retinol

 

Upon intake, vitamin A is deposited in the liver in the form of palmitic acid ester. A depot is considered sufficient if it contains vitamin A of at least 20 µg/g of newborn liver tissue and 270 µg/g of adult liver tissue.

The content of vitamin A in the liver, as well as its plasma levels, is the parameter of body supply with retinol. When the level is less than 10 µg/dL of human blood, hypovitaminosis is established. A full-term neonate has enough vitamin A for 2–3 months after intrauterine development [19, 20].

Scientific researches in recent years have shown that in addition to the well-known role in providing vision processes (photoreception — photosensitive pigment rhodopsin, located on the outer segment of the retinal rods is responsible for twilight vision), vitamin A and its derivatives are required for the normal course of reproductive development, embryonal development, functioning of the immune system, it is an effective therapeutic agent in the treatment of various diseases [21–24].

Data are available on the antiproliferative effect of retinol and its possible use in the treatment of cancers [25–28].

It is known that retinol exhibitsantioxidant properties when the body is exposed to adverse environmental factors, increased physical and emotional activity. In chronic diseases, free radical oxidation is activated, and the protective antioxidant system does not cope with the neutralization of free radicals, which leads to the development of peroxidation syndrome [29, 30, 31].

Our long-term researches, conducted among the population of different age groups living in the territories of Ukraine environmentally dangerous as a result of the Chernobyl NPP accident, have found that the actual intake of vitamin A by pregnant women was 39.6 % of the physiological demand. As for other adult age groups, retinol intake met physiological demands by only 19.8 %. [32, 33].

Retinol content in the diet of children living in environmentally dangerous regions of Ukraine reached 40.0 to 60.0 % of the physiological demand (Table 2) [34].

 

Table 2

Retinol content in the diet of children (mg/day, %)

 

At the same time, the content of b-carotene in the diets of the adult population ranged from 43.3 to 49.2 % of the recommended values, and in children — from 69.3 to 85.3 %, respectively.

Unsatisfactory retinol content in diets is associated with the under-consumption of foods such as milk, fish, liver (especially beef), and b-carotene (it is converted to vitamin A in the human body; its A vitamin activity is 1/6 of vitamin A activity) such vegetables as carrots, broccoli, peppers; greens — parsley, dill; fruits and berries — apricots, peaches, persimmon, red currants, raspberries, currants.

Vitamin D ( Lat. Сalciferolum) is a fat-soluble vitamin. Chemical formula — C₂₈H₄₄O. CAS:50-14-6. This is a group of vitamins, collectively called calciferols: D₁, D₂, D₃, D₄, D ₅. And only vitamin D₂ and D₃ are biologically relevant for the human body. Vitamin D₂ (ergocalciferol) is obtained only with food, and D₃ (cholecalciferol) is synthesized in the skin of our body under exposure to UV. Vitamin D₁ (7DHC, cholesterol) is a precursor of Vitamin D. Vitamin D₄ (25(OH)D₃, calcidiol) is a depot and transport form that helps to maintain vitamin D levels in the blood. Vitamin D₅ (1,25(OH)D₃, calcitriol) with the participation of parathormone, is converted to the active form of 1,25-OH-dihydroxy-cholecalciferol (calcitriol) [35, 36, 37].

Vitamin D discovery stems from ancient times and is associated with a disease such as rickets. The first recollections of this disease are found in the writings of Soranus of Ephesus (98–138 AD) and Galen (131–211 AD). However, the clinical description of rickets was made by the English orthopaedist F. Glisson only in 1650 [38].

Fundamental research on the study of rickets and finding ways to cure it was conducted by Elmer McCollum in the early ’20s of the XX century. E. Melanby used in his work a component of fish oil, which showed anti-rickets action. Further, the following was proposed: classify the fish oil component used in the experiment as a vitamin [39, 40].

The American biochemist Harry Stenbock has shown that the use of UV-irradiated foods increases the amount of vitamin D in the body [41].

A few years later, German biochemist Adolf Windaus discovered dehydrocholesterol, the precursor of vitamin D, for which he was awarded the Nobel Prize in Chemistry in 1928. Further, the structure of active vitamin D₃ was also established [42].

Since it was the fourth vitamin discovered by scientists, it was marked with the fourth letter of the Latin alphabet — D [16].

After the discovery of mercury-quartz lamp in 1919 by the German doctor Kurt Huldschinsky, vitamin D became known as “vitamin of the sun”. UV radiation has since been widely used in medical practice, in particular for the prevention of avitaminosis D in humans in winter and spring.

Vitamin D is the main component in ensuring the growth and normal development of the bone system and in preventing diseases such as rickets and osteoporosis [43–47].

In recent years, vitamin D deficiency has also been found to be associated with weight gain, diabetes mellitus, hypertension, venous thromboembolism, multiple sclerosis, impaired immunity, autoimmune disorders, increased risk of a number of tumours [48–54].

Vitamin D participates in the regulation of calcium-phosphorus metabolism in the body. It contributes to the retention and deposition of calcium in bone tissue, which in turn prevents them from softening or osteomalacia. This vitamin stimulates the absorption of magnesium and phosphorus in the body, enhancing the penetration of minerals through the intestinal epithelium. Calciferol improves RNA and DNA transcription, which prevents the development of hereditary diseases, increases the body’s resistance to infection and maintains muscle strength.

Vitamin D is used in the complex treatment of multiple sclerosis. For example, due to its ability to stimulate the absorption of magnesium and calcium, calciferol restores the protective membrane of the nerves, as well as prevents the development of cancer cells, therefore, it is used in the treatment of leukaemia, cancer of the prostate, ovaries, breasts and brain.

Vitamin D deficiency can occur due to liver disease, impaired bile excretion (hepatic failure, mechanical jaundice, etc.). Intake of D with food is vital. Recommended dietary allowance (RDA) for healthy subjects aged 1 to 70 years (including pregnant and breastfeeding women) is 15 µg or 600 IU (international units).

Calciferol is soluble in fats, therefore, like other fat-soluble vitamins, it has the ability to accumulate in adipose tissue. Vitamin D reserves, which are deposited by the body during summer, are gradually consumed in winter.

Epidemiological studies have shown that the majority of both adults and children, including those living in the territories contaminated due to Chernobyl NPP accident, suffer from hypovitaminosis D. Its deficiency reaches 83–96% [55–57].

It is known that when the absorption of calcium is impaired due to lack of vitamin D, the size of the thyroid gland increases (hyperplasia) up to the formation of benign (rarely malignant) tumours. When its function is impaired, primary or tertiary hyperparathyroidism can occur [58, 59].

According to the results of our research, the content of calciferol in the diets of examined pregnant women living in the environmentally hazardous regions due to Chernobyl NPP accident was 0.84 µg/day, which satisfied physiological demands by 16.8 %. As for other adult categories, their supply with vitamin D was 1.51 and 1.37 µg/day, or 60.1 and 55.4 % of the physiological demand for men and women, respectively.

Children’s diets are also deficient in vitamin D regardless of the place of residence and study period. For example, in the examined 10-year-old boys, vitamin D deficiency was 72.9 %; in 11-year-old boys — 65.8 %; in 12 and 13-year-old boys — 68.9 % and 76.2 %, respectively [32, 33, 34].

Low calciferol levels can be caused by low insolation and under-consumption of products such as fish (especially marine), marine fish caviare, milk, cheese (hard types) and liver.

The prevalence of vitamin D deficiency also depends on seasonal changes and geographic latitude. The deficiency in the body increases at the end of winter and spring and decreases in summer. An increase in the solstice angle in winter, morning, or late evening is the cause of the longer path of solar UV B-photons through the ozone layer that absorbs them. Therefore, the population of the territory, including the northern regions of Ukraine, which are outside the high solar insolation, should take a preventive dose of vitamin D in winter [60–63].

Prescription of vitamin D for prevention of diseases among persons aged 18 to 50, should correspond to a dose of at least 600–800 IU per day, for pregnant women — 900–1,200 IU, for children — 400–600 IU, respectively [18, 64, 65].

In order to enrich the diet with vitamin D, hard cheeses, caviar, egg yolk, liver, fat marine fish, fish oil, butter and whole milk should be added.

Vitamin E (Lat. Tocopherolum). Tocopherols (from ancient Greek τόκος — ancestral or promoting childbirth) include a group of natural compounds derived from tocol (α, β-, γ-tocopherols). The chemical formula of tocopherol — C₂₉H₅₀O₂. The most important biologically active compounds are tocopherols and tocotrienols.

Vitamin E was discovered in 1922 by scientists at the University of California, Herbert Evans and Catherine Scott. In 1936, α-tocopherol was first isolated by a group of scientists led by H. Evans, and in 1938, it was synthesised chemically [16].

Tocopherol deficiency is very common [57, 66]. Deep hypovitaminosis is rare, it develops mainly in preterm infants (manifested as haemolytic anaemia).

Vitamin E is the versatile protector of cell membranes from oxidative damage. At the same time, tocopherol occupies a position in the membrane that prevents oxygen from contacting with the unsaturated lipids of the membranes (forms hydrophobic complexes), and thus protects the biomembranes from their peroxide destruction.

Vitamin E is mostly deposited in the pituitary gland, testes and adrenal glands. Tocopherols promote inactivation of free radicals in the body [18, 67–69].

Vitamin E is a natural factor in protecting polyunsaturated fatty acids from oxidation. It affects the function of the reproductive and endocrine glands. The most beneficial radioprotective effect is the combination of the use of tocopherol, retinol and ascorbic acid. Vitamin E can be obtained with the foods listed in Table 3.

 

Table 3

Tocopherol content in products of animal and plant origin

 

Tomatoes are known to be rich in lycopene, β-carotene and vitamin E, which is an active antioxidant that inactivates free radicals and slows the development of atherosclerosis. These substances are effective in the treatment of patients with hypertension [70].

For adults, a single preventive dose of vitamin Eis, on average, 100 mg, a single highest dose is 400 mg; average daily dose — 200 mg, highest daily dose — 1000 mg. Vitamin E at a dose of 100 mg can be given to children after 12 years [18].

According to our research, the rate of consumption of tocopherol in pregnant women living in ecologically dangerous regions of Ukraine was 14.9 mg/day, which provided a physiological demand. Fertile-age adults consumed: men — 14.6 mg/day; women — 15.1 mg/day, which completely covered the physiological demand.

As for the children, according to our data, consumption of tocopherol was slightly higher than physiological demands (Table 4).

 

Table 4

Tocopherol content in the diet of children (mg/day, %)

 

Consumption of such foods as vegetable oil, butter and chicken meat by adults covered a physiological demand for vitamin E. As for children, consumption of butter, sour cream, vegetable oil and eggs exceeded the recommended values, which also affected the content of vitamin E in the diets of this category of children (Table 4) [32–34].

Vitamin K (Lat. Phytomenadionum). The term vitamin K is used for 2-methyl-1,4-naphthoquinone and all its derivatives. The chemical formula of the vitamin — C₃₁H₄₆O₂. It plays a significant role in the metabolism of bone and connective tissue and promotes kidney function. This vitamin is involved in the absorption of calcium and provides the interaction between calcium and vitamin D. The studies have proved that vitamin K and vitamin D, when used together, significantly slows down the loss of bone tissue, prevent osteoporosis, bone fractures, and prevent sclerosis of arteries [71–73].

To date, we know about two vitamins that are classified as Phytomenadionum, which is K₁ isolated from alfalfa and a substance isolated from decaying fish meal, K₂. A range of bacteria, in particular, Escherichia coli, are capable of synthesizing vitamin K₂ in the human colon, under certain conditions [18].

In addition to natural vitamins (K₁ and K₂), there are a number of synthetically obtained naphthoquinone derivatives that also exhibit anti-haemorrhagic activity. They include such compounds as Vitamin K₃ (2-methyl-1,4-naphthoquinone), Vitamin K₄ (2-methyl-1,4-naphthohydroquinone), Vitamin K₅ (2-methyl-4-amino-1-naphthohydroquinone), Vitamin K₆ (2-methyl-1,4-diaminonaphthoquinone), Vitamin K₇ (3-methyl-4-amino-1-naphthohydroquinone) [74, 75].

Vitamin K was discovered in 1929 by Danish scientist Henrik Dam, who researched changes in the body of chickens consuming a cholesterol-free diet. The scientist observed that in a few weeks, the experimental animals had haemorrhage into the subcutaneous tissue, muscles and other tissues of the body. Addition of purified cholesterol did not eliminate pathological changes. Cereal grains and other plant products have been found to have a curative effect. Together with cholesterol, they eliminated substances, which also contributed to the increase in blood clotting [76]. The name of vitamins K has been fixed for this group of substances. The first report of these compounds was made in a German journal called the coagulation vitamins.

In 1939, in the laboratory of the Swiss scientist P. Karrer, vitamin K was isolated from alfalfa for the first time, and it was called phylloquinone. In the same year, American biochemists S. Binkley and E. Doisy have obtained from decaying fish meal a substance that exhibited anti-haemorrhagic action but with properties other than the compound isolated from alfalfa. This substance was called vitamin K₂, as opposed to vitamin isolated from alfalfa and called vitamin K₁[77].

In 1943, H. Dam and E. Doisy were awarded the Nobel Prize for discovering and establishing the chemical structure of vitamin K.

Vitamin K is widely distributed in nature, the main source of which is green leafy vegetables such as spinach, various types of cabbage: white, cauliflower, Brussels sprouts, broccoli. Its significant amount is found in green tea, great nettle leaves, parsley, soybean and its products of processing, cereals, pumpkins, avocados and some fruits — kiwi, bananas, and in animal products — meat, milk, and dairy products, eggs [78–81].

Vitamin K in the liver stimulates the synthesis of prothrombin, proconvertine and other factors that contribute to blood clotting, which increases the resistance of blood vessels, supports the synthesis of ATP creatine phosphatase and other enzymes, and it is also one of the components of biological membranes of the cell and actively influences cell structures and properties [82, 83].

In recent years, a great attention has been paid to the neuroprotective function of vitamin K [84–87]. Vitamin K deficiency in humans under normal conditions is virtually impossible — intestinal microflora constantly produces it in small quantities.

Vitamin K is a fat-soluble vitamin, therefore, sufficient amount of fats and fatty acids should be present in the intestine for its digestion.

Hypovitaminosis K most commonly occurs with impaired fat metabolism and bile secretion in the intestine. This usually occurs in patients with hepatitis or hepatic cirrhosis. In young children, vitamin K deficiency is manifested in the form of haemorrhagic disease of the newborn, which is associated with functional immaturity of the biliary system, impaired fat absorption and, as a consequence, vitamin deficiency [88].

The recommended daily allowance of vitamin K for different age groups of the population of Ukraine is from 100 to 110 µg/day for adults, from 55 to 65 µg/day for the elderly and from 5 to 65 µg/day for children (Table 5) [89].

 

 

 

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