Selenium: Youth, Activity, Productivity
In the human body selenium stimulates the immune system, prevents cardiac dysfunction and oncological diseases, and is necessary for the normal function of the thyroid gland and the proper functioning of the nervous system.
The daily requirement for selenium in the human body is 20–70 mcg. Selenium deficiency develops when this element is introduced in amounts of 5 mcg/day or less. In parenteral nutrition, at least 30 mcg of selenium should be supplied to the human body daily.
The Food and Drug Administration of the U.S. government uses a different approach in its calculations. A safe level of Se consumption is considered to be one at which the activity of glutathione peroxidase I (GPX–I) reaches its maximum level (plateau). This amount is 70 mcg/day for adult men and 55 mcg/day for women.
It should be noted that glutathione peroxidase I was the first selenium-specific protein discovered in eukaryotes and catalyzes the reaction:
H2O2 + 2 GSH = GSSG + 2H2O
Under the action of GPX–I, oxidized glutathione (GSSG) is formed, which is immediately reduced by the flavin glutathione reductase present here using NADH.
The main biological role of GPX–I, therefore, lies in the detoxification of the reactive oxidant – hydrogen peroxide, which is formed in erythrocytes during the transport of oxygen to tissues.
Classical GPX–I is a protein with a molecular weight of about 80 kDa, formed by four identical subunits with a molecular weight of 23 kDa, organized into a square-shaped complex. Each subunit contains 1 atom of selenium in the form of selenocysteine.
The upper limit of the safe consumption area for Se is primarily determined based on epidemiological observations of populations in regions with excessive levels of Se. It has been shown that in several populations in Latin America, at dietary Se consumption levels of up to 400 mcg/day, no significant adverse effects are observed. Therefore, the amount of 350–400 mcg/day is accepted by many authors as the upper limit of the area.
Under normal conditions, Se enters the bodies of humans and animals primarily in the form of selenium-containing amino acids – selenomethionine (Se–Met) and selenocysteine (Se–Cys). Artificial supply of selenium to the body in cases of dietary deficiency can be done in the form of sodium selenite or selenate. Both organic and inorganic selenium are easily absorbed in the gastrointestinal tract.
Selenium accumulates primarily in the kidneys and liver, bone marrow, heart muscle, pancreas, lungs, skin, and hair.
The proportion of organic and inorganic selenium in the body varies significantly.
Selenate and selenite anions that enter with food are quickly reduced by the protein thioredoxin to hydrogen selenide, which is present at physiological pH values, mainly in the form of hydroselenide anion (HSe–). The necessary cofactor for this process is reduced glutathione (GSH), and it is assumed that selenodiglutathione (GS–Se–SG) is formed as an intermediate.
Some of the resulting hydrogen selenide binds to specific selenium-binding proteins. The capacity of this pool is quite limited. Excessive amounts of hydrogen selenide are slowly subjected to enzymatic methylation, sequentially forming methylhydroselenide, dimethylselenide, and the cation trimethylselenonium. These Se compounds are excreted in urine, and dimethylselenide is also excreted in large quantities through sweat.
A strictly defined amount of selenium that is part of the hydrogen selenide pool is incorporated into the highly specific process of synthesizing so-called Se-specific selenoproteins, which include components of vital antioxidant systems and other enzymes.
The aforementioned possibilities for utilizing hydrogen selenide in the body are quantitatively limited, and when excessive amounts of inorganic selenium are introduced into the body, it can accumulate in tissues in the form of free hydroselenide anion. This form of Se is extremely toxic.
Biological role in the human body. The role of the trace element selenium in the body is primarily determined by its incorporation into one of the most important antioxidant enzymes – Se-dependent glutathione peroxidase, which protects cells from the accumulation of products of peroxidative oxidation, thereby preventing damage to its nuclear and protein-synthesizing apparatus. Selenium is a synergist of vitamin E and enhances its antioxidant activity. Selenium is a component of the enzyme – iodothyronine 5-deiodinase (an enzyme that controls the formation of triiodothyronine), as well as being part of muscle tissue proteins and, importantly, myocardial proteins. In the form of selenoprotein, it is a component of testicular tissue. Therefore, selenium deficiency leads to a weakening of antioxidant status, anticancer protection, causes myocardial dystrophy, sexual dysfunction, and immunodeficiencies.
Additionally, selenium exhibits antimutagenic, antiteratogenic, radioprotective effects, stimulates detoxification protection, normalizes nucleic acid and protein metabolism, improves reproductive function, normalizes the metabolism of eicosanoids (prostaglandins, prostacyclins, leukotrienes), and regulates the function of the thyroid and pancreas. Thus, selenium is classified as a geroprotector – a substance that protects against aging.
Synergists and antagonists of selenium. In cases of selenium deficiency in the body, there is an increased accumulation of arsenic, cadmium, and mercury. Selenium is an antagonist of mercury and arsenic and can protect the body from excessive accumulation of cadmium, lead, thallium, and silver.
Vitamin E aids in the absorption of selenium. However, it is important to note that high doses of vitamin E can cause an increase in blood pressure.
Excessive intake of mercury, copper, arsenic, sulfates, paracetamol, phenacetin, and antimalarial drugs can lead to selenium deficiency in the body.
Signs of selenium deficiency. Cancer and heart diseases, fatigue, stunted growth, elevated cholesterol levels, infections, impaired liver function, pancreatic insufficiency, infertility.
There is a high degree of correlation between selenium deficiency and tumor diseases, such as stomach, prostate, colon, and breast cancer.
The result of selenium deficiency is an increase in the activity of glutathione S-transferase in the liver, kidneys, and lungs. Changes in the metabolism of thyroid hormones are observed. The combination of selenium and vitamin E deficiency serves as a cause of liver necrosis and exudative diathesis in experiments.
Thus, a diet reduced in selenium and vitamin E leads to hair loss, growth retardation, and inability to reproduce in animals. In those animals that do not receive enough selenium, the so-called “white muscle disease” develops, characterized by muscle dystrophy, liver necrosis, and protein deficiency.
Selenium deficiency in humans leads to the disruption of cellular membrane integrity, a significant decrease in the activity of enzymes grouped on them, calcium accumulation inside cells, disruption of amino acid and ketone body metabolism, and a decrease in energy-producing processes.
In 1979, Chinese scientists first described the relationship between selenium consumption and Keshan disease – endemic cardiomyopathy in children and young women. The disease is associated with low dietary selenium intake and low selenium levels in blood and hair, alongside a borderline deficiency status of vitamin E. For a long time, it was believed that selenium deficiency was the sole cause of this disease. It is now proven that the cause of the disease is an enteroviral infection (Coxsackie virus B3) against the backdrop of severe selenium deficiency and insufficient calcium intake from food. Moreover, dietary oxidative stress (deficiency of selenium and vitamin E) allows the virus to mutate into a virulent strain that causes heart damage.
Keshan disease is characterized by arrhythmias, enlargement of the heart, focal necroses of the myocardium, followed by heart failure. Signs of thromboembolism are sometimes observed. The disease has a high mortality rate.
Many countries have regions with insufficient selenium content in the environment. Such countries primarily include China, New Zealand, and countries in Northern and Central Europe.
According to the staff of the Institute of Nutrition of the Russian Academy of Medical Sciences and the results of climatic studies, selenium deficiency is observed throughout most of the Russian Federation. In Russia, the most selenium-deficient regions include, first of all, the Northwestern region, Upper Volga, Udmurtia, and Transbaikal. The reduced selenium supply to the population of Russia is manifested by an increase in the incidence of several infectious, cardiovascular, oncological, and gastroenterological diseases. Thus, the issue of selenium enrichment in the diet of the population in these regions is relevant.
When discussing the selenium supply to the human body, it should be noted that its assimilation can be sharply reduced in certain pathological conditions. In cases of gastric ulcer, acute pancreatitis, chronic pancreatitis, hepatitis (including alcoholic origin), cirrhosis of the liver, cystic fibrosis, celiac disease, and short bowel syndrome, even with normal Se intake from the diet, a disruption of its status can develop due to the inefficiency of selenium utilization or absorption mechanisms. In other cases, such as exposure to increased background ionizing radiation or chronic intoxication with Hg and Cd compounds, selenium deficiency may develop due to a sharp decrease in its retention. Therefore, some authors consider the possibility of prolonged intake of selenium supplements (especially organic) in very high dosages (up to 400–700 mcg/day) for these categories of patients.
In several countries (Finland, Sweden), the issue of enriching people’s diets with selenium has been addressed by adding selenium-containing fertilizers to the soil.
Excessive intake of selenium and its compounds is noted among workers engaged in the electronic, foundry, copper smelting, glass, paint, oil refining, chemical (pesticide production), and pharmaceutical (production of selenium sulfide, sodium selenite) industries.
Cases of selenosis in animals and humans have been described, caused by excessive intake of this element into the body through plants that are selenium concentrators (Astragalus mollis, Stanleya pinnata, Haplopappus glaucus, etc.). In the Chinese province of Hubei, cases of selenium poisoning have been recorded, with environmental intake of 3–7 mg per day. Increased selenium content in the soil is observed in significant areas of Australia and the USA.
In Russia, excess selenium in the environment is found in Tuva, Yakutia, and the Urals.
Main manifestations of selenium excess: unstable emotional states; garlic-like odor from the mouth and skin (formation of dimethylselenide), nausea and vomiting, liver dysfunction; skin erythema; runny nose, bronchopneumonia, pulmonary edema (when inhaling selenium vapors); hair loss; brittle nails.
Selenium is necessary: in diseases of the cardiovascular system, chronic liver and biliary tract diseases, hyperlipidemia, pancreatic diseases, infertility.
Dietary sources of selenium: garlic, garlic greens; mushrooms, especially white mushrooms, butter mushrooms, and champignons; pork fat, meat; grains and legumes: beans, peas, buckwheat, corn, oats, millet, soft wheat, hard wheat, long-grain white rice, brown unpolished rice, rye, soybeans, beans, lentils, barley; fruits: viburnum, black rowan; olives; seaweeds; nuts and seeds: very high selenium content is characteristic of Brazil nuts (100 g contains 1554% of the daily requirement for the human body), high – peanuts, cashews, coconut, sesame, poppy, pine nuts, sunflower seeds, pumpkin seeds, pistachios; vegetable oils: pumpkin oil.
The concentration of selenium depends on its level in the soil of the area where animals and plants are grown.
One of the best sources of selenium in an easily digestible and biologically active form is yeast, especially brewer’s yeast. Ordinary baker’s yeast (Saccharomyces cerevisiae) is also beneficial.