Introduction  

Selenium is a vital trace element that plays a key role in antioxidant protection, immune regulation, and thyroid hormone metabolism [1]. Despite its need for trace amounts, selenium deficiency remains a global problem, especially in regions with a low content of this element in the soil and, as a result, in food [2, 3]. According to the World Health Organization (WHO), about 1 billion people worldwide are deficient in selenium to one degree or another [4]. In Russia, selenium deficiency is most pronounced in the northwestern and central regions, where soils are poor in this element. According to research by the Institute of Nutrition of the Russian Academy of Medical Sciences, up to 40% of the Russian population consumes selenium below the recommended daily allowance (55-70 micrograms for adults), which creates a predisposition to the development of pathologies associated with its deficiency [5, 6]. Figure 1 shows the scheme of selenium metabolism in the body.

The main reason for insufficient intake of selenium in the body is its low content in the food chain [7]. Selenium accumulates in plants from the soil and then enters the human body through animal and plant products [8]. However, in regions with selenium-depleted soils (for example, in some parts of China, Finland, and Russia), even a balanced diet does not provide sufficient amounts of this trace element [9]. Historically, the most severe forms of selenium deficiency have been recorded in China, where, in Keshan Province in the mid-20th century, a link was found between extremely low selenium levels and the development of cardiomyopathy (Keshan disease) [10-12]. In Russia, the most vulnerable groups are residents of the Northwestern Federal District, Siberia, and the Far East, where the selenium content in soils is 2-3 times lower than in the southern regions [13, 14].

In addition to geochemical factors, selenium deficiency can lead to:

• Insufficient consumption of selenium-containing products (seafood, Brazil nuts, meat, eggs) [15].
• Malabsorption in diseases of the gastrointestinal tract (celiac disease, Crohn's disease) [16, 17].
• Increased selenium consumption in chronic inflammatory processes, pregnancy, and intense physical exertion [18-20].

The effects of selenium deficiency are diverse and affect almost all body systems. The most significant are:

• Oxidative stress. Selenium is a part of the enzymes glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), which neutralize reactive oxygen species (ROS). With a lack of selenium, the activity of these enzymes decreases, which leads to the accumulation of ROS, damage to lipids (malondialdehyde, MDA), proteins, and DNA [21-23].
• Violation of the immune response. Selenium modulates the differentiation of T-lymphocytes and the production of cytokines. Its deficiency shifts the balance towards the Th2 response, reducing antiviral and antitumor protection [24].
• Thyroid gland dysfunction. Selenium is necessary for deiodinases that convert thyroxine (T4) into active triiodothyronine (T3) [25].

Selenium is a key component of selenoproteins that perform antioxidant and immunoregulatory functions [26]. The most studied of them is glutathione peroxidase (GPx), which catalyzes the reduction of hydrogen peroxide and lipid hydroperoxides [27]. With selenium deficiency, GPx activity decreases, which leads to:

• Increased levels of malonic dialdehyde (MDA), a marker of lipid peroxidation. Studies show that in individuals with low selenium levels, plasma MDA concentrations may be 30-50% higher than normal [28].
• Accumulation of 8-hydroxydeoxyguanosine (8-OHdG) – an indicator of oxidative DNA damage associated with cancer risk [29, 30].

The effect of selenium on the immune system is realized through several mechanisms:

• Regulation of the cytokine profile. Selenium contributes to the predominance of the Th1 response (interferon-γ, IL-2), which is critical for combating intracellular pathogens. Deficiency increases the Th2 response (IL-4, IL-6), which increases the risk of allergic and autoimmune reactions [31, 32].
• Activation of NK cells and phagocytosis. Selenium deficiency reduces the cytotoxic activity of natural killers by 20-40%, which is confirmed by studies on models of viral infections [33, 34].
• Protection against immunosuppression. Under conditions of oxidative stress, selenium prevents apoptosis of immunocompetent cells, maintaining their functional activity [35, 36].

Since dietary sources of selenium are not always available, biologically active additives (dietary supplements) based on selenomethionine are becoming an effective tool for correcting deficiency [37, 38]. Selenomethionine is an organic form of selenium with high bioavailability (up to 90% compared to 50% for sodium selenite) [39]. Clinical studies demonstrate that taking 100-200 mcg/day of selenomethionine for 8-12 weeks leads to:

• Normalization of plasma selenium levels (an increase of 40-60%) [40, 41].
• Reduction of MDA and restoration of GPx activity [40].
• Improved immune parameters (increased IgA, decreased proinflammatory cytokines) [42].

In Russia, where selenium deficiency is widespread but often remains undiagnosed, the use of dietary supplements can become an important measure to prevent related conditions, from chronic fatigue to increased risk of cardiovascular and autoimmune diseases [43, 44].

The purpose of the study

In this work, we evaluate the effect of a 12-week intake of dietary supplements based on selenomethionine (200 mcg/day) on markers of oxidative stress (MDA, GPx) and immune status (IgA, IL-6, TNF-α) in people with moderate selenium deficiency. The data obtained can serve as a basis for recommendations on the correction of nutritional status in risk groups.

Materials and Methods

The present study is a prospective, randomized, double-blind, placebo-controlled trial aimed at evaluating the effect of selenomethionine in the form of dietary supplements on biochemical and immunological parameters in individuals with moderate selenium deficiency. The study was conducted on the basis of the Stavropol Regional Clinical Diagnostic Center (Stavropol, Russia) in the period from September 2024 to January 2025. The study protocol was approved by the local ethics committee, and all participants provided written informed consent.

The study included 60 volunteers aged 18 to 60 years, divided into two groups: the main group (taking selenomethionine) and the control group (placebo) (Table 1). Inclusion criteria: plasma selenium levels below 70 mcg/L, absence of chronic diseases in the stage of decompensation, absence of intake of selenium-containing supplements during the last 3 months. Exclusion criteria: pregnancy, oncological diseases, severe liver and kidney pathologies.

The groups were statistically homogeneous in the main parameters (p > 0.05), which excluded the influence of confounding factors on the results of the study.

The participants in the main group received 200 mcg/day of selenomethionine in capsule form, while the control group took a placebo (microcrystalline cellulose) in an identical package. The duration of admission was 12 weeks. All participants were instructed not to change their usual diet or take other vitamin and mineral supplements during the study.

Methods for estimating parameters

• Biochemical analyses

• Selenium levels in blood plasma were determined by inductively coupled plasma mass spectrometry (ICP-MS).
• Glutathione peroxidase (GPx) activity in red blood cells was measured spectrophotometrically using a commercial reagent kit (specify manufacturer).
• The concentration of malonic dialdehyde (MDA) was assessed by reaction with thiobarbituric acid (TBK test).

• Immunological studies

• The level of immunoglobulins (IgA, IgG) and proinflammatory cytokines (IL-6, TNF-α) was determined by enzyme immunoassay (ELISA).
• Lymphocyte subpopulations (CD4+, CD8+, NK cells) were analyzed using flow cytometry.

• The survey

For a subjective assessment of well-being, participants filled out the SF-36 questionnaire (The Short Form Health Survey), which included questions about energy levels, physical activity, emotional state, and the presence of symptoms (fatigue, headache). The survey was conducted before the start of the study and after 12 weeks of taking dietary supplements.

The data was processed using the SPSS 26.0 program. To compare the groups, the Student's t-test (normal distribution) or the Mann-Whitney criterion (nonparametric data) was used. Correlation analysis was performed using the Pearson coefficient. The level of statistical significance was set at p < 0.05.

Results and Discussion

Dynamics of selenium levels and indicators of oxidative stress

After 12 weeks of taking selenomethionine at a dose of 200 mcg /day, a statistically significant increase in selenium concentration in blood plasma was observed in the main group. The average selenium level increased from 58.2 ± 9.1 mcg/L to 92.4 ± 11.3 mcg/L (p < 0.001), while no changes were recorded in the placebo group (59.4 ± 8.7 mcg/l to 60.1 ± 9.2 mcg/l; p = 0.87). A similar trend was observed when measuring the selenium content in red blood cells: an increase from 125.6 ± 15.2 ng/ml to 178.3 ± 20.1 ng/ml (p < 0.001) in the main group (Table 2).

In parallel with the normalization of selenium status, a significant improvement in oxidative stress indicators was recorded in the main group. The activity of glutathione peroxidase (GPx) increased by 38% (from 35.2 ± 4.1 to 48.6 ± 5.3 U/mg of protein; p < 0.001), whereas no changes were observed in the placebo group. Malondialdehyde Concentration (MDA) as a marker of lipid peroxidation decreased by 33% (from 4.8 ± 0.9 to 3.2 ± 0.7 nmol/ml; p < 0.001).

Effect on immunological parameters

The intake of selenomethionine had a significant modulating effect on the immune system (Table 3). In the main group, there was an increase in the level of secretory IgA in saliva from 45.2 ± 8.1 mg/dl to 58.7 ± 9.3 mg/dl (p < 0.01), which indicates increased mucosal immunity. The concentration of the proinflammatory cytokine IL-6 decreased from 12.4 ± 2.1 pg/ml to 8.3 ± 1.7 pg/ml (p < 0.01).

Of particular interest are changes in lymphocyte subpopulations. The proportion of NK cells (CD56+) increased from 14.2 ± 2.1% to 17.6 ± 2.5% (p < 0.01), indicating an increased antitumor and antiviral immune response. The ratio of CD4+/CD8+ lymphocytes also changed towards optimal values (from 1.8 ± 0.3 to 2.1 ± 0.4; p = 0.03).

Results of the quality of life survey

Analysis of the SF-36 questionnaire data revealed a significant improvement in quality of life in the main group (Table 4). The biggest changes affected the scales of "Vital activity" (an increase of 25%, p < 0.01) and "General health" (an improvement of 19%, p < 0.05). Participants noted a decrease in fatigue and an increase in performance after 6 weeks of taking the supplement.

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