Selenium – Nutrient Fact Sheet

Part I

In the scholarly and clinical literature, trace minerals are defined as vital nutrients that are required by the body in small amounts to perform essential physiological and biochemical functions (enzyme activity, cell production, etc.). One of these trace minerals is selenium, whose biological roles are broad and mediated. For instance, selenium primarily acts through selenoproteins within the body. These (selenoproteins) are a group of proteins that contain the amino acid selenocysteine (Rayman, 2012). While selenium performs several functions, its role in antioxidant defense through glutathione peroxidases (GPx) is more recognized and appraised in the peer-reviewed and clinical literature. Steinbrenner and Sies (2013) inform through their work that GPx enzymes play a crucial part in protecting cellular membranes, DNA, and other proteins through the reduction of hydrogen peroxide. The reviewed evidence concerning selenium also reveals that the trace mineral supports thioredoxin reductases. The mentioned process contributes directly to not just DNA synthesis but also its repair and redox balance.

The appraised literature and reports on selenium also inform that it influences the metabolism through thyroid hormone. The process facilitates regulating metabolic rate, thermogenesis, and growth. Thus, it can be inferred that the selenium-related deficiency may contribute directly and robustly to hypothyroid symptoms even when iodine intake is adequate (Schomburg & Köhrle, 2008). The benefits of selenium concerning the robustness of immune function are also well-documented. Shao et al. (2020) found that systems like GPx and thioredoxin play a significant role in cytokine production and inflammatory signaling. Similarly, Addinsall et al. (2018) found that selenoproteins regulate endoplasmic reticulum stress responses and T-cell activation (Hoffmann & Berry, 2008). The discussed roles of selenium demonstrate that it is more than a constituent of an oxidative defense. Rather, it is an essential part of endocrine regulation and immune activity.

Concentration Levels in Food

Studies have found that the concentration levels of selenium in food depend on several factors. Tan et al. (2020) have higher selenium levels are reflected in the produce from that soil. Similarly, agricultural methods of a region also influence selenium levels in the agricultural products. Regarding its primary dietary sources, we learn that they include Brazilian nuts and seafood. Selenium can also be sourced through offal, eggs, poultry, and cereals. Chang et al. (2023) note that though Brazilian nuts are typically rich in selenium, the variability is high. For instance, a single nut can contain 68–91 µg depending on soil content. Selenium can also be procured through animal and plant foods. In animal foods, we learn, selenium is often available in the form of selenomethionine or selenocysteine, whereas plant foods typically contain selenomethionine. The micronutrient is also bioavailable; however, its bioavailability varies across chemical forms. For instance, selenium is highly bioavailable as selenomethionine (up to 90% absorption), whereas inorganic forms such as selenite and selenate have lower and more variable absorption (Fairweather-Tait et al., 2011).

Recommended Intakes and Guidelines Related to Selenium

Since selenium has several health-related benefits, many states have policies and guidelines regarding its intake. However, it is essential to acknowledge that these recommendations regarding selenium intake vary across countries. This is primarily because the soil selenium content is different across geographical regions. For instance, the selenium content in soil is low in Europe. Thus, regions or states recommend different daily intakes of selenium to avoid any health complications. The table below helps understand how nutrient values differ slightly across institutions and states.

Authority	Recommended Intake
UK RNI	The institution recommends 60 µg/day for women and 75 µg/day for men
EU NRV	The institution recommends 55 µg/day for both men and women
US RDA	The institution recommends 55 µg/day for both men and women

The higher intake of selenium can cause health-related complications through toxicity.

Therefore, relevant institutions have developed a tolerable upper intake level (UL)

The Tolerable Upper Intake Level (UL)

• European Food Safety Authority (EFSA): According to the institution, the upper limit for selenium intake is UL = 255 µg/day (EFSA, 2014). Above this limit, the chronic intake of selenium can have severe health implications.
• US Institute of Medicine (IOM): The institution defines the upper limit for selenium intake at UL = 400 µg/day.

Deficiency Trends and Implications

Selenium-related deficiency is not very prevalent globally. The information suggests that selenium deficiency is reported in very particular regions and populations. Studies caution that when an individual develops a deficiency of selenium, they become vulnerable to many health challenges. In this section, clinical manifestations of the deficiency will be listed and succinctly discussed.

• Fatigue and muscle weakness: Many studies have found that inadequate selenium presence in the body can cause fatigue and weaken the muscles. Consequently, the physical activities of a person are affected profoundly and adversely.
• Poor immunity: Since selenium plays a significant role in keeping the immune system robust, its deficiency can make individuals vulnerable to different diseases/infections.
• Infertility or impaired sperm motility:text> Selenium helps in DNA synthesis. Also, it repairs DNA and redox its balance.
• Metabolism: Thyroid function is impaired as selenium deficiency becomes acute. Therefore, selenium deficiency will inevitably lead to poor metabolic regulation.

It should also be acknowledged that severe deficiency is linked with two classical diseases:

1. Keshan disease: A cardiomyopathy associated with viral co-factors, historically reported in parts of China (Beck et al., 2003).
2. Kashin–Beck disease: An osteoarthropathy causing joint degeneration.

Mild insufficiency may reduce selenoprotein expression without overt clinical symptoms. Suboptimal status is associated with impaired antioxidant capacity, increased inflammatory markers, and potential thyroid dysfunction.

At-Risk Groups and Medication Interaction

At-Risk Groups

The reviewed literature identifies six (6) at-risk groups, which are as follows;

• Individuals living in low-selenium regions such as Europe and parts of China
• Selenium deficiency is very much a possibility for Individuals who are vegans and vegetarians. This is due to the fact that they take little seafood or animal protein.
• Gastrointestinal disorders also make individuals vulnerable to selenium deficiency.
• Patients receiving total parenteral nutrition without selenium.
• People with high oxidative stress (thyroid disorders, chronic inflammation) require more selenium intake than the rest.
• The selenium-related requirements of pregnant women increase significantly, making them an at-risk group.

Medication Interaction

Selenium interacts with medications in several ways. For instance, Anticonvulsants like valproate reduce the antioxidant enzymes in the body. The development leads to an increased demand for selenium. Since selenium impacts thyroid hormone metabolism, it has the potential to modify the effect of a drug. Furthermore, medications like Cisplatin can lower selenium levels in the body.

Part II

Therapeutic Use of Selenium

Selenium has been used in many clinical trials to address chronic and non-chronic healthcare challenges. In this section, three studies on the therapeutic use of selenium will be methodically reviewed.

Therapeutic Evidence I: Selenium in Autoimmune Thyroiditis

Selenium-based therapeutic interventions have been extensively employed to effectively manage and curb Hashimoto’s thyroiditis. The rationale to use selenium as a therapeutic intervention is based on its established role in antioxidant defense, inflammatory modulation, and thyroid hormone activation. It is essential to state that thyroid peroxidase antibodies (TPOAb) remain significantly high in chronic autoimmune thyroiditis because of oxidative stress and immune-mediated follicular injury. Theoretically, the prevalence of TPOAb can be curbed through selenoproteins. The research, based on a systematic review and meta-analysis by Wichman et al. (2016), tests this theory or assumption.

In their scholarly work, researchers only considered randomized clinical trials (RCTs), which compared selenium with a placebo. Also, they used common outcome measures like TPOAb, TgAb, and patient-reported wellbeing to keep findings relevant and authentic. In the included RCTs, Selenomethionine doses were set at around 200 µg/day. The primary finding of the study was that selenium statistically significantly reduced TPOAb when compared with placebo. The second important finding was that the effect was robust for the first three months.

Critical Evaluation

Although the overall research design was robust, the study still had some limitations. The researchers could not effectively determine the baseline selenium levels. Thus, the trials from low-selenium regions showed stronger benefits. Also, in many trials, dosages other than 200 µg/day selenomethionine were used, which caused dose-related heterogeneity. Furthermore, very few studies evaluated thyroid gland volume or progression to overt hypothyroidism. Despite the mentioned limitations, the study provides credible evidence of selenium’s therapeutic benefits. For instance, the study establishes that selenium supplementation statistically significantly reduces TPOAb levels in chronic autoimmune thyroiditis.

Therapeutic Use II: Selenium in Pregnancy and Maternal Fetal Outcomes

Selenium has several physiological roles in pregnancy because of its antioxidant defense, thyroid hormone metabolism, and immune system-related regulations. Many studies have found that oxidative and metabolic demands increase significantly during gestation, which makes selenium deficiency highly likely, leading to various pregnancy complications. McDougall et al. (2023) examine this presumed association between selenium deficiency and pregnancy complications in their meta-analysis.

The research design for the meta-analysis was based on eight (8) RCTs and one large prospective cohort study. The combined sample size for the RTCs was 1,851, while for the cohort study was 71,728. The outcomes related to the focus of the study were very narrow, as it only emphasized clinically significant maternal and neonatal complications. For instance, the meta-analysis emphasized pre-term birth, gestational hypertension, and neonatal abnormalities. The findings of the study could not effectively endorse the theoretical benefits of selenium supplements concerning pregnancy. The results of the meta-analysis showed no statistically significant reduction in pre-term birth and selenium supplements. The researchers also did not find any credible evidence of selenium preventing neonatal complications.

Critical Evaluation

The results of the study should be considered with caution because the research design had limitations. One of the limitations was that the included trials did not effectively stratify subjects based on aspects such as baseline selenium levels. Studies also did not consider whether subjects belonged to selenium-rich or selenium-deficient regions. The omission compromised comparability, which is essential for valid and reliable results. The sample size across RTCs also varied significantly, which created sample size-related heterogeneity (a flaw in the model). In addition, the collective sample size for RCTs was much smaller than the cohort study. The findings from the meta-analysis have clinical relevance even though the limitations are substantial. For instance, the results suggest that clinicians should not rely solely on selenium supplements to avert pregnancy-related complications. This is particularly true for outcomes like pre-birth and fetal abnormalities.

Therapeutic Use III: Selenium for Addressing Male Infertility

The broader literature on selenium supplements indicates that selenium plays an important antioxidant role in male reproduction. The literature also informs that the role is quite structured and played through its incorporation into selenoproteins. For instance, we learn that selenium supports sperm membrane integrity as selenoproteins. They also provide effective protection against oxidative stress. Furthermore, it contributes robustly to proper sperm tail formation. The scholarly evidence of it comes from an RCT conducted by Moslemi & Tavanbakhsh (2011). In their work, the researchers investigated how selenium supplements affected the idiopathic infertility of men. In their trial, they included 69 infertile men. All of these subjects, we learn, had abnormal semen parameters. During the trials, each of the subjects received 200 µg selenium (as selenomethionine) and + 400 IU vitamin E. The supplement was continued for around 100 days. Researchers conducted semen analyses twice: before the RCT to establish the baseline and after the completion of the trial for the evaluation.

The major finding from the RCT was that the combination of selenium and Vitamin E improved sperm quality. For instance, the researchers found a meaningful improvement in motility. They also observed a statistically significant improvement in morphology. The RCT also found a marked improvement in sperm vitality.

Critical Evaluation

The selected peer-reviewed work has several strengths; however, it also has some limitations. One of its strengths is its research design, which is simple and relevant to the research purpose. Also, the subjects were male infertile men, who were given a similar dose of the supplements. Moreover, the researchers compared the baseline data with post-intervention data using pertinent inferential models/methods. A significant limitation was that they administered selenium with Vitamin E. Also, they did not measure the baseline