Continuing Education Activity

Selenium is a trace metal supplement used in the management and treatment of selenium deficiency. This activity reviews the indications, contraindications, activity, adverse events, and other key elements of selenium supplementation in the clinical setting related to the essential points needed by members of an interprofessional team managing the care of patients with selenium deficiency and its related conditions and sequelae.

Objectives:

• Identify the mechanism of action of selenium.
• Describe the adverse effects of selenium.
• Review appropriate monitoring of toxicity with selenium.
• Summarize some interprofessional team strategies for improving care coordination and communication to advance selenium therapy and improve outcomes.

Indications

Selenium is a trace mineral that exists in minimal concentrations in the body but can play an important role in human health. Food sources high in selenium include Brazil nuts, seeds, mushrooms, fish, seafood, beef, and poultry.[1] Selenium presents in an organic form as selenomethionine in plant food and an inorganic form as selenate and selenite in supplements; both the organic and inorganic forms have greater than 90% bioavailability.[2] Selenium absorption occurs mainly within the duodenum of the small intestine. The mechanism of absorption depends on the form of selenium. Selenite is absorbed by simple diffusion, whereas selenate would be by a cotransport sodium selenate and exchange selenate/OH− via an active transport sodium pump.[3]

Selenium provides several functions in the human body. It plays a role in enzymatic functions to catalyze thyroid hormone production.[4] Immune system function relies on selenium, as research has associated the mineral with defending the body against infections, particularly viral in origin.[5] Selenium in the form of selenoproteins serves as an antioxidant to protect against reactive oxygen species and reactive nitrogen species.[6]

Selenium plays an essential role in treating dermatologic conditions. Selenium sulfide administration typically is as a topical lotion, foam, or shampoo. The main dermatologic indications include tinea versicolor, seborrheic dermatitis of the scalp, dandruff, and hyperkeratosis.[7][8][9][10] Intact skin does not absorb any of the topical selenium. 

Selenium supplementation is indicated to replete stores in cases of selenium deficiency. However, this is usually secondary to the localized diet versus an individual problem with the patient. Therefore, a common way to reduce selenium deficiency is via biofortification at the agricultural level.[1] On an individualized level, a therapeutic option is to add selenium-enriched foods into the diet.[1]

Selenium deficiency is rarely associated with Keshan disease, a cardiomyopathy that ranges from heart failure, cardiomegaly, and electrocardiogram abnormalities to cardiogenic shock and demise. The most common demographic includes children and women of child-bearing age in endemic areas of China.[1] In these regions, preventative selenium supplements are essential to reduce the incidence of the disease.

Selenium deficiency occurs more commonly in patients with malabsorption syndrome, particularly caused by stomach and small intestine surgical resections.[11] Removal of gastrointestinal contents reduces the ability for selenium to be absorbed through the small intestine brush border and therefore lowers the selenium serum concentrations below adequate levels. 

Mechanism of Action

Selenium displays several different mechanisms of action. Many of the various effects of selenium involve the incorporation of selenium into different proteins to create selenoproteins.[6] There at least 25 selenoproteins within human tissues that provide different functions in the body.[12]

Selenium serves as a cofactor for glutathione peroxidase and helps minimize oxidative damage through cellular metabolism.[6] Selenium, in combination with vitamin E, protects cell membranes and organelles from peroxidative destruction.[1] Thus, selenium can boost host defense and, ultimately, the immune system.

Selenium's necessity in the endocrine system is defined by its role in making active thyroid hormone. The mineral interacts with iodothyronine deiodinase, an enzyme that transforms inactive thyroid hormone (T4) into active thyroid hormone (T3).[1]

As a dermatologic treatment, selenium in the form of selenium sulfide plays an alternative role with several suggestive mechanisms. In the treatment of seborrheic dermatitis, dandruff, and tinea versicolor, selenium sulfide acts as an anti-pityrosporum agent that inhibits the growth of the fungus.[13] Selenium sulfide's cytostatic effect on the epidermis lowers the mitotic rate and cell turnover in the basal layer, consequently reducing the production rate of the stratum corneum and limiting keratotic development.[10] Selenium sulfide blocks enzymes involved in the growth of epithelial tissue.[10] Lastly, research shows that selenium sulfide increases the rate of sebum excretion.[14]

Administration

The most efficient way to obtain selenium is through a well-balanced diet. If additional supplementation is needed, selenium administration can be through both oral and parenteral routes, and the preferred route depends on the indication for use. Most cases of selenium deficiency will reverse with oral supplements or selenium-containing foods. Dermatologic conditions require the use of topical administration of selenium sulfide. Intravenous infusions of selenium are available; however, they must be diluted before injection to prevent tissue irritation.[12]

Adverse Effects

Selenium supplementation has a very low adverse effect profile. A majority of the adverse reactions center around selenium sulfide. The more common adverse effects include redness, burning, itching, stinging, scalp sores, increased oiliness, nail hyperpigmentation, and irritation of the skin, creating contact dermatitis.[15] Less common effects associated specifically with selenium sulfide shampoo include scalp hyperpigmentation, scalp discoloration, and alopecia. A rare non-dermatologic effect includes nausea due to the odor of the medication.[15][16][17][18][19][20]

Contraindications

The only true contraindication to selenium is a previous hypersensitivity reaction with topical application. There are precautions to take when administering selenium in patients with particular comorbidities. Caution is necessary for patients with gastrointestinal dysfunction, as there is evidence of selenium causing gastrointestinal symptoms in these specific patients, such as diarrhea and vomiting.[21] Clinicians should be cautious when prescribing dietary supplements to patients with renal failure due to inadequate renal excretion. However, such evidence for precaution with early chronic kidney disease is not as strong as data for patients on dialysis.[22]

Monitoring

Symptoms of selenium deficiency are rare but include [1]:

• Deformity of bones, cartilage, and joints
• Restricted movements
• Myalgias
• Extremity edema
• Shortness of breath

Can monitor selenium levels via [1]:

• Serum selenium levels
• Scalp hair selenium levels
• Nail selenium levels
• Glutathione peroxidase activity in plasma
• Glutathione peroxidase activity in erythrocytes
• Glutathione peroxidase activity in thrombocytes
• Glutathione peroxidase activity in whole blood
• The concentration of selenoprotein P (SePP)

Toxicity

Selenium is considered a relatively non-toxic supplement. However, extremely high selenium intake can result in diarrhea, fatigue, hair loss, joint pain, nail discoloration or brittleness, and nausea.[21]

Due to selenium supplementation toxicity being extremely rare, there is no current treatment for selenium overdose. If selenium toxicity is suspected, it is best to stop using the supplement. 

Enhancing Healthcare Team Outcomes

Managing selenium deficiency can be difficult, considering this phenomenon typically occurs in underdeveloped and developing regions of the world where healthcare is limited. Selenium levels are rarely tested, and physicians and healthcare providers are often unaware of deficiencies and treatment options. Therefore, the entire interprofessional healthcare team needs to work together, starting with gathering a sufficient history from the patient. Along with physicians, nurses, medical assistants, and technicians can ask questions and collect data from the patient. Specifically, it is essential to ask about diet, as many selenium-deficient patients lack selenium in the food they consume. Pharmacists must stay up to date with the most recent guidelines regarding selenium supplementation dosing so that pharmacists and physicians can communicate to ensure the most beneficial course of action for patients. This interprofessional approach will optimize selenium therapy and use it only when necessary, leading to better patient outcomes. [Level 5]