What are the clinical uses, dosing guidelines, and contraindications of selenium supplementation?

What is Selenium For?

Selenium is an essential trace element that functions primarily as a component of antioxidant enzymes (glutathione peroxidase) and is critical for thyroid hormone metabolism, immune function, and protection against oxidative tissue damage. 1

Primary Physiological Functions

Antioxidant Defense

• Selenium is an essential component of glutathione peroxidase (GSHPx), which protects against oxidative tissue damage 1
• It supports the activity of the glutathione peroxidase family of antioxidant enzymes, particularly important in critically ill patients 1
• Selenoproteins play crucial roles in cellular antioxidative defense systems and redox control 2

Thyroid Function

• Selenium is essential for the synthesis and metabolism of thyroid hormones 3, 2
• The three key enzymes involved in activation and inactivation of thyroid hormones (iodothyronine deiodinases) are selenoproteins 2
• The thyroid gland contains one of the highest selenium concentrations per mass unit in the human body 2
• Selenium protects thyroid cells from excess hydrogen peroxide and reactive oxygen species produced during thyroid hormone biosynthesis 2

Immune System Support

• Selenium stimulates antibody formation and activity of helper T cells, cytotoxic T cells, and Natural Killer (NK) cells 4
• It is needed for proper functioning of the immune system and may counteract viral virulence 5

Clinical Uses and Indications

Parenteral Nutrition Supplementation

• Selenium must be provided with parenteral nutrition at 7 mcg/kg/day in preterm infants and 2-3 mcg/kg/day in infants and children (maximum 100 mcg/day for routine supplementation) 1
• Children receiving long-term parenteral nutrition without selenium supplementation are at significant risk for deficiency 1, 6
• Selenium deficiency in this population manifests as low plasma selenium, erythrocyte macrocytosis, depigmentation, and muscle weakness 1

High-Risk Pediatric Populations

• Preterm infants are at particularly high risk: plasma selenium levels decrease during the first weeks of life in very low birth weight infants, and low selenium status has been associated with bronchopulmonary dysplasia 1, 6
• Children with chronic kidney disease stages 2-5 and those on hemodialysis have low serum selenium levels and decreased glutathione peroxidase activity 6
• Selenium status should be assessed in all children with chronic kidney disease stages 2 to 5 and 5D 6

Critical Care Settings

• Low serum selenium is associated with intense inflammation, organ failures, and poor outcomes in critically ill children and adults 1
• In sepsis, selenium doses higher than daily requirements may reduce mortality, though evidence is mixed and depends on baseline selenium status 1
• European populations tend to be selenium borderline deficient compared to North American populations, which may explain variable trial results 1

Autoimmune Thyroid Disease

• Selenium administration in autoimmune thyroiditis (Hashimoto thyroiditis) and mild Graves' disease improves clinical scores and reduces thyroperoxidase antibody titers 7
• Selenium deficiency contributes to autoimmune processes in the thyroid gland 3

Dosing Guidelines

Nutritional Requirements

• General adult population: 60-70 mcg/day for women, 70 mcg/day for men 8, 4
• Preterm infants (parenteral): 7 mcg/kg/day 1
• Term infants and children (parenteral): 2-3 mcg/kg/day, maximum 100 mcg/day 1
• Breast-fed infants: approximately 2.3 mcg/kg/day from breast milk 1
• Dietary selenium is highly bioavailable with intestinal absorption of 56-81% 8, 4

High-Dose Therapy (Critical Care)

• High-dose selenium therapy (1000-4000 mcg) has been investigated in septic shock, though recent evidence shows mixed results 1
• Critical caveat: Doses exceeding ten times the dietary reference intake should not be used without proven severe deficiency 1

Monitoring Requirements

Laboratory Assessment

• Plasma or serum selenium concentration is the primary monitoring tool 1, 6
• Glutathione peroxidase activity in plasma or red blood cells provides additional assessment 1, 6
• Erythrocyte and platelet glutathione peroxidase activity are sensitive indices in parenteral nutrition patients 1, 6

Monitoring Frequency

• Patients on long-term parenteral nutrition should be monitored regularly 1
• Patients with renal failure require regular selenium status monitoring 1, 6
• Children with particularly low dietary intake should be monitored every 4-6 months 6

Important Monitoring Caveat

• In preterm infants, glutathione peroxidase activity is NOT a useful marker of selenium status due to immaturity and oxygen exposure 1, 6

Contraindications and Safety Concerns

Renal Failure

• Doses in excess of dietary reference intakes should be avoided in renal failure because the kidney excretes selenium 1
• More frequent monitoring is warranted in this population 6

Toxicity (Selenosis)

• Selenium overload in adults causes selenosis: headache, loss of hair and nails, skin rash, discoloration of teeth, paresthesia, and paralysis 1
• No reports of selenium toxicity have been documented in children 1
• Toxicity symptoms can occur at plasma selenium levels of 6-12 mmol/L 8

Cancer and Metabolic Risks

• Selenium overexposure is positively associated with high-grade prostate cancer 8
• Selenium overexposure is positively associated with type 2 diabetes, and supplementation of people with adequate intake might increase their diabetes risk 8
• Selenium intake from food should not be exceeded through supplementation given these risks 8

Clinical Pitfalls to Avoid

Geographic Variation

• Selenium content of food depends on soil selenium content where crops are grown or animals graze 6
• European populations tend to have lower selenium status than North American populations, affecting interpretation of supplementation trials 1

Inappropriate High-Dose Use

• The short-term support of the endogenous antioxidant system in critical care should not be confused with daily nutritional doses required with parenteral nutrition 1
• High-dose selenium monotherapy has been shown to be inefficient in reducing mortality in large cohorts 1

Cholestasis

• If a patient on parenteral nutrition develops cholestasis, blood concentrations of manganese (not selenium) should be determined, as this is a separate trace element concern 1