Selenium and the Immune System

Selenium is an essential trace mineral required for many processes within the human body. However, both excessive and deficient levels of selenium in the body can be harmful.

Selenium can be taken up in the body in several chemical forms. It is then incorporated as selenocysteine into selenoproteins. There are at least 25 human selenoproteins, which are involved in redox reactions, thyroid hormone metabolism, protein folding, and many other pathways.¹

Specific selenoproteins are involved in immune cell function, calcium signalling, glucose and lipid metabolism, and muscle and bone biology.

Selenium exerts its antioxidant effects primarily through selenoenzymes including glutathione peroxidases (GPX1–4) and thioredoxin reductases (TXNRD1–3), which neutralize hydrogen peroxide and lipid peroxides generated during normal metabolism.

These enzymes play key roles in protecting cell membranes, proteins, and DNA from oxidative damage caused by these reactive oxygen species (ROS).²

These enzymes also regulate redox-sensitive signalling pathways, which means that selenium levels in the body have a significant impact on how cells respond to oxidative stress. Several additional selenoproteins - including SELENOF and SELENOS - help to maintain the health and function of various proteins by reducing oxidative stress and preventing the accumulation of dysfunctional proteins that could trigger cellular stress responses.³

The thyroid contains the highest concentration of selenium per gram of tissue in the body due to the role of selenoproteins in hormone synthesis, redox regulation, and protection against oxidative damage. These include glutathione peroxidases and iodothyronine deiodinases (DIOs).⁴ Iodothyronine deiodinases are selenoproteins that activate and inactivate thyroid hormones.

Selenium is required for the creation and growth of spermatozoa, and selenoproteins such as glutathione peroxidase guard spermatozoa against oxidative damage as they mature. Selenium is also involved in testosterone biosynthesis, which is essential for effective male reproduction, including spermatogenesis and male fertility.⁵

Selenium supports cardiovascular health primarily through selenoproteins including glutathione peroxidases (GPX1) and thioredoxin reductases, which protect cardiomyocytes and vascular endothelial cells from oxidative damage and lipid peroxidation. 

Selenium also reduces platelet aggregation and supports healthy function of vascular smooth muscle cells. Deficiency may impair selenoprotein synthesis in cardiovascular tissue, which can then lead to oxidative stress, inflammation, and endothelial dysfunction that increases risk of heart disease.⁶

Several selenoproteins are located in the endoplasmic reticulum (ER), where they help newly synthesized proteins fold into the correct three-dimensional structure, maintaining protein quality control and preventing ER stress. This is essential for preventing downstream impairments in cell signalling and survival.⁷

Dietary selenium plays a vital role in inflammation and immune function. Adequate selenium is required for the activation, proliferation, and differentiation of both innate and adaptive immune cells, as well as for regulating inflammatory signalling. Low or deficient selenium may impair these processes, potentially increasing susceptibility to infection and chronic inflammation.⁸

Selenium deficiency can lead to various health concerns affecting the cardiovascular system, the immune system and the endocrine system. These may include: 

• Hair loss or thinning hair
• White spots on nails or brittleness 
• Fatigue
• Difficulty concentrating and/or poor memory 
• Muscle weakness and pain
• Frequent infections (weakened immune system)
• Male infertility

Keshan disease (a type of congestive cardiomyopathy) is now rare but previously occurred in areas of China affected by selenium deficiency. Symptoms include heart failure, cardiac enlargement, and cardiogenic shock. Selenium supplementation and fortified foods has largely reduced incidence.

Selenium is required to make the deiodinase enzymes (DIO1, DIO2) that convert T4 into active T3. When selenium is deficient, this process is impaired, potentially leading to accumulation of T4 and reduced T3 production, and a higher FT4/FT3 ratio.⁹

Selenium deficiency reduces GPX and TXNRD activity in immune cells, impairing their ability to manage oxidative stress during activation. This can affect the healthy proliferation of immune cells and production of cytokines, as well as the removal of pathogens. 

Reduced selenoenzymes also impairs signalling processes that control the body’s inflammatory responses, potentially leading to overactivation.¹⁰

Low selenium levels have been associated with depressed mood, anxiety, and reduced cognitive function. The brain is prioritized for selenium delivery due to its role as an antioxidant.¹¹

Selenium toxicity may occur at dosages of over 900 mcg per day, and/or eating foods high in selenium.¹²

Symptoms of selenium toxicity are often similar to deficiency, so diagnosis should be based on history of selenium supplementation and symptoms. Blood or urinary tests may also be required.

Symptoms of excess selenium include:

• Gastrointestinal upset (nausea, vomiting, diarrhea)
• Hair loss 
• Abnormal nails
• Skin rash
• Fatigue
• Nerve damage
• Garlic breath 

Brazil nuts (most concentrated food source). Just two Brazil nuts per day provides around 100-180 mcg (recommended daily intake is 55 mcg, upper tolerable limit 400 mcg)

Animal products:
Organ meats (liver, kidney)
Shellfish
Meat (beef, poultry, fish)
Eggs
Milk and dairy products

Plant-based sources (content depends on soil profile)
Cereals and grains
Cruciferous vegetables (broccoli, kale)
Garlic, onions
Legumes
Tomatoes
Peppers

Selenoproteins including glutathione peroxidases (GPX1, GPX4) and thioredoxin reductases (TXNRD1, TXNRD2), are highly expressed in immune cells (lymphocytes, macrophages, neutrophils) where they act as antioxidants to neutralize reactive oxygen species (ROS) and prevent oxidative stress. This allows immune cells (including T cells) to activate, proliferate and differentiate effectively. 

Selenoproteins also regulate the signaling cascade initiated by the ROS production during immune cell activation, which helps to keep inflammation under control.¹³ Deficiency in selenium can lead to suppression of immune cell activation and chronic inflammation.

Selenium protects the thyroid gland in several ways. It is needed to make the antioxidant enzymes (GPX and thioredoxin reductases) that break down hydrogen peroxide, a by-product of thyroid hormone production that can be damaging to thyroid cells in excess amounts. 

Selenium is also required for the deiodinase enzymes that convert inactive T4 into active T3. When selenium is insufficient, oxidative damage to thyroid tissue increases, and thyroid hormone activation is impaired, which can significantly affect thyroid function and hormone production.¹⁴

Some recent research has also suggested that selenium supplementation can improve the balance of healthy gut microbiota. Further research is pending.¹⁵