Continuing Education Activity
Selenium is a trace mineral that is essential to human health. Selenium, in the form of selenoproteins, carries out various functions in normal health and metabolism. In particular, glutathione peroxidase, a selenoprotein, performs antioxidant activities that protect against reactive oxygen and nitrogen species. Iodothyronine deiodinases that convert inactive thyroxine to active thyroid hormone, triiodothyronine, are selenium-dependent. Selenium plays a role in the immune system functioning and the progression of HIV to AIDS. Selenium deficiency has been implicated in cardiovascular disease, infertility, myodegenerative diseases, and cognitive decline. The role of selenium in cancer treatment is currently being studied. This activity reviews the evaluation and management of selenium deficiency and stresses the importance of the interprofessional team in the care of affected patients.
Objectives:
- Identify the etiology of selenium deficiency.
- Describe the typical presentation of selenium deficiency.
- Describe the treatment of selenium deficiency.
- Explain the importance of enhancing coordination amongst interprofessional team members to improve outcomes for patients with selenium deficiency.
Introduction
Selenium (Se) is a trace mineral that is essential to human health. Selenium, in the form of selenoproteins, carries out various functions in normal health and metabolism. [1] In particular, glutathione peroxidase (G-Px), a selenoprotein, performs antioxidant activities that protect against reactive oxygen and nitrogen species. Iodothyronine deiodinases that convert inactive thyroxine (T4) to active thyroid hormone, triiodothyronine (T3), are selenium-dependent. [2] Selenium plays a role in the immune system functioning and the progression of HIV to AIDS. Selenium deficiency has been implicated in cardiovascular disease, infertility, myodegenerative diseases, and cognitive decline. The role of selenium in cancer treatment is currently being studied. In the 200 years since its discovery in 1817, the role of selenium in human health has evolved. Previously maligned as a carcinogen, it is now being understood as a vital nutrient, albeit one with a low window from being therapeutic to toxic.[1][3]
Etiology
Selenium is present in the soil and dictates the concentrations in plant foods. Brazil nuts, seeds, especially young barley seedlings, green vegetables, shiitake mushrooms, and button mushrooms are excellent organic sources of selenium in regions with adequate selenium content in the soil. [4] Selenium yeast is an excellent source as well and is used to make bread. Animals that consume selenium containing plant-based foods, especially fish, seafood, beef, and poultry are good sources of selenium from areas with adequate supply. Selenium is present in plant food in organic form as selenomethionine, which has 90% bioavailability. Inorganic forms such as selenate and selenite are used in supplemental forms and are also highly bioavailable.[5]
Selenium deficiency occurs when there is inadequate dietary intake of selenium, typically due to a scarcity of selenium sources in a given region. Interestingly, many selenium-deficiency diseases are linked with concurrent vitamin E deficiency. The American Recommended Dietary Allowance (RDA) daily minimum requirement of selenium for optimal biological functioning is 70 and 55 micrograms (mcg) per day for men and women, respectively, per April 2000 recommendations. However, this level is considered low based on other studies, and some literature sets the minimum requirement at 90 mcg daily per adult. Per the World Health Organization, the tolerable upper intake level for selenium in adults 19 years or older is 400 micrograms or 5.1 micromoles per day. Levels above this are considered toxic.[6]
Epidemiology
Selenium deficiency affects anywhere from 500 million to 1 billion people worldwide, due to inadequate intake. In the United States, selenium content in the soil and consequently plant sources is lowest in the Northwest, Northeast, Southeast, and areas of the Midwest abutting the Great Lakes. The Great Plains and the Southwest have adequate selenium content typically.[7]
Of note, patients with phenylketonuria or other diet-related diseases are especially vulnerable to selenium deficiency due to their diet being restricted from many products rich in this element.
Selenium content in most parts of Europe is considerably poorer than in the United States. The average intake of selenium in Eastern Europe is lower than in Western Europe. [8] At one time, Finland had the lowest intake of selenium, but they fortified their fertilizers with selenium and have since changed the equation. Brazil nuts and kidney are the mainstay sources of selenium in these countries. Crab, liver, other shellfish, and fish provide moderate sources, although the presence of different selenium compounds in these fish, and the presence of known contaminants such as arsenic and mercury limit their usefulness. Selenium deficiency has been well documented in China as well as in New Zealand. Based on the limited available data, there appears to be a wide variation in the Middle East in selenium intake, dependent on socioeconomic status.
Pathophysiology
Cardiovascular System [9][10]
Keshan disease is congestive cardiomyopathy associated with heart failure, cardiac enlargement, electrocardiogram (ECG) abnormalities, gallop rhythm, and even cardiogenic shock. This is seen typically in children and women of child-bearing age. First identified in endemic regions of China associated with selenium deficiency, it carried 50% morbidity, and mortality was not uncommon. Additional stressors such as chemical exposure or presence of Coxsackievirus were often present as well. Selenium supplementation, in the form of fortified salt, was found to decrease the incidence of this condition.
Endocrine System
Of the 35 selenoproteins that have been identified so far, 3 of them are called Iodothyronine deiodinases, and they play a role in thyroid hormone metabolism. The thyroid contains the maximum concentration of selenium of all the organs in our bodies. One of the iodothyronine deiodinases converts inactive thyroxine to its active form. The second one is abundant in the central nervous system (CNS), brown fat and skeletal muscles and also plays a role in the activation of thyroid hormones. The third has a role in deactivating thyroid hormones.
Immune System and Host Defense
Glutathione peroxidase (G-Px) is a selenium-dependent enzyme that protects cell membranes and lipid-containing organelles from peroxidative damage by inhibition and destruction. It acts in combination with vitamin E to maintain the integrity of the cell membranes, participating in redox reactions with hydrogen peroxide-producing glutathione. Selenium deficiency exacerbates the redox by-product toxicity and oxidative damage to cell membranes.
Further, selenium deficiency has been shown to turn harmless viruses in hosts into virulent pathogens, a likely etiology in the development of Keshan disease. The frequent emergence of new strains of influenza virus from China with its selenium-deficient belt has new connotations from the link between immunity and selenium deficiency.
Selenium is also a crucial nutrient in HIV –infected patients. More than 20 papers have reported the loss of CD4 count that parallels the decline in plasma selenium levels. Studies indicate that selenium promotes the differentiation of CD4+ T-cells into T-helper-1 (Th1) cells. This has, in turn, been linked to decreased hospital admissions from co-infections, particularly from mycobacterial infections, in HIV infected individuals. Selenium, therefore, is linked to the prevention of progression of HIV to AIDS. Selenium is also protective in patients infected with Hepatitis B or C in progressing to malignancy.
Although selenium has been linked to enhanced immune response, its role in cancer prevention is limited at this time to just that. It has been known to augment the cytotoxic effect of natural killer cells and increase the activity of T-cells and macrophages. It stimulates the production of antibodies and is synergistic with vitamin E regarding the aging process of cells. It protects against the toxic effects of heavy metals such as lead, cadmium, arsenic, mercury, and organic compounds such as paraquat herbicides.
Musculoskeletal System
Kashin-Beck disease is a disabling deformity of bones, cartilage, and joints leading to enlarged joints and restricted movements. Seen primarily in parts of Tibet, China, Siberia, and North Korea, it has multifactorial pathogenesis amongst which selenium deficiency is one implicating cause.
Both Keshan disease and muscular syndrome have been described in patients on total parenteral nutrition (TPN) who did not have selenium added to their supplement. Symptoms described included intermittent myalgias and tenderness as well as eventual white fingernail beds.
Neurology and Psychiatric Systems
Studies have shown that selenium deprivation can lead to depressed mood and more hostile behavior. During selenium deprivation state, the brain receives priority supplies indicating the importance of selenium in brain health. The turnover rate of some neurotransmitters has also been found to be affected by selenium deficiency. Selenium concentration in the brain of patients with Alzheimer disease was found in one study to be about 60% of that of controls.
Reproductive System
Selenium is essential for testosterone biosynthesis and the formation and development of normal spermatozoa. Testicular tissue contains large concentrations of selenium and is responsible for sperm quality and male fertility health. Data regarding female fertility and selenium are sparse.
History and Physical
Symptoms of severe selenium deficiency are primarily related to heart muscles and joints. Moderate deficiency leads to an increase in infertility in men, prostate cancer, and neurological diseases. [10] Manifestations of rheumatoid arthritis, shortened fingers and toes or growth disorders in regions endemic to shortages in selenium in the soil should raise suspicion regarding selenium deficiency, especially in children 5 to 13 years of age. It is the constellation of symptoms that will, unfortunately, point to making the diagnosis, as there is not a specific finding that will allow the clinician to hone in on the fact that the patient is selenium deficient.
Evaluation
Selenium deficiency can present with many varying symptoms. Selenium deficiency is also more likely to be prevalent in a community as a whole, rather than just sporadic cases. Typically if it is suspected, either serum or “scalp hair” or nail selenium levels may be checked, and there is a good correlation between the 2 levels. The advantage of using the latter is that in endemic regions, it is easier to collect scalp hair samples by unskilled workers, rather than to try to collect blood samples to check for selenium levels. The other parameters that can be checked are the G-Px activity in plasma (G-Px3), in erythrocytes (G-Px1), in thrombocytes (G-Px1), or whole blood (G-Px1 and G-Px3). The concentration of selenoprotein P (SePP) is also a good laboratory gauge of selenium status in patients.
Treatment / Management
Selenium deficiency is often a population-level problem rather than an individual one. It affects a community as a whole. Biofortification has been the approach used to tackle this problem by fertilizing the soil at the agricultural end of things. Alternately enrichment of food sources through fodder with selenium compounds, for instance, eggs (or rather, egg yolks) with more selenium, is also another approach that has been used to raise nutritional selenium content. In many countries, eggs, meat, and milk fortified with selenium have been introduced successfully. Using microorganisms for the production of functional foods such as selenium yeast is yet another approach that is being used. Organic selenium is less likely to reach toxic levels as quickly as supplementing with selenite and selenate (the inorganic salt forms of selenium supplements) can. However, using inorganic salts is a quick way to supplement selenium in the situation of gross and immediate deficiency. The goal to target is supplementation, achieving about 90 mcg/day for adults. Per the World Health Organization, the tolerable upper intake level for selenium in adults 19 years or older is 400 micrograms or 5.1 micromoles per day. Levels above this are considered toxic. Ultimately, a balanced diet is the best way to stave off selenium deficiency.[6]
Differential Diagnosis
- Autoimmune Thyroid Disease and Pregnancy
- Nutritional cardiomyopathy
- Thyroxine-Binding Globulin Deficiency
Prognosis
If identified, this is a condition that can be treated with supplementation.
Pearls and Other Issues
- Selenium is a vital trace element found in food that plays a role in the production of active thyroid hormones, immune system functioning, cognitive health, and is an antioxidant.
- Selenium deficiency has been found to have a role in human growth and reproduction as well.
- Moderate deficiency plays a role in myodegenerative diseases, such as muscle weakness.
- Low selenium state has been associated with depressed mood, anxiety, and confusion.
- The role of selenium in cancer treatment is still under study.
- There is a narrow therapeutic window for selenium, which can become toxic if the doses are exceeded.
- There is often concurrent vitamin E deficiency in many diseases linked to selenium-deficiency.
- Keshan disease is a disease related to selenium deficiency in endemic regions of China, which results in congestive cardiomyopathy, heart failure, cardiomegaly, and ECG changes. It is often triggered by the presence of Coxsackievirus or some chemical trigger.
- Kashin-Beck is a disease associated with deformity of bones, cartilage, and joints that causes restricted movements as a result of enlarged joints. It is seen in parts of Tibet, China, Siberia, and North Korea. The etiology of this disease is multifactorial, with one culprit being selenium-deficiency.
Enhancing Healthcare Team Outcomes
Selenium deficiency is best managed by an interprofessional team that includes dietitians and nurses. Selenium deficiency in North America is very rare. Clinicians need to be aware that selenium deficiency can present with many varying symptoms. Selenium deficiency is also more likely to be prevalent in a community as a whole, rather than just sporadic cases. Typically if it is suspected, either serum or “scalp hair” or nail selenium levels may be checked, and there is a good correlation between the two levels. The advantage of using the latter is that in endemic regions, it is easier to collect scalp hair samples by unskilled workers, rather than to try to collect blood samples to check for selenium levels. Public health nurses should be involved in the identification of high-risk populations. Dieticians should encourage patients to eat a healthy diet rather than focus on a single supplement. When there is a severe deficiency, the dosing of supplements should be reviewed by pharmacists. [Level 5]
Selenium Deficiency