- Keshan Disease, which results in an enlarged heart and poor heart function, occurs in selenium deficient children.
- Kashin-Beck Disease, which results in osteoarthropathy
- Myxedematous Endemic Cretinism, which results in mental retardation
Keshan disease was first described in the early 1930s in China, and is still seen in large areas of the Chinese countryside with selenium poor soil . Dietary intake in these areas is less than 19 micrograms per day for men and less than 13 micrograms per day for women, significantly lower than the current RDA for selenium . Researchers believe that selenium deficient people infected with a specific virus are most likely to develop Keshan disease [18,19].
Selenium deficiency has also been seen in people who rely on total parenteral nutrition (TPN) as their sole source of nutrition [20,21]. TPN is a method of feeding nutrients through an intravenous (IV) line to people whose digestive systems do not function. Forms of nutrients that do not require digestion are dissolved in liquid and infused through the IV line. It is important for TPN solutions to provide selenium in order to prevent a deficiency . Physicians can monitor the selenium status of individuals receiving TPN to make sure they are receiving adequate amounts.
Severe gastrointestinal disorders may decrease the absorption of selenium, resulting in selenium depletion or deficiency . Gastrointestinal problems that impair selenium absorption usually affect absorption of other nutrients as well, and require routine monitoring of nutritional status so that appropriate medical and nutritional treatment can be provided.
Who may need supplemental selenium?In the U.S., most cases of selenium depletion or deficiency are associated with severe gastrointestinal problems, such as Crohn's disease, or with surgical removal of part of the stomach. These and other gastrointestinal disorders can impair selenium absorption [24-26]. People with acute severe illness who develop inflammation and widespread infection often have decreased levels of selenium in their blood . Physicians will evaluate individuals who have gastrointestinal disease or severe infection for depleted blood levels of selenium to determine the need for supplementation.
People with iodine deficiency may also benefit from selenium supplementation. Iodine deficiency is rare in the U.S., but is still common in developing countries where access to iodine is limited . Researchers believe that selenium deficiency may worsen the effects of iodine deficiency on thyroid function, and that adequate selenium nutritional status may help protect against some of the neurological effects of iodine deficiency [6,7]. Researchers involved in the Supplementation en Vitamines et Mineraux AntioXydants (SU.VI.MAX) study in France, which was designed to assess the effect of vitamin and mineral supplements on chronic disease risk, evaluated the relationship between goiter and selenium in a subset of this research population. Their findings suggest that selenium supplements may be protective against goiter, which refers to enlargement of the thyroid gland .
As noted above, selenium supplementation during TPN administration is now routine [21,22]. While specific medical problems such as those described above indicate a need for selenium supplementation, evidence is lacking for recommending selenium supplements for healthy children and adults.
Selenium occurs in staple foods such as corn, wheat, and soybean as selenomethionine, the organic selenium analogue of the amino acid methionine [30,31]. Selenomethionine can be incorporated into body proteins in place of methionine, and serves as a vehicle for selenium storage in organs and tissues. Selenium supplements may also contain sodium selenite and sodium selenate, two inorganic forms of selenium. Selenomethionine is generally considered to be the best absorbed and utilized form of selenium.
Selenium is also available in 'high selenium yeasts', which may contain as much as 1,000 to 2,000 micrograms of selenium per gram . Most of the selenium in these yeasts is in the form of selenomethionine. This form of selenium was used in the large scale cancer prevention trial in 1983, which demonstrated that taking a daily supplement containing 200 micrograms of selenium per day could lower the risk of developing prostate, lung, and colorectal cancer . However, some yeasts may contain inorganic forms of selenium, which are not utilized as well as selenomethionine.
A study conducted in 1995 suggested that the organic forms of selenium increased blood selenium concentration to a greater extent than inorganic forms. However, it did not significantly improve the activity of the selenium-dependent enzyme, glutathione peroxidase . Researchers are continuing to examine the effects of different chemical forms of selenium, but the organic form currently appears to be the best choice.
What are some current issues and controversies about selenium?Selenium and cancer
Observational studies indicate that death from cancer, including lung, colorectal, and prostate cancers, is lower among people with higher blood levels or intake of selenium [34-40]. In addition, the incidence of nonmelanoma skin cancer is significantly higher in areas of the United States with low soil selenium content . The effect of selenium supplementation on the recurrence of different types of skin cancers was studied in seven dermatology clinics in the U.S. from 1983 through the early 1990s. Taking a daily supplement containing 200 μg of selenium did not affect recurrence of skin cancer, but significantly reduced the occurrence and death from total cancers. The incidence of prostate cancer, colorectal cancer, and lung cancer was notably lower in the group given selenium supplements .
Research suggests that selenium affects cancer risk in two ways. As an anti-oxidant, selenium can help protect the body from damaging effects of free radicals. Selenium may also prevent or slow tumor growth. Certain breakdown products of selenium are believed to prevent tumor growth by enhancing immune cell activity and suppressing development of blood vessels to the tumor .
However, not all studies have shown a relationship between selenium status and cancer. In 1982, over 60,000 participants of the Nurse's Health Study with no history of cancer submitted toenail clippings for selenium analysis. Toenails are thought to reflect selenium status over the previous year. After three and a half years of data collection, researchers compared toenail selenium levels of nurses with and without cancer. Those nurses with higher levels of selenium in their toenails did not have a reduced risk of cancer .
Two long-term studies, the SU.VI.MAX study in France and the Selenium and Vitamin E Cancer Prevention Trial (SELECT) in the United States and Canada, investigated whether selenium combined with at least one other dietary supplement could reduce the risk of prostate cancer in men.
The SU.VI.MAX study examined the effects of a supplement package containing moderate doses of vitamins E and C, beta-carotene, zinc, and selenium (100 μg/day) versus placebo on the risk of chronic diseases such as cancer and cardiovascular disease. Among the 5,141 men enrolled, those randomized to the supplements who began the study with a normal (<3 ng/ml) PSA (prostate specific antigen) level at baseline had their risk of prostate cancer reduced by half . Among the men whose PSA levels were elevated at baseline, however, use of the supplements was associated with an increased incidence of prostate cancer of borderline statistical significance compared to placebo.
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a very large randomized clinical trial begun in 2001 specifically designed to determine whether 7-12 years of daily supplementation with selenium (200 μg), with or without synthetic vitamin E (400 IU), reduces the number of new prostate cancers in healthy men (PSA ≤4 ng/ml at baseline) [46-47]. The trial, which had enrolled >35,000 men, was discontinued in October 2008 when an analysis found that the supplements, taken alone or together for an average of 5.5 years, did not prevent prostate cancer. Study staff members will continue to monitor participants' health for an additional 3 years.
Selenium and heart disease
Some population surveys have suggested an association between lower antioxidant intake and a greater incidence of heart disease . Evidence also suggests that oxidative stress from free radicals, which are natural by-products of oxygen metabolism, may promote heart disease [48-50]. For example, it is the oxidized form of low-density lipoproteins (LDL, often called "bad" cholesterol) that promotes plaque build-up in coronary arteries . Selenium is one of a group of antioxidants that may help limit the oxidation of LDL cholesterol and thereby help to prevent coronary artery disease [48-50]. Currently there is insufficient evidence available to recommend selenium supplements for the prevention of coronary heart disease.
Selenium and arthritis
Surveys indicate that individuals with rheumatoid arthritis, a chronic disease that causes pain, stiffness, swelling, and loss of function in joints, have reduced selenium levels in their blood [51-52]. In addition, some individuals with arthritis have a low selenium intake .
The body's immune system naturally makes free radicals that can help destroy invading organisms and damaged tissue, but that can also harm healthy tissue . Selenium, as an antioxidant, may help to relieve symptoms of arthritis by controlling levels of free radicals . Current findings are considered preliminary, and further research is needed before selenium supplements can be recommended for individuals with arthritis.
Selenium and HIV
HIV/AIDS malabsorption can deplete levels of many nutrients, including selenium. Selenium deficiency is associated with decreased immune cell counts, increased disease progression, and high risk of death in the HIV/AIDS population [56,57]. HIV/AIDS gradually destroys the immune system, and oxidative stress may contribute to further damage of immune cells. Antioxidant nutrients such as selenium help protect cells from oxidative stress, thus potentially slowing progression of the disease . Selenium also may be needed for the replication of the HIV virus, which could further deplete levels of selenium .
An examination of 125 HIV-positive men and women linked selenium deficiency with a higher rate of death from HIV . In a small study of 24 children with HIV who were observed for five years, those with low selenium levels died at a younger age, which may indicate faster disease progression . Results of research studies have led experts to suggest that selenium status may be a significant predictor of survival for those infected with HIV .
Researchers continue to investigate the relationship between selenium and HIV/AIDS, including the effect of selenium levels on disease progression and mortality. There is insufficient evidence to routinely recommend selenium supplements for individuals with HIV/AIDS, but physicians may prescribe such supplements as part of an overall treatment plan. It is also important for HIV-positive individuals to consume recommended amounts of selenium in their diet.
What is the health risk of too much selenium?High blood levels of selenium (greater than 100 μg/dL) can result in a condition called selenosis . Symptoms of selenosis include gastrointestinal upsets, hair loss, white blotchy nails, garlic breath odor, fatigue, irritability, and mild nerve damage .
Selenium toxicity is rare in the U.S. The few reported cases have been associated with industrial accidents and a manufacturing error that led to an excessively high dose of selenium in a supplement [64,65]. The Institute of Medicine of the National Academy of Sciences has set a tolerable upper intake level (UL) for selenium at 400 micrograms per day for adults to prevent the risk of developing selenosis . Table 4 lists ULs for selenium, in micrograms per day, for infants, children, and adults.
Table 4: Tolerable Upper Intake Levels for Selenium for Infants, Children, and Adults 
Age Males and Females
0 - 6 months 45 7 - 12 months 60 1-3 y 90 4-8 y 150 9-13 y 280 14-18 y 400 19 y + 400
Selecting a healthful dietThe 2000 Dietary Guidelines for Americans states, "Different foods contain different nutrients and other healthful substances. No single food can supply all the nutrients in the amounts you need" . For more information about building a healthful diet, refer to the Dietary Guidelines for Americans  (http://www.cnpp.usda.gov/Publications/DietaryGuidelines/2000/2000DGProfessionalBooklet.pdf) and the Food Guide Pyramid  (http://www.nal.usda.gov/fnic/Fpyr/pyramid.html).
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