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Selenium is a trace element that is essential in small amounts, but like all essential elements, it is toxic at high levels. Humans and animals require selenium for the function of a number of selenium-dependent enzymes, also known as selenoproteins. During selenoprotein synthesis, selenocysteine is incorporated into a very specific location in the amino acid sequence in order to form a functional protein. Unlike animals, plants do not appear to require selenium for survival. However, when selenium is present in the soil, plants incorporate it non-specifically into compounds that usually contain sulfur (1).
At least 25 selenoproteins have been identified, but the metabolic functions have been identified for only about one-half of them (2).
The selenoproteins with an identified function include:
Five selenium-containing glutathione peroxidases (GPx) have been identified: cellular or classical GPx, plasma or extracellular GPx, phospholipid hydroperoxide GPx, gastrointestinal GPx, and olfactory GPx (2). Although each GPx is a distinct selenoprotein, they are all antioxidant enzymes that reduce potentially damaging reactive oxygen species (ROS), such as hydrogen peroxide and lipid hydroperoxides, to harmless products like water and alcohols by coupling their reduction with the oxidation of glutathione (diagram). Sperm mitochondrial capsule selenoprotein, an antioxidant enzyme that protects developing sperm from oxidative damage and later forms a structural protein required by mature sperm, was once thought to be a distinct selenoprotein but now appears to be phospholipid hydroperoxide GPx (3).
In conjunction with the compound thioredoxin, thioredoxin reductase participates in the regeneration of several antioxidants, possibly including vitamin C. Maintenance of thioredoxin in a reduced form by thioredoxin reductase is important for regulating cell growth and viability (2, 4).
Iodothyronine deiodinases (thyroid hormone deiodinases)
The thyroid gland releases very small amounts of biologically active thyroid hormone (triiodothyronine or T3) and larger amounts of an inactive form of thyroid hormone (thyroxine or T4) into the circulation. Most of the biologically active T3 in the circulation and inside cells is created by the removal of one iodine atom from T4 in a reaction catalyzed by selenium-dependent iodothyronine deiodinase enzymes. Three different selenium-dependent iodothyronine deiodinases (types I, II, and III) can both activate and inactivate thyroid hormone by acting on T3, T4, or other thyroid hormone metabolites. Thus, selenium is an essential element for normal development, growth, and metabolism because of its role in the regulation of thyroid hormones (2, 5).
Selenoprotein P is found in plasma and also associated with vascular endothelial cells (cells that line the inner walls of blood vessels). The primary function of selenoprotein P appears to be a transport protein for selenium (6). It also functions as an antioxidant that protects endothelial cells from damage induced by such compuonds as peroxynitrite, a reactive nitrogen species (RNS) (7).
Selenoprotein W is found in muscle. Although its function is presently unknown, it is thought to play a role in muscle metabolism (8). There is about 80% homology of this selenoprotein from six different species of animals (9). For more information on selenoprotein W, see the Linus Pauling Institute's Spring/Summer 2007 Research Newsletter.
Incorporation of selenocysteine into selenoproteins is directed by the genetic code and requires the enzyme selenophosphate synthetase. A selenoprotein itself, selenophosphate synthetase catalyzes the synthesis of monoselenium phosphate, a precursor of selenocysteine that is required for the synthesis of selenoproteins (2).
Methionine-R-sulfoxide reductase was initially identified as selenoprotein R and selenoprotein X by two different laboratories. However, later studies revealed that the protein catalyzes stereospecific reduction of oxidized methionine residues in reactions that use thioredoxin as a reductant. There are two forms of this specific selenoprotein (2).
15 kDA selenoprotein (Sep15)
Sep15 is mammalian protein located in the endoplasmic reticulum of the cell. Here, it binds UDP-glucose:glycoprotein glucosyltransferase, an enzyme that senses protein folding. Sep 15 has a redox function and is also implicated in cancer prevention (2).
Selenoprotein V is expressed exclusively in testes and is thought to function in spermatogenesis (2).
Selenoprotein S is involved in retrotranslocation of misfolded proteins from the endoplasmic reticulum to the cytosol. This protein may also be involved in inflammatory and immune responses (2).
As an integral part of the glutathione peroxidases and thioredoxin reductase, selenium interacts with nutrients that affect cellular redox status (i.e., pro-oxidant/antioxidant balance). Other minerals that are critical components of antioxidant enzymes include copper (as superoxide dismutase), zinc (as superoxide dismutase), and iron (as catalase). Selenium as gluthathione peroxidase also appears to support the activity of vitamin E (α-tocopherol) in limiting the oxidation of lipids. Animal studies indicate that selenium and vitamin E tend to spare one another and that selenium can prevent some of the damage resulting from vitamin E deficiency in models of oxidative stress (10). Further, thioredoxin reductase maintains the antioxidant function of vitamin C by catalyzing its regeneration from its oxidized form, dehydroascorbic acid (6).
Selenium deficiency may exacerbate the effects of iodine deficiency. Iodine is essential for the synthesis of thyroid hormone; however, selenoenzymes called iodothyronine deiodinases are also required for the conversion of thyroxine (T4) to the biologically active thyroid hormone triiodothyronine (T3). Selenium supplementation in a small group of elderly individuals decreased plasma T4, indicating increased deiodinase activity and thus increased conversion of T4 to T3 (1).
Insufficient selenium intake results in decreased activity of the glutathione peroxidases as well as some other thioredoxin reductase and thyroid deiodinases. Even when severe, isolated selenium deficiency does not usually result in obvious clinical illness. However, selenium-deficient individuals appear to be more susceptible to additional physiological stresses (11).
Individuals at increased risk of selenium deficiency
Clinical selenium deficiency has been observed in chronically ill patients who were receiving total parenteral nutrition (TPN) without added selenium for prolonged periods of time. Muscular weakness, muscle wasting, and cardiomyopathy (inflammation and damage to the heart muscle) have been observed in these patients. TPN solutions are now supplemented with selenium to prevent such problems. People who have had a large portion of the small intestine surgically removed or those with severe gastrointestinal problems, such as Crohn's disease, are also at risk for selenium deficiency due to impaired absorption. Specialized medical diets used to treat metabolic disorders, such as phenylketonuria (PKU), are often low in selenium. Specialized diets that will be used exclusively over long periods of time should have their selenium content assessed to determine the need for selenium supplementation (11).
Keshan disease is a cardiomyopathy that affects young women and children in a selenium-deficient region of China. The acute form of the disease is characterized by the sudden onset of cardiac insufficiency, while the chronic form results in moderate to severe heart enlargement with varying degrees of cardiac insufficiency. The incidence of Keshan disease is closely associated with very low dietary intakes of selenium and poor selenium nutritional status. Selenium supplementation protects people from developing Keshan disease but cannot reverse heart muscle damage once it occurs (11, 12). Despite the strong evidence that selenium deficiency is a fundamental factor in the etiology of Keshan's disease, the seasonal and annual variation in its occurrence suggests that an infectious agent is involved in addition to selenium deficiency. Coxsackievirus is one of virus type that has been isolated from Keshan patients, and studies in selenium-deficient mice show that this virus is capable of causing an inflammation of the heart called myocarditis. Studies in mice also indicate that oxidative stress induced by selenium deficiency results in changes in the viral genome; such genomic changes are capable of converting a relatively harmless viral strain to a myocarditis-causing strain (13, 14). Though not proven in Keshan disease, selenium deficiency may result in a more virulent strain of virus with the potential to invade and damage the heart muscle. See Disease Prevention for more information on selenium and viral infection.
Kashin-Beck disease is characterized by the degeneration of articular cartilage between joints (osteoarthritis) and is associated with poor selenium status in areas of northern China, North Korea, and eastern Siberia. The disease affects children between the ages 5 and 13 years. Severe forms of the disease may result in joint deformities and dwarfism. Unlike Keshan disease, there is little evidence that improving selenium nutritional status prevents Kashin-Beck disease. Thus, the role of selenium deficiency in the etiology of Kashin-Beck disease is less certain. A number of other causative factors have been suggested for Kashin-Beck disease, including fungal toxins in grain, iodine deficiency, and contaminated drinking water (11, 12).
The RDA was revised in 2000 by the Food and Nutrition Board (FNB) of the Institute of Medicine. The most recent RDA is based on the amount of dietary selenium required to maximize the activity of the antioxidant enzyme glutathione peroxidase in plasma (15).
|Recommended Dietary Allowance (RDA) for Selenium|
|Life Stage||Age||Males (mcg/day)||Females (mcg/day)|
|Infants||0-6 months||15 (AI)||15 (AI)|
|Infants||7-12 months||20 (AI)||20 (AI)|
|Adults||19 years and older||55||55|
Selenium deficiency has been associated with impaired function of the immune system (16). Moreover, selenium supplementation in individuals who are not overtly selenium deficient appears to stimulate the immune response. In two small studies, healthy (17, 18) and immunosuppressed individuals (19) supplemented with 200 mcg/day of selenium as sodium selenite for eight weeks showed an enhanced immune cell response to foreign antigens compared with those taking a placebo. A considerable amount of basic research also indicates that selenium plays a role in regulating the expression of cell-signaling molecules called cytokines, which orchestrate the immune response (20).
Selenium deficiency appears to enhance the virulence or progression of some viral infections. The increased oxidative stress resulting from selenium deficiency may induce mutations or changes in the expression of some viral genes. When selenium-deficient mice are inoculated with a relatively harmless strain of coxsackievirus, mutations occur in the viral genome that result in a more virulent form of the virus, which causes an inflammation of the heart muscle known as myocarditis. Once mutated, this form of the virus also causes myocarditis in mice that are not selenium deficient, demonstrating that the increased virulence is due to a change in the virus rather than the effects of selenium deficiency on the host immune system. A study in mice that lack the cellular (classical) glutathione peroxidase enzyme (GPx-1 knockout mice) demonstrated that cellular glutathione peroxidase provides protection against myocarditis resulting from mutations in the genome of a previously benign virus. Selenium deficiency results in decreased activity of glutathione peroxidase, increasing oxidative damage and the likelihood of mutations in the viral genome. Coxsackievirus has been isolated from the blood of some sufferers of Keshan disease, suggesting that it may be a cofactor in the development of the cardiomyopathy associated with selenium deficiency in humans (21).
There is a great deal of evidence indicating that selenium supplementation at high levels reduces the incidence of cancer in animals. More than two-thirds of over 100 published studies in 20 different animal models of spontaneous, viral, and chemically induced cancers found that selenium supplementation significantly reduces tumor incidence (22). The evidence indicates that the methylated forms of selenium are the active species against tumors, and these methylated selenium compounds are produced at the greatest amounts with excess selenium intakes (23). The relationships of selenium intake to cancer in humans and selenium status to tumor incidence in animals have been summarized (24).
Geographic studies have consistently observed higher cancer mortality rates in populations living in areas with low soil selenium and relatively low dietary selenium intakes. Results of epidemiological studies of cancer incidence in groups with less variable selenium intakes have been less consistent, but such studies also show a trend for individuals with lower selenium levels (blood and nails) to have a higher incidence of several different types of cancer. However, this trend is less pronounced in women. For example, a prospective study of more than 60,000 female nurses in the U.S. found no association between toenail selenium levels and total cancer risk (25).
Hepatitis infection and cigarette smoking are known to increase one's risk for various types of cancer, and low dietary selenium intake may heighten cancer risk. Chronic infection with viral hepatitis B or C significantly increases risk of liver cancer. In a study of Taiwanese men with chronic viral hepatitis B or C infection, low plasma selenium concentrations were associated with an even greater risk of liver cancer; the inverse association between selenium levels and liver cancer was stronger in cigarette smokers and in those with lower plasma levels of vitamin A and certain carotenoids (26). A case-control study within a prospective study of over 9,000 Finnish men and women examined serum selenium levels in 95 individuals subsequently diagnosed with lung cancer and 190 matched controls (27). Lower serum selenium levels were associated with an increased risk of lung cancer, and the association was more pronounced in smokers. In this Finnish population, selenium levels were only about 60% of the level commonly observed in other western countries. Results of a recent meta-analysis of 16 studies suggest that selenium may protect against lung cancer. In this analysis, a significant lower risk (54% reduction) of lung cancer was associated with selenium status when studies assessing selenium exposure by toenail selenium content were pooled. A nonsignificant decrease (20% reduction) in lung cancer risk was found when studies assessing selenium status by serum levels were collectively analyzed (28).
Some studies have reported that low dietary selenium intakes are associated with increased risk of prostate cancer. A case-control study within a prospective study of over 50,000 male health professionals in the U.S. found a significant inverse relationship between toenail selenium content and the risk prostate cancer; 181 men diagnosed with advanced prostate cancer and 181 matched controls were included in this study (29). In this study, individuals whose toenail selenium content was consistent with an average dietary intake of 159 mcg/day of selenium daily had a 65% lower risk of advanced prostate cancer compared to those with toenail selenium content consistent with an average intake of 86 mcg/day. Within a prospective study of more than 9,000 Japanese-American men, a case-control study that examined 249 confirmed cases of prostate cancer and 249 matched controls found the risk of developing prostate cancer was 50% less in men with serum selenium levels in the highest quartile compared to those in the lowest quartile (30). A case-control study found that men with prediagnostic plasma selenium levels in the lowest quartile were four to five times more likely to develop prostate cancer than those in the highest quartile (31). A case-control study that compared 724 prostate cancer cases with 879 matched controls reported that serum selenium levels were not associated with prostate cancer (32). In contrast, one of the largest case-control studies to date found a significant inverse association between toenail selenium and the risk of colon cancer, but no associations between toenail selenium and the risk of breast cancer or prostate cancer were observed (33). A meta-analysis of 20 epidemiological studies, mainly case-control studies, found that selenium levels in the serum or toenails were significantly lower in those with prostate cancer (34). However, a recent prospective study in a cohort of over 295,000 men reported that frequent multivitamin use (> 7 times/week) and use of selenium supplements, together, was associated with significant increases in advanced and fatal prostate cancer (35). Clearly, more prospective studies as well as clinical trials are needed to understand whether selenium status is linked to prostate cancer.
Human intervention trials
Undernourished populations: An intervention trial of selenium supplementation was undertaken among a general population of 130,471 individuals in five townships of Quidong, China, a high-risk area for viral hepatitis B infection and liver cancer. This trial provided table salt enriched with sodium selenite to the population of one township (20,847 people), using the other four townships as controls. During an 8-year follow-up period, the average incidence of liver cancer was reduced by 35% in the selenium-enriched population, while no reduction was found in the control populations. In a clinical trial in the same region, 226 individuals with evidence of chronic hepatitis B infection were supplemented with either 200 mcg of selenium in the form of a selenium-enriched yeast tablet or a placebo yeast tablet daily. During the 4-year follow-up period, seven out of 113 individuals on the placebo developed primary liver cancer, while none of the 113 subjects supplemented with selenium developed liver cancer (36).
Well-nourished populations: In the U.S., a double-blind, placebo-controlled study of more than 1,300 older adults with a history of nonmelanoma skin cancer found that supplementation with 200 mcg/day of selenium-enriched yeast for an average of 7.4 years was associated with a 49% decrease in prostate cancer incidence in men (37). The protective effect of selenium supplementation was greatest in men with lower baseline plasma selenium and prostate-specific antigen (PSA) levels. Surprisingly, the most recent results from this study indicate that selenium supplementation increased the risk of one type of skin cancer (squamous cell carcinoma) by 25% (38) but did not significantly decrease the risk of lung cancer (39). Although selenium supplementation shows promise for the prevention of prostate cancer, its effects on the risk for other types of cancer are unclear. In response to the need to confirm these findings, several large placebo-controlled trials designed to further investigate the role of selenium supplementation in prostate cancer prevention are presently underway (24, 40, 41). However, a large randomized, placebo-controlled intervention study using selenium and vitamin E supplementation (i.e., the SELECT study) was recently halted because there was no evidence of benefit in preventing prostate cancer (42). After 5.5 years of follow-up in the SELECT study, selenium supplementation (200 mcg/day), alone or when co-supplemented with vitamin E, did not alter the risk for prostate, lung, or colorectal cancer (67).
Several mechanisms have been proposed for the cancer prevention effects of selenium: 1) maximizing the activity of antioxidant selenoenzymes and improving antioxidant status, 2) improving immune system function, 3) affecting the metabolism of carcinogens, 4) increasing the levels of selenium metabolites that inhibit tumor cell growth, 5) influence of selenium on apoptosis, 6) influence of selenium on DNA repair, and 7) selenium as an anti-angiogenic agent. A two-stage model has been proposed to explain the different anticarcinogenic activities of selenium at different doses. At nutritional or physiologic doses (~40-100 mcg/day in adults), selenium maximizes antioxidant selenoenzyme activity, probably enhances immune system function, and may affect carcinogen metabolism. At supranutritional or pharmacologic levels (~200-300 mcg/day in adults), the formation of selenium metabolites, especially methylated forms of selenium, may also exert anticarcinogenic effects (22, 23).
Theoretically, optimizing selenoenzyme activity could decrease the risk of cardiovascular disease by decreasing lipid peroxidation and influencing the metabolism of cell-signaling molecules known as prostaglandins. However, prospective studies in humans have not demonstrated strong support for the cardioprotective effects of selenium. While one study found a significant increase in illness and death from cardiovascular disease in individuals with serum selenium levels below 45 mcg/liter compared to matched pairs above 45 mcg/liter (43), another study, using the same cutoff points for serum selenium, found a significant difference only in deaths from stroke (44). One study in middle-aged and elderly Danish men found an increased risk of cardiovascular disease in men with serum selenium levels below 79 mcg/liter (45), but several other studies found no clear inverse association between selenium nutritional status and cardiovascular disease risk (46). In a multi-center study in Europe, toenail selenium levels and risk of myocardial infarction (heart attack) were only associated in the center where selenium levels were the lowest (47). While some epidemiological evidence suggests that low levels of selenium (lower than those commonly found in the U.S.) may increase the risk of cardiovascular diseases, definitive evidence regarding the role of selenium in preventing cardiovascular diseases will require controlled clinical trials.
Only a few studies have examined whether selenium status influences risk for type 2 diabetes mellitus and results are conflicting. One study found that lower toenail selenium levels in men with type 2 diabetes than in non-diabetic men (48); in contrast, another study reported higher serum selenium levels in type 2 diabetics (49). A recent randomized, double-blind, placebo-controlled study in 1,202 men and women participating in the Nutritional Prevention of Cancer trial found that selenium supplementation (200 mcg/day; mean follow-up of 7.7 years) was linked to an increase in prevalence of type 2 diabetes (50). In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (200 mcg/day; median follow-up of 5.5 years) was associated with a statistically nonsignificant increased risk of type 2 diabetes (67).
There appears to be a unique interaction between selenium and the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS). Declining selenium levels in HIV-infected individuals are sensitive markers of disease progression and severity, even before malnutrition becomes a factor. Low levels of plasma selenium have also been associated with a significantly increased risk of death from HIV. Adequate selenium nutritional status may increase resistance to HIV infection by enhancing the function of important immune system cells known as T cells and modifying their production of intracellular messengers known as cytokines (20, 51). In HIV infection, increased oxidative stress appears to favor viral replication, possibly by activating specific transcription pathways. As an integral component of glutathione peroxidase and thioredoxin reductase, selenium plays an important role in decreasing oxidative stress in HIV-infected cells and possibly suppressing the rate of HIV replication (51). Recent research indicates that HIV may be capable of incorporating host selenium into viral selenoproteins that have glutathione-peroxidase activity. Though the significance of these findings requires further clarification, they suggest that both the human immune system and the activity of the virus are affected by selenium nutritional status (51-53).
Only a few trials of selenium supplementation in HIV-infected individuals have been published. Two uncontrolled trials of selenium supplementation (one using 400 mcg/day of selenium-enriched yeast and the other using 80 mcg/day of sodium selenite plus 25 mg/day of vitamin C) reported subjective improvement but did not demonstrate any improvement in biological parameters related to AIDS progression (54). Another trial followed 15 HIV-infected patients supplemented with 100 mcg/day of sodium selenite and 22 unsupplemented patients for one year and found selenium supplemented patients had evidence of decreased oxidative stress and significant reductions in a biological marker of immunologic activation and HIV progression. However, there were no differences in CD4 T cell count (an important biological marker of the progress of HIV infection) or mortality between the supplemented and unsupplemented patients (55, 56). A randomized control trial in 186 HIV-positive men and women found that selenium supplementation at 200 mcg/day for two years significantly decreased hospitalization rates (57). A recent randomized, double-blind, placebo-controlled trial in 174 HIV-1-positive individuals reported that selenium supplementation (200 mcg/day of selenium-enriched yeast) for nine months was associated with increased serum selenium concentrations, increased CD4 T cell counts, and no progression of the HIV-1 viral load (58).
The richest food sources of selenium are organ meats and seafood, followed by muscle meats. In general, there is wide variation in the selenium content of plants and grains because plants do not appear to require selenium. Thus, the incorporation of selenium into plant proteins is dependent only on soil selenium content. Brazil nuts grown in areas of Brazil with selenium-rich soil may provide more than 100 mcg of selenium in one nut, while those grown in selenium-poor soil may provide ten times less (59). In the U.S., grains are a good source of selenium, but fruits and vegetables tend to be relatively poor sources of selenium. In general, drinking water is not a significant source of selenium in North America. The average dietary intake of adults in the U.S. has been found to range from about 80 to 110 mcg/day. Because of food distribution patterns in the U.S., people living in areas with low soil selenium avoid deficiency because they eat foods produced in areas with higher soil selenium (11, 15). The table below lists some good food sources of selenium and their selenium content in micrograms (mcg). For more information on the nutrient content of specific foods, search the USDA food composition database.
|Brazil nuts (from selenium-rich soil)||1 ounce (6 kernels)||544*|
|Shrimp||3 ounces (10-12)||34|
|Crab meat||3 ounces||41|
|Noodles, enriched||1 cup, cooked||38|
|Rice, brown||1 cup, cooked||19|
|Chicken (light meat)||3 ounces||13|
|Whole wheat bread||2 slices||23|
|Milk, skim||8 ounces (1 cup)||5|
|Walnuts, black||1 ounce, shelled||5|
*Above the tolerable upper intake level (UL) of 400 mcg/day.
Selenium supplements are available in several forms. Sodium selenite and sodium selenate are inorganic forms of selenium. Selenate is almost completely absorbed, but a significant amount is excreted in the urine before it can be incorporated into proteins. Selenite is only about 50% absorbed but is better retained than selenate once it is absorbed. Selenomethionine, an organic form of selenium that occurs naturally in foods, is about 90% absorbed (15). Selenomethionine and selenium-enriched yeast, which mainly supply selenomethionine, are also available as supplements. The consumer should be aware that some forms of selenium yeast on the market contain yeast plus mainly inorganic forms of selenium. Both inorganic and organic forms of selenium can be metabolized to selenocysteine by the body and incorporated into selenoenzymes (60).
Selenium-enriched garlic, broccoli, onions, and ramps (wild leeks) have been shown to reduce chemically induced tumors in rats (24, 61, 62). Selenium-enriched vegetables are of interest to scientists because some of the forms of selenium they produce (e.g., methylated forms of selenium) may be more potent inhibitors of tumor formation than the forms currently available in supplements. For more information on The Anti-cancer Effect of Selenium-enriched Ramps, see Dr. Philip D. Whanger's article in the Fall/Winter 1999 issue of the Linus Pauling Institute newsletter.
Although selenium is required for health, like other nutrients, high doses of selenium can be toxic. Acute and fatal toxicities have occurred with accidental or suicidal ingestion of gram quantities of selenium. Clinically significant selenium toxicity was reported in 13 individuals after taking supplements that contained 27.3 milligrams (27,300 mcg) per tablet due to a manufacturing error. Chronic selenium toxicity (selenosis) may occur with smaller doses of selenium over long periods of time. The most frequently reported symptoms of selenosis are hair and nail brittleness and loss. Other symptoms may include gastrointestinal disturbances, skin rashes, a garlic breath odor, fatigue, irritability, and nervous system abnormalities. In an area of China with a high prevalence of selenosis, toxic effects occurred with increasing frequency when blood selenium concentrations reached a level corresponding to an intake of 850 mcg/day. The Food and Nutrition Board (FNB) of the Institute of Medicine recently set the tolerable upper intake level (UL) for selenium at 400 mcg/day in adults based on the prevention of hair and nail brittleness and loss and early signs of chronic selenium toxicity (15). The UL of 400 mcg/day for adults (see table below) includes selenium obtained from food, which averages about 100 mcg/day for adults in the U.S., as well as selenium from supplements. For more information on the data used to set the recent RDA and UL for selenium, see The New Recommendations for Dietary Antioxidants: A Response and Position Statement by the Linus Pauling Institute in the Spring/Summer 2000 issue of the Linus Pauling Institute newsletter.
|Tolerable Upper Intake Level (UL) for Selenium|
|Age Group||UL (mcg/day)|
|Infants 0-6 months||45|
|Infants 6-12 months||60|
|Children 1-3 years||90|
|Children 4-8 years||150|
|Children 9-13 years||280|
|Adolescents 14-18 years||400|
|Adults 19 years and older||400|
At present, few interactions between selenium and medications are known (63). The anticonvulsant medication valproic acid has been found to decrease plasma selenium levels. Animal studies have found that supplemental sodium selenite decreases the toxicities of the antibiotic nitrofurantoin and the herbicide paraquat (64).
Antioxidant Supplements and HMG-CoA Reductase Inhibitors (Statins)
A 3-year randomized controlled trial in 160 patients with documented coronary heart disease (CHD) and low HDL levels found that a combination of simvastatin (Zocor) and niacin increased HDL2 levels, inhibited the progression of coronary artery stenosis (narrowing), and decreased the frequency of cardiovascular events, including myocardial infarction (heart attack) and stroke (65). Surprisingly, when an antioxidant combination (1,000 mg vitamin C, 800 IU alpha-tocopherol, 100 mcg selenium, and 25 mg beta-carotene daily) was taken with the simvastatin-niacin combination, the protective effects were diminished. Although the individual contribution of selenium to this effect cannot be determined, these findings highlight the need for further research on potential interactions between antioxidant supplements and cholesterol-lowering agents such as HMG-CoA reductase inhibitors (statins).
The average American diet is estimated to provide about 100 mcg/day of selenium, an amount that is well above the current RDA (55 mcg/day) and appears sufficient to maximize plasma and cellular glutathione peroxidase activity. Although the amount of selenium in multivitamin/multimineral supplements varies considerably, multivitamin-mineral supplements rarely provide more than the Daily Value (DV) of 70 mcg. Eating a varied diet and taking a daily multivitamin supplement should provide sufficient selenium for most people in the U.S.
A controlled trial that examined the effect of selenium supplementation on cancer risk in a well-nourished population found 200 mcg/day of supplemental selenium significantly decreased the risk of prostate cancer in men by 49% (37). However, the risk of one type of skin cancer was increased by 25% (38). Although mortality from prostate cancer is considerably higher than mortality from squamous cell cancer of the skin, these findings suggest that the overall effects of selenium supplementation on cancer risk are not yet clear enough to support a general recommendation for an extra selenium supplement. More recently, a much larger randomized, placebo-controlled intervention study, the SELECT study, found that 200 mcg/day of selenium did not alter risk of prostate cancer (67). Men taking supplemental selenium in order to reduce the risk of prostate cancer should not exceed 200 mcg/day and should take precautions to reduce the risk of squamous cell carcinoma, such as using sunscreen and avoiding prolonged sun exposure.
Because there is no evidence that selenium supplementation decreases the risk of cancer in women who are not selenium deficient, there is no reason for women to take an extra selenium supplement. However, animal studies suggest that mammary tumors are significantly reduced by selenium (66), and the two human trials presently underway should yield more definitive information on this relationship in women (24).
Older adults (65 years and older)
Because aging has not been associated with significant changes in the requirement for selenium, the Linus Pauling Institute Recommendation for selenium is the same for older men and women.
Written in October 2003 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University
Updated in November 2007 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University
Reviewed in November 2007 by:
Philip D. Whanger, Ph.D.
Dept. of Environmental and Molecular Toxicology
Oregon State University
Last updated 1/22/09 Copyright 2001-2013 Linus Pauling Institute
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