Selenium is an essential trace mineral and is required for the function of selenium-containing proteins (selenoproteins) which include enzymes with antioxidant activity, enzymes involved in production of thyroid hormone, and enzymes that participate in immune function.
Tissue selenium concentrations are highest in the kidney, liver, muscle, and thyroid.
The activities of selenium in human health are thought to be due to selenoproteins. Approximately 25 human selenoproteins have been identified.1 Selenoproteins contain selenocysteine which is an amino acid.
The two most common forms of absorbable selenium are selenomethionine and selenocysteine. Selenocysteine is found mainly in foods of animal origin.2 Selenomethionine is found mainly in plant foods.2 Selenomethionine is the best absorbed form of selenium at a rate close to 100%.
Inorganic forms of selenium are selenate and selenite. The fractional absorption of these inorganic forms from the gastrointestinal tract is less than 50%. Selenate is absorbed at a slightly higher rate while selenite is better retained.
Urinary excretion is the dominant route for selenium elimination. Small amounts of selenium are excreted through feces.
The average intake of selenium is approximately 70-100 mcg/day in the United States.
There are five classes of human selenoproteins known: glutathione peroxidases (antioxidants), iodothyronine deiodinases (thyroid hormone synthesis), selenophosphate synthase (biosynthesis of selenoproteins), thioredoxin reductase (antioxidant, redox signaling), and other selenoproteins (whose functions are unclear).3
Most selenium-containing proteins (selenoproteins) have enzymatic functions. Selenium is best known for its role in the glutathione peroxidase (GPx) enzyme system, one of the major antioxidant defense systems in the body.
Optimal activity of the glutathione peroxidase enzyme system is attained when levels of selenium in serum or plasma are at least 90 mcg/L. 2
Selenium has important antioxidant effects derived from its ability to reduce hydrogen peroxide and phospholipid hydroperoxides and thereby stop the production of free radicals and reactive forms of oxygen. It also reduces hydroperoxide intermediates thus lowering the production of inflammatory prostaglandins and leucotrienes. These effects are potentiated in the presence of vitamin E. 2
Selenium antagonizes the effects of toxic metals such as cadmium and arsenic.
Selenium-dependent thioredoxin reductases also contribute to the antioxidant role of selenium in mammals.
The selenoprotein iodothyronine deiodinase is required for synthesis of thyroid hormone.
Selenium deficiency appears when daily intake of the element is lower than 40-45 mcg. Insufficient intake may lead to defects in immune processes.2
Selenium deficiency is associated with 3 diseases: Kashin-Beck, Keshan, and Myxedematous Endemic Cretinism. Keshan disease, still seen in large areas of the Chinese countryside, results in an enlarged heart and poor heart function and mainly affects children and young women. Kashin-Beck disease results in severe osteoarthritis and occurs during pre-adolescence. Myxedematous endemic cretinism results in mental retardation.
Symptoms of selenium deficiency include muscle pain, weakness, loss of pigment in hair and skin, and whitening of the nail beds.
The National Academy of Sciences has established an upper limit of 400 mcg/day for selenium although intakes of up to 724 mcg/day appear to be safe.4
Clinical manifestations of selenium toxicity in humans usually appear when chronic intake exceeds 900 mcg.2
Prolonged intakes of selenium at 1000 mcg or higher may cause selenosis (selenium toxicity).
Symptoms of excessive selenium intake include hair and nail loss, lesions of the scalp and skin, nervous system abnormalities, vomiting, nausea, and fatigue.
In many countries, plant foods are the main source of selenium and amounts vary depending on the region's soil. In the United States, meats and breads are the most common sources of dietary selenium. Other good food sources include: eggs, wheat, bran, brazil nuts, oats, garlic, whole wheat bread, and brown rice.
Clinical selenium deficiency has been observed in patients chronically receiving total parenteral nutrition without added selenium. Selenium supplementation during total parental nutrition is now the standard.
People suffering from severe gastrointestinal disorders such as Crohn's disease and people who have had a large part of the small intestine removed are at risk for selenium deficiency.
Modified diets such as those for metabolic disorders should be assessed for selenium content.
People with iodine deficiency may benefit from selenium supplementation. Research suggests that selenium deficiency may exacerbate the effects of iodine deficiency on thyroid function. Adequate selenium nutritional status may help protect against some of the neurological effects of iodine deficiency.
Selenium may slow clotting time and should not be taken in combination with drugs that interfere with blood clotting such as include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.
Taking the combination of selenium, beta-carotene, vitamin C, and vitamin E may decrease the efficacy of medications used for lowering cholesterol (such as atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), and pravastatin (Pravachol)). This combination has also been shown to reduce efficacy of niacin. It is not known if selenium alone decreases the effectiveness of cholesterol lowering medications or niacin.
Chemotherapy drugs, such as cisplatin, may increase selenium requirements. Many studies have suggested that selenium in various forms may diminish cisplatin-induced kidney damage and bone marrow damage. Selenium supplementation may be beneficial.
The efficacy of selenium is increased by vitamin E and other antioxidant nutrients which promote glutathione peroxidase activity. Taking antioxidant vitamins may be helpful. Selenium absorption is decreased by high doses of vitamin C, zinc, and heavy metals. It is advised to consult a physician or pharmacist in order to balance dietary and supplemental intakes.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
High serum selenium and reduced risk of advanced colorectal adenoma in a colorectal cancer early detection program.
The association between serum selenium concentration and advanced colorectal adenoma, a cancer precursor, was investigated in an epidemiologic study. Subjects were randomly selected from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and included 758 cases of advanced colorectal adenoma and 767 sex and race matched controls. The study group was predominantly male (70%). An inverse association between serum selenium concentration and advanced colorectal adenoma was evident for smokers (OR 0.53) but was not present for nonsmokers or former smokers who quit more than 10 years ago. This study indicates that selenium may help reduce risk for advanced colorectal adenoma for smokers.5
Selenium supplementation and colorectal adenomas: an analysis of the nutritional prevention of cancer trial.
Selenium supplementation, colorectal adenoma, and colorectal cancer were studied during follow-up of the Nutritional Prevention of Cancer trial. The effect of selenium supplementation on colorectal adenoma and colorectal cancer prevalence was investigated. Of the 1312 subjects randomized to receive 200 mcg selenium from selenized yeast daily, 598 received an endoscopic screening. A non-significant reduction in risk for colorectal adenoma or colorectal cancer with selenium supplementation was found for prevalent cases (OR 0.67). Those in the lowest tertile of selenium concentration had a significant reduction of risk (OR 0.27) and current smokers had a significant reduction of risk (OR 0.27). Selenium supplements may reduce risk for colorectal adenoma or colorectal cancer for those with low selenium concentrations and for smokers.6
Selenium and colorectal adenoma: results of a pooled analysis.
Data from the Wheat Bran Fiber Trial, the Polyp Prevention Trial, and the Polyp Prevention Study were pooled and utilized to investigate the association between selenium concentration and risk for colorectal adenoma. Plasma selenium concentration was determined for 1763 participants. People with selenium concentrations in the highest quartile had a significantly reduced risk for development of a new adenoma versus those in the lowest quartile (OR 0.66). The results of this pooled data analysis supported the results of other trials and indicated an inverse association between plasma selenium concentration and risk for development of colorectal adenoma and, thus, possibly colorectal cancer.7
Selenium supplementation and lung cancer incidence: an update of the Nutritional Prevention Cancer Trial.
The Nutritional Prevention of Cancer Trial showed a statistically significant decrease in lung cancer incidence with selenium supplementation (200 mcg/day) after 4.9 years of follow up. The study included 1,312 people. After an additional 3 years of follow up, a reanalysis of the Nutritional Prevention of Cancer Trial indicated that selenium supplementation provided a significant decrease in lung cancer incidence only for those with low selenium concentrations at baseline, and not for the full study cohort.8
Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
A randomized, double-blind, placebo-controlled trial investigated the relationships between selenium, vitamin E, and prostate cancer10. A total of 35,533 men without prostate cancer and with prostate specific antigen (PSA) < 4.0 ng/mL participated in the trial. Follow-up was for a minimum of 7 years and a maximum of 12 years. Participants were > 50 years old for black men and > 55 years old or older for all other participants. Men were randomized to 1 of 4 groups: selenium (200 mcg/day L-selenomethionine), vitamin E (400 IU/day all rac-á-tocopheryl acetate), both selenium and vitamin E, or placebo. To ensure blinding, all men consumed 2 supplements daily, authentic or matched placebo for selenium and vitamin E. The incidence of prostate cancer was recorded for each group: 529 men developed prostate cancer in the placebo group; 620 men in the vitamin E group developed prostate cancer (compared to placebo, hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = 0.008); 575 men in the selenium group reported prostate cancer (HR, 1.09; 99% CI, 0.93-1.27; P = 0.18), and 555 men consuming selenium and vitamin E supplements (HR, 1.05; 99% CI, 0.89-1.22, P = 0.46). Prostate cancer risk significantly increased with vitamin E supplements . This report was a follow up of a previous report from the same trial which found non-significant increases in risk for prostate cancer after a median follow-up period of 5.46 years.9 Further study is warranted.10
Selenium accumulation in prostate tissue during a randomized, controlled short-term trial of L-selenomethionine: a Southwest Oncology Group Study.
A randomized clinical trial investigated the localization of selenium from supplements in prostate cancer patients. Sixty-six men with prostate cancer enrolled in the study and were randomized to receive daily L-selenomethionine supplements or for observation. Serum selenium concentrations increased 15% in the supplemented arm of the study. Selenium concentration in prostate tissue was 22% higher in the supplemented arm than in the observational arm of the study. Conversely, selenium concentrations in the seminal vesicle were similar in both groups and were lower than in the prostate tissue. This study demonstrated that supplemental selenium preferentially accumulated in the prostate, possibly contributing to the efficacy of selenium against prostate cancer.11
Toenail selenium levels and the subsequent risk of prostate cancer: a prospective cohort study.
In a cohort study in the Netherlands, the relationship between toenail selenium levels (an indicator of long term selenium status) and risk of prostate cancer was studied. Men aged 55 to 69 years were enrolled in the study (58,279 subjects). A statistically significant inverse trend was found between toenail selenium level and risk for prostate cancer after 6.3 years of follow up, especially in ex-smokers. The incidence rate of prostate cancer was 0.69 in the highest quintile of selenium relative to those in the lowest quintile. The data also indicated that the association of selenium and prostate cancer did not depend on vitamin E intake.12
Serum selenium and risk of prostate cancer in U.S. blacks and whites.
To explore the racial disparity of prostate cancer in the U.S., the National Cancer Institute conducted a multi-center population-based case-control study of prostate cancer that included 212 men with prostate cancer and 233 controls, aged 40 to 79 years. Participation was 59% African American and 61% Caucasian. Results suggested that serum selenium in both races was inversely associated with prostate cancer risk. Comparing the highest to the lowest quartile of selenium concentration in both races, the odds ratio was 0.71. This association was strongest for men with low serum vitamin E. Risk reduction was apparent at serum selenium concentrations above 0.135 mcg/mL. Prostate cancer rates vary substantially by race and geographic region and explanations remain elusive.13
Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial.
The effect of selenium supplementation (200 mcg/day) on the overall incidence of prostate cancer was investigated through the complete treatment period of the Nutritional Prevention of Cancer Trial. Selenium supplementation reduced risk of prostate cancer in the 1312 subjects in the trial (RR 0.51). The authors found that although selenium supplementation was efficacious in reducing the incidence of prostate cancer, this effect was only seen in men with lower baseline PSA (<4 ng/ml) and plasma selenium concentration (RR 0.31). No risk reduction was found in men with higher baseline PSA.14
An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status.
The effects of supplemental selenium on immune function in healthy adults was investigated. Twenty-two adults with relatively low plasma concentrations of selenium were randomly assigned to consume 50 or 100 mcg/day selenium from sodium selenite or a placebo for 15 weeks. Selenium supplementation increased plasma concentrations of selenium, the exchangeable selenium pool, and glutathione peroxidase activity in both lymphocyte phospholipids and cytosol. Cellular immune response was increased as evinced by increased production of interferon-gamma and other cytokines, earlier peak T cell proliferation, and an increase in T helper cells. Subjects who consumed selenium supplements demonstrated faster viral clearance rates. Thus, the results of this study indicated that selenium supplements may improve immune response, particularly for those with low plasma concentrations of selenium.15
Selenium and coronary heart disease: a meta-analysis.
A meta-analysis of observational and randomized controlled clinical trials investigated the association between selenium and coronary heart disease. Twenty-five observational studies and six randomized clinical trials were included in the analysis. The relative risk for coronary heart disease comparing the highest and lowest selenium categories was 0.85 in cohort studies and 0.43 in case-control studies. Observational studies demonstrated a 24% reduction in coronary heart disease risk with a 50% increase in selenium. For randomized trials, selenium supplements compared to placebo resulted in a relative risk of 0.89. Selenium concentrations were inversely associated with coronary heart disease.16
Selenium supplementation decreases nuclear factor-kappa B activity in peripheral blood mononuclear cells from type 2 diabetic patients.
The effects of selenium supplementation on NF-kappa B activity and oxidative stress parameters were assessed in people with type 2 diabetes. Fifty-six people with type 2 diabetes enrolled in the study and were randomized to receive either 960 mcg/day selenium or a placebo for three months. Ten nondiabetic subjects were also enrolled in the study as controls. NF-kappa B activity was increased by 80% in the people with diabetes relative to controls. Selenium supplements significantly increased plasma selenium concentrations and red-cell selenium glutathione peroxidase activity. Selenium supplements reduced NF-kappa B activity in people with type 2 diabetes to a level near that of the nondiabetic controls. This study supports the conclusion that selenium helps protect against cardiovascular disease.17
Life-quality indicators in elderly people are influenced by selenium status.
Two-hundred-twenty-seven elderly adults living in nursing homes completed a food-frequency questionnaire, an interview, and donated blood samples for analysis of serum selenium concentrations. Higher serum selenium concentrations were associated with higher self-perceived health. In addition, higher selenium status was associated with good chewing ability. Subjects with higher selenium status were also more likely to participate in 60 minutes or more of exercise. Overall, those in the highest tertile of selenium concentration had more than twice the probability of reporting good health status, good chewing ability, or exercise participation than those in the lowest tertile (OR 2.05 to 3.157). The authors concluded that selenium status may be an important factor in quality of life for elderly adults.18
Impact of selenium on mood and quality of life: a randomized, controlled trial.
The first large-scale clinical trial investigating the effect of selenium supplementation on mood and quality of life contradicts the results of three previous small-scale trials. This randomized, double-blind, placebo-controlled trial enrolled 448 men and women aged 60 to 74 years. Subjects were randomized to receive 100, 200, or 300 mcg selenium/day as high selenium yeast or a placebo for six months. Supplementation significantly increased plasma selenium concentrations. No changes in mood or quality of life were found. Since this trial contradicts previous findings, further investigation is warranted.19
Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1-infected drug users during the era of highly active antiretroviral therapy.
A case-control study included subjects from a cohort of 259 HIV-infected drug users who participated in a double-blind, placebo-controlled clinical trial which evaluated selenium (200 mcg/day) as a chemopreventive agent for disease progression. The efficacy of selenium to modify the risk for mycobacterial disease in HIV-1 infected drug users was investigated. During the trial, 12 cases of mycobacterial infection occurred and were compared to 32 age, sex, and HIV-status matched controls. Multivariate analysis controlling for anti-retroviral treatment and CD4 cell count revealed that both body mass index and selenium concentrations were significant factors in the relative risk for developing mycobacterial disease (RR 3). The data suggested that higher than normal levels of selenium may be necessary to maintain a functional immune system in HIV-infected individuals. The authors suggest that selenium may have a critical role in reducing the risk for development of active mycobacterial disease in HIV-1 infected drug users.20
Psychological burden in the era of HAART: impact of selenium therapy.
A longitudinal study investigated the efficacy of selenium supplementation (200 mcg/day) on anxiety in HIV-infected drug users who exhibit a high psychological burden. The neuroprotection study group included 115 participants. Measurements of psychological burden were taken at baseline and at the 12-month evaluation. Participants who received daily selenium supplements reported increased vigor and less anxiety (State, p= 0.05 and Trait p= 0.02) compared to a placebo treated group. No effect was seen with depression or distress in the selenium supplemented group. The authors concluded that these results strongly suggested that selenium may be a safe and affordable means to alleviate anxiety in people with HIV.21
Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: a randomized controlled trial.
A randomized, double-blind, placebo-controlled, intention-to-treat clinical trial investigated the effect of selenium supplementation on immune function in 174 men and women with HIV-1 infections. Subjects consumed either 200 mcg/day selenium from high-selenium yeast or a placebo for 9 months. Selenium supplementation increased serum selenium concentrations (increase of 32.2 vs 0.5 mcg/L), decreased HIV-1 viral load, and increased CD4 counts. Nonresponders in the selenium supplemented group demonstrated poor adherence to the treatment program. The authors concluded that selenium supplements offer a low-cost, simple, and safe treatment to improve immune function for people with HIV-1.22
Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV-infected participants.
A two year randomized, double-blind, placebo-controlled study evaluated the impact of selenium supplementation (200 mcg/day) on hospitalizations in 186 HIV-1 infected people. All individuals had adequate baseline plasma selenium levels. Selenium supplementation was associated with a lower rate of hospital admissions, lower costs, and fewer opportunistic infections and HIV related conditions per year. Cost for hospitalizations decreased by 58% in the selenium supplemented group versus a decrease of 30% in the placebo group. In addition, selenium supplemented patients with or without anti-retroviral therapies had significantly lower risk for hospitalizations than those given placebo.23
Selenium and the course of mild Graves' orbitopathy.
A randomized, placebo-controlled, double-blind clinical trial investigated selenium supplements or pentoxifylline for Graves’ orbitopathy. One-hundred-fifty-nine people with mild Graves’ orbitopathy participated in the trial. Participants received supplements or placebo for six months and then were followed for an additional six months after treatment was stopped. Participants were randomly assigned to receive 200 mcg/day selenium, 1200 mg/day pentoxifylline, or a placebo daily. After six months of supplementation, selenium was associated with an improved quality of life (P<0.001) and less eye involvement (P=0.01) and slowed the progression of Graves’ orbitopathy (P=0.01), as compared with placebo. Such significant improvements were not noted for pentoxifylline. Repeat evaluations at 12 months found similar results. The results of this small study suggest that selenium supplements may be beneficial for people with mild Graves’ orbitopathy. Further studies to evaluate these results are necessary.24
Selenium and zinc in patients with acute and chronic uveitis.
The association of serum selenium concentration and uveitis (an inflammation of the layer of the eye between the sclera and the retina) was investigated in a small study. Twenty-four people with uveitis enrolled in the study, 13 women and 11 men. Mean age of the participants was 40.6 years. Subjects with acute uveitis had normal serum selenium concentrations as measured by atomic absorption spectrometry. However, those with chronic uveitis had significantly decreased selenium levels, below the normal range. The authors suggest that further study is warranted.25
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