Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Intervention trial with selenium for the prevention of lung cancer among tin miners in Yunnan, China. A pilot study. Low plasma selenium as a risk factor for cancer death in middle-aged men. Serum selenium and subsequent risk of cancer among Finnish men and women. Association between serum selenium and the risk of cancer. Plasma selenium concentration and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma selenium level before diagnosis and the risk of prostate cancer development. The nutritional prevention of cancer: 400 mcg per day selenium treatment. Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk. A prospective study of plasma selenium levels and prostate cancer risk. Prediagnostic serum selenium and risk of cancer. Serum selenium and risk of prostate cancer-a nested case-control study. Serum selenium concentration associated with risk of cancer. [The prevention of primary liver cancer by selenium in high risk populations]. Is serum selenium a risk factor for cancer in men only? Selenium levels in nails of premenopausal breast cancer patients assessed prediagnostically in a cohort-nested case-referent study among women screened in the DOM project. An intervention study to prevent gastric cancer by micro-selenium and large dose of allitridum. Prospective study of toenail selenium levels and cancer among women. Is low selenium status a risk factor for lung cancer? Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults. Serum selenium and the risk of cancer, by specific sites: case-control analysis of prospective data. Selenium supplementation does not improve vascular responsiveness in healthy North American men. A prospective cohort study on toenail selenium levels and risk of gastrointestinal cancer. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Selenium and mortality in the elderly: results from the EVA study. Is serum selenium a risk factor for cancer? Selenium in human mammary carcinogenesis: a case-cohort study. Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and child outcomes. Serum selenium and risk of cancer. A prospective follow-up of nine years. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. Prediagnostic serum selenium and zinc levels and subsequent risk of lung and stomach cancer in Japan. Selenium supplementation in low-birthweight premature infants: relationship to trace metals and antioxidant enzymes. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. No effect of selenium supplementation on serum glucose levels in men with prostate cancer. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. The effect of oral selenium supplementation on human sperm motility. A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Increased consumption of wheat biofortified with selenium does not modify biomarkers of cancer risk, oxidative stress, or immune function in healthy Australian males. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). A randomized trial of selenium supplementation and risk of type-2 diabetes, as assessed by plasma adiponectin. Serum levels of selenium and retinol and the subsequent risk of cancer. Prediagnostic serum selenium in a case-control study of thyroid cancer. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. The association between baseline vitamin E, selenium, and prostate cancer in the alpha-tocopherol, beta-carotene cancer prevention study. Serum selenium and cancer mortality: a nested case-control study within an age- and sex-stratified sample of the Belgian adult population. The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group. Effect of selenium supplementation on biochemical markers and outcome in critically ill patients.
To determine whether a nutritional supplement of selenium will decrease the incidence of cancer.
                A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial.
                Seven dermatology clinics in the eastern United States.
                A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years.
                Oral administration of 200 microg of selenium per day or placebo.
                The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers.
                After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred.
                Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made This pilot study evaluated the feasibility and effectiveness of conducting a double-blind clinical trial for the prevention of lung cancer with selenium (Se) in Yunnan Tin Corporation, the People's Republic of China, where the incidence rates of lung cancer are extraordinarily high among the miners. Forty healthy miners were randomized to either 300 micrograms of Se in high Se malt cakes or an identical placebo of malt cakes daily for one year. Subjects consumed their usual daily diet. The low Se concentrations in plasma (0.05 +/- 0.008 microgram/mL) and hair (0.442 +/- 0.085 microgram/g) reflected their low dietary Se intake in the control subjects. In Se-supplemented group, the Se status was increased by 178% for serum and 194.8% for hair. The serum GSHpx activity was increased by 155.7%, whereas the lipid peroxide level was reduced by 74.5% compared to the placebo. The results of UDS assay indicated that the lymphocyte DNA damage induced by ultraviolet irradiation and carcinogen 3,4-benzpyrene could be protected by Se supplementation. Se-supplementation did not affect the liver function test (SGPT), as well as the concentrations of hemoglobin, albumin, and cholesterol. Thus, daily intake of 300 micrograms Se in form of Se-malt as a chemopreventive measure is safe and effective to humans with low Se status. In a population study, 10,000 men (aged 46-48 years) were invited to a health screening program. At follow-up, which was up to eight years later, 61 subjects had died from cancer; from 35 of these subjects, plasma samples were available that were obtained at the initial screening. These samples, together with samples from two living controls for each case, were analyzed for selenium, retinol, cholesterol, triglyceride, and a number of plasma proteins. Plasma selenium was significantly lower (p less than 0.05) in cases than in controls (means: 1.06 vs. 1.12 mumol/l). The proportion of cases increased significantly from the highest to the lowest quintile of plasma selenium, and the relative risk for cancer death was 3.8 times higher in the lowest quintile compared with the highest. Mean plasma retinol was similar in cases (2.53 mumol/l) and controls (2.56 mumol/l). Cases and controls also had similar values for plasma cholesterol, triglyceride, uric acid, apolipoprotein B, orosomucoid, prealbumin, retinol-binding protein, and beta 2-microglobulin. Apolipoprotein AI in plasma was lower among cases (p less than 0.025). Cases smoked significantly more than controls did (p less than 0.05). Data indicate that low plasma selenium was a risk factor for cancer death in middle-aged men who lived in the same area. Further studies are necessary to establish whether differences in selenium intake, selenium metabolism, or other factors related to selenium are responsible for the relations observed. At present, the available data do not justify selenium supplementation programs in the whole population. The association between the serum selenium level and the subsequent incidence of cancer was investigated in a longitudinal study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. The baseline examinations, including the collection of blood samples, were performed in 1968-1972. During a median follow-up of 10 years, 1,096 new cancer cases were identified from the files of the Finnish Cancer Registry. Selenium concentrations were measured from the stored serum samples collected from these cancer cases and from two controls per case, matched for sex, municipality, and age. The mean serum selenium level was 59.1 micrograms/L among all male cancer cases and 62.5 micrograms/L among controls. The difference was statistically significant (P less than .001). Corresponding values among women were 63.6 and 63.9 micrograms/L, respectively. Low serum selenium levels were associated with an increased risk of developing cancer at several sites, especially cancers of the stomach and lung among men. The relative risk of lung cancer between the highest and lowest decile of serum selenium was 0.11, and it differed significantly from unity (P less than .001). These findings are in agreement with the hypothesis that low selenium intake may increase the risk of some cancers among men. A matched-pair analysis was conducted with data based on a prospective six-year follow-up of a random population sample to study the association between serum selenium and the risk of cancer. Case-control pairs were from a population, after exclusions, of 8,113 persons examined in 1972 from two counties in eastern Finland. Cases were 31- to 59-year-old men and women initially free of cancer. One control was matched to each case according to age, gender, daily tobacco consumption, and serum cholesterol concentration. The mean serum selenium of the 128 cases was 50.5 micrograms/liter and that of the controls was 54.3 micrograms/liter (p = 0.012 for difference). When the residual variation in tobacco consumption and serum cholesterol as well as that in four other possible confounders was allowed for in a multiple logistic model, serum selenium of less than 45 micrograms/liter was associated with a relative risk of cancer of 3.1 (95% confidence interval, 1.5-6.7, p less than 0.01). These data support the hypothesis that selenium deficiency increases the risk of certain cancers in middle-aged persons. Some evidence indicates that a low selenium intake may be associated with an increased risk of prostate cancer.
                The aim of this study was to investigate the association of plasma selenium concentration with subsequent prostate cancer risk and to examine this association by stage and grade of disease and other factors.
                A nested case-control study was performed among men in the European Prospective Investigation into Cancer and Nutrition (EPIC). The association between plasma selenium concentration and prostate cancer risk was assessed in 959 men with incident prostate cancer and 1059 matched controls.
                Overall, plasma selenium concentration was not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of selenium concentration compared with the lowest fifth was 0.96 (95% CI: 0.70, 1.31; P for trend = 0.25). There were no significant differences in the association of plasma selenium with risk when analyzed by stage or grade of disease. Similarly, the association of selenium with risk did not differ by smoking status or by plasma alpha- or gamma-tocopherol concentration.
                Plasma selenium concentration was not associated with prostate cancer risk in this large cohort of European men. Epidemiological studies and a randomized intervention trial suggest that the risk of prostate cancer may be reduced by selenium intake. We investigated whether plasma selenium level before diagnosis correlated with the risk of later developing prostate cancer.
                A case control study was performed on men from the Baltimore Longitudinal Study of Aging registry, including 52 with known prostate cancer and 96 age matched controls with no detectable prostatic disease. Plasma selenium was measured at an average time plus or minus standard deviation of 3.83 +/- 1.85 years before the diagnosis of prostate cancer by graphite furnace atomic absorption spectrophotometry. Adjusted odds ratio and 95% confidence interval were computed with logistic regression.
                After correcting for years before diagnosis, body mass index, and smoking and alcohol use history, higher selenium was associated with a lower risk of prostate cancer. Compared with the lowest quartile of selenium (range 8.2 to 10.7 microg./dl.), the odds ratios of the second (10.8 to 11.8), third (11.9 to 13.2) and fourth (13.3 to 18.2) quartiles were 0.15 (95% confidence interval 0.05 to 0.50), 0.21 (0.07 to 0.68) and 0.24 (0.08 to 0.77, respectively, p =0.01). Furthermore, plasma selenium decreased significantly with patient age (p <0.001).
                Low plasma selenium is associated with a 4 to 5-fold increased risk of prostate cancer. These results support the hypothesis that supplemental selenium may reduce the risk of prostate cancer. Because plasma selenium decreases with patient age, supplementation may be particularly beneficial to older men. Nonexperimental studies suggest that individuals with higher selenium (Se) status are at decreased risk of cancer. The Nutritional Prevention of Cancer (NPC) study randomized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo; selenium supplementation decreased the risk of lung, colon, prostate, and total cancers but increased the risk of nonmelanoma skin cancer. In this article, we report on a small substudy in Macon, GA, which began in 1989 and randomized 424 patients to 400-mcg/day of Se or to matched placebo. The subjects from both arms had similar baseline Se levels to those treated by 200 mcg, and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg. The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25%; however, 400-mcg/day of Se had no effect on total cancer incidence. We previously reported an inverse association between prediagnostic serum selenium concentrations and the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia cancer (GCC) but not gastric noncardia cancer (GNCC) in a nested study from the Nutrition Intervention Trial in Linxian, China.
                We examined the relation between baseline serum selenium and the subsequent risk of death from ESCC, GCC, GNCC, heart disease (HD), stroke, and total death over 15 y of follow-up (1986-2001).
                We measured baseline serum selenium concentrations in 1103 subjects randomly selected from a larger trial cohort. We identified 516 deaths during the 15-y follow up, including 75 from ESCC, 36 from GCC, 116 from HD, and 167 from stroke. Relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards regression models. Reported RRs estimated the change in risk conferred by a 25% increase in serum selenium relative to the population distribution. All estimates were adjusted for sex, age, smoking, drinking, and serum cholesterol.
                We found significant inverse associations between baseline serum selenium and death from ESCC (RR: 0.83; 95% CI: 0.71, 0.98) and GCC (0.75; 0.59, 0.95). Trends toward inverse associations were noted for death from HD (0.89; 0.78, 1.01; P = 0.07), but no association was noted for total death (0.96; 0.90, 1.02) or stroke (0.99; 0.88, 1.11).
                Population-wide selenium supplementation in the region of China with low serum selenium and high incidences of ESCC and GCC merits serious consideration. Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (n = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer. Epidemiologic studies suggest that low selenium levels are associated with an increased incidence of prostate cancer, although results are conflicting. We examined the association between pre-diagnostic plasma selenium levels and risk of prostate cancer in men enrolled in the Physicians' Health Study.
                Using plasma samples obtained in 1982 from healthy men enrolled in the study, we conducted a nested case-control study among 586 men diagnosed with prostate cancer during 13 years of follow-up and 577 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of prostate cancer in pre- (before October 1990) and post- (after October 1990) prostate-specific antigen (PSA) screening eras were calculated using multivariable logistic regression.
                Pre-diagnostic plasma selenium levels were inversely associated with risk of advanced prostate cancer (5th versus 1st quintile OR = 0.52, 95% CI = 0.28 to 0.98; P(trend) =.05), even among men diagnosed after 1990 (5th versus 1st quintile OR = 0.39, 95% CI = 0.16 to 0.97). The inverse association with prostate cancer risk was observed only for case subjects with elevated baseline PSA levels (PSA >4 ng/mL, 5th versus 1st quintile OR = 0.49, 95% CI = 0.28 to 0.86; P(trend) =.002). These inverse associations were observed in both pre- and post-PSA eras.
                The inverse association between baseline plasma selenium levels and risk of advanced prostate cancer, even among men diagnosed during the post-PSA era, suggests that higher levels of selenium may slow prostate cancer tumor progression. Ongoing randomized trials of selenium supplements may help to further evaluate this issue. Selenium levels in serum samples collected in 1973 from 111 subjects in whom cancer developed during the subsequent 5 years were compared with those in serum samples from 210 cancer-free subjects matched for age, race, sex, and smoking history. The mean selenium level of cases (0.129 +/- SEM 0.002 micrograms/ml) was significantly lower than that of controls (0.136 +/- 0.002 micrograms/ml). The risk of cancer for subjects in the lowest quintile of serum selenium was twice that of subjects in the highest. Multivariate adjustment for geographical area and serum levels of lipids, vitamins A and E, and carotene, did not alter this relation. The association between low selenium level and cancer was strongest for gastrointestinal and prostatic cancers. Serum levels of vitamins A and E compounded the effect of low selenium; relative risks for the lowest tertile of selenium were 2.4 and 3.9 in the lowest tertiles of vitamins E and A, respectively. Selenium is a potential chemopreventive agent against prostate cancer, whose chemoprotective effects are possibly mediated through the antioxidative properties of selenoenzymes. Interrelations with other antioxidative agents and oxidative stressors, such as smoking, are poorly understood.
                The aims were to investigate the association between serum selenium and prostate cancer risk and to examine interactions with other antioxidants and tobacco use.
                A nested case-control study was performed within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum selenium in prospectively collected samples was compared between 724 incident prostate cancer case subjects and 879 control subjects, frequency-matched for age, time since initial screen, and year of blood draw. The men were followed for up to 8 y.
                Overall, serum selenium was not associated with prostate cancer risk (P for trend = 0.70); however, higher serum selenium was associated with lower risks in men reporting a high (more than the median: 28.0 IU/d) vitamin E intake [odds ratio (OR) for the highest compared with the lowest quartile of selenium: 0.58; 95% CI: 0.37, 0.91; P for trend = 0.05; P for interaction = 0.01] and in multivitamin users (OR for highest compared with the lowest quartile of selenium: 0.61; 95% CI: 0.36, 1.04; P for trend = 0.06; P for interaction = 0.05). Furthermore, among smokers, high serum selenium concentrations were related to reduced prostate cancer risk (OR for the highest compared with the lowest quartile of selenium: 0.65; 95% CI: 0.44, 0.97; P for trend = 0.09; P for interaction = 0.007).
                Greater prediagnostic serum selenium concentrations were not associated with prostate cancer risk in this large cohort, although greater concentrations were associated with reduced prostate cancer risks in men who reported a high intake of vitamin E, in multivitamin users, and in smokers. The association between serum selenium concentration and risk of cancer was studied in a nested case control study. Case control pairs came from a population of 9364 people examined in 1979. During the six year follow up, 60 men and women aged between 20-54 at the time of blood sampling, who had been free of malignant disease, developed cancer. The mean serum selenium concentration of 1.56 mumol/l (123.2 micrograms/l) in patients was not significantly different from that in controls (1.63 mumol/l (128.7 micrograms/l]. The difference in mean selenium concentration was largest and most significant for haematological malignancies alone. The difference in selenium concentrations in cases of fatal cancer compared with controls was significant (p less than 0.01). The risk of developing adenocarcinomas does not seem to be influenced by serum selenium concentration. To study the preventive effects of selenium on primary liver cancer.
                After screening of blood samples in 18,000 males from 20 to 65 years-old in Qidong, Jiangsu province (a high risk area for liver cancer), 2,065 cases of HBsAg positive, AFP negative and normal liver function (normal ALT values) were found. The subjects were randomly divided into two groups, based on their residence areas; 1,112 subjects (experimental group) received one tablet of sodium selenite (0.5 mg Se) every day and 953 subjects (control group) received one placebo tablet every day.
                During three years of intervention and follow up, the blood selenium concentration and glutathione peroxidase activity of the subjects in the experimental group were increased and had significant difference as compared with those of the control group (P < 0.01). At the same time, the prevalence rate of micronucleus cells in peripheral blood lymphocytes in the experimental group was significantly lower than that of the control group (P < 0.01), and the incidence of new liver cancer in the experimental group (3 057.55/10(6), 34 cases out of 1,112 subjects) was significantly lower than the control group (5 981.11/10(6); 57 cases out of 953 subjects) (P < 0.01).
                The results confirms that selenium supplementation in general populations lived in high risk is effective in the prevention of liver cancer and the using of selenium tablets is simple and feasible. The association of serum selenium with the subsequent risk of death from cancer was investigated in a case-control study that was nested in a prospective nine-year follow-up study in the Netherlands. In 1975-1978, 10,532 persons in the Dutch town of Zoetermeer who were aged five years or more participated in a medical survey. Serum samples were collected and stored at -20 C. For the 82 persons who died of cancer since the baseline examination, 164 cohort members still alive by the end of 1983 were selected as controls and matched for age, sex, and smoking. Cancer deaths that occurred in the first year of follow-up were excluded, leaving 69 cases for statistical analyses. The mean serum selenium level of 116.7 +/- 4.0 micrograms/liter among male cancer deaths (n = 40) was significantly different (p = 0.04) from that in the control subjects (126.4 +/- 3.1 micrograms/liter). In females, selenium levels were similar among cases and controls. The adjusted risk of death from cancer for men in the lowest quintile of serum selenium (below 100.8 micrograms/liter) was more than twice that of subjects with higher levels (relative risk = 2.7,90% confidence interval = 1.2-6.2). These data support recent findings of an increased cancer risk associated with low serum selenium levels in men but not in women. To determine the possible role of selenium in the pathogenesis of breast cancer, prediagnostic Se 77 m isotope levels in toenail clippings in premenopausal women were measured. The study was designed as a case-referent study nested in a cohort. Participants were recruited from the DOM-project breast-cancer screening cohorts. No decreased selenium levels were found up to two years prior to diagnosis, nor were Se levels different between prevalent and/or incident breast cancer cases, referents and women with benign breast disease. Se levels measured in nails could not detect women at higher risk for breast cancer. This study does not support the idea that Se supplementation could have a preventive potential for premenopausal breast cancer in women in the Netherlands. People have more and more concerned about allitridum as studies have shown that taking more raw garlic associated with a lower risk for cancers of the alimentary system. In the present study, we tried to examine whether a large dose of allitridum and a microdose of selenium prevent gastric cancer.
                A double-blind intervention study was performed on the participants aged (35 - 74) years, who had matched at least one of the following criteria: (1) a medical history of stomach disorder, (2) a family history of tumour, or (3) smoking and/or alcohol consumption. A total of 2,526 and 2,507 persons were randomly enrolled into intervention group and control group respectively from 288 natural villages of seven communities in Qixia County, Shandong Province, China. Each person of the intervention group orally took 200 mg synthetic allitridum every day and 100 microg selenium every other day for one month of each year during November 1989 to December 1991. At the same time, people in control group were given 2 placebo capsules containing corn oid with the identical appearance to that in the intervention group.
                For all subjects the large dose of allitridum was accepted and no harmful side effects were found during the study. In the first follow-up five years (1992 - 1997) after stopping the intervention, the morbidity rates of malignant tumours in the intervention group declined by 22%, in contrast to the control group, declined by 47.3%. After adjusting for age, gender, and other potential confounders, relative risks (RRs) for all tumours and gastric cancer of the whole population were 0.67 (95% CL: 0.43 - 1.03) and 0.48 (95% CL: 0.21 - 1.06), respectively, and for male group they were 0.51 (95% CL: 0.30 - 0.85) and 0.36 (95% CL: 0.14 - 0.92), respectively. No signigicantly protective effect was found for the female subgroup.
                The present study proves that large doses of allitridum and microdorse of selenium may effectively prevent gastric cancer, especially in men. Inverse associations between selenium status and cancer risk have been observed in animal studies, ecologic studies, and some case-control and prospective studies. Whereas results of some prospective studies have suggested an overall inverse relationship between selenium levels and cancer, other prospective studies have failed to confirm this finding. Prospective data on women are particularly limited because fewer women than men have been studied prospectively.
                The aim of this study was to prospectively examine the relationship between selenium levels in toenails (previously shown to reflect selenium intake) and incidence of cancer among women.
                The Nurses' Health Study cohort began in 1976 with 121,700 female nurses aged 30-55 years living in 11 U.S. states. In 1982, we requested toenail clippings from the members of the cohort, and 62,641 participants with no history of cancer returned these clippings. During 41 months of follow-up, 503 cases of cancer other than breast cancer (results previously reported) or nonmelanoma skin cancer were analyzed. For each case patient, a control subject was chosen from women who remained free of diagnosed cancer, matched by age and by date of nail return.
                No inverse association was observed between selenium levels in toenails and cancer risk. The age- and smoking-adjusted relative risk (RR), comparing the highest with the lowest quintile of toenail selenium level, was 1.44 (95% confidence interval [CI] = 0.97-2.13), and the trend across quintiles was marginally significant (two-sided P = .06). Comparing the highest with the lowest decile, the RR (age- and smoking-adjusted) was 1.77 (95% CI = 1.04-3.02). When these data were combined with the data from 434 breast cancer case patients and their matched control subjects identified in parallel from this same cohort, the RR comparing the highest with the lowest quintile was 1.24 (95% CI = 0.93-1.65). Toenail selenium level was not inversely associated with cancer at any major site, including uterine cancer, colorectal cancer, melanoma, ovarian cancer, or lung cancer (after adjusting for smoking); in fact, nonsignificant positive associations were observed at several sites.
                Toenail selenium levels were not inversely associated with cancer risk in this study.
                These data, in conjunction with previous findings of no association between toenail selenium status and breast cancer risk, strongly suggest that higher selenium intake within the range consumed by most U.S. women (as reflected by toenail selenium levels) is not protective against overall cancer incidence in women. The hypothesis that low selenium may in some circumstances be a risk factor for lung cancer was investigated in a case-control study nested within a longitudinal study. Serum samples from 9,101 cancer-free individuals were collected and stored at -20 degrees C by the Finnish Mobile Clinic in 1968-1971 and 1973-1976. During follow-up until the end of 1991, 95 cases of lung cancer were diagnosed. Selenium concentrations were determined from the serum samples of the cases and 190 controls, individually matched for sex, age, and place of residence. Mean levels of serum selenium in cases and controls were 53.2 microg/liter and 57.8 microg/liter, respectively. The relative risk of lung cancer between the highest and lowest tertiles of serum selenium, adjusted for smoking, serum alpha-tocopherol, serum cholesterol, serum copper, serum orosomucoid, and body mass index (kg/m2), was 0.41 (95% confidence interval (CI) 0.17-0.94). The association was stronger at lower levels (<5.9 mg/liter) of alpha-tocopherol (relative risk=0.24, 95% CI 0.07-0.85). The association was also pronounced among current smokers and at higher levels of serum orosomucoid and serum copper. The relative risk for smokers who were twice ranked in higher selenium tertiles, at an interval of 4-7 years, in comparison with smokers who remained in the lowest tertile was 0.16 (95% CI 0.04-0.74). In accordance with the hypothesis, the findings suggest that very low selenium status may contribute to the risk of lung cancer. Selenium, an essential trace element involved in defense against oxidative stress, may prevent cancer and cardiovascular disease. We evaluated the association between selenium levels and all-cause and cause-specific mortality in a representative sample of US adults.
                Serum selenium levels were measured in 13,887 adult participants in the Third National Health and Nutrition Examination Survey. Study participants were recruited from 1988 to 1994 and followed up for mortality for up to 12 years.
                The mean serum selenium level was 125.6 ng/mL. The multivariate adjusted hazard ratios comparing the highest (> or = 130.39 ng/mL) with the lowest (< 117.31 ng/mL) serum selenium level tertile were 0.83 (95% confidence interval [CI], 0.72-0.96) for all-cause mortality, 0.69 (95% CI, 0.53-0.90) for cancer mortality, and 0.94 (95% CI, 0.77-1.16) for cardiovascular mortality. However, based on spline regression models, the association between serum selenium levels and all-cause and cancer mortality was nonlinear, with an inverse association at low selenium levels (< 130 ng/mL) and a modest increase in mortality at high selenium levels (> 150 ng/mL). There was no association between serum selenium levels and cardiovascular mortality.
                In a representative sample of the US population, we found a nonlinear association between serum selenium levels and all-cause and cancer mortality. Increasing serum selenium levels were associated with decreased mortality up to 130 ng/mL. Our study, however, raises the concern that higher serum selenium levels may be associated with increased mortality. From 1971 to 1975, serum specimens were obtained from 6,860 men of Japanese ancestry in Hawaii. Since then, the following numbers of newly diagnosed cases with epithelial cancer have been identified: 82 colon, 71 lung, 66 stomach, 32 rectum, and 29 urinary bladder. The stored sera of the 280 cases and of 293 randomly selected controls were tested to determine their levels of selenium. There was no association of serum selenium with lung, stomach, or rectal cancer. An increase in relative risk (RR) was noted only for subjects in the lowest quintile of selenium values, as compared to the RR for subjects in the highest quintile, for colon (RR = 1.8) and urinary bladder cancer (RR = 3.1), but neither of these RR estimates was statistically significant (P = .09 and P = .07, respectively). Further work is needed to determine whether the antioxidant properties of selenium protect against specific types of cancer. Selenium is an essential trace nutrient required for the synthesis of selenoproteins such as glutathione peroxidase and thioredoxin reductase, the major forms of selenium in the endothelium that have important functions relevant to inflammation and cardiovascular disease. Selenium deficiency is associated with cardiomyopathy and sudden cardiac death in animals, and a low selenium status is associated with cardiovascular disease in humans. Endothelial dysfunction, measured as the impaired flow-mediated vasorelaxation of the brachial artery, is a reliable indicator of future cardiovascular disease risk in healthy individuals. To test whether selenium supplementation affects endothelial function, we conducted a randomized, placebo-controlled trial in healthy men who were administered 300 microg of selenium a day as high-selenium yeast for 48 wk. Brachial artery responsiveness to transient occlusion was assessed at baseline and after 24 and 48 wk of supplementation. The supplementation increased the selenium concentration by more than half in blood plasma and erythrocytes. However, there was no effect of selenium on arterial diameter or blood flow rate before or after transient occlusion or on the maximum dilated diameter after the administration of nitroglycerin. This study indicates that selenium supplementation is not likely to improve endothelial function or peripheral arterial responsiveness in healthy North American men receiving adequate selenium from their diets. Various animal studies and ecologic studies suggest an inverse association between low dietary selenium intake and risk of various types of cancer.
                The goal of this prospective cohort study was to investigate the association between toenail selenium levels and risks of stomach cancer and colorectal cancer.
                Our cohort study on diet and cancer started in The Netherlands in 1986 with enrollment of 120,852 subjects aged 55-69 years. Of this number, 58,279 were men and 62,573 were women. Following the case-cohort approach for analysis of the data, we randomly selected from the cohort a subcohort of 3500 subjects (1688 men and 1812 women). After 3.3 years of follow-up, 155 incident cases of microscopically confirmed stomach cancer, 313 cases of colon cancer, and 166 cases of rectal cancer had been detected in the cohort. Toenail selenium data were available for 104 patients with stomach cancer, 234 with colon cancer, and 113 with rectal cancer and for 2459 subjects from the subcohort.
                In a multivariate analysis, the relative rates (RRs) of stomach cancer for subjects in increasing quintiles of toenail selenium level were 1.00, 0.44, 0.59, 0.84, and 0.64 (trend, P = .491). For men, there was some evidence for an inverse association between toenail selenium levels and stomach cancer: The RR for those in the highest compared with the lowest quintile of toenail selenium was 0.40 (95% confidence interval = 0.17-0.96), but the trend was not statistically significant (P = .136). For stomach cancer in women, there was no negative association with toenail selenium levels. Toenail selenium level was not associated with the risk of colon or rectal cancer. After exclusion of cases diagnosed in the 1st year of follow-up, the RRs of colon cancer for increasing quintiles of toenail selenium were 1.00, 1.27, 1.17, 0.75, and 1.07 (trend, P = .544); for rectal cancer, RR estimates were 1.00, 1.73, 0.83, 1.58, and 1.12 (trend, P = .890).
                These data support a suggestive but inconsistent inverse association between selenium levels and risk of stomach cancer. Our findings, like those of other studies, do not suggest an inverse association with risk of colorectal cancer. Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.
                To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.
                A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.
                Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.
                Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.
                As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.
                Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
                clinicaltrials.gov identifier: NCT00006392. Inadequate plasma selenium can adversely affect the maintenance of optimal health; therefore, reported decreases in plasma selenium in an aging population are cause for concern. To further examine this hypothesis, we explored the relationships between plasma selenium and mortality in an elderly population: the EVA (Etude du Vieillissement Artériel) study.
                The EVA study was a 9-year longitudinal study with 6 periods of follow-up. During the 2-year period from 1991 to 1993 (EVA0), 1389 men and women born between 1922 and 1932 were recruited. The effects of plasma selenium at baseline on mortality were determined by Cox proportional hazards regression analysis, adjusting for the following variables: sociodemographic characteristics, dietary habits, health, and cognitive factors.
                During the 9-year follow-up, 101 study participants died. Baseline plasma selenium was higher in individuals who were alive at the end of follow-up [mean (SD), 1.10 (0.20) micromol/L] than in those who died during the follow-up [1.01 (0.20) micromol/L; P <10(-4)]. Mortality rates were significantly higher in individuals with low selenium [increments = 0.2 micromol/L; relative risk (RR) = 1.56 (95% confidence interval, 1.28-1.89)]. After we controlled for various potential confounding factors, this association remained significant [RR = 1.54 (1.25-1.88)]. When the underlying causes of death were considered, we found an association with cancer-related mortality [adjusted RR = 1.79 (1.32-2.44)].
                Even if it is premature to present selenium as a longevity indicator in an elderly population, our results are in accordance those of large, interventional, randomized trials with selenium, which suggest that this essential trace element plays a role in health maintenance in aging individuals. A narrow band of counties extending along the southeastern Atlantic coast from Jacksonville, Florida to Charleston, South Carolina were found to have excessively high incidence rates for esophageal cancer in non-white males. White males in the same areas have a 30% higher incidence rate for lung cancer but only average incidence rates were found for non-white males. Selenium is considered to decrease cancer risk in the animal model. In this coastal region, a study of 130 cancer patients who developed a malignancy 2-12 years after baseline examination showed no dose response relationship between baseline serum selenium levels and risk of subsequent cancer. In a prospective study conducted on the island of Guernsey a cohort of 5162 ostensibly healthy women was enrolled between 1967 and 1976. Blood samples were drawn from each participant, who also completed a questionnaire, which provided information on established risk indicators in human mammary carcinogenesis. Plasma selenium levels were measured in 46 breast cancer cases diagnosed a mean of 11 (S.D. 4) years after entry into the study cohort and in an age-stratified sample of 138 women drawn from the study base. Plasma selenium level in the cases was 109 (28) micrograms/l and in the base sample 103 (22) micrograms/l (95% confidence interval for the overall difference, -2 to 14 micrograms/l). The adjusted relative risk of developing breast cancer in the different quartiles of the selenium distribution was 0.80, 0.79, 0.72 and 1.00, respectively. Thus, in the present study selenium was not a strong indicator of human breast cancer risk. In observational studies, adequate selenium status has been associated with better pregnancy outcomes and slowed HIV disease progression.
                We investigated the effects of daily selenium supplements on CD4 cell counts, viral load, pregnancy outcomes, and maternal and infant mortality among 913 HIV-infected pregnant women.
                In this randomized, double-blind, placebo-controlled trial, eligible women between 12 and 27 wk of gestation were given daily selenium (200 mug as selenomethionine) or placebo as supplements from recruitment until 6 mo after delivery. All women received prenatal iron, folic acid, and multivitamin supplements irrespective of experimental assignment.
                The selenium regimen had no significant effect on maternal CD4 cell counts or viral load. Selenium was marginally associated with a reduced risk of low birth weight [relative risk (RR) = 0.71; 95% CI: 0.49, 1.05; P = 0.09] and increased risk of fetal death (RR = 1.58; 95% CI = 0.95, 2.63; P = 0.08), but had no effect on risk of prematurity or small-for-gestational age birth. The regimen had no significant effect on maternal mortality (RR = 1.02; 95% CI = 0.51, 2.04; P = 0.96). There was no significant effect on neonatal or overall child mortality, but selenium reduced the risk of child mortality after 6 wk (RR = 0.43; 95% CI = 0.19, 0.99; P = 0.048).
                Among HIV-infected women from Dar es Salaam, Tanzania, selenium supplements given during and after pregnancy did not improve HIV disease progression or pregnancy outcomes, but may improve child survival. This trial was registered at clinicaltrials.gov as NCT00197561. The association between serum selenium concentration and the risk of cancer was studied in 1110 men aged 55 to 74 years in two rural areas of Finland. The men were followed-up prospectively for 9 years and there were 109 new cases of cancer, with the cases of the first follow-up year excluded. The serum selenium concentrations were adjusted for age, area, smoking, serum cholesterol, and alcohol intake. The patients had a slightly lower adjusted mean serum selenium than the subjects without cancer at the end of the follow-up (+/- standard error of mean) 53.9 +/- 1.5 and 55.3 +/- 0.5 micrograms/l, respectively. The relative risks of cancer were essentially the same when these were calculated in the tertiles of the serum selenium distribution. Thirty-seven men had a history of cancer at baseline or had cancer diagnosed during the first follow-up year and their adjusted mean serum selenium was 49.4 +/- 2.6 micrograms/l, which was significantly lower (P less than 0.05) than that of the subjects without cancer during the follow-up. In a recent randomized intervention trial, the risk of prostate cancer for men receiving a daily supplement of 200 microg selenium was one third of that for men receiving placebo. By use of a nested case-control design within a prospective study, i.e., the Health Professionals Follow-Up Study, we investigated the association between risk of prostate cancer and prediagnostic level of selenium in toenails, a measure of long-term selenium intake.
                In 1986, 51,529 male health professionals aged 40-75 years responded to a mailed questionnaire to form the prospective study. In 1987, 33,737 cohort members provided toenail clippings. In 1988, 1990, 1992, and 1994, follow-up questionnaires were mailed. From 1989 through 1994, 181 new cases of advanced prostate cancer were reported. Case and control subjects were matched by age, smoking status, and month of toenail return. Selenium levels were determined by neutron activation. All P values are two-sided.
                The selenium level in toenails varied substantially among men, with quintile medians ranging from 0.66 to 1.14 microg/g for control subjects. When matched case-control data were analyzed, higher selenium levels were associated with a reduced risk of advanced prostate cancer (odds ratio [OR] for comparison of highest to lowest quintile = 0.49; 95% confidence interval [CI] = 0.25-0.96; P for trend = .11). After additionally controlling for family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the OR was 0.35 (95% CI = 0.16-0.78; P for trend = .03).
                Our results support earlier findings that higher selenium intakes may reduce the risk of prostate cancer. Further prospective studies and randomized trials of this relationship should be conducted. Serum samples were collected in Hiroshima and Nagasaki, Japan, from 1970 to 1972 for 208 persons who in 1973-1983 developed stomach cancer; for 77 who in 1973-1983 developed lung cancer; and for controls matched for age, sex, city, and season of blood collection. Average serum levels of selenium and zinc were slightly (< 5%) but not significantly lower among the cancer cases than among controls. Smoking-adjusted risks of lung cancer were elevated only among those in the lowest quartiles of serum selenium [odds ratio (OR) = 1.8] and zinc (OR = 1.3); the trends in risk of this cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with lowest levels of selenium (OR = 1.0) or zinc (OR = 1.2). These exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population. We attempted to study the effect of selenium supplementation upon trace metal metabolism in low-birthweight infants less than 1000 g birthweight. Serum levels of the trace metals copper, zinc, and selenium; and white blood cell glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were measured in conjunction with the trace metals when parenteral nutrition (TPN) was begun (sample A), at the initiation of enteral nutrition (sample B), and when TPN was discontinued (sample C). Two randomly selected groups of infants were evaluated: group S received selenium supplementation (1.34 micrograms/kg per d) in their parenteral nutrition solutions; group C was a control which did not receive selenium supplementation. Selenium levels declined to equally low levels in both groups by sample C, but were significantly higher in group S at sample B. GSH-Px activities demonstrated a significant increase at sample B in group S and then tended to decrease. In group C, GSH-Px tended to increase, then decreased significantly by sample C. Both groups received 20 micrograms/kg per d of copper in TPN, however, serum copper declined significantly at sample B in group S whereas there were no significant changes in group C. There were no significant changes in zinc and SOD levels. There were no significant differences between groups in clinical characteristics or outcome. This study suggests that a dose of supplemental selenium of 1.34 micrograms/kg per d in TPN is inadequate for low-birthweight premature infants. Selenium supplementation may also affect copper metabolism. Both experimental and epidemiologic studies have linked a low dietary intake of selenium with an increased risk of cancer. The authors examined the association between plasma selenium levels and risk of hepatocellular carcinoma (HCC) among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men in Taiwan who were recruited by personal interview and blood draw during 1988-1992. After these men were followed up for an average of 5.3 years, selenium levels in the stored plasma were measured by using hydride atomic absorption spectrometry for 69 incident HCC cases who were positive for hepatitis B surface antigen (HBsAg) and/or antibodies against hepatitis C virus (mostly HBsAg positive) and 139 matched, healthy controls who were HBsAg positive. Mean selenium levels were significantly lower in the HCC cases than in the HBsAg-positive controls (p = 0.01). Adjusted odds ratios of HCC for subjects in increasing quintiles of plasma selenium were 1.00, 0.52, 0.32, 0.19, and 0.62, respectively. The inverse association between plasma selenium levels and HCC was most striking among cigarette smokers and among subjects with low plasma levels of retinol or various carotenoids. There was no clear evidence for an interaction between selenium and alpha-tocopherol in relation to HCC risk. Literature indicates a relationship between selenium supplementation and risk of diabetes. However, because these data are inconclusive, we investigated the effect of selenium supplementation on serum glucose levels in men with prostate cancer enrolled in a clinical trial testing of the effect of selenium on prostate cancer progression.
                Subjects were randomized to receive placebo (n=46), selenium 200 microg/day (n=47), and selenium 800 microg/day (n=47). Serum glucose levels were obtained every 6 months for up to 5 years. Longitudinal analysis was carried out to assess whether rate of change of serum glucose levels was significantly different in the selenium-supplemented groups as compared with placebo. Sensitivity analyses were performed to assess the robustness of findings.
                Changes in serum glucose levels during the course of the trial were not statistically significantly different as compared with placebo for the selenium 200 microg/day (P=.56) or selenium 800 microg/day (P=.91) treatment groups.
                These results do not support a relationship between selenium supplementation and changes in serum glucose levels. Recommendations about selenium supplementation and risk of diabetes will require more definitive studies.
                Copyright 2010 Elsevier Inc. All rights reserved. Selenium and alpha-tocopherol, the major form of vitamin E in supplements, appear to have a protective effect against prostate cancer. However, little attention has been paid to the possible role of gamma-tocopherol, a major component of vitamin E in the U.S. diet and the second most common tocopherol in human serum. A nested case-control study was conducted to examine the associations of alpha-tocopherol, gamma-tocopherol, and selenium with incident prostate cancer.
                In 1989, a total of 10,456 male residents of Washington County, MD, donated blood for a specimen bank. A total of 117 of 145 men who developed prostate cancer and 233 matched control subjects had toenail and plasma samples available for assays of selenium, alpha-tocopherol, and gamma-tocopherol. The association between the micronutrient concentrations and the development of prostate cancer was assessed by conditional logistic regression analysis. All statistical tests were two-sided.
                The risk of prostate cancer declined, but not linearly, with increasing concentrations of alpha-tocopherol (odds ratio (highest versus lowest fifth) = 0.65; 95% confidence interval = 0.32--1.32; P(trend) =.28). For gamma-tocopherol, men in the highest fifth of the distribution had a fivefold reduction in the risk of developing prostate cancer than men in the lowest fifth (P:(trend) =.002). The association between selenium and prostate cancer risk was in the protective direction with individuals in the top four fifths of the distribution having a reduced risk of prostate cancer compared with individuals in the bottom fifth (P(trend) =.27). Statistically significant protective associations for high levels of selenium and alpha-tocopherol were observed only when gamma-tocopherol concentrations were high.
                The use of combined alpha- and gamma- tocopherol supplements should be considered in upcoming prostate cancer prevention trials, given the observed interaction between alpha-tocopherol, gamma-tocopherol, and selenium. Findings from animal models suggest that selenium supplementation improves glucose metabolism.
                To examine the effect of long-term selenium supplementation on the incidence of type 2 diabetes.
                Secondary analysis of a randomized, double-blind, placebo-controlled trial.
                Areas of low selenium consumption of the eastern United States.
                1202 persons seen in dermatology clinics who did not have type 2 diabetes at baseline.
                Oral administration of selenium, 200 microg/d, or placebo.
                Incidence of type 2 diabetes.
                During an average follow-up of 7.7 years (SD, 2.7), type 2 diabetes developed in 58 selenium recipients and 39 placebo recipients (incidence, 12.6 cases per 1000 person-years vs. 8.4 cases per 1000 person-years, respectively; hazard ratio, 1.55 [95% CI, 1.03 to 2.33]). The lack of benefit of selenium supplementation on the incidence of type 2 diabetes persisted in analyses stratified by age, sex, body mass index, and smoking status. An exposure-response gradient was found across tertiles of baseline plasma selenium level, with a statistically significantly increased risk for type 2 diabetes in the highest tertile of baseline plasma selenium level (hazard ratio, 2.70 [CI, 1.30 to 5.61]).
                Diabetes was a secondary outcome in the parent trial. Diagnoses of diabetes were self-reported but were validated in most participants. The sample was mostly older and white.
                Selenium supplementation does not seem to prevent type 2 diabetes, and it may increase risk for the disease. Click here for related information on selenium. To determine whether the decline in selenium intake and selenium status in men in the West of Scotland might be a contributory factor to male subfertility.
                Two semen samples were collected from patients attending a subfertility clinic and those patients with samples showing reduced motility were invited to participate in an ethically approved double-blind clinically controlled trial with informed consent. Sixty-nine patients were recruited and received either placebo, selenium alone or selenium plus vitamins A, C and E daily for 3 months. A further semen sample was collected at the end of the trial. Plasma selenium status was determined at the beginning and end of the trial period, as was total sperm density and motility.
                Plasma selenium concentrations were significantly (P < 0.001) higher in both selenium-treated groups than in controls. No significant effect of treatment on sperm density was recorded. Sperm motility increased in both selenium-treated groups, in contrast to a slight decline in the placebo group, but the difference was not significant. However, as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment. On this basis, selenium treatment significantly (P < 0.002) increased plasma selenium concentrations and sperm motility (P = 0.023) but sperm density was again unaffected. Five men (11%) achieved paternity in the treatment group, in contrast to none in the placebo group.
                This trial confirms the result of an earlier study, that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception. However, not all patients responded; 56% showed a positive response to treatment. The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet. The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly. High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC) are present in Qidong county. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as HBV infection. Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of ducks, caused by exposure to natural environmental etiologic factors. An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in selenized table salt supplemented vs the nonsupplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase. However, the inhibitory response to HBV was sustained during the 3-yr cessation of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 micrograms of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group, whereas no incidence of PLC was found in 113 subjects supplemented with Se. Again on cessation of treatment, PLC developed at a rate comparable to that in the control group, demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect. Increased intake of selenium (Se) may reduce the risk of degenerative diseases including cancer but excessive intake may be toxic. Wheat is a major source of dietary Se in humans. However, the effect of Se from wheat that is agronomically biofortified with Se on biomarkers of human health status is unknown. This study aimed to investigate whether improving Se status, by increased dietary intake of Se-biofortified wheat, affects biomarkers of cancer risk, cardiovascular disease risk, oxidative stress, and immune function in healthy South Australian men. A 24-week placebo-controlled double-blind intervention was performed in healthy older men (n = 62), with increased dose of Se intake every 8 weeks. Wheat was provided as 1, 2, and 3 puffed wheat biscuits, during weeks 1-8, 9-16, and 17-24, respectively. Blood was collected to measure a wide range of disease risk biomarkers. Consumption of Se-biofortified wheat was found to increase plasma Se concentration from a baseline level of 122 to 192 microg/L following intake of three biscuits/day, which provided 267 microg Se. Platelet glutathione peroxidase, chromosome aberrations, and DNA damage in lymphocytes measured using the cytokinesis-block micronucleus cytome assay and with the Comet assay, plasma F2-isoprostanes, protein carbonyls, plasma C-reactive protein, and leukocyte number were unaffected by the improved Se status. Improvement of Se status by consumption of Se-biofortified wheat did not substantially modify the selected biomarkers of degenerative disease risk and health status in this apparently selenium-replete cohort of healthy older men in South Australia.
                Copyright 2009 Wiley-Liss, Inc. The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.
                To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men.
                A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011.
                Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years.
                Prostate cancer incidence.
                This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination.
                Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.
                Clinicaltrials.gov Identifier: NCT00006392. Evidence that selenium affects the risk of type-2 diabetes is conflicting, with observational studies and a few randomized trials showing both lower and higher risk linked to the level of selenium intake and status. We investigated the effect of selenium supplementation on the risk of type-2 diabetes in a population of relatively low selenium status as part of the UK PRECISE (PREvention of Cancer by Intervention with SElenium) pilot study. Plasma adiponectin concentration, a recognised independent predictor of type-2 diabetes risk and known to be correlated with circulating selenoprotein P, was the biomarker chosen.
                In a randomized, double-blind, placebo-controlled trial, five hundred and one elderly volunteers were randomly assigned to a six-month intervention with 100, 200 or 300 µg selenium/d as high-selenium or placebo yeast. Adiponectin concentration was measured by ELISA at baseline and after six months of treatment in 473 participants with one or both plasma samples available.
                Mean (SD) plasma selenium concentration was 88.5 ng/g (19.1) at baseline and increased significantly in the selenium-treatment groups. In baseline cross-sectional analyses, the fully adjusted geometric mean of plasma adiponectin was 14% lower (95% CI, 0-27%) in the highest than in the lowest quartile of plasma selenium (P for linear trend = 0.04). In analyses across randomized groups, however, selenium supplementation had no effect on adiponectin levels after six months of treatment (P = 0.96).
                These findings are reassuring as they did not show a diabetogenic effect of a six-month supplementation with selenium in this sample of elderly individuals of relatively low selenium status. A nested case-control study was conducted to assess the relation between serum levels of selenium and retinol and the subsequent risk of cancer. During the years 1972-1984, in northwest Washington State, 156 cases of cancer were identified among members of two employee cohorts from whom specimens had been previously obtained and stored. Two hundred eighty-seven controls were selected from these cohorts and matched to cases on the basis of employer, age, sex, race, and date of blood draw. Selenium and retinol levels were measured by neutron activation and high pressure liquid chromatography, respectively. Information on known cancer risk factors was collected by telephone interviews of subjects and next of kin. Levels of selenium and retinol were unassociated with the incidence of cancer of all sites combined, both overall and within subgroups defined by age, sex, levels of the other micronutrient, time between blood draw and diagnosis, smoking status, and family history of cancer. These findings suggest that neither serum levels of selenium nor those of retinol have an appreciable effect on the risk of cancer. Sera from 43 persons who developed thyroid cancer on an average 4.8 years after blood sampling were compared with sera from controls. Three controls per case matched for sex, age, place of residence and year of blood sampling, with regard to serum selenium and serum copper. Cases were significantly lower in serum selenium than controls, and the estimated odds ratio of thyroid cancer increased from 1 for levels greater than or equal to 1.65 mumol/l, to 6.1 for levels 1.26-1.64 mumol/l, to 7.7 for levels less than or equal to 1.25 mumol/l. When time from blood sampling to diagnosis of the case was considered, it could be shown that the protective effect of high serum selenium concentrations was restricted to the last (less than 7) years prior to the diagnosis of thyroid cancer. The serum selenium concentration of cases tended to decrease relative to controls the shorter time was from blood sampling to the diagnosis. There was no difference between cases and controls with regard to serum copper. Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers, including cancers of the esophagus and stomach. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian County, China, have one of the world's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients.
                We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian.
                Individuals of ages 40-69 were recruited in 1985 from four Linxian communes. Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period. The subjects were randomly assigned to intervention groups according to a one-half replicate of a 2(4) factorial experimental design. This design enabled testing for the effects of four combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta carotene, vitamin E, and selenium. Doses ranged from one to two times U.S. Recommended Daily Allowances.
                A total of 2127 deaths occurred among trial participants during the intervention period. Cancer was the leading cause of death, with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%). Significantly (P = .03) lower total mortality (relative risk [RR] = 0.91; 95% confidence interval [CI] = 0.84-0.99) occurred among those receiving supplementation with beta carotene, vitamin E, and selenium. The reduction was mainly due to lower cancer rates (RR = 0.87; 95% CI = 0.75-1.00), especially stomach cancer (RR = 0.79; 95% CI = 0.64-0.99), with the reduced risk beginning to arise about 1-2 years after the start of supplementation with these vitamins and minerals. No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc, riboflavin and niacin, or vitamin C and molybdenum. Patterns of cancer incidence, on the basis of 1298 cases, generally resembled those for cancer mortality.
                The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population.
                The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements. The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,133). During up to 9 years of follow-up, 317 men developed incident prostate cancer. Multivariate Cox proportional hazards models that adjusted for intervention group, benign prostatic hyperplasia, age, smoking, and urban residence were used to evaluate associations between prostate cancer and exposures of interest. There were no significant associations between baseline serum alpha-tocopherol, dietary vitamin E, or selenium and prostate cancer overall. The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status, with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention (relative risk was 1.00, 0.68, 0.80, and 0.52 for increasing quartiles; P = 0.07). To study the predictive power of serum selenium with regard to cancer mortality in a large sample of the Belgian population given the lack of coherence in the results of observational epidemiological studies in this domain.
                A prospective case-control study within a stratified sample of the Belgian male and female population.
                A total of 201 cases randomly selected from all cancer deaths (N=343) during a 10-y mortality follow-up of a large age- and sex-stratified sample of the total Belgian population aged 25-74 y were matched for age and gender with 603 controls.
                Conditional logistic regression for both univariate and multivariate analyses using tertile distribution of serum selenium in controls. Odds ratios (ORs) are adjusted for 10 baseline characteristics.
                Unadjusted ORs of cancer deaths taking the highest tertile of serum selenium as a reference: in male subjects T1/T3 is 2.2 (CI 1.3-3.7) (P for trend 0.011), whereas in female subjects a nonsignificant OR of 0.8 is observed. In multivariate analyses, no significant modifications of the ORs are observed for the predictive relation of serum selenium with cancer mortality. Besides serum selenium, beta-carotene intake and smoking are independent predictors in male subjects.
                In this nested case-control study of a stratified sample from the Belgian population, serum selenium is an independent predictor of cancer mortality in male subjects only, in a country with rather high serum selenium levels with respect to most other European countries. Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease.
                A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency.
                No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity.
                Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted. This study aimed to assess the effect of high dose selenium (Se) supplementation on Se status in blood, oxidative stress, thyroid function and possible effects on requirement for renal replacement therapy (RRT) in severely septic patients admitted to the intensive care unit (ICU).
                This prospective single-centre study was carried out in 40 septic ICU patients who were randomized to high dose Se (Se+ group, N=18 (474, 316, 158 microg/day), each for 3 consecutive days followed by a standard dose of 31.6 microg/day of Se given as sodium selenite whereas the control group (Se-, N=22) received only the standard dose of Se. Plasma Se, glutathione peroxidase (GSH-Px), F2 isoprostanes, thyroid function tests (total T4 and total T3), C-reactive protein (CRP) and red blood cell (RBC) GSH-Px were estimated on day 0, 3, 7, 14.
                In the Se+ group, plasma Se increased by day 3 and 7 (P<0.0001) and day 14 (P=0.02), plasma GSH-Px increased by day 3 and 7 (P=0.01) as compared to Se- group. There was a significant negative correlation between plasma Se and SOFA (sepsis related organ failure assessment) (r=-0.36, P=0.03) along with low plasma Se and high CRP at the time of admission. Requirement for renal replacement therapy was not significantly different between the groups.
                Although high dose Se supplementation increased plasma Se and GSH-Px activity, it did not reduce oxidative damage or the requirement for RRT. Se levels in blood are influenced by redistribution and severity of illness and therefore should be interpreted with caution.
No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification.
The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.