Selenium. Anti-Aging-Guide -- Your plan to stay young

Neurotoxicol Teratol. 2005 Mar-Apr;27(2):241-4. Epub 2004 Dec 08.
Does selenium deficiency unmask mercury toxicity in motor neurons?
Pamphlett R, Eide R, Danscher G.
Department of Pathology D06, The University of Sydney, Sydney, New South Wales 2006, Australia.
OBJECTIVE: Inorganic mercury enters in particular motor neurons and has been implicated in motor neuron diseases. One way that cells protect themselves from mercury toxicity is via selenium, so we sought to determine whether the motor neurons of mice on a low selenium diet would be more susceptible to mercury toxicity. METHODS: Recently weaned mouse pups were placed on diets containing either low, normal or high levels of selenium. Twenty days later, half were exposed to mercury vapor. Ninety days after exposure, their spinal motor neurons and phrenic motor axons were examined histologically. Mercury in the spinal cord was sought using autometallography. RESULTS: Neither low nor high selenium diets combined with mercury vapor had any clinical effect on the mice. Mercury was seen within the spinal motor neurons of all exposed mice. Spinal motor neurons and phrenic motor axons however appeared normal in morphology and size across the groups. CONCLUSION: Diets low or high in selenium did not damage motor neurons with or without mercury. This suggests that changes in the selenium environment are unlikely to precipitate mercury toxicity in motor neurons.

Anticancer Res. 2004 May-Jun;24(3a):1401-8.
Selenium compounds regulate p53 by common and distinctive mechanisms.
Smith ML, Lancia JK, Mercer TI, Ip C.
Indiana University School of Medicine, Department of Microbiology and Walther Oncology Center, Indianapolis, IN 46202, USA.
Selenium compounds show much promise in the prevention of prostate and other human cancers. Various selenium chemical forms have been shown to differ widely in their anticancer properties. The main dietary form is selenomethionine, which we showed modulated p53 activity by causing redox regulation of key p53 cysteine residues. In the current study we included other selenium chemical forms, sodium selenite and methyl-seleninic acid. All three forms are relevant selenium sources in human populations. All three forms can affect p53 activity defined as trans-activation of a p53-dependent reporter gene. In addition to the reduction of cysteine sulfhydryl groups, p53 phosphorylation was also affected in cells treated with selenium compounds. Methyl-seleninic acid caused phosphorylation of one or more p53 threonine residues, but did not affect any known serine phosphorylation sites. By contrast sodium selenite caused phosphorylation of p53 serines 20, 37 and 46 known to mediate apoptosis. Selenomethionine did not cause detectable phosphorylation of p53 serines or threonines. Our data show that, although p53 modulation may be a common denominator of selenium compounds, specific mechanisms of p53 activation differ among selenium chemical forms. Post-translational modifications of p53 are determinants of p53 activity and probably affect the threshold for p53-mediated functions. Different selenium chemical forms may differentially modify p53 for DNA repair or apoptosis in conjunction with a given level of endogenous or exogenous DNA damage.

Eur J Biochem. 2004 Aug;271(15):3190-9.
Interaction of selenium compounds with zinc finger proteins involved in DNA repair.
Blessing H, Kraus S, Heindl P, Bal W, Hartwig A.
Institute of Food Chemistry and Toxicology, University of Karlsruhe, Germany.
As an essential element, selenium is present in enzymes from several families, including glutathione peroxidases, and is thought to exert anticarcinogenic properties. A remarkable feature of selenium consists of its ability to oxidize thiols under reducing conditions. Thus, one mode of action recently suggested is the oxidation of thiol groups of metallothionein, thereby providing zinc for essential reactions. However, tetrahedral zinc ion complexation to four thiolates, similar to that found in metallothionein, is present in one of the major classes of transcription factors and other so-called zinc finger proteins. Within this study we investigated the effect of selenium compounds on the activity of the formamidopyrimidine-DNA glycosylase (Fpg), a zinc finger protein involved in base excision repair, and on the DNA-binding capacity and integrity of xeroderma pigmentosum group A protein (XPA), a zinc finger protein essential for nucleotide excision repair. The reducible selenium compounds phenylseleninic acid, phenylselenyl chloride, selenocystine, ebselen, and 2-nitrophenylselenocyanate caused a concentration-dependent decrease of Fpg activity, while no inhibition was detected with fully reduced selenomethionine, methylselenocysteine or some sulfur-containing analogs. Furthermore, reducible selenium compounds interfered with XPA-DNA binding and released zinc from the zinc finger motif, XPAzf. Zinc release was even evident at high glutathione/oxidised glutathine ratios prevailing under cellular conditions. Finally, comparative studies with metallothionein and XPAzf revealed similar or even accelerated zinc release from XPAzf. Altogether, the results indicate that zinc finger motifs are highly reactive towards oxidizing selenium compounds. This could affect gene expression, DNA repair and, thus, genomic stability.

Environ Res. 2004 Sep;96(1):51-61.
Selenium in pregnancy: is selenium an active defective ion against environmental chemical stress?
Kantola M, Purkunen R, Kroger P, Tooming A, Juravskaja J, Pasanen M, Seppanen K, Saarikoski S, Vartiainen T.
Department of Chemistry, University of Kuopio, Kuopio, Finland.
Transportation of selenium from mother to fetus and its possible effects on mother's zinc, copper, cadmium, and mercury levels were studied together during the first trimester and at term in 216 mothers. Mothers came from three geographical places with different selenium intakes. The role of selenium as a biomarker for the vital function was estimated by studying the associations between tissue or blood selenium content and placental cytochrome P450 enzyme activities and the newborn's birth weight. Regardless of the selenium intake of the mothers, higher concentrations were found in the cord blood than in mother's blood reflecting active transportation of selenium to the fetus. Active smoking was associated with higher placental selenium concentrations like it is associated with higher placental zinc concentrations. When the cadmium concentrations were high in placenta, as in smokers, the transfer of selenium from blood to placenta was increased, decreasing the selenium levels in blood. On the other hand, the high selenium concentrations in blood were connected to lower cadmium concentrations in placenta also in nonsmokers. Selenium had correlations with copper and zinc. ECOD activity in placental tissue, mercury in mothers' hair, mothers' age, and selenium concentrations in cord blood and placental selenium all seem to have connections with xenobiotic-metabolizing enzymes linked effects among mothers. These data suggest that selenium has an active role in the mother's defense systems against the toxicity of environmental pollutants and the constituents of cigarette smoke.

Folia Microbiol (Praha). 2004;49(3):301-5.
Synergic activity of selenium and probiotic bacterium Enterococcus faecium M-74 against selected mutagens in Salmonella assay.
Belicova A, Krizkova L, Dobias J, Krajcovic J, Ebringer L.
Institute of Cell Biology, Faculty of Science, Comenius University, 811 07 Bratislava, Slovakia.
Concentrated extracts of MRS (De Man-Rogosa-Sharpe) media in which probiotic bacterium Enterococcus faecium strain M-74 was grown exerted different antimutagenic activity against ofloxacin-, N-methyl, N'-nitro-N-nitrosoguanidine- and sodium 5-nitro-2-furylacrylate-induced mutagenicity in Salmonella typhimurium assay depending on the presence (+Se) or absence of disodium selenite pentahydrate (-Se). The antimutagenicity of MRS(+Se) extract was higher than that of MRS(-Se) extract. Selenium enhanced also the antimutagenic effect of both live and killed cells of E. faecium M-74, respectively. The live bacteria decreased the mutagenicity of selected substances more than killed cells. Synergic activity of selenium with the bacterium was also manifested.

J Natl Cancer Inst. 2003 Oct 1;95(19):1477-81.
Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial.
Duffield-Lillico AJ, Slate EH, Reid ME, Turnbull BW, Wilkins PA, Combs GF Jr, Park HK, Gross EG, Graham GF, Stratton MS, Marshall JR, Clark LC; Nutritional Prevention of Cancer Study Group.
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
The Nutritional Prevention of Cancer Trial was a double-blind, randomized, placebo-controlled clinical trial designed to test whether selenium as selenized yeast (200 microg daily) could prevent nonmelanoma skin cancer among 1312 patients from the Eastern United States who had previously had this disease. Results from September 15, 1983, through December 31, 1993, showed no association between treatment and the incidence of basal and squamous cell carcinomas of the skin. This report summarizes the entire blinded treatment period, which ended on January 31, 1996. The association between treatment and time to first nonmelanoma skin cancer diagnosis and between treatment and time to multiple skin tumors overall and within subgroups, defined by baseline characteristics, was evaluated. Although results through the entire blinded period continued to show that selenium supplementation was not statistically significantly associated with the risk of basal cell carcinoma (hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 0.94 to 1.26), selenium supplementation was associated with statistically significantly elevated risk of squamous cell carcinoma (HR = 1.25, 95% CI = 1.03 to 1.51) and of total nonmelanoma skin cancer (HR = 1.17, 95% CI = 1.02 to 1.34). Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer continue to demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer.

Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1285-91.
Selenium supplementation and lung cancer incidence: an update of the nutritional prevention of cancer trial.
Reid ME, Duffield-Lillico AJ, Garland L, Turnbull BW, Clark LC, Marshall JR.
Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Interest in the chemopreventive effects of the trace element selenium has spanned the past three decades. Of >100 studies that have investigated the effects of selenium in carcinogen-exposed animals, two-thirds have observed a reduction in tumor incidence and/or preneoplastic endpoints (G. F. Combs and S. B. Combs, The Role of Selenium in Nutrition Chapter 10, pp. 413-462. San Diego, CA: Academic Press, 1986, and B. H. Patterson and O. A. Levander, Cancer Epidemiol. Biomark. Prev., 6: 63-69, 1997). The Nutritional Prevention of Cancer Trial, a randomized clinical trial reported by Clark et al. (L. C. Clark et al., JAMA, 276: 1957-1963, 1996), showed as a secondary end point, a statistically significant decrease in lung cancer incidence with selenium supplementation. The adjusted hazard ratio (HR) was 0.56 [95% confidence interval (CI), 0.31-1.01; P = 0.05]. These results were based on active follow-up of 1312 participants. This reanalysis used an extended Nutritional Prevention of Cancer Trial participant follow-up through the end of the blinded clinical trial on February 1, 1996. The additional 3 years added 8 cases to the selenium-treated group and 4 cases to the placebo group, and increased follow-up to 7.9 years. The relative risk of 0.70 (95% CI, 0.40-1.21; P = 0.18) is not statistically significant. Whereas the overall adjusted HR is not significant (HR = 0.74; 95% CI, 0.44-1.24; P = 0.26), and the HR for current and former smokers was not significant, the trend is toward a reduction in risk of incident lung cancer with selenium supplementation. In a subgroup analysis there was a nominally significant HR among subjects with baseline plasma selenium in the lowest tertile (HR = 0.42; 95% CI, 0.18-0.96; P = 0.04). The analysis for the middle and highest tertiles of baseline showed HRs of 0.91 and 1.25. The current reanalysis indicates that selenium supplementation did not significantly decrease lung cancer incidence in the full population, but a significant decrease among individuals with low baseline selenium concentrations was observed.

Biochim Biophys Acta. 2002 Dec 16;1593(1):85-92.
Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides.
Lewin MH, Arthur JR, Riemersma RA, Nicol F, Walker SW, Millar EM, Howie AF, Beckett GJ.
University Department of Clinical Biochemistry, The Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK.
The human endothelial cell line EAhy926 was used to determine the importance of selenium in preventing oxidative damage induced by tert-butyl hydroperoxide (tert-BuOOH) or oxidised low density lipoprotein (LDLox). In cells grown in a low selenium medium, tert-BuOOH and LDLox killed cells in a dose-dependent manner. At 555 mg/l LDLox or 300 microM tert-BuOOH, >80% of cells were killed after 20 h. No significant cell kill was achieved by these agents if cells were pre-incubated for 48 h with 40 nM sodium selenite, a concentration that maximally induced the activities of cytoplasmic glutathione peroxidase (cyGPX; 5.1-fold), phospholipid hydroperoxide glutathione peroxidase (PHGPX;1.9-fold) and thioredoxin reductase (TR; 3.1-fold). Selenium-deficient cells pre-treated with 1 microM gold thioglucose (GTG) (a concentration that inhibited 25% of TR activity but had no inhibitory effect on cyGPX or PHGPX activity) were significantly (P<0.05) more susceptible to tert-BuOOH toxicity (LC(50) 110 microM) than selenium-deficient cells (LC(50) 175 microM). This was also the case for LDLox. In contrast, cells pre-treated with 40 nM selenite prior to exposure to GTG were significantly more resistant to damage from tert-BuOOH and LDLox than Se-deficient cells. Treatment with GTG or selenite had no significant effect on intracellular total glutathione concentrations. These results suggest that selenium supplementation, acting through induction of TR and GPX, has the potential to protect the human endothelium from oxidative damage.

Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):630-9.
Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial.
Duffield-Lillico AJ, Reid ME, Turnbull BW, Combs GF Jr, Slate EH, Fischbach LA, Marshall JR, Clark LC.
Arizona Cancer Center, Tucson, Arizona 85724-5024, USA.
The Nutritional Prevention of Cancer Trial was a randomized, clinical trial designed to evaluate the efficacy of selenium as selenized yeast (200 microg daily) in preventing the recurrence of nonmelanoma skin cancer among 1312 residents of the Eastern United States. Original secondary analyses through December 31, 1993 showed striking inverse associations between treatment and the incidence of total [hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.46-0.82], lung, prostate, and colorectal cancer and total cancer mortality. This report presents results through February 1, 1996, the end of blinded treatment. Effect modification by baseline characteristics is also evaluated. The effects of treatment overall and within subgroups of baseline age, gender, smoking status, and plasma selenium were examined using incidence rate ratios and Cox proportional hazards models. Selenium supplementation reduced total (HR = 0.75, 95% CI = 0.58-0.97) and prostate (HR = 0.48, 95% CI = 0.28-0.80) cancer incidence but was not significantly associated with lung (HR = 0.74, 95% CI = 0.44-1.24) and colorectal (HR = 0.46, 95% CI = 0.21-1.02) cancer incidence. The effects of treatment on other site-specific cancers are also described. The protective effect of selenium was confined to males (HR = 0.67, 95% CI = 0.50-0.89) and was most pronounced in former smokers. Participants with baseline plasma selenium concentrations in the lowest two tertiles (<121.6 ng/ml) experienced reductions in total cancer incidence, whereas those in the highest tertile showed an elevated incidence (HR = 1.20, 95% CI = 0.77-1.86). The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium on cancer incidence, although not all site-specific cancers exhibited a reduction in incidence. This treatment effect was restricted to males and to those with lower baseline plasma selenium concentrations.

Biofactors. 2001;14(1-4):199-204.
The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn and trauma.
Gartner R, Albrich W, Angstwurm MW.
Klinikum der Ludwig-Maximilians-Universitat Munchen, Medizinische Klinik- Innenstadt, Germany.
Patients with systemic inflammatory response syndrome (SIRS) and sepsis exhibit decreased plasma selenium and glutathione peroxidase activity. This has been shown in several clinical studies. Moreover, the degree of selenium deficiency correlates with the severity of the disease and the incidence of mortality. Patients with SIRS and sepsis are exposed to severe oxidative stress. Selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and are involved in the regulation of inflammatory processes. Therefore, selenium substitution in those patients might be effective in the prevention of multiorgan failure. The results of randomised clinical trials investigating selenium substitution in critical ill patients with inflammation are reviewed. In two independently performed randomised, prospective clinical trials, including patients with systemic inflammatory response syndrome or sepsis, the supplementation of selenium revealed a significant reduction in multiorgan failure and, especially, a lower incidence of acute renal failure and respiratory distress syndrome. One of those trials also could demonstrate a significant reduction of mortality in the most severely ill patients. Two other studies, where selenium together with other trace elements or a mixture of antioxidants were used in the treatment of patients with severe burn injuries or trauma showed a significant reduction in the secondary infection rate, including sepsis. Thus, selenium supplementation seems to improve the outcome of patients with SIRS, sepsis and severe injury, however, pivotal prospective clinical trials with sufficient statistical power are now necessary to finally prove the efficacy of a selenium supplementation in these diseases.

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J Environ Pathol Toxicol Oncol. 1998;17(3-4):313-20.
Effects of cereal supplementation with selenium.
Milovac M, Djermanovic V, Djujic I.
The Zrenjanin Institute of Agriculture, Yugoslavia.
Selenium (Se) is an essential nutrient. Surveys of Se status showed that Serbia is a low Se area. To increase the Se concentration, we supplemented Se to domestic animals and humans. The latest results showed that increasing Se content in domestic animals and humans induces a small increase in mean Se level. Exceptions were residents of urban, economically developed communities in which an increase in Se level were significant. The soil-plant system is the main natural source of Se for animals and humans. We used field treatments to raise the Se level in plants to the desired level. Foliar application of Se as Na2SeO3 was tested on cereals growing on different soil types. The influence of different growth factors on the uptake and distribution of Se in plants was tested and discussed. The foliar application of 6 g Se/ha is sufficient to raise the native Se content in whole wheat to levels of 42 to 67 microg/kg and in corn to levels of 19 to 36 microg/kg. The application of 12 g Se/ha is sufficient to raise Se levels in wheat to 65 to 180 microg/kg and in corn to 31 to 46 microg/kg.

Br J Urol. 1998 Jul;82(1):76-80.
The effect of oral selenium supplementation on human sperm motility.
Scott R, MacPherson A, Yates RW, Hussain B, Dixon J.
Department of Urology, Glasgow Royal Infirmary, UK.
OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Br J Urol. 1998 May;81(5):730-4.
Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial.
Clark LC, Dalkin B, Krongrad A, Combs GF Jr, Turnbull BW, Slate EH, Witherington R, Herlong JH, Janosko E, Carpenter D, Borosso C, Falk S, Rounder J.
Arizona Cancer Center, College of Medicine, University of Arizona, Tucson 85716, USA.
OBJECTIVE: To test if supplemental dietary selenium is associated with changes in the incidence of prostate cancer. PATIENTS AND METHOD: A total of 974 men with a history of either a basal cell or squamous cell carcinoma were randomized to either a daily supplement of 200 microg of selenium or a placebo. Patients were treated for a mean of 4.5 years and followed for a mean of 6.5 years. RESULTS: Selenium treatment was associated with a significant (63%) reduction in the secondary endpoint of prostate cancer incidence during 1983-93. There were 13 prostate cancer cases in the selenium-treated group and 35 cases in the placebo group (relative risk, RR=0.37, P=0.002). Restricting the analysis to the 843 patients with initially normal levels of prostate-specific antigen (< or = 4 ng/mL), only four cases were diagnosed in the selenium-treated group and 16 cases were diagnosed in the placebo group after a 2 year treatment lag, (RR=0.26 P=0.009). There were significant health benefits also for the other secondary endpoints of total cancer mortality, and the incidence of total, lung and colorectal cancer. There was no significant change in incidence for the primary endpoints of basal and squamous cell carcinoma of the skin. In light of these results, the 'blinded' phase of this trial was stopped early. CONCLUSIONS: Although selenium shows no protective effects against the primary endpoint of squamous and basal cell carcinomas of the skin, the selenium-treated group had substantial reductions in the incidence of prostate cancer, and total cancer incidence and mortality that demand further evaluation in well-controlled prevention trials.

Med Klin (Munich). 1997 Sep 15;92 Suppl 3:42-5.
Reduction of cancer mortality and incidence by selenium supplementation.
Combs GF Jr, Clark LC, Turnbull BW.
Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
PATIENTS AND METHOD: In order to test the hypothesis that a dietary supplement of selenium (Se) may reduce cancer risk, 1312 patients with histories of basa/squamous cell carcinomas of the skin were assigned in random, double-blind fashion to daily oral supplements of either Se-enriched yeast (200 micrograms Se/day), or a low-Se yeast placebo. Patients were recruited in 1983 to 1990 and were followed with regular dermatologic examinations through, 1993 for a total of 8269 person-years of observation. Skin cancer diagnoses were confirmed histologically and plasma Se concentration was determined at 6 to 12 months intervals. All deaths and patient-reported illnesses were confirmed and documented by consultation with the patient medical care providers. RESULTS: Results showed that Se-supplementation did not significantly affect the incidences of recurrent basal/squamous cell carcinomas of the skin. However, Se-treatment was associated with reductions in total cancer mortality and in the incidences of lung, colorectal, prostate and total cancers. These effects were consistent over time and between study clinics. CONCLUSION: The results strongly suggest benefits of Se-supplementation for this cohort of patients and support the hypothesis that supplemental Se can reduce risks to at least some types of cancer.

JAMA. 1996 Dec 25;276(24):1957-63.
Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.
Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR.
Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, USA.
OBJECTIVE: To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. DESIGN: A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. SETTING: Seven dermatology clinics in the eastern United States. PATIENTS: 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. INTERVENTIONS: Oral administration of 200 microg of selenium per day or placebo. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Clin Chim Acta. 1995 Jan 31;234(1-2):137-46.
Effect of double-blind cross-over selenium supplementation on lipid peroxidation markers in cystic fibrosis patients.
Portal B, Richard MJ, Coudray C, Arnaud J, Favier A.
Laboratoire de Biochimie, Groupe de Recherche sur Ies pathologies oxydatives GREPO, La Tronche, France.
Lipid peroxidation was assessed in 27 cystic fibrosis children during a double-blind selenium supplementation study (2.8 micrograms of sodium selenite per kg per day) with a placebo control and inversion of treatment periods. Simultaneously, 17 healthy children living in the same area were also investigated as control subjects. Before any treatment whatsoever and despite a selenium status close to those of control subjects, cystic fibrosis patients showed significant increase in plasma lipid peroxidation markers. Thiobarbituric acid reactants (TBARs) were normalized after the first treatment period of 5 months in both cystic fibrosis groups receiving either selenium supplementation or placebo. In this latter group, TBARs were reduced despite a significant decrease in plasma selenium concentrations as compared with the control group. Organic hydroperoxide concentrations were also simultaneously normalized in both cystic fibrosis groups at the end of the second treatment period. These results showed that improvement of lipid peroxidation markers was not related to the selenium supplementation. Nevertheless, oxidative stress sustained by cystic fibrosis children must be taken into account so that it does not aggravate the prognosis of the disease.

Scand J Clin Lab Invest. 1994 Dec;54(8):585-90.
Selenium status and the effect of organic and inorganic selenium supplementation in a group of elderly people in Denmark.
Lassen KO, Horder M.
Department of Clinical Chemistry, University Hospital, Odense, Denmark.
The selenium status of 57 elderly people (> or = 65 years) has been investigated on the basis of selenium concentration in serum, whole blood and erythrocytes and on the basis of the activity of the selenium-dependent enzyme glutathione peroxidase (GSH-px) in erythrocytes and plasma. Thirty-six elderly subjects participated in a 4-month trial of supplementation: 12 subjects were supplemented with 125 micrograms organic selenium, 12 subjects were supplemented with 125 micrograms inorganic selenium and 12 subjects participated as controls. The results showed that the selenium status of the elderly people was not significantly lower than that of younger people (p > 0.05). The effect of organic and inorganic selenium on the activity of GSH-px in plasma and erythrocytes showed a nearly identical increase (25-35%) during the period of supplementation. The effect of inorganic selenium supplementation caused a 30% increase in selenium concentration in plasma and erythrocytes which stabilized after 4 weeks. The effect of organic selenium supplementation on selenium concentration in plasma and erythrocytes showed an increase of up to 100% and 120% during the period of supplementation.

Biol Trace Elem Res. 1994 Apr-May;41(1-2):115-27.
Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells.
Kiremidjian-Schumacher L, Roy M, Wishe HI, Cohen MW, Stotzky G.
New York University Dental Center, New York.
This study examined the effect of dietary (200 micrograms/d for 8 wk) supplementation with selenium (as sodium selenite) on the ability of human peripheral blood lymphocytes to respond to stimulation with alloantigen, develop into cytotoxic lymphocytes, and to destroy tumor cells, and on the activity of natural killer cells. The participants in the study were randomized for age, sex, weight, height, and nutritional habits and given selenite or placebo tablets; all participants had a selenium replete status as indicated by their plasma Se levels prior to supplementation. The data indicated that the supplementation regimen resulted in 118% increase in cytotoxic lymphocyte-mediated tumor cytotoxicity and 82.3% increase in natural killer cell activity as compared to baseline values. This apparently was related to the ability of the nutrient to enhance the expression of receptors for the growth regulatory lymphokine interleukin-2, and consequently, the rate of cell proliferation and differentiation into cytotoxic cells. The supplementation regimen did not produce significant changes in the plasma Se levels of the participants. The results indicated that the immunoenhancing effects of selenium in humans require supplementation above the replete levels produced by normal dietary intake.

Allergy. 1993 Jan;48(1):30-6.
Selenium supplementation in intrinsic asthma.
Hasselmark L, Malmgren R, Zetterstrom O, Unge G.
Department of Experimental Surgery, Karolinska Institute, Stockholm, Sweden.
The accumulated data indicate that asthma is associated with reduced circulatory selenium (Se) status and lowered activity of the Se-dependent enzyme glutathione peroxidase (GSH-Px), which may have etiological implications, considering the important role of GSH-Px in the cellular elimination of hydroperoxides. The aim of the present double-blind study was to investigate whether Se supplementation in asthmatic patients may increase GSH-Px activity and possibly bring about clinical improvement. Twenty-four patients suffering from intrinsic asthma were selected and randomized into two groups, and after a preintervention period of 4 weeks, one group received a daily supplement of 100 micrograms sodium selenite for 14 weeks, whereas the other group received placebo. In the Se-supplemented group there were significant increases in serum Se and platelet GSH-Px activity after intervention, accompanied by a significant reduction in the irreversible platelet aggregation induced by 5 mumol/l ADP, while no significant changes in these parameters could be observed in the placebo group. Further, there was a significant clinical improvement in the Se-supplemented group, as compared with the placebo group, with regard to the assembled clinical evaluation made of each patient. This improvement could, however, not be validated by significant changes in the separate clinical parameters of lung function and airway hyperresponsiveness. The results are discussed in view of the role of GSH-Px in the cellular enzymatic oxidant defense system and as a modulator of arachidonic acid metabolism.