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A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium.
Martinez, JA, Skiba, MB, Chow, HS, Chew, WM, Saboda, K, Lance, P, Ellis, NA, Jacobs, ET
Nutrients. 2021;(11)
Abstract
Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33-0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33-0.94)); and of a large adenoma with higher PGE2 ((0.52 (0.31-0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.
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Myo-inositol and selenium reduce the risk of developing overt hypothyroidism in patients with autoimmune thyroiditis.
Ferrari, SM, Fallahi, P, Di Bari, F, Vita, R, Benvenga, S, Antonelli, A
European review for medical and pharmacological sciences. 2017;(2 Suppl):36-42
Abstract
OBJECTIVE The beneficial effects obtained by myo-inositol in association with seleno-methionine in patients affected by subclinical hypothyroidism have been recently demonstrated. Here, we evaluate the immune-modulating effect of myo-inositol in association with seleno-methionine in patients with euthyroid autoimmune thyroiditis (AT). PATIENTS AND METHODS Twenty-one consecutive Caucasian patients with newly diagnosed euthyroid chronic AT were evaluated. All subjects were treated with myo-inositol in association with selenium (600 mg/83 mg) tablets, twice per day, for six months. A complete thyroid assessment was done before the treatment, and after six months. RESULTS After the treatment thyroid-stimulating hormone (TSH) levels significantly declined with respect to basal values, overall in patients with an initial TSH value in the high normal range (2.1 CONCLUSIONS We first show an immune-modulatory effect of myo-inositol in association with seleno-methionine in patients with euthyroid AT. Further studies are needed to extend the observations in a large population, to evaluate the effect on the quality of life, and to study the mechanism of the effect on chemokines.
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Concentration of selenium, zinc, copper, Cu/Zn ratio, total antioxidant status and c-reactive protein in the serum of patients with psoriasis treated by narrow-band ultraviolet B phototherapy: A case-control study.
Wacewicz, M, Socha, K, Soroczyńska, J, Niczyporuk, M, Aleksiejczuk, P, Ostrowska, J, Borawska, MH
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2017;:109-114
Abstract
BACKGROUND Psoriasis is a common, an inflammatory skin disease. Trace elements may play an active role in the pathogenesis of psoriasis. OBJECTIVE The aim of this study was to estimate the concentration of selenium (Se), zinc (Zn), copper (Cu) and Cu/Zn ratio as well as total antioxidant status (TAS) and c-reactive protein (CRP) in the serum of patients with psoriasis. METHODS In this case-control study sixty patients with psoriasis and fifty-eight healthy people were examined. Serum levels of Se, Zn and Cu were determined by atomic absorption spectrometry. Cu/Zn ratio was calculated. TAS was measured spectrophotometrically. CRP was analyzed by immunoturbidimetric method. Clinical activity of psoriasis was evaluated using Psoriasis Area and Severity Index (PASI). RESULTS Serum concentration of Se in patients with psoriasis (71.89±16.90μg/L) was lower as compared to the control group (79.42±18.97μg/L) and after NB-UVB. Cu level of patients was higher (1.151±0.320mg/L) as compared to controls (1.038±0.336mg/L), but Zn level did not differ. We observed higher Cu/Zn ratio (p<0.05) in examined patients than in the control group and after NB-UVB. We found decrease TAS before and after NB-UVB. CRP levels was found to be normal range. A significant correlation coefficient between CRP and Cu/Zn was observed. CONCLUSIONS The study showed some disturbances in the serum levels of trace elements and TAS in psoriatic patients.
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Selenium, Zinc, Copper, and Total Antioxidant Status in the Serum of Patients with Chronic Tonsillitis.
Michalska-Mosiej, M, Socha, K, Soroczyńska, J, Karpińska, E, Łazarczyk, B, Borawska, MH
Biological trace element research. 2016;(1):30-4
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Abstract
Antioxidants can play a significant role in chronic inflammatory process. The aim of this study was to evaluate the content of selenium (Se), zinc (Zn), copper (Cu), and total antioxidant status (TAS) of patients with chronic tonsillitis (CT). The study group consisted of 84 patients with CT from 18 to 62 years old and the control group of 67 healthy people aged 19-65 years. Se, Zn, and Cu concentration in serum samples were determined by atomic absorption spectrometry. Serum TAS was measured spectrophotometrically, using the test by Randox Laboratories-Us Ltd. The mean content of Se and Zn in the serum of patients with CT (61.122 ± 12.73 μg/L, 0.887 ± 0.26 mg/L, respectively) was lower compared to the control group (77.969 ± 12.73 μg/L, 0.993 ± 0.32 mg/L, respectively). The mean serum concentration of Cu in patients with CT (1.219 ± 0.35 mg/L) was higher compared to its serum concentration in healthy people (1.033 ± 0.37 mg/L). Serum TAS of patients with CT (1.171 ± 0.33 mmol/L) was lower in comparison with healthy volunteers (1.333 ± 0.42 mmol/L). The serum concentration of Se, Zn, and TAS in patients with CT was lower, whereas the concentration of Cu was higher compared to healthy volunteers. Smoking has an influence on reducing the concentration of Se and TAS of patients with CT.
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Selenium Status Is Positively Associated with Bone Mineral Density in Healthy Aging European Men.
Beukhof, CM, Medici, M, van den Beld, AW, Hollenbach, B, Hoeg, A, Visser, WE, de Herder, WW, Visser, TJ, Schomburg, L, Peeters, RP
PloS one. 2016;(4):e0152748
Abstract
OBJECTIVE It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable. DESIGN AND METHODS We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75-80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se. RESULTS The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use. CONCLUSION Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population.
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A randomized controlled trial of vitamin E and selenium on rate of decline in lung function.
Cassano, PA, Guertin, KA, Kristal, AR, Ritchie, KE, Bertoia, ML, Arnold, KB, Crowley, JJ, Hartline, J, Goodman, PJ, Tangen, CM, et al
Respiratory research. 2015;(1):35
Abstract
BACKGROUND The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers. METHODS The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 μg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function. RESULTS Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25-75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25-75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25-75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E. CONCLUSIONS Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25-75, a marker of airflow. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT00241865 .
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Selenium supplementation has no effect on serum glucose levels in men at high risk of prostate cancer.
Algotar, AM, Hsu, CH, Singh, P, Stratton, SP
Journal of diabetes. 2013;(4):465-70
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BACKGROUND Current literature regarding the effect of selenium supplementation on the risk of diabetes is inconclusive. Hence, a longitudinal study was conducted to investigate the effect of selenium supplementation on serum glucose levels in elderly men. METHODS Data were obtained from 699 men participating in a randomized double-blind placebo-controlled Phase 3 clinical trial investigating the effects of two doses of selenium (200 and 400 μg/day) compared with placebo on the incidence of prostate cancer. Subjects were followed every 6 months for up to 5 years. Serum glucose levels were obtained every 6 months. Mixed-effects regression models were used to assess whether the rate of change of serum glucose levels was significantly different in the selenium-supplemented groups compared with placebo. Sensitivity analyses were performed to assess the robustness of findings and to minimize the possibility of residual bias due to fasting status. RESULTS Of the total 2893 glucose measurements, 734 were performed when the subject had been fasting for ≥8 h. Changes in serum glucose levels during the course of the trial did not differ significantly between the placebo and selenium 200 μg/day (P = 0.98) and 400 μg/day (P = 0.81) groups. Sensitivity analyses demonstrated comparable results for models using the total population and models restricted to subjects with only fasting glucose data. CONCLUSION These results do not support a relationship between selenium supplementation and risk of diabetes. Hence, recommendations regarding selenium supplementation based on increased risk of diabetes seem premature.
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Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention.
Thompson, P, Roe, DJ, Fales, L, Buckmeier, J, Wang, F, Hamilton, SR, Bhattacharyya, A, Green, S, Hsu, CH, Chow, HH, et al
Cancer prevention research (Philadelphia, Pa.). 2012;(12):1381-93
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Abstract
COX inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women, ages 40 to 80 years, were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 μg daily as selenized yeast), or double placebo. The trial was initiated in November 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared with placebo, as determined by surveillance colonoscopy conducted three to five years after baseline. Randomization was stratified by use of low-dose aspirin (81 mg) and clinic site. Following reports of cardiovascular toxicity associated with COX-2 inhibitors, the celecoxib arm was discontinued in December 2004 when 824 participants had been randomized. Accrual continued with randomization to selenium alone or placebo. Randomization of the originally planned cohort (n = 1,621) was completed in November 2008. A further 200 patients with one or more advanced adenomas (denoting increased risk for colorectal cancer) were accrued to enhance statistical power for determining intervention efficacy in this higher-risk subgroup. Accrual of the total cohort (n = 1,824) was completed in January 2011. Baseline cohort characteristics include: mean age 62.9 years; 65% male; body mass index (BMI) 29.1 ± 5.1; 47% taking low-dose aspirin while on trial; 20% with three or more adenomas; and 38% with advanced adenomas. Intervention effects on adenoma recurrence will be determined, and their modification by genetic background and baseline selenium level. The effect of selenium supplementation on risk for type II diabetes will also be reported.
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Selenium, selenoenzymes, oxidative stress and risk of neoplastic progression from Barrett's esophagus: results from biomarkers and genetic variants.
Takata, Y, Kristal, AR, Santella, RM, King, IB, Duggan, DJ, Lampe, JW, Rayman, MP, Blount, PL, Reid, BJ, Vaughan, TL, et al
PloS one. 2012;(6):e38612
Abstract
Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA) and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX) 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1) concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85). SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR) = 3.95, 95% confidence intervals (CI) = 1.42-10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31-32.58), but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12-0.69). Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1 concentrations with the risk of EA and aneuploidy, which warrants further investigation.
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Practice effects in a longitudinal, multi-center Alzheimer's disease prevention clinical trial.
Abner, EL, Dennis, BC, Mathews, MJ, Mendiondo, MS, Caban-Holt, A, Kryscio, RJ, Schmitt, FA, , , Crowley, JJ, ,
Trials. 2012;:217
Abstract
BACKGROUND Practice effects are a known threat to reliability and validity in clinical trials. Few studies have investigated the potential influence of practice on repeated screening measures in longitudinal clinical trials with a focus on dementia prevention. The current study investigates whether practice effects exist on a screening measure commonly used in aging research, the Memory Impairment Screen (MIS). METHODS The PREADViSE trial is a clinical intervention study evaluating the efficacy of vitamin E and selenium for Alzheimer's disease prevention. Participants are screened annually for incident dementia with the MIS. Participants with baseline and three consecutive follow-ups who made less than a perfect score at one or more assessments were included in the current analyses (N=1,803). An additional subset of participants with four consecutive assessments but who received the same version of the MIS at baseline and first follow-up (N=301) was also assessed to determine the effects of alternate forms on mitigating practice. We hypothesized that despite efforts to mitigate practice effects with alternate versions, MIS scores would improve with repeated screening. Linear mixed models were used to estimate mean MIS scores over time. RESULTS Among men with four visits and alternating MIS versions, although there is little evidence of a significant practice effect at the first follow-up, mean scores clearly improve at the second and third follow-ups for all but the oldest participants. Unlike those who received alternate versions, men given the same version at first follow-up show significant practice effects. CONCLUSION While increases in the overall means were small, they represent a significant number of men whose scores improved with repeated testing. Such improvements could bias case ascertainment if not taken into account.