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1.
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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Reactive Oxygen Species Scavenger in Acute Intracerebral Hemorrhage Patients: A Multicenter, Randomized Controlled Trial.
Kim, M, Byun, J, Chung, Y, Lee, SU, Park, JE, Park, W, Park, JC, Ahn, JS, Lee, S
Stroke. 2021;(4):1172-1181
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[Figure: see text].
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3.
Effects of selenium supplementation on pregnancy outcomes and disease progression in HIV-infected pregnant women in Lagos: A randomized controlled trial.
Okunade, KS, Olowoselu, OF, John-Olabode, S, Hassan, BO, Akinsola, OJ, Nwogu, CM, Ugwu, AO, Moses, OE, Rabiu, KA, Ajepe, A, et al
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2021;(3):533-541
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Abstract
OBJECTIVE To examine the effects of selenium supplementation on pregnancy outcomes and disease progression among HIV-infected pregnant women in Lagos. METHODS A randomized, placebo-controlled trial conducted among HIV-positive pregnant women between September 2018 and August 2019. At enrollment, 90 women were randomly assigned into each treatment arm to receive either a daily tablet of 200 μg elemental selenium or a placebo. Relevant participants' sociodemographic and clinical data were collected at enrollment and delivery. RESULTS Women in the selenium arm had a significantly lower risk of preterm delivery (relative risk [RR] 0.32, 95% confidence interval [CI] 0.11-0.96) and a non-significant reduction in the risk of delivering term neonates with a low delivery weight (RR 0.24, 95% CI 0.05-1.19). Supplemental selenium does not increase the risk of perinatal death and adverse drug events. CONCLUSION The study reported a beneficial effect of prenatal selenium supplements on the risk of preterm delivery with no further reduction in risk among HIV-infected women who used the supplements for more than 14 weeks. TRIAL REGISTRATION Pan African Clinical Trial Registry (PACTR201809756724274).
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Selenium supplementation in patients with peripartum cardiomyopathy: a proof-of-concept trial.
Karaye, KM, Sa'idu, H, Balarabe, SA, Ishaq, NA, Sanni, B, Abubakar, H, Mohammed, BL, Abdulsalam, T, Tukur, J, Mohammed, IY
BMC cardiovascular disorders. 2020;(1):457
Abstract
BACKGROUND We studied the efficacy and safety of selenium supplementation in patients who had peripartum cardiomyopathy (PPCM) and selenium deficiency. METHODS We randomly assigned 100 PPCM patients with left ventricular ejection fraction (LVEF) < 45% and selenium deficiency (< 70 μg/L) to receive either oral Selenium (L-selenomethionine) 200 μg/day for 3 months or nothing, in addition to recommended therapy, in an open-label randomised trial. The primary outcome was a composite of persistence of heart failure (HF) symptoms, unrecovered LV systolic function (LVEF < 55%) or death from any cause. RESULTS Over a median of 19 months, the primary outcome occurred in 36 of 46 patients (78.3%) in the selenium group and in 43 of 54 patients (79.6%) in the control group (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.43-1.09; p = 0.113). Persistence of HF symptoms occurred in 18 patients (39.1%) in the selenium group and in 37 patients (68.5%) in the control group (HR 0.53; 95% CI 0.30-0.93; p = 0.006). LVEF < 55% occurred in 33 patients (71.7%) in the selenium group and in 38 patients (70.4%) in the control group (HR 0.91; 95% CI 0.57-1.45; p = 0.944). Death from any cause occurred in 3 patients (6.5%) in the selenium group and in 9 patients (16.7%) in the control group (HR 0.37; 95% CI 0.10-1.37; p = 0.137). CONCLUSIONS In this study, selenium supplementation did not reduce the risk of the primary outcome, but it significantly reduced HF symptoms, and there was a trend towards a reduction of all-cause mortality. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03081949.
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Functional Biomarkers for the Selenium Status in a Human Nutritional Intervention Study.
Müller, SM, Dawczynski, C, Wiest, J, Lorkowski, S, Kipp, AP, Schwerdtle, T
Nutrients. 2020;(3)
Abstract
Soils in Germany are commonly low in selenium; consequently, a sufficient dietary supply is not always ensured. The extent of such provision adequacy is estimated by the optimal effect range of biomarkers, which often reflects the physiological requirement. Preceding epidemiological studies indicate that low selenium serum concentrations could be related to cardiovascular diseases. Inter alia, risk factors for cardiovascular diseases are physical inactivity, overweight, as well as disadvantageous eating habits. In order to assess whether these risk factors can be modulated, a cardio-protective diet comprising fixed menu plans combined with physical exercise was applied in the German MoKaRi (modulation of cardiovascular risk factors) intervention study. We analyzed serum samples of the MoKaRi cohort (51 participants) for total selenium, GPx activity, and selenoprotein P at different timepoints of the study (0, 10, 20, 40 weeks) to explore the suitability of these selenium-associated markers as indicators of selenium status. Overall, the time-dependent fluctuations in serum selenium concentration suggest a successful change in nutritional and lifestyle behavior. Compared to baseline, a pronounced increase in GPx activity and selenoprotein P was observed, while serum selenium decreased in participants with initially adequate serum selenium content. SELENOP concentration showed a moderate positive monotonic correlation (r = 0.467, p < 0.0001) to total Se concentration, while only a weak linear relationship was observed for GPx activity versus total Se concentration (r = 0.186, p = 0.021). Evidently, other factors apart from the available Se pool must have an impact on the GPx activity, leading to the conclusion that, without having identified these factors, GPx activity should not be used as a status marker for Se.
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Diverse Associations of Plasma Selenium Concentrations and SELENOP Gene Polymorphism with Metabolic Syndrome and Its Components.
Zhou, L, Luo, C, Yin, J, Zhu, Y, Li, P, Chen, S, Sun, T, Xie, M, Shan, Z, Cao, B, et al
Oxidative medicine and cellular longevity. 2020;:5343014
Abstract
The relationship between selenium and metabolic syndrome (MetS) has been discussed controversially, and limited studies have examined the associations of single nucleotide polymorphisms in selenoproteins genes with MetS. Hence, to examine the associations of plasma selenium concentrations and selenoprotein P rs7579 polymorphism with MetS, a case-control study of 1279 MetS cases and 1279 sex- and age- (±2 years) matched controls was conducted based on the baseline data of the Tongji-Ezhou Cohort study. Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry. MetS was defined using the definition of the Joint Interim Statement, adjusted for the Chinese population. In addition, the rs7579 polymorphism was genotyped by the Agena MassARRAY System. Plasma selenium concentrations in the MetS group were higher than in the control group (93.88 μg/L (83.17-107.41) vs. 92.66 μg/L (82.36-103.53), P < 0.05). Compared with quartile 4 (≥103.53 μg/L), the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) associated with MetS were 0.79 (0.59-1.06) for quartile 1 (<82.36 μg/L), 0.75 (0.56-1.01) for quartile 2 (82.37-92.66 μg/L), and 0.61 (0.45-0.83) for quartile 3 (92.67-103.52 μg/L). The cubic spline analyses revealed a U-shaped association between plasma selenium and MetS, with the lowest risk at around 93.69 μg/L. Moreover, in cubic spline analyses, plasma selenium showed U-shaped associations with central obesity and high blood pressure, positive associations with hypertriglyceridemia and hyperglycemia, and a negative association with low high-density lipoprotein cholesterol. Additionally, both the GA and GA+AA genotype carriers were associated with increased ORs of MetS comparing with the GG genotype carriers. Our findings suggested a U-shaped association between plasma selenium and MetS and diverse associations between plasma selenium and components of MetS. Furthermore, our study found that the A allele of rs7579 was associated with higher odds of MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms.
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Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly.
Alehagen, U, Aaseth, J, Alexander, J, Johansson, P
PloS one. 2018;(4):e0193120
Abstract
BACKGROUND Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. METHODS From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. FINDINGS After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95%CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. CONCLUSIONS This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified. Since this was a small study, the observations should be regarded as hypothesis-generating. TRIAL REGISTRATION Clinicaltrials.gov NCT01443780.
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Selenium, Vitamin C and N-Acetylcysteine do not Reduce the Risk of Acute Kidney Injury after Off-Pump CABG: a Randomized Clinical Trial.
Amini, S, Robabi, HN, Tashnizi, MA, Vakili, V
Brazilian journal of cardiovascular surgery. 2018;(2):129-134
Abstract
OBJECTIVE The aim of this study was to investigate the impact of perioperative administration of N-acetylcysteine, selenium and vitamin C on the incidence and outcomes of acute kidney injury after off-pump coronary bypass graft surgery. METHODS 291 patients requiring elective off-pump coronary bypass graft surgery were randomized to receive either N-acetylcysteine, vitamin C and selenium 600 mg, 1500 mg, 0.5 mg, and nothing orally twice a day, respectively, from the day before to 2 days after surgery. They were assessed for the development of acute kidney injury using Acute Kidney Injury Network criteria, time of onset, its severity and duration, duration of mechanical ventilation, intensive care unit and hospital length of stay, and in-hospital mortality. RESULTS 272 patients completed the study. The total incidence of acute kidney injury was 22.1% (n=60) with 14 (20.9%), 15 (22.1%), 21 (31.8%), and 10 (14.1%) patients in the vitamin C, NAC, selenium, and control groups, respectively (P=0.096). We did not register significant differences in the incidence, the time of occurrence, the severity and the duration of acute kidney injury, as well as the duration of mechanical ventilation, the intensive care unit and hospital length of stay, and the in-hospital mortality among the four groups. CONCLUSION We found that perioperative administration of N-acetylcysteine, vitamin C and selenium were not effective in preventing acute kidney injury and associated morbidity and mortality after off-pump coronary bypass graft surgery.
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Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomised controlled trial.
Rayman, MP, Winther, KH, Pastor-Barriuso, R, Cold, F, Thvilum, M, Stranges, S, Guallar, E, Cold, S
Free radical biology & medicine. 2018;:46-54
Abstract
BACKGROUND Selenium, an essential trace element, is incorporated into selenoproteins with a wide range of health effects. Selenoproteins may reach repletion at a plasma selenium concentration of ~ 125 µg/L, at which point the concentration of selenoprotein P reaches a plateau; whether sustained concentrations higher than this are beneficial, or indeed detrimental, is unknown. OBJECTIVE In a population of relatively low selenium status, we aimed to determine the effect on mortality of long-term selenium supplementation at different dose levels. DESIGN The Denmark PRECISE study was a single-centre, randomised, double-blinded, placebo-controlled, multi-arm, parallel clinical trial with four groups. Participants were 491 male and female volunteers aged 60-74 years, recruited at Odense University Hospital, Denmark. The trial was initially designed as a 6-month pilot study, but supplemental funding allowed for extension of the study and mortality assessment. Participants were randomly assigned to treatment with 100, 200, or 300 µg selenium/d as selenium-enriched-yeast or placebo-yeast for 5 years from randomization in 1998-1999 and were followed up for mortality for a further 10 years (through March 31, 2015). RESULTS During 6871 person-years of follow-up, 158 deaths occurred. In an intention-to-treat analysis, the hazard ratio (95% confidence interval) for all-cause mortality comparing 300 µg selenium/d to placebo was 1.62 (0.66, 3.96) after 5 years of treatment and 1.59 (1.02, 2.46) over the entire follow-up period. The 100 and 200 µg/d doses showed non-significant decreases in mortality during the intervention period that disappeared after treatment cessation. Although we lacked power for endpoints other than all-cause mortality, the effects on cancer and cardiovascular mortality appeared similar. CONCLUSIONS A 300 µg/d dose of selenium taken for 5 years in a country with moderately-low selenium status increased all-cause mortality 10 years later. While our study was not initially designed to evaluate mortality and the sample size was limited, our findings indicate that total selenium intake over 300 µg/d and high-dose selenium supplements should be avoided.
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Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.
Alehagen, U, Johansson, P, Aaseth, J, Alexander, J, Wågsäter, D
PloS one. 2017;(4):e0174880
Abstract
BACKGROUND Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. METHODS Out of the 443 healthy elderly participants that were given supplementation with 200 μg Se/day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)-plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. FINDINGS On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post-treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e-8. CONCLUSIONS Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of mechanisms underlying the clinical effects earlier reported that reduced cardiovascular mortality, gave better cardiac function, and showed less signs of inflammation and oxdative stress following the intervention. However, more research is needed to understand biological mechanisms of the protective effects of selenium and Q10 supplementation.