Association of Plasma Selenium and Its Untargeted Metabolomic Profiling with Cervical Cancer Prognosis.

Selenium is an essential trace element that shows beneficial or adverse health effects depending on the dose. However, its role in the prognosis of cervical cancer (CC) has been less reported. We aimed to explore the association between selenium status and prognosis in CC patients with different prognoses and to elucidate the underlying mechanism of selenium in CC prognosis. This cross-sectional observational study had a case-control design at the Harbin Medical University Cancer Hospital and was conducted using 29 CC cases with poor prognosis and 29 CC cases with good prognosis. Plasma selenium levels were measured using an atomic fluorescence spectrometer. Untargeted metabolomics was used to identify metabolites. Plasma selenium levels of the poor prognosis group (49.90 ± 13.81 µg/L) were lower than that of the good prognosis group (59.38 ± 13.00 µg/L, t = 2.69, P = 0.009). In the logistic regression analysis, plasma selenium levels were associated with lower poor prognosis risk [odds ratio (OR) = 0.952, 95% CI: 0.909-0.998]. Receiver operating characteristic curve analysis revealed an optimal cut-off point of plasma selenium levels ≤ 47.68 µg/L for poor prognosis of CC. Based on the cut-off selenium levels, patients with different prognoses were divided into high and low selenium groups. Metabolomic analysis revealed six differential metabolites among different prognoses with low and high selenium levels, and the glycerophospholipid (GPL) metabolism was enriched. Plasma selenium levels were positively correlated with metabolite levels. Our findings provided evidence that low plasma selenium levels may associate with a poor prognosis of CC. Low plasma selenium levels might suppress GPL metabolism and influence the prognosis of CC. This finding requires confirmation in future prospective cohort studies.

Dietary Trace Element Intake and Risk of Breast Cancer: A Mini Review.

Trace elements are essentially required for various physiological and metabolic functions, and any disturbance in the trace elements homeostasis may result in the development of chronic diseases including breast cancer. Breast cancer is the most prevalent cancer type reported in women equally affecting both the high-income and low-income countries. This review therefore aimed to evaluate the impact of dietary trace element intake in relation to the incidence of breast cancer. We focused on five trace elements, thus emphasizing dietary selenium, zinc, iron, copper, and cadmium intake and risk of breast cancer. A systematic approach was applied to perform this review through entering a search term in PubMed and Scopus databases. A total of 24 articles were included after meeting the inclusion and exclusion criteria. Most of the studies regarding dietary iron intake showed a detrimental effect of increased dietary heme iron on breast cancer incidence risk. In addition, there is a limited evidence of high dietary intake of selenium and zinc to reduce the risk of breast cancer. Also, a few studies showed a relationship between high cadmium consumption and risk of breast cancer. More studies related to cadmium and copper exposure are needed to confirm this relationship. As a result, the findings of this review suggested that high dietary heme iron is a potential risk factor for breast cancer.

Preclinical Evaluation of Sodium Selenite in Mice: Toxicological and Tumor Regression Studies after Striatum Implantation of Human Glioblastoma Stem Cells.

Glioblastoma (GBM) is the most aggressive malignant glioma, with a very poor prognosis; as such, efforts to explore new treatments and GBM's etiology are a priority. We previously described human GBM cells (R2J-GS) as exhibiting the properties of cancer stem cells (growing in serum-free medium and proliferating into nude mice when orthotopically grafted). Sodium selenite (SS)-an in vitro attractive agent for cancer therapy against GBM-was evaluated in R2J-GS cells. To go further, we launched a preclinical study: SS was given orally, in an escalation-dose study (2.25 to 10.125 mg/kg/day, 5 days on, 2 days off, and 5 days on), to evaluate (1) the absorption of selenium in plasma and organs (brain, kidney, liver, and lung) and (2) the SS toxicity. A 6.75 mg/kg SS dose was chosen to perform a tumor regression assay, followed by MRI, in R2J-GS cells orthotopically implanted in nude mice, as this dose was nontoxic and increased brain selenium concentration. A group receiving TMZ (5 mg/kg) was led in parallel. Although not reaching statistical significance, the group of mice treated with SS showed a slower tumor growth vs. the control group (p = 0.08). No difference was observed between the TMZ and control groups. We provide new insights of the mechanisms of SS and its possible use in chemotherapy.

Assessment of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: In this study, we investigate the effect of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in patients with COVID-19. TRIAL DESIGN: The current study is a single-center, randomized, double-blind, placebo-controlled clinical trial with parallel groups. PARTICIPANTS: The inclusion criteria include male and female patients≥18 years of age, with a confirmed diagnosis of SARS-CoV-2 infection via polymerase chain reaction (PCR) and/or antibody test and with written informed consent to participate in this trial. The exclusion criteria include regular use of any other supplement, severe and critical COVID-19 pneumonia, pregnancy and breastfeeding. This study is being conducted at Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. INTERVENTION AND COMPARATOR: Patients are randomly assigned to four groups. The first group (A) will take one capsule containing 5 mg of boron compounds twice a day for two weeks. The second group (B) will take one capsule containing 200 mg oleoylethanolamide twice a day for two weeks. The third group (C) will take one capsule containing 5 mg boron compounds with 200 mg oleoylethanolamide twice a day for two weeks, and the fourth group (D) does not receive any additional treatment other than routine treatments. Boron-containing compounds and oleoylethanolamide capsules will be synthesized at Nutrition Research Center of Tabriz University of Medical Sciences. MAIN OUTCOMES: The primary end point of this study is to investigate the recovery rate of clinical symptoms, including fever, dry cough, and fatigue, as well as preclinical features, including complete blood count (CBC), the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) profiles within two weeks of randomization. RANDOMISATION: Patients are randomized into four equal groups in a parallel design (allocation ratio 1:1). A randomized block procedure is used to divide subjects into one of four treatment blocks (A, B, C, and D) by a computer-generated allocation schedule. BLINDING (MASKING): The participants and investigators (enrolling, assessing, and analyzing) are blinded to the intervention assignments until the end of the study and data analysis. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The calculated total sample size is 40 patients, with 10 patients in each group. TRIAL STATUS: The protocol is Version 1.0, May 17, 2020. Recruitment began May 19, 2020, and is anticipated to be completed by October 19, 2020. TRIAL REGISTRATION: This clinical trial has been registered by the title of "Assessment of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in Patients with COVID-19: A double-blind randomized placebo-controlled clinical trial" in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20090609002017N35 ", https://www.irct.ir/trial/48058 . The registration date is 17 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Traces matter: Targeted optimization of monoclonal antibody N-glycosylation based on/by implementing automated high-throughput trace element screening.

The use of high-throughput systems in cell culture process optimization offers various opportunities in biopharmaceutical process development. Here we describe the potential for acceleration and enhancement of product quality optimization and de novo bioprocess design regarding monoclonal antibody N-glycosylation by using an iterative statistical Design of Experiments (DoE) strategy based on our automated microtiter plate-based system for suspension cell culture. In our example, the combination of an initial screening of trace metal building blocks with a comprehensive DoE-based screening of 13 different trace elemental ions at three concentration levels in one run revealed most effective levers for N-glycan processing and biomass formation. Obtained results served to evaluate optimal concentration ranges and the right supplementation timing of relevant trace elements at shake flask and 2 L bioreactor scale. This setup identified manganese, copper, zinc, and iron as major factors. Manganese and copper acted as inverse key players in N-glycosylation, showing a positive effect of manganese and a negative effect of copper on glycan maturation in a zinc-dependent manner. Zinc and iron similarly improved cell growth and biomass formation. These findings allowed determining optimal concentration ranges for all four trace elements to establish control on desired product quality attributes regarding premature afucosylated and mature galactosylated glycan species. Our results demonstrates the power of combining robotics with DoE screening to enhance product quality optimization and to improve process understanding, thus, enabling targeted product quality control.

Product indiscriminate use of vitamin risks: A review.

Most of the population does not seek professional advice before taking vitamin products and their indiscriminate use can lead to serious health risks. This study aims to demonstrate, through bibliographic survey, the risks of indiscriminate use of vitamin products related to hypervitaminosis and major drug interactions which the multivitamins are involved. A bibliographic survey was conducted in the databases LILACS, SciELO, PubMed, Medline, Micromedex, Drugs.com and textbooks on the subject. Vitamins are commonly described as harmless products by the majority of the population, but these trace elements can interact with other substances, causing mild disconforts or treatment failure for the patient, severe consequences to the body and can lead to death. To avoid the indiscriminate use of vitamin products, it is necessary that health professionals know and use specific laboratory tests for the determination of vitamins in the body, preventing these products from being unnecesarily prescribed. Also, the knowledge about what the possible effects of the indiscriminate use of vitamin supplements can lead to the rational use of these products.

Selenium and Other Trace Elements in the Etiology of Parkinson's Disease: A Systematic Review and Meta-Analysis of Case-Control Studies.

BACKGROUND: Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's dementia. Whereas the exact etiology of PD remains unknown, risk of developing PD seems to be related to a combination of genetic and environmental factors. This also includes abnormal exposure to trace elements of nutritional and toxicological interest. OBJECTIVES: In this systematic review and meta-analysis, we summarized the results of case-control studies comparing levels of selenium, copper, iron, and zinc in PD patients and controls in either blood (whole blood, serum/plasma) or cerebrospinal fluid (CSF). METHODS: We performed a systematic PubMed search selecting studies reporting trace element levels in different specimens of patients and controls. We performed a meta-analysis using a random-effect model to compute the weighted mean differences (WMD) and corresponding 95% CI of selenium, copper, iron, and zinc levels in the blood or CSF of patients and their matched controls. RESULTS: We retrieved 56 papers reporting data for selenium (cases/controls: 588/721), copper (2,190/2,522), iron (2,956/3,469), and zinc (1,798/1,913) contents in CSF and blood. Cases showed considerably higher levels of selenium in CSF compared with controls (+51.6%; WMD 5.49; 95% CI 2.82 to 8.15), while levels in serum were similar (-0.2%; WMD -0.22; 95% CI -8.05 to 7.62). For copper, cases showed slightly higher levels in CSF and slightly lower concentrations in serum (+4.5%; WMD 1.87; 95% CI -3.59 to 7.33, and -4.5%; WMD -42.79; 95% CI -134.35 to 48.76, respectively). A slight increase was also found for CSF iron -levels (+9.5%; WMD 9.92; 1.23 to 18.61), while levels were -decreased in serum/plasma (-5.7%; WMD -58.19; 95% CI -106.49 to -9.89) and whole blood (-10.8%; WMD -95.69; 95% CI -157.73 to -33.65). Conversely, for zinc cases exhibited lower levels both in CSF (-10.8%; WMD -7.34; 95% CI -14.82 to 0.14) and serum/plasma (-7.5%; WMD -79.93; 95% CI -143.80 to -16.06). A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood. CONCLUSIONS: Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones, this meta-analysis suggests that overexposure in the central nervous system to selenium, and possibly to copper and iron, may be a risk factor of the disease, while zinc might have a protective -effect.

Comparison and Risk Assessment for Trace Heavy Metals in Raw Pu-erh Tea with Different Storage Years.

This research conducted an exploration of the content of microelements (As, Cr, Cd, Pb, Cu, Zn, Mn, and Hg) in raw Pu-erh tea with different storage years. The contents of As, Cr, Cd, Pb, Cu, Zn, Mn, and Hg were 0.14, 0.82, 0.02, 0.52, 14.59, 33.51, 564.02, and 0.01 µg/g, respectively, and were all less than the national standard limit values in China. The target hazard quotients (THQs) of each heavy metal were all lower than 1, and the value of combined risk hazard index (HI) of all to adults was 0.221, which presents no health risk when consumed properly by adults of the raw Pu-erh tea infusions. Interestingly, there was no significant correlation between the heavy metal element (As, Cr, Cd, Pb, Cu, Zn, Mn, and Hg) contents and the THQ values of raw Pu-erh tea samples and storage years; the correlation coefficients (R2) range from 0.01 to 0.33 and from 0.01 to 0.57, respectively. The result showed that the storage years showed no effect on the exposure risk of heavy metals; the heavy metal elements in tea samples come from the atmosphere and soil.

Anemia following zinc treatment for Wilson's disease: a case report and literature review.

BACKGROUND: Zinc therapy is considered an effective and safe treatment for Wilson's disease. Hypocupremia-related anemia is rarely reported after long-term zinc administration or combination therapy with copper-chelating agent. CASE PRESENTATION: We herein report a 12-year-old girl with pre-symptomatic Wilson's disease diagnosed 5 years ago who presented with severe anemia after high-dose oral zinc for 4 years and 4 months. Her hemoglobin was gradually restored to the normal range after the adjustment of zinc dose and diet therapy for 4 months. A review of the literature revealed eight patients with hypocupremia-associated anemia following zinc therapy for Wilson's disease, including 7 adults and 1 child. The only child patient was a 16-year-old boy, in whom the zinc therapy was succession to penicillamine administration. CONCLUSIONS: This is the first report worldwide that a child developed severe anemia following high-dose single zinc administration for Wilson's disease. It highlights the importance of regular follow-up during zinc treatment and the involvement of specialists in the long-term management of Wilson's disease. We hope that this will alert pediatricians the issue of zinc over-treatment.

An Observational Preliminary Study on the Safety of Long-Term Consumption of Micronutrients for the Treatment of Psychiatric Symptoms.

Objectives: There is an increasing body of literature documenting the efficacy of micronutrients (vitamins and minerals) interventions for the treatment of psychiatric problems in the short term; however, long-term safety is largely unexplored. The goal of this observational study was to investigate the safety of two commercially available broad-spectrum micronutrient formulas (EMPowerplus and Daily Essential Nutrients) given at doses above the Recommended Dietary Allowances for the long-term treatment of individuals with psychiatric symptoms. Design: Participants on long-term treatment with micronutrients (medication-free) for psychiatric problems (attention-deficit hyperactivity disorder [ADHD, n = 21], anxiety/depression [n = 13]) were identified from ongoing research studies and the community through purchasing records. Seventeen children and 17 adults had blood tests to assess their full blood count, coagulation profile, liver and kidney function, fasting glucose, iron studies, key nutrients, and prolactin. Questionnaires assessed psychological/psychiatric functioning. Seventeen of the participants had completed the same measures pretreatment. Results: The average length of consuming micronutrients was 2.66 years (standard deviation = 2.86). Excluding B12 (which was elevated for almost all participants), 94.6% of all blood test results were within the test reference ranges. One participant was diagnosed with hemochromatosis based on iron studies. No other clinically relevant adverse changes in blood results were identified pre- and post-treatment. No clinically significant adverse effects were reported. Post-treatment psychometrics identified that 85% of the participants were in nonclinical ranges for measures of ADHD, depression, anxiety, and stress. Conclusions: We report preliminary evidence for the safety of long-term commercially available micronutrients, although questions remain. Overall, the substantial psychiatric benefits observed appear to outweigh the minimal observed risks in these participants. Screening for potential medical problems is recommended before initiating treatment. Long-term pharmacovigilance monitoring is required to ascertain any rare but significant adverse events.

Safety Assessment of the Trace Element Impurities Ni and Cr in Pharmaceutical Herbal Products for Teething from Polish Pharmacies.

Control of elemental impurities (EIs) in pharmaceutical herbal products is currently important but not a very popular topic in modern toxicological analysis. The occurrence and concentration of EIs in the pharmaceutical herbal products should be controlled and meet the standards of directive International Conference on Harmonisation's Q3D Guideline on Elemental Impurities. An interesting area of interest is measuring EIs including toxic and allergic metals in pharmaceutical herbal products for teething. The aim of this article was determination of Ni and Cr impurities in pharmaceutical herbal products for teething available in Polish pharmacies. Justifications were (1) herbs as an important source of EIs and (2) infants may be particularly sensitive to the toxic effects of metals because they tend to absorb a higher fraction of an oral dose. The analysis was carried out using microwave-assisted wet digestion with concentrated nitric acid and electrothermal atomisation atomic absorption spectrometry. The safety assessment involved a triple approach: (1) level of Ni and Cr impurities in pharmaceutical samples; (2) level of Ni and Cr impurities including one-time administration of teething gels and (3) daily intake of metals. In all three cases, the results indicate that the standards of directive ICH Q3D are met for Ni and Cr. Overall, it can be concluded that none of the teething gels represents a health hazard to infants.

Environmental Selenium and Human Health: an Update.

PURPOSE OF REVIEW: Selenium, a trace element, is ubiquitous in the environment. The main source of human exposure is diet. Despite its nutritional benefits, it is one of the most toxic naturally occurring elements. Selenium deficiency and overexposure have been associated with adverse health effects. Its level of toxicity may depend on its chemical form, as inorganic and organic species have distinct biological properties. RECENT FINDINGS: Nonexperimental and experimental studies have generated insufficient evidence for a role of selenium deficiency in human disease, with the exception of Keshan disease, a cardiomyopathy. Conversely, recent randomized trials have indicated that selenium overexposure is positively associated with type 2 diabetes and high-grade prostate cancer. In addition, a natural experiment has suggested an association between overexposure to inorganic hexavalent selenium and two neurodegenerative diseases, amyotrophic lateral sclerosis and Parkinson's disease. Risk assessments should be revised to incorporate the results of studies demonstrating toxic effects of selenium. Additional observational studies and secondary analyses of completed randomized trials are needed to address the uncertainties regarding the health risks of selenium exposure.

Higher Plasma Selenium Concentrations Are Associated with Increased Odds of Prevalent Type 2 Diabetes.

Background: Selenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation. Objective: We examined the association between baseline plasma concentrations of selenium and the prevalence of T2D, as well as whether participant characteristics or intake of other antioxidant nutrients modified this relation. Methods: We conducted cross-sectional analyses of 1727 participants from the Selenium Trial, a randomized clinical trial of selenium supplementation for colorectal adenoma chemoprevention that had data for baseline selenium plasma concentrations, T2D status, and dietary intake. Logistic regression modeling was used to evaluate the associations between plasma selenium concentrations and prevalent T2D, adjusting for confounding factors. Heterogeneity of effect by participant characteristics was evaluated utilizing likelihood-ratio tests. Results: Mean ± SD plasma selenium concentrations for those with T2D compared with those without T2D were 143.6 ± 28.9 and 138.7 ± 27.2 ng/mL, respectively. After adjustment for confounding, higher plasma selenium concentrations were associated with a higher prevalence of T2D, with ORs (95% CIs) of 1.25 (0.80, 1.95) and 1.77 (1.16, 2.71) for the second and third tertiles of plasma selenium, respectively, compared with the lowest tertile (P-trend = 0.007). No significant effect modification was observed for age, sex, body mass index, smoking, or ethnicity. Increased odds of T2D were seen among those who were in the highest tertile of plasma selenium and the highest category of intake of ß-cryptoxanthin (P-trend = 0.03) and lycopene (P-trend = 0.008); however, interaction terms were not significant. Conclusions: These findings show that higher plasma concentrations of selenium were significantly associated with prevalent T2D among participants in a selenium supplementation trial. Future work is needed to elucidate whether there are individual characteristics, such as blood concentrations of other antioxidants, which may influence this relation.

Reviewing the effects of food provisioning on wildlife immunity.

While urban expansion increasingly encroaches on natural habitats, many wildlife species capitalize on anthropogenic food resources, which have the potential to both positively and negatively influence their responses to infection. Here we examine how food availability and key nutrients have been reported to shape innate and adaptive immunity in wildlife by drawing from field-based studies, as well as captive and food restriction studies with wildlife species. Examples of food provisioning and key nutrients enhancing immune function were seen across the three study type distinctions, as were cases of trace metals and pharmaceuticals impairing the immunity of wildlife species. More generally, food provisioning in field studies tended to increase innate and adaptive responses to certain immune challenges, whereas patterns were less clear in captive studies. Mild food restriction often enhanced, whereas severe food restriction frequently impaired immunity. However, to enable stronger conclusions we stress a need for further research, especially field studies, and highlight the importance of integrating nutritional manipulation, immune challenge, and functional outcomes. Despite current gaps in research on this topic, modern high throughput molecular approaches are increasingly feasible for wildlife studies and offer great opportunities to better understand human influences on wildlife health.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.

Copper Supplementation in Premature Infants With Parenteral Nutrition-Associated Cholestasis.

The aim of this study was to evaluate the effect of intermittent parenteral copper supplementation (IPC) on serum copper status and biochemical and hematological measures of copper toxicity and deficiency in premature infants with parenteral nutrition (PN)-associated cholestasis (PNAC). We performed a prospective nested observational study in premature infants with PNAC who received IPC after the development of PNAC. Infants with chromosomal disorders, TORCH (toxoplasmosis, parvovirus, syphilis, rubella, cytomegalovirus, herpes, human immunodeficiency virus) infection, metabolic disorder, and/or surgical abnormality of the hepatobiliary system were excluded. Serum copper concentrations were measured once every 2-4 weeks while receiving PN; 24 premature infants were studied. The mean gestational age (GA) of infants was 28.6 ± 4.7 weeks. On regression analysis, there was no significant association between IPC and serum copper concentration (coefficient 2.72, 95% CI: -27 to 32; P = .84) after controlling for GA, gender, and baseline copper intake before PNAC. There was no significant association of IPC with alanine and aspartate transaminases levels (hepatotoxicity) and platelet count, hematocrit, white blood cell count, and neutrophil count (measures of copper deficiency) after controlling for confounders. GA and postmenstrual age were independently and positively associated with serum copper concentration after controlling for confounders on regression analyses. Thus, IPC in premature infants with PNAC does not influence copper status and is not associated with biochemical and hematological measures of copper deficiency and/or toxicity. Serum copper concentration in premature infants with PNAC receiving IPC is determined by the degree of prematurity and postmenstrual age.

Selenium for preventing cancer.

BACKGROUND: This review is the third update of the Cochrane review "Selenium for preventing cancer". Selenium is a naturally occurring element with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancer. OBJECTIVES: To gather and present evidence needed to address two research questions:1. What is the aetiological relationship between selenium exposure and cancer risk in humans?2. Describe the efficacy of selenium supplementation for cancer prevention in humans. SEARCH METHODS: We updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6), as well as searches of clinical trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and longitudinal observational studies that enrolled adult participants. DATA COLLECTION AND ANALYSIS: We performed random-effects (RE) meta-analyses when two or more RCTs were available for a specific outcome. We conducted RE meta-analyses when five or more observational studies were available for a specific outcome. We assessed risk of bias in RCTs and in observational studies using Cochrane's risk assessment tool and the Newcastle-Ottawa Scale, respectively. We considered in the primary analysis data pooled from RCTs with low risk of bias. We assessed the certainty of evidence by using the GRADE approach. MAIN RESULTS: We included 83 studies in this updated review: two additional RCTs (10 in total) and a few additional trial reports for previously included studies. RCTs involved 27,232 participants allocated to either selenium supplements or placebo. For analyses of RCTs with low risk of bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95% confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high-certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80 to 1.30; 1 study, 17,444 participants). For the most frequently investigated site-specific cancers, investigators provided little evidence of any effect of selenium supplementation. Two RCTs with 19,009 participants indicated that colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69 to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2 studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2 studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1 study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2 studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14; 4 studies, 18,942 participants). Certainty of the evidence was high for all of these cancer sites, except for breast cancer, which was of moderate certainty owing to imprecision, and non-melanoma skin cancer, which we judged as moderate certainty owing to high heterogeneity. RCTs with low risk of bias suggested increased melanoma risk.Results for most outcomes were similar when we included all RCTs in the meta-analysis, regardless of risk of bias. Selenium supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to 1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to 1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers showed limited changes compared with estimates from high-quality studies alone, except for liver cancer, for which results were reversed.In the largest trial, the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks of alopecia and dermatitis, and for participants with highest background selenium status, supplementation also increased risk of high-grade prostate cancer. RCTs showed a slightly increased risk of type 2 diabetes associated with supplementation. A hypothesis generated by the Nutritional Prevention of Cancer Trial - that individuals with low blood selenium levels could reduce their risk of cancer (particularly prostate cancer) by increasing selenium intake - has not been confirmed. As RCT participants have been overwhelmingly male (88%), we could not assess the potential influence of sex or gender.We included 15 additional observational cohort studies (70 in total; over 2,360,000 participants). We found that lower cancer incidence (summary odds ratio (OR) 0.72, 95% CI 0.55 to 0.93; 7 studies, 76,239 participants) and lower cancer mortality (OR 0.76, 95% CI 0.59 to 0.97; 7 studies, 183,863 participants) were associated with the highest category of selenium exposure compared with the lowest. Cancer incidence was lower in men (OR 0.72, 95% CI 0.46 to 1.14, 4 studies, 29,365 men) than in women (OR 0.90, 95% CI 0.45 to 1.77, 2 studies, 18,244 women). Data show a decrease in risk of site-specific cancers for stomach, colorectal, lung, breast, bladder, and prostate cancers. However, these studies have major weaknesses due to study design, exposure misclassification, and potential unmeasured confounding due to lifestyle or nutritional factors covarying with selenium exposure beyond those taken into account in multi-variable analyses. In addition, no evidence of a dose-response relation between selenium status and cancer risk emerged. Certainty of evidence was very low for each outcome. Some studies suggested that genetic factors might modify the relation between selenium and cancer risk - an issue that merits further investigation. AUTHORS' CONCLUSIONS: Well-designed and well-conducted RCTs have shown no beneficial effect of selenium supplements in reducing cancer risk (high certainty of evidence). Some RCTs have raised concerns by reporting a higher incidence of high-grade prostate cancer and type 2 diabetes in participants with selenium supplementation. No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies.Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types, but null and direct relations have also been reported, and no systematic pattern suggesting dose-response relations has emerged. These studies suffer from limitations inherent to the observational design, including exposure misclassification and unmeasured confounding.Overall, there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans. However, more research is needed to assess whether selenium may modify the risk of cancer in individuals with a specific genetic background or nutritional status, and to investigate possible differential effects of various forms of selenium.

Vitamin and Mineral Supplement Use among Korean Adults: Baseline Data from the Trace Element Study of Korean Adults in Yeungnam Area.

Although dietary supplement use is believed to improve health status, the efficacy and safety of its use remains controversial. This study aimed to investigate the contribution of consumption of vitamin and mineral supplements (VMS) to the total micronutrient intake. Study participants (n = 586) were selected from the ongoing prospective cohort study of the Korean population, and baseline information on current use of dietary supplements, types of supplements, frequency of use, dosage, duration, and brand name was collected. Dietary information was assessed using a 146-item semi-quantitative food frequency questionnaire. Approximately one-fourth of the participants were categorized as VMS users. The proportion of VMS use was significantly higher in women (p = 0.02), older participants (p = 0.002), and those with a higher income level (p = 0.03) than in non-users. All vitamin and mineral intakes of both groups met the recommended nutrient intake levels by food consumption alone, except for riboflavin, calcium, and magnesium. Approximately 0.7-3.4% of the VMS users had nutrient intake levels that exceeded the tolerable upper intake levels for vitamin A, E, C, iron, and iodine. Excessive use of VMS can lead to an increased risk for adverse health effects. The results of this study provide useful baseline data for establishing guidelines for the appropriate consumption and adequate intake levels of VMS.

[Vitamins and Minerals in Oncology]. / Vitamine und Spurenelemente in der Onkologie.

The use of vitamins and minerals to prevent cancer as well as their supportive use in oncological patients is widespread and often occurs without the knowledge of the treating physician. Beyond general recommendations with regard to a balanced and healthy diet, no evidence exists supporting the use of vitamins and minerals in the prevention of cancer. Furthermore, the diet of oncological patients should contain vitamins and minerals of the same quantity as for healthy individuals. In particular, there is currently no rationale for a high-dosage administration of antioxidants.

Selenium, Vanadium, and Chromium as Micronutrients to Improve Metabolic Syndrome.

Trace metals play an important role in the proper functioning of carbohydrate and lipid metabolism. Some of the trace metals are thus essential for maintaining homeostasis, while deficiency of these trace metals can cause disorders with metabolic and physiological imbalances. This article concentrates on three trace metals (selenium, vanadium, and chromium) that may play crucial roles in controlling blood glucose concentrations possibly through their insulin-mimetic effects. For these trace metals, the level of evidence available for their health effects as supplements is weak. Thus, their potential is not fully exploited for the target of metabolic syndrome, a constellation that increases the risk for cardiovascular disease and type 2 diabetes. Given that the prevalence of metabolic syndrome is increasing throughout the world, a simpler option of interventions with food supplemented with well-studied trace metals could serve as an answer to this problem. The oxidation state and coordination chemistry play crucial roles in defining the responses to these trace metals, so further research is warranted to understand fully their metabolic and cardiovascular effects in human metabolic syndrome.

Effect of excess iodine intake on thyroid on human health.

The recommended daily intake of iodide, is 150 µg for adolescents and adults, 250 µg for pregnancy and lactation. Thyroid gland is an effective collector of iodine. The active iodine uptake along the basolateral membrane of thyroid cell is followed by its transport to the apical edge of the cell and then to the follicle lumen. TSH acts through cAMP and stimulates NIS gene expression and protein synthesis. The major proportion of iodine in the thyroid gland is bound to Thyroglobulin. The non-organic intrathyroidal iodine is usually low, but significantly greater compared to plasma. Large doses of iodine reduce both the uptake and the organification (Wolff-Chaikoff effect) and cause partial inhibition of Tg proteolysis. The thyroid gland has several protective mechanisms resulting on the maintenance of normal thyroid function despite wide fluctuations of the daily iodine intake. Ingestion of several commonly used drugs and food conservatives results in acute or chronic excessive iodine intake. Failure to escape from the iodine induced organification inhibition can cause hypothyroidism, which is temporary and subsides after iodine exposure ceases. Iodine excess may also establish a status of excessive thyroid hormone synthesis and release, thus inducing autonomic thyroid function in iodopenic areas or can contribute to the development of iodine-induced hyperthyroidism in iodine abundant areas. The anti-arrhythmic Amiodarone, is a benzofuranic product with a very high iodine content, is associated with either hypo- or hyperthyroidism development. In the presence of defective auto-protective mechanisms, excessive iodine ingestion can divert the normal thyroid function.