PMID 19066370 Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) RCT · JAMA, 2009 35,533-man randomized trial - selenium at 200 μg/day did not prevent prostate cancer (HR 1.04), with a type 2 diabetes signal in the selenium arm (RR 1.07).
Key summary
The primary report of SELECT, a large double-blind trial that randomized 35,533 men in the US, Canada, and Puerto Rico to selenium, vitamin E, the combination, or placeboAn inert dummy treatment used as the comparison baseline.. Over a median 5.46 years, selenium alone (HR 1.04), vitamin E alone (HR 1.13), and the combination (HR 1.05) all failed to significantly reduce prostate cancer versus placebo, with no differences in other prespecified cancers. Statistically nonsignificant increases were seen for prostate cancer in the vitamin E arm (P=.06) and type 2 diabetes in the selenium arm (RR 1.07). The conclusion was that at these doses and formulations neither selenium nor vitamin E prevents prostate cancer.
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CONTEXT: Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer. OBJECTIVE: To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer. INTERVENTIONS: Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer. RESULTS: As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group. CONCLUSION: Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 21990298 Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) RCT · JAMA, 2011 SELECT long-term follow-up - selenium still did not reduce prostate cancer (HR 1.09), and vitamin E raised the risk by 17% (HR 1.17, P=.008).
Key summary
The long-term follow-up of SELECT, adding 54,464 person-years and 521 prostate cancers since the initial report. Versus placeboAn inert dummy treatment used as the comparison baseline., the vitamin E arm had a significant 17% higher prostate cancer risk (HR 1.17, P=.008), while selenium (HR 1.09, P=.18) and the combination (HR 1.05, P=.46) were not significant. Absolute risk rose by 1.6 per 1000 person-years for vitamin E and 0.8 for selenium. The conclusion that vitamin E supplementation significantly increased prostate cancer risk in healthy men became a landmark rebuttal to the assumption that antioxidant supplements are harmless.
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CONTEXT: The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. OBJECTIVE: To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011. INTERVENTIONS: Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer incidence. RESULTS: This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination. CONCLUSION: Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 17620655 Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial RCT · Ann Intern Med, 2007 1,202 people in a selenium-rich area over 7.7 years - selenium at 200 μg/day did not prevent diabetes and instead raised risk (HR 1.55).
Key summary
A secondary analysis of the randomized, double-blind, placeboAn inert dummy treatment used as the comparison baseline.-controlled NPC trial conducted in a selenium-rich region of the eastern United States. Among 1,202 people without diabetes at baseline followed for an average of 7.7 years, type 2 diabetes occurred more often in the selenium 200 μg/day arm (12.6 vs 8.4 cases per 1000 person-years, HR 1.55). There was no benefit across strata of age, sex, BMI, or smoking, and risk was greater in the highest tertile of baseline blood selenium (HR 2.70). The conclusion is that selenium supplementation does not appear to prevent type 2 diabetes and may increase its risk.
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BACKGROUND: Findings from animal models suggest that selenium supplementation improves glucose metabolism. OBJECTIVE: To examine the effect of long-term selenium supplementation on the incidence of type 2 diabetes. DESIGN: Secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Areas of low selenium consumption of the eastern United States. PATIENTS: 1202 persons seen in dermatology clinics who did not have type 2 diabetes at baseline. INTERVENTION: Oral administration of selenium, 200 microg/d, or placebo. MEASUREMENTS: Incidence of type 2 diabetes. RESULTS: During an average follow-up of 7.7 years (SD, 2.7), type 2 diabetes developed in 58 selenium recipients and 39 placebo recipients (incidence, 12.6 cases per 1000 person-years vs. 8.4 cases per 1000 person-years, respectively; hazard ratio, 1.55 [95% CI, 1.03 to 2.33]). The lack of benefit of selenium supplementation on the incidence of type 2 diabetes persisted in analyses stratified by age, sex, body mass index, and smoking status. An exposure-response gradient was found across tertiles of baseline plasma selenium level, with a statistically significantly increased risk for type 2 diabetes in the highest tertile of baseline plasma selenium level (hazard ratio, 2.70 [CI, 1.30 to 5.61]). LIMITATIONS: Diabetes was a secondary outcome in the parent trial. Diagnoses of diabetes were self-reported but were validated in most participants. The sample was mostly older and white. CONCLUSIONS: Selenium supplementation does not seem to prevent type 2 diabetes, and it may increase risk for the disease. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 24683040 Selenium for preventing cancer Meta-analysis (Cochrane) · Cochrane Database Syst Rev, 2014 55 observational studies and 8 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s pooled - in randomized trials selenium reduced no cancer (RR 0.90); 'no convincing evidence' for cancer prevention.
Key summary
A CochraneAn international network that rigorously reviews and synthesizes evidence. review of selenium and cancer. In 55 observational studies (over 1.1 million people) higher selenium looked tied to less cancer incidence and mortality (OR 0.69 and 0.60), but design, quality, and heterogeneity meant this could not be read as causal. In 8 randomized trials (44,743 people), by contrast, selenium supplementation significantly reduced no cancer (RR 0.90), and had no effect on prostate cancer among low-risk-of-bias trials (RR 1.02). Non-melanoma skin cancer risk rose, and the NPC and SELECT trials suggested higher risk of type 2 diabetes, alopecia, and dermatitis. The authors conclude that to date there is no convincing evidence that selenium supplements prevent cancer in humans.
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BACKGROUND: This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES: Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans? SEARCH METHODS: We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004. SELECTION CRITERIA: We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older). DATA COLLECTION AND ANALYSIS: For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs. MAIN RESULTS: We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed. AUTHORS' CONCLUSIONS: Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 37513612 The Effects of Selenium Supplementation in the Treatment of Autoimmune Thyroiditis: An Overview of Systematic Reviews Overview of systematic reviews · Nutrients, 2023 6 systematic reviews, 75 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s pooled - selenium lowered TPO antibodies at 3 and 6 months but at very low certainty, and the difference vanished by 12 months.
Key summary
An overview pooling systematic reviews (6 reviews, 75 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s) of selenium in autoimmune (Hashimoto's) thyroiditis. In people also taking levothyroxine, selenium significantly lowered TPO antibodies at 3 months (SMD -0.53) and 6 months (SMD -1.95), but at very low certainty. In those not on levothyroxine, TPO and Tg antibodies fell at 3 and 6 months and then showed no difference at 12 months. Adverse effects did not differ significantly from controls. The conclusion is that a short-term antibody reduction is possible but at low certainty, and whether antibody levels translate into clinical benefit is beyond this analysis.
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OBJECTIVE: The available evidence on selenium supplementation in the treatment of autoimmune thyroiditis (AIT) was inconclusive. This research serves to assess the effects of selenium supplementation in the treatment of AIT. METHODS: Online databases including PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to 10 June 2022. The AMSTAR-2 tool was used to assess the methodological quality of included studies. The information on the randomized controlled trials of the included studies was extracted and synthesized. The GRADE system was used to assess the certainty of evidence. RESULTS: A total of 6 systematic reviews with 75 RCTs were included. Only one study was rated as high quality. The meta-analysis showed that in the levothyroxine (LT4)-treated population, thyroid peroxidase antibody (TPO-Ab) levels decreased significantly in the selenium group at 3 months (SMD = -0.53, 95% CI: [-0.89, -0.17], p < 0.05, very low certainty) and 6 months (SMD = -1.95, 95% CI: [-3.17, -0.74], p < 0.05, very low certainty) and that thyroglobulin antibody (Tg-Ab) levels were not decreased. In the non-LT4-treated population, TPO-Ab levels decreased significantly in the selenium group at 3 and 6 months and did not decrease at 12 months. Tg-Ab levels decreased significantly in the selenium group at 3 and 6 months and did not decrease at 12 months. The adverse effects reported in the selenium group were not significantly different from those in the control group, and the certainty of evidence was low. CONCLUSION: Although selenium supplementation might reduce TPO-Ab levels at 3 and 6 months and Tg-Ab levels at 3 and 6 months in the non-LT4-treated population, this was based on a low certainty of evidence. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 25068883 Biomonitoring Equivalents for selenium Review · Regul Toxicol Pharmacol, 2014 Selenium has a narrow gap between essentiality and toxicity - too little causes Keshan disease, too much causes selenosis (brittle nails and hair, GI upset).
Key summary
A review summarizing selenium's nutritional and toxicological properties and safety benchmarks. Selenium is an essential nutrient but has a narrow gap between adequacy and toxicity. Too little intake shows up most notably as Keshan disease, an endemic cardiomyopathy in children, while excess intake causes selenosis, with brittle nails and hair and gastrointestinal upset. Agencies therefore set guidance values against both deficiency and excess, and this paper proposes Biomonitoring Equivalents in blood, plasma, and urine (values matched to adequate intake and to protection against selenosis).
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Selenium is an essential nutrient for human health with a narrow range between essentiality and toxicity. Selenium is incorporated into several proteins that perform important functions in the body. With insufficient selenium intake, the most notable effect is Keshan disease, an endemic cardiomyopathy in children. Conversely, excessive selenium intake can result in selenosis, manifested as brittle nails and hair and gastro-intestinal disorders. As such, guidance values have been established to protect against both insufficient and excessive selenium exposures. Dietary Reference Intakes (DRIs) have been established as standard reference values for nutritional adequacy in North America. To protect against selenosis resulting from exposure to excessive amounts of selenium, several government and non-governmental agencies have established a range of guidance values. Exposure to selenium is primarily through the diet, but monitoring selenium intake is difficult. Biomonitoring is a useful means of assessing and monitoring selenium status for both insufficient and excessive exposures. However, to be able to interpret selenium biomonitoring data, levels associated with both DRIs and toxicity guidance values are required. Biomonitoring Equivalents (BEs) were developed for selenium in whole blood, plasma and urine. The BEs associated with assuring adequate selenium intake (Estimated Average Requirements - EAR) are 100, 80 and 10μg/L in whole blood, plasma and urine, respectively. The BEs associated with protection against selenosis range from 400 to 480μg/L in whole blood, 180-230μg/L in plasma, and 90-110μg/L in urine. These BE values can be used by both regulatory agencies and public health officials to interpret selenium biomonitoring data in a health risk context. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ PMID 36480969 Micronutrient Supplementation to Reduce Cardiovascular Risk Meta-analysis · J Am Coll Cardiol, 2022 884 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s, 883,627 people pooled - selenium had no effect on cardiovascular disease or type 2 diabetes risk (while beta carotene raised mortality).
Key summary
A large systematic review and meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. quantifying the cardiovascular impact of 27 micronutrients (884 RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.s, over 883,000 people). Some, such as omega-3, folic acid, and coenzyme Q10, had moderate- to high-quality evidence for lowering cardiovascular risk factors, whereas vitamins C, D, and E and selenium showed no effect on cardiovascular disease or type 2 diabetes risk. Beta carotene instead raised all-cause mortality, cardiovascular mortality, and stroke risk. In other words, this large synthesis also found no basis for taking selenium for heart health or antioxidant purposes.
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BACKGROUND: Healthy dietary patterns are rich in micronutrients, but their influence on cardiovascular disease (CVD) risks has not been systematically quantified. OBJECTIVES: The goal of this study was to provide a comprehensive and most up-to-date evidence-based map that systematically quantifies the impact of micronutrients on CVD outcomes. METHODS: This study comprised a systematic review and meta-analysis of randomized controlled intervention trials of micronutrients on CVD risk factors and clinical events. RESULTS: A total of 884 randomized controlled intervention trials evaluating 27 types of micronutrients among 883,627 participants (4,895,544 person-years) were identified. Supplementation with n-3 fatty acid, n-6 fatty acid, l-arginine, l-citrulline, folic acid, vitamin D, magnesium, zinc, α-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin showed moderate- to high-quality evidence for reducing CVD risk factors. Specifically, n-3 fatty acid supplementation decreased CVD mortality (relative risk [RR]: 0.93; 95% CI: 0.88-0.97), myocardial infarction (RR: 0.85; 95% CI: 0.78-0.92), and coronary heart disease events (RR: 0.86; 95% CI: 0.80-0.93). Folic acid supplementation decreased stroke risk (RR: 0.84; 95% CI: 0.72-0.97), and coenzyme Q10 supplementation decreased all-cause mortality events (RR: 0.68; 95% CI: 0.49-0.94). Vitamin C, vitamin D, vitamin E, and selenium showed no effect on CVD or type 2 diabetes risk. β-carotene supplementation increased all-cause mortality (RR: 1.10; 95% CI: 1.05-1.15), CVD mortality events (RR: 1.12; 95% CI: 1.06-1.18), and stroke risk (RR: 1.09; 95% CI: 1.01-1.17). CONCLUSIONS: Supplementation of some but not all micronutrients may benefit cardiometabolic health. This study highlights the importance of micronutrient diversity and the balance of benefits and risks to promote and maintain cardiovascular health in diverse populations. (Antioxidant Supplementation in the Prevention and Treatment of Cardiovascular Diseases; CRD42022315165). ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.
View original ↗ USDA FoodData Central Nuts, brazilnuts, dried, unblanched (FDC 170569)
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View original ↗ USDA FoodData Central Fish, tuna, yellowfin, fresh, cooked, dry heat (FDC 172006)
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View original ↗ USDA FoodData Central Fish, sardine, Atlantic, canned in oil, drained solids with bone (FDC 175139)
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View original ↗ USDA FoodData Central Seeds, sunflower seed kernels, dried (FDC 170562)
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View original ↗ USDA FoodData Central Egg, whole, cooked, hard-boiled (FDC 173424)
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