SELENIUM

Studies of large scale case data report that good selenium levels at diagnosis, and sustained during treatment, result in slower progression and lowered risks. Including studies of  breast, lung, esophageal, gastric and prostate and kidney cancer data, less so with colorectal, bladder and skin cancers where findings are more mixed. In emerging clinical interventions for advanced kidney cancer, the readily available L-selenomethionone supplement version at  high doses up to 4000ug has shown some very striking results. In a pilot study with relapsed patients on axitinib TKI therapy, effects included both partial and extended periods halted progression. The proposed increase in tumor uptake of oncology drugs is due to re-regulation of HIF signaling pathways which are also frequently associated with progression in breast, prostate, bladder and other cancers. These pilot trials are being expanded beyond TKI therapy to immunotherapy drug pembrolizumab.

And in advanced ovarian cancers, a phase I trial produced some similarly encouraging results with chemotherapy.(see Examples). These fascinating trials are progressing, and more evidence is needed for post-diagnostic benefit. Whilst selenium levels have not been linked to the risk of breast cancer, a meta-analysis of those studies has shown a 40% lower progression risk with higher levels following diagnosis. Others find that patients with both higher selenium and iodine levels see around 25% benefit. Lung cancer patients show depressed levels at diagnosis which can then increase during oncology treatment. And a higher recovery in serum levels is closely linked to a halved relative rate of cancer progression in localized disease. Some researchers call for interventional trials, similar to the those mentioned above in kidney and ovarian cancers.

These higher doses of 4000ug may seem less dramatic when seen as 8 to 12oz of brazil nuts. Thats said, selenium toxicity leads to range of side effects, and medical supervision is clearly essential. Its important to reach good levels of selenium both before and during oncology treatments. In metabolic health, selenium has clinical trial evidence in reducing both insulin and leptin levels, and helping reduction of systemic inflammation for instance so called c-reactive protein levels. All of which are associated with faster cancer progression rates, and indicate possible protective effect of moderate supplementation over time. Dietary sources include tofu, most oily fish and notably brazil nuts. The latter, as well as green tea extract, have shown improved blood markers in CRC patient trials.

In prevention, some recent meta-analysis shows tendencies to an overall 5-10% risk reduction with supplementation, others find no effects of either supplements or dietary sources, Overall the report findings do not recommend supplements for prevention of cancer. That said, a 2024 study of 2126 subjects over 17 years found selenium deficiency is a clear risk factor in both cancer and all cause mortality rates. Selenium deficiency is a risk (see References). Sustained higher comparative levels have even been reported as raising risks for cancer incidence in for several cancer types including skin cancer. Higher relative pre-diagnosis level can even be a risk factor in a few cases, at least one danish study shows higher levels to increased incidence of lung cancer in men, so evidence is not universally conclusive.

 

ANTI-METASTATIC ACTIONS

TYPICAL ABSORPTION LEVELS

High

EXAMPLES OF IMPROVED OUTCOMES

YES
ANALYSIS

PRE-DIAGNOSIS OR PREVENTION

YES
ANALYSIS

Highlighted Studies

..9 patients with metastatic RCC; who failed one or more prior lines of treatment; are enrolled. The first 3 patients were treated at 4000 µg, the second and third 3 patients were treated at 2500 and 3000 µg respectively… Of the 4000 µg cohort, 2 patients achieved complete remission (CR) at 18 and 20 months, 1 patient with partial response (PR) at 19 month. .. Of interest the 4000μg SLM dose yielded a plasma selenium concentration of 40-50μM which is comparable with SLM dose determ...

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Of the 3 patients found to have a deleterious mutation in either BRCA1 or BRCA2, one patient experienced a PR with an overall survival (OS) of 79 months, while two patients receiving adjuvant therapy are alive with disease at 81 and 105 months. Interestingly, seven of the nine patients in this tested group without a deleterious germline BRCA1/2 mutation experienced prolonged OS ranging from 60–120 months. Of those seven patients, three patients remain with no e...

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We also followed breast cancer patients regarding overall and breast cancer-specific mortality, comparing different Selenium quartiles….Lower overall mortality was found among women in the highest Se quartile compared to the lowest,..hazard ratio 0.63 . Similar results were seen for breast cancer-specific mortality, 0.60 . The results of our study support that [higher pre-diagnostic levels of] Se is associated with a lower mortality in breast cancer, not related to established prognosti...

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The change in selenium concentration was especially significant between t0 and t1 for the whole study group (hazard ratio [HR] = 0.5) as well as in patients with metastasized NSCLC (HR = 0.3) after adjustment. The baseline selenium value in patients with non-metastasized NSCLC was associated with overall survival (HR = 0.3). The change in selenium levels between t0 and t2 was significant in patients with metastatic lung cancer..Patients with increased serum selenium levels during ...

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TABLE OF REFERENCES

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https://pubmed.ncbi.nlm.nih.gov/39879383/4No dose limiting toxicities occurred at the 4000 μg SLM dose level. Among the 27 patients treated with 4000 μg of SLM, the overall response rate was 55.6%, median duration of response was 18.4 months, median progression-free survival was 14.8 months, and median overall survival was 19.6 months. Preliminary results have shown that plasma selenium concentrations, inhibition of TGF-β1 and stabilization of tumor vasculature by SLM are time dependent. Conclusions: SLM (4000 μg) in sequential combination with axitinib is well tolerated with encouraging efficacy.Patients were ≥18 years with histologically and radiologically confirmed advanced or metastatic ccRCC who had received at least one prior systemic therapy, which could include axitinib (last dose ≥6 months prior to enrollment). Escalating dose levels of SLM (2500, 3000 and 4000 μg) were administered orally twice daily for 14 days, then once daily concurrently with axitinib 5 mg twice daily using a 3+3 design in Phase I. Patients were treated at the 4000 μg dose level in the expansion cohort to obtain preliminary estimates of efficacy.
https://journals.sagepub.com/doi/10.1177/15347354145419634Above all, the 10-year overall survival rate in patients receiving Se supplementation, and who consequently had increased whole blood Se levels up to a mean of 90.9 µg/L (corresponding to approximately 72.1 µg/L in serum), is higher, with a borderline level of statistical significance (P = .09) compared with the control group who did not receive Se supplementation and had a mean whole blood Se level at the end of radiation therapy of 61.4 µg/L (corresponding to approximately 48.7 µg/L in serum). From these results, a positive impact of Se supplementation could also be discussed This finding may be related to a number of selective Se-mediated processes recently identified. Besides the anti-oxidative capacity in healthy tissue, an unusual selective activation of wild-type p53 by Se-dependent reduction of 2 critical cysteine residues by redox effector factor-1 might contribute to efficient activation of DNA-repair in healthy cells of the small intestinal mucosa.13-15 Furthermore, it is possible that patients with improved Se status may have benefited from a selective increase in cell death in postoperative backward tumor cells by an increase in the Se metabolism-related generation of reactive oxygen species.Screenshot from 2025-06-23 18-01-23
https://pmc.ncbi.nlm.nih.gov/articles/PMC6154492/#S233.5Twelve patients enrolled in the study were tested for germline deleterious BRCA alterations. Of the 3 patients found to have a deleterious mutation in either BRCA1 or BRCA2, one patient experienced a PR with an overall survival (OS) of 79 months, while two patients receiving adjuvant therapy are alive with disease at 81 and 105 months. Interestingly, seven of the nine patients in this tested group without a deleterious germline BRCA1/2 mutation experienced prolonged OS ranging from 60–120 months. Of those seven patients, three patients remain with no evidence of disease at 62, 69, and 114 months, while one patient is alive with disease at 120 months. Nevertheless, while these data support the conclusion that pretreatment with selenious acid followed by administration of standard chemotherapy did not negatively impact clinical outcomes, it is not possible to conclude that seleniuminduced an increase in PFS, given that the study was not powered to answer this question. However, the few cases of patients with ovarian cancer exhibiting a long-term response in this trial are noteworthy. Although this finding should be considered anecdotal, it is consistent with a similar observation made in a phase I trial of selenomethionine administered in combination with irinotecan in patients with solid tumors [17], and a phase I trial of sodium selenite in patients with advanced cancers [27].
https://link.springer.com/article/10.1007/s10654-023-01091-43.5During 17.3 years of follow-up, 2,126 study participants (30%) died. The relationship of serum SELENOP concentration with all-cause mortality was L-shaped, with mortality being significantly higher at SELENOP concentrations < 4.1 mg/L, which is near the bottom tertile’s cut-off (4.2 mg/L). All-cause mortality of participants in the bottom SELENOP tertile was significantly increased compared to subjects in the top tertile (hazard ratio [95% confidence interval]: 1.35 [1.21–1.50]). SELENOP in the bottom tertile was further associated with increased cardiovascular mortality (1.24 [1.04–1.49]), cancer mortality (1.31 [1.09–1.58]), respiratory disease mortality (2.06 [1.28–3.32]) and gastrointestinal disease mortality (2.04 [1.25–3.32]). The excess risk of all-cause mortality for those in the bottom SELENOP tertile was more than twice as strong in men as in women .In this large population-based cohort study with repeated measurements, the serum SELENOP concentration was strongly and statistically significantly associated with all-cause mortality and mortality due to CVD, cancer, respiratory diseases, and gastrointestinal diseases. The association of SELENOP concentrations with all-cause mortality was found to be a non-linear inverse association with mortality starting to increase significantly at SELENOP concentrations below 4.1 mg/L. For subjects with SELENOP concentrations < 4.2 mg/L, mortality was increased by 35%. The excess mortality was more than twice as high for men compared to women (mortality increased by 47% vs. 20%) [ but the same in cancer] and a statistically significant interaction of the SELENOP concentration with sex was determined
https://onlinelibrary.wiley.com/doi/10.1002/ijc.330313Lower overall mortality was found among women in the highest Se quartile compared to the lowest using an adjusted Cox proportional hazards model, hazard ratio 0.63 (95% confidence interval: 0.44-0.89). Similar results were seen for breast cancer-specific mortality, 0.60 (0.37-0.98). The results of our study support that Se is associated with a lower mortality in breast cancer, not related to established prognostic factors.In the present study, we found evidence of lower mortality in women who had the highest prediagnostic serum Se levels. This was seen for both breast cancer-specific and overall mortality. However, no correlation between Se status and specific breast cancer characteristics or intrinsic subtype was found, suggesting that Se might be an independent prognostic factor for mortality in breast cancer patients. Our study is the largest to date examining serum Se and breast cancer prognosisScreenshot from 2025-06-23 18-00-12
https://link.springer.com/article/10.1007/s00066-024-02276-w3The change in selenium concentration was especially significant between t0 and t1 for the whole study group (hazard ratio [HR] = 0.5, p = 0.03) as well as in patients with metastasized NSCLC (HR = 0.3, p = 0.04) after adjustment. The baseline selenium value in patients with non-metastasized NSCLC was associated with overall survival (HR = 0.3, p = 0.04). The change in selenium levels between t0 and t2 was significant in patients with metastatic lung cancer (HR = 0.1, p = 0.03). Patients with increased serum selenium levels during radiotherapy between the start of treatment (t0) and t1 had better OS In this study, we describe significant associations of relative selenium deficiency and decline in selenium status with shorter survival odds in lung cancer. A proper supply of micronutrients, such as selenium, is essential for an efficient immune response, thereby reducing the risk of cancer incidence, fast progression, and adverse therapeutic effects. So far, little information exists about serum selenium levels upon radiotherapy. This study demonstrates the prognostic value of assessing changes in serum selenium levels for the first timeScreenshot from 2025-06-23 17-58-54
https://pmc.ncbi.nlm.nih.gov/articles/PMC3467258/3In our patients, higher tumor grade and tumor stage at diagnosis correlated to lower SePP and Se concentrations. Kaplan-Meier analyses indicated that low Se status at diagnosis (SePP<2.4 mg/l, bottom tertile of patient group) was associated with a poor 5-year survival rate of 20% only. We conclude that SePP and Se concentrations are of prognostic value in RCC and may serve as additional diagnostic biomarkers identifying a Se deficit in kidney cancer patients potentially affecting therapy regimen. As poor Se status was indicative of high mortality odds, we speculate that an adjuvant Se supplementation of Se-deficient RCC patients might be beneficial in order to stabilize their selenoprotein expression hopefully prolonging their survival In our previous analyses, a tendency of increasing SePP concentrations with age was observed in healthy adult Danes [32] and Germans [26]. When analyzing our groups of NEM and RCC subjects separately, no significant correlation of SePP concentrations with age was observed. Next, we analyzed the RCC patients without control individuals stratified by their pathologic tumor characteristics. We found that lower serum concentrations of SePP were significantly associated with more aggressive cases of RCC, as indicated Screenshot from 2024-10-17 16-43-22
https://www.mdpi.com/2227-9059/12/8/17753We observed a statistically significant association of all-cause mortality when subgroups with low blood selenium levels were compared to patients with high selenium levels... this correlation was much stronger when only men were assessed ..We did not find a statistically significant association for zinc alone. When we combined selenium and zinc levels (SeQI-ZnQI vs. SeQIV-ZnQIV), we observed the hazard ratio for kidney cancer death to be 12.4.. For patients in the highest quartile of blood zinc/selenium ratio, compared to those in the lowest, the HR was 2.53... Our study suggests that selenium levels, combined selenium and zinc levels and zinc-to-selenium ratio (Zn/Se) are attractive targets for clinical trials aimed at improving the survival of kidney cancer patients.We reported that women with breast cancers and lower serum selenium levels have a worse prognosis and survival than women with higher levels despite the lack of association between serum selenium levels and tumor characteristics or treatment [17]. A similar observation was made by Sandsveden et al. They noted that lower mortality in breast cancer is associated with higher serum selenium levels and is an independent prognostic factor [28]. Several studies have been conducted showing a correlation between serum selenium levels and mortality in laryngeal, lung, prostate, kidney and pancreatic cancer. Serum selenium levels above 70 μg/L showed much better survival in patients with the aforementioned cancers Screenshot from 2025-06-23 17-57-51
https://link.springer.com/article/10.1007/s00066-024-02276-w3The change in selenium concentration was especially significant between t0 and t1 for the whole study group (hazard ratio [HR] = 0.5, p = 0.03) as well as in patients with metastasized NSCLC (HR = 0.3, p = 0.04) after adjustment. The baseline selenium value in patients with non-metastasized NSCLC was associated with overall survival (HR = 0.3, p = 0.04). The change in selenium levels between t0 and t2 was significant in patients with metastatic lung cancer (HR = 0.1, p = 0.03). Patients with increased serum selenium levels during radiotherapy between the start of treatment (t0) and t1 had better OS (HR = 0.46) Increasing selenium levels appeared to be associated with improved survival, in particular of metastatic NSCLC patients. As a result, supplementation of selenium in lung cancer patients should be discussed and respective interventional trials require consideration because patients with metastatic disease may benefit from higher selenium levels. In the future, additional independent studies are needed to assess changes in selenium status with or without adjuvant selenium supplementation in larger patient cohorts with respect to survival. This would improve the database regarding the potential importance of selenium in cancer treatment for predicting prognosis during radiotherapy and for testing the potentially beneficial effects of adjuvant supplementation with a cost-effective and safe micronutrient
https://pubmed.ncbi.nlm.nih.gov/27923410/3This is the first study to examine the potential effects of Brazil nuts and GTE alone or in combination on biomarkers related to risk for CRC. Our results suggest that supplementation of Brazil nuts or GTE might reduce risk for CRC by regulating genes associated with selenoproteins (SePP), WNT signalling (β-catenin), inflammation (NF-κB) and methylation (DNMT1), but the combination did not have additional effects on these biomarkers. These findings, combined with the excellent safety profile of the interventions and the very low cost, should encourage further investigations on these agents as potential chemopreventive agents for CRC. In a recent study, 113 men diagnosed with prostate cancer were randomised to consume six cups of brewed GTE, black tea extract or water before radical prostatectomy. The results showed that NF-κB was significantly decreased only in men consuming GTE. Moreover, thirty-two of thirty-four men taking GTE had EGCG detected in prostate tissue( Reference Henning, Wang and Said50 ). Although we did not observe a significant effect of Se on inflammation, the anti-inflammatory property of GTE appears to be consistent.
https://pubmed.ncbi.nlm.nih.gov/29376219/3Selenium 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.: 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.
https://pubmed.ncbi.nlm.nih.gov/29304040/3This study suggests that a selenium level in excess of 70 μg/L is associated with improved outcome among patients undergoing treatment for laryngeal cancer. Further studies are needed to evaluate if selenium supplementation to achieve this level might improve overall prognosis.The five-year survival after diagnosis was 82.0% (95% CI: 68% to 91%) for individuals in the highest quartile of serum selenium (> 66.8 μg/L) and was 28.6% (95% CI 19% to 42%) for individuals in the lowest quartile (<50.0 μg/L). In an age- and sex-adjusted analysis, the hazard ratio (HR) for death from all causes was 7.01 (95% CI 3.81 to 12.9) for patients in the lowest quartile of serum selenium, compared to those in the highest quartile
https://aacrjournals.org/cebp/article/11/7/630/252474/Baseline-Characteristics-and-the-Effect-of3Selenium supplementation reduced total (HR = 0.75, 95% CI = 0.58–0.97) and prostate (HR = 0.48, 95% CI = 0.28–0.80) cancer incidence but was not significantly associated with lung (HR = 0.74, 95% CI = 0.44–1.24) and colorectal (HR = 0.46, 95% CI = 0.21–1.02) cancer incidence. The effects of treatment on other site-specific cancers are also described. The protective effect of selenium was confined to males (HR = 0.67, 95% CI = 0.50–0.89) and was most pronounced in former smokersThis extended follow-up attenuated the protective effect of selenium supplementation on total cancer incidence, although selenium supplementation continued to reduce the incidence of total cancer over a mean follow-up of more than 7 years. A significant inverse association with the most common cancer, prostate cancer, was observed. For the next most common sites, lung and colorectal cancers, respectively, inverse but nonsignificant associations with selenium supplementation and incidence were determined. These results are consistent with the majority of epidemiological studies that support the efficacy of selenium as a chemopreventive agent against all cancers
https://pmc.ncbi.nlm.nih.gov/articles/PMC4946347/3Particularly intriguing is our finding that high Cu levels appear to be associated with PaCa. This finding, which is inversely related to Se levels, suggests that high Cu:Se ratios may result in higher levels of ROS that impact on the risk of developing and/or progression of PaCa. Cu is associated with ROS production [23] and Se, as a selenoprotein, acts to mitigate the effects of excessive ROS. Given that the Cu:Se was consistently greater in PaCa patients compared to age-matched control subjects suggests that the Cu:Se may be associated with high levels of ROS exposure that predispose susceptible patients to the development and/or progression of disease.Therefore, it cannot be excluded that the level of Se may be a prognostic marker in PaCa. The level of Se was far from optimal among the PaCa patients we examined, however, a longer survival time was observed even in patients whose levels of Se showed higher values. This observation must be verified in a larger series of PaCa cases, but if related to the results of prospective studies, it is not surprising. Data from meta-analysis of 49 prospective studies have also confirmed a reduction in cancer mortality by 45% in persons with an optimized Se concentration [11]. In our retrospective study, we observed that PaCa prolonged survival only in patients with higher levels of Se, but this observation is part of an overall favorable view of the importance of Se in the prevention of cancer in general
https://eprints.lums.ac.ir/1909/1/1-s2.0-S2451847620300026-main.pdf3..meta-analysis showed a non-significant reducing effect of selenium supplementation on serum CRP levels (WMD: −0.31 mg/l; 95% CI: −0.63, 0.01; P = 0.06). The results of subgroup analysis showed that selenium supplementation could only decrease significantly serum CRP levels, when the dosage of selenium supplementation is 200 μg/day (WMD: −0.52 mg/l; 95% CI = −1.04, −0.01; P = 0.043), when the trial duration is > 8 weeks (WMD: −1.01 mg/l; 95% CI = −1.88, −0.15; P = 0.021), and when the baseline level of CRP is > 3 mg/l (WMD: −2.02 mg/l; 95% CI = −2.87, −1.18; P < 0.001). Conclusion: In conclusion, results of this meta-analysis study showed that selenium supplementation can reduce significantly serum CRP level especially in patients with elevated CRP levels.The Results showed a non-significant decreasing effect of selenium supplementation on serum CRP level. Because of the existence of significant heterogeneity between studies, sub-group analysis was performed. The results showed that when the baseline level of CRP is > 3 mg/l, selenium supplementation can reduce CRP levels around 2 mg/l. This finding is in accordance with the results of other metaanalysis studies which showed that vitamin E or alpha-lipoic acid supplementation could affect significantly serum CRP levels only in patients with serum CRP > 3 mg/l (Saboori et al., 2015, 2018). Serum CRP level greater than 3 mg/l is associated with a substantial 58% increased risk of coronary heart diseases
https://link.springer.com/article/10.1007/s10549-017-4525-93This study suggests that a selenium level in excess of 64.4 µg//L might be beneficial for women undergoing treatment for breast cancer and that selenium supplementation to achieve this level may favorably impact the outcome. Further studies are needed to confirm this association and to evaluate the impact of selenium supplementation on breast cancer survival among women with low post-diagnostic selenium levels.The 5-year overall actuarial survival was 68.1% for women in the lowest ( 81.0 µg/L) quartile of serum selenium. In an adjusted analysis, the hazard ratio for death was 2.49 (95%CI 1.53–4.04; P = 0.0002) for patients in the lowest quartile of serum selenium, compared to those in all other quartiles. The effect of low selenium on breast cancer-specific mortality was stronger for women who were past smokers
https://publications.ersnet.org/content/erj/39/6/14433Overall, no association was found between baseline levels of serum selenium and subsequent risk of lung cancer mortality during a 16-yr follow-up and our hypothesis was not supported by the data presented. However, we found a statistically increased risk of lung cancer mortality among heavy smokers (those with cotinine levels above the mean among smokers) with high serum selenium. The finding of no association between serum levels and lung cancer in the whole cohort is in accordance with the results of nested case–control studies Taking into account pack-years of smoking, spirits intake, dietary markers (salt and fat preferences) and health measures (chronic bronchitis and peak flow), referencing the lowest level of serum selenium, HRs were 1.17 (95% CI 0.79-1.75) and 1.43 (95% CI 0.96-2.14), for medium and high levels respectively. Among heavy smokers, a high serum selenium concentration was associated with a significantly increased risk of lung cancer mortality after taking into account all potential confounders. The hypothesis that low serum selenium is an independent risk factor for lung cancer was not supported.
https://www.mdpi.com/2072-6643/14/22/49333The results suggested that selenium supplementation significantly reduced serum insulin levels (standardized men difference [SMD]: −0.53; 95% confidence interval [CI] [−0.84, −0.21], p = 0.001, I2 = 68%) and HOMA-IR (SMD: −0.50, 95% CI [−0.86, −0.14], p = 0.006, I2 = 75%) and increased high-density lipoprotein cholesterol (HDL-C) levels (SMD: 0.97; 95% CI [0.26, 1.68], p = 0.007, I2 = 92%), but had no significant effect on FPG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C). Conclusion: Current evidence supports the beneficial effects of selenium supplementation on reducing insulin levels, HOMA-IR, and increasing HDL-C levels. Selenium supplementation may be an effective strategy for reducing insulin resistanceHOMA-IR is often used in investigating and quantifying insulin resistance because of the simplicity of the underlying mathematical model (HOMA-IR = fasting glucose [mg] × fasting insulin [mu/L]/22.5) [68]. Furthermore, HbA1c is an essential marker of long-term glycemic control that reflects a cumulative glycemic level over the past two to three months [69]. Therefore, insulin levels, HOMA-IR, FPG and HbA1c were used to evaluate the selenium supplementation on glycemic control. In this study, comprehensive pooled results from 10 RCTs involving 526 patients supported the favorable effects of selenium supplementation in decreasing serum insulin levels and HOMA-IR. Moreover, selenium supplementation may increase HDL-C levels, but the effectiveness of selenium supplementation on FPG, TC, TG, LDL-C, and VLDL-C levels was unclear.
https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1263853/full3In this review, we found that proper selenium intake, especially supplementary selenium, has a protective effect against multiple diseases. Selenium consumption in adults may reduce the risk of several digestive system cancers (including gastrointestinal, liver, and pancreatic cancers), all-cause mortality, depression, and Keshan disease in children, which in turn reduces the risk of Kashin-Beck disease. Furthermore, selenium supplementation improves sperm quality, PCOS, ATID, CHD, and infective outcomes.Based on our study findings and owing to the adverse effects and limited advantages of selenium intake, it is not recommended to receive extra supplementary selenium for general populations, and selenium supplementation should not be continued in patients whose selenium-deficient status has been corrected. Moreover, specific optimal dosage of selenium intake for general populations is still hard to determined due to the various between different areas
https://pmc.ncbi.nlm.nih.gov/articles/PMC7275228/3Leptin resistance is a common characteristic of diet-induced obesity, in which anorectic responses to leptin are lower, and hyperleptinemia is a typical finding [4]. The mechanism that leads to leptin resistance is still unclear. Multiple factors, including inflammatory processes and oxidative stress and type of diet, may play a part. Se supplementation could therefore exert beneficial effects not only in reducing peripheral and central leptin resistance (through its antioxidant activity, by increasing selenoproteins activity, and by interacting with inflammatory biomarkers), but also may be via a direct effect on adipose tissue A comparison of the two groups showed a significant change in body composition, involving a decrease in body fat mass, between the baseline and the end of the follow-up, in the intervention group. Unlike the placebo group, the group given Se had a significant increase in lean body and muscle mass and a significant decrease in leptin levels after 3 months on diet. At the end of the follow-up, the group given Se scored higher on the PGWBI than those who did not.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/4140002.5 The mean serum selenium level was 125.6 ng/mL. The multivariate adjusted hazard ratios comparing the highest (≥ 130.39 ng/mL) with the lowest (< 117.31 ng/mL) serum selenium level tertile were 0.83 (95% confidence interval [CI], 0.72-0.96) for all-cause mortality, 0.69 (95% CI, 0.53-0.90) for cancer mortality, and 0.94 (95% CI, 0.77-1.16) for cardiovascular mortality. However, based on spline regression models, the association between serum selenium levels and all-cause and cancer mortality was nonlinear, with an inverse association at low selenium levels ( 150 ng/mL). There was no association between serum selenium levels and cardiovascular mortality.The strongest support for the hypothesis that selenium may prevent cancer comes from the NPC trial. In that trial, selenium supplementation reduced the incidence of several secondary cancer end points, including total cancer (HR, 0.75; 95% CI, 0.58-0.97), prostate cancer (HR, 0.48; 95% CI, 0.28-0.80), lung cancer (HR, 0.74; 95% CI, 0.44-1.24), and colorectal cancer (HR, 0.46; 95% CI, 0.21-1.02).26 Consistent with a nonlinear effect of selenium on cancer end points, the NPC trial found that the protective effect of selenium supplements on cancer incidence was restricted to participants with baseline plasma selenium levels of less than 121.6 ng/mL, whereas selenium supplements induced a small, statistically insignificant increase in cancer incidence among participants with higher baseline selenium levels.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5819884/2.5The results show that a 6-week intervention with Brazil nuts or GTE alone affected gene expressions associated with selenoproteins, WNT signalling, inflammation and DNA methylation. However, the combination of Brazil nuts and GTE did not appear to have any additional effect compared with either of these agents alone. Our findings indicate that supplementation of Se or green tea may play a role in reducing the risk for CRC through regulation of these biomarkers, but that there were no obvious synergistic interactions.Expression of DNMT1 mRNA was significantly reduced from baseline by 30 and 35 %, respectively, in subjects consuming GTE or the combination of Brazil nuts and GTE, P<0·05. NF-κB mRNA was also significantly reduced from baseline by 44 and 46 %, respectively, in these two groups, P<0·05, but DNMT1 and NF-κB were unchanged in subjects consuming Brazil nuts. Significantly reduced expression of β-catenin was also observed in subjects consuming Brazil nuts or consuming the combination of Brazil nuts and GTE; the reduction in these two group was 28 and 40 %, respectively, P<0·05, but no significant change in β-catenin was found in subjects consuming GTE
https://ro-journal.biomedcentral.com/articles/10.1186/1748-717X-9-1252.5The results of our summary suggest that seleniumsupplementation in the form of sodium selenite at dosesranging from 200–500 μg daily by oral administration mayoffer benefits for head and neck cancer; head and neckcancer with lymphedema; and oral, cervical and uterinecancer patients who undergo radiotherapy and have low selenium levelsSelenium supplementation improved the general conditions of the patients, improved their quality of life and reduced the side effects of radiotherapy. At the dose of selenium used in these studies (200-500 mug/day), selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported. Selenium supplementation may offer specific benefits for several types of cancer patients who undergo radiotherapy. Because high-dose selenium and long-term supplementation may be unsafe due to selenium toxicity, more evidence-based information and additional research are needed to ensure the therapeutic benefits of seleniu
https://www.researchgate.net/publication/366894425_Druggable_Biomarkers_Altered_in_Clear_Cell_Renal_Cell_Carcinoma_Strategy_for_the_Development_of_Mechanism-Based_Combination_Therapy2It was demonstrated that HIFS, miRS, Nrf2, and TGF-ß are targeted by a defined dose and schedule of a specific type of selenium-containing molecules, seleno-L-methionine (SLM) and methylselenocystein (MSC). Collectively, the demonstrated pleiotropic effects of selenium were associated with the normalization of tumor vasculature, and enhanced drug delivery and distribution to tumor tissue, resulting in enhanced efficacy of multiple chemotherapeutic drugs and biologically targeted molecules. Higher selenium doses than those used in clinical prevention trials inhibit multiple targets altered in ccRCC tumors, which could offer the potential for the development of a new and novel therapeutic modality for cancer patients with similar selenium target expression. Better understanding of the underlying mechanisms of selenium modulation of specific targets altered in ccRCC could potentially have a significant impact on the development of a more efficacious and selective mechanism-based combination for the treatment of patients with cancer.Recent research investigating the potential role of the nutritional status of patients infected with COVID-19 indicated that these patients are selenium-deficient, and that the selenium level is a factor associated with the severity of infection and morbidity [139,140]. In addition, with the knowledge that selenium targets immune response biomarkers, along with the data that we generated confirming that TGF-β is a selenium target by selenium concentrations that can be achieved clinically without host toxicity, as well as reports that TGF-β is overexpressed in patients with COVID-19 [88,141,142], sufficient evidence is available to evaluate the potential role of a defined selenium type and dose in the treatment of patients with COVID-19. Selenium supplementation alone and in combination with other treatments under evolution may reduce the onset of infection and may also reduce the severity of infection and morbidity.
https://pubs.rsc.org/en/content/articlelanding/2022/ra/d2ra01882a2.5The results of the study indicated that Se-axitinib had potent antitumor activity on renal cell carcinoma (RCC), alleviated vascular hyperpermeability, and also alleviated axitinib-related side effects including hypertension, liver dysfunction and kidney dysfunction significantly. Therefore, we suggest that Se-axitinib could be a solution to the severe side effects of VEGFR inhibitors and provide evidence to improve the outcome of RCC treatment.In conclusion, selenium substituted axitinib reduced the side effect of axitinib, especially blood pressure increasing effect possibly owing to its antioxidant and cardiovascular protective effect. And Se-axitinib displayed weight increasing effect and protective effect on hepatorenal dysfunctions. More importantly, selenium substitute of axitinib maintained the potent anticancer activity of the original drug axitinib, which means Se-axitinib is a novel anticancer agent with lower side effect.
https://www.mdpi.com/2072-6694/17/5/8393.5We conclude that HER2-positive and TNBC breast cancer patients with a selenium blood level above 107.19 μg/L before starting NAC have a higher pCR rate than patients with selenium levels below 94.29 μg/L. The association is particularly strong for the triple-negative subtype....Finally, our results suggest there may be a potential benefit for selenium supplementation in breast cancer patients with low selenium levels for whom NAC is planned. So far, selenium supplementation has been tested in a small study in a group of patients with cervical cancer undergoing chemoradiotherapy. In that study, selenium supplementation reduced the incidence of hematological side effects [65]. There are currently no clinical trials on selenium supplementation in patients with breast cancer receiving NAC. Testing this hypothesis in breast cancer patients requires planning interventional studies with random selection in subgroups. Due to the observational nature of our study, the data obtained should be confirmed in a prospective observation.In this study of breast cancer patientsundergoing neoadjuvant chemotherapy, we observed a significantly higher pCR rate in the group of patients with the highest selenium level compared to the group with the lowest level (OR = 2.75; p = 0.001). In the group with the highest selenium level, the pCR rate was 59.0%, and in the subgroup with the lowest level, it was 39.0% (p = 0.003). The association was much stronger for those with triple-negative cancer (OR = 6.70 (95% OR 2.18–20.56, p = 0.001)) than for those with HER2-positive cancer (OR = 1.65 (95% OR 0.70–3.88, p = 0.25)). To our knowledge, this is the first study to demonstrate an association between selenium levels in whole blood and pCR after neoadjuvant chemotherapy.

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