Nutritional Deficiencies - Health Concerns

Selenium - updated: 17 November 2008

The argument for increasing selenium intake

Proc Nutr Soc. 2002 May;61(2):203-15

Rayman MP, Rayman MP.

The essential trace mineral, Se, is of fundamental importance to human health. As a constituent of selenoproteins it plays both structural and enzymic roles, in the latter context being best known as an antioxidant and catalyst for the production of active thyroid hormone. While Se-deficiency diseases have been recognised for some time, evidence is mounting that less-overt deficiency can also cause adverse health effects and furthermore, that supra-nutritional levels of Se may give additional protection from disease. In the context of these effects, low or diminishing Se status in some parts of the world, notably in some European countries such as the UK, is giving cause for concern. While deficiency has an adverse effect on immunocompetence, Se supplementation appears to enhance the immune response. Se appears to be a key nutrient in counteracting certain viral infections; thus, in a Se-deficient host the benign coxsackie virus becomes virulent, causing heart damage, the influenza virus causes more serious lung pathology and HIV infection progresses more rapidly to AIDS. Long recognised as essential for successful animal reproduction, Se is required for human sperm maturation and sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking Se to cardiovascular disease risk, although other conditions involving oxidative stress and inflammation have shown some association with Se status. There is growing evidence that higher Se intakes are associated with reduced cancer risk. While persuasive evidence already exists to suggest that additional Se would be beneficial in some health conditions, results from intervention trials underway or planned have the potential to reinforce or refute the argument for increasing Se intake

Publication Types:

• Review

The importance of selenium to human health

Lancet. 2000 Jul 15;356(9225):233-41

Rayman MP.

The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.

Publication Types:

• Review

The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases

Can J Diet Pract Res. 2005 Summer;66(2):98-102

Ryan-Harshman M, Aldoori W.

Selenium is an essential trace element involved in several key metabolic activities via selenoproteins, enzymes that are essential to protect against oxidative damage and to regulate immune function. Selenium also may have other health benefits unrelated to its enzymatic functions. It may provide important health benefits to people whose oxidative stress loads are high, such as those with inflammatory or infectious diseases like rheumatoid arthritis or human immunodeficiency virus/acquired immunodeficiency syndrome, or who are at high risk for cancers, particularly prostate cancer. Some studies have generated compelling evidence that selenium is beneficial, either alone or in conjunction with other micronutrients. Additional data from large clinical trials that provide the highest level of evidence will be key to determining the benefits accrued at various selenium intake levels. When the strength of the evidence becomes sufficient, clinical health professionals will need to use dietary and clinical assessment methods to ensure that people at increased risk for cancer or inflammatory and infectious diseases can be appropriately advised about selenium intake.

Publication Types:

• Review

Selenium supplementation for asthma

Cochrane Database Syst Rev. 2004;(2):CD003538

Allam MF, Lucane RA.

BACKGROUND: Selenium deficiency may be important in chronic asthma. Observational studies have demonstrated that patients with chronic asthma may have lower levels of selenium than their control. Nevertheless, selenium supplementation has not been recommended with drug therapy for asthma. This review systematically examines RCTs that evaluated the role of selenium supplementation in chronic asthma. OBJECTIVES: Recognition that chronic asthma can be associated with selenium deficiency has led to the investigation of the role of selenium supplementation in reducing the symptoms and impact of chronic asthma. The objective of this review was to assess the efficacy of selenium supplementation as an adjunct to medication for the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register, MEDLINE/PUB MED, and EMBASE. Searches were current as of August 2003. SELECTION CRITERIA: Randomised trials comparing patients with chronic asthma receiving selenium supplementation in conjunction with asthma medication, with patients taking asthma medication only. DATA COLLECTION AND ANALYSIS: Two reviewers applied the study inclusion criteria MAIN RESULTS: One trial with a total of 24 patients suffering from chronic asthma was included. The study reported significant clinical improvement in the selenium-supplemented group, as compared with the placebo group, in terms of a 'clinical evaluation'. However, this improvement could not be validated by significant changes in separate objective parameters of lung function and airway hyper-responsiveness. REVIEWERS' CONCLUSIONS: There is some indication that selenium supplementation may be a useful adjunct to medication for patients with chronic asthma. This conclusion is limited because of insufficient studies and lack of improvement in the clinical parameters of lung function.

Publication Types:

• Review

Intake of selenium in the prevention of prostate cancer: a systematic review and meta-analysis

Cancer Causes Control. 2005 Nov;16(9):1125-31

Etminan M, FitzGerald JM, Gleave M, Chambers K.

BACKGROUND: Recent studies have suggested that selenium intake may prevent the risk of developing prostate cancer. Results from some of these studies have given conflicting results. Because of these discrepant results we sought to explore the association between selenium intake and prostate cancer by conducting a systematic review and meta-analysis of the literature. METHODS: We systematically searched MEDLINE, EMBASE and Cochrane Library between 1966 and May 2005 for articles that examined the association between intake of selenium and the risk of prostate cancer. We abstracted the data from relevant studies. A random effects model was used to estimate pooled relative risks for both cohort and case-control studies. Heterogeneity was assessed graphically using a Funnel Plot. RESULTS: Sixteen studies (eleven cohort studies and five case-control studies) were included in the final analysis. The pooled relative risk of prostate cancer for any intake of selenium was 0.72 (0.61-0.84) for cohort studies and 0.74 (0.61-1.39) for case-control studies. The pooled relative risk of moderate intake was 0.74 (0.61-0.90) for cohort studies and 0.74 (0.39-1.39) for case-control studies. A dose-response trend was observed when we stratified the studies by disease severity. CONCLUSION: The results of our systematic review suggest that selenium intake may reduce the risk of prostate cancer. The results confirm the need for large randomized controlled trials, which are ongoing, to answer this question.

Publication Types:

• Review

A prospective cohort study on selenium status and the risk of lung cancer

Cancer Res. 1993 Oct 15;53(20):4860-5

van den Brandt PA, Goldbohm RA, van 't Veer P, Bode P, Dorant E, Hermus RJ, Sturmans F.

Selenium has been suggested to be anticarcinogenic and to play a role in the cellular defense against oxidative stress. The association between toenail selenium (a marker of long-term selenium status) and lung cancer was investigated in a cohort study of diet and cancer that started in 1986 among 120,852 Dutch men and women aged 55-69 years. After 3.3 years of follow-up, 550 incident cases of lung carcinoma were detected. Toenail selenium data were available for 370 lung cancer cases and 2459 members of a randomly selected subcohort. The rate ratio of lung cancer for subjects in the highest compared to the lowest quintile of toenail selenium, after controlling for age, gender, smoking, and education, was 0.50 (95% confidence interval, 0.30-0.81), with a significant inverse trend across quintiles (P = 0.006). The protective effect of selenium was concentrated in subjects with a relatively low dietary intake of beta-carotene or vitamin C. The rate ratio in the highest compared to the lowest quintile of selenium was 0.45 in the low beta-carotene group (95% confidence interval, 0.22-0.92; trend P = 0.028) and 0.36 in the low vitamin C group (95% confidence interval, 0.17-0.75; trend P < 0.001). The results of this study support an inverse association between selenium status and lung cancer and suggest a modification of the effect of selenium by the antioxidants beta-carotene and vitamin C.

Publication Types:

• Cohort study among 120,852 Dutch men and women

A prospective cohort study on toenail selenium levels and risk of gastrointestinal cancer

J Natl Cancer Inst. 1993 Feb 3;85(3):224-9

van den Brandt PA, Goldbohm RA, van 't Veer P, Bode P, Dorant E, Hermus RJ, Sturmans F.

BACKGROUND: Various animal studies and ecologic studies suggest an inverse association between low dietary selenium intake and risk of various types of cancer. PURPOSE: The goal of this prospective cohort study was to investigate the association between toenail selenium levels and risks of stomach cancer and colorectal cancer. METHODS: Our cohort study on diet and cancer started in The Netherlands in 1986 with enrollment of 120,852 subjects aged 55-69 years. Of this number, 58,279 were men and 62,573 were women. Following the case-cohort approach for analysis of the data, we randomly selected from the cohort a subcohort of 3500 subjects (1688 men and 1812 women). After 3.3 years of follow-up, 155 incident cases of microscopically confirmed stomach cancer, 313 cases of colon cancer, and 166 cases of rectal cancer had been detected in the cohort. Toenail selenium data were available for 104 patients with stomach cancer, 234 with colon cancer, and 113 with rectal cancer and for 2459 subjects from the subcohort. RESULTS: In a multivariate analysis, the relative rates (RRs) of stomach cancer for subjects in increasing quintiles of toenail selenium level were 1.00, 0.44, 0.59, 0.84, and 0.64 (trend, P = .491). For men, there was some evidence for an inverse association between toenail selenium levels and stomach cancer: The RR for those in the highest compared with the lowest quintile of toenail selenium was 0.40 (95% confidence interval = 0.17-0.96), but the trend was not statistically significant (P = .136). For stomach cancer in women, there was no negative association with toenail selenium levels. Toenail selenium level was not associated with the risk of colon or rectal cancer. After exclusion of cases diagnosed in the 1st year of follow-up, the RRs of colon cancer for increasing quintiles of toenail selenium were 1.00, 1.27, 1.17, 0.75, and 1.07 (trend, P = .544); for rectal cancer, RR estimates were 1.00, 1.73, 0.83, 1.58, and 1.12 (trend, P = .890). CONCLUSIONS: These data support a suggestive but inconsistent inverse association between selenium levels and risk of stomach cancer. Our findings, like those of other studies, do not suggest an inverse association with risk of colorectal cancer

Publication Types:

• Cohort study among 120,852 Dutch men and women

Selenium, an antioxidant nutrient

Nutr Clin Care. 2002 Mar-Apr;5(2):75-9

Burk RF.

Selenium is an essential constituent of a number of enzymes, some of which have antioxidant functions. Deficiency of the element in animals makes them susceptible to injury by certain types of oxidative stress. At least 1 human disease occurs only in selenium-deficient individuals. Therefore, it seems prudent to avoid selenium deficiency. The plasma (or serum) selenium concentration is often used to assess selenium nutritional status. A plasma selenium concentration of 8 micrograms/dL or greater in a healthy subject indicates that plasma selenoproteins are optimized and the subject is selenium replete. The Third National Health and Nutrition Examination Survey determined plasma selenium in 17,630 subjects in the United States. Its results indicate that more than 99% of the subjects studied were selenium replete. The Institute of Medicine has set the Recommended Dietary Allowance for selenium at 55 micrograms per day for adults. Since most estimates of selenium intake in the United States are 80 micrograms per day or greater, routine selenium supplementation is not recommended in the United States.

Publication Types:

• Review

Selenium in health and disease: a review

Crit Rev Food Sci Nutr. 1997 Apr;37(3):211-28

Foster LH, Sumar

Selenium (Se) was discovered 180 years ago. The toxicological properties of Se in livestock were recognized first; its essential nutritional role for animals was discovered in the 1950s and for humans in 1973. Only one reductive metabolic pathway of Se is well characterized in biological systems, although several naturally occurring inorganic and organic forms of the element exist. The amount of Se available for assimilation by the tissues is dependent on the form and concentration of the element. Se is incorporated into a number of functionally active selenoproteins, including the enzyme glutathione peroxidase, which acts as a cellular protector against free radical oxidative damage and type 1 iodothyronine 5'-deiodinase which interacts with iodine to prevent abnormal hormone metabolism. Se deficiency has been linked with numerous diseases, including endemic cardiomyopathy in Se-deficient regions of China; cancer, muscular dystrophy, malaria, and cardiovascular disease have also been implicated, but evidence for the association is often tenuous. Information on Se levels in foods and dietary intake is limited, and an average requirement for Se in the U.K. has no been established. Available data suggest that intake in the U.K. is adequate for all, except for a few risk groups such as patients on total parenteral nutrition or restrictive diets.

Publication Types:

• Review

Selenium, selenoproteins and human health: a review

Public Health Nutr. 2001 Apr;4(2B):593-9

Brown KM, Arthur JR

Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways, including thyroid hormone metabolism, antioxidant defence systems, and immune function. The decline in blood selenium concentration in the UK and other European Union countries has therefore several potential public health implications, particularly in relation to the chronic disease prevalence of the Western world such as cancer and cardiovascular disease. Ten years have elapsed since recommended dietary intakes of selenium were introduced on the basis of blood glutathione peroxidase activity. Since then 30 new selenoproteins have been identified, of which 15 have been purified to allow characterisation of their biological function. The long term health implications in relation to declining selenium intakes have not yet been thoroughly examined, yet the implicit importance of selenium to human health is recognised universally. Selenium is incorporated as selenocysteine at the active site of a wide range of selenoproteins. The four glutathione peroxidase enzymes (classical GPx1, gastrointestinal GPx2, plasma GPx3, phospholipid hydroperoxide GPx4)) which represent a major class of functionally important selenoproteins, were the first to be characterised. Thioredoxin reductase (TR) is a recently identified seleno-cysteine containing enzyme which catalyzes the NADPH dependent reduction of thioredoxin and therefore plays a regulatory role in its metabolic activity. Approximately 60% of Se in plasma is incorporated in selenoprotein P which contains 10 Se atoms per molecule as selenocysteine, and may serve as a transport protein for Se. However, selenoprotein-P is also expressed in many tissues which suggests that although it may facilitate whole body Se distribution, this may not be its sole function. A second major class of selenoproteins are the iodothyronine deiodinase enzymes which catalyse the 5'5-mono-deiodination of the prohormone thyroxine (T4) to the active thyroid hormone 3,3'5-triiodothyronine (T3). Sperm capsule selenoprotein is localised in the mid-peice portion of spermatozoa where it stabilises the integrity of the sperm flagella. Se intake effects tissue concentrations of selenoprotein W which is reported to be necessary for muscle metabolism. It is of great concern that the health implications of the decline in Se status in the UK over the past two decades have not been systematically investigated. It is well recognised that dietary selenium is important for a healthy immune response. There is also evidence that Se has a protective effect against some forms of cancer; that it may enhance male fertility; decrease cardiovascular disease mortality, and regulate the inflammatory mediators in asthma. The potential influence of Se on these chronic diseases within the European population are important considerations when assessing Se requirement.

Publication Types:

• Review

Publication Types:

• Review