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Selenium, Se - Essential Mineral


Daily Requirement:

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Min Deficiency:

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Tolerable UL

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Date Discovered:

Short Description:

Dietary selenium comes from meat, nuts, cereals and mushrooms.



  • Se may be protective against certain cancers: 

  1. prostate, colo-rectal. Most protective in people with low Se intakes 

  2. Mechanism not clearly understood but may be related to antioxidant properties of selenoproteins and/or pro-apoptotic methylated Se metabolites 

  3. Selenium was once considered the most promising mineral in terms of cancer prevention, however the Select Trial has cast much doubt on the efficacy of selenium 

  • Se content of food is highly variable, related to where the food is grown 

  1. Countries with low soil Se, have populations with low Se intakes 

  2. Extremely difficult to recommend foods to increase Se intake without knowing geographic origin 

  • The downside: increased selenium intake may be involved in the etiology of type II diabetes and may not help with cancer prevention

• What is unique about Se incorporation into selenoproteins

Selenocysteine is inserted into the protein. Most minerals will act as a co-factor, but not part of enzyme. However, selenium is in the protein.

• How is Se deficiency related to viral mutations?

Mice, Se and Vitamin E deficient, cossacki virus mutated and more contagious. Host status caused mutations in virus.

• What is the evidence for Se in cancer protection, what populations are most likely to benefit

Good early evidence, but after looking at data, low selenium food was protecting people from cancer. Another study was wildly disappointing after 8 years supplementing. Tricky because you don't know amount of Se in food, need to know soil content. Most people probably getting enough. Trend for T2D, be cautious.

• Are Se contents of foods homogenous throughout the world? What is the primary determinant for Se content of foods?

• What does the latest evidence tell us about Se supplementation

History & Discovery:

Global Selenium Intakes

Selenium Distribution in the US - Low Se in Northeast, Florida, and Northwest.

Selenium in beef: a model system of Se variability in foods

  • Identify seleniferous areas of North Dakota

  • Determine factors responsible for selenium content of beef

  • Determine correlations between forage and soil selenium levels and selenium levels in beef


  • Started 2001

  • Randomized, double blind. 35,534 healthy men, aged >50

  • 12 yr supplementation: 200 µg Se (selenomethionine), 400 IU Vit E

  • Primary endpoints: prostate cancer, alzheimer’s disease and macular degeneration

  • Study stopped in 2008

Effect of Selenium and/or Vitamin E on Prostate Cancer -- (Lippman et al., JAMA. 2009)

Effect of Selenium and/or Vitamin E on Other Cancers

SELECT Study Conclusions

  • In conclusion, SELECT has definitively demonstrated that selenium, vitamin E, or selenium + vitamin E (at the tested doses and formulations) did not prevent prostate cancer in the generally healthy, heterogeneous population of men in SELECT.

  • These data underscore the prudence that is needed in considering recommendations to use agents for the prevention or control of disease in the absence of convincing clinical trial results.

  • These findings also compel the medical research community to continue the search for new, effective agents for prostate cancer prevention.


Absorption and Storage:

Important Pathways:

The Glutathione Peroxidase System

•4 distinct genes in humans

•Involved in the conversion of peroxide to water and O2

Glutathione Peroxidase-1 cytosol H2O2 → H2O + 1/2O2

Glutathione Peroxidase-2 cytosol (gut) H2O2 → H2O + 1/2O2

Glutathione Peroxidase-3 plasma H2O2 → H2O + 1/2O2

Glutathione Peroxidase-4 cell membranes H2O2 → H2O + 1/2O2

Thioredoxin Reductase

  • Se dependant, 56 kDa flavoprotein found in cytosol and mito [1µM]

  • 2 conserved redox sites (Cys57-Cys62 and Cys495-SeCys496)

  • Reduces thioredoxin but also has independent antioxidant function:

  • SeCys more reactive than cys residues, have lower redox potential

  • SeCys site in eukaryotes is at the C terminus, this allows increased substrate accessibility to redox site and may account for broad substrate specificity in eukaryotic thioredoxin reductase

Selenium and Human Health

• Immune Function

– coxsackie virus

– Se status and immune compromising diseases

• Cancer

– inverse correlation cancer/forage Se

– animal models

– human studies

Deficiency Diseases, Detection, Cures:

Host Selenium Deficiency and Viral Interactions

Early Epidemiological Studies

Shamberger and Frost Can. Med. Assoc. J. 104:82 (1969)—reported inverse relationship of selenium intake with cancer

Shamberger and Willis CRC Crit. Rev. Clin. Lab. Sci. 2: 211 (1971)—more detailed study showing this same inverse relationship

Schrauzer et al Bioinorganic Chem. 7:23 (1977) 27-country comparison revealed certain cancers varied inversely with estimated per capita selenium intake

Major Selenium & Cancer Human Studies

Chinese Liver Cancer Study

  • 8 year supplementation, Se-enriched table salt (n = 20,847)

  • 35% lower liver cancer incidence compared to nontreated communities

Linxian Study

  • Randomized, double blind study. >29,000 subjects, aged 40-69

  • 5 yr supplementation: 50 µg Se (Se yeast) + 15 mg β-carotene + 30 mg Vit E

  • 13% reduction in cancer mortality, 21% decrease in stomach cancer mortality, 41% decrease in gastric cancer mortality

Nutritional Prevention of Cancer Trial

  • Randomized, double blind. >1300 subjects with history of skin cancer.

  • 13 yr supplementation: 200 µg Se (yeast)

  • Total cancer incidence (RR = 0.63), prostate cancer (RR = 0.51), colonrectum (RR = 0.46)

Meta Analysis

  • Bjelakovic et al., Lancet (2004): 14 randomized trials (N=170,525). Selenium only nutrient (vitamins A, C, E also examined) to show significant beneficial effect on the incidence of gastrointestinal cancer.

  • Zhuo et al., Cancer Epi Bio & Prev. (2004): 14 studies. Overall relative lung cancer risk for people in the highest quartile of Se status: 0.74. When measured by toenail Se

  • Brinkman et al., Eur. J of Cancer. (2006): 20 studies. Showed a significant difference between serum or toenail Se levels between prostate cancer cases and controls indicating a possible inverse association between selenium levels and risk of prostate cancer.

Selenium Supplementation?

  • Editorials in major medical journals have suggested immediate supplementation to increase intakes

  • Many people interested in increasing Se intake

Genetic Diseases: