Selenium
Se
Selenium, Se - Essential Mineral
Daily Requirement:
Modified DV:
RDA ?:
Adequate Intake ?:
55
true
mcg/day
mcg/day
Min Deficiency:
Max Toxicity:
Tolerable UL
Animal:Plant Conv:
400
mcg/day
mcg/day
mcg/day
Date Discovered:
Short Description:
Dietary selenium comes from meat, nuts, cereals and mushrooms.
Interpretation:
Summary
Se may be protective against certain cancers:
prostate, colo-rectal. Most protective in people with low Se intakes
Mechanism not clearly understood but may be related to antioxidant properties of selenoproteins and/or pro-apoptotic methylated Se metabolites
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
Countries with low soil Se, have populations with low Se intakes
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
SELECT Trial
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.
Digestion:
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