1Structure and recommendations
2Functions in the body in normal dietary ranges
It normally acts in concert with a class of enzymes and transporters called Selenoproteins (proteins with selenium in it), many of which are intrinsic anti-oxidant enzymes. In these selenoproteins, selenium acts as a prosthetic group or active site.
3Different forms of selenium in the body
Selenium can take the form of various organic and non-organic compounds.
Non-organic forms typically revolve around Selenite, a triple-oxidized form of selenium. It can be converted via Glutathione into Selenade; this multiple step process produces some superoxide radicals.
Organic forms include the selenoamino acids, which include selenocysteine, selenomethione, and Se-methylselenocysteine. The main active dietary form is selenomethionine. Selenomethionine is a relatively stable compound, but has pro-oxidative metabolites such as Selenid and Methylselenol.
4Effects of various intake levels
Deficiency of Selenium occurs when overall intake is less than 11ug, and 40ug is typically recommended as the minimum intake. A slightly higher but still low dietary intake of selenium (55ug) is sufficient to support the needs of 25 selenoproteins although there may be some interindividual differences. Levels above this, but not yet into therapeutic dosages (200-300ug) are possibly in the range of what is needed to exert anti-carcinogenic effects and doses up to the range of 750-800ug daily seem to be relatively free of harm. Dosages of 1,500-1,600ug or above start to become associated with harm and doses nearing 3,000-5,000ug can cause direct DNA damage.
Selenium metabolites can also regulate cell cycles and apoptosis, and aid in tumor regulation.
5Different forms of selenium
The synthetic form called MethylSelenic Acid can be directly reduced into methylselenol and can avoid the B-lysase enzyme intermediate commonly seen with dietary selenium.
6Selenium and Glucose Metabolism
Selenium has been noted in the past to aid glucose metabolism via acting as an insulin mimetic and thus aiding the deposition of glucose into both fat and muscle cells. These effects have also been seen in vivo.
In populations that have sufficient selenium status, epidemiological research and one intervention have suggested that further supplementation may increase the risk for insulin resistance and Type II Diabetes. The intervention was dosed at 200mcg daily.
The theorized mechanism of action is that after a certain threshold of selenium intake (past the RDA, nearing the TUL) selenium builds up in pancreatic tissue and exerts oxidative stress on beta-cells that secrete insulin.
This may be an issue of selenium being anti-diabetic acutely (via acting as an insulin-mimetic and aiding in glucose deposition) but over time damaging beta-cells and exerting the opposite effect and being pro-diabetic.
Selenium was first discovered to be related to cancer via correlational research showing higher cancer rates in areas with lower crop selenium content.
Several metabolites of selenium may be involved with cancer regulation. Methylselenol is though to play a role
Selenoproteins themselves, rather than individual selenoamino acids, are also implicated in cancer prevention. These selenoproteins are typically those that exert anti-oxidative effects (Glutathione Peroxidases and Selenoprotein P) and alleviate cancer during the promotion stage.
Specific selenoproteins that have been investigated for being linked to specific cancers include Glutathione Peroxidase 1 being associated with head and neck, lung and breast, and bladder and prostate cancers, Glutathione Peroxidase 2 being associated with colorectal adenoma, Selenoprotein P being associated with both colorectal adenoma and Prostate cancer, Selenoprotein 15 being associated Head, Neck, breast and lung cancer, and Thioredoxin reductase 1 being associated generally with most cancers.
Circulating selenium (independent of supplementation) is associated with a decrease in prostate cancer as assessed by a relatively small meta-analysis in a relatively dose-dependent manner up to a serum concentration of 170ng/mL, where it results in a relative risk ratio of 0.8 relative to 60ng/mL (set as baseline). The same meta-analysis found a decreased risk of prostate cancer associated with toenail selenium levels at up to 1 μg/g, where the risk then rose again.
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no association between selenium status (as measured in toenails) and prostate cancer in any of five selenum concentration quintiles in the population, whose selenium levels ranged from 0.48-8.97μg/g (mean 0.89μg/g, 95% CI 0.55-1.43μg/g). Since there were only 13 cancer cases with toenail selenium levels less than 0.617μg/g included in this analysis, this study represents a relatively selenium-replete United States population compared to patients who were in included in the previous meta-analysis.
Much danger of excessive selenium comes through the pro-oxidant compound sodium selenite (thrice oxygenated selenium bound to sodium); this compound is able to induce tumor death via its pro-oxidant abilities, but is also toxic to other cells.