"Selenium is a cofactor of enzymes that release active thyroid hormone in cells and therefore low levels can cause similar signs and symptoms as iodine deficiency. The other important function of selenium is as an antioxidant. Around twenty-five known proteins require selenium to function. Some are enzymes involved in detoxifying free radicals and include glutathione peroxidases and thioredoxin reductase. As an integral functioning part of these enzymes, selenium aids in the regeneration of glutathione and oxidized vitamin C. Selenium as part of glutathione peroxidase also protects lipids from free radicals, and, in doing so, spares vitamin E. This is just one example of how antioxidants work together to protect the body against free-radical induced damage. Other functions of selenium-containing proteins include protecting endothelial cells that line tissues, converting the inactive thyroid hormone to the active form in cells, and mediating inflammatory and immune system responses. Observational studies have demonstrated that selenium deficiency is linked to an increased risk of cancer. A review of forty-nine observational studies published in the May 2011 issue of the Cochrane Database of Systematic Reviews concluded that higher selenium exposure reduces overall cancer incidence by about 34 percent in men and 10 percent in women, but notes these studies had several limitations, including data quality, bias, and large differences among different studies. Additionally, this review states that there is no convincing evidence from six clinical trials that selenium supplements reduce cancer risk. Because of its role as a lipid protector, selenium has been suspected to prevent cardiovascular disease. In some observational studies, low levels of selenium are associated with a decreased risk of cardiovascular disease. However, other studies have not always confirmed this association and clinical trials are lacking."