Selenium supplementation does not improve vascular responsiveness in healthy North American men. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto's thyroiditis. Effect of selenium supplementation on biochemical markers and outcome in critically ill patients.
Selenium is an essential trace nutrient required for the synthesis of selenoproteins such as glutathione peroxidase and thioredoxin reductase, the major forms of selenium in the endothelium that have important functions relevant to inflammation and cardiovascular disease. Selenium deficiency is associated with cardiomyopathy and sudden cardiac death in animals, and a low selenium status is associated with cardiovascular disease in humans. Endothelial dysfunction, measured as the impaired flow-mediated vasorelaxation of the brachial artery, is a reliable indicator of future cardiovascular disease risk in healthy individuals. To test whether selenium supplementation affects endothelial function, we conducted a randomized, placebo-controlled trial in healthy men who were administered 300 microg of selenium a day as high-selenium yeast for 48 wk. Brachial artery responsiveness to transient occlusion was assessed at baseline and after 24 and 48 wk of supplementation. The supplementation increased the selenium concentration by more than half in blood plasma and erythrocytes. However, there was no effect of selenium on arterial diameter or blood flow rate before or after transient occlusion or on the maximum dilated diameter after the administration of nitroglycerin. This study indicates that selenium supplementation is not likely to improve endothelial function or peripheral arterial responsiveness in healthy North American men receiving adequate selenium from their diets. Pregnant women who are positive for thyroid peroxidase antibodies [TPOAb(+)] are prone to develop postpartum thyroid dysfunction (PPTD) and permanent hypothyroidism. Selenium (Se) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis.
                We examined whether Se supplementation, during and after pregnancy, influences the thyroidal autoimmune pattern and function.
                This was a prospective, randomized, placebo-controlled study.
                The study was conducted in the Department of Obstetrics and Gynecology and Department of Endocrinology.
                A total of 2143 euthyroid pregnant women participated in the study; 7.9% were TPOAb(+).
                During pregnancy and the postpartum period, 77 TPOAb(+) women received selenomethionine 200 microg/d (group S1), 74 TPOAb(+) women received placebo (group S0), and 81 TPOAb(-) age-matched women were the control group (group C).
                We measured the prevalence of PPTD and hypothyroidism.
                PPTD and permanent hypothyroidism were significantly lower in group S1 compared with S0 (28.6 vs. 48.6%, P<0.01; and 11.7 vs. 20.3%, P<0.01).
                Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism. No previous study determined monocyte- and lymphocyte-suppressing effects of levothyroxine and selenomethionine and assessed whether their coadministration is superior to treatment with only one of these drugs.
                Our objective was to compare the effect of levothyroxine and selenomethionine on monocyte and lymphocyte cytokine release and systemic inflammation in patients with Hashimoto's thyroiditis. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: We conducted a randomized clinical trial involving a group of 170 ambulatory euthyroid women with recently diagnosed and previously untreated Hashimoto's thyroiditis and 41 matched healthy subjects. Participants were randomized in a double-blind fashion to receive a 6-month treatment with levothyroxine, selenomethionine, levothyroxine plus selenomethionine, or placebo. One hundred sixty-five patients completed the study.
                Monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein (CRP) were assessed.
                Compared with the control subjects, monocytes and lymphocytes of Hashimoto's thyroiditis patients released greater amounts of all cytokines studied. Levothyroxine reduced monocyte release of TNF-α, IL-1β, IL-6, and monocyte chemoattractant protein-1, whereas selenomethionine inhibited lymphocyte release of IL-2, interferon-γ, and TNF-α, which was accompanied by a reduction in plasma CRP levels. The decrease in cytokine release and in plasma CRP levels was strongest when both drugs were given together.
                Despite affecting different types of inflammatory cells, levothyroxine and selenomethionine exhibit a similar systemic antiinflammatory effect in euthyroid females with Hashimoto's thyroiditis. This action, which correlates with a reduction in thyroid peroxidase antibody titers, may be associated with clinical benefits in the prevention and management of Hashimoto's thyroiditis, particularly in subjects receiving both agents. This study aimed to assess the effect of high dose selenium (Se) supplementation on Se status in blood, oxidative stress, thyroid function and possible effects on requirement for renal replacement therapy (RRT) in severely septic patients admitted to the intensive care unit (ICU).
                This prospective single-centre study was carried out in 40 septic ICU patients who were randomized to high dose Se (Se+ group, N=18 (474, 316, 158 microg/day), each for 3 consecutive days followed by a standard dose of 31.6 microg/day of Se given as sodium selenite whereas the control group (Se-, N=22) received only the standard dose of Se. Plasma Se, glutathione peroxidase (GSH-Px), F2 isoprostanes, thyroid function tests (total T4 and total T3), C-reactive protein (CRP) and red blood cell (RBC) GSH-Px were estimated on day 0, 3, 7, 14.
                In the Se+ group, plasma Se increased by day 3 and 7 (P<0.0001) and day 14 (P=0.02), plasma GSH-Px increased by day 3 and 7 (P=0.01) as compared to Se- group. There was a significant negative correlation between plasma Se and SOFA (sepsis related organ failure assessment) (r=-0.36, P=0.03) along with low plasma Se and high CRP at the time of admission. Requirement for renal replacement therapy was not significantly different between the groups.
                Although high dose Se supplementation increased plasma Se and GSH-Px activity, it did not reduce oxidative damage or the requirement for RRT. Se levels in blood are influenced by redistribution and severity of illness and therefore should be interpreted with caution.
Results of these four studies show that evidence to support or refute the efficacy of selenium supplementation in people with Hashimoto's thyroiditis is incomplete. The current level of evidence for the efficacy of selenium supplementation in the management of people with Hashimoto's thyroiditis is based on four randomised controlled trials assessed at unclear to high risk of bias; this does not at present allow confident decision making about the use of selenium supplementation for Hashimoto's thyroiditis. This review highlights the need for randomised placebo-controlled trials to evaluate the effects of selenium in people with Hashimoto's thyroiditis and can ultimately provide reliable evidence to help inform clinical decision making.