Benefits
Antioxidant defense
Selenoproteins including glutathione peroxidases (GPx1–4) neutralize hydrogen peroxide and lipid hydroperoxides, protecting cell membranes and DNA from oxidative damage.
Thyroid hormone metabolism
Iodothyronine deiodinases are selenoenzymes that convert inactive T4 to active T3, so selenium deficiency impairs thyroid hormone activation. What supplements have been shown to change is a laboratory marker rather than thyroid function: in women with Hashimoto's thyroiditis taking levothyroxine, 200 mcg/day for 3 months lowered thyroid peroxidase antibody levels while TSH, free T4 and free T3 stayed the same, and a later 412-patient, 12-month trial reproduced the antibody drop but found no improvement in thyroid-related quality of life and no change in levothyroxine dose. Both trials were in patients with autoimmune thyroid disease on thyroid hormone, not in healthy people.
Immune function
Selenoproteins are required for normal T cell and natural killer cell function, cytokine production, and the oxidative burst in macrophages, and low selenium status is associated with greater susceptibility to viral infection. The human trial evidence is small and comes from people who started low. In 22 UK adults with plasma selenium below 1.2 micromol/L, 50 or 100 mcg/day for 15 weeks raised interferon gamma output, brought forward the peak T cell response and sped clearance of oral polio vaccine virus, while antibody responses were unchanged. In a later 117-person trial in healthy 50 to 64 year olds with marginal selenium status, 50 to 200 mcg/day of selenium yeast given before influenza vaccination changed several measures of cellular immunity in both directions, raising T cell proliferation but lowering granzyme B content of CD8 cells at the highest dose, and antibody responses were again unchanged. The trials were done in people with low or marginal status, not in people whose intake is already adequate.
Cancer prevention: not shown in trials
Randomized trials do not support selenium for cancer prevention. In SELECT, 35,533 men took 200 mcg/day L-selenomethionine or placebo and prostate cancer incidence was not reduced (575 cases on selenium versus 529 on placebo, hazard ratio 1.09, 99% CI 0.93 to 1.27). The 2018 Cochrane review of selenium for cancer prevention included 10 randomized trials in 27,232 participants; in its primary analysis of the trials at lowest risk of bias (3 trials, 19,475 participants) selenium did not reduce overall cancer incidence (risk ratio 1.01, 95% CI 0.93 to 1.10, high certainty), and there was no reduction for colorectal, lung, bladder or prostate cancer. The trials at lowest risk of bias suggested an increase in melanoma risk. The older observational finding of lower cancer rates at higher selenium status has not held up when tested.
Mechanism of action
Selenoprotein synthesis
Selenium is incorporated as selenocysteine (the 21st amino acid) into over 25 selenoproteins via a unique UGA codon recoding mechanism. These proteins serve antioxidant, anti-inflammatory, and metabolic functions.
Glutathione peroxidase activation
Selenium is the catalytic center of GPx enzymes that reduce hydrogen peroxide and organic hydroperoxides to water and alcohols using glutathione as the electron donor, directly protecting against oxidative cell damage.
Thioredoxin reductase activity
Selenium-containing thioredoxin reductases maintain thioredoxin in its reduced state, enabling DNA synthesis, peroxiredoxin recycling, and transcription factor regulation.
Clinical trials
Blinded, placebo-controlled trial of 200 µg/day sodium selenite (not selenomethionine) vs placebo in 70 women with autoimmune thyroiditis (Hashimoto's), all on levothyroxine, for 3 months. Primary outcome: anti-TPO antibody concentration. (Gärtner et al. 2002, J Clin Endocrinol Metab 87(4):1687-91, PMID 11932302)
70 women with Hashimoto's thyroiditis, mean age 47.5 years, all taking levothyroxine. A disease population, not healthy adults.
Mean anti-TPO antibody concentration fell to 63.6 percent of baseline on selenium versus 88 percent on placebo (p = 0.013), and antibodies normalised completely in 9 selenium patients versus 2 on placebo, with normalised ultrasound echogenicity reported in those patients rather than across the group. TSH, free T4 and free T3 were unchanged in both groups. Thyroglobulin antibodies fell significantly in the placebo group and were unchanged on selenium. The much larger CATALYST trial (412 patients, 200 mcg/day selenium yeast or placebo for 12 months, published 2024) reproduced the antibody drop but found no difference from placebo in thyroid-related quality of life and no change in levothyroxine dose. An antibody titre is a laboratory marker, not a symptom, and the American Thyroid Association does not endorse selenium for routine Hashimoto's management.
SELECT (Selenium and Vitamin E Cancer Prevention Trial): randomized, placebo-controlled trial of 200 µg/day L-selenomethionine, 400 IU/day vitamin E, both, or matched placebos in 35,533 men aged 50 or older, planned follow-up 7 to 12 years. Primary outcome: prostate cancer incidence. (Klein et al. 2011, JAMA 306(14):1549-56, PMID 21990298)
35,533 men aged 50 or older with PSA of 4.0 ng/mL or less, in the United States, Canada and Puerto Rico. Selenium-replete at entry.
Negative for prevention. Prostate cancer occurred in 529 men on placebo, 575 on selenium (hazard ratio 1.09, 99% CI 0.93 to 1.27), 620 on vitamin E (hazard ratio 1.17, 99% CI 1.004 to 1.36) and 555 on the combination. Vitamin E significantly increased prostate cancer risk; selenium did not lower it. In the trial's earlier report, type 2 diabetes was more common in the selenium group but not significantly so (relative risk 1.07, 99% CI 0.94 to 1.22). These men were already selenium replete, and the result reversed earlier enthusiasm for selenium as a cancer preventive.