Mineral Biomarkers: Selenium

Optimal Takeaways

Selenium is an antioxidant micronutrient that helps reduce oxidative stress and inflammation, supports immune and cardiovascular health, and facilitates the production of active T3 thyroid hormone. Low levels of selenium are associated with increased oxidative stress, mercury toxicity, low T3, inflammation, and increased cardiovascular disease and cancer risk. Significantly elevated levels are associated with dermatitis, dyslipidemia, alopecia, and brittle hair and nails.

Standard Range: 63.00 – 160.00 ug/L (0.80 – 2.03 umol/L)

The ODX Range: 70.00 – 121.00 ug/L (0.89 – 1.54 umol/L)  

Low levels of selenium may be associated with cardiomyopathy, mercury toxicity, increased T4, decreased T3, inflammatory conditions, oxidative stress, reduced immune function, increased cancer and heart disease risk (Gropper 2021), stroke (Hu X, 2019), compromised cognitive function, dysfunction of selenoproteins, Keshan disease, Kashin-Beck disease, insulin resistance (McCann 2011), smoking, iron deficiency anemia (Al-Mubarak 2022), myocarditis, decreased natural killer cells, compromised neutrophil function, reduced conversion of T4 to T3 (Fairweather-Tait 2011), hypothyroidism, enlarged thyroid, thyroid cancer, and autoimmune thyroiditis (Rayman 2019).  

High levels of selenium may be associated with selenium toxicity, increased risk of diabetes, hypertension, cancer (Gropper 2021), alopecia, dermatitis (Rayman 2018), dyslipidemia (Huang 2020), pulmonary edema, brittle hair and nails, and garlic odor emanating from the skin and breath (Fairweather-Tait 2011).

Overview

Selenium is an essential trace mineral vital to many systems in the body, including the central nervous, cardiovascular, immune, and endocrine systems. It plays a vital role in antioxidant activity, thyroid hormone metabolism, inflammation regulation, reproductive health, biotransformation, and detoxification (Avery 2018, Steinbrenner 2013, Raman 2012, Neve 1991, Flores-Mateo 2006, Santos 2014).

Several antioxidant enzymes require selenium, including glutathione peroxidase, thioredoxin reductase, methionine R-sulfoxide reductase, and selenoprotein P. Selenium is also required by the deiodinase enzymes that convert T4 to T3, the most biologically active thyroid hormone (Gropper 2021). Optimization of selenoproteins appears to occur with a serum selenium level between 70 and 90 μg/L (Flores-Mateo 2006) and may peak at a serum selenium level of 125 ug/L (1.59 umol/L). However, selenoprotein metabolism may be compromised at even higher serum selenium levels. Researchers suggest avoiding selenium supplementation or total intake above 300 ug/day when serum levels are replete, as a well-established U-shaped curve exists between selenium status and health effects (Rayman 2018). If serum levels consistently exceed 122 ug/L (1.55 umol/L), supplementation should be withheld (Rayman 2019).

Selenium is crucial to production of active thyroid hormone as a constituent of iodothyronine deiodinase, the selenoenzyme responsible for converting T4 to T3 (Fairweather-Tait 2011). Selenium concentration in the body is highest in the thyroid gland, where it is incorporated into glutathione peroxidase, iodothyronine deiodinases, thioredoxin reductase, and selenoprotein P. A randomized study of 90 subjects with Hashimoto’s autoimmune thyroiditis and 36 healthy controls found that selenium supplementation with 200 ug/day significantly reduced thyroid peroxidase and thyroglobulin antibodies, and TSH levels in those with serum selenium below 80 ug/L (1.02 umol/L), the level used in the study to determine selenium deficiency. Supplementation increased serum selenium from a mean baseline of 73.6 ug/L (0.93 umol/L) to 145.6 ug/L (1.85 umol/L) in three months, and 187.2 ug/L (2.38 umol/L) in six months. Serum glutathione peroxidase and selenoprotein-1 also increased significantly without levothyroxine treatment. Researchers suggest supplementation may benefit those with Hashimoto’s and serum selenium below 120 ug/L (1.52 umol/L) (Hu, Y 2021). A deficiency of selenium increases T-cell activation and shifts immunity to a Th1-type immune response and an increase in pro-inflammatory cytokines, exacerbating thyroid dysfunction. Maintaining adequate serum selenium in both Hashimoto’s and Graves’ disease is associated with remission and better outcomes (Duntas 2015).

Selenium insufficiency can have adverse effects beyond those related to the thyroid. One study of 668 healthy older adults found that a baseline serum selenium below 65 ug/L (0.83 umol/L) was associated with a significantly higher cardiovascular mortality rate of 24% versus 13% when selenium was 85 ug/L (1.08 umol/L) or above. Treatment with 200 ug of selenium and 200 mg of CoQ10 in those with serum selenium below 65 ug/L was associated with decreased cardiovascular mortality from 24.1% to 12.1% (Alehagen 2016).

Supplementation can help maintain optimal selenium levels, especially with selenomethionine, the organic form found in food. Intake of inorganic selenium is less effective though the liver can convert it to a form utilized in circulating selenoproteins such as glutathione peroxidase and selenoprotein P (Combs 2011, Combs 2015). Selenium supplementation should be guided by serum levels. A selenium intake of 35-45 ug/day yielded a serum selenium of 50-70 ug/L (Combs 2015), and intake should be adjusted to maintain optimal selenium status.

A review of data from the prospective PREVEND trial of 5,973 individuals found that higher selenium levels, i.e., a mean of 116 ug/L (1.47 umol/L), were associated with significantly reduced risk of iron deficiency anemia and lower C-reactive protein, as well as lower incidence of heart failure and reduced all-cause mortality in non-smokers. Significantly lower levels of selenium are observed in smokers, possibly because heavy metal toxins such as arsenic in cigarette smoke interfere with selenium metabolism and increase the excretion of selenium via the GI tract. Higher levels of selenium can protect from arsenic exposure, even in areas of high arsenic exposure (Al-Mubarak 2022).

Higher blood selenium also protects against stroke, especially in males, those over age 60, and those with higher blood mercury levels. The prevalence of stroke declined sharply as serum selenium increased until a plateaued effect at approximately 120 ug/L (1.52 umol/L). Supplementation may be beneficial for increasing low selenium levels but may have no additional benefit above 135 ug/L (1.71 umol/L). Additional research suggests a U-shaped curve where all-cause mortality may increase modestly with serum selenium above 150 ug/L (1.91 umol/L) (Hu X, 2019).

Increasing selenium above 147 ug/L (1.87 umol/L) may be associated with dyslipidemia, according to the evaluation of NHANES data from 2,903 individuals. Higher levels of selenium were significantly associated with higher triglycerides and total, LDL, and non-HDL cholesterol in participants not taking lipid-lowering drugs. Researchers note that statin use lowers selenium levels and may affect results (Huang 2020).

References

Alehagen, Urban et al. “Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial.” PloS one vol. 11,7 e0157541. 1 Jul. 2016, doi:10.1371/journal.pone.0157541

Al-Mubarak, Ali A et al. “High selenium levels associate with reduced risk of mortality and new-onset heart failure: data from PREVEND.” European journal of heart failure vol. 24,2 (2022): 299-307. doi:10.1002/ejhf.2405

Avery, Joseph C, and Peter R Hoffmann. “Selenium, Selenoproteins, and Immunity.” Nutrients vol. 10,9 1203. 1 Sep. 2018, doi:10.3390/nu10091203

Combs, Gerald F Jr. “Biomarkers of selenium status.” Nutrients vol. 7,4 2209-36. 31 Mar. 2015, doi:10.3390/nu7042209

Combs, Gerald F Jr et al. “Determinants of selenium status in healthy adults.” Nutrition journal vol. 10 75. 18 Jul. 2011, doi:10.1186/1475-2891-10-75

Duntas, L H. “The Role of Iodine and Selenium in Autoimmune Thyroiditis.” Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme vol. 47,10 (2015): 721-6. doi:10.1055/s-0035-1559631

Fairweather-Tait, Susan J et al. “Selenium in human health and disease.” Antioxidants & redox signaling vol. 14,7 (2011): 1337-83. doi:10.1089/ars.2010.3275

Flores-Mateo, Gemma et al. “Selenium and coronary heart disease: a meta-analysis.” The American journal of clinical nutrition vol. 84,4 (2006): 762-73. doi:10.1093/ajcn/84.4.762  

Gropper, Sareen S.; Smith, Jack L.; Carr, Timothy P. Advanced Nutrition and Human Metabolism. 8^th edition. Wadsworth Publishing Co Inc. 2021.

Hu, Yifang et al. “Effect of selenium on thyroid autoimmunity and regulatory T cells in patients with Hashimoto's thyroiditis: A prospective randomized-controlled trial.” Clinical and translational science vol. 14,4 (2021): 1390-1402. doi:10.1111/cts.12993

Hu, Xue Feng et al. “Circulating Selenium Concentration Is Inversely Associated With the Prevalence of Stroke: Results From the Canadian Health Measures Survey and the National Health and Nutrition Examination Survey.” Journal of the American Heart Association vol. 8,10 (2019): e012290. doi:10.1161/JAHA.119.012290

Huang, Yu-Qing et al. “Association of circulating selenium concentration with dyslipidemia: Results from the NHANES.” Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) vol. 58 (2020): 126438. doi:10.1016/j.jtemb.2019.126438

McCann, Joyce C, and Bruce N Ames. “Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging.” FASEB journal : official publication of the Federation of American Societies for Experimental Biology vol. 25,6 (2011): 1793-814. doi:10.1096/fj.11-180885  

Nève, J. “Physiological and nutritional importance of selenium.” Experientia vol. 47,2 (1991): 187-93. doi:10.1007/BF01945424  

Rayman, Margaret P. “Selenium and human health.” Lancet (London, England) vol. 379,9822 (2012): 1256-68. doi:10.1016/S0140-6736(11)61452-9

Rayman, Margaret P et al. “Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomised controlled trial.” Free radical biology & medicine vol. 127 (2018): 46-54. doi:10.1016/j.freeradbiomed.2018.02.015

Rayman, Margaret P. “Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease.” The Proceedings of the Nutrition Society vol. 78,1 (2019): 34-44. doi:10.1017/S0029665118001192

Santos, Jose R et al. “Nutritional status, oxidative stress and dementia: the role of selenium in Alzheimer's disease.” Frontiers in aging neuroscience vol. 6 206. 28 Aug. 2014, doi:10.3389/fnagi.2014.00206  

Steinbrenner, Holger, and Helmut Sies. “Selenium homeostasis and antioxidant selenoproteins in brain: implications for disorders in the central nervous system.” Archives of biochemistry and biophysics vol. 536,2 (2013): 152-7. doi:10.1016/j.abb.2013.02.021