Selenium - Serum

Selenium: You only need a little, but you need it a lot

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

Selenium is an essential trace mineral that is vital to many systems in the body including the CNS, cardiovascular, immune, and endocrine systems. It plays an important role in antioxidant activity, thyroid hormone metabolism, inflammation regulation, reproductive health, and biotransformation and detoxification.[1] [2] [3] [4] [5] [6]

Selenium is incorporated into functional selenoproteins with various functions including antioxidant protection and production of active thyroid hormone.[7] [8]

The highest concentration of selenium per gram of tissue is in the thyroid gland.[9] Intake of 60-75 ug/day of selenium helps prevent autoimmune destruction of the thyroid.[10]

Blood levels correlate with glutathione peroxidase activity and reflect tissue stores of selenium. Approximately 75% of selenium in blood is found in the serum/plasma component,[11] the preferred component to measure.[12] Glutathione peroxidase protects cell membranes and lipids from oxidative stress and can help reduce oxidation of LDL cholesterol, a major contributor to atherosclerosis.[13] [14] [15] [16] [17] [18]

Oxidative damage also contributes to chronic diseases such as kidney disease, cognitive impairment, cancer, and cardiovascular disease. Cardiac tissue is especially sensitive to selenium availability and deficiency will lead to cardiac dysfunction. [19] [20] [21] [22] [23]

Selenium also helps detoxify cadmium, arsenic, and mercury.[24] [25]

Dietary selenium comes primarily from plant foods which depend upon the selenium content of the soil. Meat, seafood, and dairy products are sources of dietary selenium as well. [26] [27] [28] Brazil nuts can be exceptionally high in selenium (68-91 ug per nut) and could contribute to selenium toxicity.[29]

Serum selenium below 85 ug/L may reflect deficiency and research revealed that subjects with levels below 79 ug/L had significantly increased risk of ischemic heart disease while those with levels below 45 ug/L sustained a 2-3 fold increase in morbidity and mortality from cardiovascular disease.[30]

Serum levels of 70-90 ug/L maximize selenoprotein activity.>[31] Intake of 35-45 ug/day yielded a serum selenium of 50-70 ug/L,[32] possibly falling short of levels needed for optimal selenoprotein production. A level below 40 ug/L is associated with loss of glutathione peroxidase activity and achieving a level above 70 ug/L is the treatment goal for deficiency.[33] A dose of 100 ug of selenium/day can increase serum levels of 82 ug/L to 122 ug/L while 200 ug/day increased levels from 67 ug/L to 190 ug/L.[34] However, benefits may plateau at ~130 ug/L while levels above 150 ug/L may be associated with adverse effects.[35] [36]

Selenium deficiency may manifest as cardiomyopathy; congestive heart failure; increased risk of stroke mortality; immune insufficiency; erythrocyte macrocytosis; elevated transaminase and creatine kinase levels; and chronic conditions such as kidney disease, heart disease, and cancer. Selenium depletion may be associated with age-related decline in brain function.[37] [38] [39] [40]

A sharp decline in stroke is seen until serum levels reach ~ 120 ug/L. All-cause mortality may decline until levels reach 130 ug/L but was found to increase moderately with levels above 150 ug/L.[41] [42]

In those who are selenium deficient, supplementation promotes antioxidant activity, reduces peroxidation of lipids, and may reduce inflammatory prostaglandin and leukotriene compounds. [43] Supplementation can stimulate immune system response[44] and even a modest selenium deficiency can contribute to immune dysfunction.[45] Doses of 100 and 200 ug/day was associate with decreased all-cause mortality but 300 ug/day increased it when taken for 5 years.[46]

Supplementation can help address insufficiencies but must be done carefully to avoid toxicity. Toxicity can be caused by excessive intake or exposure from industrial sources.[47] Symptoms include nervous system abnormalities, fatigue, red swollen skin (hands, feet), joint pain, dry brittle hair and fingernails, nail discoloration, hair loss, diarrhea, nausea, vomiting, pain, elevated total and LDL cholesterol, and an odor of garlic on the breath. Serum levels of selenium above 300 ug/L are associated with mortality (~100 ug/L is considered normal). [48] [49] [50] [51]

Unintentional excessive ingestion from a mis-labeled supplement caused toxic levels up to 751 ug/L and symptoms including diarrhea, fatigue, hair loss, joint pain, nail discoloration and brittleness, and nausea.[52]

Excess selenium may disrupt thyroid homeostasis due to interference with feedback mechanisms and actually reduce serum T3 levels.[53]

Some research associated increased selenium intake with type 2 diabetes, especially in men with baseline serum levels exceeding 121.6 ug/L.[54] [55] [56] Additional research found that risk of diabetes increased for those with a BMI of 25 or greater when serum selenium increased to or above 137.66 ug/L especially in those who were male, high school educated, and hypercholesterolemic.[57]

A positive association between selenium exposure, serum levels higher than 140 ug/L, and diabetes was observed in a 2018 meta-analysis. However, this may reflect increased exposure to more toxic inorganic forms of selenium from diet and industrial contamination versus the organic form found in supplementation trials.[58]

Another 2018 systemic review and meta-analysis did not find consistent conclusive evidence that selenium supplementation increased development of type 2 diabetes in adults.[59]

A randomized, double-blind, placebo-controlled study found that 200 ug of selenium/day actually improved glucose regulation and markers of inflammation and oxidative stress in women with gestational diabetes.[60]

Ultimately, selenium balance is crucial and both insufficiency and excess can lead to far-reaching consequences for metabolism and disease risk. Monitoring risk factors for selenium deficiency and excess is important to maintaining homeostasis and optimal health.

References

[1] Avery, Joseph C, and Peter R Hoffmann. “Selenium, Selenoproteins, and Immunity.” Nutrients vol. 10,9 1203. 1 Sep. 2018 [R]

[2] 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. [R]

[3] Rayman, Margaret P. “Selenium and human health.” Lancet (London, England) vol. 379,9822 (2012): 1256-68. [R]

[4] Nève, J. “Physiological and nutritional importance of selenium.” Experientia vol. 47,2 (1991): 187-93. [R]

[5] 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. [R]

[6] 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 [R]  

[7] Silvestrini, Andrea et al. “The Role of Selenium in Oxidative Stress and in Nonthyroidal Illness Syndrome (NTIS): An Overview.” Current medicinal chemistry vol. 27,3 (2020): 423-449. [R]

[8] Ruggeri, Rosaria M., et al. "Selenium exerts protective effects against oxidative stress and cell damage in human thyrocytes and fibroblasts." Endocrine (2019): 1-12. [R]

[9] Ventura, Mara et al. “Selenium and Thyroid Disease: From Pathophysiology to Treatment.” International journal of endocrinology vol. 2017 (2017): 1297658. [R]  

[10] Lacka K, Szeliga A. Significance of selenium in thyroid physiology and pathology. Pol Merkur Lekarski. 2015 Jun;38(228):348-53. [R]

[11] 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. [R]

[12] Combs, Gerald F Jr. “Biomarkers of selenium status.” Nutrients vol. 7,4 2209-36. 31 Mar. 2015 [R]

[13] Benstoem, Carina et al. “Selenium and its supplementation in cardiovascular disease--what do we know?.” Nutrients vol. 7,5 3094-118. 27 Apr. 2015 [R]

[14] Girotti, Albert W, and Witold Korytowski. “Cholesterol Hydroperoxide Generation, Translocation, and Reductive Turnover in Biological Systems.” Cell biochemistry and biophysics vol. 75,3-4 (2017): 413-419. [R] 

[15] Kattoor, Ajoe John et al. “Oxidative Stress in Atherosclerosis.” Current atherosclerosis reports vol. 19,11 42. 18 Sep. 2017,  [R] 

[16] Li, Huige et al. “Vascular oxidative stress, nitric oxide and atherosclerosis.” Atherosclerosis vol. 237,1 (2014): 208-19. [R]  

[17] Salvayre, R et al. “Oxidative theory of atherosclerosis and antioxidants.” Biochimie vol. 125 (2016): 281-96. [R]  

[18] 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. [R] 

[19] Avery, Joseph C, and Peter R Hoffmann. “Selenium, Selenoproteins, and Immunity.” Nutrients vol. 10,9 1203. 1 Sep. 2018, [R]

[20] Laclaustra, Martin et al. “Serum selenium and serum lipids in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004.” Atherosclerosis vol. 210,2 (2010): 643-8. [R]

[21] Linus Pauling Institute Micronutrient Information Center. Selenium. [R]

[22] Mayo Clinic Rochester 2020 Interpretive Handbook. [R]   

[23] 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 [R]  

[24] Zwolak, Iwona, and Halina Zaporowska. “Selenium interactions and toxicity: a review. Selenium interactions and toxicity.” Cell biology and toxicology vol. 28,1 (2012): 31-46 [R] 

[25] Tan, Lea Chua et al. “Selenium: environmental significance, pollution, and biological treatment technologies.” Biotechnology advances vol. 34,5 (2016): 886-907 [R]  

[26] Avery, Joseph C, and Peter R Hoffmann. “Selenium, Selenoproteins, and Immunity.” Nutrients vol. 10,9 1203. 1 Sep. 2018 [R]

[27] Mahan, L. Kathleen; Raymond, Janice L. Krause's Food & the Nutrition Care Process (Krause's Food & Nutrition Therapy) (p. 930). Elsevier Health Sciences. Kindle Edition.

[28] 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 [R]   

[29] NIH ODS Selenium. [R]

[30] Rayman, M P. “The importance of selenium to human health.” Lancet (London, England) vol. 356,9225 (2000): 233-41. [R]

[31] 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. [R]

[32] Combs, Gerald F Jr. “Biomarkers of selenium status.” Nutrients vol. 7,4 2209-36. 31 Mar. 2015, [R]

[33] Mayo Clinic Rochester 2020 Interpretive Handbook. [R]

[34] 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. [R]

[35] 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. [R]

[36] Rayman, Margaret P. “Selenium and human health.” Lancet (London, England) vol. 379,9822 (2012): 1256-68. [R]   

[37] Mayo Clinic Rochester 2020 Interpretive Handbook. [R]

[38] Lalonde, L et al. “Fluorometry of selenium in serum or urine.” Clinical chemistry vol. 28,1 (1982): 172-4. [R]

[39] Iglesias, Pedro et al. “Selenium and kidney disease.” Journal of nephrology vol. 26,2 (2013): 266-72. [R]  

[40] 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 [R]

[41] 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. [R]

[42] Bleys, Joachim et al. “Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults.” Archives of internal medicine vol. 168,4 (2008): 404-10.  [R]

[43] 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. [R] 

[44] Avery, Joseph C, and Peter R Hoffmann. “Selenium, Selenoproteins, and Immunity.” Nutrients vol. 10,9 1203. 1 Sep. 2018 [R]

[45] 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. [R]

[46] 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. [R]

[47] Tan, Lea Chua et al. “Selenium: environmental significance, pollution, and biological treatment technologies.” Biotechnology advances vol. 34,5 (2016): 886-907. [R]

[48] Laclaustra, Martin et al. “Serum selenium and serum lipids in US adults: National Health and Nutrition Examination Survey (NHANES) 2003-2004.” Atherosclerosis vol. 210,2 (2010): 643-8. [R]

[49] Jacobs DS, DeMott WR, Oxley DK, eds. Laboratory Test Handbook With Key Word Index. 5th ed. Hudson, Ohio: Lexi-Comp Inc; 2001.

[50] Hadrup, Niels, and Gitte Ravn-Haren. “Acute human toxicity and mortality after selenium ingestion: A review.” Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) vol. 58 (2020): 126435. [R]

[51] NIH ODS Selenium.  [R]

[52] MacFarquhar, Jennifer K et al. “Acute selenium toxicity associated with a dietary supplement.” Archives of internal medicine vol. 170,3 (2010): 256-61. [R]

[53] Köhrle J. Selenium and the control of thyroid hormone metabolism. Thyroid. 2005 Aug;15(8):841-53. [R]

[54] Rees, Karen et al. “Selenium supplementation for the primary prevention of cardiovascular disease.” The Cochrane database of systematic reviews vol. 2012,2 (2012): CD009671. [R]   

[55] Rees, Karen et al. “Selenium supplementation for the primary prevention of cardiovascular disease.” The Cochrane database of systematic reviews ,1 CD009671. 31 Jan. 2013, [R]

[56] Stranges, Saverio et al. “Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial.” Annals of internal medicine vol. 147,4 (2007): 217-23. [R]

[57] Bleys, Joachim et al. “Serum selenium and diabetes in U.S. adults.” Diabetes care vol. 30,4 (2007): 829-34. [R]

[58] Vinceti, Marco et al. “Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis.” European journal of epidemiology vol. 33,9 (2018): 789-810. [R]

[59] Kohler, Lindsay N et al. “Selenium and Type 2 Diabetes: Systematic Review.” Nutrients vol. 10,12 1924. 5 Dec. 2018, [R]

[60] Asemi, Zatollah et al. “Effects of selenium supplementation on glucose homeostasis, inflammation, and oxidative stress in gestational diabetes: Randomized, double-blind, placebo-controlled trial.” Nutrition (Burbank, Los Angeles County, Calif.) vol. 31,10 (2015): 1235-42. [R]

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