Selenium

• How It Works

  There is no clear evidence to support use of Selenium for cancer prevention.

  Selenium is an element obtained in the diet from Brazil nuts, seafood, meats, cereals and grains. It is an essential part of the antioxidant enzyme glutathione-peroxidase, which protects cells from damage and DNA from mutations. For this reason, it has been studied for the prevention of diseases that are caused by or aggravated by this type of cellular damage, including cancer, heart disease, and rheumatoid arthritis. Selenium is also necessary for proper function of the immune system, but it is not known whether higher-than-normal levels of selenium can stimulate the immune system. Long-term use of selenium may increase the risk of certain types of cancer.

• Purported Uses
  • To prevent and treat cancer
    Clear evidence is lacking. Some studies suggest it may actually increase the risk of aggressive and secondary cancers.
  • To reduce chemotherapy-induced adverse effects
    Selenium may help reduce fatigue and nausea in young patients.
  • To reduce secondary lymphedema (swelling due to the accumulation of lymph)
    A clinical trial suggests that selenium supplementation can reduce the swelling that occurs in patients who have undergone extensive surgery or radiation therapy.
  • To prevent heart disease
    Although low blood selenium levels have been associated with heart disease, studies in the general population have not supported the use of selenium to protect against heart disease. This use remains controversial.
  • To stimulate the immune system
    Selenium is essential for proper functioning of the immune system, and a few studies have shown an enhanced immune response in people taking selenium supplements.
  • To treat rheumatoid arthritis
    Low blood levels of selenium have been found in patients with rheumatoid arthritis. However, treatment of rheumatoid arthritis with selenium has not shown benefit in a few clinical trials.
• Do Not Take If
  • You are taking vitamin C supplements: Selenium can reduce their absorption into the bloodstream.
• Side Effects
  • Chronic selenosis can develop with doses greater than 1000 micrograms per day and results in muscle weakness, fatigue, peripheral neuropathy, dermatitis (redness and irritation of the skin), nail and hair changes/loss, garlic breath/body odor, irritability, growth retardation, and liver damage.
  • Selenium poisoning has occurred with either accidental or suicidal ingestion of gun bluing solution or sheep drench. This usually involves ingestion of grams of selenium and can cause severe gastrointestinal and neurological disturbance, acute respiratory distress syndrome, myocardial infarction (heart attack), and kidney failure.
• Special Point
  • The tolerable uptake level (TUL) of selenium is 400 micrograms per day. Dosages higher than this can cause toxicity.
  • The daily recommended intake is 55 micrograms, which is usually provided by seafood, meat, and fortified grain products.
• Clinical Summary

  Selenium, an essential dietary trace mineral, is an important component of antioxidant systems such as glutathione peroxidase ⁽¹⁾ that neutralize and protect against damage caused by free radicals and reactive oxygen species. It also plays an important role in thyroid function. Selenium can be obtained from the diet by consuming whole grains, meats, seafood, poultry and nuts, and is sold in supplemental form to boost immune function and for prevention of cardiovascular, rheumatic diseases, and cancer.

  Several studies have been conducted to determine the role of selenium in reducing the risk of cardiovascular disease but data are inconclusive ^(23) (28). Supplementation was found to reduce viral load in individuals infected with human immunodeficiency virus (HIV) ⁽¹⁹⁾. It was also shown to reduce markers of inflammation and oxidative stress in patients with diabetic nephropathy ⁽⁴¹⁾, may improve glucose metabolism, but was not useful in preventing type 2 diabetes and in some cases may increase the risk ^{(20) (30) (42)}. In another study of asymptomatic older men, selenium alone or in combination with vitamin E was ineffective in preventing dementia ⁽⁴³⁾.

  The importance of selenium in cancer prevention has been documented in epidemiological studies and clinical intervention trials. Data suggest its benefits in preventing gastrointestinal ^(16) (36) and lung ⁽¹⁷⁾ cancers although findings from bladder cancer research are conflicting ^{(26) (38) (44)}. Selenium supplementation also resulted in reduction of side effects including hair loss, abdominal pain, and loss of appetite in ovarian cancer patients undergoing chemotherapy ⁽¹⁵⁾. It was found effective in reducing head and neck lymphedema ^(12) (14); to help reduce diarrhea associated with radiation therapy ⁽²⁴⁾ in gynecological cancer patients without influencing the effectiveness or long-term survival ⁽³⁹⁾; and may decrease chemotherapy-induced fatigue and nausea in adolescents ⁽⁴⁰⁾.

  However, a recent review of randomized controlled trials did not find clear evidence of selenium’s cancer preventive potential ⁽²⁹⁾. The large prevention study SELECT (Selenium and Vitamin E Cancer Prevention Trial) ⁽⁸⁾, based on previous data indicating that selenium and vitamin E reduced the incidence of prostate cancer, also failed to find evidence of protective effects of selenium. The trial was suspended in January 2009, when initial data analysis showed that selenium, by itself or when combined with vitamin E, did not prevent prostate cancer in healthy men ⁽²¹⁾. Further, a sub-group analysis failed to find any benefit for prevention of colorectal adenomas ⁽⁴⁵⁾. In other studies, selenium when used together with soy and Vitamin E, did not prevent prostate cancer progression ⁽²⁷⁾; and when used with lycopene, had no effect on modulating risk of prostate cancer ⁽⁴⁶⁾. Moreover, results from a cross-sectional analysis of men with prostate cancer indicate that selenium levels may influence the risk of aggressive prostate cancer ⁽²²⁾, and supplementation may increase prostate cancer mortality ⁽³⁷⁾.

  A chemoprevention trial of selenium in patients with NSCLC (non small-cell lung cancer) was also halted after interim analysis as data did not show any benefit of selenium supplementation; there was an increase in secondary lung cancers in selenium users, although it was statistically insignificant ⁽²⁵⁾. Long-term use of selenium may increase the risk of certain types of skin cancer as well ⁽¹³⁾.

  Additional studies indicate no association between dietary selenium intake and thyroid cancer incidence ⁽³⁵⁾, but that it may protect radiation-induced damage to salivary glands in patients with differentiated thyroid cancer ⁽⁴⁷⁾.

• Purported Uses
  • Cancer prevention
  • Cancer treatment
  • Cardiovascular disease
  • Immunostimulation
  • Rheumatoid arthritis
• Mechanism of Action

  Selenium is an essential structural element of the antioxidant enzyme glutathione-peroxidase that converts aggressive oxidation products and intracellular free radicals into less reactive or neutral components ⁽³⁾. Other biological functions of selenium include regulation of thyroid hormone action and regulation of the reduction status of vitamin C ⁽²⁾.

  Selenium has been shown to induce a multi-targeted cell death process characterized by induction of unfolded protein response, ER-stress and occurrence of large cytoplasmic vacuoles, in addition to the formation of reactive oxygen species (ROS) ⁽³¹⁾. However, excessive intake of selenium induces hepatic insulin resistance through opposite regulation of (ROS) ⁽³²⁾.

  Recent data show that the effects of dietary selenium on progression of malignant mesothelioma tumors depend on arising cancer cells’ redox metabolism, and the tumors able to convert increased selenium into a stronger reducing capacity actually benefit from increased selenium intake ⁽³³⁾. In another study, selenium supplementation was shown to afford protection against adriamycin-induced cardiac dysfunction via restoring ATP-sensitive potassium channels (KATP) expression ⁽³⁴⁾.

• Adverse Reactions

  Case Report: Oral consumption of 10 g of sodium selenite supplement for treatment of prostate cancer resulted in the death of a 75-year-old man ⁽¹⁸⁾.
  Chronic selenosis (doses greater than 1000 mcg/day): Muscle weakness, fatigue, peripheral neuropathy, dermatitis, nail and hair changes/loss, garlic breath/body odor, irritability, growth retardation, hepatic necrosis.
  Toxicity: Acute toxicity via selenium poisoning has been reported with either accidental or suicidal ingestion of gun bluing solution or sheep drench. Consumption of gram quantities of selenium can cause severe gastrointestinal and neurological disturbances, acute respiratory distress syndrome, myocardial infarction, and renal failure.
  ^(2) (5)

• Herb-Drug Interactions

  Vitamin C: High doses of selenium may decrease absorption ⁽⁵⁾.

• References

  1. Whitney EN, et al. Understanding Normal & Clinical Nutrition, 4^th ed. Belmont (CA): West Publishing; 1994.

  2. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington (DC): National Academy Press; 2000.

  3. Suadicani P, Hein HO, Gyntelberg F. Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3000 males. Atherosclerosis 1992;96:33-42.

  4. Feifer AH, Fleshner NE, Klotz L. Analytical accuracy and reliability of commonly used nutritional supplements in prostate disease. J Urol 2002;168:150-4.

  5. Pronsky ZM. Power’s and Moore’s Food-Medication Interactions, 11^th ed. Pottstown (PA): Food Medication Interactions; 2000.

  6. Ip C. Lessons from basic research in selenium and cancer prevention (Review). J Nutr 1998;128:1845-54.

  7. El-Bayoumy K. The protective role of selenium on genetic damage and on cancer (Review). Mutat Res 2001;475:123-39.

  8. Klein EA, et al. SELECT: the selenium and vitamin E cancer prevention trial: rationale and design. Prostate Cancer Prostatic Dis 2000;3:145-51.

  9. Duffield-Lillico AJ, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiol Biomarker Prev 2002;11:630-9.

  10. Clark LC, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. JAMA 1996;276:1957-63.

  11. Klein EA, et al. SELECT: the selenium and vitamin E cancer prevention trial. Urol Oncol. 2003 Jan;21(1):59-65.

  12. Micke O, et al. Selenium in the treatment of radiation-associated secondary lymphedema. Int J Radiat Oncol Biol Phys . 2003 May 1;56(1):40-9.

  13. Duffield-Lillico AJ, et al. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst. 2003 Oct 1;95(19):1477-81.

  14. Bruns F, et al. Selenium in the treatment of head and neck lymphedema. Med. Princ Pract. 2004;13(4):185-90.

  15. Sieja K and Talerczyk M. Selenium as an element in the treatment of ovarian cancer in women receiving chemotherapy. Gynecol Oncol. 2004;93:320-327.

  16. Bjelakovic G, et al. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004;364:1219-28.

  17. Zhuo H, Smith AH, and Steinmaus C. Selenium and lung cancer: A quantitative analysis of heterogeneity in the current epidemiological literature. Cancer Epidemiol Biomarkers Prev 2004;13(5):771-778.

  18. See KA, Lavercombe PS, Dillon J, Ginsberg R. Accidental death from acute selenium poisoning. MJA 2006; 185(7):388-389.

  19. Hurwitz BE, Klaus JR, LLabre MM, et al. Suppression of Human Immunodeficiency Virus Type I Viral Load With Selenium Supplementation. Arch Intern Med 2007: 167:148-154.

  20. Stranges S, Marshall JR, Natarajan R, et al. Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes: A Randomized Trial. Ann Intern Med. 2007.

  21. Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009 Jan 7;301(1):39-51.

  22. Chan JM, Oh WK, Xie W, et al. Plasma Selenium, Manganese Superoxide Dismutase, and Intermediate- or High-Risk Prostate Cancer. J Clin Oncol. 2009 Jun 15 [Epub ahead of print].

  23. Alehagen U, Aaseth J, Alexander J, Johansson P. Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly. PLoS One. 2018 Apr 11;13(4):e0193120

  24. Muecke R, Schomburg L, Glatzel M, et al. Multicenter, Phase 3 Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology. Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):828-35.

  25. Karp DD, Lee SJ, Shaw Right GL, et al. A phase III, intergroup, randomized, double-blind, chemoprevention trial of selenium (Se) supplementation in resected stage I non-small cell lung cancer (NSCLC). J Clin Oncol 28:7s, 2010 (suppl; abstr CRA7004).

  26. Amaral AF, Cantor KP, Silverman DT, and Malats N. Selenium and Bladder Cancer Risk: a Meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010;19(9):2407-15.

  27. Fleshner NE, Kapusta L, Donnelly B, et al. Progression From High-Grade Prostatic Intraepithelial Neoplasia to Cancer: A Randomized Trial of Combination Vitamin-E, Soy, and Selenium. J Clin Oncol. Jun 10;29(17):2386-90.

  28. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental Vitamins and Minerals for CVD Prevention and Treatment. J Am Coll Cardiol. 2018 Jun 5;71(22):2570-2584.

  29. Vinceti M, Filippini T, Del Giovane C, et al. Selenium for preventing cancer. Cochrane Database Syst Rev. 2018 Jan 29;1:CD005195.

  30. Rayman MP. Selenium and human health. Lancet. 2012 Feb 29. doi:10.1016/S0140-6736(11)61452-9.

  31. Wallenberg M, Misra S, Wasik AM, et al. Selenium induces a multi-targeted cell death process in addition to ROS formation. J Cell Mol Med. 2014 Jan 8. doi: 10.1111/jcmm.12214. [Epub ahead of print]

  32. Wang X, Zhang W, Chen H, et al. High selenium impairs hepatic insulin sensitivity through opposite regulation of ROS. Toxicol Lett. 2014 Jan 3;224(1):16-23.

  33. Rose AH, Bertino P, Hoffmann FW, et al. Increasing Dietary Selenium Elevates Reducing Capacity and ERK Activation Associated with Accelerated Progression of Select Mesothelioma Tumors. Am J Pathol. 2014 Feb 1. doi: 10.1016/j.ajpath.2013.12.008. [Epub ahead of print]

  34. Liu ZW, Niu XL, Chen KL, et al. Selenium attenuates adriamycin-induced cardiac dysfunction via restoring expression of ATP-sensitive potassium channels in rats. Biol Trace Elem Res. 2013 Jun;153(1-3):220-8.

  35. O’Grady TJ, Kitahara CM, DiRienzo AG, et al. The association between selenium and other micronutrients and thyroid cancer incidence in the NIH-AARP Diet and Health Study. PLoS One. 2014 Oct 20;9(10):e110886. doi: 10.1371/journal.pone.0110886. eCollection 2014.

  36. Hughes DJ, Fedirko V, Jenab M, et al. Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort. Int J Cancer. 2015 Mar 1;136(5):1149-61. doi: 10.1002/ijc.29071.

  37. Kenfield SA, Van Blarigan EL, DuPre N, et al. Selenium supplementation and prostate cancer mortality. J Natl Cancer Inst. 2014 Dec 12;107(1):360. doi: 10.1093/jnci/dju360. Print 2015 Jan.

  38. Beane Freeman LE, Karagas MR, Baris D, et al. Is the inverse association between selenium and bladder cancer due to confounding by smoking? Am J Epidemiol. 2015 Apr 1;181(7):488-95. doi: 10.1093/aje/kwu324.

  39. Muecke R, Micke O, Schomburg L, et al. Multicenter, phase III trial comparing selenium supplementation with observation in gynecologic radiation oncology: follow-up analysis of the survival data 6 years after cessation of randomization. Integr Cancer Ther. 2014 Nov;13(6):463-7. doi: 10.1177/1534735414541963.

  40. Vieira ML, Fonseca FL, Costa LG, et al. Supplementation with selenium can influence nausea, fatigue, physical, renal, and liver function of children and adolescents with cancer. J Med Food. 2015 Jan;18(1):109-17.

  41. Bahmani F, Kia M, Soleimani A, Mohammadi AA, Asemi Z. The effects of selenium supplementation on biomarkers of inflammation and oxidative stress in patients with diabetic nephropathy: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 2016 Oct;116(7):1222-1228.

  42. Tabrizi R, Akbari M, Moosazadeh M, et al. The Effects of Selenium Supplementation on Glucose Metabolism and Lipid Profiles Among Patients with Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Horm Metab Res. 2017 Nov;49(11):826-830.

  43. Kryscio RJ, Abner EL, Caban-Holt A, et al. Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium Trial (PREADViSE). JAMA Neurol. 2017 May 1;74(5):567-573.

  44. Goossens ME, Zeegers MP, van Poppel H, et al. Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial. Eur J Cancer. 2016 Dec;69:9-18.

  45. Lance P, Alberts DS, Thompson PA, et al. Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention. Cancer Prev Res (Phila). 2017 Jan;10(1):45-54.

  46. Morgia G, Voce S, Palmieri F, et al. Association between selenium and lycopene supplementation and incidence of prostate cancer: Results from the post-hoc analysis of the procomb trial. Phytomedicine. 2017 Oct 15;34:1-5.

  47. Son H, Lee SM, Yoon RG, et al.  Effect of selenium supplementation for protection of salivary glands from iodine-131 radiation damage in patients with differentiated thyroid cancer. Hell J Nucl Med. 2017 Jan-Apr;20(1):62-70.