Health Care Professional Information

Common Name

Selenocysteine, selenomethionine, selenate, selenite

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. It is also marketed as a supplement 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).
Selenium supplementation was found to reduce the viral load in individuals infected with human immunodeficiency virus (HIV) (19). Studies also indicate that selenium may improve glucose metabolism but it was not useful in preventing type 2 diabetes and in some cases may increase the risk (20) (21) (30).

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), lung (17) and bladder cancers (26). Selenium supplementation resulted in significant reduction of side effects including hair loss, abdominal pain, and loss of appetite in ovarian cancer patients undergoing chemotherapy (15). It was also effective in reducing head and neck lymphedema (12) (14) and diarrhea associated with radiation therapy (24).

However, 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, did not find evidence of protective effects of selenium. The trial was suspended in January 2009, when initial data analysis showed no reduction in the risk of prostate cancer with selenium alone or with vitamin E (21). Another study showed selenium, when used together with soy and Vitamin E, did not prevent prostate cancer progression (27). 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). Further, a review of randomized controlled trials did not find any evidence of selenium's cancer preventive potential (29).

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 also increase the risk of certain types of skin cancer (13).

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).
But 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).

Pharmacokinetics

Absorption:
Absorption of selenium is efficient and  not regulated. More than 90 percent of selenomethionine, the major dietary form of the element, is absorbed by the same mechanism as methionine itself. Selenocysteine appears to be absorbed well also. Of the inorganic forms, selenate is almost completely absorbed, but with a significant fraction lost in the urine before incorporation into tissue. Selenite has a more variable absorption probably related to interactions with substances in the gut lumen, but it is better retained, once absorbed, than selenate. Absorption of selenite is generally greater than 50 percent. Selenate and selenite are not major dietary constituents, but are commonly used to fortify foods and as selenium supplements.
Distribution:
Selenomethionine enters the methionine pool in the body and shares the fate of methionine until catabolized by the transsulfuration pathway ultimately leading to the reduced form.
Metabolism / Excretion:
Ingested selenocysteine, selenate, and selenite are all apparently metabolized by methylation to selenide. The selenide can be metabolized to selenophosphate, the precursor of selenocysteine in selenoproteins. The mechanism that regulates production of excretory metabolites has yet to be elucidated. The excretory metabolites appear in the urine primarily.
(2)

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)

Literature Summary and Critique

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.
A randomized, placebo-controlled trial Selenium and Vitamin E Prevention Trial [SELECT]) was conducted to determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases in relatively healthy men. The study involved 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico who were randomly assigned to 4 groups selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind manner. Eligibility criteria included the age of 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination that was not suspicious for prostate cancer. Subjects were given oral selenium (200 microg/d from L-selenomethionine) and vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and selenium placebo, selenium + vitamin E, or placebo + placebo. A follow-up of minimum of 7 years and a maximum of 12 years was planned. The main outcome measures were prostate cancer and prespecified secondary outcomes including lung, colorectal, and overall primary cancer.
At the median overall follow-up of 5.46 years, the hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other cancer end points. The increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group were statistically insignficant.
The authors concluded that selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.

Dosage (Inside MSKCC Only)
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References
  1. Whitney EN, et al. Understanding Normal & Clinical Nutrition, 4th 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, 11th 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. Mozaffarian D. Fish, mercury, selenium and cardiovascular risk: current evidence and unanswered questions. Int. J. Environ. Res. Public Health. 2009;6:1894-1916.
  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. Rayman MP, Stranges S, Griffin BA, Pastor-Barriuso R, Guallar E. Effect of supplementation with high-selenium yeast on plasma lipids: a randomized trial. Ann Intern Med. 2011 May 17;154(10):656-65.
  29. Dennert G, Zwahlen M, Brinkman M, et al. Selenium for preventing cancer. Cochrane Database Syst Rev. 2011 May 11;5: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.

Consumer Information

How It Works

Bottom Line: Selenium has not been shown to treat cancer or heart disease.

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
    Clinical trials show that selenium may not help prevent cancer; it may actually increase the risk of aggressive and secondary cancers.
  • 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.
Research Evidence

Prostate Cancer:
A large randomized, placebo-controlled trial Selenium and Vitamin E Prevention Trial [SELECT]) was conducted to determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases in relatively healthy men. The study involved 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico who were randomly assigned to 4 groups selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind manner. A follow-up of minimum of 7 years and a maximum of 12 years was planned. The main outcome measures were prostate cancer and prespecified secondary outcomes including lung, colorectal, and overall primary cancer.
At the follow-up of 5.46 years, the authors did not find any benefit of selenium or vitamin E, alone or in combination at the doses and formulations used, in preventing prostate cancer in this population of relatively healthy men.

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.
E-mail your questions and comments to aboutherbs@mskcc.org.