Selenium is a stable trace-metal element that is found in such cruciferous foods as broccoli, garlic, and onions, as well as in meats, seafood, and nuts.1,2 In the human body, selenium is essential for protein synthesis and multiple enzymatic functions. Most notable, however, is the element’s role in the formation of the key antioxidative compound glutathione.1
Background
The dietary requirement for selenium occupies a narrow range. Daily ingestion of <0.1 μg/gram of food may result in deficiency, but diets containing >1.0 μg/gram of food may cause toxicity.1 Total consumption of selenium-rich foods must reach 40-100 μg/day to maintain a serum-selenium concentration of 70-135 ng/mL, the level necessary for the proper function of selenium-dependent enzymes.1
Selenium is crucial for manufacturing thyroid hormones.1 The thyroid gland has a higher selenium concentration than any other body part.1 Although selenium is found throughout the body, it is primarily metabolized in the kidney, and most of the by-product metabolites are found in urine.2
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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.2
Clinical trials investigating the potential of selenium supplementation have focused on cancer prevention and treatment, cardiovascular disease, rheumatoid arthritis, and type 2 diabetes. In trials examining the benefits of selenium, toxicity was avoided by administering the supplemental doses in combination with other synergistic antioxidants, specifically vitamins E and C.1 Research indicates the concomitant use of these vitamins reduces the potential for cytotoxicity because of the body’s competitive affinity for all three compounds.1
One large clinical trial followed 1,200 people for more than seven years in a randomized study to determine if the in-vitro effects of selenium enhancing glucose metabolism would carry through in the prevention of type 2 diabetes. Participants in the active arm of the trial were given a daily selenium supplement of 200 μg, and the control group continued with their normal diet and no supplementation. The number of people developing type 2 diabetes over the course of the trial was not significantly different from those in the nonsupplemented control group, indicating no benefit in selenium supplementation for this disease process.3
Another study explored data suggesting a protective action against radiation toxicity with selenium supplementation. Patients undergoing radiation therapy for gynecologic cancers were randomized to selenium supplementation or regular diet. Of the 80 patients enrolled, the incidence of radiation-induced diarrhea was reduced by more than half (from 44.5% to 20.5%). While this improvement had a significant effect on the daily lives of the patients, it did not correlate with any changes in overall functioning or cancer outcomes.4
Findings of a meta-analysis of lung cancer outcomes were again disappointing, with a very weak protective effect seen when patients were supplemented with oral selenium vs. routine diet.5 In all trials, the patients exhibiting the greatest benefit were those with lower baseline plasma selenium levels.5
Lastly, the SELECT trial examined the protective effect of selenium and vitamin E co-administered to prevent prostate cancer. The trial expected to monitor more than 30,000 men over a minimum of seven years. Four years into the project, however, the study was stopped because data already showed no reduction in prostate cancer with selenium and vitamin E compared with the normal population.6
Safety, drug interactions
Selenium toxicity occurs as either a chronic, daily overdose or an acute-ingestion condition. In cases of chronic toxicity (intake >1,000 μg/day), patients exhibit muscle weakness, fatigue, peripheral neuropathy, dermatitis, nail and hair changes/loss, garlic breath, body odor, irritability, growth retardation, and hepatic necrosis.2 Acute selenium toxicity or selenium poisoning can occur with consumption of multigram quantities and cause severe GI disturbance, neurologic disturbance, acute respiratory distress syndrome, MI, and renal failure. One recorded fatality occurred when a man age 75 years with prostate cancer ingested 10 g of a selenium supplement.2
When taken concomitantly, selenium supplements also potentiate the action of benzodiazepines and warfarin (Coumadin) and inhibit the actions of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors and statins.1
Cost, how supplied
Selenium is usually supplied in powder-filled capsules as a single element or combined with other antioxidants. The cost is very modest, averaging $10-$12/month in most areas.
Summary
Despite its theoretical benefits, selenium supplementation in normal, healthy people seems without purpose or proven benefit. Urge patients to eat a healthy, well-balanced diet to meet daily requirements. Selenium supplementation should be considered only in special circumstances and conducted under the guidance of a health-care provider.
References
1. Natural Medicines Comprehensive Database. Selenium.
2. Memorial Sloan-Kettering Cancer Center. Selenium. Available at www.mskcc.org/mskcc/html/69373.cfm.
3. 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;147:217-223. Available at www.annals.org/content/147/4/217.long.
4. 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;78:828-835.
5. Zhuo H, Smith AH, Steinmaus C. Selenium and lung cancer: a quantitative analysis of heterogeneity in the current epidemiological literature. Cancer Epidemiol Biomarkers Prev. 2004;13:771-778. Available at cebp.aacrjournals.org/content/13/5/771.long.
6. National Cancer Institute. Selenium and Vitamin E Cancer Prevention Trial (SELECT). Available at www.cancer.gov/newscenter/qa/2008/selectqa.
All electronic documents accessed November 15, 2010
