- Selenium is nutritionally essential for human health.
- Evidence from two systematic reviews of randomised controlled trials does not support the use of selenium supplements for cancer prevention in populations with an adequate baseline selenium status.
- Selenium is toxic in high doses and might have adverse effects when taken at supranutritional doses for longer periods of time.
The trace element selenium is a nutrient essential to human health and occurs naturally in a variety of foods. Inorganic forms (e.g. sodium selenite or selenate) and organic forms (e.g., selenomethionine) are both used in large numbers of selenium-containing medications, nutritional supplements or dietary aids that are promoted for medical or health purposes. These may contain either selenium alone (mono-supplements) or selenium in combination with other trace minerals as well as vitamins. Supplemental selenium has been advocated as an aid to cancer prevention.
Two recent systematic reviews have evaluated the preventive efficacy of selenium mono-supplements for cancer. Both reviews concordantly found no preventive effect of selenium for non-melanoma skin cancer and prostate cancer; one reported no preventive effect of selenium against stomach, colorectal, oesophageal or lung cancer. The two reviews disagreed regarding the evaluation of selenium for liver-cancer prevention: while one review reported a preventive effect (based on five studies), the other reported no strong indication of a preventive effect (based on three studies).
Although a number of health problems have been linked to selenium deficiency, selenium is also toxic in large doses. The safety of long-term intake of nutritional doses is a controversial issue, which continues to be discussed. Long-term supplementation has caused symptoms of chronic overexposure and has also been linked to increased risks of developing type 2 diabetes mellitus in two randomised clinical trials.
Summary first published in November 2010, authored by Gabriele Dennert.
Original summary divided into “Selenium – prevention” and “Selenium – during cancer treatment”, fully revised and updated in October 2013 by Gabriele Denner
Gabriele Dennert, CAM-Cancer Consortium. Selenium prevention [online document]. October 20, 2013.
The trace element selenium (Se) is nutritionally essential for human health and is naturally present in various food groups including grains, pulses, meat and fish. Although a number of health problems have been linked to selenium deficiency, selenium is also toxic in large doses. Selenium occurs naturally in a number of inorganic forms (e.g. selenite, selenate, selenide) and is also found in organic compounds (e.g. selenomethionine, selenocysteine)1.
Selenium in human nutrition
Humans usually ingest selenium in crop-grown or animal products. One slice of whole-wheat bread or a half-cup of boiled rice contains approximately 10µg selenium; one egg includes approximately 14µg selenium, and 100 g of meat or fish generally contains between 20µg and 40µg of selenium2. However, the selenium content of foods may vary significantly depending on plant and animal metabolism, growing conditions and animal nutrition, or even the geographic region from which the food originates3.
The bioavailability of ingested organic and inorganic selenium – as a function of absorption, metabolism and excretion – is reported to be between 50% and 90%, depending on the form of selenium and type of preparation, as well as on age, physiological status and polymorphisms in selenium transport protein genes4.
Subclinical selenium deficiency is sometimes defined as being a serum selenium level of below 75µg/l (0.95µM)5,6. According to this definition, subclinical selenium deficiency is rare in middle and northern European countries (e.g. studies with volunteers have found prevalence rates below 2% in Switzerland and France)5,6, but prevalence of subclinical selenium deficiency may be higher in Eastern and Southern European countries7,8 and in populations with chronic diseases and cancer9. However, there is no consensus for using the serum selenium level as a marker of selenium status, and no universal normal reference values have yet been established.
The chemical element selenium was discovered in 1817 by the Swedish chemist Jöns Jakob Berzelius. In the 1930s, toxic properties of selenium were discovered in cattle, and in 1957 selenium was identified as an essential mammal nutrient.
Licensed preparations for the treatment of selenium deficiency contain sodium selenite and can be obtained as liquid solutions for oral intake or intravenous administration. In addition, a large number of selenium-containing nutritional supplements or dietary aids are marketed for medical or health purposes. These contain either selenium alone (in inorganic or organic forms) or selenium in combination with other trace minerals as well as vitamins. Fermentation of yeast in a medium that is rich in inorganic selenium yields selenised yeast which contains 80-90% organic forms such as selenomethione, Se-methylselenocysteine and γ-glutamyl-Se-methylselenocysteine10.
Application and dosage
Selenium supplements are marketed as tablets, capsules, pellets and liquid solutions for oral intake. Mono-selenium preparations usually contain 50–300µg of selenium per single dose, while multi-component supplements usually contain 30–50µg.
Recommended daily intake of selenium differs between regulatory agencies. The US Institute of Medicine recommends the highest amount of daily selenium intake (55µg selenium for adult women and men), when compared to other regulatory agencies11. The World Health Organization (WHO) recommends a daily selenium intake range of 30–40µg/day for adults, depending on body weight12. The average dietary intake of selenium in European populations appears to meet the WHO recommendations3, with mean values of between 40µg and 93µg/day in men and women, respectively. However, estimation of individual daily selenium intake is difficult and the optimal amount of selenium intake for a person’s health is unknown.
Supplemental selenium is often taken in doses ranging from 50–800µg/day. The doses used in prevention trials have ranged from 200–400µg/day of selenised yeast to 500µg/day of sodium selenite.
Claims of efficacy/Alleged indication(s)
Selenium supplementation has been promoted for several distinct purposes in relation to cancer. Regarding primary prevention, selenium supplements have been claimed to protect against several types of cancer, in particular those of the prostate and the digestive tract.
Mechanism(s) of action
Selenium is bound to selenoproteins in the human body after intestinal absorption and incorporated into proteins either specifically, in catalytically active selenoenzymes, or non-specifically in tissue proteins13.
More than 25 selenium-containing enzymes have been identified to date. There are at least two functional groups of selenoproteins. The first is involved in redox processes in the tissues (glutathione peroxidases, thioredoxin reductase), the second in thyroid hormone metabolism (iodothyronine deiodinases). Furthermore, several selenoproteins have been linked to a variety of health problems14.
Purported mechanisms of action against cancer include, amongst others, the modulation of immune function, regulation of the cell cycle and apoptosis, alteration of DNA damage/repair (15, p1355, Figure 9). In-vitro studies showed that selenium affects Akt enzymatic activity16 and p53 expression17. The understanding of selenium biology, however, is still incomplete.
Prevalence of use
The author is not aware of any studies investigating the prevalence of supplemental selenium use for cancer prevention in general populations.
Most, but not all, forms of selenium are freely marketable for human use within the EU (selenised yeast, for example, is not). Licensed drugs for the treatment of selenium deficiency are available over the counter in most European countries; a prescription is required in Denmark and Germany (although Germany, only for preparations containing more than 50µg selenium)18.
Cost(s) and expenditures
The price of 100µg of inorganic selenium, via Internet pharmacies, is about €0.50 (€0.15–1.60); this amounts to approximately €15 a month.
Expenditures are higher for prescription drugs than for over-the-counter nutritional supplements, but may be reimbursable in some countries if the individual has a clinical diagnosis of selenium deficiency.
Two systematic reviews have investigated the effects of selenium mono-supplements on cancer prevention (Table 1).
In a Cochrane review by Dennert et al. (2011)19, six randomised controlled trials (RCTs) were included. Cross-cancer meta-analyses of study results were not conducted because of the heterogeneity of experimental interventions, primary outcomes and study participants. The authors concluded that there was no convincing evidence that selenium supplements could prevent cancer – in particular prostate, skin and liver cancer – in men or women.
Another recent systematic review on this topic reached different conclusions: Lee et al. (2011)20 reported that their meta-analysis of nine RCTs showed an overall preventive effect of selenium supplementation on liver cancer incidence. Looking at various types of cancers, the authors found no preventive effect of selenium against skin cancer, prostate cancer, stomach cancer, colorectal cancer, oesophageal or lung cancer; the preventive effect was restricted to liver cancer.
Discrepancies between both reviews can be explained by different inclusion criteria, which led to a different set of included studies, and the performance of a cross-cancer meta-analysis in the latter paper. In addition to the six RCTs which were included in both reviews, Lee et al. (2011)20, but not Dennert et al. (2011)19, also included the following: a trial with organ transplant recipients21 for skin-cancer prevention; a trial which used a combined intervention (selenium plus synthetic allitridum)22; for liver cancer; and another trial which randomised participants by area of residence, also for liver cancer23. The inclusion of trials which used a combined intervention, or randomised participants on the basis of their residential area, introduced additional bias to review results, which might have led to an overestimation of the preventive efficacy of selenium in Lee et al. (2011)20.
Furthermore, the generalisability of Lee et al. (2011)20 study on the preventive effect of selenium supplements against liver cancer is limited, because participants of all liver cancer trials were from high-risk populations (e.g. carriers of the hepatitis B surface antigen) and living in borderline selenium-deficient areas.
Early signs of selenium toxicity (garlic breath, hair and nail changes, upset stomach) were observed in participants of a clinical trial who received 1600µg or 3200µg selenised yeast/day for up to 24 months24. In the Selenium and Vitamin E Cancer Prevention Trial25, which used 200µg/day selenomethionine for 7–12 years, the rate of alopecia (overall incidence: 3% of participants) and mild dermatitis (7% of participants) was higher than in the placebo group (relative risk increase: +28% and +17%, respectively). Neither trial reported more severe adverse effects or signs of chronic toxicity.
Chronic selenium poisoning (selenosis) has been seen in seleniferous areas of North America and China, but has also been attributed to commercially available selenium supplements26. Symptoms of selenosis include hair loss, thickened nails, nausea, vomiting, fatigue and paresthesia and paralysis. The EU Scientific Committee on Food considers an upper selenium limit (for adults) of 300µg/day (including supplements) to be acceptable for the avoidance of selenosis. 27 The US Food and Nutrition Board, Institute of Medicine, have set the tolerable upper level of selenium intake to 400µg/day11.
However, there are concerns that long-term selenium supplementation may increase the risk of developing type 2 diabetes mellitus in selenium-replete populations. The relative risk for male selenium users in the SELECT trial was 1.07 (95% confidence interval (CI) 0.94–1.22), when compared to the placebo group; this meant that there were six additional cases of diabetes in every 1000 selenium users per year (diabetes risk: +7% in the selenium group compared to placebo)25. In the Nutritional Prevention of Cancer Trial (NPCT), the risk of developing diabetes mellitus in the selenium group was 1.55 (95% CI: 1.03–2.33); this meant that there were four additional cases of diabetes in 1000 selenium users per year (diabetes risk: +55% in the selenium group)28.
Lethal and non-lethal acute poisoning related to the use of selenium as a complementary and alternative medicine has been reported in a number of cases26,29. The lethal selenium dose for humans is unknown, but is estimated to be between 0.12g and 1g (120–1000mg)26. Acute poisoning is characterised by vomiting, garlic breath, abdominal pain, hypersalivation, cardiac arrhythmia, haemolysis, necrosis of the liver, cerebral and pulmonary oedema, coma and death27.
Chronic overexposure to selenium (selenosis).
According to the NPCT, selenium may increase the risk of non-melanoma cancer recurrence. Selenium supplementation may therefore be problematic, especially for light-skinned people.
Other problems or complications
Severe complications have been reported because not only consumers, but also healthcare professionals, have confused the measurements ‘milligram’ (mg) and ‘microgram’ (µg). Also, a number of websites mistakenly recommend ‘milligrams’ of selenium instead of ‘micrograms’, the ingestion of which may result in a thousand-fold overdose.
No controlled data are available on the effects of selenium supplements in non-selenium-deficient women during pregnancy or lactation.
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- Selenium. In: FAO & WHO: Human vitamin and mineral requirements. Report of a joint FAO/WHO expert consultation, Bangkok, Thailand. 2002. (accessed 01/10/2012).
- National Cancer Institute: Antioxidants and Cancer Prevention: Fact Sheet (last access 29/06/2013).
- Arnaud J, Bertrais S, Roussel AM, Arnault N, Ruffieux D, Favier A, Berthelin S, Estaquio C, Galan P, Czernichow S, et al. Serum selenium determinants in French adults: the SU.VI.M.AX study. Br J Nutr 2006; 95(2): 313-20.
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- Kvieala J, Zamrazil V, Jiranek V. Selenium Deficient Status of Inhabitants of south Moravia. In: Kumpulainen JT, Salonen JT (Ed.). Natural Antioxidants and Food Quality in Atherosclerosis and Cancer Prevention. Cambridge: The Royal Society of Chemistry; 1996. 177-87.
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- Rayman MP. The use of high-selenium yeast to raise selenium status: how does it measure up? Br J Nutr 2004; 92(4): 557-73.
- WHO 2004: Joint FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements (1998): Bangkok T. Vitamin and mineral requirements in human nutrition : report of a joint FAO/WHO expert consultation, Bangkok, Thailand, 21-30 September 1998. Accessed 2004.
- Reilly C. Selenium in food and health. 2nd Edition. New York: Springer 2006. here: pp. 46ff.
- Rayman, MP: Selenium and human health. Lancet 2012; 379: 1256–68.
- Fairweather-Tait SJ, Bao Y, Broadley MR, Collings R, Ford D, Hesketh JE, Hurst R: Selenium in Human Health and Disease. Antioxidants & Redox Signaling 2011; 14: 1337-1383
- Lee JH, Shin SH, Kang S, Lee YS, Bae S: A novel activation-induced suicidal degradation mechanism for Akt by selenium. Int J Mol Med. 2008; 21: 91–97.
- Li Z, Shi K, Guan L, Cao T, Jiang Q, Yang Y, Xu C: ROS leads to MnSOD upregulation through ERK2 translocation and p53 activation in selenite-induced apoptosis of NB4 cells. FEBS Lett. 2010; 584(11): 2291-7.
- OTC ingredients. search for “selenium” online (last access29/06/2013).
- Dennert G, Zwahlen M, Brinkmann M, Vinceti M, Zeegers MPA, Horneber MA. Selenium for preventing cancer. Cochrane Database Syst Rev 2011; 11(5): CD005195. doi: 10.1002/14651858.CD005195.pub2
- Lee, EH, Myung, SK, Jeon, YJ, Kim, Y, Chang, YJ, Ju, W, Seo, HG, Huh, BY: Effects of selenium supplements on cancer prevention: Meta-analysis of randomized controlled trials. Nutr Cancer 2011; 63: 1185-1195.
- Dreno B, Euvrard S, Frances C, Moyse D, Nandeuil A: Effect of selenium intake on the prevention of cutaneous epithelial lesions in organ transplant recipients. Eur J Dermatol 2007; 17: 140-145.
- Li H, Li HQ, Wand Y, Xu HX, Fan WT, Wang ML, Sun PH, Xie XY: An intervention study to prevent gastric cancer by micro-selenium and large dose of allitridum. Chin Med J 2004; 117: 1155-1160.
- Yu SY, Zhu YJ, Li WG, Huang QS, Huang CZ, Zhang QN, Hou C: A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China. Biol Trace Elem Res 1991; 29: 289-294.
- Reid ME, Duffield-Lillico AJ, Slate E, Natarajan N, Turnbull B, Jacobs E, Combs GF, Jr., Alberts DS, Clark LC, Marshall JR. The nutritional prevention of cancer: 400 mcg per day selenium treatment. Nutr Cancer 2008; 60(2): 155-63.
- 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; 301(1):39-51
- Sutter ME, Thomas JD, Brown J, Morgan B. Selenium toxicity: a case of selenosis caused by a nutritional supplement. Ann Intern Med 2008;148(12): 970-1.
- SCF (Scientific Committee on Food): Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Selenium. 2000. (last access 29/06/2013).
- Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, Cappuccio FP, Ceriello A, Reid ME: Effects of Long-Term Selenium Supplementation on the Incidence of Type 2 Diabetes: A Randomized Trial. Ann Intern Med 2007; 147:217-223.
- See KA, Lavercombe PS, Dillon J, Ginsberg R. Accidental death from acute selenium poisoning. Med J Aust 2006; 185(7): 388-9.
- Sandström B: Micronutrient interactions: effects on absorption and bioavailability. Br J Nutr 2001; 85: S181-S185.