Introduction:
Selenium is a trace element necessary for the maintenance of health. It is found in foods such as Brazil nuts, poultry, seafood, and meats, while significant amounts are found in oats and brown rice. This naturally occurring substance helps to limit the activities of free radicals which can be harmful to the body. It is known that selenium can enhance the antioxidant capacity of the body, and it may help to reduce cell damage. Several research reports indicate an association of selenium blood levels with a reduction in risk of cancers occurring in the lungs, colorectal, breast and prostate. A review of research on selenium by Chen YC et. al. found that selenium compounds not only have had evidences for a preventive role in cancer, but also may reduce the possibility of cancer metastasis by reducing the tendency of cells to migrate, invade and form new blood vessels (1). Selenium is important for immune system support and low levels have previously been linked to miscarriage, pre-eclampsia, and low fetal growth, but despite these concerns, there has been no evidence based recommendation for this indication by any authority. (2)
Selenium intake recommendations (3):
Selenium dietary allowance for both males and females by age: Birth to 6 months: 15 mcg per day, 7–12 months: 20 mcg per day, 1–3 years: 20 mcg per day, 4–8 years: 30 mcg per day, 9–13 years: 40 mcg per day, 14–18 years: 55 mcg per day, 19–50 years: 55 mcg per day, 51+ years: 55 mcg per day, Pregnancy: 60 mcg per day, Lactation: 70 mcg per day.
Selenium intake limits and toxicity:
Toxicity may occur over the following intake limits for males and females: Birth to 6 months: 45 mcg, 7–12 months: 60 mcg, 1–3 years: 90 mcg, 4–8 years: 150 mcg, 9–13 years: 280 mcg, 14 years and older including pregnant or lactating women: 400 mcg.
Symptoms of toxicity may include loss of, or brittle hair or nails, skin rash, fatigue, nausea, diarrhea, irritability and peripheral neuropathy.
Selenium and cancer: A Cochrane Review by Dennert G et al used 6 randomized controlled clinical trials and 49 observational studies to calculate the odds ratio of cancer incidence and mortality with selenium intake. A higher selenium intake was associated with a 31% lower risk of cancer (OR 0.69, 95% CI 0.53 to 0.91 ) and a 45% lower risk of mortality (OR 0.55, 95% CI 0.36 to 0.83). The risk reduction of cancer was greater in men than women 34% vs 10%. Despite findings of the analysis, the study concludes that a low selenium level cannot be directly linked with an increased risk of cancer and there may have been limitations of possible bias, quality, and design of the studies reviewed. (4)
Selenium and breast cancer:
Patients with high risk metastatic breast cancer (n=32, aged 32-81 yrs) were treated with standard therapeutic treatment plus Adjuvant Nutritional Intervention in Cancer protocol (ANICA protocol). This protocol contained 387 mcg selenium but also contained 2850 mg vitamin C, 2,500 IU vitamin E, 32.5 IU ß-carotene, 1.2 g gamma-linolenic acid, 3.5 g omega-3 fatty acids from fish oil, and 90 mg CoQ10. All 32 patients survived the 18 months follow-up. None showed further evidence of distal metastasis. Participants reported no weight loss and a reduced use of pain killers. Remission was also reported in 6 patients. (5)
Selenium and prostate cancer:
Researchers examined the association between prostate cancer incidence and pre-diagnostic selenium concentrations in toenails. The level of selenium in toenails reflects intake from dietary and supplementary sources. Yoshizawa et al. prospectively examined toenail selenium levels in 181 men who later developed advanced prostate cancer (stages C and D) during 2–7 years of follow-up. Results showed the mean toenail selenium level was significantly higher in control subjects than in cancer subjects. It was found that higher selenium levels were associated with a reduced risk of advanced prostate cancer. When subjects in the highest 20 percent for selenium status were compared with those in the lowest 20 percent, those with the highest selenium status were half as likely to get prostate cancer as those with the lowest levels. The authors reporting an odds ratio (OR) for prostate cancer of 0.4 comparing the highest with the lowest quintile of toenail selenium content. After additionally controlling for family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the OR was 0.35. These findings suggest that higher selenium intakes may reduce the risk of prostate cancer. (6)
Selenium and skin cancer:
A multi-center, double-blind, randomized, placebo-controlled trial of 1,312 patients with a history of basal cell cancers (BCC) or squamous cell cancers (SCC) and a mean follow-up of 6.4 years showed that 200 mcg of selenium failed to decrease the development of skin cancer and may increase the risk of BCC (by 10%) and SCC (by 14%) compared to placebo. However, the results also indicated that with supplementation, total cancer incidence was decreased by 37%, total cancer mortality was decreased 50%, and prostate cancer incidence was decreased by approximately 50% compared to placebo. All of these effects were statistically significant. Although lung and colorectal cancer incidence were decreased by 30% and 54%, respectively, those effects were not statistically significant. (7)
Nutritional Prevention of Cancer Study Group also performed a study in 1312 patients to test whether or not 200 mcg of selenium would prevent non-melanoma skin cancer in a randomized, double-blind, placebo controlled trial, but it was found that squamous cell skin cancer risk was increased by 25%, and non-melanoma skin cancer by 17% by calculating a hazard ratio (19).
Effects of a selenium, beta-carotene, and vitamin E combination::
Ten-year follow-up results from the General Population Trial, a study conducted in in Linxian, China from 1985 to 1991 that gave daily vitamin and mineral supplements (50 mcg of selenium, 30 mg of vitamin E, and 15 mg of beta-carotene) to 29,584 adults at high risk of esophageal and stomach cancers were presented. In the original study, researchers had found that treatment led to a decrease in mortality from all causes, cancer overall, and gastric cancer. Adding to these important findings, post intervention follow-up indicated that the beneficial effects of the beta-carotene–vitamin E–selenium combination in the General Population Trial remained evident up to 10 years after the intervention. Cumulative mortality decreased from 33.62% to 32.19% and cumulative gastric cancer mortality decreased from 4.28% to 3.84%. These benefits were consistently greater in participants who were younger (<55 y) at the beginning of the intervention. (8)
Selenium, beta-carotene, and vitamin E combination in two trials:
Two randomized studies were conducted in Linxian, an area of north central China whose residents have very high rates of esophageal and stomach cancers. The first trial trial, enrolled 3,318 adults aged 40–69 years with esophageal dysplasia, a precursor to esophageal cancer. Trial participants were randomly assigned to receive either a placebo or a daily supplement of 14 vitamins and 12 minerals (including beta carotene, alpha-tocopherol, and selenium) at 2 to 3 times the US RDA for 6 years. This 6-year intervention was associated with a non-significant change: a 16% reduction in the esophageal cancer mortality rate. A second trial, randomly assigned 29,594 adults aged 40–69 years to receive 1 of 4 combinations of multivitamin supplements containing retinal and zinc, riboflavin and niacin, vitamin C and molybdenum, or β-carotene, vitamin E, and selenium each day for 5.25 years. Doses were equivalent to 1 to 2 times the US Recommended Dietary Allowances (RDAs). Results from the second trial showed that those who received the beta-carotene–vitamin E–selenium combination had a 13% reduction in cancer mortality, including a 21% decrease in stomach cancer mortality, a 41% decrease in gastric cancer mortality, and a 4% decrease in deaths from esophageal cancer. The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta-carotene, vitamin E, and selenium, may affect a reduction in cancer risk in this population. (9)
Selenium and cardiovascular disease:
A meta-analysis of observational studies by Flores-Mateo G looked at the relationship of selenium to coronary heart disease and found that higher selenium levels were associated with a lower risk of coronary heart disease. However, according to the author there is a lack of randomized controlled trials and observational studies have mislead the evidence for the benefit of other anti-oxidants. Therefore selenium should not be offered as a preventive agent for cardiovascular disease at the time of publication. (10)
Selenium and thyroid disease:
Selenium vs. placebo in thyroid disease: A review by J. Köhrle expressed that selenium levels have been observed in both autoimmune thyroiditis (Hashimoto’s thyroiditis) and Graves’ disease at diagnosis. This author stated that supplementation with selenium over placebo has improved the clinical status of both of these diseases, prevents goiter, and reduces autoimmune antibody titers. (11)
Selenium for Hashimoto’s thyroiditis:
Toulis KA performed a systematic review and a meta-analysis in the use of selenium in Hashimoto’s thyroiditis. In 4 studies, selenium taken over a period of 3 months resulted in significant reduction in thyroid peroxidase autoantibodies, and 3 studies showed subjects had an improved mood and/or started to feel better in general. (12)
Selenium for Graves’ disease:
Graves’ disease is an autoimmune disorder resulting in hyperthyroidism and symptoms of bulging eyes or Graves’ ophthalmopathy. In a randomized, double-blind, placebo-controlled trial, selenium at a dose of 100 mcg oral twice per day taken for 6 months was found to improve quality of life, was associated with less eye involvement and slowed progression better than placebo and pentoxifylline. (13)
Selenium and the central nervous system:
Selenium and depression:
A study in 1995 by James D. Penland assessed the mood in 30 male volunteers and compared half of the men with a selenium rich diet of 240 mcg per day with the other half with an intake of 28 mcg of selenium per day. The selenium concentration was followed by checking levels in red blood cells and selenium dependent enzyme levels every 3 weeks. Men with more active selenium enzymes were found to have a better mood after being asked about six different states of mood. (14)
Selenium and Alzheimer’s disease:
Loef M et al reviewed 9 placebo controlled clinical trials which tested selenium supplements for their effect on Alzheimer’s disease. Their conclusion was that there was no consistent proven benefit of selenium supplements for use in treatment of Alzheimer’s disease. (15)
Selenium and infertility:
A double-blind, placebo controlled, randomized study by Safarinejad MR and Safarinejad S. found that a selenium supplement at dose of 200 mcg per day for 26 weeks improved semen function significantly (16).
Common highest selenium containing foods in micrograms (mcg):
| Nuts, brazilnuts, dried, unblanched, 1 oz (6-8 nuts) | 543.5 mcg |
| Fish, rockfish, Pacific, mixed species, cooked, dry heat, 1 fillet | 113.5 mcg |
| Turkey, whole, giblets, cooked, simmered, 1 cup | 103.1 mcg |
| Fish, tuna, yellowfin, fresh, cooked, dry heat, 3 oz | 92.0 mcg |
| Fish, halibut, Atlantic and Pacific, cooked, dry heat, 1/2 fillet | 88.1 mcg |
| Chicken, broilers or fryers, giblets, cooked, simmered, 1 cup | 86.4 mcg |
| Fish, tuna salad, 1 cup | 84.5 mcg |
| Barley, pearled, raw, 1 cup | 75.4 mcg |
| Fish, roughy, orange, cooked, dry heat, 3 oz | 75.1 mcg |
| Wheat flour, whole-grain, 1 cup | 74.2 mcg |
| Fish, swordfish, cooked, dry heat, 1 piece | 72.6 mcg |
| Fish, rockfish, Pacific, mixed species, cooked, dry heat, 3 oz | 64.8 mcg |
| Fish, tuna, light, canned in oil, drained solids, 3 oz | 64.6 mcg |
| Crustaceans, lobster, northern, cooked, moist heat, 3 oz | 62.1 mcg |
| Fast foods, submarine sandwich, with tuna salad, 1 sandwich, 6″ roll | 60.2 mcg |
| Fish, tuna, light, canned in water, drained solids, 3 oz | 60.0 mcg |
| Fish, swordfish, cooked, dry heat, 3 oz | 58.2 mcg |
| Crustaceans, crab, blue, canned, 1 cup | 57.9 mcg |
| Fish, salmon, sockeye, cooked, dry heat, 1/2 fillet | 56.6 mcg |
| Mollusks, oyster, eastern, cooked, breaded and fried, 3 oz | 56.5 mcg |
| Fish, tuna, white, canned in water, drained solids, 3 oz | 55.8 mcg |
| Turkey from whole, neck, meat only, cooked, simmered, 1 neck | 55.0 mcg |
| Wheat flour, white, bread, enriched, 1 cup | 54.4 mcg |
| Macaroni and cheese, frozen entrée, 1 package | 52.4 mcg |
| Bread stuffing, bread, dry mix, prepared, 1/2 cup | 49.8 mcg |
| Couscous, cooked, 1 cup | 43.2 mcg |
| Oat bran, raw, 1 cup | 42.5 mcg |
| Cheese, ricotta, part skim milk, 1 cup | 41.1 mcg |
| Spaghetti, cooked, enriched, without added salt, 1 cup | 37.0 mcg |
| Mushrooms, shiitake, cooked, without salt, 1 cup | 36.0 mcg |
Adapted from: Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. May be accessed at: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w317.pdf
Assessment and Plan: Selenium
- The benefits of selenium intake in the conditions described here are derived mainly from observational studies and some randomized placebo controlled trials. The dose of greatest benefit of selenium will likely be seen when taking an amount between the recommended daily allowance and up to one half the intake limit. For adults as an example, this would be a dose of somewhere between 55 and 200 mcg oral daily. The greatest benefit is also most likely to occur from the intake of selenium from food sources rather than a supplement since standards for the supplements are not thoroughly regulated and because of the benefit seen in the intake of additional nutrients that food sources contain.
- Preventive Health Advisor recommends that dietary selenium intake including the amount contained within the diet plus that contained in supplements should not exceed 200 mcg daily.
- High selenium food sources are listed above, but to research a more complete list of selenium containing foods, see here: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w317.pdf
- Selenium intake recommendations (3):
- Selenium dietary allowance for both males and females by age: Birth to 6 months: 15 mcg per day, 7–12 months: 20 mcg per day, 1–3 years: 20 mcg per day, 4–8 years: 30 mcg per day, 9–13 years: 40 mcg per day, 14–18 years: 55 mcg per day, 19–50 years: 55 mcg per day, 51+ years: 55 mcg per day, Pregnancy: 60 mcg per day, Lactation: 70 mcg per day.
- Selenium intake limits and toxicity:
- Toxicity may occur over the following intake limits for males and females: Birth to 6 months: 45 mcg, 7–12 months: 60 mcg, 1–3 years: 90 mcg, 4–8 years: 150 mcg, 9–13 years: 280 mcg, 14 years and older including pregnant or lactating women: 400 mcg.
- Symptoms of toxicity may include loss of, or brittle hair or nails, skin rash, fatigue, nausea, diarrhea, irritability and peripheral neuropathy.
- For cancers,
- A higher selenium intake from diet or supplements was associated with a 31% lower risk of cancer (OR 0.69, 95% CI 0.53 to 0.91 ) and a 45% lower risk of mortality (OR 0.55, 95% CI 0.36 to 0.83) and the risk reduction of cancer was greater in men than women 34% vs 10% (4). No protective benefit by selenium was seen in non-melanoma skin cancer and prostate cancer (4).
- For breast cancer, patients with high risk breast cancer on standard treatment plus 387 mcg selenium, 2850 mg vitamin C, 2,500 IU vitamin E, 32.5 IU ß-carotene, 1.2 g gamma-linolenic acid, 3.5 g omega-3 fatty acids from fish oil, and 90 mg CoQ10 were found to survive at least 18 months, had no further evidence of metastasis, less pain medication, no weight loss and remission resulted in 6/32 (5).
- For prostate cancer, when subjects in the highest 20 percent for selenium status were compared with those in the lowest 20 percent, those with the highest selenium status were half as likely to get prostate cancer as those with the lowest levels (6).
- For skin cancer, selenium taken by patients with a history of basal cell cancers or squamous cell cancers for about 6.4 years showed that 200 mcg of selenium did not lower risk of skin cancer and actually may increase the risk of BCC (by 10%) and SCC (by 14%) compared to placebo, but total cancer incidence was decreased by 37%, cancer mortality was decreased 50%, and prostate cancer incidence was decreased by approximately 50% compared to placebo (7).
- Nutritional Prevention of Cancer Study Group also performed a study in 1312 patients to test whether or not 200 mcg of selenium would prevent non-melanoma skin cancer in a randomized, double-blind, placebo controlled trial, but it was found that squamous cell skin cancer risk was increased by 25%, and non-melanoma skin cancer by 17% by calculating a hazard ratio (19).
- For gastrointestinal cancers, a daily vitamin and mineral supplements of 50 mcg of selenium, 30 mg of vitamin E, and 15 mg of beta-carotene given to 29,584 adults at high risk of esophageal and stomach cancers found the treatment resulted in lower mortality from all causes, cancer overall, and gastric cancer (8).
- In coronary heart disease, a meta-analysis of observational studies by Flores-Mateo G found that higher selenium levels were associated with a lower risk of coronary heart disease the author related that there is a lack of randomized controlled trials and selenium should not be offered as a preventive agent for cardiovascular disease (10).
- In thyroid disease, the most common dose of selenium used in research mentioned was 100 mcg oral twice daily. Supplementation with selenium appears to have benefit for thyroid disease over placebo resulting in improved clinical status of autoimmune thyroiditis (Hashimoto’s thyroiditis), Graves’ disease, prevents goiter, and reduces autoimmune antibody titers(11). Toulis KA noted in a systematic review and a meta-analysis that selenium taken over a period of 3 months resulted in significant reduction of thyroid peroxidase autoantibodies in Hashimoto’s thyroiditis, and 3 studies showed better mood (12). Selenium taken for 6 months was found to improve quality of life, was associated with less eye involvement and slowed progression better than placebo and pentoxifylline for Graves’ ophthalmopathy (13).
- In depression, a selenium rich diet of 240 mcg per day compared to 28 mcg of selenium per day studied in men was found to result in a better mood after being asked about six different states of mood (14).
- In Alzheimer’s disease, Loef M et al reviewed 9 placebo controlled clinical trials which showed lack of consistent benefit of selenium supplements for use in treatment of Alzheimer’s disease (15).
- In infertility, a double-blind, placebo controlled, randomized study by Safarinejad MR and Safarinejad S. found that a selenium supplement at dose of 200 mcg per day for 26 weeks improved semen function significantly (16).
References:
1.Chen YC, Prabhu KS, Mastro AM. Is selenium a potential treatment for cancer metastasis? Nutrients. 2013 Apr 8;5(4):1149-68. http://www.ncbi.nlm.nih.gov/pubmed/23567478
2.Hovdenak N, Haram K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):127-32. http://www.ncbi.nlm.nih.gov/pubmed/22771225
3.Dietary Reference Intakes fo Vitamin C, Vitamin E, Selenium, and Carotenoids. A Report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Food and Nutrition Board Institute of Medicine. National Academy Press, Washington, D.C. http://www.nap.edu/openbook.php?record_id=9810&page=R1
4.Dennert G, Zwahlen M, Brinkman M, Vinceti M, Zeegers MP, Horneber M. Selenium for preventing cancer. Cochrane Database Syst Rev. 2011 May 11;(5):CD005195. http://www.ncbi.nlm.nih.gov/pubmed/21563143
5.Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in “high risk” patients supplemented with nutritional antioxidants, essential fatty acids and CoQ10. EiMol Aspects Med. 1994;15 Suppl:s231-40. http://www.ncbi.nlm.nih.gov/pubmed/7752835
6.Yoshizawa K, Willett WC, Morris SJ, Stampfer MJ, Spiegelman D, Rimm EB, Giovannucci E. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst. 1998 Aug 19;90(16):1219-24. http://www.ncbi.nlm.nih.gov/pubmed?term=9719083
7.Clark LC, Combs GF Jr, Turnbull BW, et al.: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276 (24): 1957-63, 1996. http://www.ncbi.nlm.nih.gov/pubmed/8971064
8.Qiao YL, Dawsey SM, Kamangar F, Fan JH, Abnet CC, Sun XD, Johnson LL, Gail MH, Dong ZW, Yu B, Mark SD, Taylor PR. Total and cancer mortality after supplementation with vitamins.
9.Taylor PR, Li B, Dawsey SM, Li JY, Yang CS, Guo W, Blot WJ. Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group. Cancer Res. 1994 Apr 1;54(7 Suppl):2029s-2031s. http://www.ncbi.nlm.nih.gov/pubmed/8137333
10.Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, Guallar E. Selenium and coronary heart disease: a meta-analysis. Am J Clin Nutr. 2006 Oct;84(4):762-73. http://www.ncbi.nlm.nih.gov/pubmed/17023702
11.Köhrle J. Selenium and the thyroid. Institute of Experimental Endocrinology, Charité University Medicine Berlin, Germany. Curr Opin Endocrinol Diabetes Obes. 2013 Oct;20(5):441-8. http://www.ncbi.nlm.nih.gov/pubmed/23974773
12.Toulis KA, Anastasilakis AD, Tzellos TG, Goulis DG, Kouvelas D. Selenium supplementation in the treatment of Hashimoto’s thyroiditis: a systematic review and a meta-analysis. Thyroid. 2010 Oct;20(10):1163-73. http://www.ncbi.nlm.nih.gov/pubmed/20883174
13.Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, Altea MA, Nardi M, Pitz S, Boboridis K, Sivelli P, von Arx G, Mourits MP, Baldeschi L, Bencivelli W, Wiersinga W; European Group on Graves’ Orbitopathy.Selenium and the course of mild Graves’ orbitopathy. N Engl J Med. 2011 May 19;364(20):1920-31. http://www.ncbi.nlm.nih.gov/pubmed/21591944
14.James G. Penland. USDA ARS Grand Forks Human Nutrition Research Center “Selenium Can Lift the Spirits” October 1995. Agricultural Research magazine. http://www.ars.usda.gov/is/ar/archive/oct95/selenium1095.htm
15.Loef M, Schrauzer GN, Walach H.J. Selenium and Alzheimer’s disease: a systematic review. Alzheimers Dis. 2011;26(1):81-104. http://www.ncbi.nlm.nih.gov/pubmed/21593562
16.Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol. 2009 Feb;181(2):741-51. Epub 2008 Dec 16. http://www.ncbi.nlm.nih.gov/pubmed/19091331
17.Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. May be accessed at: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w317.pdf
18.National Institutes of Health Office of Dietary Supplements. Website accessed Sept 21, 2013. http://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/
19.Duffield-Lillico AJ1, Slate EH, Reid ME, Turnbull BW, Wilkins PA, Combs GF Jr, Park HK, Gross EG, Graham GF, Stratton MS, Marshall JR, Clark LC; Nutritional Prevention of Cancer Study Group. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst. 2003 Oct 1;95(19):1477-81. http://www.ncbi.nlm.nih.gov/pubmed/14519754