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Selenium

James Meschino DC, MS, ROHP

General Features
Selenium is present in all the tissue of the body and is most highly concentrated in the kidneys, liver, spleen, pancreas and testes.  It is readily absorbed and excreted in urine and feces.

Levels of soil selenium vary greatly from country to country.  There are low levels in Europe, parts of the United States, New Zealand and parts of China.  There are high levels in Japan, Thailand, Philippines and Puerto Rico.  In rural China, where selenium levels are very low, children are susceptible to a specific cardiomyopathy known as Keshan disease.  Keshan disease is characterized by multiple focal myocardial necroses, likely caused by free-radical damage.  Patients with Keshan disease have lower blood levels of selenium than people elsewhere in the world.  A prevention program to reduce the incidence of Keshan disease has employed the use of selenium supplementation.  It has been very effective at reducing the incidence of Keshan disease in children in China and has shown benefits in New Zealand as well.

The most well known function of selenium is that it is an important constituent of the antioxidant enzyme, glutathione peroxidase.  Glutathione peroxidase protects against accumulation of hydrogen peroxide, which can undergo further biochemical transformation to yield the very aggressive and damaging reactive oxygen species known as hydroxy-radicals.1

Some studies indicate that individuals living in areas where the selenium soil concentration is high and/or have higher blood levels of selenium, experience a lower incidence of cancer.2,3

Animal and laboratory studies indicate that selenium has other cancer-protective (chemoprevention) effects in addition to antioxidant enzyme activation.  These include the induction of apoptosis (programmed cell death of cancer cells), decreased synthesis of prostaglandin series-2, and immune system modulation.4,5

Due, primarily, to its effects on antioxidant function selenium has received much attention as a nutrient that may help to prevent cancer, heart disease, cataracts, reduce inflammatory diseases and help stimulate immune function in immune-compromised patients (e.g., HIV infection).6

Absorption and Metabolism
Absorption of selenium appears to be under no physiological control.  Absorption of selenium, given as selenite solutions is greater than 90 percent and is possibly 100 percent, according to some human studies.  It is also readily excreted to help prevent states of toxicity.  The body stores only a few micrograms of selenium in all of the body tissue combined.7

Recommended Daily Allowance (Selenium)

Age Group Dosage (mcg)
0-6 mths                 10
6-12 mths                 15
1-6 yrs                 20
7-10 yrs                 30
Males 11-14                 40
Males 15-18                 50
Males 19 and over                 70
Females 11-14                 45
Females 15-18                 50
Females 19 and over                 55
Pregnant females                 65
Lactating females                 756

Supplementation Studies and Clinical Applications

  1. Human Cancer Prevention Studies

A large body of evidence suggests that cancer rates and mortality increase under conditions of sub-optimal selenium intake.5,8  In Linxian China, where selenium soil levels are known to be low, they have one of the highest rates of esophageal and stomach cancer in the world.

In a five year study of almost 30,000 men and women (free from cancer at the outset of the study), supplementation with beta-carotene, Vitamin E, and selenium reduced death rates from cancer by 13 percent, stomach cancer by 21 percent and death rates from all causes by 9 percent as compared to other vitamin and mineral combinations and placebo.9  Death rates from lung cancer were 45 percent lower and there was a 10 percent reduction in strokes in those receiving the combination of beta-carotene, vitamin E and selenium.10  Doses were 1-2 times the RDA.

In a clinical trial of over 1,300 patients with previous skin cancer, patients receiving 200 mcg of selenium supplementation vs. placebo for 4.5 years had a 37 percent reduction in total cancer incidence and a 50 percent lower risk for colorectal cancer and a 53 percent lower risk for lung cancer.  However, the selenium group failed to show benefit in blocking skin cancer recurrence or progression compared to the placebo group.11

In a recent study by Russo, et al., they showed that patients with selenium blood levels of 107 mcg/L had a 50 percent greater chance of having multiple cancerous lesions in the colon compared to patients referred for colonoscopy, who had blood levels of selenium at or above 120 mcg/L.  Other studies also indicate that higher serum selenium levels are associated with as much as a 4.2 times lower risk of colon cancer.4

Another study found that men consuming the most dietary selenium (assessed by measuring toenail selenium, a good indicator of long-term selenium ingestion) developed 65 percent fewer cases of advanced prostate cancer than did men with the lowest selenium intake levels.12

  1. Immune Function

Selenium supplementation at 200 mcg per day has been shown to stimulate white blood cell and thymus function.  Increased killer cell activity and other parameters of heightened immune function have been shown even in otherwise healthy patients.  Some of the effect appears to be mediated through increased expression of the immune-enhancing interleukin-2.  This in turn increases the rate of white blood cell proliferation and differentiation into more capable immune system leukocytes.13,14,15

Selenium supplementation has also been able to significantly increase glutathione levels and activity in HIV-positive patients.  Reduction in glutathione levels in these patients carries a poor prognosis for the progression of HIV to AIDS.16,17

  1. Cardiovascular Disease (CVD)

Epidemiological evidence suggests that CVD increases as selenium intake decreases.  As noted earlier, Keshan disease is primarily caused by sub-optimal blood levels of selenium (< 1 mcg/ml) vs. more normal values (19-25 mcg/ml).7

Through antioxidant activation, it may help to reduce LDL-cholesterol oxidation and may also improve the HDL-to-LDL ratio and reduce blood platelet aggregation.

In a double-blind study, one milligram (1,000 mcg) of selenium and 200 I.U. of Vitamin E daily produced significant relief from angina pain vs. placebo.  However, this is preliminary evidence only.18

  1. Inflammatory Conditions

Supplementing with 50-200 mcg of selenium and 200-400 I.U. of Vitamin E has been shown to improve clinical symptoms and signs in patients with rheumatoid arthritis.  Glutathione peroxidate enzyme is especially important in activating the anti-inflammatory prostaglandins and leukotrienes.19,20  Other inflammatory conditions may also benefit from Vitamin E and selenium supplementation such as other forms of arthritis, eczema and psoriasis, where selenium and glutathione peroxidase levels are often low.21,22  In a German study, 200 mcg of selenium significantly improved signs and symptoms of rheumatoid arthritis and patients required less anti-inflammatory medications and cortisone.  Less tender joints and morning stiffness were reported by the subjects receiving the selenium.  Placebo subjects did not report the same benefits.23

  1. Cataract Prevention

One major study demonstrated that higher selenium and glutathione concentrations in the lens of the eye were associated with a lower risk of cataract development.  Other antioxidants are also known to be important in cataract prevention (e.g. Vitamin C and E).24

  1. Other Applications

Shampoos or prescription solutions containing selenium sulfide are used for treatment of fungal infections, including tinea capitis.  Selenium helps to block the undesirable absorption of cadmium, mercury and arsenic.25

Dosage Ranges and Considerations

Purpose Daily Dosage
 General Support (Adults)  50-200 mcg is often recommended25
 Arthritis  100-200 mcg19,20
 Heart Disease  100-300 mcg25
 Cancer Support  2 00-400 mcg5
 HIV-Infection and Immune Compromised States  100-300 mcg16,17

Side Effects and Toxicity
Selenium is considered extremely safe up to 1000 mcg per day.18  Populations routinely ingesting 500 mcg or more per day show no signs of toxicity.5  However, some reports suggest that doses as low as 900 mcgs daily over a prolonged period of time can produce signs of selenium toxicity (depression, nervousness, nausea, vomiting, garlic odour to breath and sweat, loss of hair and fingernails, abnormal nails and skin depigmentation).6  High dose supplementation may exacerbate low thyroid function.26

Drug-Nutrient Interactions
The following drugs have been shown to deplete selenium status:

  1. Corticosteroid drugs27
  2. Oral contraceptives28

Valproic acid, the active ingredient in many drugs used to treat epilepsy, and clozapine, used to treat schizophrenia, can decrease selenium status, thus, increased selenium intake may be warranted in these cases.

There are no well-known instances of selenium interfering with any medications.29

 Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and mineral supplements.  All other supplements or dose alterations may pose a threat to the developing fetus and there is generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other than a prenatal supplement.  Any supplementation practices beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium and the treatment of preeclampsia.)

References:  Pregnancy and Lactation
1.Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.2.     Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and Company Inc. 1998.3.     The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.4.     Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine. Institute of Applied Complementary Medicine Inc. 1997.

 

  1. Standard Textbooks of Nutritional Science:

– Shils M, Shike M, Olson J, Ross C.  Modern Nutrition in Health and Disease. 9th ed.  Baltimore, MD: Lippincott Williams & Wilkins; 1993.

– Escott-Stump S, Mahan LK, editors.  Food, Nutrition and Diet Therapy. 10th ed.  Philadelphia, PA: W.B. Saunders Company; 2000.

– Bowman B, Russell RM, editors. Present Knowledge in Nutrition, 8th ed.  Washington, DC:.ILSI Press; 2001.

– Kreutler PA, Czajka-Narins DM, editors. Nutrition in Perspective. 2nd ed.  Upper Saddle River, NJ: Prentice Hall Inc.; 1987.

  1. Schrauzer GN, White DA, Schneider CJ. Cancer mortality correlation studies III. Statistical associations with dietary Selenium intakes.  Bioinorganic Chem 1977;7:23-56.
  2. Shamberger RJ, Willis CE. Selenium distribution and human cancer mortality.  Clin Lab 1971;2:211-21.
  3. Russo MW, et al. Plasma Selenium levels and the risk of colorectal adenomas.  Nutr and Cancer 1997; 28(2):125-9.
  4. Simone C. Cancer and Nutrition.  Garden City Park, NY: Avery Publishing Group Inc.; 1992.
  5. Murray M. Encyclopedia of nutritional supplements.  Rocklin, CA: Prima Publishing; 1996.  222-8.
  6. Burk RF.   In: Nutrition Foundation.  Nutrition reviews: present knowledge in nutrition.  5th ed. Washington DC: Nutrition Foundation Inc,; 1984.  p. 519-27.
  7. Hocman G. Chemoprevention of cancer: selenium.  Int 5 Biochem 1998;20:123-32.
  8. Blot WJ, Li JY, Taylor PR, Guo W, Dawsey S, Wang GQ, et al. Nutrition intervention trials in Linxian China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population.  J Natl Cancer Inst 1993;85:1483-92.
  9. Blot WJ, Li JY, Taylor PR, Li B. Lung cancer and vitamin supplementation.  N Engl J Med 1994;331(9):614.
  10. Clark LC, Combs GF, Turnbull BW, Slate EH, Chalker DK, Chow J, 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 1996;276(24):1957-63.
  11. Yoshizawa K, Willett WC, Morris SJ, Stampfer MJ, Spiegelman D, Rimm EB, et al. Study of prediagnostic selenium levels in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst 1998;90:1219-24.
  12. Kiremidjian-Schumacher, L, Stotzky G. Selenium and immune responses.  Environmental Res 1987;42:277-303.
  13. Kiremidjian-Schumacher L, Roy M, Wishe HI, Cohen MW, Stotzky G. Supplementation with selenium and human immune cell functions; II, effect on cytotoxic lymphocytes and natural killer cells.  Biol Trace Elem Res 1994;41:115-27.
  14. Roy M, Kiremidjian-Schumacher L, Wishe HI, Cohen MW, Stotzky G. Supplementation with selenium and human immune cell functions. I. Effect on lymphocyte proliferation and interleukin-2 receptor expression.  Biol Trace Elem Res 1994;41:103-14.
  15. Delmas-Beauvieux MC, Peuchant E, Couchouron A, Constans J, Sergeant C, Simonoff M, et al. The enzymatic antioxidant system in blood and glutathione status in HIV-infected patients: effects of supplementation with selenium or beta-carotene.  Am J Clin Nutr 1996;64:101-7.
  16. Marmor M, Alcabes P, Titus S, Frenkel K, Krasinski K, Penn A, et al. Low serum thiol levels predict shorter times to death among HIV-infected injecting drug users. AIDS 1997;11:1389-93.
  17. Hendler S. The doctors’ vitamin and mineral encyclopedia.  Simon and Schuster 1990:1983-92.
  18. Tarp U, Overvad K, Thorling EB, Graudal H, Hansen JC. Selenium treatment in rheumatoid arthritis. Scand J. Rheumatol 1985:14:364-8.
  19. Munthe E, Aaseth J. Treatment of rheumatoid arthritis with selenium and Vitamin E. Scan J Rheumatol 1984;53(Suppl):103S.
  20. Tarp U, Overvad K, Hansen JC, Thorling EB. Low selenium levels in severe rheumatoid arthritis. Scand J Rheumatol 1985;14:97-101.
  21. Hinks L, et al. Trace element status in eczema and psoriasis. Clin Exp Derm 1987;12:93-7.
  22. Heinle K, Adam A, Gradl M, Wiseman M, Adam O. Selenium concentration in erythrocytes of patients with rheumatoid arthritis. Clinical and laboratory chemistry infection markers during administration of selenium.  Med Klin 1997;92(3):29-31.
  23. Karakucuk S, Ertugrul Migra G, Faruk Ekinciler O. Selenium concentrations in serum, lens and aqueous humor of patients with senile cataracts.  Acta Ophthalmol Scand 1995;73(4):329-32.
  24. Reavley N. The new encyclopedia of vitamins, minerals, supplements and herbs.  M Evans and Company Inc. 1998:294-303.
  25. Contempre B, Dumont JE, Ngo B, Thilly CH, Diplock AT, Vanderpas J. Effects of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine deficient subjects with selenium. J Clin Endocrinal Metabol 1991;73:213-5.
  26. Peretz A, Neve J, Vertongen F, Famaey JP, Molle L. Selenium status in relation to clinical variables and corticosteroid treatment in rheumatoid arthritis. J Rheumatol Dec 1987;14(6):1104-7.
  27. Heese HD, Lawrence MA, Dempster WS, Pocock F. Reference concentrations of serum selenium and manganese in health nulliparas.  S Afr Med J 1988;73(3):163-5.
  28. Healthnotes 1998-2002. Available from: URL: http://www.healthnotes.com.
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