Selenium (Se)

The Antioxidant Mineral

Stewart Eckard and Mike Darnofall

Dietary Sources

• Wheat germ (111)
• Whole wheat bread (66)
• Oats (56)
• Turnips (27)
• Brazil nuts (103)
• Bran (63)
• Brown rice (39)
• Garlic (25)

Deficiency

• Keshan disease (heart) - China
• Kashan-Beck disease (arthritis) - China
• Increased risk of cancer, heart disease, and low immune function with chronic low intake of Se.

Beneficial Effects

• Anti-oxidant activity (Se-glutathione peroxidase)
• Free radicals / strong oxidizers
• Thyroid hormone production
• Antagonistic to heavy metals (lead, mercury, cadmium, aluminum)

Principal Uses

Selenium works with vitamin E (tocopherol) in preventing free radical damage to cell membranes, proteins, and DNA

Anti-Cancer

• Low Se = increased cancer risk
• Many cancer pts. have low blood levels of Se / glutathione peroxidase
• Cancer preventive vs. antitumor effects
• men > women
• respiratory / GI cancers most significant

Immune Function

• Se increases antibody production in animals
• Protects macrophages from free radicals they produce to kill bacteria
• Increases. activity of natural killer cells (IL-2)

Cardiovascular / Circulatory Disease

• Heart disease greatest where Se intake is lowest
• "Stroke belt" (Georgia and Carolinas) an area of low soil Se
• Se supplements inc. HDL/LDL ratio and dec. platelet aggregation
• Protects smokers most

Inflammatory Conditions

• Low Se-glutathione levels = increased. tissue damage
• free radicals, oxidants, prostaglandins, leukotrienes
• Se / Vit. E may help:

• rheumatoid arthritis
• eczema
• psoriasis

Cataracts

• Patients with cataracts:
• decreased levels of Se in aqueous humor of eye
• increased levels of hydrogen peroxide (up to 25 times) in aqueous humor of eye
• Lens is unprotected against sun / free radical damage

Pregnancy / SIDS

• Deficiency in Se and vitamin E is associated with White Muscle Disease (WMD) in young animals
• WMD, Keshan Disease, SIDS associated with focal cardiac necrosis
• leads to cardiac failure / circulatory collapse
• Heart is susceptible to oxidative damage and subsequent necrosis

Available Forms

• Sodium selenite
  • less effectively absorbed

• Selenomethionine
• High selenium yeast
  • preferred forms

Dosage Ranges

Adults

• 50-200 mcg/day

Children

• 1.5 mcg/kg body weight

Safety Issues

• Toxicity with 900 mcg/day (chronic use)

• Signs / symptoms of toxicity:
  • nervousness, depression, emotional instability
  • nausea / vomiting
  • garlic odor of breath and sweat
  • loss of hair / fingernails (severe)

Interactions

• Heavy metals (lead, mercury, cadmium, aluminum) dec. Se absorption
• Vitamin C dec. Se absorption

Clinical Studies

• Effects of selenium supplementation for cancer prevention. . . (Clark et al)
• The protective role of selenium on the toxicity of cisplatin chemotherapy (Hu et al)
• Selenium treatment in rheumatoid arthritis (Tarp et al)

Clinical Trials

1) Effects of Selenium Supplementation for Cancer Prevention in Patients With Carcinoma of the Skin (Clark et. al.)

• multi-center, double-blind, randomized, placebo-controlled
• 1312 patients from ages 18-80 years with mean age of 63 years
• patients chosen from 1983-1991, treated for ~ 4.5 years, followed up for ~ 6.4 years
• 200 mcg/d of Selenium or placebo

Originally, the authors were only looking at incidence of basal and squamous cell carcinomas. After more money was allotted to the study, secondary endpoints were added. These included other types of cancer incidence, total cancer mortality, and all-cause mortality.

Authors concluded that there was no significant protection against BCC or SCC by taking Selenium supplements. However, the results of secondary endpoints support the claims that Selenium may reduce the incidences of and deaths from carcinomas of different sites.

• Total Cancer Mortality: 29 deaths in Selenium group
• 57 deaths in controls

• Total Cancer Incidence: 77 cases in Selenium group
• 119 cases in controls

• Prostate Cancer: RR = 0.37; 95% CI, 0.18-0.71; P = .002

• Colorectal Cancer: RR = 0.42; 95% CI, 0.18-0.95; P = .03

• Lung Cancer: RR= 0.54; 95% CI, 0.3-0.98; P = .04

• The other results such as BCC, SCC, and other forms of cancer were not significant with P > 0.05.

2) The Protective Role of Selenium on the Toxicity of Cisplatin-Contained Chemotherapy Regimen in Cancer Patients (Hu et. al)

• Cross-Over study design, two groups A (20 pts) and B (21 pts)
• Group A: Se-supplement during 1st cycle as case patients
• No Se during 2nd cycle as control
• Group B: No Se-supplement during 1st cycle as control
• Se-supplement during 2nd cycle as case patients
• Selenium supplementation = 4000 mcg/d divided into four doses starting four days before chemo and lasting eight days
• Cisplatin = 60-80 mg/sq meter IV on day 1 of each cycle
• Measured serum Selenium levels, liver function enzymes, BUN, Cr, urine enzymes and CBC before and after therapy

The results showed that the Selenium levels increased from 70.4 to 157.04 ng/ml in the case patients. The peripheral WBC counts were higher in the case patients (3.35 + 2.01 vs. 2.31 + 1.38 [x109L]/L), but GCSF use (110.1 + 82.2 vs. 723.6 + 92.6 IU) and transfusion volumes (0 vs. 62 + 38 ml) were lower than the control groups. The urine enzymes, used to measure the nephrotoxicity of Cisplatin, were significantly lower in the case patients than controls. The study suggests that Selenium is effective as a protective agent against Cisplatin toxicity.

1. Clark et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin, JAMA, 276(24):1957-63, 1996.

2. Hendler, S. The Doctor's Vitamin and Mineral Encyclopedia Fireside NY,NY,I990. Pp 183-192.

3. Hu et al. The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients, Biol Trace Elem Res, 276(3): 33141,1997.

4. Mayes, P.A. Harper's Biochemistry. Appleton and Lange, Stamford, Conn. 1996, P.621.

5. Murry, M. Encyclopedia of Nutritional Supplements, Prima Pub., Rocklin, CA., 1996. Pp 222-231.

6. Murry and Pizzomo. A Textbook of Natural Medicine~ Bastyr Univ. Pub., Bothell, WA, 1996. Pp V: Antiox. 1-10.

7. Tarp et al. Selenium treatment in rhe7umatoid arthritis, Scan J Rheumatol, 14(4): 364-8, 1985.

http://www.selenium.org/