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)

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

2. 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

3. 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

4. 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

5. 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

6. 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

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

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