How we know that selenium supplementation is important

Selenium?  A trace element?  You might well ask: How do we know that adequate amounts of dietary and supplemental selenium are important to us?
The first answer is: because we can see that selenium deficiency makes people sick.
A further answer is that we now know that selenium is an essential component of antioxidant enzymes.
And, on the basis of the results of randomized controlled trials, we know that selenium supplementation reduces the risk of cancer, reduces the risk of heart disease, and improves immune function.
Selenium is also very useful for reducing the toxic effects of heavy metals in the body.

Reason number one: Selenium-deficiency diseases
Keshan disease
In the 1960’s and 1970’s, thousands of people living in a region of China with selenium-poor soil, and, consequently, with selenium-poor food, died from the effects of a form of heart disease.  The disease, which took its name from Keshan county in the afflicted region of China, is characterized by inflammation and enlargement of the heart muscle and excess fluid in the lungs. The primary cause of the disease was selenium deficiency.

Medical examination of patients with Keshan disease has shown that there may also be a viral infection at play and that the viral infection may be exacerbated by the selenium deficiency, thereby making the effects of the selenium deficiency on the heart even worse.

According to the Merck Manual of Diagnosis and Therapy, the prescribed treatment for Keshan disease is selenium supplementation.  The prevention of the development of Keshan disease depends upon enrichment of selenium-poor soils with selenium and upon the use of selenium supplements.

Kashin-Beck disease
Kashin-Beck is another disease that affects people living in selenium-poor regions of the world: large parts of China, Korea, Siberia, and Tibet in particular.  The disease is characterized by the development at a young age of forms of osteoarthritis and, in the most severe cases, by the development of joint deformities.

Studies that have been carried out in the affected regions give hope that selenium supplementation can reduce the risk of Kashin-Beck disease and that long-term selenium supplementation can lead to the repair of damage to bone tissue.

Reason number two: selenium-dependent antioxidant enzymes
Sometime after bio-medical researchers became aware of the dangers of selenium deficiency, they began to learn more and more about the role of selenium in the activity of antioxidant enzymes.  The researchers discovered that selenium is a necessary component of the following antioxidant enzymes (antioxidants are necessary to neutralize the harmful free radicals that cause oxidative damage to cell structures, proteins, lipids, and DNA):

• the glutathione peroxidases
• the thioredoxin reductases
• the iodothyronine deiodinases

Altogether, selenium researchers have identified 25 selenium containing proteins (selenoproteins) in humans, and the study of the biological functions of these selenoproteins has stimulated much interest in parts of the bio-medical community.

Reason number three: selenium and cancer, heart disease, and immune function
Cancer
Animal studies have shown that selenium supplementation can reduce the risk of developing cancer. Human observational studies have shown that lower plasma selenium status is associated with a higher risk of developing cancer [Tinggi].  Large human intervention studies using selenium in conjunction with other oral antioxidant supplements have shown that supplementation significantly reduces the risk of cancer [Clark].

The mechanisms by which selenium supplementation reduces the risk of cancer are not yet fully understood.  One theory holds that the cancer-preventive effects of selenium supplementation come from selenium’s role in the body’s antioxidant defense against oxidative damage, especially DNA damage.  Other anti-cancer mechanisms of selenium that are under investigations are the following possible effects:

• inducing apoptosis (programmed cell death) of tumor cells
• inducing a halt to the progression of the tumor cell cycle
• inducing cell repair activities
• inhibiting the over-activation of protein kinase C
• regulating androgen- and estrogen-receptor expression [Tinggi]

Heart disease
Low plasma or serum selenium status (< 85 micrograms per Liter) is associated with a higher risk of heart disease [Alehagen].  Daily supplementation of healthy elderly Swedish citizens with a combination of selenium and Coenzyme Q10 in a four-year randomized controlled trial has shown that the supplementation significantly reduces the risk of heart-disease-related death, improves heart function, and decreases the extent of hospitalizations [Alehagen].

Immune function
In addition to its anti-inflammatory and anti-oxidant properties, selenium is known to have anti-viral effects.  Selenium is associated with the increased activity of various types of immune system cells: the natural killer (NK) cells, macrophages, and neutrophils of the innate immune system and the B-cells and T-cells of the adaptive immune system [Rayman].

Selenium supplementation has been shown to slow the progress of the HIV virus in randomized controlled trials [Baum].

Higher selenium status is associated with reduced risk of autoimmune thyroid disease [Rayman]. Selenium supplementation has been shown to decrease anti-thyroid antibody levels in patients with Hashimoto’s disease to improve thyroid gland structure [Drutel].  Supplementation with selenium has also been shown to help patients with Graves’ disease return more rapidly to normal thyroid function [Drutel].

There is no known effective treatment for Alzheimer’s disease at present.  A recent review (2016) has made the case for selenium supplementation of elderly patients with mild cognitive impairment to prevent the development full-blown Alzheimer’s disease [Aaseth].

Conclusion
At this writing, the best explanation of the beneficial health effects of selenium supplementation with respect to cancer risk, heart disease risk, and immune system function is that selenium supplementation raises the blood selenium status sufficiently to permit the optimal functioning of the various antioxidant enzymes including the selenoprotein SEPP1, which has an antioxidant function in addition to its other biological functions.

The diet in many regions of the world does not provide adequate amounts of selenium to permit the optimal functioning of the selenoproteins.  Moreover, to the extent that selenium in the body is used to de-toxify heavy metals such as mercury, cadmium, and lead, the body’s reserves will be depleted and will need replenishing via supplementation.

Sources

Aaseth, J., Alexander, J., Bjørklund, G., Hestad, K., Dusek, P., Roos, P. M., & Alehagen, U. (2016). Treatment strategies in Alzheimer’s disease: a review with focus on selenium supplementation. Biometals: An International Journal On The Role Of Metal Ions In Biology, Biochemistry, And Medicine, 29(5), 827-839.

Alehagen, U., Alexander, J., & Aaseth, J. (2016). Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial. Plos One, 11(7), e0157541.

Baum, M. K., Campa, A., Lai, S., Sales Martinez, S., Tsalaile, L., Burns, P., & Marlink, R. (2013). Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial. Jama, 310(20), 2154-2163.

Clark, L. C., Combs, G. J., Turnbull, B. W., Slate, E. H., Chalker, D. K., Chow, J., & … Taylor, J. R. (1996). 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), 1957-1963.

Drutel, A., Archambeaud, F., & Caron, P. (2013). Selenium and the thyroid gland: more good news for clinicians. Clinical Endocrinology, 78(2), 155-164.

Rayman, M. P. (2012). Selenium and human health. Lancet (London, England), 379(9822), 1256-1268.

Tinggi, U. (2008).  Selenium: its role as antioxidant in human health.  Environ Health Prev Med, 13: 102-108.