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LE Magazine December 2004
Getting Serious about Selenium
By Dale Kiefer

The trace element selenium was once thought to be nothing more than a curiosity. Chemically similar to sulfur, which has known biological functions, and found in soils throughout much of the world, selenium was nevertheless considered biologically irrelevant.

By the mid-twentieth century, however, scientists had discovered that selenium is an essential nutrient for animals. Without it, they realized, animals cannot function properly.1,2

Entering the twenty-first century, we now know that selenium is crucial to the health of humans and animals alike. Moreover, in the nutritional sphere, selenium is considered a rising star that offers protection against a wide range of damaging diseases and conditions.

Selenium’s promotion from irrelevant mineral to essential trace element is the result of our growing understanding of its multifaceted, indispensable roles in regulating metabolism, orchestrating normal growth, launching successful reproductive efforts, neutralizing free radicals, and defending the body against infections, among other key life processes.3

In fact, selenium is so important to the human body that it is the only essential trace element specified in the genetic code. Selenocysteine, known as the twenty-first amino acid, is incorporated in numerous proteins under the direction of human genetic code.4 Although plants do not appear to require selenium, many plants extract it from soil and store it in their tissues, where it is available for consumption by humans and animals.1,2

In the early 1970s, scientists discovered that selenium plays an integral role in protecting human cellular membranes from peroxide damage, by virtue of its inclusion in glutathione peroxidase, a natural antioxidant enzyme. Today, we know that selenium is incorporated in at least 25 unique proteins in the body. Known as selenoproteins, they play integral roles in everything from activating thyroid hormone and regenerating spent vitamin C, to promoting healthy pregnancies.5-8

Selenium’s Multiple Roles
Scientists have identified four different glutathione peroxidases containing selenium.3 In their crucial role as antioxidant enzymes, each of these distinct proteins neutralizes potentially damaging free radicals, or reactive oxygen species, by removing oxygen molecules and thus transforming the threatening compounds into harmless molecules such as water or alcohols. Their targets include destructive hydrogen peroxide and lipid hydroperoxides.

Another selenium complex, known as selenoprotein P, circulates in blood plasma and is associated with cells lining the interior of blood vessels. Although selenoprotein P’s functions remain sketchy, it is believed to protect blood vessels by neutralizing the reactive oxygen species peroxynitrate, and to act as a transport protein.5,9,10

Key to Thyroid Hormone Regulation
Still other selenium-containing proteins, the iodothyronine deiodinases, are responsible for making active thyroid hormone available in the general circulation. Indeed, the thyroid gland holds the highest selenium concentration of any organ in the body, due to selenium’s crucial role in transforming inactive thyroxine, or T4, into biologically active thyroid hormone (triiodothyronine, or T3), by catalyzing the removal of iodine from T4. Three different selenium-containing enzymes are responsible for both activation and inactivation of thyroid hormone.

Selenium is essential, therefore, to the success of important processes regulated by thyroid hormone, such as normal growth, development, and metabolism.11 Scientists recently examined selenium status and thyroid health among 1,900 people in France in a large, ongoing study of nutritional status and health. They determined that selenium may offer significant protection against the development of goiter and other abnormalities of the thyroid gland, particularly when iodine levels are low.12

Supporting Healthy Immune Response
Selenium is a crucial component of a properly functioning immune system. In recent years, scientists have discovered that selenium deficiency allows an otherwise benign virus, coxsackievirus, to mutate into a vicious microbe capable of attacking heart muscle. A heart condition known as Keshan disease is widespread in certain areas of rural China, where the soil is poor in selenium and people subsist on locally grown food. In these areas, adult life spans have been shortened and children in the most selenium-deficient areas have been reported to succumb to the fatal disease at 1 to 10 years of age.13 Selenium supplementation is known to protect against development of Keshan disease.1,2

Scientists recently have shown that selenium deficiency is directly related to the development of Keshan disease in a mouse model.14-17 It is highly likely that selenium plays a similar role in protecting humans against the viral mutation associated with the development of Keshan disease. In a related finding, scientists have discovered that selenium deficiency in mice is also associated with greater virulence of an otherwise mild strain of the influenza virus. Mice deprived of selenium experienced far worse inflammation of the lungs because of influenza infection than control mice receiving selenium in their diet. Lack of selenium promoted changes in the genetic material of the virus, allowing it to become more dangerous.15-18

This link between selenium deficiency and increased viral virulence is suspected to underlie several other diseases. Researchers in China have shown that supplementation with selenium dramatically reduces the incidence of hepatitis B viral infection in both animals and humans. In those already infected, supplementation significantly prevented progression of the infection to deadly liver cancer. When supplementation was withdrawn, liver cancer rates began climbing to previous levels.19

In numerous recent medical journal reports, researchers have noted the importance of selenium in preventing progression of HIV infection to full-blown AIDS.1,20-22 HIV-positive men and women receiving selenium supplementation were admitted to the hospital less often than HIV-positive patients receiving placebo, according to the results of a placebo-controlled, double-blind study conducted in Florida. As reported recently in the medical journal HIV Clinical Trials, researchers found that overall hospitalization costs dropped 28% among patients receiving selenium therapy compared to those receiving the placebo supplement.22

Selenium Deficiency Tied to Deadly Viruses
Scientists have long known that malnutrition is associated with a higher incidence of infection and disease. It was assumed that this susceptibility to illness results when an immune system weakened by nutritional deficiencies becomes incapable of mounting an adequate defense. However, new findings about selenium have prompted a dramatic shift in our understanding of infection and disease. As a direct result of selenium-deficiency research, we now know that malnutrition not only weakens the immune system, but also, in some instances, transforms the pathogens that seek to infect us, rendering them more destructive.

Once the pathogen’s genome has changed, subsequent progeny of that pathogen retain the newfound level of virulence; that is, they are capable of infecting even healthy individuals whose selenium levels are optimal.3,15 In essence, if you are selenium deficient, you could become a sort of viral incubator, capable of producing far more dangerous pathogens that endanger not only your health but that of your neighbor.

This amazing discovery has led to speculation that selenium deficiency, among other vitamin and mineral deficiencies, may be responsible for the emergence of devastating viral diseases. Some scientists have even proposed that the emergence of new strains of influenza, the common cold, or even the dreaded Ebola virus may be related to viral changes wrought by interactions with selenium-deficient hosts in areas of the world (such as regions of Africa and China) where the soil’s selenium content is exceptionally low.1,16

Pioneering Research Melds Nutrition, Virology
Dr. Orville A. Levander is a nutritional researcher with the United States Department of Agriculture’s Beltsville Human Nutritional Research Center in Maryland. For the past decade, he has collaborated with Dr. Melinda A. Beck, a leading virologist affiliated with the University of North Carolina at Chapel Hill. Together, they have investigated selenium’s role in enhancing viral virulence around the world and have published their work in leading medical journals.15,17,23 As far as they know, their discovery that selenium deficiency promotes changes in the basic genetic material of viruses had never before been reported or even suspected, according to Levander.

“It was such an unusual twist, it almost seemed unlikely,” says Levander. “I’ll be the first to admit we didn’t expect it.” Ordinarily, Levander adds, there’s “too big a gulf” between nutritionists and virologists for successful collaboration. His work with Dr. Beck, therefore, represents a small triumph for basic medical research. “[Our work] shows the value of interdisciplinary research,” says Levander. “You get to find something quite interesting. That’s what happened to us, I think.”

Beck, Levander, and their colleagues are evidently the first scientists in history to prove that a nutritional deficiency promotes the development of more dangerous microbes. Levander is somewhat surprised that this discovery has not made a bigger splash among virologists, or among the general public, for that matter. Given the profound implications of the research, one might expect that virologists would rush to replicate and expand on their work. But that has not happened to any great degree, says Levander. He speculates that scientists’ specialization and narrow focus may be the reason. In the meantime, he notes that the National Cancer Institute is funding a large clinical trial designed to show definitively whether selenium protects against cancer. In about three years, when those results become available, Levander predicts, “All hell may break loose.”

As one scientist has declared, the bottom line regarding our current understanding of selenium’s role in immunity is this: “Selenium supplementation appears to en-hance the immune response.”1 Even in individuals with “normal” levels of selenium, supplementation has been shown to stimulate the immune system, provoking a proliferation of activated T cells. Human lymphocytes showed an increased ability to transform into cells capable of destroying tumor cells, and natural killer cell activity increased by 82% above baseline activity after supplementation with 200 micrograms (mcg) per day of selenium.24 In subsequent work, the same research team discovered that selenium supplementation “restores age-related decline in immune cell function.”25

Selenium Is Cancer Preventive
Some of the most exciting selenium research currently under way involves the nutrient’s ability to prevent cancer. Selenium gained national attention in the mid-1990s, with the release of findings from the Nutritional Prevention of Cancer (NPC) study conducted by researchers at the University of Arizona. More than 1,300 skin-cancer patients from clinics across the eastern US were assigned to receive either 200 mcg of selenium per day or placebo. Researchers wondered whether selenium could protect subjects from repeat bouts with basal cell or squamous cell carcinoma, which ordinarily recurs in about 25% of cases. Participants were treated for an average of four and a half years, with about six and a half years of follow-up. Although the incidence of repeat skin cancers was not reduced among selenium patients, the selenium group did experience 46% fewer lung cancers, 58% fewer colorectal cancers, and a remarkable 63% fewer prostate cancers than patients in the placebo group. In all, the selenium group recorded 50% fewer cancer deaths than the placebo group.26-28

Researcher GF Combs Jr., who was involved with the investigation from its inception, told Life Extension: “When we started planning this, I was skeptical. I didn’t expect us to find anything of significance. Our formal hypothesis was that selenium would have no effect on cancer rates.” But blinded data soon revealed that one group of patients was experiencing a lower overall death rate. “One parameter we looked at was survival rates,” says Dr. Combs. A safety review committee mandated the implementation of secondary end points. Without changing the study’s initial design, researchers would now document all deaths and incidences of cancer of any type among study participants. That analysis revealed the remarkable preventive effects of selenium against prostate, lung, and colorectal cancers. “I was surprised at the magnitude of the effect,” says Dr. Combs, “and I was pleasantly surprised at the consistency of the effect.”

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