Life Extension Magazine

Life Extension Magazine November 2006

Report

Selenium

By Julius G. Goepp, MD

By Julius G. Goepp, MD

When was the last time your doctor suggested that you supplement with selenium in an effort to prevent cancer? Scientists now know that this trace mineral has extraordinary value in fighting various cancers and other conditions involving oxidative stress and inflammation.1,2

Doctors assume that we get enough selenium through plant foods. Unfortunately, in many places in America and the rest of the world, including China and Russia, the soil is badly depleted of its selenium content because of acid rain, which can dramatically change the chemical composition of the soil. As a result, soil acidification alters of the ability of the soil to bind with vital elements such as selenium for assimilation into edible plants.

Selenium’s Unique Biochemical Properties

What makes selenium unique? While scientists are still elucidating selenium’s role in a multitude of biochemical processes, one of its chief attributes is serving as a component of specific proteins called selenoproteins. Almost all of these proteins are active in the defense against reactive oxygen species (free radicals), which fuel numerous diseases and the aging process itself through their damaging effects on DNA and proteins.

Selenoproteins and their antioxidant products scavenge cell-damaging free radicals. Selenium is the only mineral nutrient that has its own DNA code, which instructs the body’s protein-synthesis “machinery” to incorporate selenium into its host proteins. Scientists interpret this unique attribute as evidence of selenium’s fundamental importance to virtually all living things on Earth.3

Selenium is available from many dietary sources, including garlic, Brazil nuts, and certain vegetables; however, the amount of bioavailable selenium from these sources varies tremendously, depending on the soil and weather conditions where the plants are grown.4 Foods containing selenium may also contain substances that limit selenium’s bioavailability.5 Therefore, selenium supplementation is often recommended as a way to assure a dependable, bioavailable supply of this nutrient.6

Selenium deficiency is increasingly associated with adverse health conditions and even life-threatening diseases. People who live in selenium-poor regions of the world suffer from dramatically increased rates of cancer, infections, and inflammatory diseases.1,7-9 Fortunately, many of these conditions can be prevented and even reversed with selenium supplementation.10-13 In this article, we will examine how oxidative stress can increase our vulnerability to inflammation, infection, cancer, and cardiovascular disease, and how selenium and the selenoproteins work to counteract oxidative stress, even in people without overt selenium deficiency.

Selenium Protects Against Oxidative Stress

Scientists now generally recognize that most disease processes produce their effects through chemically reactive molecules known as free radicals. Free radicals are composed mostly of reactive oxygen and nitrogen compounds. These reactive oxygen species initiate a destructive cycle fueled in part by the body’s own defense mechanisms. They disrupt the normal structure of proteins and the genetic information encoded in DNA. This damage always results in the release of potent chemical messengers called cytokines. Cytokines trigger the inflammatory response in tissues, signaling immune and inflammatory cells to swarm the affected area.

This inflammatory reaction activates powerful factors deep within cell nuclei—such as nuclear factor-kappa beta (NFkB). These factors “translate” infection and inflammation into the uncontrolled cell replication that produces cancer.14 Strong evidence also suggests that NFkB and related compounds are involved in the conversion of oxidative damage, stress, and inflammation into the stimuli that produce atherosclerosis and cardiovascular disease.15

Selenium not only scavenges reactive oxygen species before these free radicals can damage cells, but also regulates nuclear factor activities deep within the cells themselves.16 For this reason, scientists now call selenium “one of the most promising agents” for the prevention and control of cancer.17

Laboratory evidence also supports selenium’s role in protecting cardiac muscle from the effects of reduced blood flow, or ischemia.18 Under the extreme oxidative stress triggered by a severe infection, selenium has been shown to enhance the protective ability of intracellular antioxidant systems that use glutathione.19 Moreover, selenium specifically inhibits the activation of NFkB, which in turn inhibits the release of inflammatory cytokines. In fact, in laboratory studies, a reduction of selenium has been shown to increase levels of these inflammatory molecules.20 Research also shows that by reducing NFkB activity, selenium prevents the activation of inflammatory cells that contribute to vascular disease in type II diabetes.21

These laboratory findings underscore selenium’s promise in preventing and treating a wide array of human diseases, while reducing the cumulative oxidative damage that underlies many of the deleterious changes associated with aging.22

Selenium Combats Inflammatory and Infectious Diseases

The recognition of selenium’s ability to prevent oxidative damage has fueled research into how selenium influences various chronic inflammatory conditions. For example, in a study of 70 patients with rheumatoid arthritis, selenium concentrations were found to be significantly lower than in a healthy population. When the subjects were given selenium or placebo for three months, the selenium-supplemented group showed fewer tender or swollen joints and less morning stiffness than did the control group. The supplemented patients also required less cortisone and nonsteroidal anti-inflammatory drugs (NSAIDs) than did the controls, and demonstrated a reduction in laboratory indicators of inflammation. No side effects of selenium supplementation were noted.23

Selenium has shown great promise in the treatment of autoimmune thyroiditis as well.24 In a recent study, 48 patients with elevated levels of an antibody to thyroid enzymes were given selenium daily for three months, while 40 patients received placebo. Serum levels of the antibody dropped significantly in the supplemented group compared to the placebo group, demonstrating that selenium suppressed the autoimmune attack on these patients’ thyroid glands.25 Similar reductions in measures of autoimmune inflammatory response have been shown in other studies of selenium alone or in combination with other antioxidants.26-28

Many other autoimmune conditions are associated with low selenium levels, including autoimmune hepatitis and diabetes.29-32 Preliminary trials have demonstrated a protective effect of selenium supplementation against both hepatitis C and alcoholic hepatitis; both conditions involve a substantial inflammatory component that is thought to be mitigated by the actions of selenoproteins.33,34

FOUR DIFFERENT FORMS OF SELENIUM

Selenium is available in a number of different forms for supplementation, and each has slightly different uses and benefits. Ideally, a good supplement should contain all four of the following forms of selenium for broad-spectrum protection.

  • In the form of the salt, sodium selenite, selenium has been used to reduce post-operative swelling that is related to the increased free radical stresses produced by surgery.69 Related beneficial effects are seen when sodium selenite is used to protect against radiation treatment-induced swelling and inflammation.70,71 Sodium selenite has also demonstrated dramatic immune-boosting function in patients with borderline low selenium status.72
  • The natural metabolite of selenium, selenodiglutathione, contains a selenium ion bonded to two molecules of the potent antioxidant glutathione. This compound appears to be heavily involved in the cancer chemoprotective effects of selenium,73-76 as demonstrated by its ability to stimulate apoptosis, the programmed cell death the body uses to purge itself of incipient cancers.77,78
  • The selenium-containing amino acid, L-selenomethionine, is an essential component of the selenoproteins involved in controlling autoimmune diseases.79 It is also selectively accumulated in prostate tissue, where it has been shown to have cancer-fighting activity.80 As a component of an “antioxidant cocktail,” L-selenomethionine can increase brain blood flow and scores on psychological testing in elderly people.81
  • Another selenium-containing amino acid complex, Se-methylselenocysteine, has especially great potential in the treatment of established cancers,82 where it has been shown to radically enhance the effects of traditional chemotherapy drugs while protecting against their toxicity.83 In one study, drug treatment alone was curative in only 30% of animals bearing human squamous cell carcinoma of the head and neck; that rate rose to 100% with the addition of methylselenocysteine.84

Severe infection imposes some of the most concentrated oxidative stress of all human diseases. Selenium has shown important benefits for those with septic shock, one of the most troubling killers of people with infections, compromised immune systems, or those confined to the hospital. Now known as systemic inflammatory response syndrome, or SIRS, overwhelming infection leads to runaway release of cytokines and other inflammatory mediators, ultimately causing a dramatic failure of multiple organs and bodily systems.19 This condition, formerly known as “septic shock,” has yielded dramatically to the inclusion of selenium in treatment protocols, as evidenced by two remarkable studies published in 1999.

When 21 intensive-care patients with SIRS were given high-dose selenium (beginning at 535 mcg per day), their selenium and glutathione peroxidase levels normalized within three days; by contrast, selenium and glutathione peroxidase levels remained low in 21 control patients who received only “normal” amounts of selenium. Scores on a scale of physiological function were significantly better in the supplemented group than in the controls, and hemodialysis because of acute kidney failure was needed in only 3 of the 21 supplemented patients, compared to 9 of the 21 control patients.35 A similar study of 34 children with SIRS demonstrated markedly elevated activity of antioxidant enzymes in the selenium-supplemented group, with markers of lipid peroxidation and cell membrane destruction falling dramatically compared to controls.36