How To Obtain Optimal Benefits From SeleniumNovember 2015
By Alice Langstrom
Back in the late 1950s, a German scientist named Klaus Schwarz, working in the United States at the National Institutes of Health, was alarmed to discover that his laboratory rats were mysteriously developing liver disease.
Schwarz was again surprised to find that when he switched the source of protein in the rats’ diet from torula yeast to baker’s yeast, they no longer developed liver disease. After carefully studying this curiosity, Schwarz found that the torula yeast was deficient in a particular trace mineral, while baker’s yeast was not.
The trace element turned out to be selenium.1
This pioneering discovery led to the classification of selenium as nutritionally essential.
Since then, an enormous amount of scientific inquiry has revealed that selenium plays critical roles in numerous aspects of human health.
Via its incorporation into more than two dozen selenoproteins throughout the body,2,3 selenium provides potent defense against cancer-causing DNA damage,4,5 facilitates removal of dangerous toxins from the body,6 supports optimal thyroid function,7 maintains immune system activity,3,8,9 and much more.
Indeed, studies suggest that inadequate selenium increases risk of cardiovascular disease,3,10 some cancers,3,11-13 cognitive dysfunction,14 and even death.15-18
And while evidence indicates that selenium levels decline with advancing age,19,20 it is perhaps not surprising that when researchers studied a population of very long-lived people, they found the highest selenium levels in individuals over 100 years old.21
What The “Oldest Old” Have In Common
Selenium functions as a critical regulator of vital metabolic and physiological pathways involved in the aging process.3,22
One of the best examples of selenium’s importance in longevity came from a study of people who live in areas of China known to have the “oldest old” population. For the study, researchers evaluated the plasma selenium levels of 446 elderly participants living in these areas of notable longevity in China. The study included 208 centenarians (those over 100 years old) and 238 people between 90 and 100 years old. The researchers found that the oldest inhabitants had the highest levels of selenium and other minerals like zinc.21
Animal studies confirm that selenium can extend survival—even for those with typically life-threatening diseases. For example, laboratory mice with induced mammary cancers (like human breast cancers) die earlier than do their cancer-free peers. Supplementing the animals with selenium markedly extended their survival.23
Plasma selenium levels appear to predict mortality in humans as well. In a nine-year study of older adults living in France, those with the highest plasma selenium levels at the beginning of the study were more likely to remain alive at the end.24 The risk of dying during the study period was 54% higher in subjects with the lowest baseline selenium levels. The risk of dying specifically from cancer in this study was 79% higher in those with the lowest selenium levels.24
Selenium Protects Against Some Cancers
One way that selenium may boost longevity is by protecting against various forms of cancer. As early as 1996, selenium supplementation was shown to lower overall cancer rates, and to specifically reduce rates of lung, colorectal, and prostate cancers.25-27
By 2011, nine randomized controlled clinical trials including 152,538 participants established that selenium supplementation cut risk for all cancers by 24%. And in people with low baseline levels of selenium, the cancer-preventive effect rose significantly to 36%.28 Studies also show that adequate dietary selenium exerts powerful preventive effects on prostate and colorectal cancer, two of the most common malignancies.29-31
In addition, many studies have demonstrated that a deficiency in selenium increases cancer risk. Large-scale epidemiologic studies have shown that populations with low selenium levels are at significantly increased risk for developing many different types of cancer.26,32-35 Specifically, selenium insufficiencies are now known to significantly increase risk of cancers of the bladder, lung, stomach, esophagus, and liver.36-40
Not all forms of selenium are the same. It is important to utilize three specific forms in order to maximize selenium’s cancer-fighting potential. The three forms include sodium selenite, L-selenomethionine, and selenium-methyl L-selenocysteine. All three selenium compounds induce cell death in various cancer types, though each compound is better at destroying some cancers than others.41,42
For example, sodium selenite boosts the body’s natural immune system responsiveness to abnormal cells, helping to destroy malignancies before they can fully develop.9,43,44
The second form, L-Selenomethionine, helps stop cancer at the earliest stages of development. It’s so powerful that it has been shown to inhibit the growth of cancer cells at rates more than a thousand times greater than it does healthy normal tissue.45 L-selenomethionine requires a functioning “suicide gene” in cells in order for it to induce the desired cell death by apoptosis.41 This is an important first step that can stop cancer cells very early in the development of a malignancy. Unfortunately, as cancer cells reproduce, they gradually lose the “suicide gene,” thereby requiring backup therapy to fully close the door on cancer.
That’s why it’s beneficial to partner L-selenomethionine with the third form, selenium-methyl L-selenocysteine, which is one of the most potent forms of selenium known.46 Selenium-methyl L-selenocysteine induces apoptosis in cancer cells further down the cascade of events in a fashion that kills more mature cancer cells that have lost the “suicide gene.”41
Intervention studies examining the anti-cancer effects of selenium have produced variable results. Important differences between the studies that may have influenced the results, include initial selenium status and the form of selenium that was provided.47 An assessment of status is a key factor for all nutritional intervention studies. With respect to selenium, the form ingested may influence outcomes, since it dictates the metabolic fate and ultimately the biological function; however additional clinical research would be required to prove such a connection.48-50
A number of human studies have examined the role of three different forms of selenium and cancer risk. We describe a few of them here.
In a randomized controlled clinical trial, patients with aggressive head and neck cancers took either 200 micrograms per day of sodium selenite or a placebo. The supplemented patients showed an increased ability to destroy tumor cells, which is the result of enhanced immune responses.43 Remarkably, the enhanced immunity continued even after therapy ended.
In patients with mild precancerous changes of their esophagus, 200 micrograms of L-selenomethionine slowed the progression of potentially cancerous cells and triggered regression of precancerous cells to normal.51
In terms of prevention, sodium selenite supplementation for three years reduced the occurrence of new cases of liver cancer by 40%.52 And a reduction in new breast cancer cases was demonstrated in a group of women with the high-risk BRCA1 gene mutation, during a double-blind supplementation trial.53
In a now-famous 1996 study, 200 micrograms per day of L-selenomethionine was found to significantly protect patients from death by all cancers (a 50% reduction compared with controls), from developing any cancer (a 37% reduction), and specifically from developing lung, colorectal, and prostate cancers.25
Since then, L-selenomethionine has been found to produce a 63% reduction in occurrence of prostate cancer among men with a history of prior cancers.54
Not all studies, however, show cancer risk reduction with L-selenomethionone by itself.55-57 That’s why it is important to include more than just one form of selenium in your daily program. Since the three best-studied selenium compounds differ in the way your body handles them and in their impact on cancer risk, it is important to combine them for maximum protection.
Protecting Against DNA Damage
One of the main ways selenium supplementation helps reduce the risk of cancer is by preventing damage to DNA, which is a major trigger for the transformation of normal cells into malignant ones.58,59
An important approach in cancer prevention has been to focus on the BRCA1 gene, a tumor suppressor that prevents cells from turning cancerous by repairing damage to DNA strands.53,60,61 Mutations in the BRCA1 gene reduce its anticancer effect. In fact, women with such mutations have up to an 80% lifetime risk of developing breast cancer, and up to a 60% chance of developing ovarian cancer.62
Because of the high incidence of cancer associated with this gene mutation, many women who test positive for it elect to undergo a preventive mastectomy—one of the most well-known being Angelina Jolie.
Selenium appears to help repair DNA damage caused by mutations in the BRCA1 gene. This was demonstrated by a study published in Cancer Epidemiology, Biomarkers, & Prevention. For the study, women with mutations in the BRCA1 gene were supplemented with placebo or selenium after precautionary removal of their ovaries and adjacent tissues.53 Researchers found that levels of chemical markers for DNA damage fell markedly in selenium-supplemented women, while markers of successful DNA repair rose.53 These were exciting results because less DNA damage means lower risk for future cancers.
Animal studies show that a diet supplemented with organic selenium compounds such as selenomethionine could also protect against the spread of breast cancer to other parts of the body (metastases), which is the primary cause of death in most cancer patients.63
In 2011, a large meta-analysis (a pooled analysis of results of multiple studies) was able to demonstrate that, among people with low baseline serum selenium levels, selenium supplementation reduced the risk of developing cancer by 36%. In people at high risk for cancer (even with normal selenium levels), supplementation reduced the risk by 32%.28
Selenium Combats Immunosenescence
Aging is associated with increased susceptibility to infections and cancer, and declining immune function plays a major role in this vulnerability. This age-related reduction in immune system vigilance is called immunosenescence.64
Some studies suggest that selenium levels generally decline as we get older, and this may partly underlie immunosenescence.8,19,20
Selenium supplementation has been shown in preclinical research to enhance proliferation of cytotoxic precursor cells, which give rise to the crucial T immune cells that fight cancer and viruses within the body.8,65 Moreover, an intriguing study of healthy men found that selenium supplementation for one year led to increased expression of genes associated with natural killer cell and T-cell cytotoxicity.66
Selenium is also critical for the optimal function of neutrophils,67 which are normally the most abundant type of white blood cell.68 Neutrophils ingest invading microbes and destroy them using an intricate system that is in part regulated by selenium and selenoproteins.69,70 In fact, neutrophils from selenium-deficient animals have been shown to be less effective in killing microbes than those from animals with sufficient selenium intake.8,65
Not surprisingly, selenium supplementation may boost immune system function in aging individuals and confer protection against infections. In one study, elderly individuals who supplemented with selenium (along with zinc) were significantly less likely to develop an infection over a two-year period than those who took a placebo.71
Aside from buttressing immune defenses against infection, selenium also appears able to keep certain viruses from mutating and becoming more pathogenic once they’re inside the body. One group of researchers showed that a normally benign strain of coxsackievirus becomes virulent and damages the heart when administered to selenium-deficient mice. It was determined that replication in the low-selenium environment allowed the virus to directly change its genome to become more pathogenic. When the viral strain was administered to mice with adequate selenium, its genome did not change and the animals remained free of heart damage.72,73
Similarly, a relatively mild strain of influenza caused severe lung inflammation when administered to selenium-deficient mice.74 Follow-up research found that the virus had mutated its genome to become more aggressive in the presence of low selenium levels.75
A major consequence of age-related immunosenescence is decreased vaccine effectiveness. Vaccinations require a robust and well-organized immune response in order to establish immunity, but the aging immune system often falls short, leaving older individuals vulnerable to infections. This is such an important issue that new vaccines specifically for the elderly are being developed in hope of overcoming the barrier of immunosenescence.76
Intriguingly, selenium supplementation may enhance the immune response to vaccination among elderly individuals. In a trial of 725 elderly individuals, participants took selenium (plus zinc) or placebo for two years. Those who received selenium and zinc exhibited much higher antibody titers after influenza vaccination, and were less likely to develop a respiratory infection during the study period.77
Similarly, a study of patients with insulin-dependent diabetes showed that selenium supplementation increased their immune response to hepatitis B vaccination, regardless of age or gender. In this study, insulin-dependent diabetics were administered a three-dose hepatitis B vaccine, on days one, 10, and 21 of the study. Beginning on day one and continuing for 30 days, subjects received either a placebo or 200 micrograms of selenium along with their vaccinations. Thirty days after vaccination completion, 74% of the subjects who took selenium had protective levels of anti-hepatitis B antibodies in their blood, while protective antibody levels were found in only 48% of those who received the placebo.78
The Heart Depends On Selenium
Despite mainstream medicine’s costly diagnostics and invasive treatments, cardiovascular disease remains the leading killer of Americans. More than 61 million people in the United States have one or more types of cardiovascular disease, and 600,000 of those people die every year.79,80
There is evidence that selenium supplementation can reduce many of the risk factors that predispose people to heart attacks or other cardiovascular diseases, including oxidative damage and atherosclerosis.
One of the main reasons why selenium deficiency is so damaging to heart muscle is because of the role selenium plays in protecting the heart against free radical damage, a leading risk factor for heart disease.81-83
Selenium is essential to the proper functioning of one of the heart’s most extensively studied protective mechanisms against oxidative stress—an enzyme called glutathione peroxidase.84 This enzyme is 100% dependent on having a selenium atom at its core for proper function.85 In fact, selenium is what gives the enzyme its potency in preventing and cleaning up after destructive oxygen free radicals.
Decreased selenium in the blood leads to decreased glutathione peroxidase activity,86 which in turn makes heart tissue more vulnerable to the damage that can impair its function.87 This situation is especially grave in older adults.84,88
A study found that adding selenium to human coronary artery cells in culture significantly raised levels and activity of glutathioneperoxidase.87 And in humans, supplementing with 200 micrograms per day of selenium significantly increased glutathione peroxidase activity by 11%.87
In a particularly impressive study, 81 heart attack survivors were treated with either 100 micrograms per day of selenium or a placebo for six months (all other cardiovascular drug treatment was continued).89 As expected, the mean selenium blood concentration rose significantly in the supplemented group but remained unchanged in the placebo group.
But the real difference between the two groups showed up in the number of patients who either had heart attacks or died of heart disease. Four patients who did not receive the selenium supplements died of cardiac disease, while 100% of the patients in the selenium group survived.89
Statin Drugs And Selenoprotein Synthesis
Roughly a quarter of Americans aged 40 or older take a statin drug to control their LDL-cholesterol.90
Statins inhibit an enzyme called HMG-CoA reductase. This enzyme is involved in cholesterol production. But it also has many other important functions, including participation in metabolic pathways leading to selenoprotein synthesis,91,92 and statins have been shown to significantly reduce the synthesis and activity of glutathione peroxidase.93,94
As you just learned, the selenoprotein glutathione peroxidase protects against numerous insults that contribute to life-threatening heart disease.2
Indeed, a study of over 600 coronary artery disease patients published in the prestigious New England Journal of Medicine found that low activity levels of red blood cell glutathione peroxidase were independently associated with an increased risk of cardiovascular events. Study participants who had the highest levels of glutathione peroxidase activity were 71% less likely to have a cardiovascular event during the study period than participants with the lowest levels of glutathione peroxidase activity.95
Fortunately, supplementation with selenium bolsters glutathione peroxidase enzyme activity. A laboratory study found that culturing cells with statin drugs increased their sensitivity to oxidative damage by inhibiting glutathione peroxidase; this effect was reversed by adding sodium selenite to the cells. 93
Selenium Is Essential For Normal Brain Function
The brain is very vulnerable to the damage caused by oxidative stress.96,97
Excessive oxidative exposure has been associated, both in the lab and in living humans,98-101 with increased risk of neurodegenerative changes—the same kinds of changes seen in Alzheimer’s, Parkinson’s, and Huntington’s diseases, which are important causes of dementia in the United States.14,95,102,103 Currently, more than 6 million Americans suffer from such neurodegenerative diseases.104
Studies show that people with neurodegenerative disorders have lower selenium levels in their blood and red blood cells than those without neurodegenerative disorders.14,105,106 In fact, people with low plasma selenium levels have a 58% greater risk of cognitive decline than those with normal levels.102 Studies also show that, among people who already have Parkinson’s disease, lower selenium blood levels are associated with significantly decreased performance on neurological tests of coordination.107
Prevent Stroke-Induced Brain Damage
Selenium has also been shown, in animal models, to help protect against stroke-induced brain damage when taken before a stroke occurs.
Ischemic strokes cause major oxidative damage to vulnerable brain tissue.108,109 Preclinical studies show that animals given experimental strokes undergo sharp reductions in glutathione (a molecule that helps protect against oxidative damage), while at the same time experiencing increased levels of fat oxidation, compared with control animals.110 But when animals were pretreated with selenium, glutathione levels were protected significantly.110
The lack of oxygen immediately following a stroke111 (known as ischemia) reduces energy production in the tiny cellular powerhouses known as mitochondria.112 Mitochondria burn fuel from food, releasing energy that is then stored in a chemical “battery” called ATP (short for adenosine triphosphate). When mitochondria are impaired, they can’t make enough ATP to support brain tissue function.113-116
The negative effects of this energy disruption were clearly seen in a study on laboratory animals. In an animal model of stroke, ATP levels in brain cells dropped significantly, while chemical markers of cellular stress increased.112
However, when the animals were treated with selenium supplements before the stroke, their ATP levels and levels of stress markers remained near normal, and stroke-induced impairments in behavior were not seen. This remarkable study indicates that having adequate levels of selenium could prevent some of the brain damage caused by a stroke. Microscopic analysis of these animals’ brains showed substantially less swelling between cells and lower rates of infiltration by the immune cells called microglia.112
Higher Doses Of Selenium Not Needed
The data showing tremendous benefits in people with the highest selenium levels should not prompt people to take high doses of selenium. The reason is that the selenium contained in scientifically designed multi-nutrient formulas already provides optimal potencies of all three forms of selenium. Commercial multivitamins usually contain only one form of selenium, usually in a very low dose.
Selenium, a trace element, is essential to the proper function of enzyme systems that protect the entire body from age-accelerating damage.
Selenium deficiency has been linked to leading causes of premature death, including heart disease, cancer, and immune senescence. Selenium plays a role in decreasing the risk of cancer and cardiovascular disease, as well as promoting normal brain function.
Optimal daily dosing usually requires about 200 mcg, divided into the selenite, selenomethionine, and selenocysteine forms of selenium.
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