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http://www.lef.org/magazine/mag2006/...elenium_01.htm


Selenium

Important Health Benefits from an Overlooked Trace Mineral 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

LE Magazine November 2006

Selenium

Important Health Benefits from an Overlooked Trace Mineral By Julius G.
Goepp, MD
Selenium Shows Promise in Preventing Cancer
Selenium's antioxidant properties have spurred great interest in its
potential to prevent cancer. This is not surprising, given our increasing
awareness that cancer is caused and promoted by the same cascade of
events-oxidative stress and cytokine release-that produces the autoimmune
and other inflammatory conditions just discussed.

To date, more than 100 animal studies have investigated selenium's effects
on the mechanisms responsible for initiating cancer. In the overwhelming
majority of these studies, selenium reduced tumor incidence and tissue
changes that lead to cancer.8,37 The high incidence of various cancers in
selenium-deficient regions of the world strongly supports a
cancer-preventive role for selenium in humans as well, and epidemiological
studies have demonstrated reductions in the rates of, and mortality from,
all cancers in populations receiving selenium supplementation.38

Selenium Prevents and Slows Prostate Cancer
Additional studies of selenium's effects in helping to prevent specific
cancers have yielded results that are even more positive.

One of the most dramatic of these was the unexpected outcome of a study
designed to examine selenium's impact on skin cancer.39 This study of 1,312
individuals who received 200 mcg of selenium daily or a placebo showed no
effect against skin cancer, but demonstrated "striking" results in
preventing prostate cancer, the most common cancer in American men.40,41 The
overall risk of prostate cancer was almost 50% lower in the supplemented
group than in the controls, though the result was significant only in men
who had relatively low prostate-specific antigen (PSA) levels and low
initial selenium levels.

This result prompted a re-analysis of data from the SU.VI.MAX study, with a
specific look at prostate cancer.42 Within that group, 5,141 men took the
selenium-containing supplement or placebo for eight years, and biochemical
markers of prostate disease were measured at the beginning and end of the
study. Overall, a slight reduction in prostate cancer risk was reported;
however, among men who had normal PSA levels at the study's outset, a
significant risk reduction of nearly 50% was recorded.


A 2005 study focusing on selenium's effects in preventing prostate cancer
dramatically confirmed this protective effect.43 Forty-eight patients with
early prostate cancer took selenium, vitamin E, both L-selenomethionine and
vitamin E, or a placebo for three to six weeks before undergoing
prostatectomy (removal of the prostate). Levels of cancer markers were
measured and compared with 29 healthy control subjects. The startling result
was a change in classification from cancerous to healthy in the serum
markers of disease in the men who took supplements compared to those who did
not.

In addition to its clear role in preventing prostate cancer, selenium may
slow the progression of already established prostate cancer. In a six-week
trial, 37 men with prostate cancer and increasing PSA levels were given
either a placebo or an antioxidant supplement containing selenium, plant
estrogens, and other antioxidants.44 In the supplemented group, male hormone
levels (known to stimulate prostate cancer growth) were lower during
treatment. In addition, free PSA levels rose during treatment with the
placebo, but decreased during antioxidant supplementation.

These studies, along with recent findings that selenium is selectively
concentrated in prostate tissue,45 strongly support a role for selenium
supplementation in both preventing and slowing the progression of prostate
cancer.

Selenium Protects Against Lung Cancer
Lung cancer is the most common cause of cancer death in the world.46 The
previously mentioned skin cancer study also demonstrated that selenium
supplementation reduced rates of lung and colorectal cancers.39 Lung cancer
is associated with antioxidative stress and low levels of antioxidants,
including selenium.47 A 1993 study demonstrated a 50% reduction in lung
cancer occurrence in people with the highest dietary selenium intake
compared to those with the lowest intake.48 This finding is supported by a
more recent study of more than 27,000 male smokers who were followed for
nearly 15 years. In this study, researchers found that lung cancer risk was
significantly lower in patients who had the highest intake of antioxidant
vitamins and selenium.49

Selenium supplementation was highly effective in preventing lung cancer in a
region of China where very low natural selenium concentrations contribute to
some of the world's highest rates of lung cancer. Forty Chinese tin miners
were randomly assigned to receive either 300 mcg of selenium or a placebo
daily for one year. As expected, selenium blood levels rose dramatically in
the supplemented miners, while serum levels of the antioxidant enzyme
glutathione peroxidase increased by 156%. At the same time, levels of lipid
peroxide (a measure of cell membrane damage that leads to cancer) were
reduced by 75% in the supplemented group, and there was laboratory evidence
of protection from DNA damage, another prerequisite for cancer formation.50

Moreover, results from the US Nutritional Prevention of Cancer Trial
demonstrated a statistically significant reduction in lung cancer incidence
with selenium supplementation, with 200 mcg per day cutting the incidence of
cancer by nearly 50%.51 A later re-analysis with additional data showed the
effect to be most significant in people with low baseline selenium levels,
again suggesting that supplementation is preventive when initiated early.37

Selenium Guards Against Colon Cancer
Selenium supplementation has also shown effectiveness in preventing
colorectal cancer, the third most common cause of cancer death in the US.52
Glutathione peroxidase, a selenium-containing antioxidant enzyme, is
genetically defective in a significant percentage of patients with colon
cancer.53 Selenium actually activates the DNA repair mechanisms that help
cells protect themselves against colon and other cancers,54 while inducing
programmed cell death (apoptosis) in cancerous tissue.55 In an animal model
of cancer, selenium-containing broccoli in the diet of laboratory rats
protected the animals against chemically induced mammary and colon
cancers.56

After demonstrating that patients with colon cancer routinely have selenium
deficiencies, and that levels of vital antioxidant enzymes could be
increased with selenium supplementation, one research team concluded, "If
prospective trials confirm that selenium supplementation reduces colon
cancer incidence rates, it may be concluded that selenium supplementation
should be recommended for patients at risk."57

Such confirmation is now beyond doubt. In a 1996 study of 44 patients with
colon cancer, half were randomly assigned to receive selenium supplements
and half were given a placebo. All the subjects had their tumors surgically
removed, and all had abnormally low selenium levels at baseline. The
selenium-supplemented patients demonstrated significant increases in
anti-cancer immune system cells compared to levels in control patients,
suggesting that selenium supplementation boosts cell-mediated immunity.58

More dramatic, unexpected evidence of selenium's cancer-preventive
properties comes from a 2006 study. Seeking to determine the maximum
tolerable dose of the anti-cancer drug irinotecan, researchers administered
a massive dose of selenomethionine (containing 2200 mcg of selenium) to
protect against the drug's toxicity.59 Selenium supplementation was begun
one week before the first dose of irinotecan was administered to colon
cancer patients who had previously not responded to chemotherapy. This small
study of highly drug-resistant patients produced unexpected responses (one
patient out of six showed a partial response to treatment) and disease
stabilization. No adverse effects of the high dose were reported. The
scientists recommended further study of high-dose selenomethionine to
determine the most protective serum concentrations of selenium.

Cardiovascular Diseases, Atherogenesis, and the Metabolic Syndrome

The exciting evidence for selenium's effectiveness in preventing
inflammatory diseases and cancer has led scientists to explore its
protective effects against other conditions involving oxidative damage. Many
of these conditions were previously considered to be "natural" consequences
of aging. With the discovery that atherosclerosis, cardiovascular disease,
hypertension, obesity, and type II diabetes-components of the so-called
"metabolic syndrome-are all caused or exacerbated by oxidant stress,60
selenium may prove to have a valuable preventive and therapeutic role in
these conditions as well.

Patients with acute myocardial infarction (heart attack) have been shown to
have lower levels of selenium in their plasma, red blood cells, and urine
compared to control subjects.61 Selenium concentrations are also low in some
patients with endothelial dysfunction, the inflammatory-mediated precursor
to atherosclerosis and hypertension. Supplementation with selenium has been
shown to reverse specific chemical markers of endothelial dysfunction.62 In
addition, selenium may help protect against congestive heart failure.63,64

Oxidative stress is both a cause and consequence of chronic renal failure.
Patients who suffer form this condition experience exceptionally high levels
of cardiovascular disease and death,65 as well as impaired immune
function.66 Selenium levels are markedly reduced in these patients.67
Selenium deficiency is especially pronounced in patients on kidney dialysis,
who lose considerable amounts of selenium during the dialysis process. This
renders them even more vulnerable to further oxidative damage to their
cardiovascular systems.65 Selenium supplementation in dialysis patients has
been used successfully to reduce oxidative stress,68 and has actually been
shown to improve immune function as well.66


Conclusion
A review of recent research findings suggests that scientists have only
begun to tap selenium's potential as a vital antioxidant mineral.

As scientists continue to discover the many ways in which oxidative stress
is related to inflammation and its destructive consequences-from
atherosclerosis to prostate, lung, colon, and other cancers-the
disease-preventive powers of selenium are likely to receive even greater
scrutiny. For now, all health-conscious adults would be well advised to
incorporate this vital mineral nutrient in their daily supplement regimen as
part of a comprehensive disease-prevention program.

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