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Selenium
Selenium and cancer
Observational studies indicate
that death from cancer, including lung, colorectal, and prostate cancers, is lower among
people with higher blood levels or intake of selenium [34-40]. In addition, the incidence of nonmelanoma skin cancer is
significantly higher in areas of the United States with low soil selenium content [37]. The effect of selenium supplementation on
the recurrence of different types of skin cancers was studied in seven dermatology clinics
in the U.S. from 1983 through the early 1990s. Taking a daily supplement containing 200
µg of selenium did not affect recurrence of skin cancer, but significantly reduced the
occurrence and death from total cancers. The incidence of prostate cancer, colorectal
cancer, and lung cancer was notably lower in the group given selenium supplements [41].
Research suggests that selenium affects cancer risk in two ways. As an anti-oxidant,
selenium can help protect the body from damaging effects of free radicals. Selenium may
also prevent or slow tumor growth. Certain breakdown products of selenium are believed to
prevent tumor growth by enhancing immune cell activity and suppressing development of
blood vessels to the tumor [42].
However, not all studies have shown a relationship between selenium status and cancer. In
1982, over 60,000 participants of the Nurse's Health Study with no history of cancer
submitted toenail clippings for selenium analysis. Toenails are thought to reflect
selenium status over the previous year. After three and a half years of data collection,
researchers compared toenail selenium levels of nurses with and without cancer. Those
nurses with higher levels of selenium in their toenails did not have a reduced risk of
cancer [43].
Two important long-term studies, the SU.VI.MAX study in France and the Selenium and
Vitamin E Cancer Prevention Trial (SELECT) study in the U.S., are now underway to further
investigate the selenium/cancer prevention link.
The SU.VI.MAX Study is a prevention trial looking at the effects of antioxidant vitamins
and minerals on chronic diseases such as cancer and cardiovascular disease. Doses of the
nutrients provided in the study are one to three times higher than recommended intakes,
including a daily supplement of 100 µg selenium. The SU.VI.MAX study, which began in
1994, has followed more than 12,000 adult men and women. This study was designed to
continue for eight years, and the research community is eagerly awaiting the results of
this study [44].
The SELECT study, a long-term study sponsored by the NIH, is investigating whether
supplemental selenium and/or vitamin E can decrease the risk of prostate cancer in healthy
men. Past evidence as well as pre-clinical trials for the SELECT study suggests that these
two nutrients may be effective in preventing prostate cancer. A daily supplement
containing 200 µg of selenium will be given to individuals in the selenium-only study
group, while men in the combined-nutrients group will receive a daily supplement
containing 200 µg selenium and 400 mg vitamin E. The study, which will span from 2001 to
2013, will include 32,400 healthy adult men [45].
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Aromaa A. Is low selenium status a risk factor for lung cancer? Am J Epidemiol
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cancer prevention by selenium. BioFactors 14 2001; 153-9.
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Spate VL, Baskett CK, Rosner B, Speier FE, Willett WC, Hunter DJ. Prospective study of
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Full article here
Selenium research center
The Selenium Nutritional Research Center
(SeNRC) is involved with all nutritional and biochemical aspects of selenium research.
Selenium is a dietary-essential trace element (nutritional mineral) that is critical to
the body’s defense against cancer and other illnesses involving free radicals and
other reactive oxygen species (ROS).
At SeNRC, we direct much of our efforts
to studying the relationship of various forms of selenium compounds for the prevention of
cancer. Our scientists hold patents on the use of selenium compounds and the prevention
and treatment of cancer, as well as composition patents on specific selenium compounds and
combinations of selenium with other nutrients and/or antioxidants. (See US 6,090,414 and
EP 0 750 911 B1) Prevention is the ultimate cure. Our patents issued and allowed also
cover the composition of virtually all current multivitamins now made, distributed, or
sold in the U. S., whether they contain selenium or not.
SeNRC’s Research Director, Dr.
Richard A. Passwater, has been involved with selenium research since 1959, when selenium
was postulated to be a component of an unidentified food factor called "factor
3" in livestock feed that was thought to spare the need for vitamin E and possibly be
involved in liver and muscle health of poultry and livestock.
Cancer Prevention
Dr. Passwater’s research with
selenium as a cancer preventative began more than four decades ago, and over the decades,
thousands of mechanistic studies, hundreds of animal studies, dozens of epidemiological
(population) studies, and at least three published clinical supplementation trials have
verified his findings.
On December 25, 1996, Dr. Larry Clark and
his colleagues published their large, prospective, randomized, placebo-controlled,
double-blind Nutritional Prevention of Cancer (NPC) clinical study in the Journal of the
American Medical Association (JAMA 1996; 276:1957-1963). This landmark research effort
showed that daily supplementation of diets with 200 micrograms of selenium yeast cut the
cancer death rate in half. That is cancer mortality was reduced 50 percent (p=0.002). Lung
cancer deaths were reduced 53% (p=0.03)
Total cancer incidence was reduced 37
percent (p=0.001) and the total carcinoma incidence was reduced 45%. In addition, the
three leading sites of cancer had significantly lower incidence; lung cancer incidence was
reduced 46 percent (p=0.04), prostate cancer incidence was reduced 63 percent (p=0.002)
and colon cancer incidence was reduced 58 percent (p=0.03). There was a 17% reduction in
all cause mortality (p=0.14), which when adjusted for sex, current smoking and age yielded
a 21% reduction in deaths from all causes (p=0.07).
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Bioactivity of selenium from
Brazil nut for cancer prevention and selenoenzyme maintenance.
Ip C, Lisk DJ.
Department of Surgical Oncology, Roswell
Park Cancer Institute, Buffalo, NY 14263.
Brazil nut (Bertholletia excelsa) is one
of very few consumable products with exceptionally high levels of selenium. The mean
selenium concentrations of two shipments of Brazil nut used in the present study were
determined to be 16 and 30 micrograms/g. In contrast, most common foods contain much less
selenium, from 0.01 to 1 micrograms/g. Previous research on selenium cancer
chemoprevention invariably used a pure compound, whereas little information is available
on the efficacy of selenium delivered naturally in a food form. This paper reports the
results of two mammary cancer prevention experiments in the rat dimethylbenz[a]anthracene
model by continuous feeding of selenium-rich Brazil nut (processed to a smooth-textured
nut material for mixing in the diet). A dose-dependent inhibitory response was observed at
dietary selenium concentrations of 1-3 micrograms/g. Interestingly, Brazil nut was found
to be just as powerful as sodium selenite, if not more so, at similar levels of dietary
selenium intake. Mammary cancer protection gland, and plasma.
The magnitude of tissue selenium
accumulation was proportional to the amount of Brazil nut added to the diet. The
nutritional biopotency of selenium in Brazil nut was also evaluated by the repletion of
two selenoenzymes, glutathione peroxidase and type I 5'-deiodinase, in selenium-deficient
rats. Supplementation with Brazil nut as the sole source of selenium produced an efficient
gradient of enzyme restoration at 0.05-0.2 microgram/g of dietary selenium. A parallel
comparison with sodium selenite indicated that the selenium in Brazil nut and selenite
selenium were equally bioactive. Although at this point it can only be inferred that the
above biologic effects are likely to be attributable to the high selenium content of
Brazil nut, there is persuasive evidence to suggest that the models under investigation
are responding to the selenium rather than to the other components of Brazil nut.
Selenium and cancer
Selenium is a mineral with anti-cancer
properties. Many studies in the last several years have shown that selenium is a potent
protective nutrient for some forms of cancer. The Arizona Cancer Center posted a selenium
fact sheet listing the major functions of selenium in the body [97]. These functions are
as follows:
1. Selenium is present in the active site
of many enzymes, including thioredoxin reductase, which catalyze oxidation-reduction
reactions. These reactions may encourage cancerous cells to under apoptosis.
2. Selenium is a component of the
antioxidant enzyme glutathione peroxidase.
3. Selenium improved the immune systems'
ability to respond to infections.
4. Selenium causes the formation of
natural killer cells.
5. P450 enzymes in the liver may be
induced by selenium, leading to detoxification of some carcinogenic molecules.
6. Selenium inhibits prostaglandins that
cause inflammation.
7. Selenium enhances male fertility by
increased sperm motility.
8. Selenium can decrease the rate of
tumor growth.
A serendipitous randomized, double-blind,
controlled trial of a 200 µg/day selenium supplement in the southeastern region of the
USA (where soil selenium levels are low) found that the primary endpoints of skin cancer
were not improved by the selenium supplement, but that other cancer incidence rates were
decreased by selenium [98,99]. There was a significant reduction in total cancer incidence
(105 vs 137 cases, P = 0.03), prostate cancer (22 vs 42 cases, P = 0.005), a marginally
significant reduction in colorectal cancer incidence (9 vs 19 cases, P = 0.057), and a
reduction in cancer mortality, all cancer sites (40 vs 66 deaths, P = 0.008) (selenium
versus control group cases reported, respectively) [98]. The selenium supplement was most
effective in ex-smokers and for those who began the study with the lowest levels of serum
selenium. Several prospective studies have also examined the role of selenium in cancer
prevention, particularly for prostate cancer, summarized in Table 2.
Overall, it appears that poor selenium
levels, especially for men, are a cancer risk. If a person has low selenium levels and
other antioxidant defenses are also low the cancer risk is increased even further. Women
do not appear to be as sensitive to selenium, as breast cancer has not been found to be
influenced by selenium status in several studies [100-104], although both men and women
were found to be protected by higher levels of selenium from colon cancer [100] and lung
cancer [105,106]. Good vegetarian sources of selenium are whole grains and legumes grown
in selenium-rich soil in the western United States, brazil nuts (by far the most dense
source of selenium), nutritional yeast, brewers yeast, and sunflower seeds.
Reduction of Cancer Risk by
Consumption of Selenium-Enriched Plants: Enrichment of Broccoli with Selenium Increases
the Anticarcinogenic Properties of Broccoli
Mar 2003, Vol. 6, No. 1: 19-26
John W. Finley, PhD
States Department of Agriculture, Agricultural Research Service, Grand Forks Human
Nutrition Research Center, Grand Forks, ND, USA
Plant-based diets and phytochemicals
present in plants are associated with decreased risk of cancer. Brassica species, and
broccoli in particular, are associated with reduced risk of several important cancers.
Selenium (Se) is an essential nutrient that is covalently bound in a number of different
chemical forms found in plants. Broccoli accumulates Se many-fold beyond the concentration
of Se in the soil, and the chemical form of Se in broccoli is similar to the chemical form
in high-Se garlic, a food with unique chemoprotective properties.
Se from broccoli grown to accumulate more
than 500 µg Se/g did not accumulate in rat tissues or increase glutathione peroxidase
enzyme activity to the same extent as Se salts or seleno-amino acids. Se from high-Se
broccoli decreased the incidence of aberrant crypts in rats with chemically induced colon
cancer by more than 50%, compared with controls. Se from high-Se broccoli also decreased
the incidence of mammary tumors in rats treated with 7,12-dimethylbenz(a)anthracene (DMBA)
and tumor number and volume in APCmin mice.
These results suggest that development of
methods to increase the natural accumulation of Se in broccoli may greatly enhance its
health-promoting properties.
Brazil nuts protect from breast
cancer
The mineral selenium may help protect
some women from developing breast cancer, research has suggested. The element, which can
be found in brazil nuts, liver and kidneys, may help the body defend itself. Scientists
from the University of Illinois believe they may have worked out how selenium interacts
with a natural body chemical to offer protection.
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Selenium - daily dose
Selenium is an essential component of at
least 11 selenoenzymes or selenoproteins. There are two majorfamilies of
selenoenzymes?glutathione peroxidases and deiodinases. The metabolic function of the
glutathione peroxidases is to convert oxidized fat (lipid hydroperoxides), which is
generated as the result of normal metabolism and contributes to heart disease and stroke,
to less harmful compounds. This activity is similar to the antioxidant activity of vitamin
E. The deiodinase enzymes regulate the metabolism of thyroid hormones. Interestingly, the
recently discovered selenoenzyme thioredoxin reductase has been suggested to play a role
in vitamin C metabolism. A human disease known to be caused by selenium deficiency and
found in various regions of China is Keshan disease, a cardiomyopathy (disease of the
heart muscle) in children.
Extensive data from studies in China have
been used to establish the required and safe levels of selenium for humans. These studies
revealed significant correlations between daily selenium intake and the selenium content
of blood, breast milk, and urine. Significant correlations were also observed between
urinary, plasma, hair, fingernail, and toenail selenium levels.
Fingernail brittleness and hair loss were
used by the Chinese scientists, as well as the Panel, as the main criteria for chronic
selenium toxicity, or selenosis, which occurs at an intake of about 5 mg (5,000 mcg) of
selenium daily. Adverse effects were observed at daily dietary selenium intakes between
about 600 and 1,600 mcg. The maximum safe dietary selenium intake was calculated to be
about 800 mcg/day, but may be as low as 600 mcg in some individuals. The Panel set the UL
for selenium at 400 mcg/day, which was selected to protect sensitive individuals. The
Chinese scientists suggested a level of about 40 mcg daily as the minimum requirement,
which is similar to the new RDA of 55 mcg/day. This RDA established by the Panel is based
on the saturation of plasma glutathione peroxidase. An intake of less than 11 mcg daily of
selenium will definitely put one at risk of deficiency.
Early epidemiological studies suggested a
possible inverse relationship between selenium intake in humans and the incidence of
certain cancers. More than 100 relevant experiments with animals exposed to various
chemical and viral carcinogens have been carried out. The majority of these studies showed
anticancer effects of selenium. Three human trials on selenium and cancer have been
completed, and all of them showed positive results. In one trial, the addition of selenium
to table salt significantly reduced the incidence of liver cancer in a Chinese population.
After 5 years of supplementation with selenium, vitamin E, and beta-carotene, the
incidence of stomach and esophageal cancer in another Chinese population was significantly
reduced. However, it is not clear which supplement was mainly responsible for this effect.
A study in the U.S. showed that 970 men supplemented with 200 mcg of selenium daily (as
selenium-enriched yeast) for 4.5 years had a 63% reduction in the incidence of prostate
cancer, as well as a significantly reduced incidence of colorectal, lung, and total
cancers. These supplementation studies are consistent with a recent study showing one-half
to two-thirds reduction in the risk of prostate cancer among men with the highest selenium
status, as assessed by toenail levels of selenium that indicate long-term selenium intake.
Overall, the evidence that selenium can lower the risk of prostate and possibly other
human cancers was considered very promising by the Panel, but it concluded that there is
currently no proof for an anticancer effect of selenium.
It is estimated that Americans consume
about 100 mcg/day of dietary selenium. In the aforementioned prostate cancer study,
subjects were given 200 mcg supplements daily, which boosted their estimated daily intake
to about 300 mcg. To prevent selenium deficiency symptoms, a daily intake of 55 mcg is
required. For maximal protection against certain cancers, a total daily intake of 200-300
mcg is probably necessary.
Full article
Selenium is a nutritionally essential
trace element that naturally occurs in the soil. It enters our bodies through our food
(both plant and animal products) and, to a lesser extent, water sources. Plants absorb
selenium from the soil into their leaves, stems, seeds, and fruits. Animals eat plants
containing the selenium and this is stored in their tissues. Some foods that are good
sources of selenium are grains grown in the Midwestern U.S. and animal meats, particularly
organ meats. Certain foods like brazil nuts are especially high in selenium.
The major functions of selenium in
the body that have been discovered to date are as follows:
- Selenium is found in the active site of
many enzymes, such as thioredoxin reductase, which catalyze oxidation-reduction reactions.
These reactions help to protect against cancer by encouraging cancer cells to undergo apoptosis.
Apoptosis is a form of programmed cell death that occurs when genetic damage is detected
in the cell, thus preventing the transfer of mutations to a future generation of cells.
- An enzyme, Glutathione Peroxidase (or
GSH-PX) requires selenium for its formation. This enzyme helps to prevent a process called
oxidation, which may cause injury in cells.
- Selenium appears to improve the
functioning of the immune system and its response to infections.
- Selenium appears to cause the formation of
natural killer cells, which destroy foreign bacteria that enters the body.
- P450 enzymes may be induced by selenium.
These enzymes help detoxify some cancer-causing substances.
- Selenium inhibits prostaglandins, which
cause inflammatory reactions in the body.
- Male fertility may be enhanced by selenium
due to increased sperm motility.
- At high doses, selenium may decrease the
rates of tumor cell growth.
Selenium can be toxic at very high doses.
This was first observed in animals that eat plants with toxic levels of selenium. Toxicity
in humans has rarely been seen. However, toxicity has been reported in parts of the world
where dietary selenium levels are extremely high. The reported symptoms of human toxicity
from selenium have included increased nail and hair brittleness or crumbling, skin rashes,
"pins and needles" sensations, irritability, nausea, vomiting, or garlic breath.
These side effects were observed in approximately 10% of Chinese subjects consuming a diet
with over 1,000 micrograms of selenium daily.
Source: Arizona University
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