Focus on Dietary supplements & contract services
Supplement to AgroFood industry hi-tech - July/August 2010 - vol 21 n 4
14
Dietary selenium
and selenized yeast
GUNNARD K. JACOBSON
Lesaffre Yeast Corporation
7475 W. Main St.
Milwaukee, WI 53214, USA
Gunnard K.
Jacobson
ABSTRACT: Selenium is an essential trace element in animal nutrition. Human selenium status varies geographically and by diet.
While selenium status, as determined by serum selenium levels, of most individuals may be adequate, the role of an individual’s
genetic makeup with respect to the ability to adequately utilize selenium at the level of the 25 individual selenoproteins is just
now being studied. Data clearly show that selenized yeast is an efficient and safe form of dietary selenium. It has been shown to
be easily digestible; its selenomethionine is readily incorporated into proteins where it contributes to the body’s reservoir of this
essential element. This review will briefly discuss the importance of dietary selenium and the role that selenized yeast can play in
human nutrition.
Selenium and human selenoproteins
excretion pathways. SeMet appears to be the
predominant selenocompound in cereal grains,
Selenium is a member of Group VIA of the Periodic
meat, and selenized yeast (Se-yeast), while
Table and as such has chemistry closely resembling
g-glutamyl-Se-methylselenocysteine (GMSeCys) and
sulphur. Because their chemistries are so similar, plants
Se-methyl-selenocysteine (MSeCys) are characteristic
and yeasts can substitute selenium for sulphur in the
of Se accumulator plant species such as the
biosynthesis of methionine to produce
brassicas (broccoli, radish, cabbage, etc.) and the
selenomethionine, (SeMet). SeMet can be
genus Allium (onions and garlic) (4). Ingested SeMet is
Group VI A.
metabolized to the Se analogue of cysteine,
available for general protein synthesis, where it is nonselenocysteine (SeCys), and its metabolites. While
specifically incorporated into protein in place of
animals can incorporate SeMet into protein, they can’t
methionine. Here it can accumulate as part of the body’s
incorporate SeCys. The selenide derived from dietary SeCys
selenium stores and ultimately may become biologically
either enters into secretory pathways or is incorporated into an
available for other metabolic pathways as a function of protein
estimated 25 selenoproteins via a novel co-translational
turn over. SeCys, MSeCys, and GMSeCys do not enter protein
process. Research over the last 20 years has shown that SeCys
synthetic pools where they can be stored; rather they rapidly
so incorporated is critical to the function of these proteins.
enter secretory pools. Methylselenol (MSeH) produced in the
Selenium, therefore, is an essential trace element required for
secretory pathway is considered to be an important in vivo
proper nutrition (1).
anticarcinogenic metabolite. SeMet, via a g-lyase, can also be
In humans, SeCys forms the active centre in important redox
converted to MSeH when it enters the secretory pathway either
enzymes such as five glutathione peroxidases and three
from dietary or protein turn over sources (3, 4). In humans, the
thioredoxin reductases. In addition, there are three thyroid
whole body half life of SeMet and selenite is 252 and 102 days,
hormone iodinases involved in proper thyroid function.
respectively. At this time, no human bioavailability or retention
Selenoprotein W has been implemented in striated muscle
data are available for plant compounds such as GMSeCys and
health, and Selenoprotein H is a redox sensing protein involved
MSeCys (4).
in the regulation of glutathione synthesis and Phase II
detoxification reactions in the liver. Some isoforms of
Selenoprotein P contain up to 10 SeCys residues. It constitutes
Selenium and human health
the major source of selenium in blood plasma. Its short half-life
(3-4 hrs) and its ability to bind to endothelial cells suggest that it
While the functions of some of the selenoproteins in the
is a major selenium transport protein (2, 3).
proteome remain unknown, some, such as the glutathione
Selenoproteins contain SeCys incorporated into nascent
peroxidases and thioredoxin reductases are redox enzymes
proteins via the stop codon UGA. The codon is recognized by a
with roles in preventing oxidative and free radical damage.
specific transfer RNA carrying acetyl-serine; SeCys is formed in
They contribute to the body’s defence mechanisms against
situ via the reaction of acetyl-serine with selenophosphate. The
damage by reactive oxygen species (ROS). Accumulation of
recognition of the UGA codon
redox damage is thought to play a
requires the presence of a SeCys
role in many disease processes
insertion sequence (SECIS) present in
including cardiovascular disease,
the 3’-noncoding region of
cancer, muscle disorders and aging
the selenoprotein mRNA.
(5, 6). As an example, Keshan
Selenophosphate is derived from
Disease is a cardiomyopathy
dietary selenium (1).
endemic to regions of selenium
Dietary inorganic selenate (Se VI) or
deficient soils in the People’s
selenite (Se IV) is reduced and enters
Republic of China. This disease may
metabolic pools that either leads to
be associated with Coxsackie virus B
selenoprotein synthesis or to
infection and low selenium status,
methylated-selenoand
but it responds well to dietary
SEM Yeast 4000X.
methylated-seleno-glycoside
selenite supplementation (2, 7).
Selenium yeast can be produced by one of two techniques. In
one, sodium selenite is added to a yeast suspension and the
mixture is dried. Selenite can, to some extent, be bound to the
cell surface by ionic forces, but the selenium remains as Se IV
and is considered inorganic selenium. This product is a selenium
yeast product, but not a “selenized yeast” product. The second
form of selenium yeast is manufactured by slowing adding
sodium selenite to yeast production fermentations during
growth of the organism. In this case, the yeast’s metabolism
reduces selenite to selenide and incorporates it into cellular
constituents in place of sulphur. In this selenized yeast (Se-yeast)
50-80 percent of the selenium is “organically bound selenium”
as SeMet (21, 22), which can replace about 30 percent of the
methionine in the yeast proteome (23). Unlike mammals,
Saccharomyces yeasts do not contain specific selenoproteins,
but selenium is incorporated non-specifically into protein as
SeMet (23). In addition to SeMet, SeCys and lesser amounts of
Supplement to AgroFood industry hi-tech - July/August 2010 - vol 21 n 4
Selenized yeast
Focus on Dietary supplements & contract services
The current United States Recommended Daily Allowance
(RDA) for selenium requirements of 55 mg/day for men and
women were derived from Chinese studies that determined the
levels of selenite supplementation in the diet required to
maximize plasma glutathione peroxidase (GPx) levels in
Chinese men. The requirement for RDAs to be this high has
been questioned because of the absence of selenium
deficient pathologies in the New Zealand population which
consumes less than 30 mg Se/day (8, 9). At issue is the fact that
maximal GPx activity may not be necessary for optimum
human health and that there may be other indicators of
sufficient selenium nutritional status, such as plasma
Selenoprotein P levels (10).
Se-yeast was used in the Nutritional Prevention of Cancer Trial
(NPC), one of the first human interventional trials (11). The
endpoint for these trials was recurrent nonmelanoma skin
cancer. This endpoint was null, but secondary endpoints
revealed lower mortalities and incidences for prostate,
colorectal, and lung cancer. Another study reported a higher
incidence of lung cancer was associated with low selenium
status, especially in subjects with low intakes of vitamin C and
b-carotene (12). Extension and further analysis of lung cancer
data from this trial suggested that selenium supplementation
most benefited individuals with low selenium baseline levels or
former smokers (13).
A major follow up trial, Selenium and Vitamin E Cancer
Prevention Trial (SELECT), found no correlation between
selenium, as SeMet, and/or vitamin E supplementation and
reduced rates of prostate cancer (14). Other authors have
noted that the form of selenium in the SELECT study differed
from the form of the selenium in the NPC study and that other
forms organic selenium present in Se-yeast may be important.
As the major form of selenium in Se-yeast is SeMet with minor
levels of other selenium species, this may not be relevant. Also,
it was noted that the SELECT study used participants with higher
plasma selenium baseline levels (15, 16).
While epidemiological and supplementation studies suggest
benefits in reducing prostate, colorectal, and lung cancers
rates (11-13, 17), the benefits of supplementation on the
incidence of putative ROS related diseases such as
cardiovascular diseases are less apparent (18). The relationship
of selenium status to the ageing process has been stimulated
by reports that mortality rates were higher in elderly populations
with low plasma selenium levels as compared to individuals in
the study group with higher plasma selenium levels (19). The
potential role of selenium in proper immune function has been
suggested by data demonstrating lymphocyte stimulation by
elevated plasma selenium levels (20).
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Focus on Dietary supplements & contract services
Supplement to AgroFood industry hi-tech - July/August 2010 - vol 21 n 4
other selenium containing metabolites
are also found. These include
methionine pathway intermediates,
sulphur analogs such as Se-adenosylSe-homocysteine, and SeMet
oxidation products such as SeMetselenoxide (21). While the Association
of American Feed Control Officials
has adapted a tentative standard of
identity for Se-yeast (24), this has yet to
be done for Se-yeast for human consumption. However
Se-yeast yeast for human use has been extensively studied
and has recently been approved for incorporation into
human food supplements by the European Food Safety
Authority (11, 21, 25).
Selenium bioavailability from selenized yeast
Burk, et al. (26) have studied selenium plasma biomarkers, in
selenium-replete men. Moderate (200 mg/d) to high
(600 mg/d) supplementation as sodium selenite, SeMet, and
Se-yeast were studied. SeMet and Se-yeast raised plasma
selenium levels in a dose dependent manner while sodium
selenite did not. In these replete individuals, supplementation
did not affect glutathione peroxidase activity or selenoprotein
P levels. In Chinese men with very low selenium status, both
sodium selenite and SeMet rapidly increase plasma Se levels
and glutathione peroxidase activity. SeMet resulted in higher
circulating Se levels than selenite, but not greater glutathione
peroxidase activity (27).
Se-yeast and SeMet, like inorganic forms of selenium, can
increase bodily selenium levels, but unlike inorganic forms, the
SeMet from Se-yeast, like SeMet in pure form, can be stored as
SeMet in tissue proteins resulting in slower whole body selenium
turn-over rates (21). The absorption, and retention, of selenium
from Se-yeast, has been reported to be 90 and 75 percent,
respectively; and, is similar to that of selenium naturally
occurring in wheat (28, 29). Se-yeast, as compared to
inorganic selenite, raises serum selenium levels more effectively;
and, plasma and erythrocyte selenium levels decline more
slowly, post-supplementation, in Se-yeast supplemented
individuals. Studies have shown that the nursing infants of
lactating women receiving dietary supplements of Se-yeast (or
SeMet) had higher plasma selenium levels than infants fed
formula supplemented with selenite (30).
The intraperitoneally injected LD50s for selenate, selenite, SeMet
are similar in rodents (31). Via the oral acute, inorganic forms of
selenium are more acutely toxic than organic forms, especially
Se-yeast. This is likely due to the slower release of SeMet from
intact yeast cells during digestion. Chronic toxicity studies
indicate that incorporation of SeMet into protein provides a
buffer to toxicity. Human interventional trials with selenized
yeast suggest that doses of at least 800 mg/day Se, as Se-yeast,
do not result in toxicity, i.e., selenosis (21).
summary
The relationship between dietary selenium intake and the
selenoproteome is complex. The design and results of selenium
interventional trials need to be assessed in terms of participant
genotype and initial selenium baseline levels. Selenium
supplementation, for specific disease entities, may not benefit
all individuals due to genotypic differences within their
selenoproteome and the subsequent influence of these
differences on tissue specific selenoprotein activities. Indeed,
analysis of data from both the NPC trials and the Third National
Health and Nutrition Examination Survey (NHANESIII) showed a
16
Mineral yeast.
positive correlation between dietary selenium supplementation
and high serum selenium levels and Type II diabetes (32, 33).
Interventional trials with selenized yeast, delivering 200 mg/day
selenium, have demonstrated that its long term use is not only
safe, but is associated with decreased risk of certain cancers
and cancer mortality. Other data suggests that higher
supplementation levels may be tolerated. Current technology
permits a highly reproducible cultivation of selenized yeast in
which desired selenium levels can be specifically targeted.
Daily dietary supplementation with selenized yeast can be
considered to be a proactive use of dietary supplements.
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