Download Scientific Research Summary

A human blood study was conducted to explore “in vitro” whether
EpiCor enhanced the natural
process of the immune system to
suppress tumor cells. Ten production employees that were exposed
daily to EpiCor by inhalation during
intermittent periods at work, were
matched by age and gender to ten
non-production employees not
exposed to EpiCor. Blood samples
were analyzed for lymphocyte subpopulations, RBC total glutathione,
and an auto-immune panel. Saliva
samples were used for immunoglobulin A (IgA) determination.
25
% Dead Tumor Cells
20
15
10
5
0
Untreated K562
PBL + K562
EpiCor™ PBL
+ K562
 Significantly higher levels of
EpiCor-specific antibodies
(P<0.01)
 Significantly higher levels of
total salivary secretory IgA
(P<0.01)
 Significantly lower levels of
immune complexes (P<0.01)
Immuno-Modulation in
Human Immune Cells
Immuno modulating effects were
assessed by preincubation of
human neutrophils with EpiCor
prior to triggering of ROS formation by hydrogen peroxide (H2O2).
Treatment with EpiCor resulted in
statistically significant reduction of
ROS formation over a wide dilution
range. This finding suggests an
overall anti-oxidant effect of
EpiCor, with a strong and direct
activation of NK cells (Figure 2a
and 2b) and B lymphocytes, possibly
combined with a selective support
of Th2 over Th1 immune responsiveness.*
100
Figure 1. Addition of EpiCor™ increased
the killing efficiency in this tumor cell
assay. A separate, initial test had shown
that EpiCor™ does not directly kill the
tumor cell line K562.
Compared to the control, the
exposed group showed:
 A decrease in CD8 (suppressor)
cell number that resulted in a
significantly higher CD4 (helper)
to CD8 cell ratio (P<0.01)
 Higher cytotoxic activity of
natural killer (NK) cells (Figure 1),
despite a significant decrease in
their number (p<0.01)
 Higher killing efficiency of NK
cells (12.4% vs. 15.1%)
 Higher levels of glutathione in
erythro cytes (721 vs. 756 mM)
* These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.
Relative Marker Induction
(% Activated NK Cells)
CD69
80
CD25
60
100
% of Max
80
60
40
EpiCor™
Untreated
20
0
100
101
102
103
CD69 Intensity
Figure 2b. EpiCor™ treatment of freshly
purified human NK cells results in
expression of the activation marker CD69
on almost all CD3- CD56+ NK cells.
Why EpiCor?
A high metabolite immunogen
made from a fermented yeast
medium, EpiCor is unique as an
immune health ingredient. It
delivers three times the antioxidant
power of any known fruit as well as
B vitamins, natural phenolics and
fiber. Studies also show that EpiCor
promotes immune health by activating natural killer (NK) cells and
human B cells while also increasing
levels of secretory IgA, an
important component of the
immune system.*
For More Information
To learn more about EpiCor,
contact Embria Health Sciences at
877-362-7421 (EMBRIA1) or find us
on the web at
www.embriahealth.com
40
20
0
Epicor™ 10
uL/mL
Untreated
Figure 2a. Flow cytometric analysis of
CD69 and CD25 expression on
lymphocyte subsets cultured in the
presence and absence of EpiCor™
overnight. The presence of EpiCor
resulted in higher induction of both
markers. The induction of CD69 on NK
cells was significantly higher than that of
CD25 (p<0.03).
Scientific Research Summary
PO Box 2815, 838 1st Street NW
Cedar Rapids, IA 52406-2815
PH 877-362-7421 (Embria1) FAX 319-362-2557
www.embriahealth.com
EpiCor™ is exclusively manufactured by Embria Health Sciences™
June 2006
Immunomodulating Effects
of EpiCor™
What is EpiCor™?
Unusually low sick leave rates
over several decades in
employees working in a
fermentation facility in Cedar
Rapids, Iowa, led to a theory
that these employees’ exposure to a proprietary stressed
strain of Saccharomyces
cerevisiae (EpiCor) produced
at the facility and absorbed
daily by inhalation might have
important immune-enhancing
EpiCor is an all natural, highmetabolite immunogen that
supports the body’s immune system
to strengthen resistance and
maintain wellness.* Derived from a
fermented yeast medium, EpiCor is
supported by numerous safety
studies for everyday use, and can be
utilized as a sole-ingredient dietary
supplement or in multi-ingredient
formulations. EpiCor has also
recently achieved self-affirmed
GRAS status by an independent
expert panel—increasing delivery
options to include functional foods.
toxic gross pathological changes.
In the subacute study, 160 male
and female rats were divided into
four even groups. The first group
served as controls. The other
groups received daily oral doses of
30, 200, or 1,500 mg/kg of body
weight of EpiCor by gavage for 90
days, 7 days a week. EpiCor was
well tolerated in all groups, even
the high dosage group, for a period
of time allometrically equivalent to
1.5 years of human consumption on
a daily basis.
properties. An initial in vitro
total oxygen radical absor-
A Safe History
bance capacity (ORAC-hydro +
EpiCor is manufactured from a
species of yeast called Saccharomyces cerevisiae (SC) through our
proprietary, multi-stage fermentation and drying process, MetaGen4™.
SC, commonly known as ”brewer’s
yeast” or “baker’s yeast,” has a long
history of use in food processing for
human consumption in everything
from alcoholic beverages to baked
goods.
ORAC-lipo = Total ORAC)
assay revealed that EpiCor
possessed the second highest
peroxyl radical scavenging
activity (610 µmoleTE/g) of any
food ever tested.
Based on these observations,
studies were designed to
assess the potential of EpiCor
as a dietary supplement.
Research to date shows that
EpiCor activates natural killer
(NK) cells, human B cells and
increases the levels of salivary
secretory IgA.* Safety studies
have also been performed
showing that EpiCor is safe,
non-toxic, non-mutagenic,
non-mitogenic, non-cytotoxic,
and pesticide free.
Toxicology
Both acute (14-day) and
sub-acute (90-day) toxicology
studies have been performed on
EpiCor. In the acute study, a single
oral dose of 2,000 mg/kg of body
weight of EpiCor was administered
orally to 20 male and female rats by
gavage. Animals were weighed and
observed for toxic symptoms and
lethality for 14 days. Throughout the
course of the study, no toxic clinical
symptoms were observed and no
deaths occurred after oral
administration of EpiCor. On the
15th day, autopsies revealed no
Specifically, the following
parameters were unaffected by
taking EpiCor: body weight, food
and water consumption, eye
structure and function, sensory
reactivity, grip strength, motor
activity, hematological or serum
chemistry, prothrombin time and
urine chemistry. Additionally, no
treatment-related toxic clinical
symptoms or gross pathological
organ lesions were observed, and
no mortality occurred.
Both studies were GLP (Good
Laboratory Practices) compliant and
performed in accordance with US
Food & Drug Administration and
European Union guidelines.
* These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.
Contraindications?
None have been found to date.
An in vitro study was performed to
evaluate whether EpiCor is an
inducer of cytochrome P450 1A2
and P450 3A4 (CYP) enzymes in
immortalized human hepatocytes.
Induction of CYP enzymes is one of
the major mechanisms of drug to
drug interactions. The researchers
found that EpiCor did not induce
either enzyme’s activity, suggesting
that the ingredient does not interfere with the metabolic pathways of
common prescription medications.
This finding was confirmed in a
human pharmokinetic study (see
third panel).
Mutagenicity
Two tests were performed on
EpiCor to determine if the
ingredient causes gene mutations.
The first was a bacterial reverse
mutation assay. In this test, a strain
of microorganism, which is afflicted
with a mutation that affects its
ability to grow, is placed in the
presence of the test substance. If
the substance induces a mutation
that reverses the original mutation,
the microorganisms can grow.
EpiCor was incubated with
various strains of Salmonella
typhimurium and Escherichia coli
bacteria. This was performed in a
range of concentrations from 10 to
1,000 mcg per plate, both in the
presence and absence of an
exogenous metabolic activation
system. The bacteria did not grow;
therefore no evidence of mutagenic
activity was detected.
The second test was a mouse
lymphoma assay. This test has been
shown to detect missing classes of
mutations that are not capable of
detection in the bacterial reverse
mutation assay. Mouse lymphoma
cell lines were exposed to varying
concentrations of EpiCor, both in
the presence and absence of an
exogenous metabolic activation
system. The study found no
evidence for the induction of gene
mutation by EpiCor in any of the
concentrations tested.
Mitogenicity
A mitogen is a substance that
induces mitosis or cell division.
Because mitogens raise safety
concerns and may signal immune
over-reactivity, a lymphocyte
proliferation study was performed
to determine whether EpiCor is
mitogenic.
Healthy human lymphocytes
were incubated with a combination
of EpiCor and phosphate-buffered
saline.
Following centrifugation and
sterile filtration, some cell cultures
were treated with the extract while
others served as controls. At the
end of the study, there was no
difference between treated and
untreated cells, indicating that
EpiCor is not mitogenic.
Pharmacokinetics
Finally, the safety of EpiCor was
evaluated in real human subjects
through an open-label, single dose
pharmacokinetic study. Fifteen
healthy men and women between
the ages of 18 and 40 received a
single dose of 500 mg of EpiCor in
capsule form for 30 days. Safety was
assessed on days 0, 14, 21, 28, 29
and 30 for treatment-emerged
adverse events, vital sign measurements, serum chemistry, and
hematology and urinalysis tests.
EpiCor was well-tolerated in all
subjects. No adverse events were
reported. There was no evidence of
any clinically relevant effects of
EpiCor on any safety parameter.
What is EpiCor™?
Unusually low sick leave rates
over several decades in
employees working in a
fermentation facility in Cedar
Rapids, Iowa, led to a theory
that these employees’ exposure to a proprietary stressed
strain of Saccharomyces
cerevisiae (EpiCor) produced
at the facility and absorbed
daily by inhalation might have
important immune-enhancing
EpiCor is an all natural, high
metabolite immunogen that
supports the body’s immune system
to strengthen resistance and
maintain wellness.* Derived from a
fermented yeast medium, EpiCor is
supported by numerous safety
studies for everyday use, and can be
utilized as a sole-ingredient dietary
supplement or in multi-ingredient
formulations. EpiCor has also
recently achieved self-affirmed
GRAS status by an independent
expert panel—increasing delivery
options to include functional foods.
toxic gross pathological changes.
In the subacute study, 160 male
and female rats were divided into
four even groups. The first group
served as controls. The other
groups received daily oral doses of
30, 200, or 1,500 mg/kg of body
weight of EpiCor by gavage for 90
days, 7 days a week. EpiCor was
well tolerated in all groups, even
the high dosage group, for a period
of time allometrically equivalent to
1.5 years of human consumption on
a daily basis.
properties. An initial in vitro
total oxygen radical absor-
A Safe History
bance capacity (ORAC-hydro +
EpiCor is manufactured from a
species of yeast called Saccharomyces cerevisiae (SC) through our
proprietary, multi-stage fermentation and drying process, MetaGen4™.
SC, commonly known as ”brewer’s
yeast” or “baker’s yeast,” has a long
history of use in food processing for
human consumption in everything
from alcoholic beverages to baked
goods.
ORAC-lipo = Total ORAC)
assay revealed that EpiCor
possessed the second highest
peroxyl radical scavenging
activity (610 µmoleTE/g) of any
food ever tested.
Based on these observations,
studies were designed to
assess the potential of EpiCor
as a dietary supplement.
Research to date shows that
EpiCor activates natural killer
(NK) cells, human B cells and
increases the levels of salivary
secretory IgA.* Safety studies
have also been performed
showing that EpiCor is safe,
non-toxic, non-mutagenic,
non-mitogenic, non-cytotoxic,
and pesticide free.
Toxicology
Both acute (14-day) and
sub-acute (90-day) toxicology
studies have been performed on
EpiCor. In the acute study, a single
oral dose of 2,000 mg/kg of body
weight of EpiCor was administered
orally to 20 male and female rats by
gavage. Animals were weighed and
observed for toxic symptoms and
lethality for 14 days. Throughout the
course of the study, no toxic clinical
symptoms were observed and no
deaths occurred after oral
administration of EpiCor. On the
15th day, autopsies revealed no
Specifically, the following
parameters were unaffected by
taking EpiCor: body weight, food
and water consumption, eye
structure and function, sensory
reactivity, grip strength, motor
activity, hematological or serum
chemistry, prothrombin time and
urine chemistry. Additionally, no
treatment-related toxic clinical
symptoms or gross pathological
organ lesions were observed, and
no mortality occurred.
Both studies were GLP (Good
Laboratory Practices) compliant and
performed in accordance with US
Food & Drug Administration and
European Union guidelines.
* These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.
Contraindications?
None have been found to date.
An in vitro study was performed to
evaluate whether EpiCor is an
inducer of cytochrome P450 1A2
and P450 3A4 (CYP) enzymes in
immortalized human hepatocytes.
Induction of CYP enzymes is one of
the major mechanisms of drug to
drug interactions. The researchers
found that EpiCor did not induce
either enzyme’s activity, suggesting
that the ingredient does not interfere with the metabolic pathways of
common prescription medications.
This finding was confirmed in a
human pharmokinetic study (see
third panel).
Mutagenicity
Two tests were performed on
EpiCor to determine if the
ingredient causes gene mutations.
The first was a bacterial reverse
mutation assay. In this test, a strain
of microorganism, which is afflicted
with a mutation that affects its
ability to grow, is placed in the
presence of the test substance. If
the substance induces a mutation
that reverses the original mutation,
the microorganisms can grow.
EpiCor was incubated with
various strains of Salmonella
typhimurium and Escherichia coli
bacteria. This was performed in a
range of concentrations from 10 to
1,000 mcg per plate, both in the
presence and absence of an
exogenous metabolic activation
system. The bacteria did not grow;
therefore no evidence of mutagenic
activity was detected.
The second test was a mouse
lymphoma assay. This test has been
shown to detect missing classes of
mutations that are not capable of
detection in the bacterial reverse
mutation assay. Mouse lymphoma
cell lines were exposed to varying
concentrations of EpiCor, both in
the presence and absence of an
exogenous metabolic activation
system. The study found no
evidence for the induction of gene
mutation by EpiCor in any of the
concentrations tested.
Mitogenicity
A mitogen is a substance that
induces mitosis or cell division.
Because mitogens raise safety
concerns and may signal immune
over-reactivity, a lymphocyte
proliferation study was performed
to determine whether EpiCor is
mitogenic.
Healthy human lymphocytes
were incubated with a combination
of EpiCor and phosphate-buffered
saline.
Following centrifugation and
sterile filtration, some cell cultures
were treated with the extract while
others served as controls. At the
end of the study, there was no
difference between treated and
untreated cells, indicating that
EpiCor is not mitogenic.
Pharmacokinetics
Finally, the safety of EpiCor was
evaluated in real human subjects
through an open-label, single dose
pharmacokinetic study. Fifteen
healthy men and women between
the ages of 18 and 40 received a
single dose of 500 mg of EpiCor in
capsule form for 30 days. Safety was
assessed on days 0, 14, 21, 28, 29
and 30 for treatment-emerged
adverse events, vital sign measurements, serum chemistry, and
hematology and urinalysis tests.
EpiCor was well-tolerated in all
subjects. No adverse events were
reported. There was no evidence of
any clinically relevant effects of
EpiCor on any safety parameter.
A human blood study was conducted to explore “in vitro” whether
EpiCor enhanced the natural
process of the immune system to
suppress tumor cells. Ten production employees that were exposed
daily to EpiCor by inhalation during
intermittent periods at work, were
matched by age and gender to ten
non-production employees not
exposed to EpiCor. Blood samples
were analyzed for lymphocyte subpopulations, RBC total glutathione,
and an autoimmune panel. Saliva
samples were used for immunoglobulin A (IgA) determination.
25
% Dead Tumor Cells
20
15
10
5
 Significantly higher levels of
EpiCor-specific antibodies
(P<0.01)
 Significantly higher levels of
total salivary secretory IgA
(P<0.01)
 Significantly lower levels of
immune complexes (P<0.01)
EpiCor’s Effects on Human
Immune Cells
Immune modulating effects were
assessed by preincubation of
human neutrophils with EpiCor
prior to triggering of ROS formation by hydrogen peroxide (H2O2).
Treatment with EpiCor resulted in
statistically significant reduction of
ROS formation over a wide dilution
range. This finding suggests an
overall antioxidant effect of EpiCor,
with a strong and direct activation
of NK cells (Figure 2a and 2b) and B
lymphocytes, possibly combined
with a selective support of Th2 over
Th1 immune responsiveness.*
0
Untreated K562
PBL + K562
EpiCor™ PBL
+ K562
100
Figure 1. Addition of EpiCor™ increased
the killing efficiency in this tumor cell
assay. A separate, initial test had shown
that EpiCor does not directly kill the tumor
cell line K562.
Compared to the control, the
exposed group showed:
 A decrease in CD8 (suppressor)
cell number that resulted in a
significantly higher CD4 (helper)
to CD8 cell ratio (P<0.01)
 Higher cytotoxic activity of
natural killer (NK) cells (Figure 1),
despite a significant decrease in
their number (p<0.01)
 Higher killing efficiency of NK
cells (12.4% vs. 15.1%)
 Higher levels of glutathione in
erythro cytes (721 vs. 756 mM)
* These statements have not been evaluated by the Food and Drug Administration.
This product is not intended to diagnose, treat, cure, or prevent any disease.
Relative Marker Induction
(% Activated NK Cells)
CD69
80
100
% of Max
80
60
40
EpiCor™
Untreated
20
0
100
101
102
103
CD69 Intensity
Figure 2b. EpiCor™ treatment of freshly
purified human NK cells results in
expression of the activation marker CD69
on almost all CD3- CD56+ NK cells.
Why EpiCor?
A high-metabolite immunogen
made from a fermented yeast
medium, EpiCor is unique as an
immune health ingredient. It
delivers three times the antioxidant
power of any known fruit as well as
B vitamins, natural phenolics and
fiber. Studies also show that EpiCor
promotes immune health by activating natural killer (NK) cells and
human B cells while also increasing
levels of secretory IgA, an important
component of the immune system.*
CD25
For More Information
60
To learn more about EpiCor,
contact Embria Health Sciences at
877-362-7421 (EMBRIA1)
or find us on the web at
www.embriahealth.com
40
20
0
Epicor™ 10
uL/mL
Untreated
Figure 2a. Flow cytometric analysis
of CD69 and CD25 expression on
lymphocyte subsets cultured in the
presence and absence of EpiCor™
overnight. The presence of EpiCor
resulted in higher induction of both
markers. The induction of CD69 on NK
cells was significantly higher than that of
CD25 (p<0.03).
Scientific Research Summary
PO Box 2815, 838 1st Street NW
Cedar Rapids, IA 52406-2815
PH 877-362-7421 (Embria1) FAX 319-362-2557
www.embriahealth.com
EpiCor™ is exclusively manufactured by Embria Health Sciences™
6/06
Immune Modulating
Effects of EpiCor™