Wellmune WGP® Research Summary

Wellmune wgp
Research Summary
®
A Product of Biothera, the Immune Health Company
Contacts:
Don Cox, Ph.D.
Vice President, Healthcare Research & Development
651.256.4621
[email protected]
Steve Meredith
Vice President, Sales
U.S. and Canada
801.944.8868
smeredith@ biothera.com
Allen Porter
Vice President, Sales
International
651.256.4622
[email protected]
Biothera
3388 Mike Collins Drive
Eagan, MN 55121
USA
www.wellmune.com
Wellmune wgp :
Nature’s Immune Enhancer
®
An Innovative Functional Food and Beverage Ingredient
that is Clinically Proven to Enhance Immune Function
A Product of Biothera, the Immune Health Company
Introduction.
Wellmune wgp® is a natural food and beverage ingredient that is clinically proven to safely enhance immune responses that protect against
a wide range of health challenges. Wellmune wgp activates billions of
innate immune cells, which are the body’s first line of defense, to more
quickly recognize and kill foreign intruders without stimulating the immune system. This unique ingredient’s patented, year-round protection
is the culmination of more than $250 million in research with leading
university and government institutions.
The potential for immune-enhancing products spans virtually all food
and beverage categories now that the importance of the immune
health has reached critical mass with consumers. In fact, a 2008 survey
by the International Food Information Council (IFIC) found that 87% of
consumers have a current or future interest in products that improve
immune system function. The compelling safety and efficacy research
supporting Wellmune wgp make it an ideal ingredient for delivering real
health benefits to consumers.
Wellmune WGP® is a unique gluco 1,3/1,6 polysaccharide,
a natural carbohydrate derived from a proprietary strain
of yeast.
n A natural functional ingredient designed for foods,
beverages and supplements
n Clinically proven to enhance the immune system
n Patent-protected
n GRAS-approved under U.S. FDA regulations and
TGA-approved in Australia
n Kosher, Halal, non-allergenic and GMO-free
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Wellmune wgp Mechanism of Action.
Wellmune wgp is a natural gluco polysaccharide derived from the cell
walls of a highly purified, proprietary yeast (Saccharomyces cerevisiae).
This unique ingredient triggers human immune defenses that have
evolved over thousands of years to protect the body.
The scientific understanding of Wellmune wgp’s mechanism of action in the
body is well documented in published, peer-reviewed research. Mechanism of action studies as well as measurement of significant changes in
immune responses are changing the way researchers and physicians think
about innate immune function.
Clinical Studies
demonstrate that
Wellmune WGP signficantly increases:
• Percent of active
immune cells available to defend the
body
• Mobilization of innate immune cells
to the site of a foreign challenge
• Killing (phagocytosis) of foreign challenges, resulting in
a more complete
immune response
Once swallowed, immune cells in the gastrointestinal tract take up Wellmune wgp and
transport it to immune organs throughout
the body. While in the immune organs, immune cells called macrophages digest
Wellmune wgp into smaller fragments and
slowly release them over a number of
days. The fragments bind to neutrophils,
via complement receptor 3 (CR3), which
are the most abundant immune cells in
the body. In fact, neutrophils account for
60-70% of all immune cells.
Activated by Wellmune wgp, the neutrophils now more quickly navigate to
the site of a foreign challenge and kill
it. Unlike other immune health ingredients, Wellmune wgp enhances immune
function without stimulating the immune system. Immune boosters or
stimulators may be harmful and cause autoimmune disease.
Researchers discovered the mechanism through a series of experiments, including those with CR3-deficit mice that confirmed the criti-
Figure 1
Day 1: Wellmune wgp ingested by macrophages.
Day 2: Macrophages
degrade Wellmune wgp
and release tiny fragments
Source: Journal of Immunology, 2004 173: 807-817.
Day 3: Wellmune wgp
fragments bind to neutrophils, priming them for
activity.
3
cal role this receptor plays in triggering an immune response. Other
studies tracked fluorescently dyed Wellmune wgp as immune cells transported it throughout the body (figure 1). Within days Wellmune wgp is
carried to the spleen, bone marrow and other immune organs.
In a separate study, significant improvement was observed in the killing activity of immune cells (Figure 2). Phagocytic cells, which literally engulf
and destroy foreign challengers, showed greater microbial killing in
subjects who had taken Wellmune WGP.
Dosage Form/
Delivery
Mechanism.
Phagocytic Index
Based on published
research, Wellmune wgp
at the recommended
dosage (2.5 mg/kg of
bodyweight) provides
for sufficient uptake for
efficacious bioactivity.
Wellmune wgp should
be taken daily to
provide maximum
immune health benefits.
The reason is linked to
Wellmune wgp’s unique
Figure 2: This study demonstrates that the number of
mechanism of action.
phagocytic cells that engulf one microbe increased from
Wellmune works by
64% to 83% after 10 days of treatment with Wellmune WGP.
Highly phagocytic cells, those that engulf three or more mienhancing or activating
crobes, increased from 37% of the total cells at the start of
innate immune cells
the study to 57% after 10 days.
called neutrophils. The
average life span of
a neutrophil is several
days so it is important to continually take Wellmune wgp to prime new
immune cells that the body is constantly producing.
Applications.
Wellmune wgp is designed for the majority of food, beverage and
supplement applications. Wellmune is available in two powder forms -dispersible for food and select beverage applications and water soluble
for certain beverage applications with clarity or other manufacturing
requirements. In water at 1 mg per milliliter, soluble Wellmune wgp is odorless,
clear and mild to no taste.
4
Research - Proof of Efficacy
Biothera has initiated a multi-year clinical program to evaluate the
efficacy of Wellmune wgp in humans under various physical and
psychological stress situations. Years of research has resulted in a product with a well-defined mechanism of action, a compelling body of
credible, peer-reviewed science and increasing clinical evidence of
its efficacy.
Four clinical studies completed in the past 18 months were designed to
assess the impact of Wellmune WGP on the physical and psychological health of individuals experiencing lifestyle and physical stress that
often directly lead to illness. The studies featured four different populations including firefighters, marathoners and individuals with high
lifestyle stress. Select results from these studies are highlighted on
pages 5-8 of this summary.
The complete body of research supporting Wellmune wgp includes
additional clinical research, numerous preclinical studies and human
biomarker research. Biothera remains committed to ongoing
research that advances the science of its ingredients and understanding of immune health.
For additional information, please visit www.wellmune.com or
contact:
Don Cox, Ph.D.
Vice President, Research & Development
Healthcare Group
Biothera
651-256-4621
[email protected]
5
Wellmune wgp Alleviates Duration,
Severity and ‘Down Time’ Due to
Cold Symptoms
Compared with the placebo group, the Wellmune wgp group reported:
In a cold season study with 40 healthy subjects, Wellmune wgp reduced the
incidence of fever and eliminated the need to miss work or school due to
cold-like symptoms. The double-blind, placebo-controlled study included
subjects, aged 18-65, who were treated daily with either 250mg of Wellmune WGP or a placebo for 90 days. The study results were presented at
the 2008 Experimental Biology annual meeting. Select results are below.
Publication is pending.
• No incidence of fever
compared with 3.5 incidences over a 90-day
period
In contrast with the placebo group, the Wellmune wgp group reported an
increase in general health markers, including physical energy and emotional well-being, as measured by a clinically validated health survey questionnaire (SF-36v-2).
• No need to take a “sick
day” from work or school,
compared with 1.38 days
of work/school missed for
the placebo group
In addition, although there were no differences between groups in the
number of colds, at the end of the 12-week test period the Wellmune wgpsupplemented group exhibited significant improvements in Physical Component Summary scores as defined in the SF-36v-2 health survey.
• An increase in general
health, including physical
energy and emotional
well-being
Subjects self-administered SF-36 Quality of Life Questionnaire. The SF-36
consists of eight scaled scores, which are the sums of the questions in
their section. Each scale is directly transformed into a 0-100 scale on the
assumption that each question carries equal weight. The eight sections
are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role
functioning, and mental health.
SF-36 Quality of Life Questionnaire
Variable
Wellmune
Placebo P-value
General Health - day 0 59.7 ± 4.5 57.0 ± 5.3 0.147
General Health - day 90 58.7 ± 7.0 52.0 ± 14.6 0.038
Physical Health Summary - day 0 56.7 ± 4.5 57.3 ± 2.3 0.576
Physical Health Summary - day 90 57.5 ± 4.5 55.5 ± 3.5 0.029
Medically-verified symptoms and study outcomes
Variable
Wellmune
Placebo P-value
Incidence of Fever 0.00 3.5 ± 3.42 0.042
Average runny nose
14.1 ± 12.5 21.0 ± 8.6 NS
Average sneezing 10.8 ± 5.7 17.1 ± 12.0 NS
Average coughing 15.9 ± 16.2 17.5 ± 3.4 NS
Number of missed days of work/school
0.00 1.38 ± 1.25 0.026
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Wellmune wgp Reduces Incidence of
Health Challenges in High Lifestyle
Stress Subjects
Individuals with high lifestyle stress taking Wellmune wgp over four weeks
reported a significant increase in their general health, compared with the
placebo group. The clinical study results were presented at the American
College of Nutrition in 2007. Select results are below. Publication is pending.
Compared with the placebo group, the Wellmune wgp group reported
a:
• 42% increase in vigor
• 38% reduction in fatigue
• 19% reduction in tension
• 15% reduction in stressinduced confusion
150 subjects with high lifestyle stress were randomized, double blinded and
placebo controlled. Subjects were split into three groups: placebo, 250 mg/
day and 500 mg/day of Wellmune WGP. Subjects maintained a daily health
log with entries tracking the occurence and duration of URTI symptoms
(cough, sore throat, sneezing, etc.). They also responded to questions regarding physical health during course of study.
Table 1. Effect of Wellmune wgp treatment or placebo on physical health of subjects reporting moderate to high lifestyle stress over a four-week monitoring period.
Placebo
Q1 - During the course of the supplement regimen End of 2-week 4.3±1.0 my health has been...(1 = worse, 10 = better) period
250 mg
500 mg
WGP/day WGP/day
6.2*±1.2 7.0*±1.3
4.6±1.0 y
5.0±1.2 6.5*±1.1 7.2*±1.2
6.9*±1.6 7.4*±1.6
End of 4-week
period
5.3±1.4 7.1*±1.7 7.9*±1.9
End of 2-week
period
16 subjects 5* subjects 4* subjects
End of 4-week
period
14 subjects 4* subjects 4* subjects
End of 4-week
period
Q1 - At the END of this 2-week period how would you End of 2-week
rate your overall health...(1 = worse, 10 = better) period
Reported symptoms (headache, thirst, tiredness,
weakness, fatigue, runny nose, nasal congestion,
itchy nose, sneezing, coughing, sore throat,
general aches)
* p<0.05 vs. placebo
Subjects completed the
POMS Tension Factor
ment. The well-validated
POMS employs 65 adjective based indicators of
mood scaled for intensity
POMS Vigor Factor
POMS Score
(POMS) Survey Instru-
POMS Score
Profile of Mood State
(0-4); specific combinations of the adjectives
and depression.
POMS Score
fatigue, confusion, anger
POMS Score
factors: tension, vigor,
POMS Confusion Factor
POMS Fatigue Factor
define the 6 mood state
Figure 1. Analyzed data for specific POMS factors calculated from POMS Score Sheet. Data analysis was by paired
t-test. A value of p < 0.05 was considered significant. Each Factor was determined using answers to specific adjective
based scales as described in Profile of Mood States manual by McNair et al (28).
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Wellmune wgp Reduced Fatigue and
Infection Symptoms in Marathoners
In contrast with the placebo group, Marathoners
taking Wellmune wgp
reported a:
• 22% increase in vigor
Wellmune wgp increased vigor and mental clarity while reducing fatigue
and upper respiratory tract infection (URTI) symptoms in marathon runners.
The double-blind, placebo-controlled study included 75 marathon runners
(35 men, 40 women) ages 18-53 (mean age 36 years) who were recruited
at the 2007 Carlsbad Marathon in California. Subjects were treated daily
with Wellmune wgp, a natural carbohydrate that activates key immune cells
to more quickly recognize and kill foreign challenges, or a placebo for four
weeks. The results were presented at the 2007 annual meeting of the American College of Nutrition. Select results are below. Publication is pending.
The protocol of this study was identical to the study completed with high
lifestyle stress subjects (page 3).
• 48% reduction in fatigue
• 38% reduction in tension
Effect of Wellmune on Self-Reported Health Score
Figure 1. Total number of subjects reporting any of
eleven pre-selected upper-respiratory tract infection
symptoms. Subjects were orally administered placebo,
250 mg Wellmune wgp or 500 mg Wellmune wgp.
Statistical analysis was by paired t-tests. A value of
p ≤ 0.05 was considered significant.
Figure 2. Subjects responded to two and four week
supplement effectiveness question: “During the course
of the supplement regimen, my health has been…:”
Scores for the question were based on a scale of 0-10
with 0 being worse, 5 being same and 10 being better
health. Data analysis was by paired t-test. A value of
p ≤ 0.05 was considered significant.
Number of Subjects
Indicating URTI Symptoms
POMS Tension Factor
Profile of Mood State
(POMS) Survey Instrument. The well-validated
POMS employs 65 adjective based indicators of
POMS Score
Subjects completed the
POMS Vigor Factor
POMS Score
• 38% reduction in stressrelated confusion
Subjects Reporting URTI Symptoms
mood scaled for intensity
(0-4); specific combinations of the adjectives
and depression.
POMS Score
fatigue, confusion, anger
POMS Score
define the 6 mood state
factors: tension, vigor,
POMS Confusion Factor
POMS Fatigue Factor
Figure 3. Analyzed data for specific POMS factors calculated from POMS Score Sheet. Data analysis was by paired
t-test. A value of p < 0.05 was considered significant. Each Factor was determined using answers to specific adjective
based scales as described in Profile of Mood States manual by McNair et al (28).
8
Wildland Firefighters Report fewer
URTI infections with Wellmune wgp
A study conducted by the University of Montana, with funding from
Biothera and the U.S. Air Force, found that wildland firefighters benefited
from Wellmune wgp. The results were presented at American College of
Sports Medicine in May 2008.
In a double-blind, random cross-over design subjects completed two
14-day conditions with a three-day washout between trials. Supplements
were consumed once a day and consisted of Immune Health Basics and
a similar capsule placebo.
In comparison with the control group, Wellmune wgp subjects experienced a:
• 23% reduction in upper respiratory tract infection symptoms
• Dramatic improvement in overall physical health
Subjects completed a daily health questionnaire as used by Nieman et
al. (2002), with additional questions added that pertained specifically to
the supplement.
An individual was classified as having an URTI when they recorded a cold
or flu symptom for a minimum of two consecutive days.
At the conclusion of each trial subjects completed an overall health performance questionnaire, which contained questions regarding subjects
overall health during the 14-day trial.
9
Biothera Research
Research supporting the safety and efficacy of Biothera ingredients is the
subject of numerous peer-reviewed science and medical journals. Abstracts
of these articles are available at www.biothera.com.
Clinical Research
• Effectiveness of Wellmune wgp® in preventing upper respiratory tract
infection (URTI) symptoms and improving overall health in wildland firefighters. The results were presented at the American College of Sports
Medicine annual meeting in May 2008. Publication pending.
• Wellmune wgp reduces incidence of URTI symptoms and missed school/
work days in geographic areas reporting cold & flu activity. Results were
presented at Experimental Biology 2008 in April. Publication pending.
• Wellmune wgp reduces URTI symptoms in marathon runners. Results were
presented at the 2007 American College of Nutrition. Publication pending.
• Wellmune wgp reduces stress and URTI symptoms in highly stressed
subjects. Results were presented at the 2007 American College of
Nutrition. Publication pending.
• Wellmune wgp improves NK cell activity in subjects with cold -- report
available.
• Wellmune wgp improves general immune health biomarkers -- report
available.
Preclinical Research
Babıcek K., Cechova, I., Simon, R. R., Harwood, M., Cox, D. J. 2007. Toxicological Assessment of a Particulate Yeast (1,3)-ß-D-glucan in rats. Food and
Chemical Toxicology. doi:10.1016/j.fct.2007.03.013.
Lavigne L. M., Albina, J. E., and Reichner, J. S. 2006. ß-Glucan is a Fungal
Determinant for Adhesion-Dependent Human Neutrophil Functions.
J. Immunol. 177:8667-8675.
Li, B., Allendorf, D. J., Hansen, R. D., Marroquin, J., Ding, C., Cramer, D. E., and
Yan, J. 2006. Yeast ß-Glucan Amplifies Phagocyte Killing of iC3b-Opsonized
Tumor Cells via Complement Receptor 3-Syk- Phosphatidylinositol 3-Kinase
Pathway. J. Immunol. 177: 1661-1669.
Cramer, D. E., Allendorf, D. J., Baran, J. T., Hansen, R. D., Marroquin, J., Li, B.,
Ratajczak, J., Ratajczak, M. Z., and Yan, J. 2006. Beta-Glucan Enhances
Complemented-Mediated Hematopoietic Recovery After Bone Marrow
Injury. Blood. Volume 107, Number 2.
Allendorf, D. J., Yan, J., Ross, G. D., Hansen, R. D., Baran, J. T., Subbarao, K.,
Wang, L., and Haribabu, B. 2005. C5a-Mediated Leukotriene B4-Amplified
Neutrophil Chemotaxis is Essential in Tumor Immunotherapy Facilitated by
Anti-tumor Monoclonal Antibody and ß-Glucan. J. Immunol. 174:7050-7056.
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Yan J., Allendorf, D. J., Brandley, B. 2005. Yeast Whole Glucan Particle
ß-Glucan in Conjunction with Anti-tumour Monoclonal Antibodies to Treat
Cancer. Expert Opinion on Biological Therapy. Vol. 5, No. 5, Pages 691-702.
Tsikitis, V. L., J. E. Albina and J. S. Reichner. 2004. ß-Glucan Affects Leukocyte
Navigation in a Complex Chemotactic Gradient. Surgery;136:384-389.
Hong, F., Yan, J. Baran J. T., Allendorf, D. J., Hansen, R. D., Ostroff, G., Xing,
P.X., Cheung, N. V. and Ross, G. D. 2004. Mechanism by Which Orally
Administered ß-1,3-Glucans Enhance the Tumorcidial Activity of AntiTumor
Monoclonal Antibodies in Murine Tumor Models. J. Immunol. 173:797-806.
McNair, D. M., J. W. P. Heuchert and E. Shilony. 2003. Profile of Mood States:
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Kournikakis, B., Mandeville, R., Brousseau, P., Ostroff, G. 2003. Anthrax-Protective Effects of Yeast Beta 1,3 Glucans. Medscape General Medicine. March
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