Wellmune w g p Research Summary

Transcription

1 Wellmune w g p Research Summary A Product of Biothera, the Immune Health Company Contacts: Don Cox, Ph.D. Vice President, Healthcare Research & Development dcox@biothera.com Steve Meredith Vice President, Sales U.S. and Canada smeredith@ biothera.com Allen Porter Vice President, Sales International aporter@biothera.com Biothera 3388 Mike Collins Drive Eagan, MN USA

2 Wellmune w g p : 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 w g p 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 w g p 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 w g p 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 2

3 Wellmune w g p Mechanism of Action. Wellmune w g p 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 w g p 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 w g p and transport it to immune organs throughout the body. While in the immune organs, immune cells called macrophages digest Wellmune w g p 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 w g p, the neutrophils now more quickly navigate to the site of a foreign challenge and kill it. Unlike other immune health ingredients, Wellmune w g p 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 w g p and release tiny fragments Day 3: Wellmune w g p fragments bind to neutrophils, priming them for activity. Source: Journal of Immunology, :

4 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 w g p 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. Based on published research, Wellmune w g p at the recommended dosage (2.5 mg/kg of bodyweight) provides for sufficient uptake for efficacious bioactivity. Phagocytic Index Wellmune w g p should be taken daily to provide maximum immune health benefits. The reason is linked to Wellmune w g p s unique mechanism of action. Wellmune works by enhancing or activating innate immune cells called neutrophils. The average life span of a neutrophil is several Figure 2: This study demonstrates that the number of phagocytic cells that engulf one microbe increased from 64% to 83% after 10 days of treatment with Wellmune WGP. Highly phagocytic cells, those that engulf three or more microbes, increased from 37% of the total cells at the start of the study to 57% after 10 days. days so it is important to continually take Wellmune w g p to prime new immune cells that the body is constantly producing. Applications. Wellmune w g p 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 w g p is odorless, clear and mild to no taste. 4

5 Research - Proof of Efficacy Biothera has initiated a multi-year clinical program to evaluate the efficacy of Wellmune w g p 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 w g p 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 or contact: Don Cox, Ph.D. Vice President, Research & Development Healthcare Group Biothera dcox@biothera.com 5

6 Wellmune w g p Alleviates Duration, Severity and Down Time Due to Cold Symptoms Compared with the placebo group, the Wellmune wgp group reported: No incidence of fever compared with 3.5 incidences over a 90-day period No need to take a sick day from work or school, compared with 1.38 days of work/school missed for the placebo group An increase in general health, including physical energy and emotional well-being In a cold season study with 40 healthy subjects, Wellmune w g p 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. In contrast with the placebo group, the Wellmune w g p 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). 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 w g p - supplemented group exhibited significant improvements in Physical Component Summary scores as defined in the SF-36v-2 health survey. 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 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 ± ± General Health - day ± ± Physical Health Summary - day ± ± Physical Health Summary - day ± ± Medically-verified symptoms and study outcomes Variable Wellmune Placebo P-value Incidence of Fever ± Average runny nose 14.1 ± ± 8.6 NS Average sneezing 10.8 ± ± 12.0 NS Average coughing 15.9 ± ± 3.4 NS Number of missed days of ± work/school 6

7 Wellmune w g p Reduces Incidence of Health Challenges in High Lifestyle Stress Subjects Individuals with high lifestyle stress taking Wellmune w g p 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 Select results are below. Publication is pending. Compared with the placebo group, the Wellmune w g p 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 250 mg 500 mg WGP/day WGP/day Q1 - During the course of the supplement regimen End of 2-week 4.3± *± *±1.3 my health has been...(1 = worse, 10 = better) period End of 4-week 4.6± *± *±1.2 period y Q1 - At the END of this 2-week period how would you End of 2-week 5.0± *± *±1.6 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) End of 4-week 5.3± *± *±1.9 period End of 2-week period End of 4-week period 16 subjects 5* subjects 4* subjects 14 subjects 4* subjects 4* subjects * p<0.05 vs. placebo Subjects completed the Profile of Mood State (POMS) Survey Instrument. The well-validated POMS employs 65 adjective based indicators of mood scaled for intensity (0-4); specific combinations of the adjectives define the 6 mood state factors: tension, vigor, fatigue, confusion, anger and depression. POMS Tension Factor POMS Fatigue Factor POMS Vigor Factor POMS Confusion Factor Figure 1. Analyzed data for specific POMS factors calculated from 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). 7

8 Wellmune w g p Reduced Fatigue and Infection Symptoms in Marathoners In contrast with the placebo group, Marathoners taking Wellmune w g p reported a: 22% increase in vigor Wellmune w g p 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 (mean age 36 years) who were recruited at the 2007 Carlsbad Marathon in California. Subjects were treated daily with Wellmune w g p, 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 Subjects Reporting URTI Symptoms Effect of Wellmune on Self-Reported Health Score 38% reduction in stressrelated confusion Number of Subjects Indicating URTI Symptoms 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 w g p or 500 mg Wellmune w g p. 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. Subjects completed the Profile of Mood State (POMS) Survey Instrument. The well-validated POMS employs 65 adjective based indicators of mood scaled for intensity (0-4); specific combinations of the adjectives define the 6 mood state factors: tension, vigor, fatigue, confusion, anger and depression. POMS Tension Factor POMS Fatigue Factor POMS Vigor Factor POMS Confusion Factor Figure 3. Analyzed data for specific POMS factors calculated from 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

9 Wildland Firefighters Report fewer URTI infections with Wellmune w g p 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 w g p. The results were presented at American College of Sports Medicine in May 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

10 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 Clinical Research Effectiveness of Wellmune w g p 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 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 w g p reduces URTI symptoms in marathon runners. Results were presented at the 2007 American College of Nutrition. Publication pending. Wellmune w g p reduces stress and URTI symptoms in highly stressed subjects. Results were presented at the 2007 American College of Nutrition. Publication pending. Wellmune w g p improves NK cell activity in subjects with cold -- report available. Wellmune w g p improves general immune health biomarkers -- report available. Preclinical Research Babıcek K., Cechova, I., Simon, R. R., Harwood, M., Cox, D. J Toxicological Assessment of a Particulate Yeast (1,3)-ß-D-glucan in rats. Food and Chemical Toxicology. doi: /j.fct Lavigne L. M., Albina, J. E., and Reichner, J. S ß-Glucan is a Fungal Determinant for Adhesion-Dependent Human Neutrophil Functions. J. Immunol. 177: Li, B., Allendorf, D. J., Hansen, R. D., Marroquin, J., Ding, C., Cramer, D. E., and Yan, J Yeast ß-Glucan Amplifies Phagocyte Killing of ic3b-opsonized Tumor Cells via Complement Receptor 3-Syk- Phosphatidylinositol 3-Kinase Pathway. J. Immunol. 177: Cramer, D. E., Allendorf, D. J., Baran, J. T., Hansen, R. D., Marroquin, J., Li, B., Ratajczak, J., Ratajczak, M. Z., and Yan, J 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 C5a-Mediated Leukotriene B4-Amplified Neutrophil Chemotaxis is Essential in Tumor Immunotherapy Facilitated by Anti-tumor Monoclonal Antibody and ß-Glucan. J. Immunol. 174:

11 Yan J., Allendorf, D. J., Brandley, B 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 Tsikitis, V. L., J. E. Albina and J. S. Reichner ß-Glucan Affects Leukocyte Navigation in a Complex Chemotactic Gradient. Surgery;136: 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 Mechanism by Which Orally Administered ß-1,3-Glucans Enhance the Tumorcidial Activity of AntiTumor Monoclonal Antibodies in Murine Tumor Models. J. Immunol. 173: McNair, D. M., J. W. P. Heuchert and E. Shilony Profile of Mood States: Bibliography Toronto, Canada: Mulit-Health Systems, Inc. Kournikakis, B., Mandeville, R., Brousseau, P., Ostroff, G Anthrax-Protective Effects of Yeast Beta 1,3 Glucans. Medscape General Medicine. March 24. Hong, F., Hansen, R. D., Yan, J., Allendorf, D. J., Baran, J. T., Ostroff, G., and Ross, G ß-Glucan Functions as an Adjuvant for Monoclonal Antibody Immunotherapy by Recruiting Tumoricidal Granulocytes as Killer Cells. Cancer Research. 63,