Biochemical Markers Observed in EpiCor® Studies

MODES OF ACTION

A major portion of Embria’s research on EpiCor yeast fermentate has used double-blind, placebo-controlled human trials looking at clinical endpoints.1,2,3 A Summary of these human clinical trials can be found in Embria’s “Summary of Human Clinical Trials on EpiCor.” These clinical results demonstrate statistically

adult subjects, and have been published mostly in peer-reviewed Medline-indexed journals. Reduction in symptoms of both upper respiratory track infection (URTI) and allergies were the main thrust of the research.

This paper recognizes the importance of clinical biomarkers in

vivo biomarkers mentioned in this summary are from research conducted on healthy adult subjects. Most of the biomarkers mentioned in this paper are also represented in a table at the end of the article.

EpiCor® is a registered trademark of Embria Health Sciences, LLC. © Embria Health Sciences, LLC. All rights reserved. #38042-4

health care professionals. Not for distribution to consumers.

Marketed by:KenzaHealthUnit 51 APD Office ParkKelvin Street, Kya Sands

Contact: 0860 103 359

immunoarmour.co.za

More information contact:info@immunoarmour.co.za

1. INNATE AND ADAPTIVE IMMUNE SYSTEM

• Significantly increases Natural Killer (NK) Cell activation in vivo6 and in vitro5

• Significantly increases NK Cell activation in less than two hours post- consumption6

PHYSIOLOGY: NK cells are a type of white blood cell critical to the innate immune system. They provide a rapid immune response when needed. In many cases the NK cells will mean the adaptive response isn’t even needed. Even if an adaptive response is needed, NK cells are also known to play a role in the slower acting but more specific adaptive immune response.

• Significantly increases secretory salivary IgA (sIgA) versus placebo2,4

PHYSIOLOGY: sIgA is the main immunoglobulin (antibody) found in mucous secretions, including tears, saliva, colostrum and secretions from the genitourinary tract, gastrointestinal tract, prostate and respiratory epithelium. It is a major component of the body’s adaptive immune system in defense against foreign organisms. It is also well known as an important link between the adaptive and innate immune systems. Recent science shows that sIgA may also have other beneficial effects in overall immunity through reduced inflammation in the digestive tract.

• Increases B cell activation in vitro5

PHYSIOLOGY: B cells are an essential component of the human adaptive immune system. Their principal function is to make antibodies against antigens.

2. ENVIRONMENTAL ALLERGIES

• Strong trend toward reduction of eosinophils in EpiCor group versus placebo2

PHYSIOLOGY: Nasal eosinophils are commonly elevated in healthy people susceptible to environmental allergies.7

• 2

PHYSIOLOGY: Increased lymphocytes would be expected in the nasal smears of healthy people susceptible to environmental allergies.

• Trend toward relative decrease in serum IgE versus placebo4,2

PHYSIOLOGY: Pollen binds to IgE antibodies present on the mast cells of allergy sufferers. The mast cells, and similar cells like basophils activate to release chemicals, including histamine, into the

in surrounding tissues and causes nerve stimulation, leading to symptoms of itchy, watery eyes, sneezing, runny nose, and itching of the nose and throat.

• 8

PHYSIOLOGY: Prostaglandins, including PGE2, are also produced in large amounts during 9

• 8

PHYSIOLOGY: Studies have shown increased production of NGF in people with sensitivity to environmental allergens.

• Total white blood cell count remained constant in the EpiCor group, whereas there was a mild trend towards an increase in white blood cells in the placebo group4

PHYSIOLOGY: White blood cells tend to proliferate in people due to the onset of seasonal allergies.

3. ANTIOXIDANT

• 6

PHYSIOLOGY: Antioxidants are known to protect cells against damage by free radicals.

HEALTH AND IMMUNITY

• 10,11 (IN VITRO)

PHYSIOLOGY: B&L are lactic acid-producing bacteria constituting a major part of the

from the point of view of the host, is probably to act in colonization resistance against foreign microorganisms.12

• 10 (IN VITRO)

PHYSIOLOGY: Butyrate is the major source for the intestinal epithelial cells, is considered

mucosa.13

• 10 (IN VITRO)

PHYSIOLOGY: The change in composition of the microbial community of the gut caused a

lining.10,11

• 4

PHYSIOLOGY: IL- 10, also known as human cytokine synthesis inhibitory factor (CSIF), is an anti- ytokine.

• 2

PHYSIOLOGY: In a healthy person, sIgA inhibits the colonization of pathogenic bacteria in the gut, as well as the mucosal penetration of pathogenic antigens. At least 80% of all the body’s plasma cells, the source of sIgA, are located in the intestinal lamina propria throughout the length of the small intestine.14

5. INFLAMMATORY RESPONSE

• 8 • γ

8

PHYSIOLOGY: IFN- γ γ is

now thought to have pleiotropic effects and thus can have both promoting and suppressive roles in autoimmunity.

• 8

PHYSIOLOGY: responses because it impacts mast cells and afferent neurons.

• 8

PHYSIOLOGY: model.

• 8

PHYSIOLOGY:

function.

• 4

PHYSIOLOGY: IL- 10, also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-

•

15

PHYSIOLOGY: . The skin

SUMMARY OF SCIENTIFIC ENDPOINTS FROM EPICOR STUDIES

Proliferation or decrease of immune cells

Categories

LymphocytesProliferation of B lymphocytes

Proliferation of T lymphocytes

Decreased nasal smear lymphocytes during allergy season

Decreased eosinophils during allergy season

Activity of NK Cell

Increased production of secretory IgA

Increased production of IgG

Decreased TNF-a

Decreased IFN-ƛDecreased IL-8

Increased IL-10

CD80 on B lymphocytes

CD86 on B lymphocytes

CD25 (IL-2 receptor) on CD3+CD56+NK Cells

CD69 on CD3+CD56+NK Cells

T Cell homing

NK Cells homing

Incidence of cold/flu symptoms

Duration of cold/flu symptoms

Inhibitory activity

Occurrence and duration of allergy symptoms

Decreased need of rescue medication

Decreased carrageenan-induced localized inflammation

Collagen injection induced inflammation (arthritis)

Histamine-induced inflammation

Reduced neutrophil production of ROS

Relatively high ORAC (614 umol TE/g)

Increased antioxidant power in serum (Cap-e)

Antioxidant protection of red blood cells

Increased SCFA (butyrate, acetate &propionate)

Increased lactobacilli

Qualitative modulation of bifidobacteria

Decreased coliforms, clostridia, staphylococci and facultative anaerobes

Increased hematocrit

Biomarkers of Clinical Endpoints In vitro Animal Human

Leukocytes

Activation of the function of immunocytes

Cytotoxicity

Antibody formation

Production of Immuno-active

compounds (cytokines)

Induction of activation markers

Immunity modulation

Cold/Flu

Inhibitory (Allergy)

Inhibitory (Inflammation)

Antioxidant Effects

Pre-biotic properties

Community structure

Eythrocyte Health

Gut Health

5

5

5

10

10,11

5

5

5

5

5

5

16

16

10,11

10,11

10,11

10

8

8

8

2

2(NS)

6

2,4

4(NS)

4(NS)

6

6

6(IE)

6(IE)

1,3

1,3(NS)

2

2

2

15

6

4

(Numbers Refer to References)EpiCor Research

NS = Not SignificantIE = Indirect Evidence

1. symptoms. Urol Nurs 2008, 28 (1), 50-5.

2. Moyad, M. A.; Robinson, L. E.; Kittelsrud, J. M.; Reeves, S. G.; Weaver, S. E.; Guzman, A. I.; Bubak, M. E., Immunogenic yeast-based fermentation product reduces allergic rhinitis-induced nasal congestion: a randomized, double-blind, placebo-controlled trial. Adv Ther 2009, 26 (8), 795-804.

3. symptoms in nonvaccinated individuals. J Altern Complement Med 2010, 16 (2), 213-8.

4. Jensen, G. S.; Patterson, K. M.; Barnes, J.; Schauss, A. G.; Beaman, R.; Reeves, S.; Robinson, L., A Double-Blind Placebo-Controlled, Randomized Pilot Study:

Subjects. The Open Nutrition Journal 2008, 2, 68-75.

5. human natural killer cells and B lymphocytes in vitro. Nutrition Research 2007, 27, 327-335.

6. Jensen, G. S.; Redman, K. A.; Benson, K. F.; Carter, S. G.; Mitzner, M. A.; Reeves, S.; Robinson, L., Antioxidant bioavailability and rapid immune-modulating effects after consumption of a single acute dose of a high-metabolite yeast immunogen: results of a placebo-controlled double-blinded crossover pilot study. J Med Food 2011, 14 (9), 1002-10.

7. Indian J Otolaryngol Head Neck Surg 2005, 57 (1), 13-6.

8. Evidence-Based Complementary and Alternative Medicine 2012, 2012, 7.

9. Th1 cell differentiation and Th17 cell expansion. Nat Med 2009, 15 (6), 633-40.

10. Possemiers, S.; Pinheiro, I.; Verhelst, A.; Van den Abbeele, P.; Maignien, L.; Laukens, D.; Reeves, S. G.; Robinson, L. E.; Raas, T.; Schneider, Y. J.; Van de Wiele, T.;

an Integrated in Vitro Approach. J Agric Food Chem 2013, 61 (39), 9380-9392.

11. Marzorati, M.; Vanhoecke, B.; De Ryck, T.; Sadaghian Sadabad, M.; Pinheiro, I.; Possemiers, S.; Van den Abbeele, P.; Derycke, L.; Bracke, M.; Pieters, J.; Hennebel, T.; Harmsen, H. J.; Verstraete, W.; Van de Wiele, T., The HMI module: a new tool to study the Host-Microbiota Interaction in the human gastrointestinal tract in vitro. BMC Microbiol 2014, 14 (1), 133.

12. Lancet 2003, 361 (9371), 1831.

13. Pryde, S. E.; Duncan, S. H.; Hold, G. L.; Stewart, C. S.; Flint, H. J., The microbiology of butyrate formation in the human colon. FEMS Microbiol Lett 2002, 217 (2), 133-9.

14. Adolfsson, O.; Meydani, S. N.; Russell, R. M., Yogurt and gut function. Am J Clin Nutr 2004, 80 (2), 245-56.

15. J Med Food 2014.

16. Honzel, D.; Carter, S. G.; Redman, K. A.; Schauss, A. G.; Endres, J. R.; Jensen, G. S., Comparison of chemical and cell-based antioxidant methods for evaluation of foods and natural products: generating multifaceted data by parallel testing using erythrocytes and polymorphonuclear cells. J Agric Food Chem 2008, 56 (18), 8319-25.

Biochemical Markers Observed in EpiCor® Studies

EpiCor® is a registered trademark of Embria Health Sciences, LLC. © Embria Health Sciences, LLC.

MODE OF ACTION

Marketed by: KenzaHealth | Unit 51 APD Office Park | Kelvin Street, Kya Sands.

immunoarmour.co.za

TF: 0860 103 359 info@immunoarmour.co.za|